[(3S)-1,2,3,4-tetrahydroisoquinolin-3-yl]methanol → N-Butyl-4-chloro-N-(3,4-dichlorobenzyl)-1-(2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(8-(2-morpholinoethoxy)naphthalen-2-ylsulfonylcarbamoyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide

HRID 528946노트

반응식

HRID 528946 반응식
[CH2:1]([N:5]([CH2:49][C:50]1[CH:55]=[CH:54][C:53]([Cl:56])=[C:52]([Cl:57])[CH:51]=1)[C:6]([C:8]1[C:12]([Cl:13])=[C:11]([CH3:14])[N:10]([C:15]2[CH:23]=[CH:22][C:21]([C:24](=[O:48])[NH:25][S:26]([C:29]3[CH:38]=[CH:37][C:36]4[C:31](=[C:32]([O:39][CH2:40][CH2:41][N:42]5[CH2:47][CH2:46][O:45][CH2:44][CH2:43]5)[CH:33]=[CH:34][CH:35]=4)[CH:30]=3)(=[O:28])=[O:27])=[CH:20][C:16]=2[C:17](O)=[O:18])[N:9]=1)=[O:7])[CH2:2][CH2:3][CH3:4].[CH2:58]1[C:67]2[C:62](=[CH:63][CH:64]=[CH:65][CH:66]=2)[CH2:61][C@@H:60]([CH2:68][OH:69])[NH:59]1>>[CH2:1]([N:5]([CH2:49][C:50]1[CH:55]=[CH:54][C:53]([Cl:56])=[C:52]([Cl:57])[CH:51]=1)[C:6]([C:8]1[C:12]([Cl:13])=[C:11]([CH3:14])[N:10]([C:15]2[CH:23]=[CH:22][C:21]([C:24](=[O:48])[NH:25][S:26]([C:29]3[CH:38]=[CH:37][C:36]4[C:31](=[C:32]([O:39][CH2:40][CH2:41][N:42]5[CH2:43][CH2:44][O:45][CH2:46][CH2:47]5)[CH:33]=[CH:34][CH:35]=4)[CH:30]=3)(=[O:28])=[O:27])=[CH:20][C:16]=2[C:17]([N:59]2[C@H:60]([CH2:68][OH:69])[CH2:61][C:62]3[C:67](=[CH:66][CH:65]=[CH:64][CH:63]=3)[CH2:58]2)=[O:18])[N:9]=1)=[O:7])[CH2:2][CH2:3][CH3:4]

참가 물질

3

반응물 2

HCID 776757[(3S)-1,2,3,4-tetrahydroisoquinolin-3-yl]methanolHCID 710621802-(3-(Butyl(3,4-dichlorobenzyl)carbamoyl)-4-chloro-5-methyl-1H-pyrazol-1-yl)-5-(8-(2-morpholinoethoxy)naphthalen-2-ylsulfonylcarbamoyl)benzoic acid2회

생성물 1

HCID 86718910N-Butyl-4-chloro-N-(3,4-dichlorobenzyl)-1-(2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(8-(2-morpholinoethoxy)naphthalen-2-ylsulfonylcarbamoyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide수율 71.3%

실험 절차

Following a procedure analogous to that for the synthesis of Example 91, 2-(3-(butyl(3,4-dichlorobenzyl)carbamoyl)-4-chloro-5-methyl-1H-pyrazol-1-yl)-5-(8-(2-morpholinoethoxy)naphthalen-2-ylsulfonylcarbamoyl)benzoic acid (Intermediate 186B, 12 mg, 0.014 mmol) and (S)-(1,2,3,4-tetrahydroisoquinolin-3-yl)methanol (Aldrich, 9 mg, 0.056 mmol) were converted to the title compound (10 mg, 70%). 1H NMR (CD3OD, mixture of amide rotamers) δ 9.23-9.09 (m, 1H), 8.24 (dd, J=1.7, 8.0 Hz, 0.5H), 8.10-7.94 (m, 3.5H), 7.76-7.59 (m, 3H), 7.53-7.29 (m, 1.5H), 7.27-6.80 (m, 6H), 6.68 (d, J=7.5 Hz, 0.5H), 5.27-5.04 (m, 1H), 4.75-4.59 (m, 3H), 4.54-2.44 (m, 18H), 2.39-2.26 (m, 3H), 2.25-2.06 (m, 1H), 1.65-0.81 (m, 5.5H), 0.75-0.65 (m, 1H), 0.61-0.51 (m, 0.5H); MS(ESI+) m/z 1005.3 (M+H)+.

출처 및 근거

ORD 기록
ord-99a2a010e8224e3f8896fa5cc0b2230d
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346795B2

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