4-Chloro-2-(methylthio)pyrimidine-5-carboxylic acid ethyl ester → ethyl 4-((1S,2S)-2-hydroxycyclopentylamino)-2-(methylthio)pyrimidine-5-carboxylate

HRID 2280689Notes

Reaction equation

Cl[C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][N:5]=[C:4]([S:13][CH3:14])[N:3]=1.Cl.[NH2:16][C@H:17]1[CH2:21][CH2:20][CH2:19][C@@H:18]1[OH:22].CCN(C(C)C)C(C)C>C(O)C>[OH:22][C@H:18]1[CH2:19][CH2:20][CH2:21][C@@H:17]1[NH:16][C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][N:5]=[C:4]([S:13][CH3:14])[N:3]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of ethyl 4-chloro-2-(methylthio)pyrimidine-5-carboxylate (1.4 g, 6.0 mmol), (1S,2S)-2-aminocyclopentanol hydrochloride (0.7 g, 6.9 mmol) and DIEA (1.0 g) in ethanol (20 mL) was heated at 60° C. for 15 h. After being cooled to room temperature, the reaction solution was concentrated and the residue was purified on silica gel column (eluting with 0-10% ethyl acetate in petroleum ether) to give ethyl 4-((1S,2S)-2-hydroxycyclopentylamino)-2-(methylthio)pyrimidine-5-carboxylate (1.3 g, 4.37 mmol, yield 73%) as a white solid. MS (ESI): m/z 298.5 [M+1]+.

Workup

temperatureAfter being cooled to room temperature
concentrationthe reaction solution was concentrated
customthe residue was purified on silica gel column (eluting with 0-10% ethyl acetate in petroleum ether)

Sources & evidence

ORD record: ord-f9915cd72184477d883d49912ad1a894
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09139534B2

Reaction notes

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