核磁共振图谱解析培训手册.pdf

confidential 1wuxi pharmatech co., ltdseptember 29, 2005 ? ? wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 2wuxi pharmatech co., ltdseptember 29, 2005 ?nmr? 1h 13c 13c? ?dept135o( ch ch3, ch2) 13c? ?dept90o( ch ) 1h ? ?1h cosy (? ? ) 1h ? ?1h tocsy (!“#$? !“#$? ) 1h ? ?1h noesy (%?a?bcde4566789:?;?a?bcde wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 3wuxi pharmatech co., ltdseptember 29, 2005 ffgg ?:? 1.? 1).? !“? 2). s#p$? 3). ?% ? 5. abca$b?d:ef 6. 3jhhc?ghi?7j (karpluskl) m9(?:;=?nod:7jpq 7. r“no-nod:(j-coupling)sj 8. tubno-nod:(j-coupling)sj ? vw?xyz? ? 12? ? o_ ? a ? ?_ze? wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 5wuxi pharmatech co., ltdseptember 29, 2005 /. (?(? ,dept? 1 ? 1. hi?,4?: ;,-?)?3?3. ab?r?8?!“?:?xy+?pab ?b?2?ab,56c?“c 5.28 ppm 1.8 ppm 2.73.4 ppm; 2.13.3 ppm hh h h o r ch2h2c wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 16wuxi pharmatech co., ltdseptember 29, 2005wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 17wuxi pharmatech co., ltdseptember 29, 2005wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 18wuxi pharmatech co., ltdseptember 29, 2005 4) ?a?a?(i?i?) ?+? !“)*? ?b+?a=?1? bm?;v?_c?:ca? -? ?=(f?;v?7j?d?:?=(?1? ?+?+?6? . ?:;? ?:;?:;? ?sj? ? !?“?#?$;? ?%?z?)e?*?* +?*?*?:;?+m ,:-? .?:;?/+0?-1? ?2$?3?+m6?-? wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 26wuxi pharmatech co., ltdseptember 29, 2005 ?4*?5?ch2?67? 0.5 ppm?8?cdcl3?dmso-? ?=9?4*?7?m ? !“?# $?+%?.?d ?. #$?/?0 a e?7, #$?d?0 ae?7.#$? ?b“c?0. wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 28wuxi pharmatech co., ltdseptember 29, 2005 2. 12? ? : co?s?n?12?. c?12? ?d?e?dmso? ?=12?f ?9g1?=?3?12?f8?0?a e?e7?h“?;gd ?.?d?0?*+“,?ijhi.?gjk ?3ek12?l?.?*?(a. e?0(?0“m*?s?+ “6?d:ef?#? ;7z%*8:9?+:;?. 1.52.02.53.03.54.0pp 1.589 1.602 1.610 1.619 1.628 1.632 1.638 1.645 1.650 1.658 1.664 1.848 1.853 1.867 1.884 1.895 1.899 1.904 1.907 1.910 1.918 1.922 1.936 1.941 1.955 2.373 3.458 3.473 3.486 3.502 3.632 3.640 3.661 3.669 3.742 3.758 3.762 3.768 3.779 3.790 3.796 3.823 3.839 3.843 3.850 3.855 3.859 3.876 3.967 3.975 3.984 3.992 4.000 4.008 4.015 4.025 1.000 2.944 1.188 1.007 1.011 0.978 0.986 0.986 o oh 1 2 45 3 1 22 3 3 4 4 5 wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 47wuxi pharmatech co., ltdseptember 29, 2005 ?-?23?23(j-coupling) 3jhh*%5a?+b *%5a?+b (karpluscdcd) 3jhh aa0ee90ee180ee cc h h aa 3j=j0cos2a a+caa=0ee-90ee 3j=j180cos2a a+caa=90ee-180ee 3j=a+bcosa a+ccos2aa (a=7 b=-1 c=5) or wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 58wuxi pharmatech co., ltdseptember 29, 2005 c h h aa aa0ee90180ee 3jhh 3j=a+bcosa a+ccos2aa ha hb ococh3 ch3coo h1h2 ha hb ococh3 ch3coo h1 h2 or a b a?h1?h2?ha?hb?3j1a(b)?3j2a(b)? b?h1?h2?ha?hb?3j1a(b)?3j2a(b)? wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 59wuxi pharmatech co., ltdseptember 29, 2005 1.01.52.02.53.03.5ppm 1.009 1.030 2.241 2.943 2.951 2.955 2.965 2.969 2.973 2.977 2.986 2.990 2.999 3.008 3.012 3.178 3.204 3.213 3.239 3.477 3.490 3.513 3.526 2.974 3.042 1.000 