Sodium hydride → N-{2-[3-(3-fluoro-azetidin-1-yl)-phenyl]-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carbonyl}-methanesulfonamide

HRID 1801231Notes

Reaction equation

HRID 1801231 reaction equation
[H-].[Na+].[CH3:3][S:4]([NH2:7])(=[O:6])=[O:5].[F:8][CH:9]1[CH2:12][N:11]([C:13]2[CH:14]=[C:15]([CH:19]3[C:28]([CH3:30])([CH3:29])[CH2:27][C:26]4[C:21](=[CH:22][CH:23]=[C:24]([C:31](O)=[O:32])[CH:25]=4)[NH:20]3)[CH:16]=[CH:17][CH:18]=2)[CH2:10]1.C(N1C=CN=C1)(N1C=CN=C1)=O>CN(C)C=O>[F:8][CH:9]1[CH2:12][N:11]([C:13]2[CH:14]=[C:15]([CH:19]3[C:28]([CH3:29])([CH3:30])[CH2:27][C:26]4[C:21](=[CH:22][CH:23]=[C:24]([C:31]([NH:7][S:4]([CH3:3])(=[O:6])=[O:5])=[O:32])[CH:25]=4)[NH:20]3)[CH:16]=[CH:17][CH:18]=2)[CH2:10]1

Participants

6

Reactant 4

HCID 24758Sodium hydride2×HCID 682631,1'-CarbonyldiimidazoleHCID 72879Methanesulfonamide2×HCID 674413362-[3-(3-Fluoro-azetidin-1-yl)-phenyl]-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid

Product 1

HCID 58476263N-{2-[3-(3-fluoro-azetidin-1-yl)-phenyl]-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carbonyl}-methanesulfonamideYield 20%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
25 °C

Procedure

To a suspension of 60% sodium hydride (165 mg, 4.1 mmol) in N,N-dimethylformamide (1.5 mL) was added methanesulfonamide (400 mg, 4.2 mmol) at room temperature. The resulting mixture was stirred at 25° C. for 1 h. A solution of 2-[3-(3-fluoro-azetidin-1-yl)-phenyl]-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid (150 mg, 0.42 mmol), and 1,1′-carbonyldiimidazole (170 mg, 1.04 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 methanesulfonamide 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 N-{2-[3-(3-fluoro-azetidin-1-yl)-phenyl]-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carbonyl}-methanesulfonamide (36 mg, 20%) as a white solid: LC/MS m/e calcd for C22H26FN3O3S (M+H)+: 432.51, observed: 432.1.

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-bd5dc075b86b4d76bdc037344a0dc57e
Source dataset
uspto-grants-2013_01
Patent number
US08344137B2

Reaction notes

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