Sodium Carbonate → (4-Fluoro-2-{1-methyl-6-oxo-5-[(pyrimidin-4-yl)amino]-1,6-dihydro-pyridin-3-yl}-6-{7-oxo-3,6-diazatetracyclo[9.2.1.02,10.03,8]tetradeca-2(10),8-dien-6-yl}phenyl)methyl Acetate

HRID 1919162Notes

Reaction equation

HRID 1919162 reaction equation
[C:1]([O:4][CH2:5][C:6]1[C:11]([N:12]2[C:24](=[O:25])[C:23]3[N:15]([C:16]4[CH:17]5[CH2:26][CH:20]([C:21]=4[CH:22]=3)[CH2:19][CH2:18]5)[CH2:14][CH2:13]2)=[CH:10][C:9]([F:27])=[CH:8][C:7]=1Br)(=[O:3])[CH3:2].[CH3:29][N:30]1[CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH:33]=[C:32]([NH:45][C:46]2[CH:51]=[CH:50][N:49]=[CH:48][N:47]=2)[C:31]1=[O:52].C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.O.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]>[C:1]([O:4][CH2:5][C:6]1[C:11]([N:12]2[C:24](=[O:25])[C:23]3[N:15]([C:16]4[CH:17]5[CH2:26][CH:20]([C:21]=4[CH:22]=3)[CH2:19][CH2:18]5)[CH2:14][CH2:13]2)=[CH:10][C:9]([F:27])=[CH:8][C:7]=1[C:34]1[CH:33]=[C:32]([NH:45][C:46]2[CH:51]=[CH:50][N:49]=[CH:48][N:47]=2)[C:31](=[O:52])[N:30]([CH3:29])[CH:35]=1)(=[O:3])[CH3:2]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 580438621-methyl-3-(pyrimidin-4-ylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-oneHCID 68096577(2-Bromo-4-fluoro-6-{7-oxo-3,6-diazatetracyclo[9.2.1.02,10.03,8]tetradeca-2(10),8-dien-6-yl}phenyl)methyl acetate

Product 1

HCID 68096457(4-Fluoro-2-{1-methyl-6-oxo-5-[(pyrimidin-4-yl)amino]-1,6-dihydro-pyridin-3-yl}-6-{7-oxo-3,6-diazatetracyclo[9.2.1.02,10.03,8]tetradeca-2(10),8-dien-6-yl}phenyl)methyl AcetateYield 58.6%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A sealed tube was charged with(2-bromo-4-fluoro-6-{7-oxo-3,6-diazatetracyclo-[9.2.1.02,10.03,8]tetradeca-2(10),8-dien-6-yl}phenyl)methyl acetate 334g (400 mg, 0.9 mmol), 1-methyl-3-(pyrimidin-4-ylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one 109c (294 mg, 0.9 mmol), Na2CO3 (190 mg, 1.8 mmol), and PdCl2(dppf) (73 mg, 0.09 mmol) suspended in DMF (20 mL) and water (1 mL). The mixture was stirred at 60° C. for 6 hours. It was then partitioned between water and ethyl acetate. The organic phase was washed with water and evaporated to dryness. The residue was purified by column chromatography eluting with 15:1 methylene chloride/methanol to give 337a as a brown solid (300 mg, 58%). MS: [M+H]+ 569.

Workup

  1. customIt was then partitioned between water and ethyl acetate
  2. washThe organic phase was washed with water
  3. customevaporated to dryness
  4. customThe residue was purified by column chromatography
  5. washeluting with 15:1 methylene chloride/methanol

Sources & evidence

ORD record
ord-b3d3afd7332b42b0be2238311115c32f
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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