Thiophene-3-carboxylic acid → Thiophene-3-carboxylic acid [5-[3-(2-oxo-pyrrolidin-1-yl)-propylcarbamoyl]-2-(4-o-tolyl-piperazin-1-yl)-phenyl]-amide

HRID 710027Notes

Reaction equation

HRID 710027 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][C:19]=1[N:20]1[CH2:25][CH2:24][N:23]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[CH3:32])[CH2:22][CH2:21]1)[C:5]([NH:7][CH2:8][CH2:9][CH2:10][N:11]1[CH2:15][CH2:14][CH2:13][C:12]1=[O:16])=[O:6].C(N(CC)CC)C.[S:40]1[CH:44]=[CH:43][C:42]([C:45](O)=[O:46])=[CH:41]1>C(Cl)Cl>[O:16]=[C:12]1[CH2:13][CH2:14][CH2:15][N:11]1[CH2:10][CH2:9][CH2:8][NH:7][C:5]([C:4]1[CH:17]=[CH:18][C:19]([N:20]2[CH2:25][CH2:24][N:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[CH3:32])[CH2:22][CH2:21]2)=[C:2]([NH:1][C:45]([C:42]2[CH:43]=[CH:44][S:40][CH:41]=2)=[O:46])[CH:3]=1)=[O:6]

Participants

5

Reactant 3

HCID 6918Thiophene-3-carboxylic acidHCID 8471TriethylamineHCID 866758943-amino-N-[3-(2-oxo-pyrrolidin-1-yl)-propyl]-4-(4-o-tolyl-piperazin-1-yl)-benzamide

Product 1

HCID 71233951Thiophene-3-carboxylic acid [5-[3-(2-oxo-pyrrolidin-1-yl)-propylcarbamoyl]-2-(4-o-tolyl-piperazin-1-yl)-phenyl]-amideYield 272.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 3-amino-N-[3-(2-oxo-pyrrolidin-1-yl)-propyl]-4-(4-o-tolyl-piperazin-1-yl)-benzamide (0.1 g, 0.229 mmol) in methylene dichloride (5 ml), triethylamine (0.069 g, 0.489 mmol), thiophene-3-carboxylic acid (0.044 g, 0.344 mmol) and 1-propane phosphonic cyclic anhydride (0.21 g, 0.489 mmol) were added. The reaction mixture was stirred for 16 h at room temperature. The reaction mixture was concentrated and extracted with dichloromethane (10 ml×1). The organic layer was washed with water (10 ml×2) and dried over anhydrous sodium sulphate. The organic layer was concentrated and the crude product obtained was purified by flash chromatography using silica gel column to get (0.34 g, 34%) of the titled compound as a brown solid.

Workup

  1. additionwere added
  2. concentrationThe reaction mixture was concentrated
  3. extractionextracted with dichloromethane (10 ml×1)
  4. washThe organic layer was washed with water (10 ml×2)
  5. dry with materialdried over anhydrous sodium sulphate
  6. concentrationThe organic layer was concentrated
  7. customthe crude product obtained
  8. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-262622db38344aceb2e989ce08d09ca2
Source dataset
uspto-grants-2015_11
Patent number
US09181226B2

Reaction notes

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