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

HRID 467806ノート

反応式

HRID 467806 の反応式
[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]

参加物

5

反応物 3

HCID 74508Pyrimidine, 2,4-dichloro-5-methyl-HCID 81531DiisopropylethylamineHCID 24896496(1S,2R)-2-aminocyclopentanecarboxylic acid isopropylamide

生成物 1

HCID 57748023(1S,2R)-2-(2-chloro-5-methyl-pyrimidin-4-ylamino)-cyclopentanecarboxylic Acid Isopropylamide

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒

反応条件

温度
70 °C

実験手順

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.

後処理

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

出典と根拠

ORDレコード
ord-3b492c413f8244c3b2f5b177857cd7fa
出典データセット
uspto-grants-2014_01
特許番号
US08623887B2

反応ノート

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