3,4-Diaminopyridine → 9-oxo-9H-pyrrolo[1,2-a]indole-5-carboxylic acid (4-aminopyridin-3-yl)amide

HRID 1925571

反応式

HRID 1925571 の反応式
[O:1]=[C:2]1[C:10]2[C:5](=[C:6]([C:11]([OH:13])=O)[CH:7]=[CH:8][CH:9]=2)[N:4]2[CH:14]=[CH:15][CH:16]=[C:3]12.[NH2:17][C:18]1[CH:19]=[N:20][CH:21]=[CH:22][C:23]=1[NH2:24].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C)C=O>[NH2:24][C:23]1[CH:22]=[CH:21][N:20]=[CH:19][C:18]=1[NH:17][C:11]([C:6]1[CH:7]=[CH:8][CH:9]=[C:10]2[C:5]=1[N:4]1[CH:14]=[CH:15][CH:16]=[C:3]1[C:2]2=[O:1])=[O:13]

参加物

6

反応物 4

HCID 59183,4-DiaminopyridineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 672992929-oxo-9H-pyrrolo[1,2-a]indole-5-carboxylic acid

生成物 1

HCID 672993589-oxo-9H-pyrrolo[1,2-a]indole-5-carboxylic acid (4-aminopyridin-3-yl)amide収率 21.2%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

In a 500 ml round-bottomed flask, a mixture of 730 mg of 9-oxo-9H-pyrrolo[1,2-a]indole-5-carboxylic acid obtained according to stage 2 of Example 1, 373 mg of 3,4-diaminopyridine, 721 mg of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDCI) and 508 mg of 1-hydroxybenzotriazole (HOBt) in 60 ml of dimethylformamide is stirred for 19 hours at ambient temperature. The reaction medium is evaporated to dryness under vacuum and the solid residue is taken up in 50 ml of water. The precipitate is filtered off and the solid is washed successively with 3 times 80 ml of water, 3 times 80 ml of a saturated solution of sodium bicarbonate and again with 3 times 80 ml of water. The solid is dissolved in methanol and the solvent is evaporated to dryness under vacuum. The residue is chromatographed on silica gel (15-40 μm), elution being carried out with a gradient of methanol (5% to 10% v/v) in dichloromethane and then a mixture of dichloromethane and 5N ammoniacal methanol (90/10 v/v). 220 mg of 9-oxo-9H-pyrrolo[1,2-a]indole-5-carboxylic acid (4-aminopyridin-3-yl)amide are obtained in the form of a solid, the characteristics of which are the following:

後処理

  1. customobtained
  2. customThe reaction medium is evaporated to dryness under vacuum
  3. filtrationThe precipitate is filtered off
  4. washthe solid is washed successively with 3 times 80 ml of water, 3 times 80 ml of a saturated solution of sodium bicarbonate and again with 3 times 80 ml of water
  5. dissolutionThe solid is dissolved in methanol
  6. customthe solvent is evaporated to dryness under vacuum
  7. customThe residue is chromatographed on silica gel (15-40 μm), elution
  8. additiona mixture of dichloromethane and 5N ammoniacal methanol (90/10 v/v)

出典と根拠

ORDレコード
ord-15d1926cc0844500a7eba983a8a2cf9f
出典データセット
uspto-grants-2012_05
特許番号
US08178687B2

関連ノート

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