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

HRID 2252825Notes

Reaction equation

HRID 2252825 reaction equation
[OH:1][C:2]1[C:3]([C:21](O)=[O:22])=[N:4][C:5]([N:12]2[CH2:17][CH2:16][CH2:15][N:14]([CH3:18])[S:13]2(=[O:20])=[O:19])=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.[Cl-].[CH3:25][NH:26][C:27]([C:29]1[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=1[CH2:36][NH3+:37])=[O:28].Cl.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[F:35][C:33]1[CH:32]=[CH:31][C:30]([CH2:36][NH:37][C:21]([C:3]2[C:2]([OH:1])=[C:11]3[C:6]([CH:7]=[CH:8][CH:9]=[N:10]3)=[C:5]([N:12]3[CH2:17][CH2:16][CH2:15][N:14]([CH3:18])[S:13]3(=[O:19])=[O:20])[N:4]=2)=[O:22])=[C:29]([C:27]([NH:26][CH3:25])=[O:28])[CH:34]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 596452528-Hydroxy-5-(6-methyl-1,1-dioxido-1,2,6-thiadiazinan-2-yl)-1,6-naphthyridine-7-carboxylic acid2×HCID 866001764-Fluoro-2-[(methylamino)carbonyl]benzylamine hydrochloride2×

Product 1

HCID 3013406N-[[4-fluoro-2-(methylcarbamoyl)phenyl]methyl]-8-hydroxy-5-(6-methyl-1,1-dioxo-1,2,6-thiadiazinan-2-yl)-1,6-naphthyridine-7-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

8-Hydroxy-5-(6-methyl-1,1-dioxido-1,2,6-thiadiazinan-2-yl)-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-(6-methyl-1,1-dioxido-1,2,6-thiadiazinan-2-yl)-1,6-naphthyridine-7-carboxylic acid (200 mg, 0.59 mmol) in dry DMF (2 mL) was stirred at zero degrees. To this was added 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (147 mg, 0.77 mmol), 1-hydroxy-7-azabenzotriazole (181 mg, 1.18 mmol). The mixture was stirred for 35 minutes at which time the {4-fluoro-2-[(methylamino)carbonyl]phenyl}-methanaminium chloride (194 mg, 0.89 mmol) and diisopropylethylamine (124 μL, 0.7 mmol) was added and the reaction was stirred at room temperature for 1 hour. The reaction was filtered through a glass fiber filter. The filtrate was injected directly into the 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. washeluting with 95-5% water (0.025% TFA)/acetonitrile (0.025% TFA) at 35 mL/min)
  5. customdried

Sources & evidence

ORD record
ord-35bfe735fe3a4376aa08fd99781ff01a
Source dataset
uspto-grants-2008_01
Patent number
US07323460B2

Reaction notes

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