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

HRID 2045432Notes

Reaction equation

HRID 2045432 reaction equation
[H-].[Na+].[CH:3]1([S:6]([NH2:9])(=[O:8])=[O:7])[CH2:5][CH2:4]1.[F:10][C:11]1[CH:20]=[CH:19][C:18]2[NH:17][CH:16]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)[CH:22]=3)[C:15]([CH3:34])([CH3:33])[CH2:14][C:13]=2[C:12]=1[C:35](O)=[O:36].C(N1C=CN=C1)(N1C=CN=C1)=O>CN(C)C=O>[F:10][C:11]1[CH:20]=[CH:19][C:18]2[NH:17][CH:16]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[CH:22]=3)[C:15]([CH3:33])([CH3:34])[CH2:14][C:13]=2[C:12]=1[C:35]([NH:9][S:6]([CH:3]1[CH2:5][CH2:4]1)(=[O:8])=[O:7])=[O:36]

Participants

6

Reactant 4

HCID 24758Sodium hydride2×HCID 682631,1'-CarbonyldiimidazoleHCID 15765418Cyclopropanesulfonamide2×HCID 534921796-Fluoro-3,3-dimethyl-2-(3-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-5-carboxylic acid

Product 1

HCID 58476285Cyclopropanesulfonic acid [6-fluoro-3,3-dimethyl-2-(3-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-5-carbonyl]-amideYield 20%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
25 °C

Procedure

To a suspension of 60% sodium hydride (102 mg, 2.5 mmol) in N,N-dimethylformamide (2.5 mL) was added cyclopropanesulfonamide (315 mg, 2.6 mmol) at room temperature. The resulting mixture was stirred at 25° C. for 1 h. A solution of 6-fluoro-3,3-dimethyl-2-(3-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-5-carboxylic acid (100 mg, 0.26 mmol) and 1,1′-carbonyldiimidazole (106 mg, 0.65 mmol) in N,N-dimethylformamide (2.0 mL) was stirred at 70° C. After stirring at 70° C. for 1 h, the above suspension of cyclopropanesulfonamide 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 [6-fluoro-3,3-dimethyl-2-(3-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-5-carbonyl]-amide (25.3 mg, 20%) as a white solid: LC/MS m/e calcd for C25H30FN3O4S (M+H)+: 488.60, observed: 488.1.

Workup

  1. stirringAfter stirring at 70° C. for 1 h
  2. additionwas added
  3. stirringto stir at 25° C. for 1 h
  4. 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-e4b77bca704f49c086e0ca7dadd36268
Source dataset
uspto-grants-2013_11
Patent number
US08586747B2

Reaction notes

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