Potassium Hydroxide → HCID 73386919, compound

HRID 1056597Notes

Reaction equation

HRID 1056597 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:48])([O:41][CH:42]1[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]1)[O:37][CH:38](Cl)[CH3:39]>C1COCC1>[C:36](=[O:48])([O:41][CH:42]1[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]1)[O:37][CH:38]([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)[CH3:39]

Participants

5

Reactant 3

HCID 14797Potassium HydroxideHCID 112295291-Chloroethyl Cyclohexyl CarbonateHCID 42611257Vemurafenib

Product 1

HCID 73386919HCID 73386919, compoundYield 51.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of N-(3-(5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl)propane-1-sulfonamide (5 g, 10.2 mmol) in THF (36 mL) was added KOH (1.1 g, 20.4 mmol). The reaction was stirred at rt for 0.5 h, followed by the addition of a solution of 1-chloroethyl cyclohexyl carbonate (2.3 g, 11.2 mmol) in THF (9 mL). The mixture was refluxed for 16 h, then cooled to rtand diluted with THF (50 mL). The resulting mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (v/v)=8/1) to give the title compound as a white solid (3.49 g, 51.9%). The title compound was characterized by LC-MS and 1H NMR as shown below:

Workup

  1. temperatureThe mixture was refluxed for 16 h
  2. temperaturecooled
  3. filtrationThe resulting mixture was filtered
  4. concentrationthe filtrate was concentrated in vacuo
  5. customThe residue was purified by a silica gel column chromatography (PE/EtOAc (v/v)=8/1)

Sources & evidence

ORD record
ord-67577f02d99a4a4b9099ea51990be957
Source dataset
uspto-grants-2016_07
Patent number
US09399639B2

Reaction notes

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