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 1530116ノート

反応式

HRID 1530116 の反応式
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

参加物

7

反応物 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

生成物 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-amine収率 75.2%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 21226206Ethyl acetate hexane溶媒

反応条件

温度
112 °C

実験手順

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 (8, 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).

後処理

  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

出典と根拠

ORDレコード
ord-840cb554dab14bbab2338e460c380b11
出典データセット
uspto-grants-2015_07
特許番号
US09090601B2

反応ノート

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