Ammonium Chloride → HCID 86692622, compound

HRID 1748675Notes

Reaction equation

HRID 1748675 reaction equation
[BH4-].[Li+].C([O:5][C:6](=O)[C:7]([N:10]1[CH2:15][CH2:14][C:13]([C:41]#[N:42])([C:16]2[CH:21]=[CH:20][C:19]([NH:22][C:23]([C:25]3[CH:26]=[N:27][N:28]([C:31]4[CH:36]=[CH:35][C:34]([C:37]([F:40])([F:39])[F:38])=[CH:33][N:32]=4)[C:29]=3[CH3:30])=[O:24])=[CH:18][N:17]=2)[CH2:12][CH2:11]1)([CH3:9])[CH3:8])C.[BH4-].[Na+].[Cl-].[NH4+]>O1CCCC1.CO>[C:41]([C:13]1([C:16]2[N:17]=[CH:18][C:19]([NH:22][C:23]([C:25]3[CH:26]=[N:27][N:28]([C:31]4[CH:36]=[CH:35][C:34]([C:37]([F:39])([F:40])[F:38])=[CH:33][N:32]=4)[C:29]=3[CH3:30])=[O:24])=[CH:20][CH:21]=2)[CH2:12][CH2:11][N:10]([C:7]([CH3:8])([CH3:9])[CH2:6][OH:5])[CH2:15][CH2:14]1)#[N:42]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 4148881Lithium borohydride2×HCID 4311764Sodium borohydrideHCID 86692621HCID 86692621, compound

Product 1

HCID 86692622HCID 86692622, compoundYield 11.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-Bromo-2-methylpropanoic acid ethyl ester (193 μl) was added to a suspension of N-[6-(4-cyanopiperidin-4-yl)pyridin-3-yl]-5-methyl-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carboxamide (455 mg) described in Reference Example 169 and potassium carbonate (276 mg) in N,N-dimethylformamide (3.3 ml) and stirred at 50° C. for 12 hours. Then, 2-bromo-2-methylpropanoic acid ethyl ester (100 μl) and potassium carbonate (276 mg) were added and stirred at 50° C. for 5 hours and at 80° C. for 3 hours. Further, 2-bromo-2-methylpropanoic acid ethyl ester (100 μl) was added and stirred at 80° C. for 3 hours. Water was added to the reaction solution, the precipitated solid was purified with silica gel chromatography (chloroform/methanol) to give 2-{4-cyano-4-[5-({5-methyl-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carbonyl}amino)pyridin-2-yl]piperidin-1-yl}-2-methylpropanoic acid ethyl ester (320 mg) as a white solid. MS (ESI) m/z: 570 (M+H)+. (2) Lithium borohydride (25 mg) was added to a solution of 2-{4-cyano-4-[5-({5-methyl-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carbonyl}amino)pyridin-2-yl]piperidin-1-yl}-2-methylpropanoic acid ethyl ester (320 mg) in tetrahydrofuran (3.7 ml) and stirred at room temperature for 1.5 hours. Then, lithium borohydride (25 mg) was added and stirred at 80° C. for 2 hours. To the reaction solution, were added methanol (1.5 ml) and sodium borohydride (85 mg), and stirred at room temperature for an hour. A saturated aqueous solution of ammonium chloride was added to the reaction solution, extracted with dichloromethane, and the organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting residue was purified with silica gel chromatography (chloroform/methanol) to give the titled compound (35 mg) as a white solid.

Workup

  1. stirringstirred at 80° C. for 2 hours
  2. stirringstirred at room temperature for an hour
  3. extractionextracted with dichloromethane
  4. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified with silica gel chromatography (chloroform/methanol)

Sources & evidence

ORD record
ord-27c5a17f9dff47909cf78ba3b3a6b226
Source dataset
uspto-grants-2015_10
Patent number
US09150555B2

Reaction notes

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