Acetonitrile → 2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-(6-{imidazo[1,2-a]pyridin-7-ylamino}-4-methyl-5-oxopyrazin-2-yl)pyridine-3-carbaldehyde

HRID 1021840노트

반응식

HRID 1021840 반응식
[N:1]1[CH:2]=[CH:3][N:4]2[CH:9]=[CH:8][C:7]([NH:10][C:11]3[C:12](=[O:21])[N:13]([CH3:20])[CH:14]=[C:15](B(O)O)[N:16]=3)=[CH:6][C:5]=12.Cl[C:23]1[CH:28]=[CH:27][N:26]=[C:25]([N:29]2[CH2:40][CH2:39][N:38]3[C:31](=[CH:32][C:33]4[CH2:34][C:35]([CH3:42])([CH3:41])[CH2:36][C:37]=43)[C:30]2=[O:43])[C:24]=1[CH:44]=[O:45].C([O-])(=O)C.[K+].C(#N)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>[CH3:41][C:35]1([CH3:42])[CH2:34][C:33]2[CH:32]=[C:31]3[N:38]([CH2:39][CH2:40][N:29]([C:25]4[C:24]([CH:44]=[O:45])=[C:23]([C:15]5[N:16]=[C:11]([NH:10][C:7]6[CH:8]=[CH:9][N:4]7[CH:3]=[CH:2][N:1]=[C:5]7[CH:6]=6)[C:12](=[O:21])[N:13]([CH3:20])[CH:14]=5)[CH:28]=[CH:27][N:26]=4)[C:30]3=[O:43])[C:37]=2[CH2:36]1

참가 물질

7

반응물 4

HCID 6342AcetonitrileHCID 517044Potassium AcetateHCID 768540784-chloro-2-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta(4,5)pyrrolo(1,2-a)pyrazin-2-yl)nicotinaldehydeHCID 866843326-(Imidazo[1,2-a]pyridin-7-ylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-ylboronic Acid

생성물 1

HCID 866843332-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-(6-{imidazo[1,2-a]pyridin-7-ylamino}-4-methyl-5-oxopyrazin-2-yl)pyridine-3-carbaldehyde수율 29.3%

시약·촉매·용매 2

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

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온도
80 °C

실험 절차

A 100-mL round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 185b (400 mg, 1.40 mmol), 4-chloro-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridine-3-carbaldehyde 108a (192 mg, 0.56 mmol), potassium acetate (220 mg, 2.24 mmol), acetonitrile (20 mL), and water (0.5 mL). After bubbling nitrogen through the suspension for 30 minutes, 1,1′-bis(diphenylphosphino)Ferrocenedichloropalladium(II) (49 mg, 0.054 mmol) was added. The system was subjected to three cycles of vacuum/argon flush and heated at 80° C. for 3 h. It was then cooled to room temperature and filtered. The solid was washed with dichloromethane (2×20 mL). The combined filtrate was concentrated under reduced pressure and the residue was purified by silica-gel column chromatography eluting with dichloromethane/methanol (40:1 to 10:1) to afford 185c (90 mg, 29%) as a light yellow solid. MS-ESI: [M+H]+ 549

후처리

  1. customA 100-mL round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter bubbling nitrogen through the suspension for 30 minutes
  3. customflush
  4. temperatureIt was then cooled to room temperature
  5. filtrationfiltered
  6. washThe solid was washed with dichloromethane (2×20 mL)
  7. concentrationThe combined filtrate was concentrated under reduced pressure
  8. customthe residue was purified by silica-gel column chromatography
  9. washeluting with dichloromethane/methanol (40:1 to 10:1)

출처 및 근거

ORD 기록
ord-d61e87b397eb4af8ac6e645a1f3f92fd
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08716274B2

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