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-1-(oxetan-3-yl)-1H-pyrazol-3-yl]amino}-6-oxo-1,6-dihydropyridin-3-yl)pyridin-3-yl)methyl Acetate

HRID 1412061노트

반응식

HRID 1412061 반응식
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:15]=[C:14]([CH3:16])[N:13]([CH:17]3[CH2:20][O:19][CH2:18]3)[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH: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].CC(O[Na])=O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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:15]=[C:14]([CH3:16])[N:13]([CH:17]3[CH2:20][O:19][CH2:18]3)[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1)(=[O:23])[CH3:22]

참가 물질

8

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 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 acetateHCID 866845625-Bromo-1-methyl-3-(5-methyl-1-(oxetan-3-yl)-1H-pyrazol-3-ylamino)pyridin-2(1H)-oneHCID 178418247HCID 178418247, 화합물

생성물 1

HCID 86684563(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-1-(oxetan-3-yl)-1H-pyrazol-3-yl]amino}-6-oxo-1,6-dihydropyridin-3-yl)pyridin-3-yl)methyl Acetate수율 56.2%

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 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 312a (170 mg, 0.50 mmol), (2-{4,4-dimethyl-9-oxo-1,{3-[(acetyloxy)methyl]-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-4-yl}boronic acid 199e (200 mg, 0.50 mmol), CH3COONa (82 mg, 1.00 mmol), PdCl2(dppf) (41 mg, 0.050 mmol), K3PO4 (212 mg, 1.00 mmol), acetonitrile (10 mL), and water (0.5 mL). After bubbling nitrogen through the resulting mixture for 20 minutes, it was heated at 100° C. under nitrogen atmosphere for 2 h. The mixture was cooled to room temperature and filtered. The filtrate was evaporated under reduced pressure and the residue was purified by silica-gel column chromatography eluting with 50:1 dichloromethane/methanol to afford 312b as white solid (172 mg, 56%). MS-ESI: [M+H]+ 612.4

후처리

  1. customA 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter bubbling nitrogen through the resulting mixture for 20 minutes
  3. temperatureThe mixture was cooled to room temperature
  4. filtrationfiltered
  5. customThe filtrate was evaporated under reduced pressure
  6. customthe residue was purified by silica-gel column chromatography
  7. washeluting with 50:1 dichloromethane/methanol

출처 및 근거

ORD 기록
ord-089a942ad49743059c42c94a8ef60ba6
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08921353B2

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