Ammonia → HCID 44155227, compound

HRID 572620Notes

Reaction equation

HRID 572620 reaction equation
[C:1]([C:3]1[C:4]([C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[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:30]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]([CH3:23])=[CH:21][CH:22]=2)=[C:5]([C:14]([NH2:30])=[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 441566374-Cyano-3-(4-methylphenyl)-5-morpholin-4-ylthiophene-2-carboxylic acid

Product 1

HCID 44155227HCID 44155227, compoundYield 80.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-cyano-3-(4-methylphenyl)-5-morpholin-4-ylthiophene-2-carboxylic acid (0.030 g, 0.091 mmol), HOBT (0.024 g, 0.18 mmol) and EDCI (0.035 g, 0.18 mmol) in DCM (1 mL) was added concentrated aqueous ammonia (0.158 mL, 4.5 mmol). The reaction mixture was allowed to stir at rt for 3 h and was concentrated. The residue was diluted with 0.1N HCl and extracted with EtOAc. The organic solutions were combined, washed with sat NaHCO3, brine, dried over MgSO4, filtered and concentrated to give 4-cyano-3-(4-methylphenyl)-5-morpholin-4-ylthiophene-2-carboxamide (35) (0.024 g, 80%). LCMS: (AA) ES+ 328.2. 1H NMR (400 MHz, d6-DMSO) δ: 7.45-7.47 (m, 2H), 7.40-7.42 (m, 2H), 3.88-3.90 (m, 4H), 3.64-3.66 (m, 4H) and 2.62 (s, 3H).

Workup

  1. concentrationwas concentrated
  2. additionThe residue was diluted with 0.1N HCl
  3. extractionextracted with EtOAc
  4. washwashed with sat NaHCO3, brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-2b2b5f50a20b48f69c9134a008e60b87
Source dataset
uspto-grants-2015_05
Patent number
US09029411B2

Reaction notes

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