Sodium Hydroxide → 2-[3-(4-fluorophenyl)-1-(2-hydroxyethyl)-4-(4-pyridinyl)-1H-pyrazol-5-yl]cyclopropanecarboxylic acid

HRID 1167516ノート

反応式

HRID 1167516 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([C:13]3[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=3)=[C:11]([CH:19]3[CH2:21][CH:20]3[C:22]([O:24]CC)=[O:23])[N:10]([CH2:27][CH2:28][OH:29])[N:9]=2)=[CH:4][CH:3]=1.C1CC(NC2C3C(=CC(Cl)=C(Cl)C=3)C(C3C=CN=CC=3)=NN=2)CC1.[OH-].[Na+]>CO.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([C:13]3[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=3)=[C:11]([CH:19]3[CH2:21][CH:20]3[C:22]([OH:24])=[O:23])[N:10]([CH2:27][CH2:28][OH:29])[N:9]=2)=[CH:4][CH:3]=1

参加物

6

反応物 3

HCID 14798Sodium HydroxideHCID 22037272ethyl 2-[3-(4-fluorophenyl)-1-(2-hydroxyethyl)-4-(4-pyridinyl)-1H-pyrazol-5-yl]cyclopropanecarboxylateHCID 1170725486,7-dichloro-N-cyclopentyl-4-(pyridin-4-yl)phthalazin-1-amine

生成物 1

HCID 220373372-[3-(4-fluorophenyl)-1-(2-hydroxyethyl)-4-(4-pyridinyl)-1H-pyrazol-5-yl]cyclopropanecarboxylic acid

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 962Water溶媒

実験手順

To a solution of ethyl 2-[3-(4-fluorophenyl)-1-(2-hydroxyethyl)-4-(4-pyridinyl)-1H-pyrazol-5-yl]cyclopropanecarboxylate prepared in accordance with Example A-196 (0.21 g, 0.00045 mol) in 10 mL of methanol was added a solution of sodium hydroxide (0.09 g, 0.0022 mol) in 2 mL of water. The reaction mixture was stirred at reflux for 6 hours. After the solvent was removed, the residue was dissolved with 10 mL of 1N HCl and stirred for 30 minutes. The pH was then adjusted to 5-6 by addition of 1N sodium hydroxide solution and then extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium and filtered. The filtrate was concentrated and the crude was purified by recrystallization from ethanol and ether to give 0.1 g of product, 2-[3-(4-fluorophenyl)-1-(2-hydroxyethyl)-4-(4-pyridinyl)-1H-pyrazol-5-yl]cyclopropanecarboxylic acid, as a white solid (60% yield), mp: 253-255° C.; 1H NMR (CD3OD): δ 8.46 (m, 2H), 7.32 (m, 2H), 7.25 (m, 2H), 7.04 (m, 2H), 4.39 (t, J=5.0 Hz, 2H), 4.03 (m, 2H), 2.60 (m, 1H), 1.51 (m, 2H), 0.97 (m, 2H); Anal. Calc'd For C20H18FN3O3: C, 65.39; H, 4.94; N, 11.44. Found: C, 64.92; H, 4.77; N, 11.20.

後処理

  1. temperatureat reflux for 6 hours
  2. customAfter the solvent was removed
  3. dissolutionthe residue was dissolved with 10 mL of 1N HCl
  4. stirringstirred for 30 minutes
  5. additionThe pH was then adjusted to 5-6 by addition of 1N sodium hydroxide solution
  6. extractionextracted with ethyl acetate
  7. washThe organic layer was washed with brine
  8. dry with materialdried over magnesium
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated
  11. customthe crude was purified by recrystallization from ethanol and ether

出典と根拠

ORDレコード
ord-cadf3b7f8ff143efbed55a0d1b4e99b9
出典データセット
uspto-grants-2003_09
特許番号
US06617324B1

反応ノート

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