Ethyl chloroformate → HCID 44518473, compound

HRID 2405959Notes

Reaction equation

HRID 2405959 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([S:9]([N:12]2[CH2:17][CH2:16][C:15]3[NH:18][N:19]=[C:20]([NH:21][C:22](=[O:43])[C:23]4[CH:28]=[CH:27][C:26]([N:29]5[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]5)=[CH:25][C:24]=4[NH:36][CH:37]4[CH2:42][CH2:41][O:40][CH2:39][CH2:38]4)[C:14]=3[CH2:13]2)(=[O:11])=[O:10])[CH:5]=[C:6]([F:8])[CH:7]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Cl[C:55]([O:57][CH2:58][CH3:59])=[O:56]>C1COCC1.O>[CH2:58]([O:57][C:55]([N:18]1[C:15]2[CH2:16][CH2:17][N:12]([S:9]([C:4]3[CH:5]=[C:6]([F:8])[CH:7]=[C:2]([F:1])[CH:3]=3)(=[O:11])=[O:10])[CH2:13][C:14]=2[C:20]([NH:21][C:22](=[O:43])[C:23]2[CH:28]=[CH:27][C:26]([N:29]3[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]3)=[CH:25][C:24]=2[NH:36][CH:37]2[CH2:42][CH2:41][O:40][CH2:39][CH2:38]2)=[N:19]1)=[O:56])[CH3:59]

Participants

6

Reactant 3

HCID 10928Ethyl chloroformateHCID 2733832Lithium HexamethyldisilazideHCID 16665563HCID 16665563, compound

Product 1

HCID 44518473HCID 44518473, compoundYield 86%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of N-[5-(3,5-difluoro-benzenesulfonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-4-(4-methyl-piperazin-1-yl)-2-(tetrahydro-pyran-4-ylamino)-benzamide (1.38 g, 2.24 mmol) in anhydrous THF (150 mL), cooled to −40° C., under argon, was added lithium bis(trimethylsilyl)amide 1.0 M in THF (2.35 mL, 2.35 mmol). The mixture was stirred for 5 min. then ethyl chloroformate (0.225 mL, 2.35 mmol) was added. The reaction was stirred at −40° C. for 1 h, then was poured in water and extracted with ethyl acetate. The organic phase was washed with water, brine and dried with sodium sulfate. After filtration and evaporation the crude was triturated with ether to give the title compound as white solid (1.32 g, 86%).

Workup

  1. stirringThe reaction was stirred at −40° C. for 1 h
  2. extractionextracted with ethyl acetate
  3. washThe organic phase was washed with water, brine
  4. dry with materialdried with sodium sulfate
  5. filtrationAfter filtration and evaporation the crude
  6. customwas triturated with ether

Sources & evidence

ORD record
ord-589f9bfa43824a90983935574dfb20dd
Source dataset
uspto-grants-2014_08
Patent number
US08809337B2

Reaction notes

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