Ammonia → 4-Cyano-3-(4-methoxyphenyl)-5-morpholin-4-ylthiophene-2-carboxamide

HRID 572608Notes

Reaction equation

HRID 572608 reaction equation
[C:1]([C:3]1[C:4]([C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)=[C:5]([C:14]([OH:16])=O)[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:18]=[CH:19][C:20]([O:23][CH3:24])=[CH:21][CH:22]=2)=[C:5]([C:14]([NH2:31])=[O:16])[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 441558974-Cyano-3-(4-methoxyphenyl)-5-morpholin-4-ylthiophene-2-carboxylic acid

Product 1

HCID 441557744-Cyano-3-(4-methoxyphenyl)-5-morpholin-4-ylthiophene-2-carboxamideYield 81.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-Cyano-3-(4-methoxyphenyl)-5-morpholin-4-ylthiophene-2-carboxylic acid (0.035 g, 0.10 mmol), HOBT (0.028 g, 0.18 mmol) and EDCI (38 mg, 0.20 mmol) were suspended in DCM (5 mL). After 50 min the reagents dissolved. To the resulting solution was added concentrated aqueous ammonia (0.2 mL, 5 mmol) and the solution was allowed to stir vigorously at rt for 2 h. 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 4-cyano-3-(4-methoxyphenyl)-5-morpholin-4-ylthiophene-2-carboxamide (66) (0.028 g, 80%). LCMS: (AA) ES+ 344. 1H NMR (400 MHz, d6-DMSO) δ: 7.32-7.35 (m, 2H), 7.06-7.09 (m, 2H), 3.82 (s, 3H), 3.76-3.78 (m, 4H) and 3.52-3.54 (m, 4H).

Workup

  1. dissolutionAfter 50 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

Sources & evidence

ORD record
ord-b336dc46c97547f6ba95714aceccc052
Source dataset
uspto-grants-2015_05
Patent number
US09029411B2

Reaction notes

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