Potassium Hydroxide → HCID 67997989, compound

HRID 1969674Notes

Reaction equation

HRID 1969674 reaction equation
[CH2:1]([CH:3]1[CH:7]([C:8]2[N:12]3[C:13]4[CH:19]=[CH:18][N:17]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:14]=4[N:15]=[CH:16][C:11]3=[N:10][N:9]=2)[CH2:6][CH:5]([OH:28])[CH2:4]1)[CH3:2].[OH-].[K+].O1CCOCC1.Br[CH2:38][C:39]1[CH:43]=[C:42]([CH3:44])[O:41][N:40]=1>CCCC[N+](CCCC)(CCCC)CCCC.[Br-].O.CCOC(C)=O>[CH2:1]([C@H:3]1[C@@H:7]([C:8]2[N:12]3[C:13]4[CH:19]=[CH:18][N:17]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:26])([CH3:25])[CH3:27])[C:14]=4[N:15]=[CH:16][C:11]3=[N:10][N:9]=2)[CH2:6][C@H:5]([O:28][CH2:38][C:39]2[CH:43]=[C:42]([CH3:44])[O:41][N:40]=2)[CH2:4]1)[CH3:2]

Participants

8

Reactant 4

HCID 14797Potassium Hydroxide2×HCID 312751,4-DioxaneHCID 27763043-(Bromomethyl)-5-methylisoxazole2×HCID 585572033-ethyl-4-(6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanol

Product 1

HCID 67997989HCID 67997989, compoundYield 72%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 3-ethyl-4-(6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanol (0.072 g, 0.179 mmol, Example #35, Step H), KOH aqueous (50% w/v 0.118 g, 2.10 mmol) and 1,4-dioxane (0.1 mL) was heated to about 70° C. To the reaction mixture was added 3-(bromomethyl)-5-methylisoxazole (0.063 g, 0.359 mmol, Maybridge) and TBAB (0.004 g, 0.01 mmol) and the reaction mixture was stirred for about 24 h. To the reaction mixture was added 3-(bromomethyl)-5-methylisoxazole (0.063 g, 0.36 mmol, Maybridge) and aqueous KOH (50% w/v 0.118 g, 2.10 mmol) and stirring was continued for about 24 h. The reaction was cooled to ambient temperature and EtOAc (10 mL) and water (5 mL) were added. The layers were separated and the aqueous layer was extracted with EtOAc (10 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concd under reduced pressure. The crude material was purified by silica gel chromatography eluting with a gradient of 0-5% MeOH in DCM to give 3-(((1R,3R,4S)-3-ethyl-4-(6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyloxy)methyl)-5-methylisoxazole (0.064 g, 72%): LC/MS (Table 1, Method b) Rt=2.58 min; MS m/z: 497 (M+H)+.

Workup

  1. stirringstirring
  2. waitwas continued for about 24 h
  3. temperatureThe reaction was cooled to ambient temperature
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with EtOAc (10 mL)
  6. dry with materialThe combined organic layers were dried over anhydrous MgSO4
  7. filtrationfiltered
  8. customThe crude material was purified by silica gel chromatography
  9. washeluting with a gradient of 0-5% MeOH in DCM

Sources & evidence

ORD record
ord-016ff4c9ba6647d0b87df8cd82b17c22
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

Loading…