Ethyl Acrylate → ethyl (2E)-3-[4-amino-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-7-yl]prop-2-enoate

HRID 244884

反応式

HRID 244884 の反応式
Br[C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:15]([CH2:16][CH:17]4[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)[C:14]([CH2:23][CH3:24])=[N:13][C:7]=3[C:8]([NH2:12])=[N:9][C:10]=2[CH:11]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[C:47]([O:51][CH2:52][CH3:53])(=[O:50])[CH:48]=[CH2:49]>CN(C)C=O.C(N(CC)CC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:12][C:8]1[C:7]2[N:13]=[C:14]([CH2:23][CH3:24])[N:15]([CH2:16][CH:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)[C:6]=2[C:5]2[CH:4]=[CH:3][C:2](/[CH:49]=[CH:48]/[C:47]([O:51][CH2:52][CH3:53])=[O:50])=[CH:11][C:10]=2[N:9]=1

参加物

7

反応物 3

HCID 8821Ethyl AcrylateHCID 80271Tri-o-tolylphosphineHCID 690807877-bromo-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-4-amine

生成物 1

HCID 57657271ethyl (2E)-3-[4-amino-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-7-yl]prop-2-enoate収率 72.4%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 6228Dimethylformamide溶媒3 回HCID 8471Triethylamine溶媒

反応条件

温度
120 °C

実験手順

A thick walled glass vessel, equipped with a stir bar, was charged with a warmed solution of 7-bromo-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-4-amine (2.5 g, 6.42 mmol) in N,N-dimethylformamide (50 mL). To the solution was added in succession, a solution of palladium acetate (144 mg, 0.642 mmol) and tri-ortho-tolylphosphine (390 mg, 1.28 mmol) in N,N-dimethylformamide (5 mL), triethylamine (2.7 mL) and a solution of ethyl acrylate (0.77 g, 7.7 mmol) in N,N-dimethylformamide (2 mL). The reaction mixture was purged with nitrogen. The vessel was sealed and heated at 120° C. for 18 hours. The reaction was cooled to ambient temperature and then concentrated to dryness under reduced pressure. The resulting solid was dissolved in dichloromethane (150 mL) and washed with saturated aqueous potassium carbonate (100 mL). The fractions were separated and the organic fraction was concentrated to dryness under reduced pressure. The resulting off-white solid was purified by chromatography using a HORIZON HPFC system (silica cartridge, 0-15% CMA/chloroform). A final recrystallization from acetonitrile provided 1.9 g of ethyl (2E)-3-[4-amino-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-7-yl]prop-2-enoate as an off-white crystalline solid, mp 209-210° C.

後処理

  1. customA thick walled glass vessel, equipped with a stir bar
  2. additionTo the solution was added in succession
  3. customThe reaction mixture was purged with nitrogen
  4. customThe vessel was sealed
  5. temperatureThe reaction was cooled to ambient temperature
  6. concentrationconcentrated to dryness under reduced pressure
  7. dissolutionThe resulting solid was dissolved in dichloromethane (150 mL)
  8. washwashed with saturated aqueous potassium carbonate (100 mL)
  9. customThe fractions were separated
  10. concentrationthe organic fraction was concentrated to dryness under reduced pressure
  11. customThe resulting off-white solid was purified by chromatography
  12. customA final recrystallization from acetonitrile

出典と根拠

ORDレコード
ord-c46d12fddfa547939f6da4c9638b1689
出典データセット
uspto-grants-2014_02
特許番号
US08658666B2

関連ノート

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