N,N,N',N'-Tetramethylethylenediamine → HCID 56848134, compound

HRID 2093727Notes

Reaction equation

HRID 2093727 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][C:22]([F:25])=[CH:21][CH:20]=3)=[O:16])[C:8]([CH:12]3[CH2:14][CH2:13]3)=[N:9]2)=[CH:4][CH:3]=1.[CH3:27][N:28](CCN(C)C)C.CCOC(C)=O.C1CCCCC1>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].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>[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][C:22]([F:25])=[CH:21][CH:20]=3)=[O:16])[C:8]([CH:12]3[CH2:13][CH2:14]3)=[N:9]2)=[CH:4][CH:3]=1)#[N:28]

Participants

8

Reactant 3

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 21867204Cyclohexane ethylacetateHCID 568480807-Bromo-2-cyclopropyl-N-[(4-fluorophenyl)-methyl]-4-methyl-quinoline-3-carboxylic acid amide

Product 1

HCID 56848134HCID 56848134, compoundYield 191.5%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
160 °C

Procedure

To a solution of 880 mg (2.13 mmol) 7-Bromo-2-cyclopropyl-N-[(4-fluorophenyl)-methyl]-4-methyl-quinoline-3-carboxylic acid amide (example 28) in DMF (3 mL) were added 70 μL (0.47 mmol) TMEDA, 152 mg (1.28 mmol) Zinccyanide, 4 mg (0.007 mmol) Pd2 dba3 and 25 mg (0.040 mmol) 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/cyclohexane 1:2) of the residue, 325 mg (0.90 mmol, 42%) 7-Cyano-2-cyclopropyl-N-[(4-fluorophenyl)-methyl]-4-methyl-quinoline-3-carboxylic acid amide (example 38) were obtained. MS: m/z 360.1 [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-78188a9e4d9f41d0b380faacf1ed9dde
Source dataset
uspto-grants-2013_05
Patent number
US08445512B2

Reaction notes

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