6-(4-(trifluoromethyl)-1H-pyrazol-1-yl)pyridin-3-amine → (+/-)-methyl 4-((tetrahydro-2H-pyran-4-yl)((6-(4-(trifluoromethyl)-1H-pyrazol-1-yl)pyridin-3-yl)amino)methyl)benzoate

HRID 1520868Notes

Reaction equation

HRID 1520868 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([C:7]([C:9]2[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][CH:10]=2)=O)[CH2:3][CH2:2]1.[F:19][C:20]([F:34])([F:33])[C:21]1[CH:22]=[N:23][N:24]([C:26]2[N:31]=[CH:30][C:29]([NH2:32])=[CH:28][CH:27]=2)[CH:25]=1.[B][B][B][B][B][B][B][B][B][B]>CO>[O:1]1[CH2:6][CH2:5][CH:4]([CH:7]([NH:32][C:29]2[CH:30]=[N:31][C:26]([N:24]3[CH:25]=[C:21]([C:20]([F:34])([F:33])[F:19])[CH:22]=[N:23]3)=[CH:27][CH:28]=2)[C:9]2[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][CH:10]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 641732966-(4-(trifluoromethyl)-1H-pyrazol-1-yl)pyridin-3-amineHCID 68156933methyl 4-(tetrahydro-2H-pyran-4-carbonyl)benzoateHCID 178419135HCID 178419135, compound

Product 1

HCID 68156806(+/-)-methyl 4-((tetrahydro-2H-pyran-4-yl)((6-(4-(trifluoromethyl)-1H-pyrazol-1-yl)pyridin-3-yl)amino)methyl)benzoateYield 78%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A round bottom flask was charged with methyl 4-(tetrahydro-2H-pyran-4-carbonyl)benzoate (150 mg, 572 mmol), 6-(4-(trifluoromethyl)-1H-pyrazol-1-yl)pyridin-3-amine (130 mg, 572 mmol) and MeOH (1.2 mL). Decaborane reagent (26.4 mg, 229 mmol) was added in one portion and the reaction stirred over the week-end. The reaction mixture was quenched with HCl solution (1 N, aq.) and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. Purification by silica gel flash chromatography (ethyl acetate/heptane) provide (±)-methyl 4-((tetrahydro-2H-pyran-4-yl)((6-(4-(trifluoromethyl)-1H-pyrazol-1-yl)pyridin-3-yl)amino)methyl)benzoate (206 mg, 78%) as a colorless gum. MS (M+1): 461.3.

Workup

  1. customThe reaction mixture was quenched with HCl solution (1 N, aq.)
  2. extractionextracted with EtOAc twice
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customPurification by silica gel flash chromatography (ethyl acetate/heptane)

Sources & evidence

ORD record
ord-d06a1fd53b68450f9ca2b3cdc5e7c970
Source dataset
uspto-grants-2015_07
Patent number
US09073871B2

Reaction notes

Loading…