Dimethylformamide → HCID 66585051, compound

HRID 589889Notes

Reaction equation

HRID 589889 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:9]([C:24]([O:26][CH2:27][CH3:28])=[O:25])=[C:10]3[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13][CH2:12][N:11]3[CH:23]=2)[CH:5]=[CH:6][CH:7]=1.ClS([N:33]=[C:34]=O)(=O)=O.CN(C)C=O.[OH-].[Na+]>ClCCl>[C:34]([C:23]1[N:11]2[CH2:12][CH2:13][N:14]([C:16]([O:18][C:19]([CH3:21])([CH3:22])[CH3:20])=[O:17])[CH2:15][C:10]2=[C:9]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[C:8]=1[C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=1)#[N:33]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 14798Sodium HydroxideHCID 70918Chlorosulfonyl isocyanateHCID 66584850HCID 66584850, compound

Product 1

HCID 66585051HCID 66585051, compoundYield 46.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution, under argon and cooled to 10° C., of 2.52 g (6.49 mmol) of 2-tert-butyl 8-ethyl 7-(3-fluorophenyl)-3,4-dihydropyrrolo[1,2-a]pyrazine-2,8(1H)-dicarboxylate in 20 ml of dichloromethane is added dropwise 0.62 ml (7.14 mmol) of chlorosulfonyl isocyanate (CAS 1189-71-5) and the mixture is left stirring at 0° C. for 1 hour. 3.3 ml (65 mmol) of dimethylformamide are then added dropwise to the mixture, cooled to −10° C. After stirring for 5 hours at room temperature, the mixture is poured into 60 ml of aqueous 1N sodium hydroxide solution and the product is extracted with dichloromethane. The solution is dried over sodium sulfate and the solvent is evaporated off under reduced pressure, to give a yellow oil, which is chromatographed on a column of 80 g of silica gel, eluting with a mixture of 20% ethyl acetate in cyclohexane, to give 1.24 g of 2-tert-butyl 8-ethyl 6-cyano-7-(3-fluorophenyl)-3,4-dihydropyrrolo[1,2-a]pyrazine-2,8(1H)-dicarboxylate in the form of a white powder after crystallizing from diisopropyl ether, filtering off and drying.

Workup

  1. waitthe mixture is left
  2. temperaturecooled to −10° C
  3. stirringAfter stirring for 5 hours at room temperature
  4. extractionthe product is extracted with dichloromethane
  5. dry with materialThe solution is dried over sodium sulfate
  6. customthe solvent is evaporated off under reduced pressure
  7. customto give a yellow oil, which
  8. customis chromatographed on a column of 80 g of silica gel
  9. washeluting with a mixture of 20% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-fcdcc78b5ed84475811cd835954e1082
Source dataset
uspto-grants-2016_01
Patent number
US09233965B2

Reaction notes

Loading…