Phosphorus oxychloride → 1-Chloro-6-methoxy-3-(pyrrolidin-1-yl)isoquinoline

HRID 1852105Notes

Reaction equation

HRID 1852105 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](O)=[N:8][C:7]([N:14]1[CH2:18][CH2:17][CH2:16][CH2:15]1)=[CH:6]2.O=P(Cl)(Cl)[Cl:21]>>[Cl:21][C:9]1[C:10]2[C:5](=[CH:4][C:3]([O:2][CH3:1])=[CH:12][CH:11]=2)[CH:6]=[C:7]([N:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)[N:8]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178487758HCID 178487758, compound

Product 1

HCID 866831891-Chloro-6-methoxy-3-(pyrrolidin-1-yl)isoquinolineYield 48.3%

Conditions

Temperature
0 °C

Procedure

A solution of 6-methoxy-3-(pyrrolidin-1-yl)isoquinolin-1-ol (300 mg, 1.228 mmol) in POCl3 (8 mL) was refluxed for 4 h. After concentration, the residue was taken into a mixture of 100 mL of DCM and 50 mL of water, cooled to 0° C., neutralized with 3 N NaOH, dried over MgSO4, concentrated and purified via silica gel chromatography (5-20% EtOAc:Hex) to give 1-chloro-6-methoxy-3-(pyrrolidin-1-yl)isoquinoline (156 mg, 48.3% yield) as a yellow solid. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.95 (d, J=9.5 Hz, 1H), 6.85 (d, J=9.2 Hz, 1H), 6.80 (s, 1H), 6.43 (br. s., 1H), 3.89 (s, 3H), 3.56-3.49 (m, 4H), 2.08-2.03 (m, 4H); MS m/z 263.1 (M++1).

Workup

  1. concentrationAfter concentration
  2. additionthe residue was taken into a mixture of 100 mL of DCM and 50 mL of water
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. custompurified via silica gel chromatography (5-20% EtOAc:Hex)

Sources & evidence

ORD record
ord-912f5b35b28e4005be40b30225083392
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

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