N,N,N',N'-Tetramethylethylenediamine → HCID 56848439, compound

HRID 1519127Notes

Reaction equation

HRID 1519127 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([C:6]([CH3:26])=[C:7]([C:15]([NH:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[CH:20]=3)=[O:16])[C:8]([O:12][CH2:13][CH3:14])=[N:9]2)=[CH:4][CH:3]=1.[CH3:27][N:28](CCN(C)C)C.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CCOC(C)=O.CCCCCC>CN(C=O)C.[C-]#N.[Zn+2].[C-]#N.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]>[C:27]([C:2]1[CH:11]=[C:10]2[C:5]([C:6]([CH3:26])=[C:7]([C:15]([NH:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[CH:20]=3)=[O:16])[C:8]([O:12][CH2:13][CH3:14])=[N:9]2)=[CH:4][CH:3]=1)#[N:28]

Participants

8

Reactant 4

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 21226206Ethyl acetate hexaneHCID 56848435HCID 56848435, compound

Product 1

HCID 56848439HCID 56848439, compoundYield 265.6%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
160 °C

Procedure

To a solution of 600 mg (1.44 mmol) 7-bromo-2-ethoxy-N-[(3-fluorophenyl)-methyl]-4-methyl-quinoline-3-carboxylic acid amide (example 32) in DMF (3 mL) were added 46 μL (0.32 mmol) TMEDA, 102 mg (0.86 mmol) zinc cyanide, 2 mg (0.007 mmol) Pd2dba3 and Xantphos. The reaction solution was degasses and flushed with nitrogen three times and then heated in MW to 160° C. for 4 min. After cooling to RT the mixture was filtered through celite and it was washed with dichloromethane. The combined organic layers were concentrated in vacuo. After CC (EtOAc/hexane 1:2) of the residue, 310 mg (0.85 mmol, 59%) 7-Cyano-2-ethoxy-N-[(3-fluorophenyl)-methyl]-4-methyl-quinoline-3-carboxylic acid amide (example 36) were obtained. MS: m/z 364.1 [M+H]+.

Workup

  1. customflushed with nitrogen three times
  2. temperatureAfter cooling to RT the mixture
  3. filtrationwas filtered through celite and it
  4. washwas washed with dichloromethane
  5. concentrationThe combined organic layers were concentrated in vacuo

Sources & evidence

ORD record
ord-73739220b12f4dfbbdcce32d6abdcb39
Source dataset
uspto-grants-2015_07
Patent number
US09073862B2

Reaction notes

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