Water → HCID 42633339, compound

HRID 239857Notes

Reaction equation

HRID 239857 reaction equation
[C:1]([C@@H:3]([NH:12][C:13](=[O:42])[C@H:14]([CH2:37][C:38]([F:41])([CH3:40])[CH3:39])[NH:15][C@@H:16]([C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:32]=[CH:31][C:30]([S:33]([CH3:36])(=[O:35])=[O:34])=[CH:29][CH:28]=2)=[CH:23][CH:22]=1)[C:17]([F:20])([F:19])[F:18])[CH2:4][C:5]1[CH:10]=[CH:9][C:8](I)=[CH:7][CH:6]=1)#[N:2].O.[CH3:44][N:45](C=O)C>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].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].[C-]#N.[Zn+2].[C-]#N>[C:1]([C@@H:3]([NH:12][C:13](=[O:42])[C@@H:14]([NH:15][C@@H:16]([C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:32]=[CH:31][C:30]([S:33]([CH3:36])(=[O:35])=[O:34])=[CH:29][CH:28]=2)=[CH:23][CH:22]=1)[C:17]([F:20])([F:19])[F:18])[CH2:37][C:38]([F:41])([CH3:40])[CH3:39])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:44]#[N:45])=[CH:7][CH:6]=1)#[N:2]

Participants

7

Reactant 3

HCID 962WaterHCID 6228DimethylformamideHCID 68779841HCID 68779841, compound

Product 1

HCID 42633339HCID 42633339, compound

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
90 °C

Procedure

To N-[(1S)-1-cyano-2-(4-iodophenyl)ethyl]-4-fluoro-N2-{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)biphenyl-4-yl]ethyl}-L-leucinamide (1 eq) in DMF (0.1 M) were added Pd2(dba)3 (0.05 eq), dppf (0.05 eq), water (10 eq) and zinc cyanide (2.5 eq). N2 was bubbled into the mixture for 5 minutes and the mixture was then heated to 90° C. for 2 h. The reaction mixture was cooled and diluted with EtOAc and saturated aqueous ammonium chloride, the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine and water, filtered and concentrated. The crude compound was purified by automated SiO2 flash chromatography system using solvent gradient of 40% EtOAc/Hex to 100% EtOAc/Hex.

Workup

  1. customN2 was bubbled into the mixture for 5 minutes
  2. temperatureThe reaction mixture was cooled
  3. additiondiluted with EtOAc and saturated aqueous ammonium chloride
  4. extractionthe aqueous layer was extracted with EtOAc
  5. washThe combined organic layers were washed with brine and water
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude compound was purified by automated SiO2 flash chromatography system

Sources & evidence

ORD record
ord-2c7ba90f37774153860cca70edf311d1
Source dataset
uspto-grants-2014_02
Patent number
US08642799B2

Reaction notes

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