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

HRID 1645177Notes

Reaction equation

HRID 1645177 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, 1 H), 7.85 (s, 1 H), 7.70 (s, 1 H), 6.65 (s, 1 H), 4.80 (s, 2 H), 4.41 (t, 1 H), 2.50 (m, 2 H), 2.20 (m, 1 H), 2.00-1.73 (m, 4 H), 1.15 (, 2 H), 0.85 (m, 2 H). 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-b27b109e313d428b9b9decfb2264cd7a
Source dataset
uspto-grants-2012_02
Patent number
US08124641B2

Reaction notes

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