Trimethyl orthoformate → HCID 68681006, compound

HRID 2245843Notes

Reaction equation

HRID 2245843 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[C:16]([C:22]([NH:24][NH2:25])=O)=[N:17][CH:18]=[C:19]([Cl:21])[CH:20]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH:26](OC)(OC)OC.C(OC)(=O)NN.[C:39]([N:46]1[CH2:50][CH2:49][CH:48]([NH2:51])[CH2:47]1)([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40]>O1CCOCC1.CC(O)=O>[C:42]([O:41][C:39]([N:46]1[CH2:50][CH2:49][CH:48]([N:51]2[CH:26]=[N:25][N:24]=[C:22]2[C:16]2[C:15]([NH:14][S:11]([C:8]3[CH:9]=[CH:10][C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])=[CH:6][CH:7]=3)(=[O:13])=[O:12])=[CH:20][C:19]([Cl:21])=[CH:18][N:17]=2)[CH2:47]1)=[O:40])([CH3:45])([CH3:44])[CH3:43]

Participants

7

Reactant 4

HCID 9005Trimethyl orthoformateHCID 80519Methyl carbazateHCID 27563701-Boc-3-aminopyrrolidineHCID 59216816HCID 59216816, compound

Product 1

HCID 68681006HCID 68681006, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A 25 mL scintillation vial was charged with 4-tert-butyl-N-(5-chloro-2-hydrazinocarbonyl-pyridin-3-yl)-benzenesulfonamide (191 mg, 0.50 mmol), trimethyl orthoformate (0.072 mL, 0.65 mmol), AcOH (0.60 mL), and dioxane (1.5 mL). The vial was sealed, heated to 110° C., and stirred overnight. The following day, the intermediate methyl carbazate was observed at m/z 425 (via LCMS). 1-Boc-3-aminopyrrolidine (187 mg, 1.0 mmol) was subsequently added and the reaction continued at 110° C. until LCMS analysis indicated consumption of the oxadiazole intermediate. The volatiles were subsequently evacuated in vacuo and the residue was purified via reverse-phase HPLC to provide 3-{3-[3-(4-tert-butyl-benzenesulfonylamino)-5-chloro-pyridin-2-yl]-[1,2,4]triazol-4-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester as a white solid: MS (ES) M+H expected 561.1, found 561.1.

Workup

  1. customThe vial was sealed
  2. customcontinued at 110° C. until LCMS analysis
  3. customconsumption of the oxadiazole intermediate
  4. customThe volatiles were subsequently evacuated in vacuo
  5. customthe residue was purified via reverse-phase HPLC

Sources & evidence

ORD record
ord-beb513d5c8054af791fb96855fbb5e52
Source dataset
uspto-grants-2010_03
Patent number
US07683176B2

Reaction notes

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