Trichloroacetyl isocyanate → HCID 58960232, compound

HRID 2068099Notes

Reaction equation

[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([O:10][C:11]3[C:20]4[C:15](=[CH:16][C:17]([O:23][CH2:24][CH2:25][CH2:26][N:27]5[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]5)=[C:18]([O:21][CH3:22])[CH:19]=4)[N:14]=[CH:13][N:12]=3)=[CH:7][N:8]=2)[CH:3]=[CH:2]1.ClC(Cl)(Cl)[C:35]([N:37]=C=O)=[O:36]>N1C=CC=CC=1>[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([O:10][C:11]3[C:20]4[C:15](=[CH:16][C:17]([O:23][CH2:24][CH2:25][CH2:26][N:27]5[CH2:32][CH2:31][N:30]([C:35](=[O:36])[NH2:37])[CH2:29][CH2:28]5)=[C:18]([O:21][CH3:22])[CH:19]=4)[N:14]=[CH:13][N:12]=3)=[CH:7][N:8]=2)[CH:3]=[CH:2]1

Participants

Conditions

Temperature: 0 °C

Procedure

4-(7-Azaindol-5-yloxy)-6-methoxy-7-(3-piperazin-1-ylpropoxy)quinazoline (200 mg, 0.46 mmol) was dissolved in pyridine (5 ml) and cooled to 0° C. Trichloroacetyl isocyanate (55 μl, 0.46 mmol) was added and the mixture stirred at ambient temperature for 3 hours. The mixture was concentrated under reduced pressure and the residue dissolved in 7N ammonia in methanol and stirred at ambient temperature for 20 hours. The solvent was removed under reduced pressure and the residue was purified by column chromatography eluting with methylene chloride/methanol (90/10) to give 4-(7-azaindol-5-yloxy)-6-methoxy-7-[3-(4-carbamoylpiperazin-1-yl)propoxy]quinazoline (95 mg, 43%) as a white solid.

Workup

concentrationThe mixture was concentrated under reduced pressure
dissolutionthe residue dissolved in 7N ammonia in methanol
stirringstirred at ambient temperature for 20 hours
customThe solvent was removed under reduced pressure
customthe residue was purified by column chromatography
washeluting with methylene chloride/methanol (90/10)

Sources & evidence

ORD record: ord-c7bcea9cc0ce4b52974a79fce31d4f81
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08293902B2

Reaction notes

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