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

HRID 2387561ノート

反応式

HRID 2387561 の反応式
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

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 44611232[4-(3-Bromo-5-trifluoromethyl-benzenesulfonylamino)-4,5,6,7-tetrahydro-indazol-1-yl]-acetic acid ethyl ester

生成物 1

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

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 1140Toluene溶媒

反応条件

温度
180 °C

実験手順

[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.

後処理

  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

出典と根拠

ORDレコード
ord-c83f50a02d0046e7bad4ddd56d77bb1d
出典データセット
uspto-grants-2012_09
特許番号
US08268870B2

反応ノート

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