Ammonium Chloride → (R)-[4-(3-isopropenyl-5-trifluoromethyl-benzenesulfonylamino)-4,5,6,7-tetrahydro-indazol-1-yl]-acetic acid ethyl ester

HRID 1645162Notes

Reaction equation

HRID 1645162 reaction equation
[CH2:1]([O:3][C:4](=[O:30])[CH2:5][N:6]1[C:14]2[CH2:13][CH2:12][CH2:11][C@@H: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)[CH3:2].[CH3:31][C:32](C)([O-])[CH3:33].[K+].C(B1OC(C)(C)C(C)(C)O1)(C)=C.[Cl-].[NH4+]>CN(C)C=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:3][C:4](=[O:30])[CH2:5][N:6]1[C:14]2[CH2:13][CH2:12][CH2:11][C@@H:10]([NH:15][S:16]([C:19]3[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[C:21]([C:32]([CH3:33])=[CH2:31])[CH:20]=3)(=[O:18])=[O:17])[C:9]=2[CH:8]=[N:7]1)[CH3:2]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 109974264,4,5,5-Tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolaneHCID 23665647Potassium tert-butoxideHCID 44611775HCID 44611775, compound

Product 1

HCID 59152889(R)-[4-(3-isopropenyl-5-trifluoromethyl-benzenesulfonylamino)-4,5,6,7-tetrahydro-indazol-1-yl]-acetic acid ethyl esterYield 36.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of [(R)-4-(3-bromo-5-trifluoromethyl-benzenesulfonylamino)-4,5,6,7-tetrahydro-indazol-1-yl]-acetic acid ethyl ester (Example 1-1, 100 mg, 0.196 mmol) in N,N-dimethylformamide (2 mL) in a microwave vial (5 mL), tetrakis(triphenylphosphine)palladium(0) (22 mg, 0.19 mmol), potassium tert-butoxide (45 mg, 0.4 mmol) and isopropenyl boronic acid pinacol ester (55 μl, 0.294 mmol) were added. After being heated in a microwave oven (130° C., 15 min.), the mixture was poured into aq. ammonium chloride (10 mL) and extracted with dichloromethane (20 mL×3). The combined organic layers were washed with water (10 mL×3) and brine (20 mL), dried over sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography (gradient elution, 0-5% methanol in dichloromethane) to afford [(R)-4-(3-isopropenyl-5-trifluoromethyl-benzene-sulfonylamino)-4,5,6,7-tetrahydro-indazol-1-yl]-acetic acid ethyl ester (34 mg, 36.8%) as a white solid, MS calcd. for C21H24F3N3O4S 471, obsd. (ESI+) [(M+H)+] 472.

Workup

  1. extractionextracted with dichloromethane (20 mL×3)
  2. washThe combined organic layers were washed with water (10 mL×3) and brine (20 mL)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography (gradient elution, 0-5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-f2dcc566ef784746a174ac625fb306a0
Source dataset
uspto-grants-2012_02
Patent number
US08124641B2

Reaction notes

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