Toluene → n-(4-Amino-6-isopropyl-pyridin-3-yl)-2-(2-thiazol-2-yl-imidazol-1-yl)-acetamide

HRID 1594081ノート

反応式

HRID 1594081 の反応式
Cl.[CH:2]([C:5]1[N:10]=[CH:9][C:8]([NH2:11])=[C:7]([NH2:12])[CH:6]=1)([CH3:4])[CH3:3].C[Al](C)C.C1(C)C=CC=CC=1.C[O:25][C:26](=O)[CH2:27][N:28]1[CH:32]=[CH:31][N:30]=[C:29]1[C:33]1[S:34][CH:35]=[CH:36][N:37]=1>ClCCCl>[NH2:12][C:7]1[CH:6]=[C:5]([CH:2]([CH3:4])[CH3:3])[N:10]=[CH:9][C:8]=1[NH:11][C:26](=[O:25])[CH2:27][N:28]1[CH:32]=[CH:31][N:30]=[C:29]1[C:33]1[S:34][CH:35]=[CH:36][N:37]=1

参加物

6

反応物 4

HCID 1140TolueneHCID 16682925TrimethylaluminumHCID 223803456-Isopropylpyridine-3,4-diaminehydrochlorideHCID 68495873(2-Thiazol-2-yl-imidazol-1-yl)-acetic acid methyl ester

生成物 1

HCID 22380082n-(4-Amino-6-isopropyl-pyridin-3-yl)-2-(2-thiazol-2-yl-imidazol-1-yl)-acetamide

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒2 回

実験手順

To a mixture of 6-isopropyl-pyridine-3,4-diamine hydrochloride (265 mg, 1.41 mmol) in 1,2-dichloroethane (10 mL) at room temperature under N2 is added 2.0 M AlMe3 in toluene (2.12 mL, 4.24 mmol). The mixture is stirred at room temperature for 45 min and then treated with a solution of (2-thiazol-2-yl-imidazol-1-yl)-acetic acid methyl ester (252 mg, 1.13 mmol) in 1,2-dichloroethane (2 mL) via cannula, followed by a 1 mL rinse. The reaction mixture is then stirred at reflux for 20 h. After cooling, the reaction mixture is diluted with some MeOH (˜2 mL), followed by some water and then saturated aq NaHCO3. The resulting mixture is stirred vigorously for 15 min. The mixture is then extracted thrice with CHCl3 containing some (˜5%) MeOH. The combined extracts are dried over Na2SO4 and concentrated. The crude residue is then triturated with CHCl3, and the resulting mixture filtered. The solid is washed with a small amount of CHCl3 and dried, affording N-(4-amino-6-isopropyl-pyridin-3-yl)-2-(2-thiazol-2-yl-imidazol-1-yl)-acetamide as an off-white solid. 1H NMR (DMSO-ds, 300 MHz) δ 9.52 (s, 1H), 7.86 (s, 1H), 7.85 (d, J=3.3 Hz, 1H), 7.75 (d, J=3.6 Hz, 1H), 7.39 (s, 1H), 7.04 (d, J=0.9 Hz, 1H), 6.45 (s, 1H), 5.65 (s, 2H), 5.38 (s, 2H), 2.74 (sept, J=6.9 Hz, 1H), 1.13 (d, J=6.9 Hz, 6H) ppm. The filtrate is concentrated and further purified by flash chromatography on silica gel. Elution with 20:1 CHCl3-MeOH followed by 15:1 CHCl3-MeOH affords 6-isopropyl-2-(2-thiazol-2-yl-imidazol-1-ylmethyl)-1H-imidazo[4,5-c]pyridine (160 mg, 44%). 1H NMR (CDCl3, 300 MHz) δ 12.23 (br, 1H), 8.97 (br, 1H), 7.94 (d, J=2.7 Hz, 1H), 7.43 (d, J=3.3 Hz, 1H), 7.23 (br, 1H), 7.20 (d, J=0.9 Hz, 1H), 7.04 (s, 1H), 5.82 (s, 2H), 3.14 (sept, J=6.9 Hz, 1H), 1.30 (d, J=6.9 Hz, 6H) ppm.

後処理

  1. washrinse
  2. stirringThe reaction mixture is then stirred
  3. temperatureat reflux for 20 h
  4. temperatureAfter cooling
  5. additionthe reaction mixture is diluted with some MeOH (˜2 mL)
  6. stirringThe resulting mixture is stirred vigorously for 15 min
  7. extractionThe mixture is then extracted thrice with CHCl3 containing some (˜5%) MeOH
  8. dry with materialThe combined extracts are dried over Na2SO4
  9. concentrationconcentrated
  10. customThe crude residue is then triturated with CHCl3
  11. filtrationthe resulting mixture filtered
  12. washThe solid is washed with a small amount of CHCl3
  13. customdried

出典と根拠

ORDレコード
ord-9e44104a0e664cf981864b43d2edf058
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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