Potassium Phosphate, Tribasic → 1-(1-acetyl-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl)-3-(2-amino-6-quinazolinyl)-4-methyl-2(1H)-pyridinone

HRID 558465Notes

Reaction equation

HRID 558465 reaction equation
P([O-])([O-])([O-])=O.[K+].[K+].[K+].CC1(C)C(C)(C)OB([C:17]2[CH:18]=[C:19]3[C:24](=[CH:25][CH:26]=2)[N:23]=[C:22]([NH2:27])[N:21]=[CH:20]3)O1.[C:29]([N:32]1[C:40]2[C:35](=[CH:36][CH:37]=[C:38]([N:41]3[CH:46]=[CH:45][C:44]([CH3:47])=[C:43](I)[C:42]3=[O:49])[CH:39]=2)[C:34]([CH3:51])([CH3:50])[CH2:33]1)(=[O:31])[CH3:30].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>CCOC(C)=O.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(O)(C)C>[C:29]([N:32]1[C:40]2[C:35](=[CH:36][CH:37]=[C:38]([N:41]3[CH:46]=[CH:45][C:44]([CH3:47])=[C:43]([C:17]4[CH:18]=[C:19]5[C:24](=[CH:25][CH:26]=4)[N:23]=[C:22]([NH2:27])[N:21]=[CH:20]5)[C:42]3=[O:49])[CH:39]=2)[C:34]([CH3:51])([CH3:50])[CH2:33]1)(=[O:31])[CH3:30]

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 160861386-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)quinazolin-2-amineHCID 670000331-(1-acetyl-3,3-dimethylindolin-6-yl)-3-iodo-4-methylpyridin-2(1H)-one

Product 1

HCID 250687791-(1-acetyl-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl)-3-(2-amino-6-quinazolinyl)-4-methyl-2(1H)-pyridinone

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

To a resealable tube charged with potassium phosphate (0.588 g, 2.77 mmol), 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinazolin-2-amine (0.275 g, 1.02 mmol), 1-(1-acetyl-3,3-dimethylindolin-6-yl)-3-iodo-4-methylpyridin-2(1H)-one (0.390 g, 0.924 mmol), S-Phos (0.0227 g, 0.0554 mmol), and palladium acetate (0.0104 g, 0.0462 mmol) was added isopropyl alcohol (6.0 mL) and water (2 mL). The mixture was heated at 75° C. After 5 hrs, the mixture was diluted with EtOAc and water. The organic fraction was washed with brine and dried with sodium sulfate. After concentration in vacuo, the resulting solid was adsorbed onto silica gel and purified by silica gel chromatography using 2-10% MeOH in CH2Cl2 to afford 1-(1-acetyl-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl)-3-(2-amino-6-quinazolinyl)-4-methyl-2(1H)-pyridinone as a white solid. M+H+=440.2.

Workup

  1. washThe organic fraction was washed with brine
  2. dry with materialdried with sodium sulfate
  3. concentrationAfter concentration in vacuo
  4. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-a41aa584b88d4f17b509c70ed696bfdb
Source dataset
uspto-grants-2011_11
Patent number
US08063055B2

Reaction notes

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