Hydroxyamine hydrochloride → HCID 58997139, compound

HRID 251025Notes

Reaction equation

HRID 251025 reaction equation
[NH2:1][OH:2].Cl.C[O:5][C:6](=O)[CH2:7][CH2:8][CH2:9][CH2:10][N:11]([CH2:20][C:21]1[C:26]([CH3:27])=[CH:25][CH:24]=[CH:23][N:22]=1)[CH2:12][C:13]1[C:18]([CH3:19])=[CH:17][CH:16]=[CH:15][N:14]=1>CO>[OH:2][NH:1][C:6](=[O:5])[CH2:7][CH2:8][CH2:9][CH2:10][N:11]([CH2:20][C:21]1[C:26]([CH3:27])=[CH:25][CH:24]=[CH:23][N:22]=1)[CH2:12][C:13]1[C:18]([CH3:19])=[CH:17][CH:16]=[CH:15][N:14]=1

Participants

4

Reactant 2

HCID 443297Hydroxyamine hydrochloride2×HCID 67271509HCID 67271509, compound

Product 1

HCID 58997139HCID 58997139, compoundYield 37.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a mixture of Na metal (1—mg, 4.91 mmol) in MeOH (5 mL) was added NH2OH—HCl (204 mg, 2.94 mmol) followed by a solution of 5-[Bis-(3-methyl-pyridin-2-ylmethyl)-amino]-pentanoic acid methyl ester (126 mg, 0.37 mmol) in MeOH (7 mL) and the reaction stirred 1.5 h. An additional amount of Na (134 mg, 5.83 mmol) and NH2OH—HCl (208 mg, 2.99 mmol) was then added and the mixture stirred another 40 min then quenched with water (2-3 mL). The mixture was concentrated and diluted with H2O (10 mL), saturated aqueous NaHCO3 (to pH 10) and CHCl3 (25 mL) and stirred vigorously overnight. The layers were separated and the aqueous was extracted with CHCl3 (2×15 mL). The combined organic extracts were dried (Na2SO4), concentrated and purified by radial chromatography on silica gel (1 mm plate, CH2Cl2/MeOH/NH4OH, 50:1:1 then 25:1:1 then 10:1:1) to give COMPOUND 172 (47 mg, 37%) as a white solid: 1H NMR (CDCl3) δ 1.54-1.58 (m, 4H), 2.11 (s, 6H), 2.12-2.15 (m, 2H), 2.52-2.55 (m, 2H), 3.71 (s, 4H), 7.12 (dd, 2H, J=9, 6 Hz), 7.42 (d, 2H, J=9 Hz), 8.36 (d, 2H, J=6 Hz). 13C NMR (CDCl3) δ 17.91, 21.92, 23.16, 31.68, 52.73, 57.23, 122.58, 133.61, 138.43, 145.52, 156.61, 170.55. ES-MS m/z 343 (M+H). Anal. Calcd. for C19H26N4O2.1.3CH3OH: C, 63.48; H, 8.19; N, 14.59. Found: C, 63.66; H, 8.03; N, 14.33.

Workup

  1. stirringthe mixture stirred another 40 min
  2. customthen quenched with water (2-3 mL)
  3. concentrationThe mixture was concentrated
  4. additiondiluted with H2O (10 mL), saturated aqueous NaHCO3 (to pH 10) and CHCl3 (25 mL)
  5. stirringstirred vigorously overnight
  6. customThe layers were separated
  7. extractionthe aqueous was extracted with CHCl3 (2×15 mL)
  8. dry with materialThe combined organic extracts were dried (Na2SO4)
  9. concentrationconcentrated
  10. custompurified by radial chromatography on silica gel (1 mm plate, CH2Cl2/MeOH/NH4OH, 50:1:1

Sources & evidence

ORD record
ord-5d02867c91da4ac5ae2b3c7faaee9d3f
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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