Triethylamine → 7-Chloro-6-phenyl-2-(thiophene-2-sulfonyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxylic acid amide

HRID 857882Notes

Reaction equation

HRID 857882 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[C:10]([C:24]([NH2:26])=[O:25])=[C:11]2[CH2:16][NH:15][CH2:14][CH2:13][N:12]2[C:17]=1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(N(CC)CC)C.[S:34]1[CH:38]=[CH:37][CH:36]=[C:35]1[S:39](Cl)(=[O:41])=[O:40]>C(#N)C>[Cl:8][C:9]1[C:10]([C:24]([NH2:26])=[O:25])=[C:11]2[CH2:16][N:15]([S:39]([C:35]3[S:34][CH:38]=[CH:37][CH:36]=3)(=[O:41])=[O:40])[CH2:14][CH2:13][N:12]2[C:17]=1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 855182-Thiophenesulfonyl chlorideHCID 68886670HCID 68886670, compound

Product 1

HCID 587620357-Chloro-6-phenyl-2-(thiophene-2-sulfonyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxylic acid amideYield 92.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

A suspension of 7-chloro-6-phenyl-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxylic acid amide trifluoroacetic acid salt (100 mg, Reference Example 1) in dry acetonitrile (15 mL) was treated with dry triethylamine (0.11 mL), then with 2-thiophenesulfonyl chloride (52 mg). After stirring at 60° C. for 7 hours the reaction mixture was allowed to cool to room temperature and then stand overnight. The solvent was removed under reduced pressure and the residue then treated with water and dichloromethane. The organic phase was separated, then dried over magnesium sulfate and evaporated. The residue was subjected to column chromatography on silica eluting with a mixture of methanol and dichloromethane (1:19, v/v) to give 7-chloro-6-phenyl-2-(thiophene-2-sulfonyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxylic acid amide (100 mg) as a white solid, m.p. 240–242° C. [Elemental analysis: C, 50.95; H, 4.06; N, 9.98%; Calculated for C18H16ClN3O3S2: C, 51.24; H, 3.82; N, 9.96%].

Workup

  1. temperatureto cool to room temperature
  2. waitstand overnight
  3. customThe solvent was removed under reduced pressure
  4. additionthe residue then treated with water and dichloromethane
  5. customThe organic phase was separated
  6. dry with materialdried over magnesium sulfate
  7. customevaporated
  8. additionThe residue was subjected to column chromatography on silica eluting with a mixture of methanol and dichloromethane (1:19, v/v)

Sources & evidence

ORD record
ord-4208f05ac45749babda12706ac5407d0
Source dataset
uspto-grants-2006_12
Patent number
US07148215B2

Reaction notes

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