1,3-Propanedithiol → 6-Cyclopropylmethoxy-5-pyrrolidin-1-yl-pyridine-2-carboxylic acid ((S)-1-aminomethyl-3-methyl-butyl)-amide

HRID 927809Notes

Reaction equation

HRID 927809 reaction equation
[N:1]([CH2:4][C@@H:5]([NH:10][C:11]([C:13]1[CH:18]=[CH:17][C:16]([N:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)=[C:15]([O:24][CH2:25][CH:26]2[CH2:28][CH2:27]2)[N:14]=1)=[O:12])[CH2:6][CH:7]([CH3:9])[CH3:8])=[N+]=[N-].C(N(CC)CC)C.C(S)CCS.[BH4-].[Na+]>CC(O)C>[NH2:1][CH2:4][C@@H:5]([NH:10][C:11]([C:13]1[CH:18]=[CH:17][C:16]([N:19]2[CH2:20][CH2:21][CH2:22][CH2:23]2)=[C:15]([O:24][CH2:25][CH:26]2[CH2:27][CH2:28]2)[N:14]=1)=[O:12])[CH2:6][CH:7]([CH3:8])[CH3:9]

Participants

6

Reactant 4

HCID 80131,3-PropanedithiolHCID 8471TriethylamineHCID 4311764Sodium borohydrideHCID 711057256-Cyclopropylmethoxy-5-pyrrolidin-1-yl-pyridine-2-carboxylic acid ((S)-1-azidomethyl-3-methyl-butyl)-amide

Product 1

HCID 711057266-Cyclopropylmethoxy-5-pyrrolidin-1-yl-pyridine-2-carboxylic acid ((S)-1-aminomethyl-3-methyl-butyl)-amideYield 32%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

6-Cyclopropylmethoxy-5-pyrrolidin-1-yl-pyridine-2-carboxylic acid ((S)-1-azidomethyl-3-methyl-butyl)-amide (107 mg, 277 μmol) was combined with 2-propanol (725 μl) to give an off-white suspension. To this suspension was added triethylamine (56.0 mg, 77.2 μl, 554 μmol), 1,3-propanedithiol (3.00 mg, 2.8 μl, 27.7 μmol) and sodium borohydride (15.7 mg, 415 μmol). The resulting reaction mixture was stirred at room temperature for 20 hours. Volatiles were removed in vacuo and the residue was stirred with 10% citric acid solution (5 mL) and a mixture of ethyl acetate/heptane (5 mL, 1:1). The aqueous layer was brought with 2N NaOH to pH=12 and extracted twice with ethyl acetate. The organic phases were combined, dried with Na2SO4, and concentrated in vacuo to give the title compound (32 mg, 32%) as colorless, viscous oil that was used without further purification in the next step; MS (ESI) 361.3 (M+H)+.

Workup

  1. customto give an off-white suspension
  2. customThe resulting reaction mixture
  3. customVolatiles were removed in vacuo
  4. stirringthe residue was stirred with 10% citric acid solution (5 mL)
  5. additiona mixture of ethyl acetate/heptane (5 mL, 1:1)
  6. extractionextracted twice with ethyl acetate
  7. dry with materialdried with Na2SO4
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-124e76c3a0994dfaba6940a46ee855d3
Source dataset
uspto-grants-2016_03
Patent number
US09290451B2

Reaction notes

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