Hydroxyamine hydrochloride → 4-(Dimethylamino)-n-[5-(hydroxyamino)-5-oxopentyl]-1-naphthamide

HRID 1362575Notes

Reaction equation

HRID 1362575 reaction equation
C[O:2][C:3](=O)[CH2:4][CH2:5][CH2:6][CH2:7][NH:8][C:9]([C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14]([N:21]([CH3:23])[CH3:22])=[CH:13][CH:12]=1)=[O:10].Cl.[NH2:26][OH:27].C[O-].[Na+]>CO>[CH3:22][N:21]([CH3:23])[C:14]1[C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:11]([C:9]([NH:8][CH2:7][CH2:6][CH2:5][CH2:4][C:3]([NH:26][OH:27])=[O:2])=[O:10])=[CH:12][CH:13]=1

Participants

5

Reactant 3

HCID 443297Hydroxyamine hydrochlorideHCID 10942334Sodium MethoxideHCID 574954285-[[[4-(Dimethylamino)-1-naphthalenyl]carbonyl]amino]-pentanoic acid methyl ester

Product 1

HCID 99020184-(Dimethylamino)-n-[5-(hydroxyamino)-5-oxopentyl]-1-naphthamideYield 19.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

(Method J9B) To the solution of 5-[[[4-(dimethylamino)-1-naphthalenyl]carbonyl]amino]-pentanoic acid methyl ester (3/62) (0.31 g, 0.94 mmol) and hydroxylamine hydrochloride (0.26 g, 3.8 mmol) in absolute methanol was added NaOMe solution made by dissolving Na (0.18 g, 8 mmol) in absolute methanol. A white precipitate immediately appeared. After 0.5 h the reaction was complete (TLC), and the reaction mixture was evaporated, suspended in 1M phosphate buffer (pH 4), and extracted with 3 portions of methylene chloride. The organic phase became turbid, therefore the solvent was removed, and the residue was dried under reduced pressure yielding the crude product (0.27 g). Recrystallisation from acetonitrile gave the title product (0.06 g, 19%) of acceptable purity. Rf 0.50 (CHCl3—MeOH 4:1). M.p. 129° C. 1H NMR (DMSO-d6, TMS) δ: 1.53-1.57 (4H, m), 1.97-2.01 (2H, m), 2.84 (6H, s), 3.32-3.33 (m, overlapped with a signal from DMSO), 7.08 (1H, d, J=8.2 Hz), 7.46-7.56 (3H, m), 8.14-8.24 (2H, m), 8.39 (1H, br t, J=5.2 Hz), 8.69 (1H, br s), 10.37 (1H, br s). HPLC analysis on Symmetry 18 column: impurities <1% (column size 3.9×150 mm; mobile phase acetonitrile −0.1M phosphate buffer (pH 2.5), 10:90; detector UV 220 nm; flow rate 1.3 ml/min). Anal. Calcd for C18H23N3O3: C, 65.63; H, 7.04; N, 12.76. Found: C, 65.50; H, 6.90; N, 12.73.

Workup

  1. custom(TLC), and the reaction mixture was evaporated
  2. extractionextracted with 3 portions of methylene chloride
  3. customthe solvent was removed
  4. customthe residue was dried under reduced pressure
  5. customyielding the crude product (0.27 g)
  6. customRecrystallisation from acetonitrile

Sources & evidence

ORD record
ord-39357ed0a96a4f6ebfd0a87d2c8afdf3
Source dataset
uspto-grants-2011_02
Patent number
US07880020B2

Reaction notes

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