3-Chloro-4-fluoroaniline → HCID 86617309, compound

HRID 1517410Notes

Reaction equation

HRID 1517410 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH:23]2[C:28](=[O:37])[NH:29][C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([CH3:36])[CH:31]=2)[C:5]2[N:11]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[CH:13]=3)[CH:9]=[CH:8][C:6]=2[N:7]=1.C([O-])([O-])=O.[K+].[K+].[Cl:44][C:45]1[CH:46]=[C:47]([CH:49]=[CH:50][C:51]=1[F:52])[NH2:48]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1.CC(O)(C)C>[Cl:44][C:45]1[CH:46]=[C:47]([CH:49]=[CH:50][C:51]=1[F:52])[NH:48][C:2]1[N:3]=[C:4]([N:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH:23]2[C:28](=[O:37])[NH:29][C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([CH3:36])[CH:31]=2)[C:5]2[N:11]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[CH:13]=3)[CH:9]=[CH:8][C:6]=2[N:7]=1

Participants

6

Reactant 3

HCID 97083-Chloro-4-fluoroanilineHCID 11430Potassium CarbonateHCID 86617308HCID 86617308, compound

Product 1

HCID 86617309HCID 86617309, compoundYield 47.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 68492063Tert-butyl alcohol dioxaneSolvent

Procedure

A suspension of 2-chloro-4-[(N-3-methyl-phenylcarbamoyl)-piperazin-1-yl]-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidine (106 mg, 0.20 mmole), K2CO3 (62 mg, 0.45 mmole) and 3-chloro-4-fluoroaniline (60 mg 0.40 mmole) in a 1,4-dioxane/t-BuOH 5:1 mixture (2 ml) was purged with nitrogen for 15 minutes. Thereafter, tetrakis(triphenylphosphine)palladium(0) (28 mg, 24 μmol) was added and the reaction mixture was heated at reflux under a N2 atmosphere for 20 hours. Upon cooling, the mixture was partitioned between ethyl acetate and brine. The organic phase was evaporated under reduced pressure and the crude residue was purified by flash chromatography on silica, using an ethyl acetate/n-hexane mixture as the mobile phase (in a ratio gradually ranging from 1:1 to 4:1), thus affording the pure title compound (60 mg, yield 47%) which was characterized by its mass spectrum as follows: MS (m/z): 628 ([M+H]+, 100).

Workup

  1. customwas purged with nitrogen for 15 minutes
  2. temperaturethe reaction mixture was heated
  3. temperatureat reflux under a N2 atmosphere for 20 hours
  4. temperatureUpon cooling
  5. customthe mixture was partitioned between ethyl acetate and brine
  6. customThe organic phase was evaporated under reduced pressure
  7. customthe crude residue was purified by flash chromatography on silica

Sources & evidence

ORD record
ord-1cc3de6d21484023aff9b7b974879cbf
Source dataset
uspto-grants-2012_07
Patent number
US08232278B2

Reaction notes

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