Phosphorus oxychloride → 4-chloro-1-(2-(trifluoromethyl)phenyl)-1H-pyrazolo[3,4-d]pyrimidine

HRID 1098137Notes

Reaction equation

HRID 1098137 reaction equation
P(Cl)(Cl)([Cl:3])=O.[F:6][C:7]([F:25])([F:24])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[N:14]1[C:18]2=[N:19][CH:20]=[N:21][C:22](O)=[C:17]2[CH:16]=[N:15]1>>[Cl:3][C:22]1[N:21]=[CH:20][N:19]=[C:18]2[N:14]([C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=3[C:7]([F:25])([F:24])[F:6])[N:15]=[CH:16][C:17]=12

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178517918HCID 178517918, compound

Product 1

HCID 114834004-chloro-1-(2-(trifluoromethyl)phenyl)-1H-pyrazolo[3,4-d]pyrimidineYield 85%

Conditions

Temperature
100 °C

Procedure

Phosphoryl trichloride (34.2 ml, 356.88 mmol) was added to 1-(2-(trifluoromethyl)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ol (Intermediate P2) (5.0 g, 17.84 mmol). The resulting solution was stirred at 100° C. for 4 hours. The mixture was evaporated and the residue added to ice (˜200 g) with vigorous stirring. The mixture was stirred for 30 mins and the solid was collected by filtration washed with water (3×50 mL) and dried by suction. The solid was dissolved in ethyl acetate (250 mL), dried (MgSO4) and evaporated to give the product (4.5 g, 85%). 1H NMR (400 MHz, DMSO) δ 7.75-7.80 (1H, m), 7.88-7.91 (1H, m), 7.95-7.98 (1H, m), 8.05-8.07 (1H, m), 8.79 (1H, s), 8.88 (1H, s); m/z (ESI+) (M+H)+=299; HPLC tR=2.39 min.

Workup

  1. customThe mixture was evaporated
  2. additionthe residue added to ice (˜200 g) with vigorous stirring
  3. stirringThe mixture was stirred for 30 mins
  4. filtrationthe solid was collected by filtration
  5. washwashed with water (3×50 mL)
  6. customdried by suction
  7. dissolutionThe solid was dissolved in ethyl acetate (250 mL)
  8. dry with materialdried (MgSO4)
  9. customevaporated

Sources & evidence

ORD record
ord-e0b102b6a44a4a898f8365f1455a92f8
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

Loading…