Potassium Phosphate, Tribasic → [4-Fluoro-2-(1-methyl-5-{[5-(4-methylpiperazin-1-yl)pyridin-2-yl]amino}-6-oxo-1,6-dihydropyridin-3-yl)-6-{6-oxo-8-thia-5-azatricyclo[7.4.0.02,7]-trideca-1(9),2(7)-dien-5-yl}phenyl]methyl Acetate

HRID 1919004Notes

Reaction equation

HRID 1919004 reaction equation
[C:1]([O:4][CH2:5][C:6]1[C:11]([N:12]2[CH2:17][CH2:16][C:15]3[C:18]4[CH2:24][CH2:23][CH2:22][CH2:21][C:19]=4[S:20][C:14]=3[C:13]2=[O:25])=[CH:10][C:9]([F:26])=[CH:8][C:7]=1B1OC(C)(C)C(C)(C)O1)(=[O:3])[CH3:2].Br[C:37]1[CH:38]=[C:39]([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:40](=[O:44])[N:41]([CH3:43])[CH:42]=1.CC(O[Na])=O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC#N.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:13](=[O:25])[C:14]3[S:20][C:19]4[CH2:21][CH2:22][CH2:23][CH2:24][C:18]=4[C:15]=3[CH2:16][CH2:17]2)=[CH:10][C:9]([F:26])=[CH:8][C:7]=1[C:37]1[CH:38]=[C:39]([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:40](=[O:44])[N:41]([CH3:43])[CH:42]=1)(=[O:3])[CH3:2]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 592164475-bromo-1-methyl-3-((5-(4-methylpiperazin-1-yl)pyridin-2-yl)amino)pyridin-2(1H)-oneHCID 670162052-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-4-fluoro-6-(1-oxo-3,4,5,6,7,8-hexahydrobenzothieno[2,3-c]pyridin-2(1H)-yl)benzyl AcetateHCID 178418247HCID 178418247, compound

Product 1

HCID 67016196[4-Fluoro-2-(1-methyl-5-{[5-(4-methylpiperazin-1-yl)pyridin-2-yl]amino}-6-oxo-1,6-dihydropyridin-3-yl)-6-{6-oxo-8-thia-5-azatricyclo[7.4.0.02,7]-trideca-1(9),2(7)-dien-5-yl}phenyl]methyl AcetateYield 57.3%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
110 °C

Procedure

A 25 mL sealed tube was charged with 212b (990 mg, 2 mmol), 5-bromo-1-methyl-3-(5-(4-methylpiperazin-1-yl)pyridin-2-ylamino)pyridine-2(1H)-one 198e (500 mg, 1.3 mmol), CH3COONa (220 mg, 2.6 mmol), K3PO4 (700 mg, 2.6 mmol), and PdCl2(dppf) (110 mg, 0.13 mmol) suspended in CH3CN (25 mL) and water (1 mL). The mixture was heated at 110° C. for 2 hours. It was evaporated and the residue was purified by silical-gel column eluting with 20:1 methylene chloride/methanol to give 212c as a brown solid (500 mg, 56%). LCMS: [M+H]+ 670

Workup

  1. customA 25 mL sealed tube
  2. customIt was evaporated
  3. customthe residue was purified by silical-gel column
  4. washeluting with 20:1 methylene chloride/methanol

Sources & evidence

ORD record
ord-1c47785217114cbb989d30007616e28c
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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