Water → 3-(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)phenyl) propanamide

HRID 1487156Notes

Reaction equation

HRID 1487156 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]([CH2:59][CH2:60][C:61]([NH2:63])=[O:62])[CH:56]=[CH:57][CH:58]=1.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]([CH2:59][CH2:60][C:61]([NH2:63])=[O:62])[CH:56]=[CH:57][CH:58]=3)[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 79372,6-LutidineHCID 433091803-(3-Aminophenyl)propanamide2×HCID 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 898161213-(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)phenyl) propanamideYield 85.9%

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 (xxx) (2 gm, 2.79 mmol) in DMA (5 ml) was added 2,6-lutidine (0.597 g, 5.57 mmol) and 3-(3-aminophenyl)propanamide (intermediate xxvi) (0.915 gm, 5.57 mmole). The reaction mixture was heated at 130° C. for 16 h. The reaction mixture was cooled to room temperature and added water until a solid precipitate was obtained. The solid was filtered, washed with water and small amount of MeOH. The solid was purified by silica gel column chromatography, eluting with DCM:Methanol (9:1), to yield the titled compound (1b) (1.7 g) [m/z=710.20 (M+1)].

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customwas obtained
  3. filtrationThe solid was filtered
  4. washwashed with water and small amount of MeOH
  5. customThe solid was purified by silica gel column chromatography
  6. washeluting with DCM:Methanol (9:1)

Sources & evidence

ORD record
ord-28b05492a173455b9cae8ae4bc48609c
Source dataset
uspto-grants-2016_08
Patent number
US09428499B2

Reaction notes

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