2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → 8-(cyclopropylmethoxy)-4-(3,5-dimethylpyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one

HRID 1095811Notes

Reaction equation

HRID 1095811 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[C:7]([O:14][CH2:15][CH:16]3[CH2:18][CH2:17]3)[C:8]([O:12][CH3:13])=[CH:9][CH:10]=2)[NH:5][C:4](=[O:19])[CH:3]=1.Br[C:21]1[C:26]([CH3:27])=[CH:25][N:24]=[CH:23][C:22]=1[CH3:28].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.CC(C)([O-])C.[Na+]>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].C1(C)C=CC=CC=1>[CH:16]1([CH2:15][O:14][C:7]2[C:8]([O:12][CH3:13])=[CH:9][CH:10]=[C:11]3[C:6]=2[NH:5][C:4](=[O:19])[CH:3]=[C:2]3[NH:1][C:21]2[C:26]([CH3:27])=[CH:25][N:24]=[CH:23][C:22]=2[CH3:28])[CH2:17][CH2:18]1

Participants

7

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 223232464-Bromo-3,5-dimethylpyridineHCID 23676156Sodium t-butoxideHCID 592681194-amino-8-(cyclopropylmethoxy)-7-methoxyquinolin-2(1H)-one

Product 1

HCID 236492908-(cyclopropylmethoxy)-4-(3,5-dimethylpyridin-4-ylamino)-7-methoxyquinolin-2(1H)-oneYield 23.3%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 4-amino-8-(cyclopropylmethoxy)-7-methoxyquinolin-2(1H)-one (500 mg, 1.92 mmol), 4-bromo-3,5-dimethylpyridine (350 mg, 1.88 mmol), Pd2(dba)3 (88 mg, 0.19 mmol Pd), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (XPhos) (181 mg, 0.38 mmol), sodium tert-butoxide (370 mg, 3.85 mmol), and toluene (20 mL) was heated at 110° C. for 3 h under N2, and then allowed to cool to room temperature. The reaction was filtered and washed with 5% methanol in dichloromethane (500 mL×3). The filtrate was concentrated and purified by silica gel chromatography (40:1; ethyl acetate/methanol) and then reverse-phase HPLC to give 0.16 g of 8-(cyclopropylmethoxy)-4-(3,5-dimethylpyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one as white solid. MS (ESI): 366.2

Workup

  1. temperatureto cool to room temperature
  2. filtrationThe reaction was filtered
  3. washwashed with 5% methanol in dichloromethane (500 mL×3)
  4. concentrationThe filtrate was concentrated
  5. custompurified by silica gel chromatography (40:1; ethyl acetate/methanol)

Sources & evidence

ORD record
ord-f415815e1945425f9ed63b0139216cb8
Source dataset
uspto-grants-2012_03
Patent number
US08138205B2

Reaction notes

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