Sodium Carbonate → (S)-2-(1-((2-aminopyrido[3,2-d]pyrimidin-4-yl)amino)ethyl)-5-(2-methylpyrimidin-5-yl)-3-phenylquinazolin-4(3H)-one

HRID 869467Notes

Reaction equation

HRID 869467 reaction equation
[NH2:1][C:2]1[N:3]=[C:4]([NH:12][C@H:13]([C:15]2[N:24]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:23](=[O:31])[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][C:21]=3Cl)[N:16]=2)[CH3:14])[C:5]2[N:11]=[CH:10][CH:9]=[CH:8][C:6]=2[N:7]=1.[CH3:33][C:34]1[N:39]=[CH:38][C:37](B2OC(C)(C)C(C)(C)O2)=[CH:36][N:35]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC(C)C)=CC=CC=2OC(C)C)CCCCC1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:1][C:2]1[N:3]=[C:4]([NH:12][C@H:13]([C:15]2[N:24]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:23](=[O:31])[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][C:21]=3[C:37]3[CH:36]=[N:35][C:34]([CH3:33])=[N:39][CH:38]=3)[N:16]=2)[CH3:14])[C:5]2[N:11]=[CH:10][CH:9]=[CH:8][C:6]=2[N:7]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 457872822-Methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidineHCID 71232775(S)-2-(1-((2-aminopyrido[3,2-d]pyrimidin-4-yl)amino)ethyl)-5-chloro-3-phenylquinazolin-4(3H)-one

Product 1

HCID 71226709(S)-2-(1-((2-aminopyrido[3,2-d]pyrimidin-4-yl)amino)ethyl)-5-(2-methylpyrimidin-5-yl)-3-phenylquinazolin-4(3H)-oneYield 50.6%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
120 °C

Procedure

To a solution of (S)-2-(1-((2-aminopyrido[3,2-d]pyrimidin-4-yl)amino)ethyl)-5-chloro-3-phenylquinazolin-4(3H)-one (30 mg, 0.067 mmol) and 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine (22 mg, 0.1 mmol) in 1,4-dioxane-H2O (4:1, 2 mL) in a sealed tube, 2-dicyclohexylphosphino-2′,6′-diisopropoxybiphenyl (15.6 mg, 0.034 mmol), palladium(II) acetate (3.8 mg, 0.017 mmol), and Na2CO3 (21 mg, 0.20 mmol) were added sequentially. The mixture was degassed and backfilled with argon (three cycles), and then stirred at 120° C. for 1 h. The mixture was allowed to cool to RT, and then partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by ISCO column chromatography (silica gel cartridge, 0-10% MeOH/DCM) to afford compound I-91, (S)-2-(1-((2-aminopyrido[3,2-d]pyrimidin-4-yl)amino)ethyl)-5-(2-methylpyrimidin-5-yl)-3-phenylquinazolin-4(3H)-one (17 mg, 50% yield). ESI-MS m/z: 502.2 [M+H]+.

Workup

  1. customThe mixture was degassed
  2. temperatureto cool to RT
  3. custompartitioned between ethyl acetate and water
  4. washThe organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue was purified by ISCO column chromatography (silica gel cartridge, 0-10% MeOH/DCM)

Sources & evidence

ORD record
ord-314b257151eb418aa1e45b1ab754281d
Source dataset
uspto-grants-2015_03
Patent number
US08969363B2

Reaction notes

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