Phosphorus oxychloride → 5-Chloro-2-(morpholin-4-ylmethyl)-7-[4-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-c]pyrimidine

HRID 2389818Notes

Reaction equation

HRID 2389818 reaction equation
[N:1]1([CH2:7][C:8]2[N:16]=[C:15]3[N:10]([C:11](O)=[N:12][C:13]([C:17]4[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=4)=[CH:14]3)[N:9]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(=O)(O)[O-].[Na+].P(Cl)(Cl)([Cl:35])=O>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1>[Cl:35][C:11]1[N:10]2[N:9]=[C:8]([CH2:7][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[N:16]=[C:15]2[CH:14]=[C:13]([C:17]2[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=2)[N:12]=1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 178517471HCID 178517471, compound

Product 1

HCID 593131385-Chloro-2-(morpholin-4-ylmethyl)-7-[4-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-c]pyrimidine

Reagents, catalysts & solvents 1

HCID 66133Benzyl triethylammonium chlorideCatalyst

Conditions

Temperature
120 °C

Procedure

850 mg (2.2 mmol) of 2-(morpholin-4-ylmethyl)-7-[4-(trifluoromethyl)phenyl][1,2,4]triazolo-[1,5-c]pyrimidin-5-ol (Example 135A) are introduced into phosphoryl chloride (20 ml), 1.98 g (8.7 mmol) of benzyltriethylammonium chloride are added, and the reaction mixture is stirred at 120° C. for 2 h. The reaction mixture is slowly poured, while stirring vigorously, into ice-water, and solid sodium bicarbonate is added until a pH of 8 is reached. The reaction mixture is extracted with ethyl acetate (150 ml), and the organic phase is separated off, dried (magnesium sulphate) and concentrated. The residue is chromatographed on silica gel (mobile phase dichloromethane/ethanol 100:1 to 20:1). 650 mg (75% of theory) of the product are obtained as a solid.

Workup

  1. additionare added
  2. additionThe reaction mixture is slowly poured
  3. additionis added until a pH of 8
  4. extractionThe reaction mixture is extracted with ethyl acetate (150 ml)
  5. customthe organic phase is separated off
  6. dry with materialdried (magnesium sulphate)
  7. concentrationconcentrated
  8. customThe residue is chromatographed on silica gel (mobile phase dichloromethane/ethanol 100:1 to 20:1)
  9. custom650 mg (75% of theory) of the product are obtained as a solid

Sources & evidence

ORD record
ord-84ee823158044240bf2b6cf9f15c8370
Source dataset
uspto-grants-2012_09
Patent number
US08273752B2

Reaction notes

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