Methylhydrazine → HCID 117678143, compound

HRID 931349Notes

Reaction equation

HRID 931349 reaction equation
[CH3:1]NN.[CH:4]1([C:7]2[N:8](C)[N:9]=[C:10]3[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][C:11]=23)[CH2:6][CH2:5]1>CO>[CH:4]1([C:7]2[C:11]3[CH2:12][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:14][CH2:15][C:10]=3[N:9]([CH3:1])[N:8]=2)[CH2:6][CH2:5]1

Participants

4

Reactant 2

HCID 6061MethylhydrazineHCID 117678189HCID 117678189, compound

Product 1

HCID 117678143HCID 117678143, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of C28 (100 g, 0.374 mol) in methanol (1.2 L) was added methylhydrazine (40% solution in water, 47.4 g, 0.411 mol). The reaction mixture was heated at reflux for 2 hours, then concentrated to dryness. Purification via silica gel chromatography (Gradient: 5% to 9% ethyl acetate in petroleum ether) provided a mixture of product C49 and tert-butyl 3-cyclopropyl-2-methyl-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxylate (C50). LCMS m/z 278.0 [M+H]+. Separation via supercritical fluid chromatography (Column: Chiral Technologies, Chiralcel OJ-H, 5 um; Eluent: 97:3 carbon dioxide/methanol) afforded the product C49 as the second-eluting isomer, isolated as a solid. NOE studies supported the indicated regiochemical assignment. Yield: 33 g, 120 mmol, 32%. 1H NMR (400 MHz, CDCl3) δ 4.40 (br s, 2H), 3.65-3.73 (br m, 2H), 3.65 (s, 3H), 2.57-2.64 (m, 2H), 1.68-1.76 (m, 1H), 1.49 (s, 9H), 0.77-0.89 (m, 4H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 2 hours
  3. concentrationconcentrated to dryness
  4. customPurification via silica gel chromatography (Gradient: 5% to 9% ethyl acetate in petroleum ether)
  5. customprovided
  6. additiona mixture of product
  7. customSeparation via supercritical fluid chromatography (Column: Chiral Technologies, Chiralcel OJ-H, 5 um; Eluent: 97:3 carbon dioxide/methanol)
  8. customafforded the product C49 as the second-eluting isomer
  9. customisolated as a solid

Sources & evidence

ORD record
ord-0c22138510c24643b48b2d7fe13b012f
Source dataset
uspto-grants-2016_03
Patent number
US09296761B2

Reaction notes

Loading…