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(2-Methylpropyl)boronic acid → {(1R)-2-cyclobutyl-1-[((2S)-2-{[(6-phenoxypyridin-3-yl)sulfonyl]amino}-3-phenylpropanoyl)amino]ethyl}boronic acid

HRID 1182696
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HRID 1182696 반응식
[CH:1]1([CH2:5][C@H:6]([NH:20][C:21](=[O:47])[C@@H:22]([NH:30][S:31]([C:34]2[CH:35]=[N:36][C:37]([O:40][C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)=[CH:38][CH:39]=2)(=[O:33])=[O:32])[CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[B:7]2[O:11][C@@H]3C[C@@H]4C[C@H]([C@]3(C)[O:8]2)C4(C)C)[CH2:4][CH2:3][CH2:2]1.CC(C)CB(O)O>CO>[CH:1]1([CH2:5][C@@H:6]([B:7]([OH:11])[OH:8])[NH:20][C:21](=[O:47])[C@@H:22]([NH:30][S:31]([C:34]2[CH:35]=[N:36][C:37]([O:40][C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)=[CH:38][CH:39]=2)(=[O:33])=[O:32])[CH2:23][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH2:2][CH2:3][CH2:4]1
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참가 물질

4

반응물 2

HCID 2734395(2-Methylpropyl)boronic acidHCID 68527475(2S)-N-{(1R)-2-cyclobutyl-1-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-4,6-methano-1,3,2-benzodioxaborol-2-yl]ethyl}-2-{[(6-phenoxypyridin-3-yl)sulfonyl]amino}-3-phenylpropanamide

생성물 1

HCID 45255496{(1R)-2-cyclobutyl-1-[((2S)-2-{[(6-phenoxypyridin-3-yl)sulfonyl]amino}-3-phenylpropanoyl)amino]ethyl}boronic acid수율 74.8%

시약·촉매·용매 1

HCID 887
Methanol
용매

실험 절차

Into a 20 mL vial was added (25)-N-{(1R)-2-cyclobutyl-1-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-4,6-methano-1,3,2-benzodioxaborol-2-yl]ethyl}-2-{[(6-phenoxypyridin-3-yl)sulfonyl]amino}-3-phenylpropanamide (31.2 mg, 0.047 mmol), (2-methylpropyl)boronic acid (10.4 mg) 1N hydrochloric acid (0.107 mmol), methanol (0.285 mL and hexanes (0.285 mL.) The mixture was stirred at room temperature overnight, then the hexane layer was separated and discarded. The remaining solvent was removed in vacuo and the residue purified by preparative TLC on silica plates using 10% MeOH in CH2Cl2 to give 18.4 mg (74% yield) of desired product as a white solid. 1H NMR (CD3OD, 300 MHz, δ): 8.36 (s, 1H); 7.95-7.84 (m, 1H); 7.52-7.39 (m, 2H); 7.33-7.06 (m, 10H); 6.95-6.83 (m, 1H); 4.25-4.13 (m, 1H); 3.09-2.94 (m, 1H); 2.93-2.78 (m, 1H); 2.46-2.32 (m, 1H); 2.26-1.93 (m, 3H); 1.92-1.71 (m, 2H); 1.64-1.37 (m, 3H); 1.37-1.22 (m, 1H).

후처리

  1. customthe hexane layer was separated
  2. customThe remaining solvent was removed in vacuo
  3. customthe residue purified by preparative TLC on silica plates

출처 및 근거

ORD 기록
ord-07ecea87ecc24f45b4f7044a3174f50e
출처 데이터셋
uspto-grants-2014_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08664200B2

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