Methylamine → 3-(4-(6-fluoro-1-(phenylsulfonyl)-1H-indol-3-yl)-1H-pyrazol-1-yl)-N-methylazetidine-1-carboxamide

HRID 2274798Notes

Reaction equation

HRID 2274798 reaction equation
C1N=[CH:4][N:3]([C:6]([N:8]2[CH:12]=[N:11][CH:10]=[CH:9]2)=[O:7])C=1.CN.Cl.N1CC(N2[CH:24]=[C:23]([C:25]3[C:33]4[C:28](=[CH:29][C:30]([F:34])=[CH:31][CH:32]=4)[N:27]([S:35]([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=4)(=[O:37])=[O:36])[CH:26]=3)[CH:22]=[N:21]2)C1.CCN(CC)CC>C1COCC1>[F:34][C:30]1[CH:29]=[C:28]2[C:33]([C:25]([C:23]3[CH:22]=[N:21][N:11]([CH:10]4[CH2:9][N:8]([C:6]([NH:3][CH3:4])=[O:7])[CH2:12]4)[CH:24]=3)=[CH:26][N:27]2[S:35]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)(=[O:37])=[O:36])=[CH:32][CH:31]=1

Participants

6

Reactant 4

HCID 6329MethylamineHCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 1180602323-(1-(azetidin-3-yl)-1H-pyrazol-4-yl)-6-fluoro-1-(phenylsulfonyl)-1H-indole hydrochloride2×

Product 1

HCID 1180607113-(4-(6-fluoro-1-(phenylsulfonyl)-1H-indol-3-yl)-1H-pyrazol-1-yl)-N-methylazetidine-1-carboxamideYield 101%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of CDI (62 mg; 0.38 mmol) and MeNH2 (0.20 ml; 0.40 mmol; 2.0 M in THF) of THF (10 mL) was stirred for 1 hour and added a premixed mixture of 3-(1-(azetidin-3-yl)-1H-pyrazol-4-yl)-6-fluoro-1-(phenylsulfonyl)-1H-indole hydrochloride (Intermediate 24; 200 mg; 0.46 mmol) and Et3N (0.10 ml; 0.72 mmol) in THF (2 mL) was stirred at rt for 10 min. The reaction mixture was stirred overnight and concentrated. The residue was diluted with EtOAc (50 mL), washed with water (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated to afford 174 mg (100%) of the title compound as a yellow oil, which was used directly without further purification.

Workup

  1. additionadded
  2. stirringwas stirred at rt for 10 min
  3. stirringThe reaction mixture was stirred overnight
  4. concentrationconcentrated
  5. additionThe residue was diluted with EtOAc (50 mL)
  6. washwashed with water (20 mL)
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-72699ba5df1141eea01edd4b4436da80
Source dataset
uspto-grants-2015_09
Patent number
US09126984B2

Reaction notes

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