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Potassium Phosphate, Tribasic → Acetic acid 2-{5-[5-(1-amino-1-methyl-ethyl)-pyridin-2-ylamino]-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl}-6-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-benzyl ester

HRID 2069865
ノート
印刷プレビュー

反応式

HRID 2069865 の反応式
[NH2:1][C:2]([C:5]1[CH:6]=[CH:7][C:8]([NH:11][C:12]2[C:13](=[O:20])[N:14]([CH3:19])[CH:15]=[C:16](Br)[CH:17]=2)=[N:9][CH:10]=1)([CH3:4])[CH3:3].[C:21]([C:25]1[CH:26]=[C:27]2[C:32](=[C:33]([F:35])[CH:34]=1)[C:31](=[O:36])[N:30]([C:37]1[CH:47]=[CH:46][CH:45]=[C:44](B3OC(C)(C)C(C)(C)O3)[C:38]=1[CH2:39][O:40][C:41](=[O:43])[CH3:42])[N:29]=[CH:28]2)([CH3:24])([CH3:23])[CH3:22].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.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]>[NH2:1][C:2]([C:5]1[CH:6]=[CH:7][C:8]([NH:11][C:12]2[C:13](=[O:20])[N:14]([CH3:19])[CH:15]=[C:16]([C:44]3[CH:45]=[CH:46][CH:47]=[C:37]([N:30]4[N:29]=[CH:28][C:27]5[C:32](=[C:33]([F:35])[CH:34]=[C:25]([C:21]([CH3:23])([CH3:22])[CH3:24])[CH:26]=5)[C:31]4=[O:36])[C:38]=3[CH2:39][O:40][C:41](=[O:43])[CH3:42])[CH:17]=2)=[N:9][CH:10]=1)([CH3:4])[CH3:3]
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

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 594737692-(6-(tert-Butyl)-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetateHCID 594738243-[5-(1-Amino-1-methyl-ethyl)-pyridin-2-ylamino]-5-bromo-1-methyl-1H-pyridin-2-one

生成物 1

HCID 59473787
Acetic acid 2-{5-[5-(1-amino-1-methyl-ethyl)-pyridin-2-ylamino]-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl}-6-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-benzyl ester
収率 54%

試薬・触媒・溶媒 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
125 °C

実験手順

3-[5-(1-Amino-1-methyl-ethyl)-pyridin-2-ylamino]-5-bromo-1-methyl-1H-pyridin-2-one (160 mg, 0.474 mmol), Acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl ester (235 mg, 0.474 mmol), x-phos (34 mg, 0.0712 mmol), potassium phosphate (252 mg, 1.186 mmol) were dissolved in dioxane (4 ml) and water (1 ml). Finally bis(dibenzylideneacetone)palladium (41 mg, 0.0712 mmol) was added and heated in the microwave to 125° C. for 30 min. The reaction mixture was filtered, washed with dioxane, partially concentrated and dry loaded to a 24 g SiOH column. Purification by chromatography with 0-10% MeOH (contains 1% NH4OH) in DCM for 30 min afforded Acetic acid 2-{5-[5-(1-amino-1-methyl-ethyl)-pyridin-2-ylamino]-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl}-6-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-benzyl ester (159 mg, 54%) as a yellow solid. MS (H+) 625.2.

後処理

  1. filtrationThe reaction mixture was filtered
  2. washwashed with dioxane
  3. concentrationpartially concentrated
  4. customdry
  5. customPurification by chromatography with 0-10% MeOH (contains 1% NH4OH) in DCM for 30 min

出典と根拠

ORDレコード
ord-b8b318cef5ac40c79e128ab0c4a919cf
出典データセット
uspto-grants-2012_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08299077B2

反応ノート

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