Potassium Phosphate, Tribasic → [4-(3-Cyclopropyl-5-trifluoromethyl-benzenesulfonylamino)-4,5,6,7-tetrahydro-indazol-1-yl]-acetic acid

HRID 2387561Notes

Reaction equation

HRID 2387561 reaction equation
C([O:3][C:4](=[O:30])[CH2:5][N:6]1[C:14]2[CH2:13][CH2:12][CH2:11][CH:10]([NH:15][S:16]([C:19]3[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[C:21](Br)[CH:20]=3)(=[O:18])=[O:17])[C:9]=2[CH:8]=[N:7]1)C.[CH:31]1(B(O)O)[CH2:33][CH2:32]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:31]1([C:21]2[CH:20]=[C:19]([S:16]([NH:15][CH:10]3[CH2:11][CH2:12][CH2:13][C:14]4[N:6]([CH2:5][C:4]([OH:3])=[O:30])[N:7]=[CH:8][C:9]3=4)(=[O:18])=[O:17])[CH:24]=[C:23]([C:25]([F:26])([F:27])[F:28])[CH:22]=2)[CH2:33][CH2:32]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 44611232HCID 44611232, compound

Product 1

HCID 44610990[4-(3-Cyclopropyl-5-trifluoromethyl-benzenesulfonylamino)-4,5,6,7-tetrahydro-indazol-1-yl]-acetic acidYield 18.9%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
180 °C

Procedure

[4-(3-Bromo-5-trifluoromethyl-benzenesulfonylamino)-4,5,6,7-tetrahydro-indazol-1-yl]-acetic acid ethyl ester (51.0 mg, 0.10 mmol, example 1-8), cyclopropylboronic acid (10.4 mg, 0.12 mmol), palladium (II) acetate (1.2 mg, 0.005 mmol), tricyclohexylphosphine (2.8 mg, 0.010 mmol) and potassium phosphate (76.4 mg, 0.36 mmol) were dissolved in toluene (0.5 mL) and water (0.1 mL). The mixture was heated in a microwave oven at 180° C. for 30 minutes under an argon atmosphere. The resulting mixture was quenched with saturated ammonium chloride solution, and then extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by preparative HPLC to afford [4-(3-cyclopropyl-5-trifluoromethyl-benzenesulfonylamino)-4,5,6,7-tetrahydro-indazol-1-yl]-acetic acid (4.2 mg, 18.9%) as a white powder. 1H NMR (400 MHz, CD3OD) δ ppm 7.97 (s, 1H), 7.85 (s, 1H), 7.70 (s, 1H), 6.65 (s, 1H), 4.80 (s, 2H), 4.41 (t, 1H), 2.50 (m, 2H), 2.20 (m, 1H), 2.00-1.73 (m, 4H), 1.15 (, 2H), 0.85 (m, 2H). MS cald. for C19H20F3N3O4S 443, obsd. (ESI+) [(M+H)+] 444.

Workup

  1. customThe resulting mixture was quenched with saturated ammonium chloride solution
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-c83f50a02d0046e7bad4ddd56d77bb1d
Source dataset
uspto-grants-2012_09
Patent number
US08268870B2

Reaction notes

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