Potassium Phosphate, Tribasic → HCID 118116899, compound

HRID 1774653Notes

Reaction equation

HRID 1774653 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[N:16]=[C:15]([N:17]([CH3:25])[CH2:18][CH2:19][NH:20][C:21](=[O:24])[CH:22]=[CH2:23])[CH:14]=[CH:13][CH:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:26]([O:29][CH2:30][C:31]1[C:36](B2OC(C)(C)C(C)(C)O2)=[CH:35][C:34]([F:46])=[CH:33][C:32]=1[N:47]1[C:59](=[O:60])[C:58]2[S:57][C:56]3[CH2:55][CH2:54][CH2:53][CH2:52][C:51]=3[C:50]=2[CH:49]=[N:48]1)(=[O:28])[CH3:27].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(#N)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]>[F:46][C:34]1[CH:33]=[C:32]([N:47]2[C:59](=[O:60])[C:58]3[S:57][C:56]4[CH2:55][CH2:54][CH2:53][CH2:52][C:51]=4[C:50]=3[CH:49]=[N:48]2)[C:31]([CH2:30][O:29][C:26](=[O:28])[CH3:27])=[C:36]([C:2]2[CH:3]=[C:4]([NH:10][C:11]3[N:16]=[C:15]([N:17]([CH3:25])[CH2:18][CH2:19][NH:20][C:21](=[O:24])[CH:22]=[CH2:23])[CH:14]=[CH:13][CH:12]=3)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=2)[CH:35]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 58043634(4-Fluoro-2-{6-oxo-8-thia-4,5-diazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3-trien-5-yl}-6-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methyl acetateHCID 118116564HCID 118116564, compound

Product 1

HCID 118116899HCID 118116899, compoundYield 71.7%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
90 °C

Procedure

A mixture of N-(2-((6-(5-bromo-1-methyl-2-oxo-1,2-dihydropyridin-3-ylamino)pyridin-2-yl)(methyl)amino)ethyl)acrylamide 110f (120 mg, 0.3 mmol), (4-fluoro-2-{6-oxo-8-thia-4,5-diazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3-triene-5-yl}-6-(tetra-methyl-1,3,2-dioxaborolan-2-yl)phenyl)methyl acetate 108c (179 mg, 0.36 mmol), Pd(dppf)Cl2 (23 mg, 0.03 mmol) and K3PO4 (159 mg, 0.75 mmol) in acetonitrile (5 mL) and water (1.0 mL) was stirred at 90° C. under N2 for 7 h. The mixture was filtered and the filtrate was concentrated. The residue was purified by prep-TLC (EA/MeOH=25/1) to give N-[2-[[6-[[5-[5-fluoro-2-(acetoxymethyl)-3-(4-oxo-6,7,8,9-tetrahydrobenzothiopheno[2,3-d]pyridazin-3-yl)phenyl]-1-methyl-2-oxo-3-pyridyl]amino]-2-pyridyl]-methyl-amino]ethyl]prop-2-enamide 111a (150 mg, 60%) as a light yellow solid. ESI-LCMS: m/z=698.2

Workup

  1. filtrationThe mixture was filtered
  2. concentrationthe filtrate was concentrated
  3. customThe residue was purified by prep-TLC (EA/MeOH=25/1)

Sources & evidence

ORD record
ord-d68a78311d4d4c7f99e5bf17647fa643
Source dataset
uspto-grants-2016_02
Patent number
US09260415B2

Reaction notes

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