Sodium hydride → Cyclopropanesulfonic acid [6-chloro-2-(4'-dimethylamino-biphenyl-3-yl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-8-carbonyl]-amide

HRID 2045478Notes

Reaction equation

HRID 2045478 reaction equation
[H-].[Na+].[CH:3]1([S:6]([NH2:9])(=[O:8])=[O:7])[CH2:5][CH2:4]1.[Cl:10][C:11]1[CH:12]=[C:13]2[C:18](=[C:19]([C:21](O)=[O:22])[CH:20]=1)[NH:17][CH:16]([C:24]1[CH:25]=[C:26]([C:30]3[CH:35]=[CH:34][C:33]([N:36]([CH3:38])[CH3:37])=[CH:32][CH:31]=3)[CH:27]=[CH:28][CH:29]=1)[C:15]([CH3:40])([CH3:39])[CH2:14]2.C(N1C=CN=C1)(N1C=CN=C1)=O>CN(C)C=O>[Cl:10][C:11]1[CH:12]=[C:13]2[C:18](=[C:19]([C:21]([NH:9][S:6]([CH:3]3[CH2:5][CH2:4]3)(=[O:8])=[O:7])=[O:22])[CH:20]=1)[NH:17][CH:16]([C:24]1[CH:25]=[C:26]([C:30]3[CH:31]=[CH:32][C:33]([N:36]([CH3:38])[CH3:37])=[CH:34][CH:35]=3)[CH:27]=[CH:28][CH:29]=1)[C:15]([CH3:40])([CH3:39])[CH2:14]2

Participants

6

Reactant 4

HCID 24758Sodium hydride2×HCID 682631,1'-CarbonyldiimidazoleHCID 15765418Cyclopropanesulfonamide2×HCID 674414576-Chloro-2-(4'-dimethylamino-biphenyl-3-yl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid

Product 1

HCID 58476199Cyclopropanesulfonic acid [6-chloro-2-(4'-dimethylamino-biphenyl-3-yl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-8-carbonyl]-amideYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
25 °C

Procedure

To a suspension of 60% sodium hydride (91 mg, 2.2 mmol) in N,N-dimethylformamide (1.5 mL) was added cyclopropanesulfonamide (280 mg, 2.3 mmol) at room temperature. The resulting mixture was stirred at 25° C. for 1 h. A solution of 6-chloro-2-(4′-dimethylamino-biphenyl-3-yl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid (100 mg, 0.23 mmol) and 1,1′-carbonyldiimidazole (94 mg, 0.58 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-chloro-2-(4′-dimethylamino-biphenyl-3-yl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-8-carbonyl]-amide (49 mg, 40%) as a white solid: LC/MS m/e calcd for C29H32ClN3O3S (M+H)+: 539.11, observed: 538.1.

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-6571d4484d984d0895809b88a8985aeb
Source dataset
uspto-grants-2013_11
Patent number
US08586747B2

Reaction notes

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