Phosphorus oxychloride → HCID 46912982, compound

HRID 535981Notes

Reaction equation

HRID 535981 reaction equation
[NH2:1][C:2]1[NH:7][C:6](=O)[N:5]([CH2:9][CH2:10][CH3:11])[C:4](=[O:12])[C:3]=1[NH:13][C:14]([C:16]1[CH:17]=[N:18][N:19]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[C:24]([F:32])[CH:23]=2)[CH:20]=1)=O.O=P(Cl)(Cl)[Cl:35].P(Cl)(Cl)(Cl)(Cl)Cl>>[Cl:35][C:6]1[N:5]([CH2:9][CH2:10][CH3:11])[C:4](=[O:12])[C:3]2[NH:13][C:14]([C:16]3[CH:17]=[N:18][N:19]([CH2:21][C:22]4[CH:27]=[CH:26][C:25]([C:28]([F:30])([F:29])[F:31])=[C:24]([F:32])[CH:23]=4)[CH:20]=3)=[N:1][C:2]=2[N:7]=1

Participants

4

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 24819Phosphorus pentachlorideHCID 69481133HCID 69481133, compound

Product 1

HCID 46912982HCID 46912982, compoundYield 50%

Conditions

Temperature
127.5 °C

Procedure

A mixture of 1-(3-fluoro-4-trifluoromethyl-benzyl)-1H-pyrazole-4-carboxylic acid (6-amino-2,4-dioxo-3-propyl-1,2,3,4-tetrahydro-pyrimidin-5-yl)-amide (0.8 g, 1.76 mmol), POCl3 (25 ml) and PCl5 (0.2 g) were heated at 125-130° C. for 20 hours. Reaction mixture was cooled to 20-25° C. and it was concentrated under vacuum. To this reaction mixture brine (50 ml) was added and extracted with ethyl acetate (3×2 ml). The combined organic layer was dried over Na2SO4 and evaporated to dryness. The crude product was purified by column chromatography using silica gel (100-200 mesh) and 2 to 4% methanol in DCM as an eluent to obtain 2-Chloro-8-[1-(3-fluoro-4-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1-propyl-1,7-dihydro-purin-6-one (0.4 g, 50%) as a pale brown solid.

Workup

  1. customReaction mixture
  2. temperaturewas cooled to 20-25° C.
  3. concentrationit was concentrated under vacuum
  4. additionTo this reaction mixture brine (50 ml) was added
  5. extractionextracted with ethyl acetate (3×2 ml)
  6. dry with materialThe combined organic layer was dried over Na2SO4
  7. customevaporated to dryness
  8. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-dac47beea17e43c4950fe7b64a08e80c
Source dataset
uspto-grants-2014_10
Patent number
US08859566B2

Reaction notes

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