Dimethylformamide → HCID 58856189, compound

HRID 133478Notes

Reaction equation

HRID 133478 reaction equation
[Cl:1][C:2]1[CH:31]=[CH:30][C:5]([CH2:6][C@@H:7]([C:22]2[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=2)[C:25]#[N:26])[C@@H:8]([NH:10][CH:11]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17](Br)[CH:16]=2)[CH2:12][C:13]#[N:14])[CH3:9])=[CH:4][CH:3]=1.[CH3:32][N:33](C=O)C>O.[C-]#N.[Zn+2].[C-]#N.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[Cl:1][C:2]1[CH:31]=[CH:30][C:5]([CH2:6][C@@H:7]([C:22]2[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=2)[C:25]#[N:26])[C@@H:8]([NH:10][CH:11]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:32]#[N:33])[CH:16]=2)[CH2:12][C:13]#[N:14])[CH3:9])=[CH:4][CH:3]=1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 58856187HCID 58856187, compound

Product 1

HCID 58856189HCID 58856189, compound

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 962WaterSolvent

Conditions

Temperature
180 °C

Procedure

A solution of 164 mg (0.33 mmol) of 3-(1(S)-(4-chlorobenzyl)-2(S)-((1-(3-bromophenyl)-2-cyanoethyl)amino)propyl)benzonitrile (mixture of two diastereomers) in 2 mL of DMF and 0.02 mL of water was treated with 35 mg of Zinc cyanide, 7 mg (0.008 mmol) of tris(dibenzylidineacetone) dipalladium and 11 mg (0.02 mmol) of 1,1′-bis(diphenylphosphino)ferrocene. The solution was degassed by bubbling N2 for 30 min, while the color changed from brown to yellow-orange. The vial was sealed and heated in a microwave reactor at 180° C. for 1 hr. After the reaction cooled, it was filtered through a pad of CELITE, diatomaceous earth, and the solids were washed with ether. The filtrate was diluted with ether, washed with water, and brine, then dried and concentrated. The residue was purified by prep TLC to obtain the less polar isomer, 3-(1(S)-(4-chlorobenzyl)-2(S)-((1-(3-cyanophenyl)-2-cyanoethyl)amino)propyl)benzonitrile (Diastereomer A); LC-MS: m/e=439 (M+1), 441 (M+3) (3.62 min) and more polar isomer 3-(1(S)-(4-Chlorobenzyl)-2(S)-((1-(3-cyanophenyl)-2-cyanoethyl)amino)propyl)benzonitrile (Diastereomer B); LC-MS: m/e=439 (M+1), 441 (M+3) (3.41 min).

Workup

  1. customThe solution was degassed
  2. customby bubbling N2 for 30 min
  3. customThe vial was sealed
  4. temperatureAfter the reaction cooled
  5. filtrationit was filtered through a pad of CELITE, diatomaceous earth
  6. washthe solids were washed with ether
  7. additionThe filtrate was diluted with ether
  8. washwashed with water, and brine
  9. customdried
  10. concentrationconcentrated
  11. customThe residue was purified by prep TLC

Sources & evidence

ORD record
ord-8ea1fcb54d3742608ba9f568b53dc226
Source dataset
uspto-grants-2008_06
Patent number
US07390835B2

Reaction notes

Loading…