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

HRID 402935ノート

反応式

HRID 402935 の反応式
Cl[C:2]1[CH:3]=[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)[N:5]=[N:6][CH:7]=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:3]=[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)[N:5]=[N:6][CH:7]=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 86686834[6-(5-Chloro-pyridazin-3-ylamino)-pyridin-3-yl]-morpholin-4-yl-methanone

生成物 1

HCID 86686833acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-{6-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-pyridazin-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-(5-Chloro-pyridazin-3-ylamino)-pyridin-3-yl]-morpholin-4-yl-methanone (200 mg, 0.63 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 (470 mg, 1.25 mmol) and K2CO3 (173 mg, 1.25 mmol) were dissolved in dioxane/H2O (10:1, 11 ml). Under N2 atmosphere, Pd2(dba)3 (58 mg, 0.063 mmol) and X-phos (120 mg, 0.25 mmol) were 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 (240 mg, yield 59%). LC-MS: 652[M+1]+, tR=1.459 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-b22010f547c24d96a8c2d465ba4cbeae
出典データセット
uspto-grants-2014_06
特許番号
US08742098B2

反応ノート

読み込み中…