Methanol → HCID 178435508、化合物

HRID 541354ノート

反応式

HRID 541354 の反応式
[NH2:1][C:2]1[O:6][C:5]([C:7]2[C:8]([CH:32]3[CH2:35][CH2:34][CH2:33]3)=[CH:9][C:10]([CH2:30][CH3:31])=[C:11]([CH:29]=2)[C:12]([N:14]2[CH2:19][CH2:18][C:17]([C:21]3[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][CH:22]=3)([F:20])[CH2:16][CH2:15]2)=[O:13])=[N:4][N:3]=1.[OH-].[K+].[CH3:38]O>>[CH:32]1([C:8]2[C:7]([C:5]3[NH:1][C:2]([O:6][CH3:38])=[N:3][N:4]=3)=[CH:29][C:11]([C:12]([N:14]3[CH2:15][CH2:16][C:17]([C:21]4[CH:22]=[CH:23][C:24]([C:25]#[N:26])=[CH:27][CH:28]=4)([F:20])[CH2:18][CH2:19]3)=[O:13])=[C:10]([CH2:30][CH3:31])[CH:9]=2)[CH2:35][CH2:34][CH2:33]1

参加物

4

反応物 3

HCID 887MethanolHCID 14797Potassium HydroxideHCID 682889534-(1-(5-(5-Amino-1,3,4-oxadiazol-2-yl)-4-cyclobutyl-2-ethylbenzoyl)-4-fluoropiperidin-4-yl)benzonitrile2 回

生成物 1

HCID 178435508HCID 178435508、化合物収率 10%

反応条件

温度
70 °C

実験手順

To a round-bottom flask, which was purged and maintained with a nitrogen atmosphere, was added a solution of 4-(1-(5-(5-amino-1,3,4-oxadiazol-2-yl)-4-cyclobutyl-2-ethylbenzoyl)-4-fluoropiperidin-4-yl)benzonitrile (compound 217.3, 200 mg, 0.420 mmol, 1.00 equiv) in methanol (20 mL). Potassium hydroxide (237 mg, 4.22 mmol, 10.0 equiv) was added to the reaction mixture. The resulting solution was stirred for 15 h at 70° C. After cooling to ambient temperature, the organic solvent was removed under reduced pressure. The residue was diluted with 30 mL of H2O, then extracted with 2×50 mL of ethyl acetate. The combined organic layers were washed with 2×50 mL of brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product (50 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU)): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, water with 0.05% TFA and CH3CN (49.0% CH3CN up to 63.0% in 8 min, up to 100.0% in 1 min, down to 49.0% in 1 min); Detector, Waters 2489 254&220 nm. The fractions containing pure compound were combined and lyophilized to yield 20 mg (10%) of the title compound as a white. m/z (ES+) 488 (M+H)+. 1H-NMR (300 MHz, CD3OD): δ 7.72 (d, 2H), 7.64-7.61 (m, 2H), 7.39-7.25 (m, 2H), 4.85-4.78 (m, 1H), 4.00-3.93 (m, 4H), 3.54-3.49 (m, 2H), 3.28-3.22 (m, 1H), 2.80-2.65 (m, 2H), 2.26-1.84 (m, 10H), 1.45-1.27 (m, 3H).

後処理

  1. customTo a round-bottom flask, which was purged
  2. temperaturemaintained with a nitrogen atmosphere
  3. temperatureAfter cooling to ambient temperature
  4. customthe organic solvent was removed under reduced pressure
  5. additionThe residue was diluted with 30 mL of H2O
  6. extractionextracted with 2×50 mL of ethyl acetate
  7. washThe combined organic layers were washed with 2×50 mL of brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated in vacuo
  10. customThe crude product (50 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU))
  11. waitmobile phase, water with 0.05% TFA and CH3CN (49.0% CH3CN up to 63.0% in 8 min
  12. waitup to 100.0% in 1 min
  13. waitdown to 49.0% in 1 min)
  14. additionThe fractions containing pure compound

出典と根拠

ORDレコード
ord-24fcb53449a74714882e3262427fd1ab
出典データセット
uspto-grants-2014_10
特許番号
US08871790B2

反応ノート

読み込み中…