Diisopropylethylamine → (S)-methyl 2-((6-carbamoyl-2-chloropyrimidin-4-yl)amino)propanoate

HRID 1752389Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6]([C:8]([NH2:10])=[O:9])[CH:5]=[C:4](Cl)[N:3]=1.Cl.[NH2:13][C@@H:14]([CH3:19])[C:15]([O:17][CH3:18])=[O:16].CCN(C(C)C)C(C)C>C(#N)C>[C:8]([C:6]1[N:7]=[C:2]([Cl:1])[N:3]=[C:4]([NH:13][C@@H:14]([CH3:19])[C:15]([O:17][CH3:18])=[O:16])[CH:5]=1)(=[O:9])[NH2:10]

Participants

Conditions

Temperature: 50 °C

Procedure

To a mixture of 2,6-dichloropyrimidine-4-carboxamide (4.800 g, 25.00 mmol) in acetonitrile (100 mL) was added (S)-methyl 2-aminopropanoate hydrochloride (3.565 g, 25.54 mmol) and iPr2NEt (9.60 mL, 55.11 mmol). The mixture was heated at 50° C. overnight then concentrated in vacuo. The residue was chromatographed over silica gel with 20-60% acetone in hexanes. Two isomers were obtained from the chromatography. The first isomer to elute was (S)-methyl 2-((6-carbamoyl-2-chloropyrimidin-4-yl)amino)propanoate (A) and the second to elute was (S)-methyl 2-((4-carbamoyl-6-chloropyrimidin-2-yl)amino)propanoate (B). Separately, the appropriate product fractions were evaporated in vacuo to give (S)-methyl 2-((6-carbamoyl-2-chloropyrimidin-4-yl)amino)propanoate (A) as a pale tan powder (5.133 g, 19.84 mmol, 79% yield). LC/MS: m/z=259.2 [M+H]+ and (S)-methyl 2-((4-carbamoyl-6-chloropyrimidin-2-yl)amino)propanoate (B) as a tan powder (0.652 g, 2.52 mmol, 10% yield). LC/MS: m/z=259.2 [M+H]+.

Workup

concentrationthen concentrated in vacuo
customThe residue was chromatographed over silica gel with 20-60% acetone in hexanes
customTwo isomers were obtained from the chromatography
washThe first isomer to elute
washthe second to elute
customSeparately, the appropriate product fractions were evaporated in vacuo

Sources & evidence

ORD record: ord-4499a0926ea8404782049839db2ed2c3
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09163008B2

Reaction notes

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