Pyrimidine, 2,4-dichloro-5-methyl- → (1S,2R)-2-(2-chloro-5-methyl-pyrimidin-4-ylamino)-cyclopentanecarboxylic Acid Isopropylamide

HRID 467806Notes

Reaction equation

[CH3:1][C:2]1[C:3](Cl)=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.CCN(C(C)C)C(C)C.[CH:19]([NH:22][C:23]([C@H:25]1[CH2:29][CH2:28][CH2:27][C@H:26]1[NH2:30])=[O:24])([CH3:21])[CH3:20]>CC(N(C)C)=O>[CH:19]([NH:22][C:23]([C@H:25]1[CH2:29][CH2:28][CH2:27][C@H:26]1[NH:30][C:3]1[C:2]([CH3:1])=[CH:7][N:6]=[C:5]([Cl:8])[N:4]=1)=[O:24])([CH3:21])[CH3:20]

Participants

Conditions

Temperature: 70 °C

Procedure

1 g (6.1 mmol, 1 eq) 5-methyl-2,4-dichloropyrimidine (prepared analogously to A-1a) are dissolved in 3 mL DMA and then 5.3 mL (30.5 mmol, 5 eq) Hünig base are added dropwise. 1.03 g (6.1 mmol, 1 eq) (1S,2R)-2-aminocyclopentanecarboxylic acid isopropylamide are added and the reaction mixture is stirred for 1 h at 70° C. HPLC monitoring shows that the reaction is total and only one regioisomer is formed. The reaction mixture is combined with RP gel, the volatile constituents are eliminated in vacuo, the product is purified by column chromatography through an RP phase and isolated (from water/MeCN (+0.2% HCOOH in each case) from 82/18 to 60/40 in 15 min). Corresponding product fractions are combined, freed from the solvent by freeze-drying and 956 mg of C-1d are obtained.

Workup

customonly one regioisomer is formed
customthe product is purified by column chromatography through an RP phase
customisolated (from water/MeCN (+0.2% HCOOH in each case) from 82/18 to 60/40 in 15 min)
customby freeze-drying
custom956 mg of C-1d are obtained

Sources & evidence

ORD record: ord-3b492c413f8244c3b2f5b177857cd7fa
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08623887B2

Reaction notes

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