1,4-Cyclohexadiene → N-[(3R,4S)-4-ethoxypyrrolidin-3-yl]-3,6-diethyl-5-(6-methoxy-2-methylpyridin-3-yl)pyrazin-2-amine

HRID 1297292Notes

Reaction equation

HRID 1297292 reaction equation
[CH2:1]([C:3]1[C:4]([NH:20][C@H:21]2[C@@H:25]([O:26][CH2:27][CH3:28])[CH2:24][N:23](C(OCC3C=CC=CC=3)=O)[CH2:22]2)=[N:5][C:6]([CH2:18][CH3:19])=[C:7]([C:9]2[C:10]([CH3:17])=[N:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=2)[N:8]=1)[CH3:2].C1CC=CCC=1>C(O)C.[Pd]>[CH2:27]([O:26][C@H:25]1[CH2:24][NH:23][CH2:22][C@H:21]1[NH:20][C:4]1[C:3]([CH2:1][CH3:2])=[N:8][C:7]([C:9]2[C:10]([CH3:17])=[N:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=2)=[C:6]([CH2:18][CH3:19])[N:5]=1)[CH3:28]

Participants

5

Reactant 2

HCID 123431,4-CyclohexadieneHCID 58914559HCID 58914559, compound

Product 1

HCID 58914560N-[(3R,4S)-4-ethoxypyrrolidin-3-yl]-3,6-diethyl-5-(6-methoxy-2-methylpyridin-3-yl)pyrazin-2-amineYield 87%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a solution of benzyl (3R,4S)-3-{[3,6-diethyl-5-(6-methoxy-2-methylpyridin-3-yl)pyrazin-2-yl]amino}-4-ethoxypyrrolidine-1-carboxylate (1.35 g) in ethanol (26 ml) was added 1,4 cyclohexadiene (2.45 ml, 10 eq.) and 10% Pd/C (1.5 g). The reaction mixture stirred 2 h, was filtered through celite and concentrated. Purification via MPLC chromatography eluting with 2–6% methanol/CH2Cl2 with 0.5% ammonium hydroxide afforded the title compound as an amber oil (870 mg, 87%): 1H NMR (400 MHz, CDCl3) δ) 7.41, 6.64, 5.34–5.32, 4.52, 4.05, 3.97, 3.68, 3.53, 3.43, 3.22, 3.15, 2.92, 2.70, 2.46, 2.29, 1.32–1.25, 1.14; IR (liq.) 2972, 2935, 2408 (w), 2238 (w), 2019 (w), 1971 (w), 1596, 1563 (s), 1499, 1474 (s), 1426, 1394, 1304 (s), 1251, 1042 cm−1 HRMS (ESI) calcd for C21H31N5O2+H1 386.2556. found 386.2544.

Workup

  1. filtrationwas filtered through celite and
  2. concentrationconcentrated
  3. customPurification via MPLC chromatography
  4. washeluting with 2–6% methanol/CH2Cl2 with 0.5% ammonium hydroxide

Sources & evidence

ORD record
ord-161fbf7c7b024035bada060d13711c2a
Source dataset
uspto-grants-2007_07
Patent number
US07250418B2

Reaction notes

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