(2-Nitrophenyl)acetic acid → 4,6-Dimethoxy-2-(2-nitrobenzyl)pyrimidine

HRID 743975Notes

Reaction equation

HRID 743975 reaction equation
C(N(C(C)C)C(C)C)C.Cl.Cl.[C:12](=[NH:20])([O:18][CH3:19])[CH2:13][C:14](=[NH:17])[O:15][CH3:16].[N+:21]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[CH2:30][C:31](O)=O)([O-:23])=[O:22].C(C1NC=CN=1)(C1NC=CN=1)=O>ClCCl.CC(O)C>[CH3:16][O:15][C:14]1[CH:13]=[C:12]([O:18][CH3:19])[N:20]=[C:31]([CH2:30][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[N+:21]([O-:23])=[O:22])[N:17]=1

Participants

7

Reactant 4

HCID 77337(2-Nitrophenyl)acetic acidHCID 81531DiisopropylethylamineHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 12896693Dimethyl malonimidate dihydrochloride

Product 1

HCID 539772304,6-Dimethoxy-2-(2-nitrobenzyl)pyrimidineYield 32.9%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-40 °C

Procedure

Ethyl diisopropylamine (240 ml) was added dropwise to a stirred suspension of dimethyl malonimidate dihydrochloride (73.2 g) in dichloromethane (400 ml) at -40° C. under nitrogen, and the mixture was stirred at -40° C. for 25 minutes to give suspension A. 2-Nitrophenylacetic acid (65.16 g) was added portionwise to a stirred suspension of carbonyl diimidazole (53.3 g) in dichloromethane (400 ml) at room temperature. The resulting solution was stirred for 10 minutes and was added dropwise over 30 minutes to the suspension A at -40° C. The mixture was stirred at -40° C. for a further 45 minutes and then at room temperature overnight, after which the solution was washed with water (400 ml), 2N HCl (400 ml) and saturated sodium bicarbonate solution (400 ml), dried and evaporated to give an orange solid. It was then stirred with propan-2-ol (50 ml) for 10 minutes and filtered. The solid was washed with a further 50 ml of propan-2-ol and then dried to give 32.6 g of the desired product as a yellow solid, mp 92°-93° C.

Workup

  1. customto give suspension A
  2. stirringThe resulting solution was stirred for 10 minutes
  3. additionwas added dropwise over 30 minutes to the suspension A at -40° C
  4. stirringThe mixture was stirred at -40° C. for a further 45 minutes
  5. washat room temperature overnight, after which the solution was washed with water (400 ml), 2N HCl (400 ml) and saturated sodium bicarbonate solution (400 ml)
  6. customdried
  7. customevaporated
  8. customto give an orange solid
  9. filtrationfiltered
  10. washThe solid was washed with a further 50 ml of propan-2-ol
  11. customdried

Sources & evidence

ORD record
ord-6bc8715185bf4c238d04bac23d77e81c
Source dataset
uspto-grants-1996_09
Patent number
US05559081

Reaction notes

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