Pyrrolidine → (1-(5-(2-Fluorophenyl)pyrimidin-2-yl)-3-(methylsulfinyl)-1H-indol-6-yl)(pyrrolidin-1-yl)methanone

HRID 630469Notes

Reaction equation

HRID 630469 reaction equation
OC1SC2C=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.C(N(C(C)C)CC)(C)C.N1CCCC1.[F:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[C:32]1[CH:33]=[N:34][C:35]([N:38]2[C:46]3[C:41](=[CH:42][CH:43]=[C:44]([C:47]([OH:49])=O)[CH:45]=3)[C:40]([S:50]([CH3:52])=[O:51])=[CH:39]2)=[N:36][CH:37]=1>ClCCl>[F:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[C:32]1[CH:37]=[N:36][C:35]([N:38]2[C:46]3[C:41](=[CH:42][CH:43]=[C:44]([C:47]([N:6]4[CH2:5][CH2:7][CH2:8][CH2:9]4)=[O:49])[CH:45]=3)[C:40]([S:50]([CH3:52])=[O:51])=[CH:39]2)=[N:34][CH:33]=1

Participants

6

Reactant 4

HCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 1186660891-(5-(2-Fluorophenyl)pyrimidin-2-yl)-3-(methylsulfinyl)-1H-indole-6-carboxylic acidHCID 178517143HCID 178517143, compound

Product 1

HCID 118671731(1-(5-(2-Fluorophenyl)pyrimidin-2-yl)-3-(methylsulfinyl)-1H-indol-6-yl)(pyrrolidin-1-yl)methanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

EDCxHCl (115 mg, 0.60 mmol), hydroxybenzothiazol (82 mg, 0.60 mmol), diisopropylethylamine (0.35 ml, 2.02 mmol) and pyrrolidine (0.05 mL, 0.60 mmol) were added to an ice-cooled suspension of 51e) (200 mg, 0.50 mmol) in dichloromethane (10 mL). The reaction mixture was stirred at room temperature for 16 h and then diluted with dichloromethane (40 mL). The organic phase was successively washed with saturated ammonium chloride solution (2×50 mL), saturated sodium hydrogen carbonate solution (2×30 mL), water (30 mL), and brine (30 mL), dried over anhydrous sodium sulfate and evaporated. The residue was purified by column chromatography [100-200 mesh silica; 2% methanol in dichloromethane]. White solid. Yield: 65 mg (28% of theory). HPLC-MS (method 5): Rt=3.13 min; m/z [M+H]+=449.1

Workup

  1. temperaturecooled
  2. washThe organic phase was successively washed with saturated ammonium chloride solution (2×50 mL), saturated sodium hydrogen carbonate solution (2×30 mL), water (30 mL), and brine (30 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. customevaporated
  5. customThe residue was purified by column chromatography [100-200 mesh silica; 2% methanol in dichloromethane]

Sources & evidence

ORD record
ord-87f2220d03154137b30b68dade8f739e
Source dataset
uspto-grants-2016_04
Patent number
US09315490B2

Reaction notes

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