Triethylamine → (+/-)-4-[2-(3-Chloro-phenyl)-2-hydroxy-ethylamino]-3-[6-(4,5-dihydro-thiazol-2-yl)-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one

HRID 1793741Notes

Reaction equation

HRID 1793741 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]([OH:30])[CH2:9][NH:10][C:11]2[CH:16]=[CH:15][NH:14][C:13](=[O:17])[C:12]=2[C:18]2[NH:19][C:20]3[CH:26]=[C:25]([C:27]#[N:28])[CH:24]=[C:23]([CH3:29])[C:21]=3[N:22]=2)[CH:5]=[CH:6][CH:7]=1.Cl.N[CH2:33][CH2:34][SH:35].C(N(CC)CC)C>CO>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]([OH:30])[CH2:9][NH:10][C:11]2[CH:16]=[CH:15][NH:14][C:13](=[O:17])[C:12]=2[C:18]2[NH:19][C:20]3[CH:26]=[C:25]([C:27]4[S:35][CH2:34][CH2:33][N:28]=4)[CH:24]=[C:23]([CH3:29])[C:21]=3[N:22]=2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 9082Cysteamine HydrochlorideHCID 136380435(+/-)-2-{4-[2-(3-chloro-phenyl)-2-hydroxy-ethylamino]-2-oxo-1,2-dihydro-pyridin-3-yl}-7-methyl-3H-benzimidazole-5-carbonitrile

Product 1

HCID 135681898(+/-)-4-[2-(3-Chloro-phenyl)-2-hydroxy-ethylamino]-3-[6-(4,5-dihydro-thiazol-2-yl)-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-oneYield 66%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (±)-2-{4-[2-(3-chloro-phenyl)-2-hydroxy-ethylamino]-2-oxo-1,2-dihydro-pyridin-3-yl}-7-methyl-3H-benzimidazole-5-carbonitrile (100 mg, 0.24 mmol) in methanol (20 mL) was added 2-aminoethanethiol hydrochloride (41 mg, 0.36 mmol) and triethylamine (0.1 mL, excess). The reaction mixture was heated to reflux for 14 h and cooled to room temperature. After concentration, the residue was purified by prep. HPLC to yield the title compound (76 mg, 66%) as a yellow solid. 1H NMR (300 MHz, CD3OD) δ 8.10 (1H, s), 7.71 (1H, s), 7.66 (1H, s), 7.25–7.53 (4H, m), 6.33 (1H, d, J=7.6 Hz), 5.01 (1H, dd, J=4.2, 7.0 Hz), 4.58 (2H, t, J=8.6 Hz), 3.91 (2H, t, J=8.6 Hz), 3.73 (1H, dd, J=4.2, 13.7 Hz), 3.63 (1H, dd, J=7.0, 13.7 Hz), 2.64 (3H, s). LCMS (M+H)+ m/z 480 (t=1.70 min.).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 14 h
  3. concentrationAfter concentration
  4. customthe residue was purified by prep

Sources & evidence

ORD record
ord-206e81d9f3434b4fa34c3bb75a51c123
Source dataset
uspto-grants-2006_07
Patent number
US07081454B2

Reaction notes

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