Potassium Phosphate, Tribasic → HCID 89783825, compound

HRID 1056269Notes

Reaction equation

HRID 1056269 reaction equation
[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.CC1(C)C(C)(C)OB([C:51]2[NH:59][C:58]3[CH2:57][CH2:56][NH:55][C:54](=[O:60])[C:53]=3[CH:52]=2)O1.Br[C:63]1[CH:64]=[CH:65][CH:66]=[C:67]2[C:72]=1[N:71]=[C:70]([NH:73][CH:74]([CH3:76])[CH3:75])[N:69]([C:77]1[CH:82]=[CH:81][CH:80]=[CH:79][CH:78]=1)[C:68]2=[O:83]>O1CCOCC1.O.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]>[CH:74]([NH:73][C:70]1[N:69]([C:77]2[CH:78]=[CH:79][CH:80]=[CH:81][CH:82]=2)[C:68](=[O:83])[C:67]2[C:72](=[C:63]([C:51]3[NH:59][C:58]4[CH2:57][CH2:56][NH:55][C:54](=[O:60])[C:53]=4[CH:52]=3)[CH:64]=[CH:65][CH:66]=2)[N:71]=1)([CH3:76])[CH3:75]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 89782256HCID 89782256, compoundHCID 897834962-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-YL)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-C]pyridin-4-one

Product 1

HCID 89783825HCID 89783825, compoundYield 43.8%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
80 °C

Procedure

Argon was bubbled into a mixture of potassium phosphate tribasic (0.26 g, 1.22 mmol), Xphos (Strem; 0.015 g, 0.030 mmol), Pd2dba3 (Strem; 0.014 g, 0.015 mmol), 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (609) (0.32 g, 1.22 mmol), 8-bromo-2-(isopropylamino)-3-phenylquinazolin-4(3H)-one (402c, 0.109 g, 0.304 mmol) in 2 mL dioxane and 0.4 mL water for 2 min. The reaction was sealed and heated to 80° C. After 2 h the reaction was concentrated onto 1.5 g silica gel and dried. The material was purified by silica gel chromatography (24 g column) using 0-100% 90/10 DCM/MeOH in DCM. The product-containing fractions were concentrated to afford 2-(isopropylamino)-8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)-3-phenylquinazolin-4(3H)-one (55 mg, 0.133 mmol, 43.7% yield) as a light-yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.15 (1H, br. s.), 8.03 (1H, dd, J=7.7, 1.5 Hz), 7.78 (1H, dd, J=7.7, 1.5 Hz), 7.52-7.66 (3H, m), 7.35-7.46 (2H, m), 7.17 (1H, t, J=7.7 Hz), 7.07 (1H, d, J=2.0 Hz), 6.94 (1H, s), 5.25 (1H, d, J=7.2 Hz), 4.13-4.28 (1H, m), 3.42 (2H, td, J=6.8, 2.3 Hz), 2.86 (2H, t, J=6.8 Hz), 1.20 (6H, d, J=6.5 Hz). m/z (ESI, +ve) 414.1 (M+H)+.

Workup

  1. customThe reaction was sealed
  2. concentrationAfter 2 h the reaction was concentrated onto 1.5 g silica gel
  3. customdried
  4. customThe material was purified by silica gel chromatography (24 g column)
  5. concentrationThe product-containing fractions were concentrated

Sources & evidence

ORD record
ord-15e0e65c1864447baf8e60fb59c2a64f
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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