N-{4-[4-bromo-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-5-yl)-1,3-thiazol-2-yl]pyridin-2-yl}acetamide → N-{4-[4-(4-Chlorobenzyl)-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-5-yl)-1,3-thiazol-2-yl]pyridin-2-yl}acetamide

HRID 2402021Notes

Reaction equation

HRID 2402021 reaction equation
Br[C:2]1[N:3]=[C:4]([C:20]2[CH:25]=[CH:24][N:23]=[C:22]([NH:26][C:27](=[O:29])[CH3:28])[CH:21]=2)[S:5][C:6]=1[C:7]1[N:11]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[N:10]=[CH:9][N:8]=1.[Cl-].[Cl:31][C:32]1[CH:39]=[CH:38][C:35]([CH2:36][Zn+])=[CH:34][CH:33]=1>O1CCCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[Cl:31][C:32]1[CH:39]=[CH:38][C:35]([CH2:36][C:2]2[N:3]=[C:4]([C:20]3[CH:25]=[CH:24][N:23]=[C:22]([NH:26][C:27](=[O:29])[CH3:28])[CH:21]=3)[S:5][C:6]=2[C:7]2[N:11]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[N:10]=[CH:9][N:8]=2)=[CH:34][CH:33]=1

Participants

5

Reactant 2

HCID 66749382N-{4-[4-bromo-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-5-yl)-1,3-thiazol-2-yl]pyridin-2-yl}acetamideHCID 178478120HCID 178478120, compound2×

Product 1

HCID 66749545N-{4-[4-(4-Chlorobenzyl)-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-5-yl)-1,3-thiazol-2-yl]pyridin-2-yl}acetamideYield 35.1%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of N-{4-[4-bromo-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-5-yl)-1,3-thiazol-2-yl]pyridin-2-yl}acetamide (0.292 g, 0.589 mmol) in tetrahydrofuran (4.1 mL) was added 4-chlorobenzylzinc chloride (0.50M solution in tetrahydrofuran, 2.36 mL, 1.18 mmol) and bis(tri-t-butylphosphine)palladium(0) (0.0226 g, 0.0442 mmol) under argon. The solution was stirred at 60° C. for 2 hours. The reaction was incomplete by LCMS, so additional 4-chlorobenzylzinc chloride (0.50M solution in tetrahydrofuran, 2 mL, 1 mmole) was added, then the reaction was stirred at 60° C. for an additional 2 hours. The reaction was allowed to cool to room temperature then the solvent was evaporated in vacuo. Column chromatography was performed to yield the title compound (0.112 g, 35%). LCMS: (FA) ES+, 542. 1H NMR (400 MHz, d4-methanol) δ: 8.73-8.69 (m, 1H), 8.42-8.38 (m, 1H), 8.14 (s, 1H), 7.58-7.55 (m, 1H), 7.27-7.20 (m, 4H), 5.52 (s, 2H), 4.32 (s, 2H), 3.68-3.61 (m, 2H), 2.20 (s, 3H), 0.90-0.84 (m, 2H), 0.040 (s, 9H).

Workup

  1. additionwas added
  2. stirringthe reaction was stirred at 60° C. for an additional 2 hours
  3. temperatureto cool to room temperature
  4. customthe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-1b3d85532eb44d88941463a8f9bea7c2
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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