Water → HCID 58094807, compound

HRID 1530118Notes

Reaction equation

HRID 1530118 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:12]3[S:13][C:14]([C:23]4[N:27]=[CH:26][N:25]([CH:28]5[CH2:33][CH2:32][CH2:31][CH2:30][O:29]5)[N:24]=4)=[C:15]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[N:16]=3)=[C:9]([CH3:11])[N:10]=2)[CH:7]=1.[CH:34]([B-](F)(F)F)=[CH2:35].[K+].ClCCl.C(=O)([O-])[O-].[Cs+].[Cs+].COCCOC.O>CCOC(C)=O.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].CO.C(Cl)Cl>[CH3:11][C:9]1[N:10]=[C:5]2[CH:4]=[CH:3][C:2]([CH:34]=[CH2:35])=[CH:7][N:6]2[C:8]=1[C:12]1[S:13][C:14]([C:23]2[N:27]=[CH:26][N:25]([CH:28]3[CH2:33][CH2:32][CH2:31][CH2:30][O:29]3)[N:24]=2)=[C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:16]=1

Participants

10

Reactant 6

HCID 962WaterHCID 6344DichloromethaneHCID 80711,2-DimethoxyethaneHCID 10796Cesium carbonateHCID 23679353Potassium vinyltrifluoroborateHCID 58094803HCID 58094803, compound

Product 1

HCID 58094807HCID 58094807, compoundYield 79.7%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

A mixture (suspension) of [A] 6-bromo-2-methyl-3-{4-phenyl-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-1,3-thiazol-2-yl}imidazo[1,2-a]pyridine (1.04 g, 2.00 mmol), Potassiumvinyltrifluoroborate (0.402 g, 3.00 mmol), [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (0.163 g, 0.200 mmol) and Cesium Carbonate (1.95 g, 6.00 mmol) in 1,2-Dimethoxyethane (70 mL, 700 mmol) and Water (14 mL, 780 mmol) was heated to 95° C. under atmosphere of N2 for 4 hours. The mixture was cooled to r.t., diluted with EtOAc (40 mL), filtered through Celite. The filtrate was diluted further with EtOAc (500 mL), washed with water, brine, dried over Na2SO4, filtered, rotavaped to give a crude product. Chromatograph in a 40 g ISCO column using MeOH/DCM (0/100 to 5/95) gave a solid product (0.747 g, 79.7% yield). LCMS: (FA) ES+ 468. 1H NMR (400 MHz, dr-chloroform) δ 9.97 s, 1H), 8.29 (σ, 1H), 7.95-7.98 (m, 2H), 7.56-7.62 (m, 2H), 7.42-7.46 (m, 3H), 6.71-6.78 (dd, J=17.57, 10.79 Hz, 1H), 5.76-5.81 (d, J=17.57 Hz, 1H), 5.48-5.51 (dd, J=8.53, 3.26 Hz, 1H), 5.33-5.36 (d, J=11.04 Hz, 1H), 4.06-4.10 (m, 1H), 3.70-3.77 (m, 1H), 2.81 (s, 3H), 2.00-2.18 (m, 3H), 1.63-1.74 (m, 3H).

Workup

  1. filtrationfiltered through Celite
  2. additionThe filtrate was diluted further with EtOAc (500 mL)
  3. washwashed with water, brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customto give a crude product

Sources & evidence

ORD record
ord-e844091ed8b04a5e9da7e8bfc83cc9e9
Source dataset
uspto-grants-2015_07
Patent number
US09090601B2

Reaction notes

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