4-Methylmorpholine → (S)-3-(6-bromo-4-methyl-1H-benzo[d]imidazol-2-yl)-4-(1-hydroxy-3-phenylpropan-2-ylamino)pyridin-2(1H)-one

HRID 1354611Notes

Reaction equation

HRID 1354611 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH3:19])[C:5]2[N:9]=[C:8]([C:10]3[C:11](=[O:17])[NH:12][CH:13]=[CH:14][C:15]=3Cl)[NH:7][C:6]=2[CH:18]=1.[NH2:20][C@@H:21]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH2:22][OH:23].CN1CCOCC1>CN(C=O)C>[CH2:24]([C@H:21]([NH:20][C:15]1[CH:14]=[CH:13][NH:12][C:11](=[O:17])[C:10]=1[C:8]1[NH:7][C:6]2[CH:18]=[C:2]([Br:1])[CH:3]=[C:4]([CH3:19])[C:5]=2[N:9]=1)[CH2:22][OH:23])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 447213phenylalaninol, (S)-HCID 1356816443-(6-Bromo-4-methyl-1H-benzimidazol-2-yl)-4-chloro-1H-pyridin-2-one

Product 1

HCID 136118015(S)-3-(6-bromo-4-methyl-1H-benzo[d]imidazol-2-yl)-4-(1-hydroxy-3-phenylpropan-2-ylamino)pyridin-2(1H)-oneYield 74%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 3-(6-bromo-4-methyl-1H-benzimidazol-2-yl)-4-chloro-1H-pyridin-2-one (1.42 g, 3.78 mmol) in DMF (15 mL) were added (S)-(−)-2-amino-3-phenyl-1-propanol (1.43 g, 9.45 mmol) and N-methyl morpholine (1.5 mL). The reaction mixture was heated to 80° C. for 6 h and cooled to room temperature. The solvent was removed with high vacuum and the residue was purified by flash chromatography (5% MeOH/CH2Cl2) to yield the title compound (1.26 g, 74%) as a yellow foam. 1H NMR (300 MHz, CDCl3) δ 6.9–7.2 (8H, m), 5.86 (1H, d, J=7.1 Hz), 3.7–3.9 (3H, m), 2.9–3.1(2H, m), 2.57 (3H, s). LCMS (M+H)+ m/z 453 (t=2.03 min.).

Workup

  1. temperaturecooled to room temperature
  2. customThe solvent was removed with high vacuum
  3. customthe residue was purified by flash chromatography (5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-9ce6abcf265c4d02abbfabcab5f706ba
Source dataset
uspto-grants-2007_05
Patent number
US07223757B2

Reaction notes

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