Methyl chloroformate → Ethyl 4-(4-(6-((cyclopropylmethyl)(propyl)amino)pyrimidine-4-carboxamido)phenylsulfonyl)butanoate

HRID 1946809Notes

Reaction equation

[CH:1]1([CH2:4][N:5]([CH2:15][CH2:16][CH3:17])[C:6]2[N:11]=[CH:10][N:9]=[C:8]([C:12]([OH:14])=O)[CH:7]=2)[CH2:3][CH2:2]1.C(N(CC)CC)C.ClC(OC)=O.[NH2:30][C:31]1[CH:36]=[CH:35][C:34]([S:37]([CH2:40][CH2:41][CH2:42][C:43]([O:45][CH2:46][CH3:47])=[O:44])(=[O:39])=[O:38])=[CH:33][CH:32]=1>C(Cl)Cl.O>[CH:1]1([CH2:4][N:5]([CH2:15][CH2:16][CH3:17])[C:6]2[N:11]=[CH:10][N:9]=[C:8]([C:12]([NH:30][C:31]3[CH:36]=[CH:35][C:34]([S:37]([CH2:40][CH2:41][CH2:42][C:43]([O:45][CH2:46][CH3:47])=[O:44])(=[O:39])=[O:38])=[CH:33][CH:32]=3)=[O:14])[CH:7]=2)[CH2:2][CH2:3]1

Participants

Conditions

Temperature: 0 °C

Procedure

A cooled (0° C.) solution of 6-((cyclopropylmethyl)(propyl)amino)pyrimidine-4-carboxylic acid (Intermediate 21, 100 mg; 0.43 mmol) in DCM (5 ml) was treated with triethylamine (0.1 ml; 0.72 mmol) and methyl chloroformate (0.060 ml; 0.78 mmol). After stirring at 0° C. for 30 minutes, ethyl 4-(4-aminophenylsulfonyl)butanoate (Intermediate 48, 125 mg; 0.46 mmol) was added. After stirring at 0° C. for 5 minutes and RT for 1 hour water was added and the mixture passed through a hydrophobic frit. The solvent was removed in vacuo and the residue purified by column chromatography (silica) eluting with petroleum ether containing increasing amounts of EtOAc to give ethyl 4-(4-(6-((cyclopropylmethyl)(propyl)amino)pyrimidine-4-carboxamido)phenylsulfonyl)butanoate. The intermediate was redissolved in ethanol (3 ml) and treated with 10% sodium hydroxide solution (2 ml). After stirring at RT for 18 hours the mixture was acidified to pH 3 with dilute HCl and EtOAc added. The organic phase was removed in vacuo and the aqueous phase extracted with EtOAc. The combined organic extracts were passed through a hydrophobic frit and the solvent removed in vacuo. The residue was triturated with diisopropyl ether and allowed to dry to give the title compound as an off-white solid.

Workup

additionwas added
customThe solvent was removed in vacuo
customthe residue purified by column chromatography (silica)
washeluting with petroleum ether containing
temperatureincreasing amounts of EtOAc

Sources & evidence

ORD record: ord-8878887864864ed6bc2e050936cebb18
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08399448B2

Reaction notes

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