Methanol → (R)-2-(4-oxo-8-(3-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)-2-phenylacetic acid

HRID 2362902Notes

Reaction equation

HRID 2362902 reaction equation
[O:1]=[C:2]1[C:6]2([CH2:11][CH2:10][N:9]([CH2:12][CH2:13][CH2:14][N:15]3[C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=4[NH:17][C:16]3=[O:24])[CH2:8][CH2:7]2)[N:5]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:4][N:3]1[C@H:31]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:32]([O:34]C)=[O:33].[OH-].[Li+].CO>O>[O:1]=[C:2]1[C:6]2([CH2:11][CH2:10][N:9]([CH2:12][CH2:13][CH2:14][N:15]3[C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=4[NH:17][C:16]3=[O:24])[CH2:8][CH2:7]2)[N:5]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH2:4][N:3]1[C@H:31]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:32]([OH:34])=[O:33]

Participants

5

Reactant 3

HCID 887MethanolHCID 3939Lithium HydroxideHCID 66652206(R)-methyl 2-(4-oxo-8-(3-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)-2-phenylacetate

Product 1

HCID 54771529(R)-2-(4-oxo-8-(3-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)-2-phenylacetic acidYield 20.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of (R)-methyl 2-(4-oxo-8-(3-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)-2-phenylacetate (105 mg, 0.189 mmol, 1 equiv) and lithium hydroxide (15.9 mg, 0.38 mmol, 2.0 equiv) in a 3:1 mixture of methanol and water (5 ml t/v) was stirred at ambient temperature for 24 hrs. The reaction was concentrated in vacuo and purified using preparatory high performance liquid chromatography. The combined pure fractions were lyophilized to afford the acetate salt of the title compound as a white solid (21 mg, 20%); 1H NMR (400 MHz, DMSO-d6): δ 1.57-1.66 (m, 2H), 1.87-1.91 (m, 2H); 2.79-2.85 (m, 4H); 3.27-3.42 (bs, 4H); 3.85 (t, 2H, J=6.8 Hz); 4.11 (d, 1H, J=4.8 Hz); 4.91 (d, 1H, J=4.8 Hz); 5.71 (s, 1H); 6.76-6.82 (m, 3H); 6.97-6.98 (m, 3H); 7.17-7.23 (m, 3H); 7.35-7.43 (m, 5H); 10.83 (s, 1H); 12.5 (bs, 1H); MS for C31H33ClN5O4 540.01 (M+H)+.

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. custompurified

Sources & evidence

ORD record
ord-03c25c21930c4e19a23d4e1cdb350e2c
Source dataset
uspto-grants-2014_04
Patent number
US08691836B2

Reaction notes

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