Cesium carbonate → (2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-(oxetan-3-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)pyridin-3-yl)methyl Acetate

HRID 1185221노트

반응식

HRID 1185221 반응식
Cl[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:23]=[C:14]3[CH2:15][N:16]([CH:19]4[CH2:22][O:21][CH2:20]4)[CH2:17][CH2:18][N:13]3[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.[C:24]([O:27][CH2:28][C:29]1[C:30]([N:44]2[N:53]=[CH:52][C:51]3[C:46](=[C:47]([F:58])[CH:48]=[C:49]([C:54]([CH3:57])([CH3:56])[CH3:55])[CH:50]=3)[C:45]2=[O:59])=[N:31][CH:32]=[CH:33][C:34]=1B1OC(C)(C)C(C)(C)O1)(=[O:26])[CH3:25].C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C([O-])([O-])=O.[Cs+].[Cs+]>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].O.O1CCOCC1>[C:24]([O:27][CH2:28][C:29]1[C:30]([N:44]2[N:53]=[CH:52][C:51]3[C:46](=[C:47]([F:58])[CH:48]=[C:49]([C:54]([CH3:56])([CH3:55])[CH3:57])[CH:50]=3)[C:45]2=[O:59])=[N:31][CH:32]=[CH:33][C:34]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:23]=[C:14]3[CH2:15][N:16]([CH:19]4[CH2:22][O:21][CH2:20]4)[CH2:17][CH2:18][N:13]3[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1)(=[O:26])[CH3:25]

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 75806TricyclohexylphosphineHCID 667422666-Chloro-2-methyl-4-(5-(oxetan-3-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl amino)pyridazin-3(2H)-oneHCID 86683972(2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methyl acetate

생성물 1

HCID 86684068(2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-(oxetan-3-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)pyridin-3-yl)methyl Acetate수율 16.3%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 312751,4-Dioxane용매

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온도
110 °C

실험 절차

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 155c (367 mg, 1.1 mmol), 3-(acetoxymethyl)-2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)pyridine-4-ylboronic acid 116c (908.6 mg, 2.2 mmol), Pd2(dba)3 (100.6 mg, 0.11 mmol), P(cy)3 (122.8 mg, 0.44 mmol), Cs2CO3 (717 mg, 2.2 mmol), dioxane (20 mL), and water (0.5 mL). After three cycles of vacuum/argon flush, the mixture was heated at 110° C. for 2 h. It was then filtered and the filtrate was evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 35:1 dichloromethane/methanol to afford 155d (120 mg, 16%) as a yellow solid. MS-ESI: [M+H]+ 669.8

후처리

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. filtrationIt was then filtered
  4. customthe filtrate was evaporated under reduced pressure
  5. customThe residue was purified by silica-gel column chromatography
  6. washeluting with 35:1 dichloromethane/methanol

출처 및 근거

ORD 기록
ord-26a6b29ec65346b9abcd8954e21835f7
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08669251B2

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