Potassium Phosphate, Tribasic → 4-(5-(5-Ethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydro-pyrido[3,4-b]indolizin-2(1H)-yl)nicotinaldehyde

HRID 592878노트

반응식

HRID 592878 반응식
[CH2:1]([N:3]1[CH2:8][CH2:7][N:6]2[N:9]=[C:10]([NH:12][C:13]3[C:14](=[O:29])[N:15]([CH3:28])[CH:16]=[C:17](B4OC(C)(C)C(C)(C)O4)[CH:18]=3)[CH:11]=[C:5]2[CH2:4]1)[CH3:2].Cl[C:31]1[C:36]([CH:37]=[O:38])=[C:35]([N:39]2[CH2:51][CH2:50][C:49]3[N:48]4[C:43]([CH2:44][CH2:45][CH2:46][CH2:47]4)=[CH:42][C:41]=3[C:40]2=[O:52])[N:34]=[CH:33][CH:32]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C([O-])(=O)C.[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O.C(#N)C>[CH2:1]([N:3]1[CH2:8][CH2:7][N:6]2[N:9]=[C:10]([NH:12][C:13]3[C:14](=[O:29])[N:15]([CH3:28])[CH:16]=[C:17]([C:31]4[C:36]([CH:37]=[O:38])=[C:35]([N:39]5[CH2:51][CH2:50][C:49]6[N:48]7[C:43]([CH2:44][CH2:45][CH2:46][CH2:47]7)=[CH:42][C:41]=6[C:40]5=[O:52])[N:34]=[CH:33][CH:32]=4)[CH:18]=3)[CH:11]=[C:5]2[CH2:4]1)[CH3:2]

참가 물질

8

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 866842464-Chloro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)nicotinaldehydeHCID 866843903-(5-Ethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one

생성물 1

HCID 866843894-(5-(5-Ethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(1-oxo-3,4,6,7,8,9-hexahydro-pyrido[3,4-b]indolizin-2(1H)-yl)nicotinaldehyde수율 56%

시약·촉매·용매 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 6342Acetonitrile용매

반응 조건

온도
100 °C

실험 절차

A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 208d (120 mg, 0.30 mmol), 4-chloro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrido-[3,4-b]indolizin-2(1H)-yl)nicotinaldehyde 139a (99 mg, 0.30 mmol), PdCl2(dppf) (13 mg, 0.015 mmol), K3PO4 (127 mg, 0.60 mmol), sodium acetate (49 mg, 0.60 mmol), acetonitrile (10 mL), and water (0.5 mL). The system was evacuated and refilled with N2. The reaction mixture was heated at 100° C. for 2 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica-gel column chromatography eluting with 30:1 dichloromethane/methanol to afford the 208e (95 mg, 56%) as a yellow solid. MS-ESI: [M+H]+ 567.2.

후처리

  1. customA 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customThe system was evacuated
  3. additionrefilled with N2
  4. temperatureIt was then cooled to room temperature
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe resulting residue was purified by silica-gel column chromatography
  8. washeluting with 30:1 dichloromethane/methanol

출처 및 근거

ORD 기록
ord-cffc8678342c4e9291e2d537fbbeee4d
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09238655B2

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