2-Chloro-4,6-dimethylpyrimidine → (1S,6R)-3-(4,6-Dimethylpyrimidin-2-yl)-8-{[2-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]carbonyl}-3,8-diazabicyclo[4.2.0]octane

HRID 2175041Notes

Reaction equation

[C@H:1]12[N:8]([C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[C:17]3[O:21][N:20]=[C:19]([CH3:22])[N:18]=3)=[O:10])[CH2:7][C@H:6]1[CH2:5][CH2:4][NH:3][CH2:2]2.Cl[C:24]1[N:29]=[C:28]([CH3:30])[CH:27]=[C:26]([CH3:31])[N:25]=1.CCN(C(C)C)C(C)C>C(#N)C>[CH3:31][C:26]1[CH:27]=[C:28]([CH3:30])[N:29]=[C:24]([N:3]2[CH2:4][CH2:5][C@H:6]3[C@H:1]([N:8]([C:9]([C:11]4[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=4[C:17]4[O:21][N:20]=[C:19]([CH3:22])[N:18]=4)=[O:10])[CH2:7]3)[CH2:2]2)[N:25]=1

Participants

Conditions

Temperature: 200 °C

Procedure

A mixture of Intermediate 12 (50 mg, 0.17 mmol), 2-chloro-4,6-dimethylpyrimidine (24 mg, 0.17 mmol) and DIPEA (0.87 mL, 0.5 mmol) in ACN (1 mL) was heated in the microwave at 200° C. for 90 min. The mixture was concentrated in vacuo and was purified on a Prep Agilent system with a XBridge C18 OBD 50×100 mm column eluting with 5 to 99% 0.05% NH4OH in H2O/ACN over 17 min to afford the desired product as a colorless foam (41 mg, 60%). MS (ESI) mass calculated for C22H24N6O2, 404.20; m/z found, 405.2. 1H NMR (500 MHz, CDCl3): 8.12-8.03 (m, 1H), 7.59-7.49 (m, 2H), 7.41-7.36 (m, 1H), 6.31-6.26 (m, 1H), 4.41-4.23 (m, 3H), 4.11-4.05 (m, 1H), 4.05-3.78 (m, 2H), 3.68-3.64 (m, 0H), 3.05-2.83 (m, 2H), 2.46-2.40 (m, 3H), 2.34-2.24 (m, 6H), 2.15-2.04 (m, 1H), 2.00-1.86 (m, 1H).

Workup

concentrationThe mixture was concentrated in vacuo
customwas purified on a Prep Agilent system with a XBridge C18 OBD 50×100 mm column
washeluting with 5 to 99% 0.05% NH4OH in H2O/ACN over 17 min

Sources & evidence

ORD record: ord-d5831e73f5994920b92a282467faf6b1
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09062044B2

Reaction notes

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