Phosphorus oxychloride → 1-chloro-6-methoxy-N,N-dimethylisoquinolin-3-amine

HRID 1852103Notes

Reaction equation

HRID 1852103 reaction equation
[CH3:1][N:2]([CH3:16])[C:3]1[N:4]=[C:5](O)[C:6]2[C:11]([CH:12]=1)=[CH:10][C:9]([O:13][CH3:14])=[CH:8][CH:7]=2.O=P(Cl)(Cl)[Cl:19]>>[Cl:19][C:5]1[C:6]2[C:11](=[CH:10][C:9]([O:13][CH3:14])=[CH:8][CH:7]=2)[CH:12]=[C:3]([N:2]([CH3:16])[CH3:1])[N:4]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178487765HCID 178487765, compound

Product 1

HCID 594234521-chloro-6-methoxy-N,N-dimethylisoquinolin-3-amineYield 53%

Procedure

A solution of 3-(dimethylamino)-6-methoxyisoquinolin-1-ol (700 mg, 3.21 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 as eluent. The product fractions were collected and the solvent was removed under vacuum to give 1-chloro-6-methoxy-N,N-dimethylisoquinolin-3-amine (400 mg, 53% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.96 (d, J=9.3 Hz, 1H), 6.87 (dd, J=9.2, 2.4 Hz, 1H), 6.80 (d, J=2.3 Hz, 1H), 6.43 (s, 1H), 3.91 (s, 3H), 3.14 (s, 6H); MS m/z 237.0 (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-ef2830236b6a44c3acaf1161a8718682
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

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