Methanamine, N-methoxy-, hydrochloride (1:1) → N-(1-(4-chlorophenyl)-3-(methoxy(methyl)carbamoyl)cyclobutyl)benzamide

HRID 1778591Notes

Reaction equation

HRID 1778591 reaction equation
[C:1]([NH:9][C:10]1([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[CH2:13][CH:12]([C:14]([OH:16])=O)[CH2:11]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.Cl.[CH3:34][NH:35][O:36][CH3:37].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl>[Cl:23][C:20]1[CH:21]=[CH:22][C:17]([C:10]2([NH:9][C:1](=[O:8])[C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH2:13][CH:12]([C:14](=[O:16])[N:35]([O:36][CH3:37])[CH3:34])[CH2:11]2)=[CH:18][CH:19]=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 895142713-Benzamido-3-(4-chlorophenyl)cyclobutanecarboxylic acid

Product 1

HCID 89514268N-(1-(4-chlorophenyl)-3-(methoxy(methyl)carbamoyl)cyclobutyl)benzamideYield 86.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 3-benzamido-3-(4-chlorophenyl)cyclobutanecarboxylic acid (1.16 g, 3.52 mmol), diisopropylethylamine (1.57 mL, 9.14 mmol) and N,O-dimethylhydroxylamine hydrochloride (0.446 g, 4.572 mmol) in dichloromethane (45 mL) was treated with HATU (1.61 g, 4.22 mmol). After stirring overnight, the solution was diluted with dichloromethane (50 mL), washed successively with 1 M HCl (3×), 5% aqueous NaHCO3 and saturated aqueous sodium chloride. The organic phase dried over MgSO4, filtered and concentrated to give a colorless gum. Crystallization from diethyl ether gave the subject compound as a white crystalline solid (1.13 g 86%). 1H NMR (CDCl3, 600 MHz) δ 7.79 (d, J=7.5 Hz, 2H), 7.49-7.52 (m, 3H), 7.42-7.45 (m, 2H), 7.35 (d, J=8.5 Hz, 2H), 7.08 (bs, 1H), 3.68 (s, 3H), 3.43-3.47 (m, 1H), 3.22 (s, 3H), 2.98-3.01 (m, 2H), 2.87-2.91 (m, 2H). ESI MS found for C20H21ClN2O3 m/z [395.4/397.3 (M+NO, 373.3/375.3 (M+1), 371.3/373.3 (M−1)].

Workup

  1. washwashed successively with 1 M HCl (3×), 5% aqueous NaHCO3 and saturated aqueous sodium chloride
  2. dry with materialThe organic phase dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a colorless gum
  6. customCrystallization from diethyl ether

Sources & evidence

ORD record
ord-47e9452f37fa459c9021ae50d0def308
Source dataset
uspto-grants-2016_02
Patent number
US09266908B2

Reaction notes

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