Acetic Acid → (S)-6-(1-Hydroxymethyl-2-phenyl-ethylamino)-5-(6-imidazol-1-yl-4-methyl-1H-benzimidazol-2-yl)-3H-pyrimidin-4-one

HRID 1354642Notes

Reaction equation

HRID 1354642 reaction equation
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C@@H:9]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:10][OH:11])[C:3]=1[C:19]1[NH:23][C:22]2[CH:24]=[C:25]([N:29]3[CH:33]=[CH:32][N:31]=[CH:30]3)[CH:26]=[C:27]([CH3:28])[C:21]=2[N:20]=1.N.C(O)(=[O:37])C>Cl.O.CO>[OH:11][CH2:10][C@@H:9]([NH:8][C:4]1[N:5]=[CH:6][NH:7][C:2](=[O:37])[C:3]=1[C:19]1[NH:23][C:22]2[CH:24]=[C:25]([N:29]3[CH:33]=[CH:32][N:31]=[CH:30]3)[CH:26]=[C:27]([CH3:28])[C:21]=2[N:20]=1)[CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

7

Reactant 3

HCID 176Acetic AcidHCID 222AmmoniaHCID 86591317(S)-2-[6-chloro-5-(6-imidazol-1-yl-4-methyl-1H-benzimidazol-2-yl)-pyrimidin-4-ylamino]-3-phenyl-propan-1-ol

Product 1

HCID 136191209(S)-6-(1-Hydroxymethyl-2-phenyl-ethylamino)-5-(6-imidazol-1-yl-4-methyl-1H-benzimidazol-2-yl)-3H-pyrimidin-4-oneYield 37%

Reagents, catalysts & solvents 3

HCID 962WaterCatalystHCID 313Hydrochloric AcidSolventHCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (S)-2-[6-chloro-5-(6-imidazol-1-yl-4-methyl-1H-benzimidazol-2-yl)-pyrimidin-4-ylamino]-3-phenyl-propan-1-ol in 4 N HCl (0.5 mL) and acetic acid (0.5 mL) was added two drops of water. The reaction mixture was heated to 100° C. for 8 h, cooled to room temperature, and neutralized with ammonia in methanol. After concentration, the residue was purified by prep. HPLC to yield the title compound (26 mg, 37% for two steps). 1H NMR (400 MHz, CD3OD) δ 9.41 (1H, narrow t, J=1.5 Hz), 8.06 (1H, narrow dd, J=1.6, 1.9 Hz), 7.93 91H, s), 7.77 (1H, narrow dd, J=1.6, 1.8 Hz), 7.73 (1H, narrow d, J=1.9 Hz), 7.11–7.21 (6H, m), 4.70–4.74 (1H, m), 3.74 (2H, d, J=4.7 Hz), 3.11 (1H, dd, J=6.1, 13.5 Hz), 3.00 (1H, dd, J=7.8, 13.5 Hz), 2.70 (3H, s). LCMS (M+H)+ m/z 442 (t=2.17 min.).

Workup

  1. temperaturecooled to room temperature
  2. concentrationAfter concentration
  3. customthe residue was purified by prep

Sources & evidence

ORD record
ord-1a5ba06a26954edb851212c31e2c6544
Source dataset
uspto-grants-2007_05
Patent number
US07223757B2

Reaction notes

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