Potassium Hydroxide → HCID 73388040, compound

HRID 1056567Notes

Reaction equation

HRID 1056567 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.[OH-].[K+].[C:36]([O:42][CH:43](Cl)[CH3:44])(=[O:41])[CH2:37][CH2:38][CH2:39][CH3:40]>CN(C=O)C.CCOC(C)=O>[C:36]([O:42][CH: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)[CH3:44])(=[O:41])[CH2:37][CH2:38][CH2:39][CH3:40]

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 130142851-Chloroethyl pentanoateHCID 42611257Vemurafenib

Product 1

HCID 73388040HCID 73388040, compoundYield 37.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
10 °C

Procedure

To a suspension of N-(3-(5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl)propane-1-sulfonamide (0.3 g, 0.61 mmol) in anhydrous DMF (2.5 mL) was added KOH (69 mg, 1.23 mmol). The reaction was stirred at 10° C. for 30 min, followed by adding a solution of 1-chloroethyl pentanoate (0.1 g, 0.61 mmol) in anhydrous DMF (0.5 mL) dropwise over 30 min. The mixture was stirred at 10° C. for another 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)=7/1) to give the crude product. The crude product was recrystallized in PE/EtOAc (10/1) to give the title compound as a white solid (0.14 g, 37.8%). 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 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)=7/1)
  5. customto give the crude product
  6. customThe crude product was recrystallized in PE/EtOAc (10/1)

Sources & evidence

ORD record
ord-9709665b9f7f4cc7b19a8a248ed4c30a
Source dataset
uspto-grants-2016_07
Patent number
US09399639B2

Reaction notes

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