Toluene → 1-ethyl-2-{[2-(1,3-thiazol-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]methyl}-1H-imidazo[4,5-c]pyridine

HRID 1594088ノート

反応式

HRID 1594088 の反応式
[CH2:1]([NH:3][C:4]1[CH:9]=[CH:8][N:7]=[CH:6][C:5]=1[NH2:10])[CH3:2].C[Al](C)C.C1(C)C=CC=CC=1.CO[C:24](=O)[CH2:25][N:26]1[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[N:28]=[C:27]1[C:35]1[S:36][CH:37]=[CH:38][N:39]=1>C(Cl)Cl.[OH-].[Na+].CO>[CH2:1]([N:3]1[C:4]2[CH:9]=[CH:8][N:7]=[CH:6][C:5]=2[N:10]=[C:24]1[CH2:25][N:26]1[CH:30]=[C:29]([C:31]([F:32])([F:33])[F:34])[N:28]=[C:27]1[C:35]1[S:36][CH:37]=[CH:38][N:39]=1)[CH3:2]

参加物

8

反応物 4

HCID 1140TolueneHCID 120363924-N-ethylpyridine-3,4-diamineHCID 16682925TrimethylaluminumHCID 68499036(2-Thiazol-2-yl-4-trifluoromethyl-imidazol-1-yl)-acetic acid methyl ester

生成物 1

HCID 223801071-ethyl-2-{[2-(1,3-thiazol-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]methyl}-1H-imidazo[4,5-c]pyridine

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒2 回HCID 14798Sodium Hydroxide溶媒

実験手順

To a mixture of N4-ethyl-pyridine-3,4-diamine (94 mg, 0.687 mmol) in CH2Cl2 (5 mL) at room temperature under N2 is added 2.0 M AlMe3 in toluene (0.43 mL, 0.858 mmol), and the resulting mixture is stirred at room temperature for 1 h. Next, a solution of (2-thiazol-2-yl-4-trifluoromethyl-imidazol-1-yl)-acetic acid methyl ester (100 mg, 0.343 mmol) in CH2Cl2 is added via cannula. The reaction mixture is then stirred at reflux overnight. After cooling to rt, it is treated with MeOH (˜1 mL)). The mixture is further diluted with 0.5 N aq NaOH (10 mL) and then stirred vigorously for 30 min. The mixture is then extracted thrice with CH2Cl2 containing some (˜5%) MeOH, and the combined extracts are dried over K2CO3 and concentrated. The crude mixture of 1-ethyl-2-{[2-(1,3-thiazol-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]methyl}-1H-imidazo[4,5-c]pyridine and N-(4-amino-pyridin-3-yl)-2-(2-thiazol-2-yl-4-trifluoromethyl-imidazol-1-yl)-acetamide is dissolved in AcOH (6 mL), and the resulting solution stirred at reflux overnight. The reaction mixture is then concentrated, and the residue is dissolved in CH2Cl2 and washed with 0.5 N aq NaOH. The aqueous layer is reextracted once with CH2Cl2, and the combined extracts are dried over K2CO3 and concentrated. The crude residue is purified by preparative TLC. Developing with 15:1 CHCl3-MeOH affords 1-ethyl-2-{[2-(1,3-thiazol-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]methyl}-1H-imidazo[4,5-c]pyridine. 1H NMR (CDCl3, 400 MHz) δ 9.10 (s, 1H), 8.47 (d, J=6.0 Hz, 1H), 7.88 (d, J=3.2 Hz, 1H), 7.58 (s, 1H), 7.48 (d, J=3.2 Hz, 1H), 7.31 (d, J=5.6 Hz, 1H), 6.37 (s, 2H), 4.31 (q, J=7.2 Hz, 2H), 1.24 (t, J=7.2 Hz, 3H) ppm.

後処理

  1. stirringThe reaction mixture is then stirred
  2. temperatureat reflux overnight
  3. temperatureAfter cooling to rt
  4. stirringstirred vigorously for 30 min
  5. extractionThe mixture is then extracted thrice with CH2Cl2 containing some (˜5%) MeOH
  6. dry with materialthe combined extracts are dried over K2CO3
  7. concentrationconcentrated
  8. additionThe crude mixture of 1-ethyl-2-{[2-(1,3-thiazol-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]methyl}-1H-imidazo[4,5-c]pyridine and N-(4-amino-pyridin-3-yl)-2-(2-thiazol-2-yl-4-trifluoromethyl-imidazol-1-yl)-acetamide
  9. dissolutionis dissolved in AcOH (6 mL)
  10. stirringthe resulting solution stirred
  11. temperatureat reflux overnight
  12. concentrationThe reaction mixture is then concentrated
  13. dissolutionthe residue is dissolved in CH2Cl2
  14. washwashed with 0.5 N aq NaOH
  15. dry with materialthe combined extracts are dried over K2CO3
  16. concentrationconcentrated
  17. customThe crude residue is purified by preparative TLC

出典と根拠

ORDレコード
ord-54ef94a4acb24483a146fe73c72352f8
出典データセット
uspto-grants-2007_11
特許番号
US07300945B2

反応ノート

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