Sodium Hydroxide → HCID 136009251, compound

HRID 1969894Notes

Reaction equation

HRID 1969894 reaction equation
[CH2:1]([C@H:3]1[C@@H:7]([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)[CH2:6][N:5]([C:30]([NH:32][CH2:33][C:34]([F:37])([F:36])[F:35])=[O:31])[CH2:4]1)[CH3:2].[OH-].[Na+]>O1CCOCC1>[CH2:1]([C@H:3]1[C@@H:7]([C:8]2[N:12]3[C:13]4[CH:19]=[CH:18][NH:17][C:14]=4[N:15]=[CH:16][C:11]3=[N:10][N:9]=2)[CH2:6][N:5]([C:30]([NH:32][CH2:33][C:34]([F:37])([F:36])[F:35])=[O:31])[CH2:4]1)[CH3:2]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 67216455HCID 67216455, compound

Product 1

HCID 136009251HCID 136009251, compoundYield 14.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of (cis)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide (0.306 g, 0.571 mmol) in 1,4-dioxane (10 mL) was added aqueous NaOH (1 N, 1.50 mL, 1.50 mmol). The reaction was heated at about 50° C. for about 1 h. The layers were partitioned between DCM (25 mL) and water (10 mL). The aqueous layer was acidified with 20% aqueous citric acid to about pH 4 and extracted with DCM (4×25 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concd under reduced pressure to give a brown residue. The crude material was purified by flash chromatography on silica gel eluting with a gradient of 0-10% MeOH in DCM to give a racemic mixture of products as a brown residue. The compound was further purified using chiral preparative HPLC (Table 2, Method 55) to afford (3S,4R)-3-ethyl-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide (Rt=14.5 min, or =negative) (0.031 g, 14%)[Example #36]: LC/MS (Table 1, Method a) Rt=1.62 min; MS m/z: 382 (M+H)1 and (3R,4S)-3-ethyl-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide (Rt=17.3 min, or =positive) (0.033 g, 15%)[Example #37]: LC/MS (Table 1, Method a) Rt=1.62 min; MS m/z: 382 (M+H)+.

Workup

  1. customThe layers were partitioned between DCM (25 mL) and water (10 mL)
  2. extractionextracted with DCM (4×25 mL)
  3. dry with materialThe combined organic layers were dried over anhydrous MgSO4
  4. filtrationfiltered
  5. customconcd under reduced pressure to give a brown residue
  6. customThe crude material was purified by flash chromatography on silica gel eluting with a gradient of 0-10% MeOH in DCM
  7. customto give
  8. additiona racemic mixture of products as a brown residue
  9. customThe compound was further purified

Sources & evidence

ORD record
ord-95549ae8f5d141bcbf2b2c60f6608756
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

Loading…