Triethylamine → Methyl {6-[(1-methoxy-2-methylindolizin-3-yl)carbonyl]-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}acetate

HRID 535443ノート

反応式

HRID 535443 の反応式
Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[NH2:13][C:14]1[CH:23]=[CH:22][C:21]([C:24]([C:26]2[N:34]3[C:29]([CH:30]=[CH:31][CH:32]=[CH:33]3)=[C:28]([O:35][CH3:36])[CH:27]=2)=[O:25])=[CH:20][C:15]=1[C:16](OC)=[O:17].[NH2:37][CH2:38][C:39]([O:41][CH3:42])=[O:40].[CH2:43](N(CC)CC)C.C1CCN2C(=NCCC2)CC1>O1CCOCC1.O>[CH3:36][O:35][C:28]1[C:27]([CH3:43])=[C:26]([C:24]([C:21]2[CH:20]=[C:15]3[C:14](=[CH:23][CH:22]=2)[NH:13][C:2](=[O:4])[N:37]([CH2:38][C:39]([O:41][CH3:42])=[O:40])[C:16]3=[O:17])=[O:25])[N:34]2[C:29]=1[CH:30]=[CH:31][CH:32]=[CH:33]2

参加物

8

反応物 5

HCID 8471TriethylamineHCID 69221Glycine methyl esterHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 94429TriphosgeneHCID 66653221Methyl 2-amino-5-[(1-methoxyindolizin-3-yl)carbonyl]benzoate

生成物 1

HCID 66653305Methyl {6-[(1-methoxy-2-methylindolizin-3-yl)carbonyl]-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}acetate収率 86%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 312751,4-Dioxane溶媒2 回

実験手順

1.22 g (4.14 mmol) of triphosgene diluted in 15 ml of dioxane are added, under an inert atmosphere at ambient temperature, to 2 g (5.91 mmol) of methyl 2-amino-5-[(1-methoxyindolizin-3-yl)carbonyl]benzoate in 65 ml of dioxane. The reaction medium is stirred for 1 hour at ambient temperature and then 1.48 g (11.82 mmol) of methyl glycinate and 4.12 ml (29.55 mmol) of triethylamine are added. The reaction medium is stirred for 18 hours and then 1.08 g (5.91 mmol) of DBU are added. After stirring for 24 hours, the medium is hydrolysed with water. The aqueous phase is extracted with dichloromethane. The organic phase obtained is washed with water, dried over sodium sulphate, filtered, and then concentrated under reduced pressure. The solid is purified by silica gel column chromatography, elution being carried out with a dichloromethane/methanol (95/5) mixture. The solid obtained is recrystallized, under hot conditions, from methanol. 1.5 g of a yellow solid are obtained.

後処理

  1. stirringThe reaction medium is stirred for 18 hours
  2. stirringAfter stirring for 24 hours
  3. extractionThe aqueous phase is extracted with dichloromethane
  4. customThe organic phase obtained
  5. washis washed with water
  6. dry with materialdried over sodium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe solid is purified by silica gel column chromatography, elution
  10. customThe solid obtained
  11. customis recrystallized, under hot conditions, from methanol

出典と根拠

ORDレコード
ord-c7fd8677fb4e4edf93f40553eb53d9c5
出典データセット
uspto-grants-2014_10
特許番号
US08859544B2

反応ノート

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