Water → 3-((1-(2-Fluoro-4-iodophenyl)-3-(4-methoxybenzyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidin-5-yl)amino)benzoic acid

HRID 1487159Notes

Reaction equation

HRID 1487159 reaction equation
CC1C=CC(S(O[C:12]2[C:21]3[C:20](=[O:22])[N:19]([CH2:23][C:24]4[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=4)[C:18](=[O:32])[N:17]([C:33]4[CH:38]=[CH:37][C:36]([I:39])=[CH:35][C:34]=4[F:40])[C:16]=3[N:15]([CH3:41])[C:14](=[O:42])[C:13]=2[CH3:43])(=O)=O)=CC=1.N1C(C)=CC=CC=1C.[NH2:52][C:53]1[CH:54]=[C:55]([CH:59]=[CH:60][CH:61]=1)[C:56]([OH:58])=[O:57].O>CC(N(C)C)=O>[F:40][C:34]1[CH:35]=[C:36]([I:39])[CH:37]=[CH:38][C:33]=1[N:17]1[C:16]2[N:15]([CH3:41])[C:14](=[O:42])[C:13]([CH3:43])=[C:12]([NH:52][C:53]3[CH:54]=[C:55]([CH:59]=[CH:60][CH:61]=3)[C:56]([OH:58])=[O:57])[C:21]=2[C:20](=[O:22])[N:19]([CH2:23][C:24]2[CH:25]=[CH:26][C:27]([O:30][CH3:31])=[CH:28][CH:29]=2)[C:18]1=[O:32]

Participants

6

Reactant 4

HCID 962WaterHCID 74193-Aminobenzoic AcidHCID 79372,6-LutidineHCID 898158801-(2-Fluoro-4-iodophenyl)-3-(4-methoxybenzyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidin-5-yl 4-methylbenzene sulfonate

Product 1

HCID 898280583-((1-(2-Fluoro-4-iodophenyl)-3-(4-methoxybenzyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidin-5-yl)amino)benzoic acidYield 73.5%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
130 °C

Procedure

To a stirred solution of 1-(2-fluoro-4-iodophenyl)-3-(4-methoxybenzyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidin-5-yl 4-methylbenzene sulfonate (2a) (2.0 gm, 2.79 mmol) in DMA (5 ml) was added 2,6-lutidine (0.98 ml, 8.36 mmol) and 3-aminobenzoic acid (1.147 gm, 8.36 mmol). The reaction mixture was heated at 130° C. for 16 h. The reaction mixture was cooled to room temperature and water was added followed by extraction with Ethyl acetate. The organic phase was dried over sodium sulphate. The solvent was evaporated in vacuo and the residual solid was purified by silica gel column chromatography, eluting with Hexane:Ethyl acetate (1:1), to yield the titled compound (2b) (1.4 g)

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionfollowed by extraction with Ethyl acetate
  3. dry with materialThe organic phase was dried over sodium sulphate
  4. customThe solvent was evaporated in vacuo
  5. customthe residual solid was purified by silica gel column chromatography
  6. washeluting with Hexane:Ethyl acetate (1:1)

Sources & evidence

ORD record
ord-445100b0913f400fbe2a33fe2928043b
Source dataset
uspto-grants-2016_08
Patent number
US09428499B2

Reaction notes

Loading…