2-Chloro-4,6-dimethylpyrimidine → N,N-Dimethyl-6-[(1S,6R)-8-{[2-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]carbonyl}-3,8-diazabicyclo[4.2.0]oct-3-yl]pyrimidin-4-amine

HRID 2175043Notes

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](C)[CH:27]=[C:26](C)[N:25]=1.C[CH2:33][N:34](C(C)C)[CH:35](C)C>C(#N)C>[CH3:33][N:34]([CH3:35])[C:26]1[CH:27]=[C:28]([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:29]=[CH:24][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 2 h. The mixture was concentrated in vacuo and chromatography (Hex to 100% EtOAc/Hex) to afford the desired product as a pale yellow foam (39 mg, 55%). MS (ESI) mass calculated for C22H25N7O2, 419.2; m/z found, 420.2. 1H NMR (500 MHz, CDCl3): 8.15 (s, 1H), 8.12-8.04 (m, 1H), 7.59-7.50 (m, 2H), 7.25-7.17 (m, 1H), 5.22 (s, 1H), 4.44-4.33 (m, 2H), 4.11-3.99 (m, 1H), 3.94-3.73 (m, 2H), 3.68-3.60 (m, 1H), 3.11-3.05 (m, 6H), 3.02-2.86 (m, 2H), 2.45-2.42 (m, 3H), 2.22-1.97 (m, 2H).

Workup

concentrationThe mixture was concentrated in vacuo and chromatography (Hex to 100% EtOAc/Hex)

Sources & evidence

ORD record: ord-5f3b977fabb64f1ebeb2facec22f9f69
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09062044B2

Reaction notes

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