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

HRID 2045429Notes

Reaction equation

HRID 2045429 reaction equation
[H-].[Na+].[CH:3]1([S:6]([NH2:9])(=[O:8])=[O:7])[CH2:5][CH2:4]1.[CH3:10][C:11]1([CH3:36])[CH2:20][C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:21](O)=[O:22])[CH:18]=2)[NH:13][CH:12]1[C:24]1[CH:25]=[N:26][CH:27]=[C:28]([N:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)[CH:29]=1.C(N1C=CN=C1)(N1C=CN=C1)=O>CN(C)C=O>[CH3:10][C:11]1([CH3:36])[CH2:20][C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:21]([NH:9][S:6]([CH:3]3[CH2:5][CH2:4]3)(=[O:8])=[O:7])=[O:22])[CH:18]=2)[NH:13][CH:12]1[C:24]1[CH:25]=[N:26][CH:27]=[C:28]([N:30]2[CH2:31][CH2:32][O:33][CH2:34][CH2:35]2)[CH:29]=1

Participants

6

Reactant 4

HCID 24758Sodium hydride2×HCID 682631,1'-CarbonyldiimidazoleHCID 15765418Cyclopropanesulfonamide2×HCID 674435563,3-Dimethyl-2-(5-morpholin-4-yl-pyridin-3-yl)-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid

Product 1

HCID 58476216Cyclopropanesulfonic acid [3,3-dimethyl-2-(5-morpholin-4-yl-pyridin-3-yl)-1,2,3,4-tetrahydro-quinoline-6-carbonyl]-amideYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
25 °C

Procedure

To a suspension of 60% sodium hydride (535 mg, 13.7 mmol) in N,N-dimethylformamide (2.5 mL) was added cyclopropanesulfonamide (1.65 g, 13.8 mmol) at room temperature. The resulting mixture was stirred at 25° C. for 1 h. A solution of 3,3-dimethyl-2-(5-morpholin-4-yl-pyridin-3-yl)-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid (500 mg, 1.38 mmol) and 1,1′-carbonyldiimidazole (442 mg, 2.76 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 [3,3-dimethyl-2-(5-morpholin-4-yl-pyridin-3-yl)-1,2,3,4-tetrahydro-quinoline-6-carbonyl]-amide (256 mg, 40%) as a white solid: LC/MS m/e calcd for C24H30N4O4S (M+H)+: 471.6, observed: 471.1.

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-5c40c1fad3734c749ac5ee6b853cc971
Source dataset
uspto-grants-2013_11
Patent number
US08586747B2

Reaction notes

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