Methanamine, N-methoxy-, hydrochloride (1:1) → 3-(4-chlorobenzyl)-3-formamido-N-methoxy-N-methylcyclobutanecarboxamide

HRID 1778597Notes

Reaction equation

HRID 1778597 reaction equation
[Cl:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][C:7]2([NH:14][CH:15]=[O:16])[CH2:10][CH:9]([C:11]([OH:13])=O)[CH2:8]2)=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.Cl.[CH3:29][O:30][NH:31][CH3:32].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][C:7]2([NH:14][CH:15]=[O:16])[CH2:8][CH:9]([C:11]([N:31]([O:30][CH3:29])[CH3:32])=[O:13])[CH2:10]2)=[CH:17][CH:18]=1

Participants

6

Reactant 4

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 895142413-(4-Chlorobenzyl)-3-formamidocyclobutanecarboxylic acid

Product 1

HCID 895144553-(4-chlorobenzyl)-3-formamido-N-methoxy-N-methylcyclobutanecarboxamideYield 33.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 3-(4-chlorobenzyl)-3-formamidocyclobutanecarboxylic acid (1.3 g, 4.87 mmol), DIPEA (2.17 mL, 12.6 mmol), O,N-dimethylhydroxylamine hydrochloride (617 mg, 6.33 mmol) in dichloromethane (20 mL) was treated with HATU (2.2 g, 5.84 mmol) and stirred at room temperature for 16 h. The solution was diluted with dichloromethane (20 mL), washed successively with 1 M HCl (2×), 5% aqueous NaHCO3 and saturated aqueous sodium chloride, dried over MgSO4, filtered and concentrated. The crude product was purified by column chromatography (gradient 0.5-1.0% methanol in dichloromethane) to give the subject compound (0.5 g, 33.3%). ESI MS found for C15H19ClN2O3 m/z [211.4 (M+1), 233.4 (M+Na+)].

Workup

  1. washwashed successively with 1 M HCl (2×), 5% aqueous NaHCO3 and saturated aqueous sodium chloride
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product was purified by column chromatography (gradient 0.5-1.0% methanol in dichloromethane)

Sources & evidence

ORD record
ord-185232224a2a474ab3a89fcf72b289a3
Source dataset
uspto-grants-2016_02
Patent number
US09266908B2

Reaction notes

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