Sodium Bicarbonate → (S,E)-N-(4-amino-5-(quinolin-3-yl)-6,7,8,9-tetrahydropyrimido[5,4-b]indolizin-8-yl)-3-chloroacrylamide

HRID 336147ノート

反応式

HRID 336147 の反応式
[Cl:1]/[CH:2]=[CH:3]/[C:4]([OH:6])=O.[N:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[C:9]([C:17]2[C:18]3[C:30]([NH2:31])=[N:29][CH:28]=[N:27][C:19]=3[N:20]3[C:25]=2[CH2:24][CH2:23][CH:22]([NH2:26])[CH2:21]3)[CH:8]=1.Cl.CN(C)CCCN=C=NCC.C(=O)(O)[O-].[Na+]>CN(C=O)C>[NH2:31][C:30]1[C:18]2[C:17]([C:9]3[CH:8]=[N:7][C:16]4[C:11]([CH:10]=3)=[CH:12][CH:13]=[CH:14][CH:15]=4)=[C:25]3[N:20]([C:19]=2[N:27]=[CH:28][N:29]=1)[CH2:21][C@@H:22]([NH:26][C:4](=[O:6])/[CH:3]=[CH:2]/[Cl:1])[CH2:23][CH2:24]3

参加物

6

反応物 4

HCID 516892Sodium BicarbonateHCID 638124trans-3-Chloroacrylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 867112835-(Quinolin-3-yl)-6,7,8,9-tetrahydropyrimido[5,4-b]indolizine-4,8-diamine

生成物 1

HCID 71721578(S,E)-N-(4-amino-5-(quinolin-3-yl)-6,7,8,9-tetrahydropyrimido[5,4-b]indolizin-8-yl)-3-chloroacrylamide収率 41.4%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

Trans-3-chloroacrylic acid (399.5 mg) was added to a suspension of 5-(quinolin-3-yl)-6,7,8,9-tetrahydropyrimido[5,4-b]indolizine-4,8-diamine (498.0 mg) obtained in Step 11 of Example 1 in DMF (8 ml) at room temperature. After dissolving, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (350.1 mg) was added thereto under ice-cooling, and the mixture was stirred for 1 hour at the same temperature. The reaction mixture was poured into a saturated aqueous sodium bicarbonate solution, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and the solvent was then distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography (developing solvent: ethyl acetate/methanol) to obtain the title compound as a light-yellow solid (261.2 mg).

後処理

  1. dissolutionAfter dissolving
  2. temperatureunder ice-cooling
  3. extractionfollowed by extraction with ethyl acetate
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. distillationthe solvent was then distilled off under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography (developing solvent: ethyl acetate/methanol)

出典と根拠

ORDレコード
ord-13b66f8bef744d98b813520777918d70
出典データセット
uspto-grants-2014_11
特許番号
US08889666B2

反応ノート

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