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 2401797노트

반응식

HRID 2401797 반응식
[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

참가 물질

5

반응물 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-triazole2회HCID 866674771-Amino-4-(diethoxymethyl)pyridinium 2,4,6-trimethylbenzenesulfonate

생성물 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]pyridine수율 70.5%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

실험 절차

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, 2113.68-3.77 (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)

후처리

  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

출처 및 근거

ORD 기록
ord-cb6546636c9a46209fe835211133136f
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08796268B2

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