Lithium Chloride → HCID 66748152, compound

HRID 2402078Notes

Reaction equation

HRID 2402078 reaction equation
Br[C:2]1[S:6][C:5]([C:7]2[N:11]=[CH:10][N:9]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[N:8]=2)=[C:4]([CH:20]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=2)[OH:21])[CH:3]=1.C[Sn](C)(C)[C:31]1[CH:36]=[CH:35][N:34]=[C:33]([NH:37][C:38](=[O:40])[CH3:39])[CH:32]=1.[Cl-].[Li+]>O1CCOCC1.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.[Cu]I>[Cl:28][C:25]1[CH:26]=[CH:27][C:22]([CH:20]([OH:21])[C:4]2[CH:3]=[C:2]([C:31]3[CH:36]=[CH:35][N:34]=[C:33]([NH:37][C:38](=[O:40])[CH3:39])[CH:32]=3)[S:6][C:5]=2[C:7]2[N:11]=[CH:10][N:9]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[N:8]=2)=[CH:23][CH:24]=1

Participants

7

Reactant 3

HCID 433294Lithium ChlorideHCID 59529632N-(4-(trimethylstannyl)pyridin-2-yl)acetamideHCID 68006722HCID 68006722, compound

Product 1

HCID 66748152HCID 66748152, compoundYield 80.8%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of [5-bromo-2-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-3-thienyl](4-chlorophenyl)methanol (3.07 g, 5.52 mmol)) (synthesized in an analogous way as described in Example 2), N-[4-(trimethylstannyl)pyridin-2-yl]acetamide (1.81 g, 6.07 mmol), tetrakis(triphenylphosphine)palladium(0) (319 mg, 0.28 mmol), copper(I) iodide (315 mg, 1.65 mmol) and lithium chloride (702 mg, 16.5 mmol) in 1,4-dioxane (25.0 mL) was stirred at 100° C. for 2 hours under an atmosphere of nitrogen. The reaction was cooled to room temperature and concentrated with Celite. The crude mixture was purified by column chromatography (SiO2, eluent with methanol in dichloromethane, 0-5% gradient) to afford a yellow solid (2.48 g, 80%). LCMS: (AA) ES+ 556, 558; 1H NMR (400 MHz, CDCl3) δ: 8.48 (br s, 1H), 8.43 (br s, 1H), 8.25 (s, 1H), 8.19 (d, J=5.6 Hz, 1H), 7.41 (d, J=8.4 Hz, 2H), 7.33-7.24 (m, 2H), 7.19 (s, 1H), 7.16 (dd, J=1.2, 5.6 Hz, 1H), 6.22 (s, 1H), 6.05 (br s, 1H), 5.51 (s, 2H), 3.66 (t, J=8.4 Hz, 2H), 2.22 (s, 3H), 0.94 (t, J=8.4 Hz, 2H), −0.01 (s, 9H).

Workup

  1. customsynthesized in an analogous way
  2. temperatureThe reaction was cooled to room temperature
  3. concentrationconcentrated with Celite
  4. customThe crude mixture was purified by column chromatography (SiO2, eluent with methanol in dichloromethane, 0-5% gradient)

Sources & evidence

ORD record
ord-6552c8ea737e4dae8784e48141df3663
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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