Potassium Phosphate, Tribasic → 3-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-5-{1-methyl-5-[(2-methylpyrimidin-4-yl)amino]-6-oxo-1,6-dihydropyridin-3-yl}pyridine-4-carbaldehyde

HRID 1411833Notes

Reaction equation

HRID 1411833 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([N:10]2[CH2:21][CH2:20][N:19]3[C:12](=[CH:13][C:14]4[CH2:15][C:16]([CH3:23])([CH3:22])[CH2:17][C:18]=43)[C:11]2=[O:24])[C:7]=1[CH:8]=[O:9].[CH3:25][N:26]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[C:28]([NH:41][C:42]2[CH:47]=[CH:46][N:45]=[C:44]([CH3:48])[N:43]=2)[C:27]1=[O:49].[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>[CH3:22][C:16]1([CH3:23])[CH2:15][C:14]2[CH:13]=[C:12]3[N:19]([CH2:20][CH2:21][N:10]([C:6]4[CH:5]=[N:4][CH:3]=[C:2]([C:30]5[CH:29]=[C:28]([NH:41][C:42]6[CH:47]=[CH:46][N:45]=[C:44]([CH3:48])[N:43]=6)[C:27](=[O:49])[N:26]([CH3:25])[CH:31]=5)[C:7]=4[CH:8]=[O:9])[C:11]3=[O:24])[C:18]=2[CH2:17]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 866839351-Methyl-3-(2-methylpyrimidin-4-ylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-oneHCID 866841823-Bromo-5-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridine-4-carbaldehyde

Product 1

HCID 866843973-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-5-{1-methyl-5-[(2-methylpyrimidin-4-yl)amino]-6-oxo-1,6-dihydropyridin-3-yl}pyridine-4-carbaldehydeYield 53.1%

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 sealed tube was charged with 3-bromo-5-{4,4-dimethyl-9-oxo-1,10-diazatricyclo-[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-pyridine-4-carbaldehyde 107f (210 mg, 0.54 mmol), 1-methyl-3-(pyrimidin-4-ylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-one 213b (177 mg, 0.54 mmol), PdCl2(dppf) (42 mg, 0.050 mmol), K3PO4 (210 mg, 1.0 mmol), and sodium acetate (85 mg, 1.0 mmol), acetonitrile (8 mL), and water (0.5 mL). After three cycles of vacuum/argon flush, the mixture was heated at 100° C. for 4 h. It was then filtered and the filtrate was evaporated in vacuo. The residue was purified by silica-gel column chromatography eluting with 20:1 dichloromethane/methanol to afford 215a (150 mg, 53%). MS-ESI: [M+H]+ 524.2.

Workup

  1. customAfter three cycles of vacuum/argon flush
  2. filtrationIt was then filtered
  3. customthe filtrate was evaporated in vacuo
  4. customThe residue was purified by silica-gel column chromatography
  5. washeluting with 20:1 dichloromethane/methanol

Sources & evidence

ORD record
ord-63ba7a98631949be877264ef80f53944
Source dataset
uspto-grants-2014_12
Patent number
US08921353B2

Reaction notes

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