HCID 86723981, compound → HCID 86723982, compound

HRID 1475372Notes

Reaction equation

HRID 1475372 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]([N:17]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:26]([CH3:28])=[CH2:27])[CH:24]=3)[CH2:19][CH2:18]2)=[O:16])[CH2:10][C@H:9]1[CH3:29])=[O:7])([CH3:4])([CH3:3])[CH3:2]>[Pd].CO>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]([N:17]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([CH:26]([CH3:28])[CH3:27])[CH:24]=3)[CH2:19][CH2:18]2)=[O:16])[CH2:10][C@H:9]1[CH3:29])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 1

HCID 86723981HCID 86723981, compound

Product 1

HCID 86723982HCID 86723982, compoundYield 86.8%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

Pd(PPh3)4 (32 mg, 0.03 mmol), (R)-4-[2-(6-bromo-2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-2-methyl-piperazine-1-carboxylic acid tert-butyl ester (246 mg, 0.56 mmol) and 2-isopropenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (113 mg, 0.67 mmol) were dissolved in DMF (1.87 mL). Cs2CO3 (549 mg, 1.7 mmol) dissolved in water (0.37 mL) was added to the DMF solution. The reaction was degassed and heated to 85° C. for 18 h then was filtered and concentrated. Column chromatography on silica gel (gradient elution, 0-100% EtOAc/petrol), gave (R)-4-[2-(6-isopropenyl-2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-2-methyl-piperazine-1-carboxylic acid tert-butyl ester (0.18 g) as a yellow oil. 10% Pd/C (48 mg, 0.05 mmol) and (R)-4-[2-(6-isopropenyl-2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-2-methyl-piperazine-1-carboxylic acid tert-butyl ester (0.18 g) were mixed with MeOH (4.5 mL). The reaction was hydrogenated at 1 bar for 30 min at ambient temperature then filtered under vacuum and concentrated, to give the title compound (157 mg, 86%) as a colourless oil. 1H NMR (Me-d3-OD): 8.08 (1H, s), 7.15 (1H, d), 6.95 (1H, d), 4.35-4.18 (3H, m), 3.83 (1H, d), 3.30 (2H, s), 3.25-3.12 (3H, m), 2.97-2.76 (3H, m), 2.33 (1H, dd), 2.20-2.08 (1H, m), 1.48 (9H, s), 1.31 (3H, d), 1.25 (6H, d).

Workup

  1. filtrationthen filtered under vacuum
  2. concentrationconcentrated

Sources & evidence

ORD record
ord-1a0777ee42554a969682428945b793c9
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

Loading…