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 336147Notes

Reaction equation

HRID 336147 reaction equation
[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

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-13b66f8bef744d98b813520777918d70
Source dataset
uspto-grants-2014_11
Patent number
US08889666B2

Reaction notes

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