Nitrogen → N-(4'-fluoro-5-(6-(thiazol-2-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-[1,1'-biphenyl]-3-yl)acetamide
Reaction equation
Br[C:2]1[CH:3]=[C:4]2[N:10]=[CH:9][N:8]([C:11]3[CH:12]=[C:13]([NH:24][C:25](=[O:27])[CH3:26])[CH:14]=[C:15]([C:17]4[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=4)[CH:16]=3)[C:5]2=[N:6][CH:7]=1.N#N.[Br-].[S:31]1[CH:35]=[CH:34][N:33]=[C:32]1[Zn+]>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:23][C:20]1[CH:21]=[CH:22][C:17]([C:15]2[CH:16]=[C:11]([N:8]3[C:5]4=[N:6][CH:7]=[C:2]([C:32]5[S:31][CH:35]=[CH:34][N:33]=5)[CH:3]=[C:4]4[N:10]=[CH:9]3)[CH:12]=[C:13]([NH:24][C:25](=[O:27])[CH3:26])[CH:14]=2)=[CH:18][CH:19]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Procedure
A solution of N-(5-(6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)-4′-fluoro-[1,1′-biphenyl]-3-yl)acetamide (300 mg, 0.705 mmol) in THF (8 ml) was degassed by N2 bubbling for 5 min. Thiazol-2-yl zinc(II) bromide (485 mg, 2.11 mmol, 3.0 eq.) was added and the mixture was degassed for another 5 min. Pd(dppf)Cl2 (57 mg, 0.070 mmol, 0.1 eq.) aqueous sodium carbonate were added and the procedure of Example 1(d) was followed. The crude residue of the product was purified by preparative HPLC to yield the title product in 40% yield (120 mg) 1H NMR (400 MHz, DMSO-D6): 610.43 (s, 1H), 8.78 (s, 1H), 8.45 (s, 1H), 8.08 (s, 1H), 8.01 (d, 1H), 7.94 (d, 1H), 7.85-7.73 (m, 4H), 7.55 (s, 1H), 7.45 (t, 1H), 7.27 (t, 1H), 2.13 (s, 3H), LC-MS (ESI): Calculated mass: 429.47; Observed mass: 430.00 [M+H]+ (rt: 1.33 min).
Workup
- customthe mixture was degassed for another 5 min
- customThe crude residue of the product was purified by preparative HPLC
Sources & evidence
- ORD record
- ord-550d8101723948a4a3bdd40ee334b77b
- Source dataset
- uspto-grants-2016_09
- Patent number
- US09447091B2
Reaction notes
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