Tetrahydrofuran → 9-[dimethylsulfamoyl(methyl)amino]-N-[(4-fluorophenyl)methyl]-3-hydroxy-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidine-2-carboxamide

HRID 2219047Notes

Reaction equation

HRID 2219047 reaction equation
[F:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][NH:7][C:8]([C:10]2[N:11]=[C:12]3[CH:21]([NH:22][CH3:23])[CH2:20][CH2:19][CH2:18][N:13]3[C:14](=[O:17])[C:15]=2[OH:16])=[O:9])=[CH:4][CH:3]=1.O1CCCC1.[OH-].[Na+].[CH3:33][N:34]([CH3:39])[S:35](Cl)(=[O:37])=[O:36]>O.C(#N)C>[CH3:33][N:34]([CH3:39])[S:35]([N:22]([CH3:23])[CH:21]1[C:12]2=[N:11][C:10]([C:8]([NH:7][CH2:6][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:25][CH:24]=3)=[O:9])=[C:15]([OH:16])[C:14](=[O:17])[N:13]2[CH2:18][CH2:19][CH2:20]1)(=[O:37])=[O:36]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 83372Dimethylsulphamoyl chlorideHCID 54709855N-(4-Fluorobenzyl)-3-hydroxy-9-(methylamino)-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-2-carboxamide

Product 1

HCID 547098389-[dimethylsulfamoyl(methyl)amino]-N-[(4-fluorophenyl)methyl]-3-hydroxy-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidine-2-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of crude compound obtained in Step 3 in a 2:1 mixture of tetrahydrofuran and 2 M aq. sodium hydroxide was added N,N-dimethylsulfamoyl chloride (4.6 eq.). The mixture was stirred at room temperature for 16 h. The mixture was concentrated under reduced pressure and the product was isolated by preparative RP-HPLC, using water (0.1% TFA) and acetonitrile (0.1% TEA) as eluents (column: C18). The pooled product fractions were lyophilized to afford the title compound as a fluffy, slightly pink material.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. customthe product was isolated by preparative RP-HPLC

Sources & evidence

ORD record
ord-90f9795941e24222a062b81c2e13d2e5
Source dataset
uspto-grants-2008_08
Patent number
US07414045B2

Reaction notes

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