Methanamine, N-methoxy-, hydrochloride (1:1) → N,2-dimethoxy-N-methyl-2-(4-(1-(tris(4-methoxyphenyl)methyl)-1H-pyrazol-4-yl)phenyl)acetamide

HRID 56512

Reaction equation

HRID 56512 reaction equation
[CH3:1][O:2][CH:3]([C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:14]=[N:15][N:16]([C:18]([C:35]3[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=3)([C:27]3[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=3)[C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)[CH:17]=2)=[CH:9][CH:8]=1)[C:4]([O-])=[O:5].[K+].C(N(C(C)C)CC)(C)C.COCCN(S(F)(F)F)CCOC.Cl.[CH3:67][NH:68][O:69][CH3:70]>CN(C=O)C.O>[CH3:70][O:69][N:68]([CH3:67])[C:4](=[O:5])[CH:3]([O:2][CH3:1])[C:7]1[CH:8]=[CH:9][C:10]([C:13]2[CH:14]=[N:15][N:16]([C:18]([C:19]3[CH:20]=[CH:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=3)([C:27]3[CH:28]=[CH:29][C:30]([O:33][CH3:34])=[CH:31][CH:32]=3)[C:35]3[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=3)[CH:17]=2)=[CH:11][CH:12]=1

Participants

7

Reactant 4

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 2734690(Bis(2-methoxyethyl)amino)sulfur trifluorideHCID 67388959potassium 2-methoxy-2-(4-(1-(tris(4-methoxyphenyl)methyl)-1H-pyrazol-4-yl)phenyl)acetate

Product 1

HCID 58432018N,2-dimethoxy-N-methyl-2-(4-(1-(tris(4-methoxyphenyl)methyl)-1H-pyrazol-4-yl)phenyl)acetamideYield 37.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To an ice-cold solution of potassium 2-methoxy-2-(4-(1-(tris(4-methoxyphenyl)methyl)-1H-pyrazol-4-yl)phenyl)acetate (1.25 g, 2.1 mmol) in anhydrous DMF (10 mL) under argon was added diisopropylethylamine (0.54 mL, 3.1 mmol) and bis(2-methoxyethyl)aminosulfur trifluoride (0.46 mL, 2.5 mmol) dropwise. The reaction was stirred for 30 min then N,O-dimethylhydroxylamine hydrochloride (0.303 g, 3.1 mmol) was added. After stirring for a further 15 min over an ice bath, the mixture was allowed to warm to room temperature and stirred for 3.5 hrs. H2O was added and the mixture was extracted with EtOAc. The combined organics were washed with H2O, saturated aqueous NH4Cl, saturated aqueous NaHCO3, and brine then dried over Na2SO4 and concentrated in vacuo. Purification by chromatography (45-90% EtOAc-hexanes; EtOAc containing 1% Et3N) to give N,2-dimethoxy-N-methyl-2-(4-(1-(tris(4-methoxyphenyl)methyl)-1H-pyrazol-4-yl)phenyl)acetamide (0.478 g from two reactions, 32% yield overall).

Workup

  1. stirringAfter stirring for a further 15 min over an ice bath
  2. stirringstirred for 3.5 hrs
  3. extractionthe mixture was extracted with EtOAc
  4. washThe combined organics were washed with H2O, saturated aqueous NH4Cl, saturated aqueous NaHCO3, and brine
  5. dry with materialthen dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customPurification by chromatography (45-90% EtOAc-hexanes; EtOAc containing 1% Et3N)

Sources & evidence

ORD record
ord-8f416dc8b4d6400f92d6519f712cb4e7
Source dataset
uspto-grants-2016_09
Patent number
US09434707B2

Linked notes

Loading…