Methylamine → 2-(2-(4-(1-(methylamino)ethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide

HRID 1162763Notes

Reaction equation

HRID 1162763 reaction equation
[CH3:1][NH2:2].C1COCC1.[C:8]([C:11]1[C:12]([C:32]([F:35])([F:34])[F:33])=[N:13][N:14]([CH2:16][C:17]([NH:19][C:20]2[S:24][C:23]3[CH2:25][CH2:26][CH2:27][CH2:28][C:22]=3[C:21]=2[C:29]([NH2:31])=[O:30])=[O:18])[CH:15]=1)(=O)[CH3:9].[Na]>C(O)(=O)C.CO>[CH3:1][NH:2][CH:8]([C:11]1[C:12]([C:32]([F:34])([F:35])[F:33])=[N:13][N:14]([CH2:16][C:17]([NH:19][C:20]2[S:24][C:23]3[CH2:25][CH2:26][CH2:27][CH2:28][C:22]=3[C:21]=2[C:29]([NH2:31])=[O:30])=[O:18])[CH:15]=1)[CH3:9]

Participants

7

Reactant 4

HCID 6329MethylamineHCID 8028TetrahydrofuranHCID 5360545SodiumHCID 595205152-(2-(4-acetyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide

Product 1

HCID 595205242-(2-(4-(1-(methylamino)ethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamideYield 14%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

To MeOH (1.5 mL) was added 2M methylamine in THF (0.724 mL, 1.448 mmol). Acetic acid was added to the mixture to adjust the pH to 4-5. 2-(2-(4-acetyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (50 mg, 0.121 mmol) and sodium cyanoborohyde (7.58 mg, 0.121 mmol) were added before heating the reaction to 100° C. for 30 min by microwave irradiation. The reaction mixture was quenched with water before purification by preparative reverse phase HPLC. The product fractions were acidified to pH 3 with acetic acid before applying to a strong cation exchange cartridge (500 mg). The cartridge was washed with DCM/MeOH (1:1) before eluting the product with 2M NH3 in MeOH. The solvent was removed in vacuo to give the title compound (7.1 mg, 0.017 mmol, 14%).

Workup

  1. temperaturebefore heating
  2. customthe reaction to 100° C. for 30 min
  3. customby microwave irradiation
  4. customThe reaction mixture was quenched with water before purification by preparative reverse phase HPLC
  5. washThe cartridge was washed with DCM/MeOH (1:1)
  6. washbefore eluting the product with 2M NH3 in MeOH
  7. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-1b08c47067794f56a36fb454edb68163
Source dataset
uspto-grants-2010_10
Patent number
US07820707B2

Reaction notes

Loading…