Sodium Hydroxide → HCID 136064508, compound

HRID 1969930Notes

Reaction equation

HRID 1969930 reaction equation
[C:1](=O)([O:32]C1C=CC([N+]([O-])=O)=CC=1)[O:2][C@@H:3]1[CH2:7][C@H:6]([C:8]2[N:12]3[C:13]4[CH:19]=[CH:18][N:17](S(C5C=CC(C)=CC=5)(=O)=O)[C:14]=4[N:15]=[CH:16][C:11]3=[N:10][N:9]=2)[C@H:5]([CH2:30][CH3:31])[CH2:4]1.[CH:43]1([NH2:47])[CH2:46][CH2:45][CH2:44]1.[OH-].[Na+]>O1CCOCC1>[CH:43]1([NH:47][C:1](=[O:32])[O:2][C@@H:3]2[CH2:7][C@H:6]([C:8]3[N:12]4[C:13]5[CH:19]=[CH:18][NH:17][C:14]=5[N:15]=[CH:16][C:11]4=[N:10][N:9]=3)[C@H:5]([CH2:30][CH3:31])[CH2:4]2)[CH2:46][CH2:45][CH2:44]1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 75645CyclobutylamineHCID 58558041HCID 58558041, compound

Product 1

HCID 136064508HCID 136064508, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
60 °C

Procedure

A solution of a scalemic mixture enriched in (1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl 4-nitrophenyl carbonate (0.150 g, 0.254 mmol) in 1,4-dioxane (1 mL) was added to a solution of cyclobutanamine (0.090 g, 1.27 mmol) in 1,4-dioxane (0.2 mL). After about 1 h, aqueous NaOH (1 N, 1.5 mL, 1.50 mmol) was added and the reaction mixture was heated at about 60° C. for about 2 h before cooling to rt. The organic solvent was removed under reduced pressure. The resulting aqueous layer mixture was acidified with AcOH to pH about 5 and extracted with DCM (3×5 mL). The combined organic extracts were concentrated under reduced pressure. The residue was purified by preparative HPLC (Table 1 method d) to give (1S,3R,4S)-3-ethyl-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl cyclobutylcarbamate (0.0468 g, 50%): LC/MS (Table 1, Method c) Rt=1.17 min; MS m/z: 369 (M+H)+.

Workup

  1. temperaturebefore cooling to rt
  2. customThe organic solvent was removed under reduced pressure
  3. extractionextracted with DCM (3×5 mL)
  4. concentrationThe combined organic extracts were concentrated under reduced pressure
  5. customThe residue was purified by preparative HPLC (Table 1 method d)

Sources & evidence

ORD record
ord-a488df86401747a686aeac604183fb85
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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