Dimethylformamide → (2S)-N-(cyanomethyl)-4-methyl-2-{[(R)-phenyl(4'-piperazin-1-yl-1,1'-biphenyl-4-yl)methyl]oxy}pentanamide

HRID 1180372Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:9][C@@H:10]([CH2:17][CH:18]([CH3:20])[CH3:19])[C:11]([NH:13][CH2:14][C:15]#[N:16])=[O:12])=[CH:4][CH:3]=1.C([O-])([O-])=O.[Na+].[Na+].[CH3:33][N:34]([CH:36]=O)[CH3:35]>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.Cl[Pd]Cl.[Fe+2]>[C:15]([CH2:14][NH:13][C:11](=[O:12])[C@@H:10]([O:9][C@H:8]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:5]1[CH:6]=[CH:7][C:2]([C:2]2[CH:7]=[CH:6][C:33]([N:34]3[CH2:36][CH2:14][NH:13][CH2:11][CH2:35]3)=[CH:4][CH:3]=2)=[CH:3][CH:4]=1)[CH2:17][CH:18]([CH3:20])[CH3:19])#[N:16]

Participants

Conditions

Temperature: 85 °C

Procedure

(2S)-2-{[(R)-(4-bromophenyl)(phenyl)methyl]oxy}-N-(cyanomethyl)-4-methylpentanamide (1 g, 2.41 mmol) 1-[4-(dihydroxyboryl)phenyl]piperazin-4-ium chloride (642 mg, 2.65 mmol), PdCl2(dppf) (88 mg, 0.120 mmol) and 2M Na2CO3 (4.8 ml, 9.63 mmol) were dissolved in 25 ml DMF, the solution was degassed 3 times and heated for 10 h @ 85° C. The solution was cooled, poured into 125 ml NaHCO3 (sat.) and the product extracted with 3×25 ml ethyl acetate. The combined organic layers were then washed with 4× water, then dried with Na2SO4. The product was then purified on silica gel (5% MeOH/5% NH4OH/90% DCM).

Workup

customthe solution was degassed 3 times
temperatureThe solution was cooled
additionpoured into 125 ml NaHCO3 (sat.)
extractionthe product extracted with 3×25 ml ethyl acetate
washThe combined organic layers were then washed with 4× water
dry with materialdried with Na2SO4
customThe product was then purified on silica gel (5% MeOH/5% NH4OH/90% DCM)

Sources & evidence

ORD record: ord-c38e11882c874e98b9cbb5a8286a097e
Source dataset: uspto-grants-2007_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07279478B2

Reaction notes

Loading…