Nitrogen → HCID 117777513, compound

HRID 64178Notes

Reaction equation

HRID 64178 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:25][S:26]([CH2:29][CH3:30])(=[O:28])=[O:27])[CH:14]=[C:15]([C:17]4[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=4[F:24])[CH:16]=3)[C:5]2=[N:6][CH:7]=1.N#N.[CH:33]([N:36]1[CH:40]=[CH:39][C:38](B2OC(C)(C)C(C)(C)O2)=[N:37]1)([CH3:35])[CH3:34].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.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:24][C:18]1[CH:19]=[C:20]([F:23])[CH:21]=[CH:22][C:17]=1[C:15]1[CH:16]=[C:11]([N:8]2[C:5]3=[N:6][CH:7]=[C:2]([C:39]4[CH:38]=[N:37][N:36]([CH:33]([CH3:35])[CH3:34])[CH:40]=4)[CH:3]=[C:4]3[N:10]=[CH:9]2)[CH:12]=[C:13]([NH:25][S:26]([CH2:29][CH3:30])(=[O:28])=[O:27])[CH:14]=1

Participants

7

Reactant 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 665094051-Isopropyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 89501294HCID 89501294, compound

Product 1

HCID 117777513HCID 117777513, compoundYield 52.1%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of N-(5-(6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)-2′,4′-difluoro-[1,1′-biphenyl]-3-yl)ethanesulfonamide (0.2 g, 0.405 mmol) in 1,2-dimethoxyethane (5 ml) was degassed by N2 bubbling for 5 min. 1-Isopropyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.191 g, 0.810 mmol, 2.0 eq.) was added and the mixture was degassed for another 5 min. Pd(dppf)Cl2 (0.032 g, 0.040 mmol, 0.1 eq.) and aqueous sodium carbonate (0.17 g, 1.012 mmol, 2.5 eq.) were added and the procedure of Example 1(d) was followed. The crude residue of the product was purified by column chromatography (60-120 silica gel, 80% ethyl acetate in hexane) to yield the product in 52.1% yield (0.11 g). 1H NMR (400 MHz, DMSO-d6): δ 10.42 (s, 1H), 8.94 (s, 1H), 8.75 (d, 1H), 8.44-8.42 (dd, 2H), 8.05 (s, 1H), 7.95 (s, 1H), 7.77-7.70 (m, 2H), 7.48-7.43 (m, 2H), 7.30-7.26 (m, 1H), 4.54-4.51 (m, 1H), 4.13-4.11 (m, 1H); 3.28-3.26 (m, 2H), 3.17-3.16 (d, 1H), 1.48-1.46 (d, 6H), 1.28-1.25 (t, 3H), LC-MS (ESI): Calculated mass: 522.57 Observed mass: 523.0 [M+H]+ (rt: 1.52 min).

Workup

  1. customthe mixture was degassed for another 5 min
  2. customThe crude residue of the product was purified by column chromatography (60-120 silica gel, 80% ethyl acetate in hexane)
  3. customto yield the product in 52.1% yield (0.11 g)
  4. custom523.0 [M+H]+ (rt: 1.52 min)

Sources & evidence

ORD record
ord-ccde8d67e5ef4105a0bb6f22ab529cbb
Source dataset
uspto-grants-2016_09
Patent number
US09447091B2

Reaction notes

Loading…