1-(6-(((3,3-Difluorocyclobutyl)methoxy)methyl)-2-(3-methoxy-4-(6-methylpyridazin-4-yl)phenylamino)pyrimidin-4-yl)ethanone → 2-(6-(((3,3-Difluorocyclobutyl)methoxy)methyl)-2-(3-methoxy-4-(6-methylpyridazin-4-yl)phenylamino)pyrimidin-4-yl)propan-2-ol

HRID 59148Notes

Reaction equation

HRID 59148 reaction equation
[CH3:1][Mg]Br.[F:4][C:5]1([F:37])[CH2:8][CH:7]([CH2:9][O:10][CH2:11][C:12]2[N:17]=[C:16]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]4[CH:30]=[C:29]([CH3:31])[N:28]=[N:27][CH:26]=4)=[C:21]([O:32][CH3:33])[CH:20]=3)[N:15]=[C:14]([C:34](=[O:36])[CH3:35])[CH:13]=2)[CH2:6]1>C1COCC1>[F:37][C:5]1([F:4])[CH2:8][CH:7]([CH2:9][O:10][CH2:11][C:12]2[N:17]=[C:16]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]4[CH:30]=[C:29]([CH3:31])[N:28]=[N:27][CH:26]=4)=[C:21]([O:32][CH3:33])[CH:20]=3)[N:15]=[C:14]([C:34]([OH:36])([CH3:1])[CH3:35])[CH:13]=2)[CH2:6]1

Participants

4

Reactant 2

HCID 1178211701-(6-(((3,3-Difluorocyclobutyl)methoxy)methyl)-2-(3-methoxy-4-(6-methylpyridazin-4-yl)phenylamino)pyrimidin-4-yl)ethanoneHCID 178418573HCID 178418573, compound

Product 1

HCID 863446172-(6-(((3,3-Difluorocyclobutyl)methoxy)methyl)-2-(3-methoxy-4-(6-methylpyridazin-4-yl)phenylamino)pyrimidin-4-yl)propan-2-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To an ice-cold solution of methylmagnesium bromide (1.430 mL, 2.00 mmol) in THF (6 mL) a solution of 1-(6-(((3,3-difluorocyclobutyl)methoxy)methyl)-2-(3-methoxy-4-(6-methylpyridazin-4-yl)phenylamino)pyrimidin-4-yl)ethanone (94 mg, 0.20 mmol) in THF (3 mL) was added over 5 min. The mixture was stirred on ice-bath for 30 minutes before it was quenched with ammonium chloride (aq, sat). The solvent volume was reduced by evaporation. The mixture was extracted with dichloromethane and the organic phase was passed through a phase separator. The residue was purified by preparative HPLC to give the title compound as a dry film 38 mg (39%).

Workup

  1. customwas quenched with ammonium chloride (aq, sat)
  2. customThe solvent volume was reduced by evaporation
  3. extractionThe mixture was extracted with dichloromethane
  4. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-3f747fa4272244849eecc5a832ea3c7a
Source dataset
uspto-grants-2016_09
Patent number
US09439904B2

Reaction notes

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