N,N-Dimethylformamide--water (1/1) → HCID 66705772, compound

HRID 603001Notes

Reaction equation

HRID 603001 reaction equation
Br[C:2]1[CH:3]=[C:4]([C@H:9]([CH:14]2[CH2:17][N:16]([C@@H:18]([C:30]3[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=3)[C:19]3[CH:20]=[C:21]([C:25]4[N:29]=[CH:28][O:27][N:26]=4)[CH:22]=[CH:23][CH:24]=3)[CH2:15]2)[C:10]([F:13])([CH3:12])[CH3:11])[CH:5]=[C:6]([F:8])[CH:7]=1.[CH3:37][N:38](C=O)C.O>[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].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]>[Cl:36][C:33]1[CH:34]=[CH:35][C:30]([C@@H:18]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]3[N:29]=[CH:28][O:27][N:26]=3)[CH:20]=2)[N:16]2[CH2:15][CH:14]([C@@H:9]([C:4]3[CH:3]=[C:2]([CH:7]=[C:6]([F:8])[CH:5]=3)[C:37]#[N:38])[C:10]([F:13])([CH3:12])[CH3:11])[CH2:17]2)=[CH:31][CH:32]=1

Participants

6

Reactant 2

HCID 21962138N,N-Dimethylformamide--water (1/1)HCID 67055373HCID 67055373, compound

Product 1

HCID 66705772HCID 66705772, compound

Reagents, catalysts & solvents 3

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

Conditions

Temperature
135 °C

Procedure

A mixture of 60 mg (0.104 mmol) of 3-{3-[(S)-{3-[(1S)-1-(3-bromo-5-fluorophenyl)-2-fluoro-2-methyl propyl]azetidin-1-yl}(4-chlorophenyl)methyl]phenyl}-1,2,4-oxadiazole, 48.5 mg (0.84 mmol) of zinc cyanide, 4 mg (0.004 mmol) of tris(dibenzylideneacetone)-dipalladium, and 5 mg (0.009 mmol) of DPPF in 3 mL of DMF/H2O (99/1) was degassed with N2 for 1 h at rt. Then it was stirred at 135° C. After 14 h, the reaction mixture was concentrated to remove solvents. Then the mixture was poured into 20 mL of CH2Cl2 and 5 mL of aq NaHCO3 (pH>7). The aqueous layer was extracted with CH2Cl2 and the combined organic layer was dried over Na2S04 and concentrated. The residue was purified by silica gel chromatography with hexanes/acetone to afford the title compound as a white solid; Mass Spectrum: m/e=519 (M+1, 35Cl), 521 (M+1, 37Cl).

Workup

  1. customwas degassed with N2 for 1 h at rt
  2. concentrationthe reaction mixture was concentrated
  3. customto remove solvents
  4. additionThen the mixture was poured into 20 mL of CH2Cl2 and 5 mL of aq NaHCO3 (pH>7)
  5. extractionThe aqueous layer was extracted with CH2Cl2
  6. customthe combined organic layer was dried over Na2S04
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography with hexanes/acetone

Sources & evidence

ORD record
ord-e7495bf963a544c6a9ea652020c511a2
Source dataset
uspto-grants-2011_03
Patent number
US07906652B2

Reaction notes

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