Potassium Carbonate → acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-{2-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-pyridin-4-yl}-benzyl ester

HRID 402937ノート

反応式

HRID 402937 の反応式
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[N:14]=[CH:13][C:12]([C:15]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[O:16])=[CH:11][CH:10]=2)[CH:3]=1.[C:23]([C:27]1[CH:28]=[C:29]2[C:34](=[C:35]([F:37])[CH:36]=1)[C:33](=[O:38])[N:32]([C:39]1[CH:49]=[CH:48][CH:47]=[C:46](B3OC(C)(C)C(C)(C)O3)[C:40]=1[CH2:41][O:42][C:43](=[O:45])[CH3:44])[N:31]=[CH:30]2)([CH3:26])([CH3:25])[CH3:24].C([O-])([O-])=O.[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:23]([C:27]1[CH:28]=[C:29]2[C:34](=[C:35]([F:37])[CH:36]=1)[C:33](=[O:38])[N:32]([C:39]1[CH:49]=[CH:48][CH:47]=[C:46]([C:2]3[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]4[CH:10]=[CH:11][C:12]([C:15]([N:17]5[CH2:22][CH2:21][O:20][CH2:19][CH2:18]5)=[O:16])=[CH:13][N:14]=4)[CH:3]=3)[C:40]=1[CH2:41][O:42][C:43](=[O:45])[CH3:44])[N:31]=[CH:30]2)([CH3:24])([CH3:25])[CH3:26]

参加物

7

反応物 4

HCID 11430Potassium CarbonateHCID 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 86686837[6-(4-Bromo-pyridin-2-ylamino)-pyridin-3-yl]-morpholin-4-yl-methanone

生成物 1

HCID 86686836acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-{2-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-pyridin-4-yl}-benzyl ester

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 218864351,4-Dioxane--water (1/1)溶媒

実験手順

[6-(4-Bromo-pyridin-2-ylamino)-pyridin-3-yl]-morpholin-4-yl-methanone (200 mg, 0.55 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 (410 mg, 0.83 mmol) and K2CO3(152 mg, 1.10 mmol) were dissolved in dioxane/H2O (10:1, 11 ml). Under N2 atmosphere, Pd2(dba)3 (50 mg, 0.055 mmol) and X-phos (105 mg, 0.22 mmol) was added and the mixture was stirred at reflux temperature overnight. After the completion of the reaction, the mixture was cooled to room temperature and filtered. The organic layer was washed with saturated brine, dried over sodium sulfate and concentrated. The residue was purified by silica gel column (petroleum ether:ethyl acetate=2:1). The desired product was obtained as a yellow solid (200 mg, yield 56%). LC-MS: 651[M+1]+, tR=1.397 min.

後処理

  1. temperatureat reflux temperature overnight
  2. customAfter the completion of the reaction
  3. filtrationfiltered
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel column (petroleum ether:ethyl acetate=2:1)

出典と根拠

ORDレコード
ord-a1ef462ef80443c2953a867ed11cc4fb
出典データセット
uspto-grants-2014_06
特許番号
US08742098B2

反応ノート

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