Acetic Acid → HCID 178433750、化合物

HRID 2401799ノート

反応式

HRID 2401799 の反応式
[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

参加物

7

反応物 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

生成物 1

HCID 178433750HCID 178433750、化合物収率 97.2%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-0c52e691263f420a83eff8447f243ae9
出典データセット
uspto-grants-2014_08
特許番号
US08796268B2

反応ノート

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