Potassium Carbonate → 6-[3,5-Bis(trifluoromethyl)benzyl]-4-chloro-5,6,7,8,9,10-hexahydro-2-(methylthio)-5-oxopyrimido[4,5-b][1,5]diazocine

HRID 1829640Notes

Reaction equation

Cl.[F:2][C:3]([F:33])([F:32])[C:4]1[CH:5]=[C:6]([CH:25]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:27]=1)[CH2:7][N:8]([CH2:21][CH2:22][CH2:23][NH2:24])[C:9]([C:11]1[C:12]([Cl:20])=[N:13][C:14]([S:18][CH3:19])=[N:15][C:16]=1Cl)=[O:10].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C(OCC)(=O)C>[F:30][C:28]([F:31])([F:29])[C:26]1[CH:25]=[C:6]([CH:5]=[C:4]([C:3]([F:33])([F:2])[F:32])[CH:27]=1)[CH2:7][N:8]1[CH2:21][CH2:22][CH2:23][NH:24][C:16]2[N:15]=[C:14]([S:18][CH3:19])[N:13]=[C:12]([Cl:20])[C:11]=2[C:9]1=[O:10]

Participants

Conditions

Temperature: 100 °C

Procedure

N-[3,5-bis(trifluoromethyl)benzyl]-N-(3-aminopropyl)-4,6-dichloro-2-(methylthio)pyrimidine-5-carboxylic acid amide hydrochloride (Compound of Reference Example 6; 3.35 g) was dissolved in N,N-dimethylformamide (6 mL). To this solution, potassium carbonate (4.15 g) was added and the mixture was stirred at 100° C. for 1 hour. The reaction mixture was diluted with ethyl acetate, was sequentially washed with water and a saturated aqueous solution of sodium chloride, and was then dried over anhydrous sodium sulfate. Following removal of the solvent, the residue was purified on a silica gel column chromatography (ethyl acetate:hexane=1:1) to obtain 6-[3,5-bis(trifluoromethyl)benzyl]-4-chloro-5,6,7,8,9,10-hexahydro-2-(methylthio)-5-oxopyrimido[4,5-b][1,5]diazocine (2.05 g, 70%).

Workup

washwas sequentially washed with water
dry with materiala saturated aqueous solution of sodium chloride, and was then dried over anhydrous sodium sulfate
customremoval of the solvent
customthe residue was purified on a silica gel column chromatography (ethyl acetate:hexane=1:1)

Sources & evidence

ORD record: ord-cf8b3143ec404b608c0f65ccd38fba0e
Source dataset: uspto-grants-2006_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07064119B2

Reaction notes

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