Dimethylformamide → HCID 69482278, compound

HRID 2364423Notes

Reaction equation

HRID 2364423 reaction equation
[NH2:1][CH2:2][CH2:3][N:4]1[C:13]2[C:8](=[N:9][CH:10]=[C:11]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)[CH:12]=2)[C:7]([OH:22])=[C:6]([C:23]([NH:25][CH2:26][CH2:27][CH2:28][N:29]2[CH2:34][CH2:33][O:32][CH2:31][CH2:30]2)=[O:24])[C:5]1=[O:35].C(N(C(C)C)CC)(C)C.[CH3:45][N:46]([CH:48]=[O:49])[CH3:47]>>[CH3:45][N:46]([CH3:47])[C:48]([NH:1][CH2:2][CH2:3][N:4]1[C:13]2[C:8](=[N:9][CH:10]=[C:11]([CH2:14][C:15]3[CH:16]=[CH:17][C:18]([F:21])=[CH:19][CH:20]=3)[CH:12]=2)[C:7]([OH:22])=[C:6]([C:23]([NH:25][CH2:26][CH2:27][CH2:28][N:29]2[CH2:30][CH2:31][O:32][CH2:33][CH2:34]2)=[O:24])[C:5]1=[O:35])=[O:49]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 69482012HCID 69482012, compound

Product 1

HCID 69482278HCID 69482278, compound

Procedure

A solution of 1-(2-aminoethyl)-7-[(4-fluorophenyl)methyl]-4-hydroxy-N-[3-(4-morpholinyl)propyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide (0.025 g, 0.057 mmol) and diisopropyl ethylamine (0.05 mL, 0.29 mmol) in DMF (3 mL) under nitrogen was treated with N,N-dimethyl carbonyl chloride (0.0055 mL, 0.06 mmol)@40° C. After 2½ h the reaction was cooled, concentrated in vacuo, and the resulting residue treated with 1N NaHSO4. Extracted the mixture 3× with EtOAc and concentrated the organics. The residue was then dissolved in EtOAc and washed with saturated NaHCO3 (aqueous) then concentrated the organics. Triturated the residue with Et2O, filtered, and dried in vacuo to provide the title compound as an orange solid: 1H NMR (300 MHz, DMSO-d6) δ ppm 1.66-1.79 (m, 2 H), 1.76-1.93 (m, 1 H), 2.35 (t, J=6.18 Hz, 6 H), 2.70 (s, 6 H), 3.19-3.31 (m, 2 H), 3.40-3.48 (m, 2 H), 3.53-3.63 (m, 4 H), 4.11 (s, 2 H), 4.25 (s, 2 H), 6.54-6.59 (m, 1 H), 7.14 (t, J=8.84 Hz, 2 H), 7.37-7.44 (m, 2 H), 8.17-8.39 (m, 1 H), 8.52 (s, 1 H), 10.38 (s, 1 H); ES+ MS: 555 (M+H+).

Workup

  1. temperatureAfter 2½ h the reaction was cooled
  2. concentrationconcentrated in vacuo
  3. additionthe resulting residue treated with 1N NaHSO4
  4. extractionExtracted the mixture 3× with EtOAc
  5. concentrationconcentrated the organics
  6. dissolutionThe residue was then dissolved in EtOAc
  7. washwashed with saturated NaHCO3 (aqueous)
  8. concentrationthen concentrated the organics
  9. customTriturated the residue with Et2O
  10. filtrationfiltered
  11. customdried in vacuo

Sources & evidence

ORD record
ord-13e22a1c8ae441f1b83e2d3649c7b821
Source dataset
uspto-grants-2014_04
Patent number
US08691991B2

Reaction notes

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