Acetonitrile → 2-(10-Fluoro-1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-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-dihydropyridin-3-yl)nicotinaldehyde

HRID 1411994노트

반응식

HRID 1411994 반응식
[CH3:1][N:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[C:4]([NH:17][C:18]2[CH:30]=[C:21]3[CH2:22][N:23]([CH:26]4[CH2:29][O:28][CH2:27]4)[CH2:24][CH2:25][N:20]3[N:19]=2)[C:3]1=[O:31].Cl[C:33]1[C:38]([CH:39]=[O:40])=[C:37]([N:41]2[CH2:53][CH2:52]C3N4[C:45]([CH2:46][CH2:47][CH2:48][CH2:49]4)=[C:44]([F:54])[C:43]=3[C:42]2=[O:55])[N:36]=[CH:35][CH:34]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C([O-])(=O)C.[Na+].[C:69](#[N:71])C>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>[F:54][C:44]1[C:45]2[CH2:46][CH2:47][CH2:48][CH2:49][C:69]=2[N:71]2[CH2:52][CH2:53][N:41]([C:37]3[N:36]=[CH:35][CH:34]=[C:33]([C:6]4[CH:5]=[C:4]([NH:17][C:18]5[CH:30]=[C:21]6[CH2:22][N:23]([CH:26]7[CH2:29][O:28][CH2:27]7)[CH2:24][CH2:25][N:20]6[N:19]=5)[C:3](=[O:31])[N:2]([CH3:1])[CH:7]=4)[C:38]=3[CH:39]=[O:40])[C:42](=[O:55])[C:43]=12

참가 물질

8

반응물 5

HCID 6342AcetonitrileHCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 866842921-methyl-3-(5-(oxetan-3-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-oneHCID 866844464-chloro-2-(10-fluoro-1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)nicotinaldehyde

생성물 1

HCID 866842912-(10-Fluoro-1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-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-dihydropyridin-3-yl)nicotinaldehyde수율 60%

시약·촉매·용매 2

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

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온도
100 °C

실험 절차

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and reflux condenser was charged with 1-methyl-3-(5-(oxetan-3-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one 163a (354 mg, 0.83 mmol), 4-chloro-2-(10-fluoro-1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)nicotinaldehyde 134c (289 mg, 0.83 mmol), PdCl2(dppf) (68 mg, 0.08 mmol), K3PO4 (352 mg, 1.66 mmol), sodium acetate (136 mg, 1.66 mmol), acetonitrile (50 mL), and water (3 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 284a (305 mg, 60%) as a brown solid. MS-ESI: [M+H]+: 613.6.

후처리

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. temperaturereflux condenser
  3. customThe system was evacuated
  4. additionrefilled with N2
  5. temperatureIt was then cooled to room temperature
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe resulting residue was purified by silica-gel column chromatography
  9. washeluting with 30:1 dichloromethane/methanol

출처 및 근거

ORD 기록
ord-b2600a782f2446b38fecb27057a41181
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08921353B2

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