Lithium Hexamethyldisilazide → HCID 44553733, compound

HRID 1254060Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[N:11]([CH3:21])[C:12]=2[S:13][C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)=[CH:4][CH:3]=1.[Li+].C[Si]([N-:33][Si](C)(C)C)(C)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[Cl:20][C:17]1[CH:18]=[CH:19][C:14]([S:13][C:12]2[N:11]([CH3:21])[C:10]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)=[N:9][C:8]=2[C:5]2[CH:6]=[CH:7][C:2]([NH2:33])=[CH:3][CH:4]=2)=[CH:15][CH:16]=1

Participants

Conditions

Temperature: 75 °C

Procedure

2-{4-(4-Bromophenyl)-5-[(4-chlorophenyl)thio]-1-methyl-1H-imidazol-2-yl}pyridine (Example 15, 300 mg, 0.57 mmol), Pd(dba)2 (19 mg, 0.03 mmol), and biphenyl-PCy2 (11.5 mg, 0.03 mmol) were charged into a flask that was flushed with nitrogen. Toluene (2.2 mL) was added, followed by LiHMDS (1M in PhMe, 2 mL, 2 mmol). After heating at 75° C. overnight, the reaction was quenched with aqueous NH4Cl and diluted with EtOAc. The organic layer was washed with water and brine. The volatiles were evaporated and the residue was purified by reverse phase HPLC to afford the title compound. 1H NMR (500 MHz, (CD3OD): 8.58 (broads, 1H), 8.18 (broad s, 1H), 7.98 (t, 1H), 8.27 (d, 2H), 7.68 (d, 2H), 7.46 (broad s, 7.07 (d, 2H), 6.78 (d, 2H), 3.98 (s, 3H). LCMS: m/z 393 (M+H)+.

Workup

customwas flushed with nitrogen
additionToluene (2.2 mL) was added
customthe reaction was quenched with aqueous NH4Cl
additiondiluted with EtOAc
washThe organic layer was washed with water and brine
customThe volatiles were evaporated
customthe residue was purified by reverse phase HPLC

Sources & evidence

ORD record: ord-6c7f058d35874f3392fabb75f2b6d5e2
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08455528B2

Reaction notes

Loading…