N-bromobutanimide → HCID 59432132, compound

HRID 245300Notes

Reaction equation

HRID 245300 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:10]([CH:11]=[CH2:12])=[C:9]([NH2:13])[N:8]=[C:7]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[C:16]([O:21][CH3:22])[C:15]=2F)[N:6]=1)=[O:4].[Br:24]N1C(=O)CCC1=O.[FH:32].[FH:33].F.C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>ClCCl.O>[CH3:1][O:2][C:3]([C:5]1[C:10]([CH:11]([F:32])[CH2:12][Br:24])=[C:9]([NH2:13])[N:8]=[C:7]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[C:16]([O:21][CH3:22])[C:15]=2[F:33])[N:6]=1)=[O:4]

Participants

7

Reactant 4

HCID 67184N-bromobutanimideHCID 175505N,N-Diethylethanamine trihydrofluorideHCID 516892Sodium BicarbonateHCID 594321224-Amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-ethenyl-6-methoxycarbonylpyrimidine

Product 1

HCID 59432132HCID 59432132, compoundYield 44.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

6-Amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-vinyl-pyrimidine-4-carboxylic acid methyl ester (0.611 g, 1.809 mmol) and N-bromosuccinimide (0.386 g, 2.171 mmol) were dissolved in dichloromethane (10 ml) and the reaction mixture was cooled to 0° C. Triethylamine trihydrofluoride (0.884 mL, 5.43 mmol) was then added dropwise and the reaction mixture was allowed to warm to ambient temperature and stirred overnight. Water and additional dichloromethane were added. Sodium bicarbonate (0.760 g, 9.05 mmol) was added in several portions until no further gas evolution was noted. The organic phase was dried and concentrated under vacuum. The product was purified by flash chromatography on silica gel twice (first with dichloromethane/ethyl acetate gradient followed by hexane/ethyl acetate gradient) to provide the title compound (352 mg, 0.806 mmol, 44.6% yield) as a white solid, mp 144-146° C.: 1H NMR (CDCl3) δ 7.67 (dd, 1H), 7.23 (dd, 1H), 6.32 (ddd, 1H), 5.77 (br s, 2H), 4.01 (s, 3H), 4.0 (d, 3H), 3.77-3.94 (m, 2H).

Workup

  1. temperatureto warm to ambient temperature
  2. customThe organic phase was dried
  3. concentrationconcentrated under vacuum
  4. customThe product was purified by flash chromatography on silica gel twice (first with dichloromethane/ethyl acetate gradient followed by hexane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-8974ff19dc2b46cbabe3a09e0d8c6a03
Source dataset
uspto-grants-2014_02
Patent number
US08658791B2

Reaction notes

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