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

HRID 1162783Notes

Reaction equation

HRID 1162783 reaction equation
[C:1]([C:5]1[C:9]([CH:10]=O)=[CH:8][N:7]([CH2:12][C:13]([NH:15][C:16]2[S:20][C:19]3[CH2:21][CH2:22][CH2:23][CH2:24][C:18]=3[C:17]=2[C:25]([NH:27][CH2:28][CH2:29][OH:30])=[O:26])=[O:14])[N:6]=1)([CH3:4])([CH3:3])[CH3:2].C(O)(=O)C.[CH2:35]([NH2:37])[CH3:36]>C(Cl)Cl.[Pd]>[C:1]([C:5]1[C:9]([CH2:10][NH:37][CH2:35][CH3:36])=[CH:8][N:7]([CH2:12][C:13]([NH:15][C:16]2[S:20][C:19]3[CH2:21][CH2:22][CH2:23][CH2:24][C:18]=3[C:17]=2[C:25]([NH:27][CH2:28][CH2:29][OH:30])=[O:26])=[O:14])[N:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 6341EthylamineHCID 595205022-(2-(3-Tert-butyl-4-formyl-1H-pyrazol-1-yl)acetamido)-N-(2-hydroxyethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide

Product 1

HCID 595204642-(2-(3-Tert-butyl-4-((ethylamino)methyl)-1H-pyrazol-1-yl)acetamido)-N-(2-hydroxyethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamideYield 45.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6344DichloromethaneSolvent2×

Procedure

2-(2-(3-Tert-butyl-4-formyl-1H-pyrazol-1-yl)acetamido)-N-(2-hydroxyethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (1.66 g, 3.84 mmol) was dissolved in DCM (40 mL) and acetic acid (20.98 g, 20 mL, 349 mmol). Ethylamine (2M in THF, 7.68 mL, 15.35 mmol) was added and the mixture was stirred for 90 min. A slurry of palladium on charcoal (10%, 1.51 g, 1.420 mmol) in DCM (30 mL) was added and the mixture hydrogenated at 4 barr for 72 h at 20° C. The catalyst was filtered through dicalite and the dicalite washed with water, DCM and MeOH. All volatiles were removed under reduced pressure and the aqueous residue was basified to pH 8 using sodium bicarbonate. The crude product was extracted with EtOAc. The organics were combined and washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by chromatography (DCM, 0-30% MeOH/DCM and 0-20% 7 N NH3 in MeOH/DCM). Concentration in vacuo yielded a white solid (800 mg, 1.73 mmol, 45%).

Workup

  1. waitthe mixture hydrogenated at 4 barr for 72 h at 20° C
  2. filtrationThe catalyst was filtered through dicalite
  3. washthe dicalite washed with water, DCM and MeOH
  4. customAll volatiles were removed under reduced pressure
  5. extractionThe crude product was extracted with EtOAc
  6. washwashed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude material was purified by chromatography (DCM, 0-30% MeOH/DCM and 0-20% 7 N NH3 in MeOH/DCM)
  11. concentrationConcentration in vacuo

Sources & evidence

ORD record
ord-79986d63297a461e8efe21351e1dd174
Source dataset
uspto-grants-2010_10
Patent number
US07820707B2

Reaction notes

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