Ammonia → 4-Cyano-3-(2,4-dichlorophenyl)-5-morpholinothiophene-2-carboxamide

HRID 2091672Notes

Reaction equation

HRID 2091672 reaction equation
[C:1]([C:3]1[C:4]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=2[Cl:24])=[C:5]([C:14](O)=[O:15])[S:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)#[N:2].C1C=CC2N(O)N=[N:31]C=2C=1.CCN=C=NCCCN(C)C.N>C(Cl)Cl>[C:1]([C:3]1[C:4]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=2[Cl:24])=[C:5]([C:14]([NH2:31])=[O:15])[S:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)#[N:2]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 441556654-Cyano-3-(2,4-dichlorophenyl)-5-morpholin-4-ylthiophene-2-carboxylic acid

Product 1

HCID 441554464-Cyano-3-(2,4-dichlorophenyl)-5-morpholinothiophene-2-carboxamideYield 49%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-Cyano-3-(2,4-dichlorophenyl)-5-morpholin-4-ylthiophene-2-carboxylic acid (0.050 g, 0.13 mmol), HOBT (0.037 g, 0.274 mmol) and EDCI (50 mg, 0.261 mmol) were suspended in DCM (6.5 mL). After 30 min the reagents dissolved. To the resulting solution was added concentrated aqueous ammonia (0.26 mL, 6.5 mmol) and the solution was allowed to stir vigorously at rt overnight. The reaction mixture was concentrated and the residue was diluted with 1N HCl and extracted with EtOAc. The organic solutions were combined, washed with sat NaHCO3 and brine, dried over MgSO4 filtered and concentrated to give a brown solid. The solid was triturated with hexanes and cold EtOAc to give 4-cyano-3-(2,4-dichlorophenyl)-5-morpholin-4-ylthiophene-2-carboxamide (0.024 g, 49%). LCMS: (AA) ES+ 382, ES− 380. 1H NMR (400 MHz, d6-DMSO) δ: 7.78 (s, 1H), 7.54 (d, 2H), 7.43 (d, 2H), 3.79-3.77 (m, 4H) and 3.55-3.52 (m, 4H).

Workup

  1. dissolutionAfter 30 min the reagents dissolved
  2. concentrationThe reaction mixture was concentrated
  3. additionthe residue was diluted with 1N HCl
  4. extractionextracted with EtOAc
  5. washwashed with sat NaHCO3 and brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a brown solid
  10. customThe solid was triturated with hexanes and cold EtOAc

Sources & evidence

ORD record
ord-aaf227b0694a4991a1762a50f21c5643
Source dataset
uspto-grants-2013_05
Patent number
US08440664B2

Reaction notes

Loading…