Phosphorus oxychloride → cis-4-(4-Chloro-5-(2-methylpyridin-4-yl)pyrimidin-2-yl)-2,6-dimethylmorpholine

HRID 2278434Notes

Reaction equation

HRID 2278434 reaction equation
[CH3:1][C@H:2]1[CH2:7][N:6]([C:8]2[N:13]=[C:12](O)[C:11]([C:15]3[CH:20]=[CH:19][N:18]=[C:17]([CH3:21])[CH:16]=3)=[CH:10][N:9]=2)[CH2:5][C@@H:4]([CH3:22])[O:3]1.P(Cl)(Cl)([Cl:25])=O>>[Cl:25][C:12]1[C:11]([C:15]2[CH:20]=[CH:19][N:18]=[C:17]([CH3:21])[CH:16]=2)=[CH:10][N:9]=[C:8]([N:6]2[CH2:7][C@H:2]([CH3:1])[O:3][C@H:4]([CH3:22])[CH2:5]2)[N:13]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychloride2×HCID 1784229212-(cis-2,6-Dimethylmorpholino)-5-(2-methylpyridin-4-yl)pyrimidin-4-ol

Product 1

HCID 86702425cis-4-(4-Chloro-5-(2-methylpyridin-4-yl)pyrimidin-2-yl)-2,6-dimethylmorpholineYield 7.1%

Conditions

Temperature
110 °C

Procedure

To solid 2-(cis-2,6-dimethylmorpholino)-5-(2-methylpyridin-4-yl)pyrimidin-4-ol (8.3 g, 27.6 mmol) at 20° C. was added neat phosphorus oxychloride (79 ml, 848 mmol). The reaction mixture was stirred at 110° C. for 3 hours. After cooling to 30° C., most of the phosphorus oxychloride was removed and 20 ml of dichloromethane was added. The solution was added into ice-water. The pH was adjusted to 8 using sodium bicarbonate. The dichloromethane layer was separated, washed with water, dried and evaporated. The crude product was added to a silica gel column and was eluted with dichloromethane and then dichloromethane/methanol (5:1). Collected fractions were evaporated to give the title compound (680 mg, 1.960 mmol, 7.09% yield). LC/MS [M+H]+=319/321.

Workup

  1. customwas removed
  2. addition20 ml of dichloromethane was added
  3. additionThe solution was added into ice-water
  4. customThe dichloromethane layer was separated
  5. washwashed with water
  6. customdried
  7. customevaporated
  8. additionThe crude product was added to a silica gel column
  9. washwas eluted with dichloromethane
  10. customCollected fractions were evaporated

Sources & evidence

ORD record
ord-cc5a853bb795417ebcc59fe0727f1fe8
Source dataset
uspto-grants-2015_09
Patent number
US09133178B2

Reaction notes

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