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

HRID 1411950Notes

Reaction equation

HRID 1411950 reaction equation
C[N:2]1[C:6]([CH3:7])=[CH:5][C:4]([NH:8][C:9]2[C:10](=[O:25])[N:11]([CH3:24])[CH:12]=[C:13](B3OC(C)(C)C(C)(C)O3)[CH:14]=2)=[N:3]1.[C:26]([O:29][CH2:30][C:31]1[C:32]([N:46]2[CH2:57][CH2:56][N:55]3[C:48](=[CH:49][C:50]4[CH2:51][C:52]([CH3:59])([CH3:58])[CH2:53][C:54]=43)[C:47]2=[O:60])=[N:33][CH:34]=[CH:35][C:36]=1B1OC(C)(C)C(C)(C)O1)(=[O:28])[CH3:27].[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:26]([O:29][CH2:30][C:31]1[C:32]([N:46]2[CH2:57][CH2:56][N:55]3[C:48](=[CH:49][C:50]4[CH2:51][C:52]([CH3:59])([CH3:58])[CH2:53][C:54]=43)[C:47]2=[O:60])=[N:33][CH:34]=[CH:35][C:36]=1[C:13]1[CH:14]=[C:9]([NH:8][C:4]2[CH:5]=[C:6]([CH3:7])[NH:2][N:3]=2)[C:10](=[O:25])[N:11]([CH3:24])[CH:12]=1)(=[O:28])[CH3:27]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 580441963-(1,5-Dimethyl-1H-pyrazol-3-ylamino)-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-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

Product 1

HCID 86684492(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-1H-pyrazol-3-yl)amino]-6-oxo-1,6-dihydropyridin-3-yl}pyridin-3-yl)methyl AcetateYield 38%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

A round-bottomed flask equipped with a reflux condenser was charged with 5-bromo-1-methyl-3-(5-methyl-1H-pyrazol-3-ylamino)pyridin-2(1H)-one 218a (201 mg, 0.71 mmol), {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 (282 mg, 0.71 mmol), Pd(dppf)Cl2 (51 mg, 0.07 mmol), K3PO4 (301 mg, 1.42 mmol), sodium acetate (116 mg, 1.42 mmol), acetonitrile (10 mL), and water (0.2 mL). After three cycles of vacuum/argon flush, the mixture was heated at 100° C. for 3 h. It was then filtered and the filtrate was evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 1:20 methanol/dichloromethane to afford 260a as a red solid (150 mg, 38%). MS-ESI: [M+H]+ 556.3

Workup

  1. customA round-bottomed flask equipped with a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. filtrationIt was then filtered
  4. customthe filtrate was evaporated under reduced pressure
  5. customThe residue was purified by silica-gel column chromatography
  6. washeluting with 1:20 methanol/dichloromethane

Sources & evidence

ORD record
ord-a2834b1e27b4452b97e7b4053d2247cb
Source dataset
uspto-grants-2014_12
Patent number
US08921353B2

Reaction notes

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