1.011 0.997 ba8793 yl005-7-15 cdcl3 wuxi pharmatechco. ltd. c b a 2j bc=10.8hz 3j ab=7hz 3j ac=4.3hz h h oh nh2 h a c b ? b,c?, jac?jab?a?b?c? ? wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 60wuxi pharmatech co., ltdseptember 29, 2005 o ho n h h h h 1a 2 3 4 5 1b j1a2=(3.989-3.971)*400=7.2hz j1b2=(3.923-3.909)*400=5.6hz j1a1b=(3.989-3.965)*400=9.6hz 2.12.22.32.42.52.62.72.82.93.03.13.23.33.43.53.63.73.83.94.04.14.24.34.4ppm 2.239 2.683 2.691 2.700 2.707 2.716 2.723 3.595 3.611 3.619 3.635 3.645 3.884 3.898 3.909 3.923 3.948 3.965 3.971 3.989 4.230 4.238 4.245 4.252 4.260 6.005 0.991 2.063 1.218 1.101 1.000 ai1758 h01368-097-1 cdcl3 wuxi pharmatech co.,ltd. 2 1a 1b 5 4 3 wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 61wuxi pharmatech co., ltdseptember 29, 2005 7.?-?23?23(j-coupling)rbrb ?r“?:;=?l?d:ef?e? 11 #14hz?ld:ef?14#18 hz?m? ?d:ef?7j?m?r“? ?7j?b?r“=?ub,?ub,?ubr “=d:ef?j= 0.5-7.0hz;?tubm j=8.5-13 hz. wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 62wuxi pharmatech co., ltdseptember 29, 2005 brh h h a b c d ? jab=(5.163-5.130)300=9.9hz ? jac?(5.342-5.286)300=16.8hz jad?3.942-3.924)300?7.5hz 3.54.04.55.05.56.06.57.07.5ppm 3.924 3.949 5.130 5.163 5.286 5.289 5.342 5.345 5.965 5.989 5.997 6.014 6.022 6.046 6.053 6.070 6.078 6.103 7.257 2.032 1.018 1.021 1.000 ba8169 yl005-7-8 cdcl3 wuxi pharmatech co. ltd. a c b d wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 63wuxi pharmatech co., ltdseptember 29, 2005 8.mmyz?yz?-?23?23(j-coupling)rbrb tubsj?sj?e ?sj?jae(% )?jaaz?8# 12hz?jaez?jeez?2#5hz? ?(sj?9(=?tub?:; ?e?8 ?,? ?0.5-1ppm,?pd:?7j?a0 e0?,?: wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 64wuxi pharmatech co., ltdseptember 29, 2005 h3 h1 h2 h4 r3 r1 r2 r4 r1 r2 r3 r4 3j12=3jaa=8-11hz 3j13=3j24=3jae=2-5hz 3j34=3jee=2-5hz a ? e ? wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 65wuxi pharmatech co., ltdseptember 29, 2005 0.60.70.80.91.01.11.21.31.41.51.61.71.81.92.02.12.22.32.42.52.62.72.82.93.03.13.23.33.4ppm 1.286 1.296 1.317 1.326 1.347 1.357 1.377 1.387 1.517 1.547 2.037 2.046 2.055 2.066 2.075 2.084 2.095 2.105 2.114 2.200 2.230 2.299 2.333 2.338 2.363 2.368 2.393 2.398 2.472 2.851 2.881 2.071 2.057 1.209 2.139 2.086 n h on h2 1 4 3 5 2 1,5e 1,5a 3a 2,4e2,4a wuxwwi pharmatech co., ltdseptember 29,m2005 2 2 confidential 66wuxi pharmatech co., ltdseptember 29, 2005 1.01.52.02.53.03.5ppm 0.998 1.010 1.024 1.033 1.048 1.059 1.099 1.115 1.132 1.139 1.149 1.157 1.177 1.244 1.268 1.640 1.669 1.765 1.774 1.784 1.797 1.807 1.816 1.967 1.976 1.987 1.998 2.007 2.331 2.485 2.490 2.494 2.576 2.590 2.600 2.610 2.623 2.821 2.846 2.873 3.090 3.120 3.147 3.354 3.384 3.551 3.555 3.585 3.769 1.972 1.969 1.054 1.000 0.997 1.016 3.002 1.025 1.092 1.243 1.257 1.247 3.146 n r h h nh h h h h h h h 1 2 3 4 5 3a 4a 4e3e 2a 1a5a 5e 1e wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 67wuxi pharmatech co., ltdseptember 29, 2005 9.ffg?hi?jk?g?hi?jk? 6l? lm?,hnop? !?c“?#)*?n-co?! ?0?(-? o_+$n?%?#n(ch3)2=? =1x?(a?.?:;=?(a ?2?%?*?3“g#?4?1#2? ?xp5?a?)6? 