Acetic Acid → N-(2-hydroxyethyl)-2-(2-(4-((methylamino)methyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide

HRID 1162779Notes

Reaction equation

HRID 1162779 reaction equation
[CH:1]([C:3]1[C:4]([C:27]([F:30])([F:29])[F:28])=[N:5][N:6]([CH2:8][C:9]([NH:11][C:12]2[S:16][C:15]3[CH2:17][CH2:18][CH2:19][CH2:20][C:14]=3[C:13]=2[C:21]([NH:23][CH2:24][CH2:25][OH:26])=[O:22])=[O:10])[CH:7]=1)=O.[CH3:31][NH2:32].C(O)(=O)C.[H][H]>C(Cl)Cl.[Pd]>[OH:26][CH2:25][CH2:24][NH:23][C:21]([C:13]1[C:14]2[CH2:20][CH2:19][CH2:18][CH2:17][C:15]=2[S:16][C:12]=1[NH:11][C:9](=[O:10])[CH2:8][N:6]1[CH:7]=[C:3]([CH2:1][NH:32][CH3:31])[C:4]([C:27]([F:28])([F:29])[F:30])=[N:5]1)=[O:22]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 6329MethylamineHCID 595204812-(2-(4-Formyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetamido)-N-(2-hydroxyethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamideHCID 178418361HCID 178418361, compound

Product 1

HCID 24967423N-(2-hydroxyethyl)-2-(2-(4-((methylamino)methyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamideYield 193.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6344DichloromethaneSolvent2×

Procedure

2-(2-(4-Formyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetamido)-N-(2-hydroxyethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (100 mg, 0.225 mmol), Methylamine (2 M in THF, 0.45 mL, 0.90 mmol) and DCM (3 mL) were treated with acetic acid (13.51 mg, 0.225 mmol) to give pH 4-5 and the solution stirred at RT for 20 min. 10% Pd/C (20 mg) was added as a slurry in DCM and the mixture stirred under 4 barr hydrogen overnight. The mixture was taken into a 20 mL syringe and the residue of the flask washed with MeOH/DCM and also taken into the syringe. The mixture was filtered through a filter tip and concentrated to give a yellow oil (˜200 mg). Purification was achieved on silica eluting with 4% 2 M NH3 in MeOH/DCM and the product obtained as a light yellow glass (74.2 mg, 0.160 mmol, 71%).

Workup

  1. customto give pH 4-5
  2. customThe mixture was taken into a 20 mL syringe
  3. washthe residue of the flask washed with MeOH/DCM
  4. filtrationThe mixture was filtered through a filter tip
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-7ed9a6bdc33e4c26ae4499ace1d144ba
Source dataset
uspto-grants-2010_10
Patent number
US07820707B2

Reaction notes

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