N,N-Diethylaniline → 2-Chloro-4-(3-chloro-4-methoxybenzylamino)-5-ethoxycarbonylpyrimidine

HRID 917603Notes

Reaction equation

O[C:2]1[N:7]=[C:6]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([Cl:18])[CH:11]=2)[C:5]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:4][N:3]=1.CCN(C1C=CC=CC=1)CC.P(Cl)(Cl)([Cl:37])=O>O>[Cl:37][C:2]1[N:7]=[C:6]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([Cl:18])[CH:11]=2)[C:5]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:4][N:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 2-hydroxy-4-(3-chloro-4-methoxybenzylamino)-5-ethoxycarbonylpyrimidine (prepared in Example 92) 500 mg, diethylaniline 2 ml and phosphoryl chloride 4 ml is stirred at 80° C. for 30 minutes and then at 100° C. for 5 hours. After cooling, the reaction solution is poured into water in ice and the mixture is stirred at room temperature for 30 minutes. The product is extracted with ethyl acetate and the organic layer is washed with water and an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue is purified by silica gel chromatography (silica gel 7 g, solvent; chloroform) to give 2-chloro-4-(3-chloro-4-methoxybenzylamino)-5-ethoxycarbonylpyrimidine as a slightly yellow crystalline powder, 375 mg. mp 114-115° C. MS(m/z): 356(M+H)+

Workup

waitat 100° C. for 5 hours
temperatureAfter cooling
stirringthe mixture is stirred at room temperature for 30 minutes
extractionThe product is extracted with ethyl acetate
washthe organic layer is washed with water
dry with materialan aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate
concentrationconcentrated in vacuo
customThe residue is purified by silica gel chromatography (silica gel 7 g, solvent; chloroform)

Sources & evidence

ORD record: ord-b5c019f7d92640fc9254607d4f0875fe
Source dataset: uspto-grants-2007_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07273868B2

Reaction notes

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