Dimethylformamide → HCID 69480157, compound

HRID 2364425Notes

Reaction equation

HRID 2364425 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][O:28][CH2:29][CH2:30][OH:31])=[O:24])[C:5]1=[O:32].C(N([CH:39]([CH3:41])C)CC)(C)C.CN(C=[O:46])C>>[C:39]([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][O:28][CH2:29][CH2:30][OH:31])=[O:24])[C:5]1=[O:32])(=[O:46])[CH3:41]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 69482715HCID 69482715, compound

Product 1

HCID 69480157HCID 69480157, compound

Procedure

A solution of 1-(2-aminoethyl)-7-[(4-fluorophenyl)methyl]-4-hydroxy-N-{2-[(2-hydroxyethyl)oxy]ethyl}-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 (0.06 mL, 0.63 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 purified on silica gel by prep TLC (9:1 CH2Cl2:MeOH). Pure bands were collected to provide the title compound as an off-white solid: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.98 (s, 3 H), 3.46-3.54 (m, 2 H), 3.68 (d, J=4.76 Hz, 2 H), 3.71 (s, 4 H), 3.77-3.88 (m, 2 H), 4.17 (s, 2 H), 4.36 (t, J=7.23 Hz, 2 H), 5.31 (s, 1 H), 6.14 (s, 1 H), 7.02 (t, J=8.79 Hz, 2 H), 7.22-7.25 (m, 2 H), 8.07 (s, 1 H), 8.58 (s, 1 H), 10.51 (s, 1 H); ES+ MS: 487 (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. customThe residue was then purified on silica gel by prep TLC (9:1 CH2Cl2:MeOH)
  7. customPure bands were collected

Sources & evidence

ORD record
ord-67a45632405e4a14b397cf0aa5455c39
Source dataset
uspto-grants-2014_04
Patent number
US08691991B2

Reaction notes

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