Phosphorus oxychloride → HCID 86683184, compound

HRID 1852086Notes

Reaction equation

[CH:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:20]=[C:19](O)[C:18]3[C:13](=[CH:14][C:15]([O:22][CH3:23])=[CH:16][CH:17]=3)[N:12]=2)=[CH:7][CH:6]=1)([CH3:3])[CH3:2].O=P(Cl)(Cl)[Cl:26]>>[Cl:26][C:19]1[C:18]2[C:13](=[CH:14][C:15]([O:22][CH3:23])=[CH:16][CH:17]=2)[N:12]=[C:11]([C:8]2[CH:9]=[CH:10][C:5]([O:4][CH:1]([CH3:3])[CH3:2])=[CH:6][CH:7]=2)[N:20]=1

Participants

Reactant 2

HCID 24813Phosphorus oxychloride

HCID 178487734HCID 178487734, compound

Product 1

HCID 86683184HCID 86683184, compoundYield 80.1%

Procedure

A solution of 2-(4-isopropoxyphenyl)-7-methoxyquinazolin-4-ol (495 mg, 1.595 mmol) in POCl3 (2 ml, 21.46 mmol) was refluxed for 4 h. The reaction mixture was concentrated. The residue was dissolved in DCM and the pH was adjusted to 7 with 4N NaOH. The organic phase was collected and dried over sodium sulfate, filtered, then concentrated under vacuum. The crude material was purified by silica gel chromatography using 50% DCM in hexanes. The product fractions were collected and the solvent was removed under vacuum to give 4-chloro-2-(4-isopropoxyphenyl)-7-methoxyquinazoline (420 mg, 80% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.59-8.53 (m, 2H), 8.11 (d, J=9.3 Hz, 1H), 7.24 (dd, J=9.2, 2.4 Hz, 1H), 7.04-7.00 (m, 3H), 4.70 (quin, J=6.0 Hz, 1H), 4.03 (s, 3H), 1.40 (d, J=6.0 Hz, 6H); MS: MS m/z 329.1 (M++1).

Workup

concentrationThe reaction mixture was concentrated
dissolutionThe residue was dissolved in DCM
customThe organic phase was collected
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated under vacuum
customThe crude material was purified by silica gel chromatography
customThe product fractions were collected
customthe solvent was removed under vacuum

Sources & evidence

ORD record: ord-07dacd43acfb496cb768d29e32ce6698
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08957203B2

Reaction notes

Loading…