Sodium Carbonate → 4-(4-Methyl-3'-nitro-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-6'-yl)-piperazine-1-carboxylic acid benzyl ester

HRID 646938Notes

Reaction equation

HRID 646938 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH:11]([CH3:14])[CH2:10][CH2:9]2)[C:5]([N+:15]([O-:17])=[O:16])=[CH:4][CH:3]=1.C([O-])([O-])=O.[Na+].[Na+].[CH2:24]([O:31][C:32]([N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1)=[O:33])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>CN(C=O)C>[CH2:24]([O:31][C:32]([N:34]1[CH2:39][CH2:38][N:37]([C:2]2[N:7]=[C:6]([N:8]3[CH2:13][CH2:12][CH:11]([CH3:14])[CH2:10][CH2:9]3)[C:5]([N+:15]([O-:17])=[O:16])=[CH:4][CH:3]=2)[CH2:36][CH2:35]1)=[O:33])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 643495Benzyl piperazine-1-carboxylateHCID 431526786'-Chloro-4-methyl-3'-nitro-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl

Product 1

HCID 586385214-(4-Methyl-3'-nitro-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-6'-yl)-piperazine-1-carboxylic acid benzyl esterYield 94%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

A solution of 6′-chloro-4-methyl-3′-nitro-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl (as prepared in the previous step, 2.0 g, 7.8 mmol) in DMF (40 mL) was treated with solid Na2CO3 (0.99 g, 9.4 mmol) and piperazine-1-carboxylic acid benzyl ester (1.5 mL, 7.8 mmol), then heated to 90° C. for 1 h and to 40° C. for 15 h. The reaction was concentrated to 20 mL volume, diluted with EtOAc, and washed well with water. The combined aqueous layers were further extracted with EtOAc. The combined organic layers were dried over MgSO4 and concentrated in vacuo. Silica gel chromatography (25% EtOAc in hexane) afforded the title compound (3.2 g, 94%) as a yellow solid. 1H-NMR (CDCl3; 400 MHz): δ 8.19 (d, 1H, J=9.2 Hz), 7.39-7.31 (m, 5H), 6.01 (d, 1H, J=9.2 Hz), 5.16 (s, 2H), 3.84-3.76 (m, 2H), 3.71-3.65 (m, 4H), 3.64-3.58 (m, 4H), 3.02-2.93 (m, 2H), 1.74-1.65 (m, 2H), 1.66-1.60 (m, 1H), 1.38-1.26 (m, 2H), 0.97 (d, 3H, J=6.4 Hz). LC-MS (ESI, m/z): Calcd. for C23H29N5O4, 440.2 (M+H), found 439.9.

Workup

  1. concentrationThe reaction was concentrated to 20 mL volume
  2. additiondiluted with EtOAc
  3. washwashed well with water
  4. extractionThe combined aqueous layers were further extracted with EtOAc
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c964cae289ea4428b02d4d60efaffd03
Source dataset
uspto-grants-2010_04
Patent number
US07705042B2

Reaction notes

Loading…