Acetone → HCID 59508853, compound

HRID 81637Notes

Reaction equation

HRID 81637 reaction equation
[CH3:1][C:2]([CH3:4])=O.[NH:5]1[CH2:8][CH:7]([O:9][C:10]2[CH:11]=[CH:12][C:13]([O:16][C:17]3[CH:18]=[C:19]4[C:24](=[CH:25][CH:26]=3)[N:23]=[CH:22][N:21]=[C:20]4[NH:27][C:28]3[CH:32]=[CH:31][N:30]([CH3:33])[N:29]=3)=[N:14][CH:15]=2)[CH2:6]1.[OH-].[Na+]>CO>[CH:2]([N:5]1[CH2:6][CH:7]([O:9][C:10]2[CH:11]=[CH:12][C:13]([O:16][C:17]3[CH:18]=[C:19]4[C:24](=[CH:25][CH:26]=3)[N:23]=[CH:22][N:21]=[C:20]4[NH:27][C:28]3[CH:32]=[CH:31][N:30]([CH3:33])[N:29]=3)=[N:14][CH:15]=2)[CH2:8]1)([CH3:4])[CH3:1]

Participants

5

Reactant 3

HCID 180AcetoneHCID 14798Sodium HydroxideHCID 68428829HCID 68428829, compound

Product 1

HCID 59508853HCID 59508853, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

Acetone (0.019 ml, 0.26 mmol) was added to a methanol solution (1 ml) of 6-{[5-(azetidin-3-yloxy)pyridin-2-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)quinazoline-4-amine (50 mg, 0.13 mmol) obtained in Example 6-5), stirred for 10 minutes, then a methanol solution (1.7 ml, 0.26 mmol) of 0.15 M zinc cyanotrihydroborate was added and stirred for 1 hour. 1 N sodium hydroxide was added to the reaction solution, then extracted with a mixed solution of chloroform/methanol (9:1). The organic layer was washed with saturated saline water, then dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by thin-layer silica gel column chromatography (chloroform:methanol=90:10) to obtain 6-({5-[(1-isopropylazetidin-3-yl)oxy]pyridin-2-yl}oxy)-N-(1-methyl-1H-pyrazol-3-yl)quinazoline-4-amine. The compound was dissolved in methanol, then aqueous 5 M hydrochloric acid solution (0.017 ml, 0.085 mmol) was added and concentrated under reduced pressure to obtain the entitled compound (40 mg, yield: 67%) as a pale yellow solid.

Workup

  1. stirringstirred for 1 hour
  2. extractionextracted with a mixed solution of chloroform/methanol (9:1)
  3. washThe organic layer was washed with saturated saline water
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue was purified by thin-layer silica gel column chromatography (chloroform:methanol=90:10)

Sources & evidence

ORD record
ord-35fa4e12c5114e02a095db26caadc54d
Source dataset
uspto-grants-2014_09
Patent number
US08846700B2

Reaction notes

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