Phosphorus oxychloride → HCID 58942249, compound

HRID 2092274Notes

Reaction equation

HRID 2092274 reaction equation
[CH3:1][C:2]1[C:3]([C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][CH:22]=2)[N:19]=[C:18]([NH:23][CH3:24])[N:17]=[CH:16]3)=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=O)[NH:7][CH:6]=[CH:5]2.O=P(Cl)(Cl)[Cl:27]>>[Cl:27][C:8]1[C:9]2[C:4](=[C:3]([C:13]3[CH:14]=[C:15]4[C:20](=[CH:21][CH:22]=3)[N:19]=[C:18]([NH:23][CH3:24])[N:17]=[CH:16]4)[C:2]([CH3:1])=[CH:11][CH:10]=2)[CH:5]=[CH:6][N:7]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 58829301HCID 58829301, compound

Product 1

HCID 58942249HCID 58942249, compoundYield 68%

Conditions

Temperature
100 °C

Procedure

6-Methyl-5-(2-(methylamino)quinazolin-6-yl)isoquinolin-1(2H)-one (13.00 g, 41.1 mmol) was treated with POCl3 (57.5 mL, 616 mmol) and the mixture heated to 100° C. while stirring. After 4 h, the volatiles were removed under vacuum and residual POCl3 was removed by azeotroping with toluene. Crushed ice was added to the residue and the mixture was stirred for 1 h. The resulting free flowing solid was washed with water and and saturated sodium bicarbonate, filtered off and dissolved in a 9:1 mixture of DCM and MeOH. The solution was loaded onto silica gel and purified by column chromatography using a gradient of 2 to 10% MeOH in DCM to give 6-(1-chloro-6-methylisoquinolin-5-yl)-N-methylquinazolin-2-amine (9.34 g, 68%) as a yellow foam. MS (M+H)+ 335.

Workup

  1. customthe volatiles were removed under vacuum and residual POCl3
  2. customwas removed
  3. customby azeotroping with toluene
  4. additionCrushed ice was added to the residue
  5. stirringthe mixture was stirred for 1 h
  6. washwas washed with water and and saturated sodium bicarbonate
  7. filtrationfiltered off
  8. dissolutiondissolved in a 9:1 mixture of DCM and MeOH
  9. custompurified by column chromatography

Sources & evidence

ORD record
ord-2fb17beeb3214b4f9c61909dbc22a8f4
Source dataset
uspto-grants-2013_05
Patent number
US08440674B2

Reaction notes

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