Methanol → (S)-4-{2-[4-(1-Hydroxymethyl-2-phenyl-ethylamino)-2-oxo-1,2-dihydro-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl}-piperazine-1-carboxylic acid isopropylamide

HRID 1354638Notes

Reaction equation

HRID 1354638 reaction equation
[OH:1][CH2:2][C@@H:3]([NH:11][C:12]1[CH:17]=[CH:16][NH:15][C:14](=[O:18])[C:13]=1[C:19]1[NH:23][C:22]2[CH:24]=[C:25]([N:29]3[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]3)[CH:26]=[C:27]([CH3:28])[C:21]=2[N:20]=1)[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[CH3:35][OH:36]>C(N=C=O)(C)C>[CH:3]([NH:11][C:35]([N:32]1[CH2:31][CH2:30][N:29]([C:25]2[CH:26]=[C:27]([CH3:28])[C:21]3[N:20]=[C:19]([C:13]4[C:14](=[O:18])[NH:15][CH:16]=[CH:17][C:12]=4[NH:11][C@H:3]([CH2:2][OH:1])[CH2:4][C:5]4[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=4)[NH:23][C:22]=3[CH:24]=2)[CH2:34][CH2:33]1)=[O:36])([CH3:4])[CH3:2]

Participants

4

Reactant 2

HCID 887MethanolHCID 136191205(S)-4-(1-Hydroxymethyl-2-phenyl-ethylamino)-3-(4-methyl-6-piperazin-1-yl-1H-benzimidazol-2-yl)-1H-pyridin-2-one

Product 1

HCID 136191359(S)-4-{2-[4-(1-Hydroxymethyl-2-phenyl-ethylamino)-2-oxo-1,2-dihydro-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl}-piperazine-1-carboxylic acid isopropylamideYield 69%

Reagents, catalysts & solvents 1

HCID 61277Isopropyl isocyanateCatalyst

Procedure

To a solution of (S)-4-(1-hydroxymethyl-2-phenyl-ethylamino)-3-(4-methyl-6-piperazin-1-yl-1H-benzimidazol-2-yl)-1H-pyridin-2-one (30 mg, 0.063 mmol) in methanol (2 mL) was added isopropyl isocyanate (2 drops). The reaction mixture was stirred at room temperature for 5 min. Concentration gave the residue, which was purified by prep. HPLC to yield the title compound (23.8 mg, 69%). 1H NMR (400 MHz, CD3OD) δ 7.55 (1H, s), 7.14–7.28 (7H, m), 6.12 (1H, d, J=7.8 Hz), 4.01–4.03 (1H, m), 3.92 (quintet, J=6.6 Hz), 3.80 (4H, m), 3.76 (1H, dd, J=4.8, 11.2 Hz), 3.70 (1H, dd, J=5.2, 11.2 Hz), 3.61–3.64 (4H, m), 3.09 (11H, dd, J=5.6, 13.7 Hz), 2.91 (1H, dd, J=8.0, 13.7 Hz), 2.64 (3H, s), 1.19 (6H, d, J=6.8 Hz). LCMS (M+H)+ m/z 545 (t=1.99 min.).

Workup

  1. concentrationConcentration
  2. customgave the residue, which
  3. customwas purified by prep

Sources & evidence

ORD record
ord-bd882d7ce0b24c45a140b5a893ff177a
Source dataset
uspto-grants-2007_05
Patent number
US07223757B2

Reaction notes

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