Potassium Carbonate → HCID 73386918, compound

HRID 1056595Notes

Reaction equation

HRID 1056595 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]3[C:16]([C:17]([C:19]4[C:20]([F:33])=[C:21]([NH:26][S:27]([CH2:30][CH2:31][CH3:32])(=[O:29])=[O:28])[CH:22]=[CH:23][C:24]=4[F:25])=[O:18])=[CH:15][NH:14][C:11]3=[N:12][CH:13]=2)=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[C:40](=[O:48])([O:45][CH2:46][CH3:47])[O:41][CH:42](Cl)[CH3:43]>CN(C=O)C.CCCC[N+](CCCC)(CCCC)CCCC.[Br-].CCOC(C)=O>[C:40](=[O:48])([O:45][CH2:46][CH3:47])[O:41][CH:42]([N:14]1[C:11]2=[N:12][CH:13]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)[CH:9]=[C:10]2[C:16]([C:17](=[O:18])[C:19]2[C:24]([F:25])=[CH:23][CH:22]=[C:21]([NH:26][S:27]([CH2:30][CH2:31][CH3:32])(=[O:28])=[O:29])[C:20]=2[F:33])=[CH:15]1)[CH3:43]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 162095Carbonic acid, 1-chloroethyl ethyl esterHCID 42611257Vemurafenib

Product 1

HCID 73386918HCID 73386918, compoundYield 50.3%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-(3-(5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl)propane-1-sulfonamide (0.1 g, 0.2 mmol) in DMF (1 mL) was added K2CO3 (85 mg, 0.6 mmol). The reaction was stirred at rt for 10 min, followed by the addition of TBAB (132 mg, 0.4 mmol) and a solution of 1-chloroethyl ethyl carbonate (35 mg, 0.25 mmol) in DMF (100 μA). The mixture was stirred at rt for 16 h, then diluted with EtOAc (40 mL) and filtered. The filtrate was concentrated in vacuo and the residue was purified by a silica gel column chromatography (PE/EtOAc (v/v)=4/1) to afford the title compound as a white solid (61 mg, 50%). The title compound was characterized by LC-MS and 1H NMR as shown below:

Workup

  1. stirringThe mixture was stirred at rt for 16 h
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated in vacuo
  4. customthe residue was purified by a silica gel column chromatography (PE/EtOAc (v/v)=4/1)

Sources & evidence

ORD record
ord-7dd92609a6de4700abb22b1b3e75375d
Source dataset
uspto-grants-2016_07
Patent number
US09399639B2

Reaction notes

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