Ammonium Hydroxide → 1-(2-Amino-2-oxoethyl)-7-[(4-fluorophenyl)methyl]-4-hydroxy-N-[2-(methyloxy)ethyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide

HRID 2364237Notes

Reaction equation

HRID 2364237 reaction equation
C[N:2](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32][C:33]2[CH:42]=[C:41]3[C:36]([C:37]([OH:55])=[C:38]([C:48]([NH:50][CH2:51][CH2:52][O:53][CH3:54])=[O:49])[C:39](=[O:47])[N:40]3[CH2:43][C:44]([OH:46])=O)=[N:35][CH:34]=2)=[CH:28][CH:27]=1.[OH-].[NH4+]>CN(C=O)C.O>[NH2:2][C:44](=[O:46])[CH2:43][N:40]1[C:41]2[C:36](=[N:35][CH:34]=[C:33]([CH2:32][C:29]3[CH:28]=[CH:27][C:26]([F:25])=[CH:31][CH:30]=3)[CH:42]=2)[C:37]([OH:55])=[C:38]([C:48]([NH:50][CH2:51][CH2:52][O:53][CH3:54])=[O:49])[C:39]1=[O:47]

Participants

6

Reactant 3

HCID 14923Ammonium Hydroxide2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 59776534[7-[(4-fluorophenyl)methyl]-4-hydroxy-3-({[2-(methyloxy)ethyl]amino}carbonyl)-2-oxo-1,5-naphthyridin-1(2H)-yl]acetic acid

Product 1

HCID 694821081-(2-Amino-2-oxoethyl)-7-[(4-fluorophenyl)methyl]-4-hydroxy-N-[2-(methyloxy)ethyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Procedure

A solution of HATU (1.14 g, 3 mmol) in DMF (4 mL) was added in portions to a stirred suspension of [7-[(4-fluorophenyl)methyl]-4-hydroxy-3-({[2-(methyloxy)ethyl]amino}carbonyl)-2-oxo-1,5-naphthyridine-1(2H)-yl]acetic acid (1 g, 2.3 mmol) in 29% ammonium hydroxide (0.4 mL, 2.9 mmol), TEA (0.4 mL, 2.9 mmol) and DMF (4 mL) at 60° C. The mixture was stirred 40 min at rt and additional HATU (350 mg, 0.92 mmol), 29% ammonium hydroxide (0.15 mL, 1 mmol) and DMF (3 mL) were added. Stirring was continued 20 min and the suspension was diluted with water and filtered. The filter cake was washed with water and EtOH; then dried in a vacuum oven to afford the product as a white solid: 1H NMR (d6-DMSO) δ 10.25 (1H, t, J=5 Hz), 8.52 (1H, d, J=1 Hz), 7.83 (1H, s), 7.64 (1H, br s), 7.33 (2H, dd, J=8.6, 5.7 Hz), 7.27 (1H, br s), 7.11 (2H, t, J=8.6 Hz), 4.83 (2H, s), 4.11 (2H, s), 3.50 (4H, m), 3.28 (3H, s); HRMS calcd for C21H21FN4O5+H+: 429.1574. Found: 429.1575.

Workup

  1. stirringStirring
  2. waitwas continued 20 min
  3. filtrationfiltered
  4. washThe filter cake was washed with water and EtOH
  5. customthen dried in a vacuum oven

Sources & evidence

ORD record
ord-b5f77edf70c04ef6801173dba1572519
Source dataset
uspto-grants-2014_04
Patent number
US08691991B2

Reaction notes

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