Ethyl Acetate → 1-(7-Fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-yl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-6-carbonitrile

HRID 1618532Notes

Reaction equation

HRID 1618532 reaction equation
Br[C:2]1[CH:3]=[C:4]2[N:10]([C:11]3[C:20]4[C:15](=[CH:16][C:17]([F:21])=[CH:18][CH:19]=4)[N:14]=[C:13]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)[C:12]=3[CH3:28])[CH2:9][C:8]([CH3:30])([CH3:29])[C:5]2=[N:6][CH:7]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[C:65]([Sn](CCCC)(CCCC)CCCC)#[N:66].CCOC(C)=O>C1(C(N)C2CCCCC2)CCCCC1.CN1C(=O)CCC1.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].O>[F:21][C:17]1[CH:16]=[C:15]2[C:20]([C:11]([N:10]3[C:4]4[C:5](=[N:6][CH:7]=[C:2]([C:65]#[N:66])[CH:3]=4)[C:8]([CH3:30])([CH3:29])[CH2:9]3)=[C:12]([CH3:28])[C:13]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)=[N:14]2)=[CH:19][CH:18]=1

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 200512Stannanecarbonitrile, tributyl-HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 672855904-(6-Bromo-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-methyl-2-(pyridin-2-yl)quinoline

Product 1

HCID 672852091-(7-Fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-yl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-6-carbonitrile

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolventHCID 10774245alpha-CyclohexylcyclohexanemethanamineSolvent

Procedure

A stirred solution of 4-(6-bromo-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]-pyridin-1-yl)-7-fluoro-3-methyl-2-(pyridin-2-yl)quinoline (95 mg, 0.20 mmol), Pd2dba3 (56 mg, 0.06 mmol), XPhos (58 mg, 0.6 mmol) and cyanotributyltin (65 mg, 0.20 mmol) in dicyclohexylmethylamine (1.5 mL) and NMP (1.0 mL) was heated in the microwave at 150° C. After this time the reaction was treated with EtOAc (100 mL) and water (50 mL). The separated organic layer was dried over MgSO4, filtered and evaporated in vacuo. Reverse phase HPLC (10% to 60% acetonitrile in water) gave 1-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine-6-carbonitrile. Mass Spectrum (ESI) m/e=410 (M+1).

Workup

  1. dry with materialThe separated organic layer was dried over MgSO4
  2. filtrationfiltered
  3. customevaporated in vacuo

Sources & evidence

ORD record
ord-4e85132c1f9849a590790ad023002cd9
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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