Potassium Phosphate, Tribasic → HCID 118116658, compound

HRID 1774664Notes

Reaction equation

HRID 1774664 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[N:16]=[C:15]([N:17]3[CH2:22][CH2:21][CH2:20][C@H:19]([NH:23][C:24](=[O:27])[CH:25]=[CH2:26])[CH2:18]3)[CH:14]=[CH:13][CH:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:28]([O:31][CH2:32][C:33]1[C:38](B2OC(C)(C)C(C)(C)O2)=[CH:37][C:36]([F:48])=[CH:35][C:34]=1[N:49]1[C:61](=[O:62])[C:60]2[S:59][C:58]3[CH2:57][CH2:56][CH2:55][CH2:54][C:53]=3[C:52]=2[CH:51]=[N:50]1)(=[O:30])[CH3:29].[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:48][C:36]1[CH:35]=[C:34]([N:49]2[C:61](=[O:62])[C:60]3[S:59][C:58]4[CH2:57][CH2:56][CH2:55][CH2:54][C:53]=4[C:52]=3[CH:51]=[N:50]2)[C:33]([CH2:32][O:31][C:28](=[O:30])[CH3:29])=[C:38]([C:2]2[CH:3]=[C:4]([NH:10][C:11]3[N:16]=[C:15]([N:17]4[CH2:22][CH2:21][CH2:20][C@H:19]([NH:23][C:24](=[O:27])[CH:25]=[CH2:26])[CH2:18]4)[CH:14]=[CH:13][CH:12]=3)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=2)[CH:37]=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 118116911HCID 118116911, compound

Product 1

HCID 118116658HCID 118116658, compoundYield 33.6%

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 (S)—N-(1-(6-(5-bromo-1-methyl-2-oxo-1,2-dihydropyridin-3-ylamino)pyridin-2-yl)piperidin-3-yl)acrylamide 114f (127 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-[(3S)-1-[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]-3-piperidyl]prop-2-enamide 115a (73 mg, 33%) as yellow solid. MS-ESI: [M+H]+ 724.3

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-3d35cd2863b346b6a409eda75bbb4d5b
Source dataset
uspto-grants-2016_02
Patent number
US09260415B2

Reaction notes

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