Hydrogen Sulfide → 4'-[[3(R)-[(3-t-Butoxycarbonylamino-3-methyl-1-oxobutyl)amino]-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-1-yl]methyl][1,1'-biphenyl]-2-thioamide

HRID 1591478

반응식

HRID 1591478 반응식
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:14]=[CH:13][C:12]([CH2:15][N:16]2[C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=3[CH2:20][CH2:19][C@@H:18]([NH:27][C:28](=[O:41])[CH2:29][C:30]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:32])[CH3:31])[C:17]2=[O:42])=[CH:11][CH:10]=1)#[N:2].C(N(CC)CC)C.[SH2:50].[OH-].[Na+]>N1C=CC=CC=1.O>[C:36]([O:35][C:34]([NH:33][C:30]([CH3:32])([CH3:31])[CH2:29][C:28]([NH:27][C@@H:18]1[CH2:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[N:16]([CH2:15][C:12]2[CH:11]=[CH:10][C:9]([C:4]3[C:3]([C:1](=[S:50])[NH2:2])=[CH:8][CH:7]=[CH:6][CH:5]=3)=[CH:14][CH:13]=2)[C:17]1=[O:42])=[O:41])=[O:40])([CH3:37])([CH3:39])[CH3:38]

참가 물질

7

반응물 4

HCID 402Hydrogen SulfideHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 571704893-[[1-[[2'-Cyano-[1,1'-biphenyl]-4-yl]methyl]-2,3,4,5-tetrahydro-2-oxo-1H-benzazepin-3(R)-yl]amino]-1,1-dimethyl-3-oxopropylcarbamic acid, 1,1-dimethylethyl ester

생성물 1

HCID 186515014'-[[3(R)-[(3-t-Butoxycarbonylamino-3-methyl-1-oxobutyl)amino]-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-1-yl]methyl][1,1'-biphenyl]-2-thioamide수율 82%

시약·촉매·용매 2

HCID 962Water용매HCID 1049Pyridine용매

반응 조건

온도
90 °C

실험 절차

A solution of 380 mg (0.67 mmol) of 3-[[1-[[2'-cyano-[1,1'-biphenyl]-4-yl]methyl]-2,3,4,5-tetrahydro-2-oxo-1H-benzazepin-3(R)-yl]amino]-1,1-dimethyl-3-oxopropylcarbamic acid, 1,1-dimethylethyl ester (Example 69, Step D), in 5 mL of pyridine was placed in a bomb and treated with 5 mL of triethylamine and excess hydrogen sulfide was introduced under pressure. The bomb was sealed and heated for 12 hours at 90° C. The bomb was vented into 5 M sodium hydroxide and the contents poured into 40 mL of water, then extracted with ether (3×). The combined extracts were washed with water (3×), dried over magnesium sulfate, filtered and evaporated under vacuum to afford 330 mg (0.53 mmol, 82%) of product. 1H NMR (200 MHz,CDCl3): 1.38 (s,6H), 1.45 (s,9H), 1.90 (m,1H), 2.4-2.7 (m,4H), 2.92 (m,1H), 4.55 (m,1H), 4.94 (d,15 Hz,1H), 5.22 (d,15 Hz,1H), 5.31 (br s,1H), 6.50 (br s,1H), 6.70 (m,1H), 7.1-7.5 (m,12H), 7.82 (m,1H). FAB-MS (Li+ spike): calculated for C34H40N4O4S 600; found 607 (M+Li,65%).

후처리

  1. additionwas introduced under pressure
  2. customThe bomb was sealed
  3. extractionextracted with ether (3×)
  4. washThe combined extracts were washed with water (3×)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated under vacuum

출처 및 근거

ORD 기록
ord-591fcc746e16438cb6430264745a4046
출처 데이터셋
uspto-grants-1993_04
특허 번호
US05206235

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