Acetic Acid → HCID 178433750, compound

HRID 2402059Notes

Reaction equation

HRID 2402059 reaction equation
[Cl:1][C:2]1[CH:43]=[CH:42][C:5]([CH2:6][C:7]2[N:8]=[C:9]([C:25]3[C:26]([CH3:41])=[N:27][N:28]4[CH:33]=[CH:32][C:31]([CH:34](OCC)[O:35]CC)=[CH:30][C:29]=34)[S:10][C:11]=2[C:12]2[N:16]=[CH:15][N:14](COCC[Si](C)(C)C)[N:13]=2)=[CH:4][CH:3]=1.Cl.C(O)(=O)C.C([O-])(O)=O.[Na+]>O1CCOCC1.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][C:7]2[N:8]=[C:9]([C:25]3[C:26]([CH3:41])=[N:27][N:28]4[CH:33]=[CH:32][C:31]([CH:34]=[O:35])=[CH:30][C:29]=34)[S:10][C:11]=2[C:12]2[NH:16][CH:15]=[N:14][N:13]=2)=[CH:42][CH:43]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 667491933-[4-(4-Chlorobenzyl)-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-1,3-thiazol-2-yl]-5-(diethoxymethyl)-2-methylpyrazolo[1,5-a]pyridine

Product 1

HCID 178433750HCID 178433750, compoundYield 97.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

3-[4-(4-Chlorobenzyl)-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-1,3-thiazol-2-yl]-5-(diethoxymethyl)-2-methylpyrazolo[1,5-a]pyridine (1.17 g, 1.83 mmol) was dissolved in 1,4-dioxane (45 mL) and cooled in a water bath. 12 M hydrochloric acid (15 mL) was added and the mixture was stirred at rt for 15 hours. Acetic acid (40 mL, 700 mmol) was added and the suspension was stirred at rt for 24 hours then heated to 70° C. for 2 hours, then evaporated. The solid residue was stirred with 1.00 hydrochloric acid (100 mL) and methanol (120 mL) at rt for 14 hours. The mixture was evaporated on a rotovap at 45° C. to dryness and then azeotroped with DCM to give a crude product. The crude product was suspended in water, basified with NaHCO3 to ˜pH 8, extracted with EtOAc (300 mL, 3×80 mL), washed with brine, dried over Na2SO4, filtered, and evaporated to afford a yellow solid product (0.773 g, yield 97.2%). LCMS: (FA) ES+ 435, 437. 1H NMR (400 MHz, CDCl3) δ: 10.84 (s, br, 1H), 9.99 (s, 1H), 8.75 (m, 1H), 8.43-8.46 (d, J=7.28 Hz, 1H), 8.36 (s, 1H), 7.41-7.44 (d, J=8.53 Hz, 2H), 7.32-7.35 (dd, J=7.03, 2.01 Hz, 1H), 7.27-7.30 (d, J=8.53 Hz, 2H), 4.69 (s, 2H), 2.79 (s, 3H).

Workup

  1. temperaturecooled in a water bath
  2. stirringthe suspension was stirred at rt for 24 hours
  3. temperaturethen heated to 70° C. for 2 hours
  4. customevaporated
  5. stirringThe solid residue was stirred with 1.00 hydrochloric acid (100 mL) and methanol (120 mL) at rt for 14 hours
  6. customThe mixture was evaporated on a rotovap at 45° C. to dryness
  7. customazeotroped with DCM
  8. customto give a crude product
  9. extractionextracted with EtOAc (300 mL, 3×80 mL)
  10. washwashed with brine
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. customevaporated

Sources & evidence

ORD record
ord-b80da1a25bd5428889e309e1eb718f8a
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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