Dichloromethane → 1-Cyclopentyl-3-ethyl-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one

HRID 2268144ノート

反応式

HRID 2268144 の反応式
[CH:1]1([N:6]2[C:10]3[C:11](=[O:24])[N:12](CC4C=CC(OC)=CC=4)[CH2:13][CH2:14][C:9]=3[C:8]([CH2:25][CH3:26])=[N:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.FC(F)(F)C(O)=O.CS(O)(=O)=O.C(Cl)Cl>O>[CH:1]1([N:6]2[C:10]3[C:11](=[O:24])[NH:12][CH2:13][CH2:14][C:9]=3[C:8]([CH2:25][CH3:26])=[N:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1

参加物

6

反応物 4

HCID 6344DichloromethaneHCID 6395Methanesulfonic AcidHCID 6422Trifluoroacetic acidHCID 98064151-Cyclopentyl-3-ethyl-6-(4-methoxybenzyl)-5,6-dihydro-1H-pyrazolo[3,4-c]pyridin-7(4H)-one

生成物 1

HCID 108235421-Cyclopentyl-3-ethyl-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
70 °C

実験手順

The reaction mixture from Example 8 was cooled to 55° C. and slowly thereto trifluoroacetic acid (87.3 kg, 764 moles) was added while keeping the temperature between 50-60° C. The first ⅓ of the charge was exothermic and required external cooling. Methanesulfonic acid (6342 ml, 97.7 moles) was added and the reaction was warmed to ˜70° C. for two hours. The reaction was cooled to 20-25° C. and methylene chloride (17 gal, 64 L) was added followed by the slow addition of water (17 gal, 64 L). The layers were separated and the aqueous layer was diluted further with water (6 gal, 22.7 L) and then re-extracted with methylene chloride (6 gal, 22.7 L). The combined methylene chloride layers were mixed with water (29 gal, 110 L) and then brought to pH˜7.0 by the addition of saturated sodium bicarbonate (ca. 45 gal, 170 L). The layers were separated and the methylene chloride atmospherically distilled to about 9 gal (35 L). Ethyl acetate (13 gal, 49 L) was added and the reaction mixture was distilled to about 9 gal (35 L). The resulting slurry was cooled and granulated. The solids were collected by filtration, washed with ethyl acetate and vacuum dried at 40° C. under full vacuum. The yield was 7.91 kg, 71.2%; mp 152-153° C.

後処理

  1. custombetween 50-60° C
  2. temperatureThe reaction was cooled to 20-25° C.
  3. customThe layers were separated
  4. additionthe aqueous layer was diluted further with water (6 gal, 22.7 L)
  5. extractionre-extracted with methylene chloride (6 gal, 22.7 L)
  6. additionThe combined methylene chloride layers were mixed with water (29 gal, 110 L)
  7. additionbrought to pH˜7.0 by the addition of saturated sodium bicarbonate (ca. 45 gal, 170 L)
  8. customThe layers were separated
  9. distillationthe methylene chloride atmospherically distilled to about 9 gal (35 L)
  10. additionEthyl acetate (13 gal, 49 L) was added
  11. distillationthe reaction mixture was distilled to about 9 gal (35 L)
  12. temperatureThe resulting slurry was cooled
  13. filtrationThe solids were collected by filtration
  14. washwashed with ethyl acetate and vacuum
  15. customdried at 40° C. under full vacuum

出典と根拠

ORDレコード
ord-f250e9a5cd8741cbbb5e1620b869b791
出典データセット
uspto-grants-2001_12
特許番号
US06326495B2

反応ノート

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