Phosphorus oxychloride → HCID 86683182, compound

HRID 1852082Notes

Reaction equation

HRID 1852082 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7](O)=[N:8][C:9]([N:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)=[N:10]2)=[CH:5][CH:4]=1.O=P(Cl)(Cl)[Cl:21]>>[Cl:21][C:7]1[C:6]2[C:11](=[CH:12][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[N:10]=[C:9]([N:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)[N:8]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178487759HCID 178487759, compound

Product 1

HCID 86683182HCID 86683182, compoundYield 84%

Procedure

A solution of 7-methoxy-2-(pyrrolidin-1-yl)quinazolin-4-ol (155 mg, 0.632 mmol) in POCl3 (2 ml, 21.46 mmol) was refluxed at 90° C. 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-7-methoxy-2-(pyrrolidin-1-yl)quinazoline (140 mg, 84% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.86 (d, J=9.0 Hz, 1H), 6.91 (d, J=2.3 Hz, 1H), 6.82 (dd, J=9.0, 2.5 Hz, 1H), 3.92 (s, 3H), 3.69 (br. s., 4H), 2.03 (t, J=6.8 Hz, 4H); MS: MS m/z 264.1 (M++1).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionThe residue was dissolved in DCM
  3. customThe organic phase was collected
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe crude material was purified by silica gel chromatography
  8. customThe product fractions were collected
  9. customthe solvent was removed under vacuum

Sources & evidence

ORD record
ord-76c08322f3cd405bbe44ce91270945c9
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

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