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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
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HRID 2069865 반응식
[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]
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참가 물질

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반응물 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

생성물 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
수율 54%

시약·촉매·용매 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium촉매HCID 962Water용매HCID 312751,4-Dioxane용매

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온도
125 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-b8b318cef5ac40c79e128ab0c4a919cf
출처 데이터셋
uspto-grants-2012_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08299077B2

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