Sodium Carbonate → 5-(2-(1H-pyrazol-4-yl)ethoxy)-3-methyl-7-(4-morpholinophenyl)pyrido[4,3-d]pyrimidin-4(3H)-one

HRID 1023321Notes

Reaction equation

HRID 1023321 reaction equation
[NH:1]1[CH:5]=[C:4]([CH2:6][CH2:7][O:8][C:9]2[C:18]3[C:17](=[O:19])[N:16]([CH3:20])[CH:15]=[N:14][C:13]=3[CH:12]=[C:11](Cl)[N:10]=2)[CH:3]=[N:2]1.[O:22]1[CH2:27][CH2:26][N:25]([C:28]2[CH:33]=[CH:32][C:31](B3OC(C)(C)C(C)(C)O3)=[CH:30][CH:29]=2)[CH2:24][CH2:23]1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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]>[NH:1]1[CH:5]=[C:4]([CH2:6][CH2:7][O:8][C:9]2[C:18]3[C:17](=[O:19])[N:16]([CH3:20])[CH:15]=[N:14][C:13]=3[CH:12]=[C:11]([C:31]3[CH:30]=[CH:29][C:28]([N:25]4[CH2:24][CH2:23][O:22][CH2:27][CH2:26]4)=[CH:33][CH:32]=3)[N:10]=2)[CH:3]=[N:2]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27953614-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]morpholineHCID 866679855-(2-(1H-pyrazol-4-yl)ethoxy)-7-chloro-3-methylpyrido[4,3-d]pyrimidin-4(3H)-one

Product 1

HCID 669598025-(2-(1H-pyrazol-4-yl)ethoxy)-3-methyl-7-(4-morpholinophenyl)pyrido[4,3-d]pyrimidin-4(3H)-one

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 5-(2-(1H-pyrazol-4-yl)ethoxy)-7-chloro-3-methylpyrido[4,3-d]pyrimidin-4(3H)-one (31.6 mg, 0.10 mmol) in 1,4-dioxane (1 mL) were added 4-morpholinophenylboronic acid pinacol ester (29.9 mg, 0.10 mmol), 2M aqueous Na2CO3 solution (155 μL, 0.30 mmol), and a catalytic amount of Pd(dppf)2Cl2. The reaction mixture was purged with N2 and heated at 140° C. by a microwave reactor for 15 minutes. The mixture was then cooled, quenched with H2O and extracted with EtOAc. The combined organic layer was dried over MgSO4, concentrated, and purified by silica gel chromatography (eluent: 0-10% MeOH in DCM) to provide the title compound as a yellow solid. 1H NMR (CD3OD, 400 MHz) δ 8.37 (s, 1H), 8.06 (d, J=9.2 Hz, 2H), 7.71 (s, 2H), 7.43 (s, 1H), 7.04 (d, J=9.2 Hz, 2H), 4.71 (t, J=6.4 Hz, 2H), 3.85 (t, J=4.8 Hz, 4H), 3.55 (s, 3H), 3.27 (t, J=4.8 Hz, 4H), 3.10 (t, J=6.4 Hz, 2H); ESI-MS m/z 433.1 (MH+).

Workup

  1. customThe reaction mixture was purged with N2
  2. temperatureThe mixture was then cooled
  3. customquenched with H2O
  4. extractionextracted with EtOAc
  5. dry with materialThe combined organic layer was dried over MgSO4
  6. concentrationconcentrated
  7. custompurified by silica gel chromatography (eluent: 0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-8afbf1c9a60b416084595086b85f9cbc
Source dataset
uspto-grants-2014_05
Patent number
US08722692B2

Reaction notes

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