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

HRID 2045509Notes

Reaction equation

HRID 2045509 reaction equation
[H-].[Na+].[CH:3]1([S:6]([NH2:9])(=[O:8])=[O:7])[CH2:5][CH2:4]1.[F:10][CH:11]1[CH2:14][N:13]([C:15]2[CH:16]=[C:17]([CH:21]3[C:30]([CH3:32])([CH3:31])[CH2:29][C:28]4[C:23](=[CH:24][CH:25]=[C:26]([C:33](O)=[O:34])[CH:27]=4)[NH:22]3)[CH:18]=[CH:19][CH:20]=2)[CH2:12]1.C(N1C=CN=C1)(N1C=CN=C1)=O>CN(C)C=O>[F:10][CH:11]1[CH2:14][N:13]([C:15]2[CH:16]=[C:17]([CH:21]3[C:30]([CH3:31])([CH3:32])[CH2:29][C:28]4[C:23](=[CH:24][CH:25]=[C:26]([C:33]([NH:9][S:6]([CH:3]5[CH2:5][CH2:4]5)(=[O:8])=[O:7])=[O:34])[CH:27]=4)[NH:22]3)[CH:18]=[CH:19][CH:20]=2)[CH2:12]1

Participants

6

Reactant 4

HCID 24758Sodium hydride2×HCID 682631,1'-CarbonyldiimidazoleHCID 15765418Cyclopropanesulfonamide2×HCID 674413362-[3-(3-Fluoro-azetidin-1-yl)-phenyl]-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid

Product 1

HCID 58476272Cyclopropanesulfonic acid {2-[3-(3-fluoro-azetidin-1-yl)-phenyl]-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carbonyl}-amideYield 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 cyclopropanesulfonamide (510 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 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 {2-[3-(3-fluoro-azetidin-1-yl)-phenyl]-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carbonyl}-amide (38 mg, 20%) as a white solid: LC/MS m/e calcd for C24H28FN3O3S (M+H)+: 458.57, observed: 458.1.

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-f9efd704673f4d84a44acdf96392610c
Source dataset
uspto-grants-2013_11
Patent number
US08586747B2

Reaction notes

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