Sodium Carbonate → {4-Fluoro-2-[1-methyl-5-({5-[4-methylpiperazin-1-yl]pyridin-2-yl}amino)-6-oxo-1,6-dihydropyridin-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 1919165Notes

Reaction equation

HRID 1919165 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][C:49]([N:52]3[CH2:57][CH2:56][N:55]([CH3:58])[CH2:54][CH2:53]3)=[CH:48][N:47]=2)[C:31]1=[O:59].C([O-])([O-])=O.[Na+].[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].COCCOC>[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][C:49]([N:52]3[CH2:53][CH2:54][N:55]([CH3:58])[CH2:56][CH2:57]3)=[CH:48][N:47]=2)[C:31](=[O:59])[N:30]([CH3:29])[CH:35]=1)(=[O:3])[CH3:2]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 580437641-methyl-3-((5-(4-methylpiperazin-1-yl)pyridin-2-yl)amino)-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 68096615{4-Fluoro-2-[1-methyl-5-({5-[4-methylpiperazin-1-yl]pyridin-2-yl}amino)-6-oxo-1,6-dihydropyridin-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 33%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
130 °C

Procedure

A microwave vial equipped with a magnetic stirrer 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 (293 mg, 0.65 mmol), 1-methyl-5-(5-(4-methylpiperazin-1-yl)pyridine-2-ylamino)-6-oxo-1,6-dihydropyridin-3-ylboronic acid 197f (450 mg, 1.3 mmol), PdCl2(dppf) (54 mg, 0.065 mmol), 2.0 M Na2CO3 (2.0 equiv), and 1,2-dimethoxyethane (18 mL). After three cycles of vacuum/argon flash, the mixture was heated at 130° C. under microwave irradiation for 0.5 h. It was then filtered and the filtrate was evaporated in vacuo. The residue was purified on flash column chromatography eluting with 10:1 dichloromethane/methanol to afford 340a as a brown solid (130 mg, 33%). LCMS: [M+H]+ 666

Workup

  1. customA microwave vial equipped with a magnetic stirrer
  2. filtrationIt was then filtered
  3. customthe filtrate was evaporated in vacuo
  4. customThe residue was purified on flash column chromatography
  5. washeluting with 10:1 dichloromethane/methanol

Sources & evidence

ORD record
ord-6c4b9b0719cd4ee39c4cbf415332b65b
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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