Sodium Carbonate → Tert-butyl 4-[3'-(2-{[(cyanomethyl)amino]carbonyl}-1-piperidinyl)[1,1'-biphenyl]-4-yl]-1-piperazinecarboxylate

HRID 1744161Notes

Reaction equation

HRID 1744161 reaction equation
Br[C:2]1[CH:3]=[C:4]([N:8]2[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]2[C:14]([NH:16][CH2:17][C:18]#[N:19])=[O:15])[CH:5]=[CH:6][CH:7]=1.[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][N:30]([C:33]2[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=2)[CH2:29][CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21].C([O-])([O-])=O.[Na+].[Na+]>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:18]([CH2:17][NH:16][C:14]([CH:9]1[CH2:10][CH2:11][CH2:12][CH2:13][N:8]1[C:4]1[CH:3]=[C:2]([C:36]2[CH:35]=[CH:34][C:33]([N:30]3[CH2:29][CH2:28][N:27]([C:25]([O:24][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:26])[CH2:32][CH2:31]3)=[CH:38][CH:37]=2)[CH:7]=[CH:6][CH:5]=1)=[O:15])#[N:19]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 52330144-(4-BOC-Piperazino)phenylboronic acidHCID 222359221-(3-bromophenyl)-N-(cyanomethyl)-2-piperidinecarboxamide

Product 1

HCID 22236171Tert-butyl 4-[3'-(2-{[(cyanomethyl)amino]carbonyl}-1-piperidinyl)[1,1'-biphenyl]-4-yl]-1-piperazinecarboxylate

Reagents, catalysts & solvents 2

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

Conditions

Temperature
60 °C

Procedure

A mixture of 1-(3-bromophenyl)-N-(cyanomethyl)-2-piperidinecarboxamide (209 mg, 0.65 mmol), 4-[4-(tert-butoxycarbonyl)-1-piperazinyl]phenylboronic acid (219 mg, 0.71 mmol), and PdCl2(dppf) (41 mg, 0.05 mmol) in DMF (4 mL) was heated to 60° C. 2N Na2CO3 (0.65 mL, 1.3 mmol) was added dropwise, and the mixture was heated to 85° C. overnight. The mixture was cooled and partitioned between water and ethyl acetate. The organic layer was washed with 1 M NaOH and brine, then dried over MgSO4 and concentrated. Purification by flash chromatography (50% EtOAc/hexanes) gave tert-butyl 4-[3′-(2-{[(cyanomethyl)amino]carbonyl}-1-piperidinyl)[1,1′-biphenyl]-4-yl]-1-piperazinecarboxylate.

Workup

  1. temperaturethe mixture was heated to 85° C. overnight
  2. temperatureThe mixture was cooled
  3. custompartitioned between water and ethyl acetate
  4. washThe organic layer was washed with 1 M NaOH and brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customPurification by flash chromatography (50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-14a6df670b554437957f0fe0afc01c60
Source dataset
uspto-grants-2006_03
Patent number
US07012075B2

Reaction notes

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