Potassium Phosphate, Tribasic → HCID 89783356, compound

HRID 1056058Notes

Reaction equation

HRID 1056058 reaction equation
Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[C:5]([C:13]3[NH:21][C:20]4[CH2:19][CH2:18][NH:17][C:16](=[O:22])[C:15]=4[CH:14]=3)[C:6]([F:12])=[CH:7][CH:8]=2)[N:3]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:65][N:66]1[CH:70]=[C:69](B2OC(C)(C)C(C)(C)O2)[CH:68]=[N:67]1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.O1CCOCC1>[F:12][C:6]1[C:5]([C:13]2[NH:21][C:20]3[CH2:19][CH2:18][NH:17][C:16](=[O:22])[C:15]=3[CH:14]=2)=[C:4]2[C:9]([CH:10]=[CH:11][C:2]([C:69]3[CH:68]=[N:67][N:66]([CH3:65])[CH:70]=3)=[N:3]2)=[CH:8][CH:7]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 89783869HCID 89783869, compound

Product 1

HCID 89783356HCID 89783356, compoundYield 1.8%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

In a 5-mL glass microwave tube 2-(2-chloro-7-fluoroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 230; 64 mg, 0.20 mmoles), XPhos (Strem, 5.80 mg, 0.012 mmol), Pd2(dba)3 (5.57 mg, 6.08 μmol), K3PO4 (129 mg, 0.608 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (Boron Molecular, Research Triangle, N.C.; 50.6 mg, 0.24 mmol) were purged with argon, treated with dioxane (3 mL) and water (0.60 mL) and heated at 130° C. for 30 min. The mixture was treated with water, extracted with DCM, washed with brine and concentrated. Purification by rpHPLC (20-95% 0.1% TFA/ACN in 0.1% TFA/water, Silicycle Silichrome XT C18 column; 30×150 mm, 5 μm) afforded 2-(7-fluoro-2-(1-methyl-1H-pyrazol-4-yl)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (1.3 mg, 3.60 μmol, 1.8% yield) as an orange amorphous solid: 1H NMR (400 MHz, MeOH-d4) δ ppm 8.60 (1H, d, J=8.8 Hz), 8.57 (1H, s), 8.35 (1H, s), 8.27 (1H, d, J=6.7 Hz), 8.01 (1H, d, J=8.8 Hz), 7.88 (1H, d, J=11.7 Hz), 7.19 (1H, s), 4.05 (3H, s), 3.62 (2H, t, J=6.9 Hz), 3.02 (2H, t, J=6.9 Hz). 19F NMR (376 MHz, MeOH-d4) δ ppm −77.32 (1F, s). m/z (ESI, +ve ion) 362.1 (M+H)+.

Workup

  1. extractionextracted with DCM
  2. washwashed with brine
  3. concentrationconcentrated
  4. customPurification by rpHPLC (20-95% 0.1% TFA/ACN in 0.1% TFA/water, Silicycle Silichrome XT C18 column; 30×150 mm, 5 μm)

Sources & evidence

ORD record
ord-e104b7ce01d34f79ae68f15a337c6e85
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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