Diisopropylethylamine → (1R,6S)-tert-butyl 8-(6-methylpyridin-2-yl)-3,8-diazabicyclo[4.2.0]octane-3-carboxylate

HRID 1193091Notes

Reaction equation

HRID 1193091 reaction equation
[C@@H:1]12[NH:8][CH2:7][C@@H:6]1[CH2:5][CH2:4][N:3]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:2]2.Cl[C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH3:23])[N:18]=1.CCN(C(C)C)C(C)C>CC#N>[CH3:23][C:19]1[N:18]=[C:17]([N:8]2[C@@H:1]3[C@@H:6]([CH2:5][CH2:4][N:3]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:2]3)[CH2:7]2)[CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 876016-Chloro-2-picolineHCID 16099092cis-3-Boc-3,8-diazabicyclo[4.2.0]octane

Product 1

HCID 67116757(1R,6S)-tert-butyl 8-(6-methylpyridin-2-yl)-3,8-diazabicyclo[4.2.0]octane-3-carboxylateYield 15%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a microwave safe vial was added Intermediate 39 (375 mg, 1.77 mmol), 2-chloro-6-methylpyridine (0.39 mL, 3.53 mmol), CH3CN (10 mL) and DIPEA (0.61 mL, 3.53 mmol). The resulting mixture was heated to 180 C in a microwave reactor. After 3 h the crude mixture was concentrated and purified directly by FCC (SiO2, ethyl acetate/hexanes, 0-40%) to yield (1R,6S)-tert-butyl 8-(6-methylpyridin-2-yl)-3,8-diazabicyclo[4.2.0]octane-3-carboxylate (80 mg, 15%). MS (ESI) mass calcd. for C17H25N3O2, 303.2; m/z found, 304.1 [M+H]+. 1H NMR (500 MHz, CDCl3): 7.31 (t, J=7.7 Hz, 1H), 6.50-6.40 (m, 1H), 6.09 (dd, J=45.4, 8.1 Hz, 1H), 4.44-4.27 (m, Hz, 2H), 4.04-3.89 (m, 1H), 3.84-3.66 (m, 2H), 3.60-3.22 (m, 2H), 2.86-2.72 (m, 1H), 2.37 (s, 3H), 2.07-1.96 (m, 1H), 1.92-1.80 (m, 1H), 1.44-1.28 (m, 9H).

Workup

  1. temperatureThe resulting mixture was heated to 180 C in a microwave reactor
  2. concentrationAfter 3 h the crude mixture was concentrated
  3. custompurified directly by FCC (SiO2, ethyl acetate/hexanes, 0-40%)

Sources & evidence

ORD record
ord-aab2f702e16d4db9977a0a260bce2048
Source dataset
uspto-grants-2014_03
Patent number
US08680275B2

Reaction notes

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