Triethylamine → 4-[(S)-2-(3-Chloro-phenyl)-2-hydroxy-ethylamino]-3-[6-(7-ethyl-2,7-diaza-spiro[4.4]non-2-yl)-4-methyl-1H-benzoimidazol-2-yl]-1H-pyridin-2-one

HRID 470310Notes

Reaction equation

HRID 470310 reaction equation
Cl[C:2]1[CH:7]=[CH:6][NH:5][C:4](=[O:8])[C:3]=1[C:9]1[NH:13][C:12]2[CH:14]=[C:15]([N:19]3[CH2:23][CH2:22][C:21]4([CH2:27][CH2:26][N:25]([CH2:28][CH3:29])[CH2:24]4)[CH2:20]3)[CH:16]=[C:17]([CH3:18])[C:11]=2[N:10]=1.[NH2:30][CH2:31][C@H:32]([C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([Cl:40])[CH:35]=1)[OH:33].CCN(CC)CC>CCO>[Cl:40][C:36]1[CH:35]=[C:34]([C@H:32]([OH:33])[CH2:31][NH:30][C:2]2[CH:7]=[CH:6][NH:5][C:4](=[O:8])[C:3]=2[C:9]2[NH:13][C:12]3[CH:14]=[C:15]([N:19]4[CH2:23][CH2:22][C:21]5([CH2:27][CH2:26][N:25]([CH2:28][CH3:29])[CH2:24]5)[CH2:20]4)[CH:16]=[C:17]([CH3:18])[C:11]=3[N:10]=2)[CH:39]=[CH:38][CH:37]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 9855591(S)-2-amino-1-(3-chlorophenyl)ethanolHCID 1361066854-chloro-3-[6-(7-ethyl-2,7-diaza-spiro[4.4]non-2-yl)-4-methyl-1H-benzoimidazol-2-yl]-1H-pyridin-2-one

Product 1

HCID 1361065544-[(S)-2-(3-Chloro-phenyl)-2-hydroxy-ethylamino]-3-[6-(7-ethyl-2,7-diaza-spiro[4.4]non-2-yl)-4-methyl-1H-benzoimidazol-2-yl]-1H-pyridin-2-oneYield 35.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 4-chloro-3-[6-(7-ethyl-2,7-diaza-spiro[4.4]non-2-yl)-4-methyl-1H-benzoimidazol-2-yl]-1H-pyridin-2-one (53 mg, 0.13 mmol), (S)-2-amino-1-(3-chlorophenyl)-ethanol (27 mg, 0.156 mmol) and Et3N (26 mg, 0.26 mmol) in EtOH (0.5 mL) was heated at 80° C. for 18 h and then the reaction mixture was evaporated. The residue was purified by chromatography (150:8:1 CH2Cl2/MeOH/28% aqueous NH4OH) to afford the title compound (25 mg, 35%). 1H NMR (MeOH-d4) δ 1.16 (t, J=8 Hz, 3H), 1.80-2.02 (4H), 2.48-2.80 (4H), 2.50 (s, 3H), 3.19-3.39 (4H), 3.63 (m, 2H), 4.81 (m, 1H), 4.95 (m, 2H), 6.18 (d, J=6 Hz, 1H), 6.38 (s, 1H), 6.44 (s, 1H), 7.17-7.31 (3H), 7.38 (d, J=6 Hz, 1H), 7.55 (s, 1H). ESI-MS m/z 547 (MH+).

Workup

  1. customthe reaction mixture was evaporated
  2. customThe residue was purified by chromatography (150:8:1 CH2Cl2/MeOH/28% aqueous NH4OH)

Sources & evidence

ORD record
ord-ac70fd7daf5c48a7a4c178adbe31d250
Source dataset
uspto-grants-2014_01
Patent number
US08629147B2

Reaction notes

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