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Cesium carbonate → Acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-{1-methyl-5-[6-((1S,4S)-5-methyl-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-pyridazin-3-ylamino]-6-oxo-1,6-dihydro-pyridazin-3-yl}-benzyl ester

HRID 1431153
ノート
印刷プレビュー

反応式

HRID 1431153 の反応式
[CH3:1][N:2]1[CH2:7][C@@H:6]2[CH2:8][C@H:3]1[CH2:4][N:5]2[C:9]1[N:14]=[N:13][C:12]([NH2:15])=[CH:11][CH:10]=1.Br[C:17]1[C:22](=[O:23])[N:21]([CH3:24])[N:20]=[C:19]([C:25]2[CH:35]=[CH:34][CH:33]=[C:32]([N:36]3[N:45]=[CH:44][C:43]4[C:38](=[C:39]([F:50])[CH:40]=[C:41]([C:46]([CH3:49])([CH3:48])[CH3:47])[CH:42]=4)[C:37]3=[O:51])[C:26]=2[CH2:27][O:28][C:29](=[O:31])[CH3:30])[CH:18]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[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:32]1[CH:33]=[CH:34][CH:35]=[C:25]([C:19]3[CH:18]=[C:17]([NH:15][C:12]4[N:13]=[N:14][C:9]([N:5]5[CH2:4][C@@H:3]6[CH2:8][C@H:6]5[CH2:7][N:2]6[CH3:1])=[CH:10][CH:11]=4)[C:22](=[O:23])[N:21]([CH3:24])[N:20]=3)[C:26]=1[CH2:27][O:28][C:29](=[O:31])[CH3:30])[N:45]=[CH:44]2)([CH3:47])([CH3:48])[CH3:49]
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 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 667421922-(5-bromo-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)-6-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)benzyl acetateHCID 667430796-((1S,4S)-5-Methyl-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-pyridazin-3-ylamine

生成物 1

HCID 66743398
Acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-{1-methyl-5-[6-((1S,4S)-5-methyl-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-pyridazin-3-ylamino]-6-oxo-1,6-dihydro-pyridazin-3-yl}-benzyl ester

試薬・触媒・溶媒 1

HCID 9811564Bis(dibenzylideneacetone)palladium触媒

反応条件

温度
100 °C

実験手順

6-((1S,4S)-5-Methyl-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-pyridazin-3-ylamine (100 mg, 0.487 mmol, Eq: 1.00), acetic acid 2-(5-bromo-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl)-6-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-benzyl ester (284 mg, 0.512 mmol, Eq: 1.05), xantphos (42.3 mg, 0.073 mmol, Eq: 0.15), tris(dibenzylideneacetone)-dipalladium (0) (33.5 mg, 0.036 mmol, Eq: 0.075) and cesium carbonate (476 mg, 1.46 mmol, Eq: 3.00) were added to a microwave vial. The vial was capped and purged. Degassed dioxane (about 5 ml) was added through a syringe and the vial was purged again and back filled with nitrogen. The reaction was heated at 100° C. overnight in a sand bath. The reaction was filtered through celite and concentrated. The crude product was purified by chromatography using a gradient of 0% to 25% methanol in DCM. LCMS and NMR showed major impurities. Took on to next step without further purification.

後処理

  1. customThe vial was capped
  2. custompurged
  3. additionDegassed dioxane (about 5 ml) was added through a syringe
  4. customthe vial was purged again
  5. additionback filled with nitrogen
  6. filtrationThe reaction was filtered through celite
  7. concentrationconcentrated
  8. customThe crude product was purified by chromatography
  9. customTook on to next step without further purification

出典と根拠

ORDレコード
ord-41c79ba0c8eb45608435530ccce6d75a
出典データセット
uspto-grants-2015_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08940741B2

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