Ammonia → 5-[2-Amino-5-(3-chloro-phenyl)-pyridin-3-yl]-3-[1-(2-chloro-phenyl)-ethoxy]-thiophene-2-carboxylic acid amide

HRID 533231Notes

Reaction equation

HRID 533231 reaction equation
C[O:2][C:3]([C:5]1[S:6][C:7]([C:20]2[C:21]([NH2:33])=[N:22][CH:23]=[C:24]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([Cl:32])[CH:27]=3)[CH:25]=2)=[CH:8][C:9]=1[O:10][CH:11]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[Cl:19])[CH3:12])=O.[NH3:34]>CO>[NH2:33][C:21]1[C:20]([C:7]2[S:6][C:5]([C:3]([NH2:34])=[O:2])=[C:9]([O:10][CH:11]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:19])[CH3:12])[CH:8]=2)=[CH:25][C:24]([C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([Cl:32])[CH:27]=2)=[CH:23][N:22]=1

Participants

4

Reactant 2

HCID 222AmmoniaHCID 59667357HCID 59667357, compound

Product 1

HCID 236243025-[2-Amino-5-(3-chloro-phenyl)-pyridin-3-yl]-3-[1-(2-chloro-phenyl)-ethoxy]-thiophene-2-carboxylic acid amideYield 54%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

5-[2-Amino-5-(3-chloro-phenyl)-pyridin-3-yl]-3-[1-(2-chloro-phenyl)-ethoxy]-thiophene-2-carboxylic acid methyl ester (57 mg, 0.11 mmol, 1.0 Eq.) was suspended in 7M NH3 in MeOH (10 mL) and heated to 100° C. in a pressure tube for 3 days. The reaction was allowed to cool to ambient temperature, the solvent was removed in vacuo and the product purified by column chromatography (ISCO Companion™, 12 g column, 0-10% MeOH/DCM). The solvent was removed in vacuo and the compound was partitioned between DCM (10 mL) and water (10 mL). The organic layer was extracted with DCM (2×7 mL), dried (MgSO4) and concentrated in vacuo to give the title compound as a yellow solid (20 mg, 0.08 mmol, 54%); 1H NMR (400 MHz, d-6 DMSO) δ 1.71 (3H, d), 6.04 (1H, q), 6.30 (2H, br s), 7.05 (1H, s), 7.12 (1 h, br s), 7.33-7.36 (2H, m), 7.40-7.48 (3H, m), 7.58-7.63 (2H, m), 7.70-7.72 (1H, br m), 8.35 (1H, d).

Workup

  1. temperatureto cool to ambient temperature
  2. customthe solvent was removed in vacuo
  3. customthe product purified by column chromatography (ISCO Companion™, 12 g column, 0-10% MeOH/DCM)
  4. customThe solvent was removed in vacuo
  5. customthe compound was partitioned between DCM (10 mL) and water (10 mL)
  6. extractionThe organic layer was extracted with DCM (2×7 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-476f78d11e9d4adaa0081a8f5e1dd9cb
Source dataset
uspto-grants-2014_10
Patent number
US08853244B2

Reaction notes

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