Hydrochloric Acid → HCID 73297045, compound

HRID 592412Notes

Reaction equation

HRID 592412 reaction equation
C([O-])(=O)C.[NH4+].[C:6]([C:9]1[N:14]=[CH:13][C:12]([NH:15][C:16]2[N:21]=[C:20]([CH2:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[C:30]3([C:33]([NH2:35])=[O:34])[CH2:32][CH2:31]3)[C:19]([Cl:36])=[CH:18][N:17]=2)=[CH:11][CH:10]=1)(=O)[CH3:7].C([BH3-])#[N:38].[Na+].Cl>CO.C1COCC1.O>[NH2:38][CH:6]([C:9]1[N:14]=[CH:13][C:12]([NH:15][C:16]2[N:21]=[C:20]([CH2:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[C:30]3([C:33]([NH2:35])=[O:34])[CH2:31][CH2:32]3)[C:19]([Cl:36])=[CH:18][N:17]=2)=[CH:11][CH:10]=1)[CH3:7]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 517165Ammonium AcetateHCID 5003444Sodium cyanoborohydride2×HCID 73297044HCID 73297044, compound

Product 1

HCID 73297045HCID 73297045, compoundYield 85.6%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Ammonium acetate (0.587 g, 7.61 mmol) was added to a solution of 1-(2-(2-(2-((6-Acetylpyridin-3-yl)amino)-5-chloropyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide 32 (0.166 g, 0.381 mmol) in MeOH (5 mL) and THF (5 mL) and the mixture was stirred for 20 minutes under a nitrogen atmosphere. Sodium cyanoborohydride (0.017 g, 0.27 mmol) was added and the mixture was stirred for 5 hours. Additional sodium cyanoborohydride (0.017 g, 0.27 mmol) was added and the mixture was stirred for 22 hours at 35° C. Water (10 mL) was added to the mixture which was then acidified with 20% aqueous hydrochloride (10 mL). The aqueous phase was washed with Et2O (2×30 mL) and then basified with solid potassium hydroxide to pH 10. The aqueous phase was extracted with DCM (3×30 mL) and the combined organics were washed with brine, dried (Na2SO4), adsorbed onto silica and purified by silica column chromatography (Combiflash Rf, 12 g SiO2 Cartridge, 0-30% MeOH in DCM) to give the title compound 33 as a white solid (0.101 g, 60%). LCMS-B: rt 4.32 min; m/z 437 [M+H]+.

Workup

  1. stirringthe mixture was stirred for 5 hours
  2. stirringthe mixture was stirred for 22 hours at 35° C
  3. washThe aqueous phase was washed with Et2O (2×30 mL)
  4. extractionThe aqueous phase was extracted with DCM (3×30 mL)
  5. washthe combined organics were washed with brine
  6. dry with materialdried (Na2SO4)
  7. custompurified by silica column chromatography (Combiflash Rf, 12 g SiO2 Cartridge, 0-30% MeOH in DCM)

Sources & evidence

ORD record
ord-77b0edcb93784adfa399e36224a51527
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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