Tetrahydrofuran → N-{3-[5-(2-fluoro-4-iodophenylamino)-3-(4-methoxybenzyl)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide

HRID 75677Notes

Reaction equation

HRID 75677 reaction equation
C[O-].[Na+].O1CCCC1.[F:9][C:10]1[CH:15]=[C:14]([I:16])[CH:13]=[CH:12][C:11]=1[N:17]1[C:22]2[N:23]([CH3:40])[C:24](=[O:39])[C:25]([CH3:38])=[C:26]([NH:27][C:28]3[CH:29]=[C:30]([NH:34][C:35](=[O:37])[CH3:36])[CH:31]=[CH:32][CH:33]=3)[C:21]=2[C:20](=[O:41])[N:19]([CH2:42][C:43]2[CH:48]=[CH:47][C:46]([O:49][CH3:50])=[CH:45][CH:44]=2)[C:18]1=[O:51]>CO>[F:9][C:10]1[CH:15]=[C:14]([I:16])[CH:13]=[CH:12][C:11]=1[NH:17][C:22]1[N:23]([CH3:40])[C:24](=[O:39])[C:25]([CH3:38])=[C:26]2[C:21]=1[C:20](=[O:41])[N:19]([CH2:42][C:43]1[CH:48]=[CH:47][C:46]([O:49][CH3:50])=[CH:45][CH:44]=1)[C:18](=[O:51])[N:27]2[C:28]1[CH:29]=[C:30]([NH:34][C:35](=[O:37])[CH3:36])[CH:31]=[CH:32][CH:33]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 10942334Sodium MethoxideHCID 59717402N-{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-ylamino]-phenyl}-acetamide

Product 1

HCID 59717341N-{3-[5-(2-fluoro-4-iodophenylamino)-3-(4-methoxybenzyl)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamideYield 97.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution (305 mg) of 28% sodium methoxide in methanol were added tetrahydrofuran (4.00 ml) and N-{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-ylamino]-phenyl}-acetamide 87 (1.00 g). The wall was washed with tetrahydrofuran (4.00 ml). The mixture was stirred at room temperature for 1.5 hrs., 2N hydrochloric acid (900 μl) was added, and the mixture was concentrated under reduced pressure. To the residue was added isopropyl alcohol, methanol and water, and after refluxing, the mixture was allowed to cool to room temperature with stirring. The precipitated crystals were collected by filtration, washed with methanol, and dried to give N-{3-[5-(2-fluoro-4-iodophenylamino)-3-(4-methoxybenzyl)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide 88 (974 mg, yield 97.2%) as colorless crystals.

Workup

  1. washThe wall was washed with tetrahydrofuran (4.00 ml)
  2. addition, 2N hydrochloric acid (900 μl) was added
  3. concentrationthe mixture was concentrated under reduced pressure
  4. additionTo the residue was added isopropyl alcohol, methanol and water
  5. temperatureafter refluxing
  6. temperatureto cool to room temperature
  7. stirringwith stirring
  8. filtrationThe precipitated crystals were collected by filtration
  9. washwashed with methanol
  10. customdried

Sources & evidence

ORD record
ord-9f99bf3669cf493490d623c644a4ed46
Source dataset
uspto-grants-2014_09
Patent number
US08835443B2

Reaction notes

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