Sodium Carbonate → (2S)-N-(cyanomethyl)-4-methyl-2-{[(S)-(4'-piperazin-1-yl-1,1'-biphenyl-4-yl)(thien-2-yl)methyl]oxy}pentanamide

HRID 1180386Notes

Reaction equation

HRID 1180386 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([C:21]2[S:22][CH:23]=[CH:24][CH:25]=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.[N:26]1([C:32]2[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=2)[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C>[C:15]([CH2:14][NH:13][C:11](=[O:12])[C@@H:10]([O:9][C@@H:8]([C:5]1[CH:6]=[CH:7][C:2]([C:35]2[CH:34]=[CH:33][C:32]([N:26]3[CH2:27][CH2:28][NH:29][CH2:30][CH2:31]3)=[CH:37][CH:36]=2)=[CH:3][CH:4]=1)[C:21]1[S:22][CH:23]=[CH:24][CH:25]=1)[CH2:17][CH:18]([CH3:20])[CH3:19])#[N:16]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 5233013[4-(Piperazin-1-yl)phenyl]boronic acidHCID 10342122(2S)-2-{[(S)-(4-bromophenyl)(thien-2-yl)methyl]oxy}-N-(cyanomethyl)-4-methylpentanamide

Product 1

HCID 10051796(2S)-N-(cyanomethyl)-4-methyl-2-{[(S)-(4'-piperazin-1-yl-1,1'-biphenyl-4-yl)(thien-2-yl)methyl]oxy}pentanamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of (2S)-2-{[(S)-(4-bromophenyl)(thien-2-yl)methyl]oxy}-N-(cyanomethyl)-4-methylpentanamide, from example 20, step 3 (113 mg, 0.27 mmol) in DMF (3 mL) was added 4-piperazin-1-ylphenylboronic acid (73 mg, 0.30 mmol), and a 2.0M aqueous solution of Na2CO3 (0.54 mL, 1.08 mmol). The mixture was placed under vacuum and purged with nitrogen 3 times before the PdCl2(dppf)2 was added (10 mg, 0.014 mmol). The reaction mixture was purged 3 other times with nitrogen and the reaction was heated to 85° C. for 16 hours. The mixture was then diluted with dichloromethane and filtered over celite. The organic layer was isolated and washed with a saturated solution of NaHCO3 and brine, dried and evaporated. The crude residue was chromatographed on silica gel using 1% NH4OH and 9% methanol in dichloromethane to afford the title compound.

Workup

  1. custompurged with nitrogen 3 times before the PdCl2(dppf)2
  2. additionwas added (10 mg, 0.014 mmol)
  3. customThe reaction mixture was purged 3 other times with nitrogen
  4. additionThe mixture was then diluted with dichloromethane
  5. filtrationfiltered over celite
  6. customThe organic layer was isolated
  7. washwashed with a saturated solution of NaHCO3 and brine
  8. customdried
  9. customevaporated
  10. customThe crude residue was chromatographed on silica gel using 1% NH4OH and 9% methanol in dichloromethane

Sources & evidence

ORD record
ord-b5e90da037934bacafcb22cf4fbc68dd
Source dataset
uspto-grants-2007_10
Patent number
US07279478B2

Reaction notes

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