Sodium hydride → HCID 59053878, compound

HRID 2408134Notes

Reaction equation

HRID 2408134 reaction equation
[H-].[Na+].[CH3:3][S:4]([NH2:7])(=[O:6])=[O:5].[Cl:8][C:9]1[CH:10]=[C:11]([CH:16]2[CH2:25][C:24]([CH3:27])([CH3:26])[C:23]3[N:22]=[C:21]([C:28](O)=[O:29])[CH:20]=[CH:19][C:18]=3[NH:17]2)[CH:12]=[CH:13][C:14]=1[F:15].C(N1C=CN=C1)(N1C=CN=C1)=O>CN(C)C=O.O>[Cl:8][C:9]1[CH:10]=[C:11]([CH:16]2[CH2:25][C:24]([CH3:26])([CH3:27])[C:23]3[N:22]=[C:21]([C:28]([NH:7][S:4]([CH3:3])(=[O:6])=[O:5])=[O:29])[CH:20]=[CH:19][C:18]=3[NH:17]2)[CH:12]=[CH:13][C:14]=1[F:15]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 682631,1'-CarbonyldiimidazoleHCID 72879MethanesulfonamideHCID 70496379HCID 70496379, compound

Product 1

HCID 59053878HCID 59053878, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
25 °C

Procedure

To a suspension of 60% sodium hydride (267.5 mg, 6.9 mmol) in N,N-dimethylformamide (2.5 mL) was added methanesulfonamide (0.66 g, 6.9 mmol) at room temperature. The resulting mixture was stirred at 25° C. for 1 h to afford Solution A81. A solution of 6-(3-chloro-4-fluoro-phenyl)-8,8-dimethyl-5,6,7,8-tetrahydro-[1,5]naphthyridine-2-carboxylic acid (233.8 mg, 0.7 mmol) and 1,1′-carbonyldiimidazole (221.0 mg, 1.4 mmol) in N,N-dimethylformamide (2.0 mL) was stirred at 70° C. for 1 h and cooled to room temperature to afford Solution B81. Solution B81 was added to Solution A81 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 N-[6-(3-chloro-4-fluoro-phenyl)-8,8-dimethyl-5,6,7,8-tetrahydro-[1,5]naphthyridine-2-carbonyl]-methanesulfonamide (115.1 mg, 40%) as a white solid: MS (ESI) M+1=412.1.

Workup

  1. customto afford Solution A81
  2. temperaturecooled to room temperature
  3. customto afford Solution B81
  4. additionSolution B81 was added to Solution A81
  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-ae463adc74f341c98b59c5c095e650ba
Source dataset
uspto-grants-2014_08
Patent number
US08809369B2

Reaction notes

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