Potassium Phosphate, Tribasic → (2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-[1-methyl-5-({5-methyl-4H,5H,6H,7H-pyrazolo[1,5-a]pyrazin-2-yl}amino)-6-oxo-1,6-dihydropyridazin-3-yl]pyridin-3-yl)methyl Acetate

HRID 1022161노트

반응식

HRID 1022161 반응식
Cl[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:20]=[C:14]3[CH2:15][N:16]([CH3:19])[CH2:17][CH2:18][N:13]3[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.[C:21]([O:24][CH2:25][C:26]1[C:27]([N:41]2[CH2:52][CH2:51][N:50]3[C:43](=[CH:44][C:45]4[CH2:46][C:47]([CH3:54])([CH3:53])[CH2:48][C:49]=43)[C:42]2=[O:55])=[N:28][CH:29]=[CH:30][C:31]=1B1OC(C)(C)C(C)(C)O1)(=[O:23])[CH3:22].[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>[C:21]([O:24][CH2:25][C:26]1[C:27]([N:41]2[CH2:52][CH2:51][N:50]3[C:43](=[CH:44][C:45]4[CH2:46][C:47]([CH3:54])([CH3:53])[CH2:48][C:49]=43)[C:42]2=[O:55])=[N:28][CH:29]=[CH:30][C:31]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:20]=[C:14]3[CH2:15][N:16]([CH3:19])[CH2:17][CH2:18][N:13]3[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1)(=[O:23])[CH3:22]

참가 물질

8

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 666346996-chloro-2-methyl-4-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)pyridazin-3(2H)-oneHCID 86684419(2-(7,7-dimethyl-1-oxo-3,4,7,8-tetrahydro-1H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2(6H)-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methyl acetate

생성물 1

HCID 86684542(2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-[1-methyl-5-({5-methyl-4H,5H,6H,7H-pyrazolo[1,5-a]pyrazin-2-yl}amino)-6-oxo-1,6-dihydropyridazin-3-yl]pyridin-3-yl)methyl Acetate수율 38%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 6342Acetonitrile용매

반응 조건

온도
100 °C

실험 절차

A 25-mL round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 297a (195 mg, 0.66 mmol), (2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methyl acetate 199e (315 mg, 0.66 mmol), PdCl2(dppf) (40 mg, 0.050 mmol), K3PO4 (250 mg, 1.2 mmol), sodium acetate (100 mg, 1.20 mmol), acetonitrile (8 mL), and water (1 mL). The system was evacuated and then refilled with N2. It was then heated at 100° C. for 1 h. The mixture was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by silica-gel column chromatography eluting with 20:1 dichloromethane/methanol to afford 297b as a yellow solid (150 mg, 38%). MS-ESI: [M+H]+ 612.3.

후처리

  1. customA 25-mL round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customThe system was evacuated
  3. additionrefilled with N2
  4. temperatureThe mixture was cooled to room temperature
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe residue was purified by silica-gel column chromatography
  8. washeluting with 20:1 dichloromethane/methanol

출처 및 근거

ORD 기록
ord-8ca3264ab40147ff86240ba9b2120ecc
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08716274B2

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