Dimethylformamide → HCID 86762323, compound

HRID 2364422Notes

Reaction equation

HRID 2364422 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.Cl[C:46]([O:48][CH3:49])=O.[CH3:50][N:51]([CH:53]=[O:54])[CH3:52]>>[F:21][C:18]1[CH:17]=[CH:16][C:15]([CH2:14][C:11]2[CH:12]=[C:13]3[C:8]([C:7]([OH:22])=[C:6]([C:23]([NH:25][CH2:26][CH2:27][CH2:28][N:29]4[CH2:30][CH2:31][O:32][CH2:33][CH2:34]4)=[O:24])[C:5](=[O:35])[N:4]3[CH2:3][CH2:2][NH:1][C:53]([N:51]3[CH2:52][CH2:49][O:48][CH2:46][CH2:50]3)=[O:54])=[N:9][CH:10]=2)=[CH:20][CH:19]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 69482012HCID 69482012, compound

Product 1

HCID 86762323HCID 86762323, 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, 0.052 mmol) and diisopropyl ethylamine (0.05 mL, 0.29 mmol) in DMF (5 mL) under nitrogen was treated with methyl chloroformate (0.008 mL, 0.07 mmol) at 40° C. for 1 h then 3½ h at ambient temperature. The reaction was concentrated in vacuo and the resulting residue was triturated with Et2O:MeOH, and concentrated again in vacuo, before triturating again with EtOAc. Filtered the resulting suspension and dried in vacuo to provide the title compound as an orange solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 1.23-1.29 (m, 2 H), 1.99-2.05 (m, 1 H), 3.04-3.08 (m, 2 H), 3.10-3.19 (m, 7 H), 3.42 (s, 2 H), 3.44-3.49 (m, 6 H), 3.70 (t, J=11.81 Hz, 2 H), 3.96 (d, J=13.19 Hz, 2 H), 4.14 (s, 2 H), 4.29 (t, J=6.59 Hz, 2 H), 6.81 (t, J=4.67 Hz, 1 H), 7.14 (t, J=8.79 Hz, 2 H), 7.42 (dd, J=8.70, 5.59 Hz, 2 H), 8.32 (s, 1 H), 8.55 (d, J=1.28 Hz, 1 H), 10.15 (s, 1 H), 10.37 (t, J=6.50 Hz, 1 H); ES+ MS: 597 (M+H+).

Workup

  1. custom3½ h
  2. customat ambient temperature
  3. concentrationThe reaction was concentrated in vacuo
  4. customthe resulting residue was triturated with Et2O
  5. concentrationMeOH, and concentrated again in vacuo
  6. custombefore triturating again with EtOAc
  7. filtrationFiltered the resulting suspension
  8. customdried in vacuo

Sources & evidence

ORD record
ord-315cee2f37ee4aaa9b28df80cacfb38a
Source dataset
uspto-grants-2014_04
Patent number
US08691991B2

Reaction notes

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