Toluene → HCID 178453989, compound

HRID 707441Notes

Reaction equation

HRID 707441 reaction equation
O[C@@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4][CH2:3]1.[CH:16]1([N:19]2[C:23]3=[N:24][CH:25]=[CH:26][N:27]=[C:22]3[NH:21][C:20]2=[O:28])[CH2:18][CH2:17]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.C1(C)C=CC=CC=1>C1COCC1>[C:12]([O:11][C:9](=[O:10])[NH:8][C@H:5]1[CH2:6][CH2:7][C@H:2]([N:21]2[C:22]3=[N:27][CH:26]=[CH:25][N:24]=[C:23]3[N:19]([CH:16]3[CH2:17][CH2:18]3)[C:20]2=[O:28])[CH2:3][CH2:4]1)([CH3:15])([CH3:14])[CH3:13]

Participants

7

Reactant 5

HCID 1140TolueneHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 866941511-CYCLOPROPYL-1H-IMIDAZO[4,5-b]PYRAZIN-2(3H)-ONEHCID 178418813HCID 178418813, compound

Product 1

HCID 178453989HCID 178453989, compoundYield 61.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a cooled solution (0° C.) of tert-butyl cis-4-hydroxycyclohexanecarbamate (0.682 g, 3.17 mmol, Biofine International), 1-cyclopropyl-1H-imidazo[4,5-b]pyrazin-2(3H)-one (0.5578 g, 3.17 mmol), and triphenylphosphine (1.100 ml, 4.75 mmol, Sigma-Aldrich Chemical Company) in THF (17.49 ml) was added diethyl azodicarboxylate, 40 wt. % solution in toluene (1.870 ml, 4.75 mmol, Chem Impex International) dropwise. After 10 mins, the round bottomed flask was removed from the ice bath and allowed to warm to room temperature to stir. Reaction was allowed to stir for 5 h and was then concentrated in vacuo. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage SNAP HP-silica gel column (50 g), eluting with a gradient of 10% to 100% EtOAc in hexane, to provide the title compound (0.7301 g, 1.955 mmol, 61.7% yield). LCMS showed product peak at 2.13 min (m+1=374.0). NMR showed some biproduct from DEAD reagent. Product was carried on without further purification.

Workup

  1. customthe round bottomed flask was removed from the ice bath
  2. customReaction
  3. stirringto stir for 5 h
  4. concentrationwas then concentrated in vacuo
  5. customchromatographed through a Biotage SNAP HP-silica gel column (50 g)
  6. washeluting with a gradient of 10% to 100% EtOAc in hexane

Sources & evidence

ORD record
ord-19cf98a4e26e4cc8b778d2da97a23a90
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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