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

HRID 1182696Notes

Reaction equation

HRID 1182696 reaction equation
[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

Participants

4

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

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).

Workup

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

Sources & evidence

ORD record
ord-07ecea87ecc24f45b4f7044a3174f50e
Source dataset
uspto-grants-2014_03
Patent number
US08664200B2

Reaction notes

Loading…