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

HRID 1056565Notes

Reaction equation

HRID 1056565 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:45][CH:46](Cl)[CH3:47])(=[O:44])[CH2:42][CH3:43]>CN(C=O)C.CCCC[N+](CCCC)(CCCC)CCCC.[Br-].CCOC(C)=O>[C:41]([O:45][CH:46]([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)[CH3:47])(=[O:44])[CH2:42][CH3:43]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 135066761-Chloroethyl propionateHCID 42611257Vemurafenib

Product 1

HCID 733879381-(5-(4-chlorophenyl)-3-(2,6-difluoro-3-(propylsulfonamido)benzoyl)-1H-pyrrolo[2,3-b]pyridin-1-yl)ethyl propionateYield 58.3%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 6228DimethylformamideSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
10 °C

Procedure

To a solution of N-(3-(5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl)propane-1-sulfonamide (0.2 g, 0.41 mmol) in DMF (1 mL) was added Et3N (165 mg, 1.64 mmol). The reaction was stirred at 10° C. for 10 min, followed by the dropwise addition of a solution of TBAB (264 mg, 1.64 mmol) in DMF (0.5 mL) and a solution of 1-chloroethyl propionate (67 mg, 0.41 mmol) in DMF (0.5 mL) over 30 min. 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)=4/1) to afford the title compound as a white solid (141 mg, 58%). The title compound was characterized by LCMS 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)=4/1)

Sources & evidence

ORD record
ord-f27cb92c9dc74f3f9913b5a9e2929301
Source dataset
uspto-grants-2016_07
Patent number
US09399639B2

Reaction notes

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