Cesium carbonate → 1-Methyl-2-(1-(2-methyl-6-(2-methylpyridin-3-yl)pyrimidin-4-yl)azetidin-3-yl)-1H-benzo[d]imidazole

HRID 2202822Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([N:9]2[CH2:12][CH:11]([C:13]3[N:17]([CH3:18])[C:16]4[CH:19]=[CH:20][CH:21]=[CH:22][C:15]=4[N:14]=3)[CH2:10]2)[CH:3]=1.[CH3:23][C:24]1[C:29](B(O)O)=[CH:28][CH:27]=[CH:26][N:25]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1COCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH3:18][N:17]1[C:16]2[CH:19]=[CH:20][CH:21]=[CH:22][C:15]=2[N:14]=[C:13]1[CH:11]1[CH2:12][N:9]([C:4]2[CH:3]=[C:2]([C:29]3[C:24]([CH3:23])=[N:25][CH:26]=[CH:27][CH:28]=3)[N:7]=[C:6]([CH3:8])[N:5]=2)[CH2:10]1

Participants

Conditions

Temperature: 100 °C

Procedure

A solution of Intermediate 3 (0.015 g, 0.048 mmol), (2-methylpyridin-3-yl)boronic acid (9.9 mg, 0.072 mmol), and cesium carbonate (1 M, 0.12 mL, 0.12 mmol) in THF (0.5 mL) under an atmosphere of nitrogen was treated with bis(tri-tert-butylphosphine)palladium(0) (1.5 mg, 0.0029 mmol) and heated to 100° C. overnight. The mixture was cooled, stirred with Quadrapure for 3 h, filtered, and concentrated. The residue was purified by reverse phase HPLC to give Example 80. 1H NMR: (400 MHz, d6-DMSO) δ 8.68 (d, J=1.2 Hz, 1H), 7.91 (d, J=15.0 Hz, 1H), 7.68-7.63 (m, 2H), 7.51-7.48 (m, 1H), 7.35-7.27 (m, 2H), 6.83 (s, 1H), 4.79-4.74 (m, 2H), 4.65-4.56 (m, 3H), 3.80 (s, 3H), 2.56 (s, 3H), 2.53 (s, 3H). MS: m/z=371.4 (M+H).

Workup

temperatureThe mixture was cooled
filtrationfiltered
concentrationconcentrated
customThe residue was purified by reverse phase HPLC
customto give Example 80

Sources & evidence

ORD record: ord-c140fccf58f64fa3851d9610d0081c9d
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09365562B2

Reaction notes

Loading…