Sodium hydride → HCID 59053692, compound

HRID 2408105Notes

Reaction equation

HRID 2408105 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([CH3:37])[C:20]2[C:15](=[C:16]([CH3:24])[CH:17]=[C:18]([C:21](O)=[O:22])[CH:19]=2)[NH:14][CH:13]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)[CH:26]=2)[CH2:12]1.C(N1C=CN=C1)(N1C=CN=C1)=O>CN(C)C=O.O>[CH3:10][C:11]1([CH3:37])[C:20]2[C:15](=[C:16]([CH3:24])[CH:17]=[C:18]([C:21]([NH:9][S:6]([CH:3]3[CH2:5][CH2:4]3)(=[O:8])=[O:7])=[O:22])[CH:19]=2)[NH:14][CH:13]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)[CH:26]=2)[CH2:12]1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 682631,1'-CarbonyldiimidazoleHCID 15765418CyclopropanesulfonamideHCID 70496052HCID 70496052, compound

Product 1

HCID 59053692HCID 59053692, compoundYield 9.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
25 °C

Procedure

To a suspension of 60% sodium hydride (664 mg, 16.6 mmol) in N,N-dimethylformamide (5 mL) was added cyclopropanesulfonic acid amide (2.01 g, 16.6 mmol) at room temperature. The resulting mixture was stirred at 25° C. for 1 h to afford Solution A66. A solution of 4,4,8-trimethyl-2-(3-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid (0.9 g, 2.37 mmol) and 1,1′-carbonyldiimidazole (768 mg, 4.74 mmol) in N,N-dimethylformamide (5 mL) was stirred at 70° C. for 1 h and cooled to room temperature to afford Solution B66. Solution B66 was added to Solution A66 and the resulting mixture was stirred at 25° C. for 1 h. To the reaction mixture was added water (0.5 mL). The mixture was filtered to remove the insoluble solid, and the filtrate was purified 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 [4,4,8-trimethyl-2-(3-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-6-carbonyl]-amide (107 mg, 9%) as a brown solid: MS (ESI) M+1=484.2.

Workup

  1. customto afford Solution A66
  2. temperaturecooled to room temperature
  3. customto afford Solution B66
  4. additionSolution B66 was added to Solution A66
  5. stirringthe resulting mixture was stirred at 25° C. for 1 h
  6. filtrationThe mixture was filtered
  7. customto remove the insoluble solid
  8. customthe filtrate was purified 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-66f9fe96d3934222b47b54a2011dc9dc
Source dataset
uspto-grants-2014_08
Patent number
US08809369B2

Reaction notes

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