Tributylphosphine → 1-(2-ethyl-4-(2,2,2-trifluoroethylthio)cyclopentyl)-6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine

HRID 1969654Notes

Reaction equation

HRID 1969654 reaction equation
CC(OC(/N=N/C(OC(C)C)=O)=O)C.P(CCCC)(CCCC)CCCC.[CH2:28]([CH:30]1[CH:34]([C:35]2[N:39]3[C:40]4[CH:46]=[CH:45][N:44]([CH2:47][O:48][CH2:49][CH2:50][Si:51]([CH3:54])([CH3:53])[CH3:52])[C:41]=4[N:42]=[CH:43][C:38]3=[N:37][N:36]=2)[CH2:33][CH:32](O)[CH2:31]1)[CH3:29].[F:56][C:57]([F:61])([F:60])[CH2:58][SH:59]>C1COCC1>[CH2:28]([CH:30]1[CH2:31][CH:32]([S:59][CH2:58][C:57]([F:61])([F:60])[F:56])[CH2:33][CH:34]1[C:35]1[N:39]2[C:40]3[CH:46]=[CH:45][N:44]([CH2:47][O:48][CH2:49][CH2:50][Si:51]([CH3:52])([CH3:54])[CH3:53])[C:41]=3[N:42]=[CH:43][C:38]2=[N:37][N:36]=1)[CH3:29]

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 41339242,2,2-TrifluoroethanethiolHCID 5363146Diisopropyl azodicarboxylateHCID 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 585574931-(2-ethyl-4-(2,2,2-trifluoroethylthio)cyclopentyl)-6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazineYield 44.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

An oven-dried flask was charged with DIAD (0.177 mL, 0.896 mmol) and THF (3.74 mL). The reaction flask was cooled to 0° C. before the addition of P(n-Bu)3 (0.221 mL, 0.896 mmol), 3-ethyl-4-(6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanol (0.300 g, 0.747 mmol, prepared from Preparation #20 using KK and SS), TEA (0.125 mL, 0.896 mmol) and 2,2,2-trifluoroethanthiol (0.080 mL, 0.896 mmol). The reaction was stirred at ambient temperature for about 16 h. The reaction mixture was partitioned between water (10 mL) and EtOAc (10 mL). The aqueous layer was extracted with EtOAc (3×10 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concd under reduced pressure to afford a crude oil. The crude material was purified by silica gel chromatography eluting with a gradient of 0-60% EtOAc in DCM to afford 1-(2-ethyl-4-(2,2,2-trifluoroethylthio)cyclopentyl)-6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine (0.165 g, 44%) as an orange solid: LC/MS (Table 1, Method a) Rt=3.02 min; MS m/z: 500 (M+H)+.

Workup

  1. customThe reaction mixture was partitioned between water (10 mL) and EtOAc (10 mL)
  2. extractionThe aqueous layer was extracted with EtOAc (3×10 mL)
  3. dry with materialThe combined organic layers were dried over anhydrous MgSO4
  4. filtrationfiltered
  5. customconcd under reduced pressure to afford a crude oil
  6. customThe crude material was purified by silica gel chromatography
  7. washeluting with a gradient of 0-60% EtOAc in DCM

Sources & evidence

ORD record
ord-3b48e0e1df3547128639db02662b1150
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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