Dimethylformamide → 4-bromo-2-(2-methylpyrazolo[1,5-a]pyridin-3-yl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)thiazole

HRID 2401764Notes

Reaction equation

HRID 2401764 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([C:20]#[C:21][CH3:22])[S:5][C:6]=1[C:7]1[N:11]=[CH:10][N:9]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[N:8]=1.[I-].[NH2:24][N+:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>>[Br:1][C:2]1[N:3]=[C:4]([C:20]2[C:21]([CH3:22])=[N:24][N:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=23)[S:5][C:6]=1[C:7]1[N:11]=[CH:10][N:9]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[N:8]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 2733704Pyridinium, 1-amino-, iodide (1:1)HCID 580949523-(4-bromo-2-prop-1-yn-1-yl-1,3-thiazol-5-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazole

Product 1

HCID 580948524-bromo-2-(2-methylpyrazolo[1,5-a]pyridin-3-yl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)thiazoleYield 64.8%

Procedure

A mixture of 3-(4-bromo-2-prop-1-yn-1-yl-1,3-thiazol-5-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazole (0.514 g, 1.29 mmol), 1-aminopyridinium iodide (0.343 g, 1.54 mmol) and potassium carbonate (0.231 g, 1.67 mmol) in N,N-dimethylformamide (8.0 mL, 1.0E2 mmol) was stirred at rt for 29 hours. The mixture was quenched with ice water (80 mL) then extracted with EtOAc 3 times. The combined EtOAc solution was washed with water, brine, dried over Na2SO4, filtered and purified by column chromatography (SiO2, elution with 0-100% EtOAc in hexane) to afford a solid product. (0.410 g, 64.8% yield). LCMS: (FA) ES+ 491, 493. 1H NMR (400 MHz, CDCl3) δ: 8.43-8.46 (m, 2H), 8.32 (s, 1H), 7.39-7.42 (m, 1H), 6.90-6.93 (m, 1H), 5.57 (m, 2H), 3.72-3.76 (m, 2H), 2.76 (s, 3H), 0.96-1.00 (m, 2H), 0.00 (s, 9H).

Workup

  1. customThe mixture was quenched with ice water (80 mL)
  2. extractionthen extracted with EtOAc 3 times
  3. washThe combined EtOAc solution was washed with water, brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. custompurified by column chromatography (SiO2, elution with 0-100% EtOAc in hexane)
  7. customto afford a solid product

Sources & evidence

ORD record
ord-cb6774e26d5c418288061d028a4260f6
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

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