Benzoylacetonitrile → HCID 178434234, compound

HRID 1474453Notes

Reaction equation

HRID 1474453 reaction equation
[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH:11]=O)[CH:9]=2)[NH:4][N:3]=1.O=[C:14]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH2:15][C:16]#[N:17].[NH2:24][C:25]([CH:29]([F:31])[F:30])=[CH:26][C:27]#[N:28]>C(O)CCCC.C(#N)C>[F:30][CH:29]([F:31])[C:25]1[NH:24][C:14]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:15]([C:16]#[N:17])[CH:11]([C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[NH:4][N:3]=[C:2]3[CH3:1])[C:26]=1[C:27]#[N:28]

Participants

6

Reactant 3

HCID 64799BenzoylacetonitrileHCID 762236343-Amino-4,4-difluorobut-2-enenitrileHCID 178434286HCID 178434286, compound

Product 1

HCID 178434234HCID 178434234, compound

Reagents, catalysts & solvents 2

HCID 62761-PentanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of 200 mg (1.25 mmol) 3-methyl-1H-indazole-5-carbaldehyde (Example 1A), 217 mg (1.50 mmol) 3-oxo-3-phenylpropanenitrile and 147 mg (1.25 mmol) 3-amino-4,4-difluorobut-2-enenitrile [obtainable by Thorpe reaction of acetonitrile with 2,2-difluoroacetonitrile, cf. Org. React. 15, 1 (1967), ibid. 31, 1 (1984)] in 1-pentanol (1.2 ml) containing powdered 4 Å molecular sieve was heated to 105° C. overnight. After cooling, the reaction mixture was diluted with acetonitrile and directly purified by preparative RP-HPLC (acetonitrile/water+0.1% TFA gradient) followed by chromatography on silica gel (eluent: toluene/dichloromethane/methanol 10:5:1 v/v) to afford 93 mg (19% of th.) of the racemic title compound.

Workup

  1. additioncontaining
  2. temperatureAfter cooling
  3. customdirectly purified by preparative RP-HPLC (acetonitrile/water+0.1% TFA gradient)

Sources & evidence

ORD record
ord-8e5e2efd662247b389e4973f174f72e2
Source dataset
uspto-grants-2015_04
Patent number
US09018234B2

Reaction notes

Loading…