HCID 58558018, compound → HCID 58557504, compound

HRID 1969677Notes

Reaction equation

HRID 1969677 reaction equation
[S:1]([N:11]1[C:15]2=[N:16][CH:17]=[C:18]([NH:20][CH2:21][C:22]([CH:24]3[CH2:40][C:26]4([CH2:29][N:28]([S:30]([C:33]5[CH:39]=[CH:38][C:36]([CH3:37])=[CH:35][CH:34]=5)(=[O:32])=[O:31])[CH2:27]4)[CH2:25]3)=O)[N:19]=[C:14]2[CH:13]=[CH:12]1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2]>CC#N>[S:1]([N:11]1[C:15]2[N:16]=[CH:17][C:18]3[N:19]([C:22]([CH:24]4[CH2:40][C:26]5([CH2:29][N:28]([S:30]([C:33]6[CH:39]=[CH:38][C:36]([CH3:37])=[CH:35][CH:34]=6)(=[O:32])=[O:31])[CH2:27]5)[CH2:25]4)=[CH:21][N:20]=3)[C:14]=2[CH:13]=[CH:12]1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2]

Participants

3

Reactant 1

HCID 58558018HCID 58558018, compound

Product 1

HCID 58557504HCID 58557504, compoundYield 76.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)-1-(2-tosyl-2-azaspiro[3.3]heptan-6-yl)ethanone (0.631 g, 1.089 mmol, prepared using R with 2-tosyl-2-azaspiro[3.3]heptane-6-carboxylic acid [prepared as described in J. Org. Chem, 2010, 75, 5941] and trimethylsilyl diazomethane, S with Example #3 Step E, E with TFA) in MeCN (5 mL) was added PFPAA (2.15 mL, 10.9 mmol). The mixture was heated at about 60° C. for about 2 h. The reaction mixture was partitioned between DCM (30 mL) and saturated aqueous NaHCO3 (50 mL). The layers were separated and the aqueous layer was extracted further with DCM (2×30 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated to dryness under reduced pressure. The crude material was purified using silica gel flash chromatography eluting with a gradient of 50-100% EtOAc in heptane to give 3-tosyl-8-(2-tosyl-2-azaspiro[3.3]heptan-6-yl)-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazine (0.467 g, 76%) as a white solid: LC/MS (Table 1, Method b) Rt=2.53 min; MS m/z 562 (M+H)+.

Workup

  1. customThe reaction mixture was partitioned between DCM (30 mL) and saturated aqueous NaHCO3 (50 mL)
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted further with DCM (2×30 mL)
  4. dry with materialThe combined organic layers were dried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under reduced pressure
  7. customThe crude material was purified
  8. washeluting with a gradient of 50-100% EtOAc in heptane

Sources & evidence

ORD record
ord-937db35f7cab4d32a59159b552c868a5
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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