Sodium Bicarbonate → [2-Methoxy-6-(3-methoxy-phenyl)-pyrimidin-4-yl]-[2-(4-methoxy-phenyl)-2-methyl-propyl]-amine

HRID 216134

Reaction equation

[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([CH3:13])([CH3:12])[CH2:10][NH2:11])=[CH:5][CH:4]=1.C(=O)(O)[O-].[Na+].Cl[C:20]1[CH:25]=[C:24]([C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([O:32][CH3:33])[CH:27]=2)[N:23]=[C:22]([O:34][CH3:35])[N:21]=1>CN1CCCC1.O>[CH3:35][O:34][C:22]1[N:21]=[C:20]([NH:11][CH2:10][C:9]([C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)([CH3:13])[CH3:12])[CH:25]=[C:24]([C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([O:32][CH3:33])[CH:27]=2)[N:23]=1

Participants

Conditions

Temperature: 175 °C

Procedure

A mixture of 2-(4-methoxy-phenyl)-2-methyl-propylamine [172 mg, 0.96 mmol, Intermediate (35)], sodium bicarbonate (0.12 g), and 4-chloro-2-methoxy-6-(3-methoxy-phenyl)-pyrimidine [120 mg, 0.48 mmol, Intermediate (53)] in N-methylpyrrolidine (3 mL), is heated to 175° C. for 3 hours. The mixture is diluted with water, and extracted with ethyl acetate. The extracts are washed with water, dried over magnesium sulfate, filtered and concentrated. The residue is subjected to chromatography on silica gel eluting with 30% EtOAc in heptane to afford [2-methoxy-6-(3-methoxy-phenyl)-pyrimidin-4-yl]-[2-(4-methoxy-phenyl)-2-methyl-propyl]-amine [131 mg, 69%, Example 29]. LCMS: RT=2.73 minutes, MS: 394 (M+H). 1H NMR (300 MHz, CDCl3): □7.59 (1H, s), 7.51 (1H, d, J=7.8 Hz), 7.35-7.27 (3H, m), 6.96 (1H, dd, J=8.1, 2.4 Hz), 6.88 (2H, d, J=9 Hz), 6.31 (1H, s), 4.02 (3H, s), 3.86 (3H, s), 3.79 (3H, s), 3.62 (2H, brs), 1.4 (6H, s). IC50=792 nM

Workup

extractionextracted with ethyl acetate
washThe extracts are washed with water
dry with materialdried over magnesium sulfate
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-be496aedbd9546e79392ec7703a70b03
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08193183B2

Linked notes

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