HCID 58266390, compound → HCID 58266744, compound

HRID 1506042Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[CH:6][C:5]([NH2:8])=[C:4]([C:9]2[C:10]([F:24])=[N:11][CH:12]=[C:13](B3OC(C)(C)C(C)(C)O3)[CH:14]=2)[CH:3]=1.Br[C:26]1[S:34][C:33]2[CH2:32][CH2:31][N:30]([CH2:35][CH3:36])[CH2:29][C:28]=2[CH:27]=1>[F-].[K+].C(#N)C>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([NH2:8])=[C:4]([C:9]2[C:10]([F:24])=[N:11][CH:12]=[C:13]([C:26]3[S:34][C:33]4[CH2:32][CH2:31][N:30]([CH2:35][CH3:36])[CH2:29][C:28]=4[CH:27]=3)[CH:14]=2)[CH:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A degassed mixture of 6′-chloro-2-fluoro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-[3,4′]bipyridinyl-3′-ylamine (1.99 g, 5.70 mmol), 2-bromo-5-ethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine (1.54 g, 6.30 mmol), 1,1′-[bis(diphenylphosphino) ferrocene]dichloropalladium(II) (466 mg, 0.57 mmol) in 1N aqueous potassium fluoride solution (22.5 mL) and acetonitrile (22.5 mL) was heated under microwave irradiation at 100° C. for 30 minutes. The cooled reaction mixture was loaded onto an SCX-2 cartridge (50 g) and eluted with 2N ammonia in methanol to afford impure product as a brown solid. The resultant brown residue was purified by flash chromatography (silica, 40 g column, ISCO, 0-10% methanol in DCM) to afford the title compound as an off-white solid (1.05 g, 47%). 1H NMR (DMSO-D6, 300 MHz): 8.48 (d, J=2.4 Hz, 1H), 8.12 (dd, J=9.0, 2.6 Hz, 1H), 7.89 (s, 1H), 7.36 (s, 1H), 7.21 (s, 1H), 5.54 (s, 2H), 3.45 (s, 2H), 2.86-2.79 (m, 2H), 2.75-2.68 (m, 2H), 2.58-2.51 (m, 2H), 1.08 (t, J=7.1 Hz, 3H).

Workup

customThe cooled reaction mixture
washeluted with 2N ammonia in methanol
customto afford impure product as a brown solid
customThe resultant brown residue was purified by flash chromatography (silica, 40 g column, ISCO, 0-10% methanol in DCM)

Sources & evidence

ORD record: ord-a7db35fa73be49aaa1ef6045b60daa8b
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09216980B2

Reaction notes

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