Benzylamine → 2-(benzylamino)-5-bromo-3-methylpyrimidin-4(3H)-one

HRID 1676382Notes

Reaction equation

[Br:1][C:2]1[C:3](=[O:10])[N:4]([CH3:9])[C:5](Cl)=[N:6][CH:7]=1.[C:11]1([CH2:17][NH2:18])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C([O-])(O)=O.[Na+]>CCCCO.CCOC(C)=O>[CH2:17]([NH:18][C:5]1[N:4]([CH3:9])[C:3](=[O:10])[C:2]([Br:1])=[CH:7][N:6]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of 5-bromo-2-chloro-3-methylpyrimidin-4(3H)-one (Example 143, Step B, 0.100 g, 0.448 mmol), phenylmethanamine (0.064 ml, 0.582 mmol) and NaHCO3 (0.150 g, 1.79 mmol) in n-BuOH (3 mL) was stirred at 60° C. for 4 hours. The reaction mixture was cooled to room temperature and then diluted with EtOAc. The EtOAc layer was washed with H2O and saturated aqueous NaCl. The aqueous phase was re-extracted with EtOAc (1×). The combined EtOAc layers were dried (Na2SO4), filtered and concentrated to yield the desired product (0.130 g, 99%) as a pale yellow solid that was used without further purification. 1H NMR (400 MHz, DMSO-d6) δ 7.96 (t, 1H), 7.90 (s, 1H), 7.32 (s, 2H), 7.31 (m, 2H), 7.23 (m, 1H), 4.57 (d, 2H), 3.39 (s, 3H). LRMS (ESI pos) m/e 294, 296 (M+, Br pattern).

Workup

temperatureThe reaction mixture was cooled to room temperature
washThe EtOAc layer was washed with H2O and saturated aqueous NaCl
extractionThe aqueous phase was re-extracted with EtOAc (1×)
dry with materialThe combined EtOAc layers were dried (Na2SO4)
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-43f656c05c4a4ca28d7e76f6a61ad7fa
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08003662B2

Reaction notes

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