4-Methylmorpholine → (S)-3-[6-(4-Acetyl-piperazin-1-yl)-4-methyl-1H-benzimidazol-2-yl]-4-(1-hydroxymethyl-2-phenyl-ethylamino)-1H-pyridin-2-one

HRID 1793713Notes

Reaction equation

[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[C:12]([CH3:27])[C:13]3[N:17]=[C:16]([C:18]4[C:19](=[O:25])[NH:20][CH:21]=[CH:22][C:23]=4Cl)[NH:15][C:14]=3[CH:26]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[NH2:28][C@@H:29]([CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[CH2:30][OH:31].CN1CCOCC1>CN(C=O)C>[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[C:12]([CH3:27])[C:13]3[N:17]=[C:16]([C:18]4[C:19](=[O:25])[NH:20][CH:21]=[CH:22][C:23]=4[NH:28][C@H:29]([CH2:30][OH:31])[CH2:32][C:33]4[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=4)[NH:15][C:14]=3[CH:26]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 3-[6-(4-acetyl-piperazin-1-yl)-4-methyl-1H-benzimidazol-2-yl]-4-chloro-1 H-pyridin-2-one (1 g, 2.6 mmol) in DMF (10 mL) was added (S)-(−)-2-amino-3-phenyl-propanol (0.78 mg, 5.2 mmol) and N-methyl morpholine (2 mL). The reaction mixture was heated to 80° C. for 12 h, cooled to room temperature and concentrated with high vacuum. The residue was purified by flash column chromatography (10% MeOH/CH2Cl2) to yield the title compound (0.90 g, 69%). 1H NMR (400 MHz, CD3OD) δ 7.36 (1H, s), 7.02–7.23 (6H, m), 6.80 (1H, s), 5.98 (1H, d, J=7.5 Hz), 4.10–4.12 (3H, m), 3.67–3.78 (6H, m), 3.06–3.11 (3H, m), 2.90 (1H, dd, J=7.8, 13.6 Hz), 2.54 (3H, s), 2.12 (3H, s). LCMS (M+H)+ m/z 501 (t=1.30 min.).

Workup

temperaturecooled to room temperature
concentrationconcentrated with high vacuum
customThe residue was purified by flash column chromatography (10% MeOH/CH2Cl2)

Sources & evidence

ORD record: ord-da0b643c52044c48bbae7a61052bcc6d
Source dataset: uspto-grants-2006_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07081454B2

Reaction notes

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