Cesium fluoride → HCID 136216273, compound

HRID 1748733Notes

Reaction equation

HRID 1748733 reaction equation
Br[C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[S:15][CH2:14][CH2:13][NH:12][C:11]2[N:16]([CH3:25])[N:17]=[C:18]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=3)[C:10]1=2.[CH2:26]([Sn](CCCC)(CCCC)C=C)[CH2:27]CC.[F-].[Cs+]>CN(C=O)C.C(Cl)Cl.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:8][C:6]1[CH:5]=[CH:4][C:3]([CH:9]2[S:15][CH2:14][CH2:13][NH:12][C:11]3[N:16]([CH3:25])[N:17]=[C:18]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=4)[C:10]2=3)=[C:2]([CH:26]=[CH2:27])[CH:7]=1

Participants

8

Reactant 3

HCID 25953Cesium fluorideHCID 81998TributylvinyltinHCID 136216236HCID 136216236, compound

Product 1

HCID 136216273HCID 136216273, compoundYield 63%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
45 °C

Procedure

To a degassed mixture of 4-(2-bromo-4-chloro-phenyl)-1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine (0.50 g, 1.2 mmol, Example #D.37) and tributyl(vinyl)stannane (0.37 mL, 1.3 mmol) in DMF (5 mL) was added cesium fluoride (0.35 g, 2.3 mmol), copper(I) iodide (0.022 g, 0.12 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.066 g, 0.058 mmol). The resulting mixture was heated at about 45° C. overnight; then diluted with DCM (50 mL), washed with water (20 mL) and brine (20 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO2, ethyl acetate/hexanes 1:1) to give 4-(4-chloro-2-vinyl-phenyl)-1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine (0.28 g, 0.73 mmol, 63%) as an off white solid: LC-MS (Table 1, Method a) Rt=4.07 min; m/z 383 (M+H)+; 1H-NMR (CDCl3, Bruker 400 MHz) 2.69-2.78 (1 H, m) 2.81-2.89 (1 H, m) 3.19-3.28 (1 H, m) 3.52-3.61 (1 H, m) 3.77-3.86 (1 H, m) 3.84 (3 H, s) 5.47 (1 H, dd, J=11.0, 1.5 Hz) 5.73 (1 H, dd, J=17.5, 1.5 Hz) 6.79 (1 H, s) 7.02-7.08 (2 H, m) 7.14 (1 H, d, J=8.5 Hz) 7.38 (1 H, dd, J=17.5, 11.0 Hz) 7.45 (1 H, d, J=2.0 Hz) 7.58 (1 H, td, J=7.5, 2.0 Hz) 7.77 (1 H, br.d, J=8.0 Hz) 8.42 (1 H, br.d, J=5.0 Hz).

Workup

  1. washwashed with water (20 mL) and brine (20 mL)
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography (SiO2, ethyl acetate/hexanes 1:1)

Sources & evidence

ORD record
ord-45f9aa04576149a0997814bab8b3b0b3
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

Loading…