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Cyclobutanone → 4-(4-(1-Cyanocyclobutylamino)-2-fluorophenyl)-N-methylbutanamide

HRID 1192869
Notes
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Reaction equation

HRID 1192869 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][C:11]([NH:13][CH3:14])=[O:12])=[C:4]([F:15])[CH:3]=1.[C:16]1(=O)[CH2:19][CH2:18][CH2:17]1.C[Si]([C:25]#[N:26])(C)C>C(OCC)(=O)C>[C:25]([C:16]1([NH:1][C:2]2[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][C:11]([NH:13][CH3:14])=[O:12])=[C:4]([F:15])[CH:3]=2)[CH2:19][CH2:18][CH2:17]1)#[N:26]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 14496CyclobutanoneHCID 82115Trimethylsilyl cyanideHCID 687332914-(4-amino-2-fluorophenyl)-N-methylbutanamide

Product 1

HCID 689425014-(4-(1-Cyanocyclobutylamino)-2-fluorophenyl)-N-methylbutanamideYield 92%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4-(4-Amino-2-fluorophenyl)-N-methylbutanamide (80) (8 mg, 0.04 mmol), cyclobutanone (5 mg, 0.08 mmol) and trimethylsilyl cyanide (TMSCN, 8 mg, 0.08 mmol) was heated to 80° C. and stirred for 15 h. To the medium was added ethyl acetate (2×20 mL) and then washed with water (2×20 mL). The organic layer was dried over MgSO4 and concentrated and the residue was purified with silica gel column chromatography (dichloromethane:acetone, 9:1) to give 4-(4-(1-Cyanocyclobutylamino)-2-fluorophenyl)-N-methylbutanamide (79) (10 mg, 92%).

Workup

  1. washwashed with water (2×20 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated
  4. customthe residue was purified with silica gel column chromatography (dichloromethane:acetone, 9:1)

Sources & evidence

ORD record
ord-905785bdb8064407ab9b80d3547520c0
Source dataset
uspto-grants-2014_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08680291B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes