Water → HCID 86594585, compound

HRID 1744169Notes

Reaction equation

HRID 1744169 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:20])=[C:6]([N:8]2[CH2:18][C@@H:17]([CH3:19])[CH2:16][C@H:9]2[C:10]([NH:12][CH2:13][C:14]#[N:15])=[O:11])[CH:7]=1.[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][N:31]([C:34]2[CH:39]=[CH:38][C:37](B(O)O)=[CH:36][CH:35]=2)[CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22].C(=O)([O-])[O-].[Na+].[Na+].O>CN(C=O)C.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:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][N:31]([C:34]2[CH:39]=[CH:38][C:37]([C:2]3[CH:3]=[CH:4][C:5]([Cl:20])=[C:6]([N:8]4[CH2:18][C@@H:17]([CH3:19])[CH2:16][C@H:9]4[C:10]([NH:12][CH2:13][C:14]#[N:15])=[O:11])[CH:7]=3)=[CH:36][CH:35]=2)[CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:22])[CH3:23]

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 52330144-(4-BOC-Piperazino)phenylboronic acidHCID 10269678HCID 10269678, compound

Product 1

HCID 86594585HCID 86594585, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

To (4S)-1-(5-bromo-2-chlorophenyl)-N-(cyanomethyl)-4-methyl-L-prolinamide (40 mg, 0.112 mmol),4-[4-(tert-butoxycarbonyl)-1-piperazinyl]phenylboronic acid (42 mg, 0.135 mmol, prepared as described in Example 1) and catalyst PdCl2(dppf) (5 mg, 0.0034 mmol) in DMF (2 mL) under dry nitrogen was added aqueous sodium carbonate (2.0 M, 0.17 mL, 0.336 mmol). The reaction was heated to 95° C. for 1 hour and an additional aliquot of PdCl2(dppf) (365 mg, 0.45 mmol) was added and the reaction mixture was heated for 3 hours. Water was added and the product extracted with ether (3×), dried over Na2SO4, concentrated in vacuo and purified by flash chromatography over silica gel (EtOAc/Hex, 4/6) to afford (4S)-1-{4′-[4-(tert-butoxycarbonyl)piperazin-1-yl]-4-chloro-1,1′-biphenyl-3-yl}-N-(cyanomethyl)-4-methyl-L-prolinamide.

Workup

  1. temperaturethe reaction mixture was heated for 3 hours
  2. extractionthe product extracted with ether (3×)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. custompurified by flash chromatography over silica gel (EtOAc/Hex, 4/6)

Sources & evidence

ORD record
ord-36bbf189d9004f5fa56695853a54c6ef
Source dataset
uspto-grants-2006_03
Patent number
US07012075B2

Reaction notes

Loading…