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tert-butyl 4-(6-(6-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)piperidine-1-carboxylate → 6-tert-butyl-8-fluoro-2-(2-(hydroxymethyl)-3-(1-methyl-6-oxo-5-(5-(piperidin-4-yl)pyridin-2-ylamino)-1,6-dihydropyridazin-3-yl)phenyl)phthalazin-1(2H)-one

HRID 449695
ノート
印刷プレビュー

反応式

HRID 449695 の反応式
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[C:18]([CH2:51][OH:52])=[C:19]([C:23]3[CH:24]=[C:25]([NH:31][C:32]4[N:37]=[CH:36][C:35]([CH:38]5[CH2:43][CH2:42][N:41](C(OC(C)(C)C)=O)[CH2:40][CH2:39]5)=[CH:34][CH:33]=4)[C:26](=[O:30])[N:27]([CH3:29])[N:28]=3)[CH:20]=[CH:21][CH:22]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2]>ClCCl>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23]3[CH:24]=[C:25]([NH:31][C:32]4[CH:33]=[CH:34][C:35]([CH:38]5[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]5)=[CH:36][N:37]=4)[C:26](=[O:30])[N:27]([CH3:29])[N:28]=3)[C:18]=1[CH2:51][OH:52])[N:9]=[CH:8]2)([CH3:4])([CH3:2])[CH3:3]
参加物実験手順後処理出典と根拠反応ノート

参加物

3

反応物 1

HCID 66742289tert-butyl 4-(6-(6-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)piperidine-1-carboxylate

生成物 1

HCID 566563386-tert-butyl-8-fluoro-2-(2-(hydroxymethyl)-3-(1-methyl-6-oxo-5-(5-(piperidin-4-yl)pyridin-2-ylamino)-1,6-dihydropyridazin-3-yl)phenyl)phthalazin-1(2H)-one収率 65.7%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

tert-butyl 4-(6-(6-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)piperidine-1-carboxylate (85 mg, 120 μmol) was deprotected by treatment with 50% trifluoro acid in dichloromethane (10 mL) for 2 hr. The reaction mixture was concentrated to dryness, then partitioned between ethyl acetate and saturated sodium bicarbonate. The organic phase was dried over sodium sulfate, filtered and concentrated. The resulting crude product was further purified by crystallization from hot isopropylacetate/hexanes. A crystalline product was collected by filtration, providing the desired product as a white solid (48 mg, 65.7%). (M+H)+=610 m/e. 1H NMR (300 MHz, CHLOROFORM-d) δ: 8.63 (s, 1H), 8.27-8.33 (m, 2H), 8.21 (d, J=2.0 Hz, 1H), 7.44-7.72 (m, 6H), 6.94 (d, J=8.5 Hz, 1H), 4.46 (s, 2H), 3.88-3.96 (m, 3H), 3.35-3.44 (m, 2H), 2.85-2.99 (m, 2H), 2.65-2.78 (m, 1H), 1.83-1.97 (m, 4H), 1.43 (s, 9H).

後処理

  1. concentrationThe reaction mixture was concentrated to dryness
  2. custompartitioned between ethyl acetate and saturated sodium bicarbonate
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting crude product was further purified by crystallization from hot isopropylacetate/hexanes
  7. filtrationA crystalline product was collected by filtration

出典と根拠

ORDレコード
ord-c3b31ec6e9ed45e9ab133513f1376fe0
出典データセット
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08481540B2

反応ノート

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このページの内容参加物実験手順後処理出典と根拠反応ノート