Ethyl Acetate → N-(2-Amino-6-methylpyridin-3-ylmethyl)-N-(4-hydroxy-1-methyl-2-propyldisulfanylbut-1-enyl)formamide

HRID 1360833Notes

Reaction equation

HRID 1360833 reaction equation
[NH2:1][C:2]1[C:7]([CH2:8][N:9]([C:12]([CH3:37])=[C:13](SSC(CCO)=C(NC(CC2C(N)=NC(C)=CC=2)=O)C)[CH2:14][CH2:15][OH:16])[CH:10]=[O:11])=[CH:6][CH:5]=[C:4]([CH3:38])[N:3]=1.[CH2:39]([S:42][S:43]CCC)[CH2:40][CH3:41].[OH-].[Na+].C(OCC)(=O)C>CO.O.C(Cl)(Cl)Cl>[NH2:1][C:2]1[C:7]([CH2:8][N:9]([C:12]([CH3:37])=[CH:13][CH2:14][CH:15]([S:43][S:42][CH2:39][CH2:40][CH3:41])[OH:16])[CH:10]=[O:11])=[CH:6][CH:5]=[C:4]([CH3:38])[N:3]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 12377Dipropyl disulfideHCID 14798Sodium HydroxideHCID 86616941N-(2-amino-6-methylpyridin-3-ylmethyl)-N-{2-[2-[(2-amino-6-methyl-pyridin-3-ylmethyl)formylamino]-1-(2-hydroxyethyl)-propenyldisulfanyl]-4-hydroxy-1-methylbut-1-enyl}formamide

Product 1

HCID 86616940N-(2-Amino-6-methylpyridin-3-ylmethyl)-N-(4-hydroxy-1-methyl-2-propyldisulfanylbut-1-enyl)formamideYield 81.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 962WaterSolventHCID 6212ChloroformSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of N-(2-amino-6-methylpyridin-3-ylmethyl)-N-{2-[2-[(2-amino-6-methyl-pyridin-3-ylmethyl)formylamino]-1-(2-hydroxyethyl)-propenyldisulfanyl]-4-hydroxy-1-methylbut-1-enyl}formamide (250 mg, 0.45 mmol) and propyl disulfide (0.21 mL, 1.34 mmol) in methanol (3 ml) was added 1 molar aqueous sodium hydroxide (0.089 mL, 0.089 mmol). The resulting solution was stirred at 35-45° C. for 18 hr. The solution was diluted with water (10 mL) and chloroform (10 mL), but the product remained as a milky insoluble layer. Addition of ethyl acetate (10 mL) and methanol (2 mL) resulted in the formation of two clear layers. The product was contained in the lower layer. This layer was washed with brine (10 mL) dried over sodium sulfate, and evaporated. The residual oil was dissolved in chloroform (1 mL) and chromatographed on silica gel (Waters Sep-Pak 5 g column, using 97.5/2.5 chloroform/methanol as eluent, Fraction size 9 mL). Fractions 4-9 were pooled and evaporated to give 130 mg (41%) of the title compound as nearly colorless oil. MS (LCMS): 356.0 (M+H)+. 1H NMR (CDCl3) δ 0.95 (t, 3H), 1.55 (m, 3H), 1.97 (s, 3H), 2.35 (s, 3H), 2.42 (t, 2H), 2.84 (t, 2H) 3.76 (t, 2H), 5.36 (br. s, 1H), 6.35 (d, 1H), 7.02 (d, 1H), 7.96 (s, 1H).

Workup

  1. customresulted in the formation of two clear layers
  2. washThis layer was washed with brine (10 mL)
  3. dry with materialdried over sodium sulfate
  4. customevaporated
  5. dissolutionThe residual oil was dissolved in chloroform (1 mL)
  6. customchromatographed on silica gel (Waters Sep-Pak 5 g column, using 97.5/2.5 chloroform/methanol as eluent, Fraction size 9 mL)
  7. customevaporated

Sources & evidence

ORD record
ord-d24d588c57824ce5a9a788ce8ddbb71f
Source dataset
uspto-grants-2011_02
Patent number
US07879885B2

Reaction notes

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