Triethylamine → N'-[2-[(4-fluorophenyl)methylcarbamoyl]-3-hydroxy-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-9-yl]-N,N,N'-trimethyl-oxamide

HRID 2426261Notes

Reaction equation

HRID 2426261 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.[CH2:26]([N:28](CC)[CH2:29]C)C.Cl[C:34](=[O:39])[C:35](OC)=[O:36]>ClCCl.O.C(#N)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][C:8]([C:10]2[N:11]=[C:12]3[CH:21]([N:22]([CH3:23])[C:35](=[O:36])[C:34]([N:28]([CH3:29])[CH3:26])=[O:39])[CH2:20][CH2:19][CH2:18][N:13]3[C:14](=[O:17])[C:15]=2[OH:16])=[O:9])=[CH:24][CH:25]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 79846Methyl chloroglyoxylateHCID 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 54709859N'-[2-[(4-fluorophenyl)methylcarbamoyl]-3-hydroxy-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-9-yl]-N,N,N'-trimethyl-oxamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of crude N-(4-fluorobenzyl)-3-hydroxy-9-(methylamino)-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-2-carboxamide (synthesized as described in Example 3, Step 3) in dichloromethane were added 6 eq. of triethylamine and 6 eq. of methyl chlorooxoacetate. The mixture was stirred at room temperature for 2 h, the solvent was removed under reduced pressure and the residue was dissolved in a solution of dimethylamine (2 M) in tetrahydrofuran. The mixture was stirred at 57° C. overnight. After cooling to room temperature, the solvent was removed under reduced pressure and the product was isolated by preparative RP-HPLC, using water (0.1% TFA) and acetonitrile (0.1% TFA) as eluents (column: C18). The pooled product fractions were lyophilized to afford the title compound as a fluffy, slightly pink material. The product was a mixture of rotamers by NMR.

Workup

  1. customthe solvent was removed under reduced pressure
  2. dissolutionthe residue was dissolved in a solution of dimethylamine (2 M) in tetrahydrofuran
  3. stirringThe mixture was stirred at 57° C. overnight
  4. temperatureAfter cooling to room temperature
  5. customthe solvent was removed under reduced pressure
  6. customthe product was isolated by preparative RP-HPLC

Sources & evidence

ORD record
ord-dcb8ffd9223b4d90ab8a059816efb993
Source dataset
uspto-grants-2011_06
Patent number
US07968553B2

Reaction notes

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