Phosphorus oxychloride → Methyl 4-{[3-(trifluoromethyl)benzyl]amino}quinazoline-8-carboxylate

HRID 578626Notes

Reaction equation

O=[C:2]1[C:11]2[C:6](=[C:7]([C:12]([O:14][CH3:15])=[O:13])[CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][NH:3]1.O=P(Cl)(Cl)Cl.CCN(C(C)C)C(C)C.[F:30][C:31]([F:41])([F:40])[C:32]1[CH:33]=[C:34]([CH:37]=[CH:38][CH:39]=1)[CH2:35][NH2:36]>ClCCCl>[F:30][C:31]([F:40])([F:41])[C:32]1[CH:33]=[C:34]([CH:37]=[CH:38][CH:39]=1)[CH2:35][NH:36][C:2]1[C:11]2[C:6](=[C:7]([C:12]([O:14][CH3:15])=[O:13])[CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a suspension of methyl 4-oxo-3,4-dihydroquinazoline-8-carboxylate (150 mg, 0.73 mmol) in 4 mL of anhydrous DCE, POCl3 (80 μL, 0.87 mmol, 1.2 equiv.) was added followed by DIPEA (630 μL, 3.6 mmol, 5.0 equiv.). The resulting mixture was stirred at 90° C. for 1-2 h. After cooling down to rt, 3-(trifluoromethyl)benzylamine (97 μL, 0.81 mmol, 1.1 equiv.) was added. The reaction mixture was stirred at 80° C. for 2-4 h. After work-up, the crude was purified by chromatography to yield the title compound in 66% yield. 1HNMR (in CDCl3): 3.19 (s, 3H), 4.90 (s, 2H), 7.41-7.45 (m, 2H), 7.53 (t, J=8.9 Hz, 2H), 7.58 (s, 1H), 7.97 (dd, J=1.5 and 8.4 Hz, 1H), 8.04 (dd, J=1.5 and 7.3 Hz, 1H). Mass: M+H+: 362.

Workup

additionwas added
temperatureAfter cooling down to rt
stirringThe reaction mixture was stirred at 80° C. for 2-4 h
customAfter work-up, the crude was purified by chromatography

Sources & evidence

ORD record: ord-fcbe02c6aa6b4bc4b0ecaa5b1c1eec52
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040560B2

Reaction notes

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