Methanol → (S)-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

HRID 2362891Notes

Reaction equation

HRID 2362891 reaction equation
[O:1]=[C:2]1[C:6]2([CH2:11][CH2:10][NH:9][CH2:8][CH2:7]2)[N:5]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:4][N:3]1[C@@H:18]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:19]([O:21][CH3:22])=[O:20].I[CH2:30][CH2:31][CH2:32][N:33]1[C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=2[NH:35][C:34]1=[O:42].C(=O)([O-])[O-].[K+].[K+].CO>CN(C)C=O.ClCCl.O>[O:1]=[C:2]1[C:6]2([CH2:7][CH2:8][N:9]([CH2:30][CH2:31][CH2:32][N:33]3[C:37]4[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=4[NH:35][C:34]3=[O:42])[CH2:10][CH2:11]2)[N:5]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:4][N:3]1[C@@H:18]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)[C:19]([O:21][CH3:22])=[O:20]

Participants

8

Reactant 4

HCID 887MethanolHCID 11430Potassium CarbonateHCID 13564030HCID 13564030, compoundHCID 66652128(S)-methyl 2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)-2-phenylacetate

Product 1

HCID 66652239(S)-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-phenylacetateYield 11.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of (S)-methyl 2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)-2-phenylacetate (159 mg, 0.383 mmol, 1 equiv), 1-(3-iodopropyl)-1,3-dihydro-2H-benzimidazol-2-one (115.6 mg, 0.38 mmol, 1 equiv) and potassium carbonate (158.6 mg, 1.148 mmol, 3 equiv) in N,N-dimethylformamide was heated at 65° C. for 16 h. The reaction was cooled to ambient temperature and worked up using 5% methanol in dichloromethane and water. The organic layer was dried over MgSO4, and concentrated in vacuo under a high vacuum. The crude mixture was purified by preparatory thin layer chromatography using 7% methanol in dichloromethane. The purified extract was lyophilized to afford the title compound as a white solid (25 mg, <10%); 1H NMR (400 MHz, DMSO-d6): δ 1.61 (bs, 2H), 1.84 (bs, 2H), 2.46 (bs, 4H); 2.50-2.51 (m, 4H); 3.74 (s, 3H); 3.85 (t, 2H, J=7.2 and 6.4 Hz); 4.15 (d, 1H, J=4.8 Hz); 4.80 (d, 1H, J=4.8 Hz); 5.89 (s, 1H)); 6.79-6.85 (m, 3H); 6.97 (d, 3H, J=2.8 Hz); 7.16-7.18 (m, 1H); 7.23 (t, 2H, J=7.2 and 8.8 Hz); 7.39-7.46 (m, 5H); 10.82 (s, 1H); MS for C32H35N5O4 m/z 554.11 (M+H)+.

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated in vacuo under a high vacuum
  4. customThe crude mixture was purified by preparatory thin layer chromatography
  5. extractionThe purified extract

Sources & evidence

ORD record
ord-320a4280f57e4e3697045e6419e5b95a
Source dataset
uspto-grants-2014_04
Patent number
US08691836B2

Reaction notes

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