Phosphorus oxychloride → Methyl 2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetate

HRID 574332Notes

Reaction equation

HRID 574332 reaction equation
O[C:2]1[N:7]2[N:8]=[C:9]([C:11]3[CH:20]=[CH:19][C:18]4[CH2:17][CH2:16][CH2:15][CH2:14][C:13]=4[CH:12]=3)[CH:10]=[C:6]2[N:5]=[C:4]([CH3:21])[C:3]=1[CH2:22][C:23]([O:25][CH3:26])=[O:24].P(Cl)(Cl)([Cl:29])=O>>[Cl:29][C:2]1[N:7]2[N:8]=[C:9]([C:11]3[CH:20]=[CH:19][C:18]4[CH2:17][CH2:16][CH2:15][CH2:14][C:13]=4[CH:12]=3)[CH:10]=[C:6]2[N:5]=[C:4]([CH3:21])[C:3]=1[CH2:22][C:23]([O:25][CH3:26])=[O:24]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178499488HCID 178499488, compound

Product 1

HCID 86670285Methyl 2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetateYield 63.3%

Procedure

Mixture of methyl 2-(7-hydroxy-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetate (8.4 g, 23.90 mmol) and phosphoryl trichloride (10.94 ml, 120 mmol) was heated at reflux for 4 h. Then, cooled, concentrated and the dark residue taken up in EtOAc (500 mL) and stirred with ice-water for 30 min. Aqueous layer separated and organic layer washed with water (2×50 mL). The combine aq layers extracted with EtOAc (2×100 mL) and the combined organic layers washed with brine (100 mL), dried (Na2SO4/C), filtered and concentrated to give dark paste. Purification by flash column chromatography on silica gel column using 5-20% EtOAc/Hex afforded methyl 2-(7-chloro-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetate (5.6 g, 15.14 mmol, 63.3% yield) as off-white solid. 1H NMR (500 MHz, CDCl3) δ 7.76-7.71 (m, 2H), 7.18 (d, J=7.6 Hz, 1H), 6.92 (s, 1H), 3.93 (s, 2H), 3.78 (s, 3H), 2.89-2.84 (m, 4H), 2.63 (s, 3H), 1.86 (dt, J=6.5, 3.3 Hz, 4H). LCMS (M+H)=370.11.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 4 h
  3. temperatureThen, cooled
  4. concentrationconcentrated
  5. customAqueous layer separated
  6. washorganic layer washed with water (2×50 mL)
  7. extractionThe combine aq layers extracted with EtOAc (2×100 mL)
  8. washthe combined organic layers washed with brine (100 mL)
  9. dry with materialdried (Na2SO4/C)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto give dark paste
  13. customPurification by flash column chromatography on silica gel column

Sources & evidence

ORD record
ord-c7fd36ae7cf54962a1203f37a8b56a4c
Source dataset
uspto-grants-2015_05
Patent number
US09034882B2

Reaction notes

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