Potassium Carbonate → 3-[4-Bromo-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-1,3-thiazol-2-yl]-5-(diethoxymethyl)-2-methylpyrazolo[1,5-a]pyridine

HRID 2402057Notes

Reaction equation

HRID 2402057 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.C(=O)([O-])[O-].[K+].[K+].CC1C=C(C)C=C(C)C=1S([O-])(=O)=O.[NH2:42][N+:43]1[CH:48]=[CH:47][C:46]([CH:49]([O:53][CH2:54][CH3:55])[O:50][CH2:51][CH3:52])=[CH:45][CH:44]=1>CN(C)C=O>[Br:1][C:2]1[N:3]=[C:4]([C:20]2[C:21]([CH3:22])=[N:42][N:43]3[CH:48]=[CH:47][C:46]([CH:49]([O:50][CH2:51][CH3:52])[O:53][CH2:54][CH3:55])=[CH:45][C:44]=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 3

HCID 11430Potassium CarbonateHCID 580949523-(4-bromo-2-prop-1-yn-1-yl-1,3-thiazol-5-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazole2×HCID 866674771-Amino-4-(diethoxymethyl)pyridinium 2,4,6-trimethylbenzenesulfonate

Product 1

HCID 667494563-[4-Bromo-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-1,3-thiazol-2-yl]-5-(diethoxymethyl)-2-methylpyrazolo[1,5-a]pyridineYield 70.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To 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 [Prepared as described in Example 14 (4.37 g, 10.9 mmol)] and potassium carbonate (3.00 g, 21.7 mmol) in dry N,N-dimethylformamide (20.0 mL) was added a solution of 1-amino-4-(diethoxymethyl)pyridinium 2,4,6-trimethylbenzenesulfonate (6.37 g, 15.6 mmol) in dry N,N-dimethylformamide (20.0 mL) over 10 min. The resulting dark brown solution was stirred at rt for 40 hours. The mixture was added to ˜250 mL of ice water with stirring, then was extracted with EtOAc (100 mL×5) until the aqueous layer turned into a clear solution. The combined EtOAc extracts were washed with water, brine, dried over Na2SO4, filtered, and evaporated. The crude product was purified by column chromatography on silica gel, using EtOAc/hexane (0/100 to 50/50) as an eluant to give a solid product (4.56 g, 70.2%). LCMS: (FA) ES+ 593, 595. 1H NMR (400 MHz, CDCl3) δ: 8.46 (d, J=2.01 Hz, 1H), 8.40-8.42 (d, J=7.28 Hz, 1H), 8.32 (s, 2H), 7.05-7.08 (dd, J=2.01, 7.03 Hz, 1H), 5.57 (s, 2H, 3.68-3.77 (m, 4H), 3.58-3.63 (m, 2H), 2.75 (s, 3H), 1.28-1.32 (m, 6H), 0.95-1.00 (m, 2H), 0.02 (s, 9H)

Workup

  1. stirringwith stirring
  2. extractionwas extracted with EtOAc (100 mL×5) until the aqueous layer
  3. washThe combined EtOAc extracts were washed with water, brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude product was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-dda5afc7d561466cba20231e7c4a5bfc
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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