Sodium hydride → Cyclopropanesulfonic acid [2-(5-fluoro-2-methyl-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carbonyl]-amide

HRID 1801016Notes

Reaction equation

HRID 1801016 reaction equation
[CH:1]1([S:4]([NH2:7])(=[O:6])=[O:5])[CH2:3][CH2:2]1.[H-].[Na+].[F:10][C:11]1[CH:12]=[CH:13][C:14]([CH3:32])=[C:15]([CH:17]2[C:26]([CH3:28])([CH3:27])[CH2:25][C:24]3[C:19](=[CH:20][CH:21]=[C:22]([C:29](O)=[O:30])[CH:23]=3)[NH:18]2)[CH:16]=1.C(N1C=CN=C1)(N1C=CN=C1)=O>CN(C)C=O>[F:10][C:11]1[CH:12]=[CH:13][C:14]([CH3:32])=[C:15]([CH:17]2[C:26]([CH3:27])([CH3:28])[CH2:25][C:24]3[C:19](=[CH:20][CH:21]=[C:22]([C:29]([NH:7][S:4]([CH:1]4[CH2:3][CH2:2]4)(=[O:6])=[O:5])=[O:30])[CH:23]=3)[NH:18]2)[CH:16]=1

Participants

6

Reactant 4

HCID 24758Sodium hydride2×HCID 682631,1'-CarbonyldiimidazoleHCID 15765418Cyclopropanesulfonamide2×HCID 674418742-(5-Fluoro-2-methyl-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid

Product 1

HCID 53491695Cyclopropanesulfonic acid [2-(5-fluoro-2-methyl-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carbonyl]-amideYield 23%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
25 °C

Procedure

To a suspension of cyclopropanesulfonic acid amide (250 mg, 2.1 mmol) in N,N-dimethylformamide (3 mL) was added sodium hydride (84 mg, 2.1 mmol). The resulting mixture was stirred at 25° C. for 1 hour. A solution of 2-(5-fluoro-2-methyl-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid (130 mg, 0.42 mmol) and 1,1′-carbonyldiimidazole (130 mg, 0.84 mmol) in N,N-dimethylformamide (3 mL) was stirred at 70° C. for 1 h. Then the above suspension of cyclopropanesulfonic acid amide and sodium hydride in N,N-dimethylformamide was added and the mixture was allowed to stir at 25° C. for 1 h. Purification by Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water) afforded cyclopropanesulfonic acid [2-(5-fluoro-2-methyl-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carbonyl]-amide (40 mg, 23%) as a white solid: LC/MS m/e calcd for C22H25FN2O3S (M+H)+: 417.5, observed: 417.3.

Workup

  1. additionwas added
  2. stirringto stir at 25° C. for 1 h
  3. customPurification by Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water)

Sources & evidence

ORD record
ord-6ebbee68929e49a3a816a19238b9d674
Source dataset
uspto-grants-2013_01
Patent number
US08344137B2

Reaction notes

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