Ethanol → HCID 10283119, compound

HRID 412303Notes

Reaction equation

HRID 412303 reaction equation
C(C1CC([CH:11]=[O:12])CCN1C(O)=O)(C)(C)C.[NH2:16][C:17]1[C:22]([CH:23]=O)=[C:21]([CH:25]2[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26]2)[CH:20]=[C:19]([C:38]2[C:43]([O:44][CH2:45][C:46]3[CH:51]=[CH:50][C:49]([O:52][CH3:53])=[CH:48][CH:47]=3)=[CH:42][CH:41]=[CH:40][C:39]=2[O:54][CH2:55][CH:56]2[CH2:58][CH2:57]2)[N:18]=1.[NH:59]1CCCCC1.[CH2:65]([OH:67])[CH3:66]>>[NH2:59][C:65]([C:66]1[C:11](=[O:12])[NH:16][C:17]2[N:18]=[C:19]([C:38]3[C:43]([O:44][CH2:45][C:46]4[CH:51]=[CH:50][C:49]([O:52][CH3:53])=[CH:48][CH:47]=4)=[CH:42][CH:41]=[CH:40][C:39]=3[O:54][CH2:55][CH:56]3[CH2:57][CH2:58]3)[CH:20]=[C:21]([CH:25]3[CH2:26][CH2:27][N:28]([C:31]([O:33][C:34]([CH3:35])([CH3:37])[CH3:36])=[O:32])[CH2:29][CH2:30]3)[C:22]=2[CH:23]=1)=[O:67]

Participants

5

Reactant 4

HCID 702EthanolHCID 8082PiperidineHCID 11421930HCID 11421930, compound2×HCID 22258792HCID 22258792, compound

Product 1

HCID 10283119HCID 10283119, compound

Procedure

With the use of the starting compound 1G and tert-butyl 4-formyl piperidine-1-carboxylic acid, tert-butyl 4-(2-amino-6-{2-(cyclopropylmethoxy)-6-[(4-methoxybenzyl)oxy]phenyl)-3-formyl-4-pyridinyl)-1-piperidinecarboxylate was prepared in a similar manner as that of the step (1) of Example 25-2. To a solution of tert-butyl 4-(2-amino-6-{2-(cyclopropylmethoxy)-6-[(4-methoxybenzyl)oxy]phenyl}-3-formyl-4-pyridinyl)-1-piperidinecarboxylate (0.400 g, 0.681 mmol) in ethyl alcohol (5.0 mL) was added ethyl malonate monoamine (1.780 g, 13.612 mmol) and piperidine (0.580 g, 6.806 mmol). The mixture was refluxed 12 hrs. The reaction mixture was extracted with ethyl acetate and water. The separated organic phase was washed with NaHCO3 and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting residue (liquid) was purified by column chromatography on silica gel (hexane/ethyl acetate=1/1 and ethylacetate 100%) to give tert-butyl 4-(6-(aminocarbonyl)-2-{2-(cyclopropylmethoxy)-6-[(4-methoxybenzyl)oxy]phenyl}-7-oxo-7,8-dihydro-1,8-naphthyridin-4-yl)-1-piperidinecarboxylate as a yellow form. (0.455 g, yield; quant.)

Workup

  1. temperatureThe mixture was refluxed 12 hrs
  2. extractionThe reaction mixture was extracted with ethyl acetate and water
  3. washThe separated organic phase was washed with NaHCO3 and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue (liquid) was purified by column chromatography on silica gel (hexane/ethyl acetate=1/1 and ethylacetate 100%)

Sources & evidence

ORD record
ord-799889e232d34ac8b9c268a6836f2003
Source dataset
uspto-grants-2003_05
Patent number
US06562811B1

Reaction notes

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