Ammonium Chloride → HCID 11639916, compound

HRID 2113701Notes

Reaction equation

HRID 2113701 reaction equation
[CH:1]1([N:6]2[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:15]4[N:19]([C:20]5[CH:28]=[CH:27][C:23](C(O)=O)=[CH:22][CH:21]=5)[N:18]=[CH:17][CH:16]=4)[CH:13]=3)[C:8]([CH2:29][CH3:30])=[N:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C1C[N:34]([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[Cl-].[NH4+].[C:85]([O-:88])(O)=O.[Na+]>C(OCC)(=O)C.CN(C)C=O>[CH:1]1([N:6]2[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:15]4[N:19]([C:20]5[CH:28]=[CH:27][C:23]([C:85]([NH2:34])=[O:88])=[CH:22][CH:21]=5)[N:18]=[CH:17][CH:16]=4)[CH:13]=3)[C:8]([CH2:29][CH3:30])=[N:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

9

Reactant 6

HCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2724699PyBOPHCID 11524159HCID 11524159, compound

Product 1

HCID 11639916HCID 11639916, compoundYield 62%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-[5-(1-Cyclopentyl-3-ethyl-1H-indazol-6-yl)-1H-pyrazol-1-yl]benzoic acid (7 mg, 0.02 mmol), PYBOP (14 mg, 0.026 mmol), 1.0 mL of N,N-dimethylformamide, 1-hydroxybenzotriazole (3.5 mg, 0.026 mmol), N,N-diisopropylethylamine (12 uL, 0.070 mmol) and ammonium chloride (1.9 mg, 0.035 mmol) were combined in a 1-neck round-bottom flask and stirred at room temperature for two hours. The mixture was treated with 10 mL of saturated aqueous NaHCO3 and 10 mL of ethyl acetate. The organic layer was separated, dried over sodium sulfate, filtered and approximately 500 mg of silica gel was added. The mixture was evaporated to dryness under reduced pressure and the residue was purified by column chromatography over silica gel eluting with a gradient of 10% ethyl acetate in hexanes for 5 minutes and then increasing linearly to 100% ethyl acetate at 25 minutes to yield 4-[5-(1-cyclopentyl-3-ethyl-1H-indazol-6-yl)-1H-pyrazol-1-yl]benzamide (5 mg, 62%) as a white solid. LC/MS (EI) tR 4.09 (Method C), m/z 400.2 (M++1). 1H NMR (CDCl3 300 MHz) δ 1.4 (t, 3H); 1.6 (m, 2H); 1.8 (m, 2H); 2.1 (m, 4H); 3.0 (q, 2H); 4.8 (m, 1H); 5.7 (br s, 1H); 6.0 (br s, 1H); 6.6 (s, 1H); 6.9 (d, 1H); 7.3-7.5 (m, 3H); 7.6 (d, 1H); 7.8 (m, 3H).

Workup

  1. customThe organic layer was separated
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. additionapproximately 500 mg of silica gel was added
  5. customThe mixture was evaporated to dryness under reduced pressure
  6. customthe residue was purified by column chromatography over silica gel eluting with a gradient of 10% ethyl acetate in hexanes for 5 minutes
  7. temperatureincreasing linearly to 100% ethyl acetate at 25 minutes

Sources & evidence

ORD record
ord-ab3767a2b14846be9b1a1008187b919b
Source dataset
uspto-grants-2008_10
Patent number
US07432266B2

Reaction notes

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