Water → 7-(2-Chloro-4-methoxyphenyl)-2,6-dimethylpyrazolo[1,5-a]pyridin-3-amine

HRID 859146Notes

Reaction equation

HRID 859146 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[C:10]1[N:15]2[N:16]=[C:17]([CH3:22])[C:18](C(O)=O)=[C:14]2[CH:13]=[CH:12][C:11]=1[CH3:23].C([N:26](CC)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.O>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[C:10]1[N:15]2[N:16]=[C:17]([CH3:22])[C:18]([NH2:26])=[C:14]2[CH:13]=[CH:12][C:11]=1[CH3:23]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 695888007-(2-Chloro-4-methoxyphenyl)-2,6-dimethylpyrazolo[1,5-a]pyridine-3-carboxylic acid

Product 1

HCID 695891127-(2-Chloro-4-methoxyphenyl)-2,6-dimethylpyrazolo[1,5-a]pyridin-3-amineYield 9%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

A 0° C. solution of 7-(2-chloro-4-methoxyphenyl)-2,6-dimethylpyrazolo[1,5-a]pyridine-3-carboxylic acid (0.58 g, 1.8 mmol) and triethylamine (0.30 mL, 2.2 mmol) in toluene (10 mL) was treated with diphenylphosphoryl azide (0.40 mL, 1.8 mmol) and stirred for 2.5 hours at 0° C. The reaction mixture was poured into H2O, extracted with Et2O, washed with brine, dried over MgSO4, and filtered. The filtrate was concentrated in vacuo to remove the Et2O. Toluene (20 mL) was added and the reaction was heated to reflux for 3 hours. The reaction was treated with 2N HCl (5 mL) and stirred at reflux for 1 hour then cooled to room temperature. The layers were separated and the aqueous layer was basified with solid K2CO3. The residue was extracted with CH2Cl2, dried over MgSO4 and filtered. The filtrate was concentrated in vacuo to give 0.046 g (9%) of a yellow oily solid as the title compound: 1H NMR (400 MHz, CDCl3) δ 7.42 (d, J=7.1 Hz, 1H), 7.35 (d, J=9.3 Hz, 1H), 7.13 (d, J=2.5 Hz, 1H), 7.01 (dd, J=8.5, 2.5 Hz, 1H), 6.96 (d, J=8.8 Hz, 1H), 3.90 (s, 3H), 2.38 (s, 3H), 2.08 (s, 3H); MS (EI) m/z 302.18 (M++H).

Workup

  1. extractionextracted with Et2O
  2. washwashed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customto remove the Et2O
  7. additionToluene (20 mL) was added
  8. temperaturethe reaction was heated
  9. temperatureto reflux for 3 hours
  10. additionThe reaction was treated with 2N HCl (5 mL)
  11. stirringstirred
  12. temperatureat reflux for 1 hour
  13. temperaturethen cooled to room temperature
  14. customThe layers were separated
  15. extractionThe residue was extracted with CH2Cl2
  16. dry with materialdried over MgSO4
  17. filtrationfiltered
  18. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-fd586dc197084aca85889d499b4cc217
Source dataset
uspto-grants-2006_12
Patent number
US07151109B2

Reaction notes

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