Trichloroacetyl isocyanate → HCID 10289225, compound

HRID 916456Notes

Reaction equation

HRID 916456 reaction equation
[F:1][C:2]1[C:10]([O:11][C:12]2[C:21]3[C:16](=[CH:17][C:18]([O:24][CH2:25][CH2:26][CH2:27][N:28]4[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]4)=[C:19]([O:22][CH3:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([CH3:34])[NH:6]2.ClC(Cl)(Cl)[C:37]([N:39]=C=O)=[O:38]>N1C=CC=CC=1.CO>[C:37]([N:31]1[CH2:32][CH2:33][N:28]([CH2:27][CH2:26][CH2:25][O:24][C:18]2[CH:17]=[C:16]3[C:21]([C:12]([O:11][C:10]4[C:2]([F:1])=[C:3]5[C:7](=[CH:8][CH:9]=4)[NH:6][C:5]([CH3:34])=[CH:4]5)=[N:13][CH:14]=[N:15]3)=[CH:20][C:19]=2[O:22][CH3:23])[CH2:29][CH2:30]1)(=[O:38])[NH2:39]

Participants

5

Reactant 2

HCID 76400Trichloroacetyl isocyanateHCID 58960233HCID 58960233, compound

Product 1

HCID 10289225HCID 10289225, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

4-[(4-Fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-(3-piperazin-1-ylpropoxy)quinazoline (240 mg, 0.52 mmol), (prepared as described for the starting material in Example 15), was dissolved in pyridine (5 ml) and cooled to 0° C. Trichloroacetyl isocyanate (61 μl, 0.52 mmol) was added and the mixture stirred at ambient temperature for 1 hour. The mixture was concentrated under reduced pressure and the residue dissolved in 7N ammonia in methanol and stirred at 45° C. for 2.5 hours. Aqueous ammonia (1 ml) was added and the mixture was stirred at 60° C. for 1.5 hours and then at ambient temperature overnight. The solvent was removed under reduced pressure. Column chromatography of the residue using methylne chloride/methanol (90/10) followed by methylene chloride/methanol (saturated with ammonia) (90/10) gave a solid which was suspended in methanol and filtered to give 7-(3-[4-carbamoylpiperazin-1-yl]propoxy]-4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazoline (120 mg, 46%) as a pale yellow solid.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. dissolutionthe residue dissolved in 7N ammonia in methanol
  3. stirringstirred at 45° C. for 2.5 hours
  4. additionAqueous ammonia (1 ml) was added
  5. stirringthe mixture was stirred at 60° C. for 1.5 hours
  6. customat ambient temperature
  7. customovernight
  8. customThe solvent was removed under reduced pressure
  9. customgave a solid which
  10. filtrationfiltered

Sources & evidence

ORD record
ord-9886af3505f74c5fa3f3912f3657a193
Source dataset
uspto-grants-2007_09
Patent number
US07268230B2

Reaction notes

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