Dimethylformamide → 4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazoline-6-carbaldehyde

HRID 1867671Notes

Reaction equation

HRID 1867671 reaction equation
FC(F)(F)S(O[C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][C:16]=1[O:17][CH3:18])[N:13]=[CH:12][N:11]=[C:10]2[NH:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[C:21]=1[F:27])(=O)=O.C(N(CC)CC)C.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([SiH](CCCCCCCC)CCCCCCCC)CCCCCCC.CN(C)[CH:93]=[O:94]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:26][C:22]1[C:21]([F:27])=[C:20]([NH:19][C:10]2[C:9]3[C:14](=[CH:15][C:16]([O:17][CH3:18])=[C:7]([CH:93]=[O:94])[CH:8]=3)[N:13]=[CH:12][N:11]=2)[CH:25]=[CH:24][CH:23]=1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 812191,3-Bis(diphenylphosphino)propaneHCID 87780Trioctylsilane, 95%HCID 160500604-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl trifluoromethanesulfonate

Product 1

HCID 115734924-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazoline-6-carbaldehydeYield 41%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
70 °C

Procedure

A high pressure vessel was charged with 4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl trifluoromethanesulfonate (10 g, 22.1 mmol), palladium (II) acetate (700 mg, 3.12 mmol), triethylamine (7.6 ml, 54.5 mmol), 1,3-bis diphenylphosphinopropane (1.46 g, 3.54 mmol), trioctylsilane (13.2 ml, 29.4 mmol) and N,N-dimethylformamide (110 ml). The reaction mixture was heated at 70° C. under a carbon monoxide atmosphere (13 Bar) for 3 hours. The mixture was cooled and the lower N,N-dimethylformamide layer was separated, filtered and concentrated under reduced pressure. The residue was suspended in methanol, filtered, washed with isohexane and dried to give 4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazoline-6-carbaldehyde (3.0 g, 41%) as a pale orange solid; 1H NMR spectrum: (DMSO d6) 4.07 (s, 3H), 7.29 (t, 1H), 7.36 (s, 1H), 7.51 (t, 2H), 8.52 (s, 1H), 8.95 (s, 1H), 10.36 (s, 1H), 10.45 (s, 1H); Mass Spectrum: (M+H)+ 332.

Workup

  1. temperatureThe mixture was cooled
  2. customthe lower N,N-dimethylformamide layer was separated
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. filtrationfiltered
  6. washwashed with isohexane
  7. customdried

Sources & evidence

ORD record
ord-9ef12fe0101e4aa485da1a603df54b8b
Source dataset
uspto-grants-2009_12
Patent number
US07632840B2

Reaction notes

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