Methyl iodide → (+/-)-10-Methyl-2-pyrimidin-4-yl-7,8,9,10-tetrahydro-6H-pyrimido[1,2-alpha]azepin-4-one

HRID 1520419Notes

Reaction equation

[N:1]1[CH:6]=[CH:5][C:4]([C:7]2[N:8]=[C:9]3[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][N:10]3[C:16](=[O:18])[CH:17]=2)=[N:3][CH:2]=1.[CH3:19][Si]([N-][Si](C)(C)C)(C)C.[Li+].CI>O1CCCC1>[CH3:19][CH:15]1[CH2:14][CH2:13][CH2:12][CH2:11][N:10]2[C:16](=[O:18])[CH:17]=[C:7]([C:4]3[CH:5]=[CH:6][N:1]=[CH:2][N:3]=3)[N:8]=[C:9]12

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 10.00 g (41.27 mmol) of 2-pyrimidin-4-yl-7,8,9,10-tetrahydro-6H-pyrimido[1,2-α]azepin-4-one in dry tetrahydrofuran (200 mL) under argon at −78° C. was added 82.5 mL (82.5 mmol) of lithium bis(trimethylsilyl)amide (1M in tetrahydrofuran). The solution was stirred at −78° C. for 10 min and 25.7 mL of methyl iodide (412.7 mmol) was added. The reaction was stirred at −78° C. for 1 h and then at 0° C. for 2 h. The mixture was quenched with the addition of a saturated solution of ammonium chloride and extracted with ethyl acetate. The organic phase was dried over sodium sulfate and concentrated. The residue was purified by flash chromatography (dichloromethane with 1% of methanol) to afford 11.0 g of a white solid (40%).

Workup

stirringThe reaction was stirred at −78° C. for 1 h
waitat 0° C. for 2 h
customThe mixture was quenched with the addition of a saturated solution of ammonium chloride
extractionextracted with ethyl acetate
dry with materialThe organic phase was dried over sodium sulfate
concentrationconcentrated
customThe residue was purified by flash chromatography (dichloromethane with 1% of methanol)

Sources & evidence

ORD record: ord-f507a6c19849452c80bfe75043aa8856
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09073914B2

Reaction notes

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