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 402935노트

반응식

HRID 402935 반응식
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]

참가 물질

7

반응물 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

생성물 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

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 218864351,4-Dioxane--water (1/1)용매

실험 절차

[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.

후처리

  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)

출처 및 근거

ORD 기록
ord-b22010f547c24d96a8c2d465ba4cbeae
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08742098B2

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