Triethylamine → (5-(4-chlorophenyl)-3-(2,6-difluoro-3-(propylsulfonamido)benzoyl)-1H-pyrrolo[2,3-b]pyridin-1-yl)methyl ethyl carbonate

HRID 1056591Notes

Reaction equation

HRID 1056591 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.CCN(CC)CC.[C:41](=[O:48])([O:45][CH2:46][CH3:47])[O:42][CH2:43]Cl>CN(C=O)C.CCCC[N+](CCCC)(CCCC)CCCC.[Br-].CCOC(C)=O>[C:41](=[O:48])([O:45][CH2:46][CH3:47])[O:42][CH2:43][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

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 5325479Chloromethyl Ethyl CarbonateHCID 42611257Vemurafenib

Product 1

HCID 73386916(5-(4-chlorophenyl)-3-(2,6-difluoro-3-(propylsulfonamido)benzoyl)-1H-pyrrolo[2,3-b]pyridin-1-yl)methyl ethyl carbonateYield 73%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 6228DimethylformamideSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
10 °C

Procedure

To a mixture 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) and Et3N (114 μL, 0.8 mmol) in DMF (0.6 mL) was added a solution of TBAB (132 mg, 0.4 mmol) in DMF (0.2 mL). The reaction was stirred at 10° C. for 30 min, followed by dropwise addition of a solution of chloromethyl ethyl carbonate (34 mg, 0.25 mmol) in DMF (0.2 mL). The mixture was stirred at 10° C. for another 3 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)=2/1) to afford the title compound as a white solid (85 mg, 73%). The title compound was characterized by LC-MS and 1H NMR as shown below:

Workup

  1. stirringThe mixture was stirred at 10° C. for another 3 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)=2/1)

Sources & evidence

ORD record
ord-a2b8c964b44245aaae0d1250f57b5256
Source dataset
uspto-grants-2016_07
Patent number
US09399639B2

Reaction notes

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