Tetrahydrofuran → 3-ethyl-4-(6((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamine

HRID 1969683Notes

Reaction equation

HRID 1969683 reaction equation
[N:1]([CH:4]1[CH2:8][CH:7]([C:9]2[N:13]3[C:14]4[CH:20]=[CH:19][N:18]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:15]=4[N:16]=[CH:17][C:12]3=[N:11][N:10]=2)[CH:6]([CH2:29][CH3:30])[CH2:5]1)=[N+]=[N-].C1COCC1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O.CCOC(C)=O>[CH2:29]([CH:6]1[CH:7]([C:9]2[N:13]3[C:14]4[CH:20]=[CH:19][N:18]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:26])([CH3:28])[CH3:27])[C:15]=4[N:16]=[CH:17][C:12]3=[N:11][N:10]=2)[CH2:8][CH:4]([NH2:1])[CH2:5]1)[CH3:30]

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 11776TriphenylphosphineHCID 585579061-(-4-azido-2-ethylcyclopentyl)-6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine

Product 1

HCID 672172213-ethyl-4-(6((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamineYield 80.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

A round bottom flask was charged with 1-(-4-azido-2-ethylcyclopentyl)-6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine (0.650 g, 1.52 mmol, prepared using D from Preparation #25 with NaOH, KK, P with NaBH4, IIII, JJJJ with NaN3), THF (8.0 mL), and water (1.6 mL). To the flask was added triphenylphosphine (0.480 g, 1.83 mmol). The reaction mixture was heated to about 45° C. for about 7 h. The reaction mixture was cooled to room temperature and EtOAc (20 mL) and water (15 mL) were added. The layers were separated and the organic solution was dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to give an oil that solidified upon standing. The crude material was purified via flash silica gel chromatography eluting with a gradient of 1-10% DCM/MeOH/DEA (900:90:10) in DCM. The product containing fractions were combined and concentrated under reduced pressure to give an oil that was then dried on a vacuum pump overnight to give 3-ethyl-4-(6((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamine as a tacky oil (0.49 g, 80%): LC/MS (Table 1, Method b) Rt=1.85 min; MS m/z 401 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe layers were separated
  3. dry with materialthe organic solution was dried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto give an oil that
  7. customThe crude material was purified via flash silica gel chromatography
  8. washeluting with a gradient of 1-10% DCM/MeOH/DEA (900:90:10) in DCM
  9. additionThe product containing fractions
  10. concentrationconcentrated under reduced pressure
  11. customto give an oil that
  12. customwas then dried on a vacuum pump overnight

Sources & evidence

ORD record
ord-5d7ee0260d95413c8e37e5d0cc0e10d1
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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