Lithium Hydroxide → N-(5-{4-[6-amino-5-(4-fluorobenzoyl)-2-oxopyridin-1(2H)-yl]-3,5-difluorophenoxy}pentyl)-L-leucine

HRID 1667385ノート

反応式

HRID 1667385 の反応式
[NH2:1][C:2]1[N:7]([C:8]2[C:33]([F:34])=[CH:32][C:11]([O:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C@H:19]([C:24]([O:26]C3CCCC3)=[O:25])[CH2:20][CH:21]([CH3:23])[CH3:22])=[CH:10][C:9]=2[F:35])[C:6](=[O:36])[CH:5]=[CH:4][C:3]=1[C:37](=[O:45])[C:38]1[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=1.[Li+].[OH-]>C1COCC1.O>[NH2:1][C:2]1[N:7]([C:8]2[C:9]([F:35])=[CH:10][C:11]([O:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C@H:19]([C:24]([OH:26])=[O:25])[CH2:20][CH:21]([CH3:23])[CH3:22])=[CH:32][C:33]=2[F:34])[C:6](=[O:36])[CH:5]=[CH:4][C:3]=1[C:37](=[O:45])[C:38]1[CH:39]=[CH:40][C:41]([F:44])=[CH:42][CH:43]=1

参加物

5

反応物 2

HCID 3939Lithium HydroxideHCID 24798351Cyclopentyl N-(5-{4-[6-amino-5-(4-fluorobenzoyl)-2-oxopyridin-1(2H)-yl]-3,5-difluorophenoxy}pentyl)-L-leucinate

生成物 1

HCID 57658443N-(5-{4-[6-amino-5-(4-fluorobenzoyl)-2-oxopyridin-1(2H)-yl]-3,5-difluorophenoxy}pentyl)-L-leucine

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

From Example 55. To a solution of cyclopentyl N-(5-{4-[6-amino-5-(4-fluorobenzoyl)-2-oxopyridin-1(2H)-yl]-3,5-difluorophenoxy}pentyl)-L-leucinate (33 mg, 0.05 mmol) in THF (1 ml) and water (1 ml) was added LiOH (25 mg, 1.05 mmol, 20 eq). The mixture was stirred at room temperature for 16 hours, before being heated at 80° C. for 10 hours. The mixture was concentrated under reduced pressure and water (5 ml) added. The pH was adjusted to 7 using 1M HCl and the aqueous layer extracted with 1-butanol (3×5 ml). The combined organic extracts were concentrated under reduced pressure. The solid residue was triturated with Et2O, collected by filtration and purified by preparative HPLC to provide the title compound as a white solid as the mono-TFA salt (7 mg, 24% yield). LC/MS: m/z 560 [M+H]+. 1H NMR (300 MHz, DMSO-d6) δ: 7.62-7.51 (3H, m), 7.34 (2H, m), 7.05 (2H, m), 5.72 (1H, d, J=9.8 Hz), 4.09 (2H, t, J=5.7 Hz), 3.23 (1H, m), 2.80 (2H, m), 1.79-1.43 (9H, m), 0.89 (6H, t, J=6.7 Hz).

後処理

  1. temperaturebefore being heated at 80° C. for 10 hours
  2. concentrationThe mixture was concentrated under reduced pressure and water (5 ml)
  3. additionadded
  4. extractionthe aqueous layer extracted with 1-butanol (3×5 ml)
  5. concentrationThe combined organic extracts were concentrated under reduced pressure
  6. customThe solid residue was triturated with Et2O
  7. filtrationcollected by filtration
  8. custompurified by preparative HPLC

出典と根拠

ORDレコード
ord-1ae9bb94225b4fbe92711b34d8959b13
出典データセット
uspto-grants-2011_10
特許番号
US08044211B2

反応ノート

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