Potassium Phosphate, Tribasic → HCID 87054905, compound

HRID 2201569Notes

Reaction equation

HRID 2201569 reaction equation
BrC1C=N[C:5]2[N:6]=[CH:7][N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[F:17])[C:9](=[O:10])[C:4]=2C=1.[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[O:28][C:29]3[CH:39]=[C:38]([N:40]([CH3:45])[S:41]([CH3:44])(=[O:43])=[O:42])[C:37](B4OC(C)(C)C(C)(C)O4)=[CH:36][C:30]=3[C:31]=2[C:32]([NH:34][CH3:35])=[O:33])=[CH:23][CH:22]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C)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:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[O:28][C:29]3[CH:39]=[C:38]([N:40]([CH3:45])[S:41]([CH3:44])(=[O:43])=[O:42])[C:37]([C:5]4[CH:4]=[CH:9][C:5]5[N:6]=[CH:7][N:8]([C:11]6[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=6[F:17])[C:9](=[O:10])[C:4]=5[N:6]=4)=[CH:36][C:30]=3[C:31]=2[C:32]([NH:34][CH3:35])=[O:33])=[CH:23][CH:22]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 682394022-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamideHCID 117771590HCID 117771590, compound

Product 1

HCID 87054905HCID 87054905, compoundYield 41.7%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

To a degassed mixture of 6-bromo-3-(2-fluorophenyl)pyrido[2,3-d]pyrimidin-4(3H)-one (75 mg, 0.234 mmol) and 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (100 mg, 0.199 mmol) in N, N-dimethyl-formamide (5 mL) were added Pd(dppf)Cl2 (15 mg) and K3PO4 (127 mg, 0.468 mmol) under N2. The mixture was heated to 80° C. overnight. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated, and the residue was purified by prep-HPLC to give 2-(4-fluorophenyl)-5-(3-(2-fluorophenyl)-4-oxo-3,4-dihydropyrido[3,2-d]pyrimidin-6-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (30 mg, yield: 30%). 1H-NMR (CDCl3, 400 MHz) δ 8.22 (d, J=8.8 Hz, 1H), 8.08˜8.14 (m, 3H), 7.96˜7.99 (m, 2H), 7.65 (s, 1H), 7.47˜7.57 (m, 2H), 7.32˜7.38 (m, 2H), 7.19 (t, J=8.8 Hz, 2H), 6.47 (br s, 1H), 3.27 (s, 3H), 2.98 (d, J=4.8 Hz, 3H), 2.93 (s, 3H). MS (M+H)+: 616.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated
  4. customthe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-6fb8fbe98d594c64aedbf0696b9d66ab
Source dataset
uspto-grants-2016_06
Patent number
US09364482B2

Reaction notes

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