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 537494Notes

Reaction equation

HRID 537494 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 (1N, aq.) and extracted with EtOAc twice. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. Purification by slica 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 (1N, 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 slica gel flash chromatography (ethyl acetate/heptane)

Sources & evidence

ORD record
ord-3b2b80f1c7834ca5a5f5e8b59efffe49
Source dataset
uspto-grants-2014_10
Patent number
US08859591B2

Reaction notes

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