Toluene → N-(4-chlorophenyl)-N-methyl-2-(2-methylpyrazolo[1,5-a]pyridin-3-yl)-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-1,3-thiazol-4-amine

HRID 2282280노트

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HRID 2282280 반응식
Br[C:2]1[N:3]=[C:4]([C:20]2[C:21]([CH3:29])=[N:22][N:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=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.[Cl:30][C:31]1[CH:38]=[CH:37][C:34]([NH:35][CH3:36])=[CH:33][CH:32]=1.CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CCOC(C)=O.CCCCCC>[Cl:30][C:31]1[CH:38]=[CH:37][C:34]([N:35]([CH3:36])[C:2]2[N:3]=[C:4]([C:20]3[C:21]([CH3:29])=[N:22][N:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=34)[S:5][C:6]=2[C:7]2[N:11]=[CH:10][N:9]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:17])([CH3:18])[CH3:19])[N:8]=2)=[CH:33][CH:32]=1

참가 물질

7

반응물 4

HCID 1140TolueneHCID 702724-Chloro-N-methylbenzenamineHCID 23676156Sodium t-butoxideHCID 580948524-bromo-2-(2-methylpyrazolo[1,5-a]pyridin-3-yl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)thiazole

생성물 1

HCID 58094762N-(4-chlorophenyl)-N-methyl-2-(2-methylpyrazolo[1,5-a]pyridin-3-yl)-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-1,3-thiazol-4-amine수율 75.2%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 21226206Ethyl acetate hexane용매

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온도
112 °C

실험 절차

The mixture of 3-[4-bromo-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-1,3-thiazol-2-yl]-2-methylpyrazolo[1,5-a]pyridine (0.0700 g, 0.142 mmol), p-Chloro-N-methylaniline (33.5 mg, 0.236 mmol), Tris(dibenzylideneacetone)dipalladium(0) (4.4 mg, 0.0048 mmol.), racemic 1,1′-binaphthalene-2,2′-diylbis(diphenylphosphine) (8.8 mg, 0.014 mmol) and Sodium tert-butoxide (22.7 mg, 0.236 mmol) in dry Toluene (2.0 mL, 19 mmol) was degassed by vacuum and backfilling with N2 for 5 times, sonicated under N2 for 1 min to dissolve all material, degassed for 5 more times. The resulted brown solution was heated under N2 in a capped vial to 112° C. for 18 hours. The mixture was partitioned in EtOAc (80 mL) and water (30 mL). The EtOAc layer was washed with water, brine, dried over Na2SO4, filtered, rotavaped to give a crude product. Chromatograph in a 24 g ISCO column using EtOAc/hexane (0/100 to 40/60) afforded a solid product (0.059 g, 75% yield). LCMS: (FA) ES+ 552, 554. 1H NMR (400 MHz, d1-chloroform) δ 8.43 (d, J=6.53 Hz, 1H), 8.32 (d, J=9.04 Hz, 1H), 8.13 (s, 1H), 7.29-7.33 (m, 1H), 7.10-7.12 (d, J=9.04 Hz, 2H), 6.84-6.88 (m, 1H), 6.82-6.84 (d, J=9.04 Hz, 2H), 5.39 (s, 2H), 3.55 (t, J=7.78 Hz, 2H), 3.51 (s, 3H), 2.78 (s, 3H), 0.90 (t, J=7.78 Hz, 2H), 0.00 (s, 9H).

후처리

  1. customwas degassed by vacuum and backfilling with N2 for 5 times
  2. customsonicated under N2 for 1 min
  3. dissolutionto dissolve all material
  4. customdegassed for 5 more times
  5. customThe mixture was partitioned in EtOAc (80 mL)
  6. washThe EtOAc layer was washed with water, brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customto give a crude product

출처 및 근거

ORD 기록
ord-fa9c533ab85843fc8628d2274caa0711
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09139589B2

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