Cyclohexanecarbonitrile, 1-amino-, hydrochloride → HCID 24772730, compound

HRID 1696173Notes

Reaction equation

HRID 1696173 reaction equation
[C:1]([C:4]1[CH:5]=[N:6][N:7]2[C:12]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=3)=[C:11]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[Cl:26])[CH:10]=[N:9][C:8]=12)(O)=[O:2].Cl.[C:28]([C:30]1([NH2:36])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1)#[N:29].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl.CN(C)C=O.C(N(CC)CC)C.O>[Cl:26][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[C:11]1[CH:10]=[N:9][C:8]2[N:7]([N:6]=[CH:5][C:4]=2[C:1](=[O:2])[NH:36][C:30]2([C:28]#[N:29])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]2)[C:12]=1[C:13]1[CH:14]=[CH:15][C:16]([Cl:19])=[CH:17][CH:18]=1

Participants

10

Reactant 5

HCID 198262Cyclohexanecarbonitrile, 1-amino-, hydrochlorideHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 67272265HCID 67272265, compound

Product 1

HCID 24772730HCID 24772730, compoundYield 21.1%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6212ChloroformSolvent3×HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 3-carboxy-6-(2-chlorophenyl)-7-(4-chlorophenyl)pyrazolo-[1,5-a]pyrimidine (compound obtained in Reference Example 1-(4); 58 mg) and 1-cyanocyclohexylamine hydrochloride (25 mg) in chloroform (1.0 mL containing amylene) were added a 0.5 M solution of 1-hydroxybenzotriazole monohydrate in chloroform (0.45 mL containing amylene), a 0.5 M solution of 1-(3-dimethylamino-propyl)-3-ethylcarbodiimide hydrochloride in N,N-dimethylformamide (0.45 mL) and triethylamine (63 μL), and the mixture was stirred at room temperature overnight. To the reaction mixture were added an aqueous saturated sodium hydrogencarbonate solution (2 mL), water (2 mL) and chloroform (4 mL), and the mixture was vigorously stirred for 15 minutes. The organic layer was separated, and the aqueous layer was extracted with chloroform (3 mL). The combined organic layer was washed successively with an aqueous saturated sodium hydrogencarbonate solution (3 mL) and brine (3 mL) and concentrated in vacuo. The resultant crude product was purified by liquid chromatograph-mass spectrometer (LCMS, column; XTerra MS C18, solvent; 10 mM ammonium carbonate/methanol 40/60 to 10/90) and lyophilized to give 6-(2-chlorophenyl)-7-(4-chlorophenyl)-3-[N-(1-cyanocyclohexyl)carbamoyl]pyrazolo[1,5-a]pyrimidine (15.6 mg; yield: 21%) as a powder.

Workup

  1. customThe organic layer was separated
  2. extractionthe aqueous layer was extracted with chloroform (3 mL)
  3. washThe combined organic layer was washed successively with an aqueous saturated sodium hydrogencarbonate solution (3 mL) and brine (3 mL)
  4. concentrationconcentrated in vacuo
  5. customThe resultant crude product was purified by liquid chromatograph-mass spectrometer (LCMS, column; XTerra MS C18, solvent; 10 mM ammonium carbonate/methanol 40/60 to 10/90)

Sources & evidence

ORD record
ord-bd72c6172b0944b3992a51caa522dd21
Source dataset
uspto-grants-2012_04
Patent number
US08163759B2

Reaction notes

Loading…