Diisopropylethylamine → (S)-methyl 2-chloro-6-((1-methoxy-1-oxopropan-2-yl)amino)pyrimidine-4-carboxylate

HRID 1752402Notes

Reaction equation

HRID 1752402 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[C:4](Cl)[N:3]=1.Cl.[NH2:14][C@@H:15]([CH3:20])[C:16]([O:18][CH3:19])=[O:17].CCN(C(C)C)C(C)C>C(#N)C>[Cl:1][C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[C:4]([NH:14][C@@H:15]([CH3:20])[C:16]([O:18][CH3:19])=[O:17])[N:3]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 239689Methyl 2,4-dichloropyrimidine-6-carboxylateHCID 2733257Alanine methyl ester hydrochloride

Product 1

HCID 89422478(S)-methyl 2-chloro-6-((1-methoxy-1-oxopropan-2-yl)amino)pyrimidine-4-carboxylateYield 61.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of methyl 2,6-dichloropyrimidine-4-carboxylate (5.175 g, 25.00 mmol) in acetonitrile (100 mL) was added (S)-methyl 2-aminopropanoate hydrochloride (3.497 g, 25.05 mmol) and iPr2NEt (9.6 mL, 55.1 mmol). The mixture was heated at 50° C. overnight then concentrated in vacuo. The residue was chromatographed over silica gel with 30-70% EtOAc in hexanes. The product fractions were evaporated in vacuo to yield (S)-methyl 2-chloro-6-((1-methoxy-1-oxopropan-2-yl)amino)pyrimidine-4-carboxylate as a thick yellow-orange oil (4.194 g, 15.33 mmol, 61% yield). LC/MS: m/z=274.2 [M+H]+.

Workup

  1. concentrationthen concentrated in vacuo
  2. customThe residue was chromatographed over silica gel with 30-70% EtOAc in hexanes
  3. customThe product fractions were evaporated in vacuo

Sources & evidence

ORD record
ord-bd9a1756a23c436db3dd3a6e275afdf3
Source dataset
uspto-grants-2015_10
Patent number
US09163008B2

Reaction notes

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