Pyridine → N-{(7R)-6-Cyano-7-(4-cyanophenyl)-5-methyl-4-[3-(trifluoromethyl)phenyl]-4,7-dihydro[1,2,4]-triazolo[1,5-a]pyrimidin-2-yl}-2,2-difluoro-1-methylcyclopropanecarboxamide

HRID 2200946

反応式

HRID 2200946 の反応式
Cl.[NH2:2][C:3]1[N:32]=[C:6]2[N:7]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=3)[C:8]([CH3:21])=[C:9]([C:19]#[N:20])[C@@H:10]([C:11]3[CH:16]=[CH:15][C:14]([C:17]#[N:18])=[CH:13][CH:12]=3)[N:5]2[N:4]=1.N1C=CC=CC=1.[F:39][C:40]1([F:47])[CH2:42][C:41]1([CH3:46])[C:43](Cl)=[O:44]>C1COCC1>[C:19]([C:9]1[C@@H:10]([C:11]2[CH:16]=[CH:15][C:14]([C:17]#[N:18])=[CH:13][CH:12]=2)[N:5]2[N:4]=[C:3]([NH:2][C:43]([C:41]3([CH3:46])[CH2:42][C:40]3([F:47])[F:39])=[O:44])[N:32]=[C:6]2[N:7]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:29])([F:31])[F:30])[CH:23]=2)[C:8]=1[CH3:21])#[N:20]

参加物

5

反応物 3

HCID 1049PyridineHCID 146952322,2-Difluoro-1-methylcyclopropane-1-carbonyl chlorideHCID 66627899(7R)-2-amino-7-(4-cyanophenyl)-5-methyl-4-[3-(trifluoromethyl)phenyl]-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-carbonitrile hydrochloride

生成物 1

HCID 66628463N-{(7R)-6-Cyano-7-(4-cyanophenyl)-5-methyl-4-[3-(trifluoromethyl)phenyl]-4,7-dihydro[1,2,4]-triazolo[1,5-a]pyrimidin-2-yl}-2,2-difluoro-1-methylcyclopropanecarboxamide

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

Under an atmosphere of argon protective gas, (7R)-2-amino-7-(4-cyanophenyl)-5-methyl-4-[3-(trifluoromethyl)phenyl]-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-carbonitrile hydrochloride (30 mg, 66 μmol) was dissolved in abs. pyridine (1.5 ml). At room temperature, a solution of 2,2-difluoro-1-methylcyclopropanecarbonyl chloride (25 mg, 165 μmol, 2.5 eq.) in abs. THF (1 ml) was added in two portions. Once analysis of the reaction by HPLC showed substantial conversion (3 h), the reaction mixture was concentrated under reduced pressure and directly purified by preparative HPLC (Kromasil C18 column, 5 μm, 50×20 mm; mobile phase: acetonitrile-water-0.1% TFA). After lyophilization, the product was obtained as a solid (26.8 mg, 76% of theory).

後処理

  1. customAt room temperature
  2. customOnce analysis of the reaction by HPLC
  3. customconversion (3 h)
  4. concentrationthe reaction mixture was concentrated under reduced pressure
  5. customdirectly purified by preparative HPLC (Kromasil C18 column, 5 μm, 50×20 mm; mobile phase: acetonitrile-water-0.1% TFA)
  6. customAfter lyophilization, the product was obtained as a solid (26.8 mg, 76% of theory)

出典と根拠

ORDレコード
ord-658ed240efe146da99da6b5024608fb8
出典データセット
uspto-grants-2016_06
特許番号
US09359362B2

関連ノート

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