Methylamine → 2-(methylamino)-6-(4-{[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]methyl}phenyl)-5-phenylnicotinonitrile

HRID 2105524Notes

Reaction equation

Cl[C:2]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][N:17]3[CH2:22][CH2:21][CH:20]([N:23]4[C:27]5[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=5[NH:25][C:24]4=[O:32])[CH2:19][CH2:18]3)=[CH:12][CH:11]=2)[C:7]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[CH:6][C:3]=1[C:4]#[N:5].[CH3:39][NH2:40]>CC(O)C>[CH3:39][NH:40][C:2]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][N:17]3[CH2:22][CH2:21][CH:20]([N:23]4[C:27]5[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=5[NH:25][C:24]4=[O:32])[CH2:19][CH2:18]3)=[CH:12][CH:11]=2)[C:7]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[CH:6][C:3]=1[C:4]#[N:5]

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of 2-Chloro-6-(4-{[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]methyl}phenyl]-5-phenylnicotinonitrile (2-6, 0.040 g, 0.077 mmol) and methylamine (2M in THF, 0.192 mL, 0.385 mmol) in i-PrOH (1 mL) were heated@150° C. for 15 min. in the microwave. The mixture was concentrated, taken up in DMF and purified by reverse phase HPLC (6-1; 5% CH3CN: 95% H2O+0.01% TFA to 95% CH3CN: 5% H2O+0.01% TFA). 1H-NMR (500 MHz, d6 DMSO) δ 10.93 (s, 1H), 9.59 (bs, 1H), 8.00 (s, 1H), 7.37-7.47 (m, 4H), 7.18-7.37 (m, 5H), 7.12 (dd, J=1.96, 8.06, 2H), 6.95-7.05 (m, 3H), 4.43-4.53 (m, 1H), 4.32 (d, J=5.00, 2H), 3.47 (d, J=10.99, 2H), 3.10-3.25 (m, 2H), 2.94 (d, J=4.39, 3H), 255-2.69 (m, 2H), 1.92 (d, J=11.48, 2H). HRMS m/z (M+H) Calcd: 515.2554, found: 515.2552.

Workup

concentrationThe mixture was concentrated
custompurified by reverse phase HPLC (6-1; 5% CH3CN: 95% H2O+0.01% TFA to 95% CH3CN: 5% H2O+0.01% TFA)

Sources & evidence

ORD record: ord-4ac3f9f25cf241de850bd27bc7ae33fa
Source dataset: uspto-grants-2009_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07579355B2

Reaction notes

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