7?,8 $? n n h r 1 r 2 r 3 n h n r 3 r 2 r 1 r1 oo r2 r1 o r2 oh wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 73wuxi pharmatech co., ltdseptember 29, 2005 confidential 74wuxi pharmatech co., ltdseptember 29, 2005 9. !:_ wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 75wuxi pharmatech co., ltdseptember 29, 2005 )(?./;e?-? ?$?!?:_%? !0a?aya?#m*?axp? :;?bc(dy?+e?e*dmso=,c40 #60+?cdcl3 meod=?)m?* cdcl3 meod?+fp60,+?#m,c60+? ?,?boc-? ?m?xy, ?p?xy?e?,?m? ?p?:;+ ,!“m#-lc-ms$: g%.?g)m*+,?! 0#80 ppm)?$? /(?k?s? ?,t ) 4? ?h.?(?g?q(. wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 83wuxi pharmatech co., ltdseptember 29, 2005 13c dept-90 -uvv?-uvv? 13c dept-135 13c c o ch2ch2c o ohh2chc h3c h3c wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 84wuxi pharmatech co., ltdseptember 29, 2005 170160150140130120110100908070605040302010ppm 8.784 9.059 17.747 29.564 76.742 77.060 77.378 118.883 120.271 122.032 124.898 139.414 140.259 144.379 152.064 154.094 160.652 168.975 1.013 1.207 1.110 1.104 1.000 0.454 0.972 0.550 0.568 0.972 1.025 0.975 0.447 0.343 0.553 170160150140130120110100908070605040302010ppm 170160150140130120110100908070605040302010ppm 2 14 1 12 4 8 6 7 13 9 11 10 3 5 dept90 dept135 c13 n h n n n o 1 2 4 56 7 8 910 11 12 13 14 2 3 wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 85wuxi pharmatech co., ltdseptember 29, 2005 11.hi?t?t?g? ? ? wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 86wuxi pharmatech co., ltdseptember 29, 2005 confidential 87wuxi pharmatech co., ltdseptember 29, 2005 7.17.27.37.47.57.67.77.87.9ppm 7.437 7.455 7.476 7.506 7.523 7.540 7.559 7.611 7.635 7.749 7.768 1.013 1.032 0.996 1.000 ai734 yl005-7-25 dmso wuxi pharmatech co. ltd. 4 1 2 3 f o oh 1 2 3 4 jf1=(7.635-7.611)*400=9.6hz jf4?0hz jf3=(7.559-7.540)*400?7.6hz? jf2=9.6hz j23?7.6hz? ? !“#$%“x*7j.? 0$“?7!?3? e?:?j?p7hz? ?8?7j?hmbc?=?1?x?0 d:?m?hz?x4? ?z?#? wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 98wuxi pharmatech co., ltdseptember 29, 2005 hmbc ? ?(? -.?+? ? ?(? -.?+? c o ch2ch2c o ohh2chc h3c h3c wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 99wuxi pharmatech co., ltdseptember 29, 2005 ?.?noeopiq“r?s opiq“r?s 4?:?=? e?xas ,4asa! ?$“=?noe?#?e?9$?noe? ?:;%a?7j, ?0 f*7?m4?noe?11m,?*ug?/noe0?$“as ?aq8? wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 100wuxi pharmatech co., ltdseptember 29, 2005 oh cl ab c oh cl a b c confidential 101wuxi pharmatech co., ltdseptember 29, 2005 h-hnoesy confidential 102wuxi pharmatech co., ltdseptember 29, 2005 =?-?mb“a?:;?b %a?*/-noesy-m(? a? ?noe?7?m?m?ap ?a?2ca,b? ?noe?7? oh cl a b c oh cl a b c wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 103wuxi pharmatech co., ltdseptember 29, 2005 noesy ?i? z? ?c? ?i? z? ?c? 1g?c6d6 cdcl3?+c?=? ?m(?c6d6=?2?2? ? ? =?m(!1c2?2? noe?3c2?2“?noe?m? ?ap? #-?m$%?p? ?ch5ac-ch3n-?d?noe?;(?2r,4r?a =roch2-?ch5bch4?noe?. ?m- ?!h4ch5a , h5b?=,al?