Triethylamine → HCID 68713643, compound

HRID 506409Notes

Reaction equation

HRID 506409 reaction equation
[C:1]1([C@@H:7]([OH:9])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:10](N1C=CN=C1)(N1C=CN=C1)=[O:11].[CH2:22]([O:24][C:25]([N:27]1[C:36]2[C:31](=[N:32][C:33]([O:37][CH3:38])=[CH:34][CH:35]=2)[C@@H:30]([NH2:39])[CH2:29][C@H:28]1[CH2:40][CH3:41])=[O:26])[CH3:23].C(N(CC)CC)C>O1CCCC1>[CH2:22]([O:24][C:25]([N:27]1[C:36]2[C:31](=[N:32][C:33]([O:37][CH3:38])=[CH:34][CH:35]=2)[C@@H:30]([NH:39][C:10]([O:9][C@H:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH3:8])=[O:11])[CH2:29][C@H:28]1[CH2:40][CH3:41])=[O:26])[CH3:23]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 4431351-Phenylethanol, (S)-HCID 68715298HCID 68715298, compound

Product 1

HCID 68713643HCID 68713643, compoundYield 11.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

(S)-1-Phenylethyl alcohol (1.0 g) and 1,1′-carbonyldiimidazole (1.33 g) are dissolved in tetrahydrofuran (20 ml), and the mixture is stirred at 80° C. for 2 hours. To the reaction solution are added (2R*,4S*)-4-amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (1.91 g) and triethylamine (1.14 ml), and the mixture is heated to reflux for 3 days. The reaction solution is partitioned by adding ethyl acetate and a saturated aqueous sodium bicarbonate solution, and then the organic layer is washed with saturated brine and dried over magnesium sulfate, then concentrated under reduced pressure. The residue is purified by column chromatography (silica gel; hexane:ethyl acetate=90:10→70:30). The resulting mixture of diastereomers is recrystallized from hexane to give (2R,4S)-2-ethyl-6-methoxy-4-((S)-1-phenylethoxycarbonylamino)-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (345 mg). The physical property data are the same as the compound obtained in Example 2 (3).

Workup

  1. temperaturethe mixture is heated
  2. temperatureto reflux for 3 days
  3. customThe reaction solution is partitioned
  4. additionby adding ethyl acetate
  5. washa saturated aqueous sodium bicarbonate solution, and then the organic layer is washed with saturated brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue is purified by column chromatography (silica gel; hexane:ethyl acetate=90:10→70:30)
  9. additionThe resulting mixture of diastereomers
  10. customis recrystallized from hexane

Sources & evidence

ORD record
ord-a11d7e3be6b4466ea97aeba94f84d199
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

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