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 336147노트

반응식

HRID 336147 반응식
[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

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-13b66f8bef744d98b813520777918d70
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08889666B2

반응 노트

불러오는 중…