*?l?2. (3g?q8? o o ch2 r1 ro h h ch3n h i- 4 5a 5b 2 4 5 2s,4r o o h h ch3n h c h2 ro r1 i- 4 5a 5b 2 4 5 2r,4r wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 109wuxi pharmatech co., ltdseptember 29, 2005 1 3 2 r1 4 5 4b 2b 4a 2a oh r2 1 3 2 r1 4 5 4b 2b 4a 2a oh r2 cd% wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 110wuxi pharmatech co., ltdseptember 29, 2005 9.08.58.07.57.06.56.05.55.04.54.03.53.02.52.01.51.00.50.0 ppm 2.080 2.087 2.092 2.151 2.169 2.184 2.203 2.378 2.391 2.403 2.415 2.426 2.439 2.451 2.958 2.972 2.980 2.983 2.993 2.996 3.004 3.017 3.615 3.666 3.770 3.790 3.798 3.810 3.818 3.838 4.485 4.492 4.498 4.503 4.510 6.753 6.760 6.776 6.784 6.793 6.800 6.802 6.809 6.814 6.821 6.831 1.305 1.177 1.293 1.164 0.973 1.000 1 3 2 r1 4 5 4b 2b 4a 2a oh r2 wuxwwi pharmatech co., ltdseptember 29,m2005 0 1 h c confidential 111wuxi pharmatech co., ltdseptember 29, 2005 9.08.58.07.57.06.56.05.55.04.54.03.53.02.52.01.51.00.50.0ppm 2.121 2.124 2.135 2.141 2.144 2.149 2.160 2.169 2.174 2.529 2.543 2.552 2.566 2.578 2.587 2.602 3.159 3.184 3.204 3.209 3.229 3.555 3.578 3.601 3.615 4.507 4.512 4.521 4.530 4.535 6.729 6.736 6.752 6.758 6.762 6.778 6.784 6.809 6.812 6.816 6.818 6.832 6.837 6.851 6.854 6.857 1.186 2.137 1.028 1.012 1.076 1.000 1 3 2 r1 4 5 4b 2b 4a 2a oh r2 wuxwwi pharmatech co., ltdseptember 29,m2005 1 d d 1. .0 d d 0 1 o., o., 0 1 m ma a 1 a a .0 0 confidential 112wuxi pharmatech co., ltdseptember 29, 2005 ppm 87654321ppm 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 3 51 4a 4b 2 cosy 1 3 2 r1 4 5 4b 2b 4a 2a oh r2 wuxwwi pharmatech co., ltdseptember 29,m2005 8 2929 765 ww 4 m m 3 o o confidential 113wuxi pharmatech co., ltdseptember 29, 2005 1 3 2 r1 4 5 4b 2b 4a 2a oh r2 ppm 87654321ppm 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 3 51 4a 4b 2 noesy wuxwwi pharmatech co., ltdseptember 29,m2005 8765432 2 2 confidential 114wuxi pharmatech co., ltdseptember 29, 2005 1 3 2 r1 4 5 4b 2b 4a 2a oh r2 ppm 2.02.53.03.54.04.55.05.5ppm 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 3 5 1 4b 4a 2a cosy 2b wuxwwi pharmatech co., ltdseptember 29,m2005 2d d.5ecech ch c3p p.5haha4 4 0.04.550 0.05 55m mb bm mberber confidential 115wuxi pharmatech co., ltdseptember 29, 2005 1 3 2 r1 4 5 4b 2b 4a 2a oh r2 ppm 2.02.53.03.54.04.55.05.56.06.57.07.58.0ppm 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 3 5 1 4b 4a 2a noesy 2b wuxwwi pharmatech co., ltdseptember 29,m2005 3 33 l .5 d d 4 c c .0 c c 4.5 t 5 p p .0 h h 5.56.06.57.07 0 0.55 8 2 2.09 9 confidential 116wuxi pharmatech co., ltdseptember 29, 2005 ?#-cosy noe4?:;?, ?56?:;=3?5? ?noe?77?:;= 1?3?noe?77? 1 3 2 r1 4 5 4b 2b 4a 2a oh r2 1 3 2 r1 4 5 4b 2b 4a 2a oh r2 wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 117wuxi pharmatech co., ltdseptember 29, 2005 ?noe?myz?“?myz?“? ?tubsj=?c?a?l ; c?a?l?d?,8?9e:!?. ;?,?ptub?em?layp ?,?d:ef ?sj(?d:?, n h r1 h1 h2 r2 n h r1 h1 r2 h2 n h h1 r2 r1 h2 n h r1 r2 h1 h2 wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 118wuxi pharmatech co., ltdseptember 29, 2005 !-“#?- noe?.?.tu bsj=?c?noe/?,? e0?a0?noe%+?m ?,g?*+ ? wuxwwi pharmatech co., ltdseptember 29,m2005 confidential 119wuxi pharmatech