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 2200946Notes

Reaction equation

HRID 2200946 reaction equation
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]

Participants

5

Reactant 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

Product 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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-658ed240efe146da99da6b5024608fb8
Source dataset
uspto-grants-2016_06
Patent number
US09359362B2

Reaction notes

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