Diiodomethane → {(R)-4-[3-(1-methyl-cyclopropyl)-5-trifluoromethyl-benzenesulfonylamino]-4,5,6,7-tetrahydro-indazol-1-yl}-acetic acid ethyl ester

HRID 2387547Notes

Reaction equation

HRID 2387547 reaction equation
ICI.[CH2:4]([Zn]CC)C.[CH2:9]([O:11][C:12](=[O:40])[CH2:13][N:14]1[C:22]2[CH2:21][CH2:20][CH2:19][C@@H:18]([NH:23][S:24]([C:27]3[CH:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:30]=[C:29]([C:37]([CH3:39])=[CH2:38])[CH:28]=3)(=[O:26])=[O:25])[C:17]=2[CH:16]=[N:15]1)[CH3:10].[Cl-].[NH4+]>C1(C)C=CC=CC=1>[CH2:9]([O:11][C:12](=[O:40])[CH2:13][N:14]1[C:22]2[CH2:21][CH2:20][CH2:19][C@@H:18]([NH:23][S:24]([C:27]3[CH:32]=[C:31]([C:33]([F:35])([F:36])[F:34])[CH:30]=[C:29]([C:37]4([CH3:4])[CH2:39][CH2:38]4)[CH:28]=3)(=[O:26])=[O:25])[C:17]=2[CH:16]=[N:15]1)[CH3:10]

Participants

6

Reactant 4

HCID 6346DiiodomethaneHCID 25517Ammonium ChlorideHCID 59152889(R)-[4-(3-isopropenyl-5-trifluoromethyl-benzenesulfonylamino)-4,5,6,7-tetrahydro-indazol-1-yl]-acetic acid ethyl esterHCID 178418750HCID 178418750, compound

Product 1

HCID 59152883{(R)-4-[3-(1-methyl-cyclopropyl)-5-trifluoromethyl-benzenesulfonylamino]-4,5,6,7-tetrahydro-indazol-1-yl}-acetic acid ethyl esterYield 18%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

To a solution of diiodomethane (1.0 mL, 16 mmol) in toluene (10 mL) was added diethylzinc (15% in hexane, 10 mL, 8.8 mmol) under an argon atmosphere at 0° C. and the mixture was stirred for 15 minutes. To the mixture was added [(R)-4-(3-isopropenyl-5-trifluoromethyl-benzenesulfonylamino)-4,5,6,7-tetrahydro-indazol-1-yl]-acetic acid ethyl ester (0.2 g, 0.46 mmol) in toluene (4 ml) and the mixture was stirred at 0° C. and then room temperature for 4 hours. The mixture was poured into aqueous ammonium chloride (20 mL) and extracted with dichloromethane (30 mL×3). The combined organic layers were washed with water (20 mL×3), then brine (30 mL), dried over sodium sulfate, concentrated and purified by preparative HPLC to afford {(R)-4-[3-(1-methyl-cyclopropyl)-5-trifluoromethyl-benzenesulfonylamino]-4,5,6,7-tetrahydro-indazol-1-yl}-acetic acid ethyl ester (40 mg, 18%) as a white solid. MS calcd. for C22H26F3N3O4S 485, obsd. (ESI+) [(M+H)+] 486.

Workup

  1. stirringthe mixture was stirred at 0° C.
  2. waitroom temperature for 4 hours
  3. extractionextracted with dichloromethane (30 mL×3)
  4. washThe combined organic layers were washed with water (20 mL×3)
  5. dry with materialbrine (30 mL), dried over sodium sulfate
  6. concentrationconcentrated
  7. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-899b8bf90bd649fc98323754457977dd
Source dataset
uspto-grants-2012_09
Patent number
US08268870B2

Reaction notes

Loading…