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Sodium Hydroxide → 6-tert-butyl-8-fluoro-2-(2-hydroxymethyl-3-{8-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-phenyl)-2H-phthalazin-1-one

HRID 402928
ノート
印刷プレビュー

反応式

HRID 402928 の反応式
C([O:4][CH2:5][C:6]1[C:11]([C:12]2[CH:13]=[C:14]([NH:21][C:22]3[CH:27]=[CH:26][C:25]([C:28]([N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)=[O:29])=[CH:24][N:23]=3)[C:15]3[N:16]([N:18]=[CH:19][N:20]=3)[CH:17]=2)=[CH:10][CH:9]=[CH:8][C:7]=1[N:36]1[N:45]=[CH:44][C:43]2[C:38](=[C:39]([F:50])[CH:40]=[C:41]([C:46]([CH3:49])([CH3:48])[CH3:47])[CH:42]=2)[C:37]1=[O:51])(=O)C.[OH-].[Na+]>C1COCC1.C([O-])(O)=O.[Na+].C(Cl)Cl>[C:46]([C:41]1[CH:42]=[C:43]2[C:38](=[C:39]([F:50])[CH:40]=1)[C:37](=[O:51])[N:36]([C:7]1[CH:8]=[CH:9][CH:10]=[C:11]([C:12]3[CH:13]=[C:14]([NH:21][C:22]4[CH:27]=[CH:26][C:25]([C:28]([N:30]5[CH2:31][CH2:32][O:33][CH2:34][CH2:35]5)=[O:29])=[CH:24][N:23]=4)[C:15]4[N:16]([N:18]=[CH:19][N:20]=4)[CH:17]=3)[C:6]=1[CH2:5][OH:4])[N:45]=[CH:44]2)([CH3:49])([CH3:47])[CH3:48]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 2

HCID 14798Sodium HydroxideHCID 866868282-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(8-(5-(morpholine-4-carbonyl)pyridin-2-ylamino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)benzyl acetate

生成物 1

HCID 866868306-tert-butyl-8-fluoro-2-(2-hydroxymethyl-3-{8-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-phenyl)-2H-phthalazin-1-one収率 23%

試薬・触媒・溶媒 3

HCID 6344
Dichloromethane
溶媒
HCID 8028Tetrahydrofuran溶媒
HCID 516892Sodium Bicarbonate溶媒

反応条件

温度
60 °C

実験手順

To a solution of 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(8-(5-(morpholine-4-carbonyl)pyridin-2-ylamino)-[1,2,4]triazolo[1,5-a]pyridin-6-yl)benzyl acetate (289 mg, 418 μmol, Eq: 1.00) in THF (5.0 ml) was added NaOH (1.0 N, 5.0 ml, 5.00 mmol, Eq: 12.0). The solution was heated to 60° C. for 18 h. The reaction was cooled to room temperature. The reaction was diluted with sat NaHCO3 (aq) and DCM. The layers were separated. The aqueous layer was extracted three times with DCM, and then dried over MgSO4. The solid was removed by filtration. The filtrate was concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 0% to 10% MeOH/DCM gradient) to give a residue. The residue was triturated with Et2O to give 6-tert-butyl-8-fluoro-2-(2-hydroxymethyl-3-{8-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-[1,2,4]triazolo[1,5-a]pyridin-6-yl}-phenyl)-2H-phthalazin-1-one (61 mg, 23%). 1H NMR (300 MHz, CHLOROFORM-d) d ppm 1.36-1.49 (m, 9H) 3.51-3.95 (m, 8H) 4.40 (s, 2H) 7.20 (dd, J=18.13, 7.18 Hz, 1H) 7.41-7.67 (m, 6H) 7.76 (dd, J=8.31, 2.27 Hz, 1H) 8.31 (d, J=2.64 Hz, 1H) 8.36-8.48 (m, 2H) 8.66 (s, 1H) 8.95 (s, 1H) LC/MS-ESI observed [M+H]+ 649.

後処理

  1. temperatureThe reaction was cooled to room temperature
  2. customThe layers were separated
  3. extractionThe aqueous layer was extracted three times with DCM
  4. dry with materialdried over MgSO4
  5. customThe solid was removed by filtration
  6. concentrationThe filtrate was concentrated in vacuo
  7. customThe crude material was purified by flash chromatography (silica gel, 0% to 10% MeOH/DCM gradient)
  8. customto give a residue
  9. customThe residue was triturated with Et2O

出典と根拠

ORDレコード
ord-940a1ed9f93c45739ba4b7afba7ad196
出典データセット
uspto-grants-2014_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08742098B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート