Water → 6-Cyclopropylmethoxy-5-pyrrolidin-1-yl-pyridine-2-carboxylic acid {(S)-3-methyl-1-[(7-nitro-benzo[1,2,5]oxadiazol-4-ylamino)-methyl]-butyl}-amide

HRID 927810Notes

Reaction equation

HRID 927810 reaction equation
[NH2:1][CH2:2][C@@H:3]([NH:8][C:9]([C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)=[C:13]([O:22][CH2:23][CH:24]2[CH2:26][CH2:25]2)[N:12]=1)=[O:10])[CH2:4][CH:5]([CH3:7])[CH3:6].[N+:27]([C:30]1[C:35]2=[N:36][O:37][N:38]=[C:34]2[C:33](N)=[CH:32][CH:31]=1)([O-:29])=[O:28].O>C1COCC1>[CH3:7][CH:5]([CH3:6])[CH2:4][C@H:3]([NH:8][C:9]([C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH2:18][CH2:19][CH2:20][CH2:21]2)=[C:13]([O:22][CH2:23][CH:24]2[CH2:25][CH2:26]2)[N:12]=1)=[O:10])[CH2:2][NH:1][C:33]1[C:34]2=[N:38][O:37][N:36]=[C:35]2[C:30]([N+:27]([O-:29])=[O:28])=[CH:31][CH:32]=1

Participants

5

Reactant 3

HCID 962WaterHCID 6018944-Amino-7-nitrobenzofurazanHCID 711057266-Cyclopropylmethoxy-5-pyrrolidin-1-yl-pyridine-2-carboxylic acid ((S)-1-aminomethyl-3-methyl-butyl)-amide

Product 1

HCID 866748006-Cyclopropylmethoxy-5-pyrrolidin-1-yl-pyridine-2-carboxylic acid {(S)-3-methyl-1-[(7-nitro-benzo[1,2,5]oxadiazol-4-ylamino)-methyl]-butyl}-amideYield 57.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a colorless solution of 6-cyclopropylmethoxy-5-pyrrolidin-1-yl-pyridine-2-carboxylic acid ((S)-1-aminomethyl-3-methyl-butyl)-amide (30 mg, 83.2 μmol) in THF (555 μl) was added 7-nitro-2,1,3-benzoxadiazol-4-amine (CAN 10199-91-4, 19.9 mg, 100 μmol). The reaction mixture was stirred at room temperature for 30 minutes, followed by stirring at reflux temperature for 2 hours. After cooling to room temperature the mixture was poured into water (20 mL) and extracted with ethyl acetate (20 mL). The organic phase was washed with brine; and the aqueous phases were extracted with ethyl acetate. The organic phases were combined, dried with Na2SO4, and concentrated in vacuo. The black, solid residue was purified by flash chromatography (basic silica gel, 10 g, 0% to 100% ethyl acetate in a 1:1 mixture of dichloromethane and heptane) to give the title compound (25 mg, 57%) as brown solid; LC-MS (UV peak area/ESI) 100%, 524.2609 (M+H)+.

Workup

  1. stirringby stirring
  2. temperatureat reflux temperature for 2 hours
  3. temperatureAfter cooling to room temperature the mixture
  4. extractionextracted with ethyl acetate (20 mL)
  5. washThe organic phase was washed with brine
  6. extractionand the aqueous phases were extracted with ethyl acetate
  7. dry with materialdried with Na2SO4
  8. concentrationconcentrated in vacuo
  9. customThe black, solid residue was purified by flash chromatography (basic silica gel, 10 g, 0% to 100% ethyl acetate
  10. additionin a 1:1 mixture of dichloromethane and heptane)

Sources & evidence

ORD record
ord-b116ddedd45948d08ef442cd5dfd6b88
Source dataset
uspto-grants-2016_03
Patent number
US09290451B2

Reaction notes

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