Triethylamine → 2-ethyl-7-[2-(methylsulfonyl)ethenyl]-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-4-amine

HRID 244872

反応式

HRID 244872 の反応式
[CH:1]([S:3]([CH3:6])(=[O:5])=[O:4])=[CH2:2].C(N(CC)CC)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.Br[C:37]1[CH:38]=[CH:39][C:40]2[C:41]3[N:50]([CH2:51][CH:52]4[CH2:57][CH2:56][O:55][CH2:54][CH2:53]4)[C:49]([CH2:58][CH3:59])=[N:48][C:42]=3[C:43]([NH2:47])=[N:44][C:45]=2[CH:46]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C)C=O.C(#N)C>[CH2:58]([C:49]1[N:50]([CH2:51][CH:52]2[CH2:57][CH2:56][O:55][CH2:54][CH2:53]2)[C:41]2[C:40]3[CH:39]=[CH:38][C:37]([CH:2]=[CH:1][S:3]([CH3:6])(=[O:5])=[O:4])=[CH:46][C:45]=3[N:44]=[C:43]([NH2:47])[C:42]=2[N:48]=1)[CH3:59]

参加物

8

反応物 4

HCID 8471TriethylamineHCID 19354Methyl vinyl sulfoneHCID 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 866293922-ethyl-7-[2-(methylsulfonyl)ethenyl]-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-4-amine収率 59.4%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 6228Dimethylformamide溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
120 °C

実験手順

A thick walled glass tube, equipped with a stir bar, was charged with palladium (II) acetate (7 mg, 0.03 mmol), acetonitrile (15 mL), N,N-dimethylformamide (15 mL), methyl vinyl sulfone (150 mg, 1.41 mmol), triethylamine (0.53 mL, 3.8 mmol), tri-o-tolylphosphine (23 mg, 0.08 mmol) and 7-bromo-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-4-amine (500 g, 1.28 mmol). The reaction mixture was purged with nitrogen and the tube was sealed and heated at 120° C. in an oil bath for 16 hours. The reaction mixture was cooled to ambient temperature and then concentrated under reduced pressure. The resulting solid was partitioned between chloroform (100 mL) and 1% aqueous sodium carbonate (100 mL). The fractions were separated and the aqueous fraction was extracted with chloroform (2×50 mL). The combined organic fractions were sequentially dried (MgSO4), filtered, and purified by chromatography using a HORIZON HPFC system (silica cartridge, eluting with a CMA:chloroform gradient, 0-15% CMA over 1200 mL followed by 15-20% CMA over 1100 mL). Recrystallization from methanol provided 315 mg of 2-ethyl-7-[2-(methylsulfonyl)ethenyl]-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-4-amine as a pale yellow solid.

後処理

  1. customA thick walled glass tube, equipped with a stir bar
  2. customThe reaction mixture was purged with nitrogen
  3. customthe tube was sealed
  4. temperatureThe reaction mixture was cooled to ambient temperature
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting solid was partitioned between chloroform (100 mL) and 1% aqueous sodium carbonate (100 mL)
  7. customThe fractions were separated
  8. extractionthe aqueous fraction was extracted with chloroform (2×50 mL)
  9. dry with materialThe combined organic fractions were sequentially dried (MgSO4)
  10. filtrationfiltered
  11. custompurified by chromatography
  12. washeluting with a CMA
  13. customRecrystallization from methanol

出典と根拠

ORDレコード
ord-c3bb327c0c654ae4ac5c7f667b19d43b
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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