Diisopropylethylamine → 5-[ethylsulfonyl(methyl)amino]-N-[[4-fluoro-2-(methylcarbamoyl)phenyl]methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide

HRID 2252823Notes

Reaction equation

HRID 2252823 reaction equation
[OH:1][C:2]1[C:3]([C:19]([OH:21])=O)=[N:4][C:5]([N:12]([CH3:18])[S:13]([CH2:16][CH3:17])(=[O:15])=[O:14])=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.[Cl-].[CH3:23][NH:24][C:25]([C:27]1[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:28]=1[CH2:34][NH3+:35])=[O:26].Cl.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[CH2:16]([S:13]([N:12]([CH3:18])[C:5]1[N:4]=[C:3]([C:19]([NH:35][CH2:34][C:28]2[CH:29]=[CH:30][C:31]([F:33])=[CH:32][C:27]=2[C:25]([NH:24][CH3:23])=[O:26])=[O:21])[C:2]([OH:1])=[C:11]2[C:6]=1[CH:7]=[CH:8][CH:9]=[N:10]2)(=[O:14])=[O:15])[CH3:17]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 596452568-Hydroxy-5-[methyl(ethylsulfonyl)amino]-1,6-naphthyridine-7-carboxylic acid2×HCID 866001764-Fluoro-2-[(methylamino)carbonyl]benzylamine hydrochloride2×

Product 1

HCID 30134055-[ethylsulfonyl(methyl)amino]-N-[[4-fluoro-2-(methylcarbamoyl)phenyl]methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

8-Hydroxy-5-[methyl(ethylsulfonyl)amino]-1,6-naphthyridine-7-carboxylic acid was coupled with {2-[(methylamino)carbonyl]4-fluorophenyl}methanaminium chloride (prepared as described in Example 3). A solution of 8-Hydroxy-5-[methyl(ethylsulfonyl)amino]-1,6-naphthyridine-7-carboxylic acid (50 mg, 0.16 mmol) in dry DMF (15 mL) was stirred at zero degrees. To this was added 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (40 mg, 0.21 mmol), 1-hydroxy-7-azabenzotriazole (28 mg, 0.21 mmol). The mixture was stirred for 35 minutes at which time the {4-fluoro-2-[(methylamino)carbonyl]phenyl}-methanaminium chloride (38 mg, 0.21 mmol) and diisopropylethylamine (27 mg, 0.21 mmol) was added and the reaction was stirred at room temperature overnight. The reaction was filtered through a glass fiber filter. The filtrate was vacuum reduced and purified by preparative HPLC (Gilson semi preparative HPLC system using a Waters Nova pak column (10×40 mm I.D. cartridges, C18, 6 μM pore size) eluting with 95-5% water (0.025% TFA)/acetonitrile (0.025% TFA) at 35 mL/min). The desired fractions were freeze dried to give the desired product as a white solid.

Workup

  1. additionwas added
  2. filtrationThe reaction was filtered through a glass fiber
  3. filtrationfilter
  4. custompurified by preparative HPLC (Gilson semi preparative HPLC system
  5. washeluting with 95-5% water (0.025% TFA)/acetonitrile (0.025% TFA) at 35 mL/min)
  6. customdried

Sources & evidence

ORD record
ord-d6cc0c734705483facda4a8a1e74923d
Source dataset
uspto-grants-2008_01
Patent number
US07323460B2

Reaction notes

Loading…