Chloromethyl Methyl Ether → HCID 25175790, compound

HRID 1907136Notes

Reaction equation

HRID 1907136 reaction equation
[CH:1]([NH:4][C:5]([C:7]1[C:8]([NH:17][C:18]([C:20]2[N:21]([C:29]3[C:34]([Cl:35])=[CH:33][CH:32]=[CH:31][N:30]=3)[N:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=2)=[O:19])=[C:9]([Cl:16])[CH:10]=[C:11]2[C:15]=1[NH:14][N:13]=[CH:12]2)=[O:6])([CH3:3])[CH3:2].[OH-].[K+].CC([O-])(C)C.[K+].Cl[CH2:45][O:46][CH3:47]>C1COCC1.O.CCOC(C)=O>[CH:1]([NH:4][C:5]([C:7]1[C:8]([NH:17][C:18]([C:20]2[N:21]([C:29]3[C:34]([Cl:35])=[CH:33][CH:32]=[CH:31][N:30]=3)[N:22]=[C:23]([C:25]([F:28])([F:26])[F:27])[CH:24]=2)=[O:19])=[C:9]([Cl:16])[CH:10]=[C:11]2[C:15]=1[N:14]([CH2:45][O:46][CH3:47])[N:13]=[CH:12]2)=[O:6])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 7864Chloromethyl Methyl EtherHCID 14797Potassium HydroxideHCID 23665647Potassium tert-butoxideHCID 57990205HCID 57990205, compound

Product 1

HCID 25175790HCID 25175790, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 5-chloro-6-{[2-(3-chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazole-3-carbonyl]-amino}-1H-indazole-7-carboxylic acid isopropylamide (1.00 g, 1.90 mmol), KOH (310 mgs, 5.70 mmol) and t-BuOK (6.4 mg, 0.02 mmol) in THF (5 mL) was treated dropwise with chloro-methoxy-methane (0.39 mL, 5.1 mmol). The resulting reaction mixture was stirred at ambient temperature for 18 h. AcOEt and water was added. The phases were separated. The aqueous layer was extracted with AcOEt. The organic layers were washed with water, combined, dried over MgSO4 and concentrated in vacuo. Purification of the residue by reverse phase HPLC affords the title product as a colorless solid. M.p. 180-182° C., LC/MS: 570/572 (M+H)+, 592/594 (M+Na)+.

Workup

  1. customThe resulting reaction mixture
  2. customThe phases were separated
  3. extractionThe aqueous layer was extracted with AcOEt
  4. washThe organic layers were washed with water
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by reverse phase HPLC

Sources & evidence

ORD record
ord-ee44c8c82b5e454185d02de4b544952e
Source dataset
uspto-grants-2013_12
Patent number
US08598078B2

Reaction notes

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