2-Methylindole → Methyl 1,2,3,4-tetrahydro-3-methyl-6-[(2-methyl-1H-indol-3-yl)methyl]-1-(isobutyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxylate

HRID 900746Notes

Reaction equation

HRID 900746 reaction equation
[CH3:1][N:2]1[C:7](=[O:8])[C:6]2[C:9]([C:13]([O:15][CH3:16])=[O:14])=[C:10]([CH3:12])[S:11][C:5]=2[N:4]([CH2:17][CH:18]([CH3:20])[CH3:19])[C:3]1=[O:21].BrN1C(=O)CCC1=O.C(=O)(O)[O-].[Na+].[CH3:35][C:36]1[NH:37][C:38]2[C:43]([CH:44]=1)=[CH:42][CH:41]=[CH:40][CH:39]=2>C(Cl)(Cl)Cl>[CH3:1][N:2]1[C:7](=[O:8])[C:6]2[C:9]([C:13]([O:15][CH3:16])=[O:14])=[C:10]([CH2:12][C:44]3[C:43]4[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=4)[NH:37][C:36]=3[CH3:35])[S:11][C:5]=2[N:4]([CH2:17][CH:18]([CH3:19])[CH3:20])[C:3]1=[O:21]

Participants

6

Reactant 4

HCID 72242-MethylindoleHCID 67184N-bromobutanimideHCID 516892Sodium BicarbonateHCID 5282532Methyl 1-isobutyl-3,6-dimethyl-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carboxylate

Product 1

HCID 68805728Methyl 1,2,3,4-tetrahydro-3-methyl-6-[(2-methyl-1H-indol-3-yl)methyl]-1-(isobutyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxylate

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

A solution of methyl 1,2,3,4-tetrahydro-3,6-dimethyl-1-(2-methylpropyl)-2,4-dioxo-thieno[2,3-d]pyrimidine-5-carboxylate [example 1 step a), 7.00 g) and N-bromosuccinimide (4.42 g) in chloroform (140 ml) was refluxed under illumination from a tungsten lamp for 2 hours. The solution was cooled to room temperature, saturated aqueous sodium bicarbonate solution (140 ml) and 2-methylindole (5.92 g) were added and the mixture stirred rapidly for 48 hours. The phases were separated and the aqueous phase extracted with dichloromethane (100 ml). Combined organic extracts were dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure. The residue was purified by column chromatography over silica, eluting with ethyl acetate/i-hexane (1:3) to give the sub-title compound as a pale brown solid (6.68 g).

Workup

  1. customThe phases were separated
  2. extractionthe aqueous phase extracted with dichloromethane (100 ml)
  3. dry with materialCombined organic extracts were dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customevaporated under reduced pressure
  6. customThe residue was purified by column chromatography over silica
  7. washeluting with ethyl acetate/i-hexane (1:3)

Sources & evidence

ORD record
ord-91d157422d4442b1855567827be78702
Source dataset
uspto-grants-2008_04
Patent number
US07361660B2

Reaction notes

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