Ethanol → HCID 178470866, compound

HRID 1955640Notes

Reaction equation

HRID 1955640 reaction equation
[CH:1]1([CH2:7][N:8]2[C:16](=[O:17])[C:15]3[N:14]=[C:13]([C:18]4[CH:28]=[CH:27][C:21](/[CH:22]=[CH:23]/[C:24]([OH:26])=[O:25])=[CH:20][CH:19]=4)[NH:12][C:11]=3[N:10]([CH2:29][CH:30]3[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]3)[C:9]2=[O:36])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:37]1COC[CH2:38]1.C(O)C.C1CCN2C(=NCCC2)CC1>CN(C=O)C>[CH2:37]([O:25][C:24](=[O:26])/[CH:23]=[CH:22]/[C:21]1[CH:20]=[CH:19][C:18]([C:13]2[NH:12][C:11]3[N:10]([CH2:29][CH:30]4[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]4)[C:9](=[O:36])[N:8]([CH2:7][CH:1]4[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]4)[C:16](=[O:17])[C:15]=3[N:14]=2)=[CH:28][CH:27]=1)[CH3:38]

Participants

6

Reactant 4

HCID 702Ethanol2×HCID 8028TetrahydrofuranHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 178525288HCID 178525288, compound

Product 1

HCID 178470866HCID 178470866, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N,N'-Carbonyldiimidazole (Lancaster Synthesis, 908 mg, 5.6 mmol) was added to a pale yellow slurry of (E)-4-[1,3 bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl]cinnamic acid (from step (d) example 1, 1.962 g, 4.0 mmol) in anhydrous DMF (15 mL)-THF (15 mL) under nitrogen. The slurry was stirred for 3.75 h, during which time it became bright yellow as a gas evolved. Absolute ethanol (460 mL, 8 mmol) was then added, followed by DBU (Aldrich, 837 mL, 5.6 mmol). Addition of the base produced a deep red reaction mixture and caused almost complete dissolution of the acyl imidazole. After stirring for 18 h, the reaction mixture was treated with an additional equivalent of absolute ethanol (230 mL, 4 mmol). The orange solution was stirred for 2.5 h before volatiles were removed at 1Torr. The resulting brown mixture was chromatographed on silica gel, eluting with a gradient from 0-6% methanol in dichloromethane. The title compound eluted in 0-1% methanol in dichloromethane as an off-white solid (1.643 g, 79%). Recrystallization from dichloromethane-hexanes provided a white powder (1.501 g, 72%), m.p. >300° C.; 1H-NMR (DMSO-d6) consistent with structure.

Workup

  1. additionAddition of the base
  2. customproduced
  3. customa deep red reaction mixture
  4. stirringAfter stirring for 18 h
  5. stirringThe orange solution was stirred for 2.5 h before volatiles
  6. customwere removed at 1Torr
  7. customThe resulting brown mixture was chromatographed on silica gel
  8. washeluting with a gradient from 0-6% methanol in dichloromethane
  9. washThe title compound eluted in 0-1% methanol in dichloromethane as an off-white solid (1.643 g, 79%)
  10. customRecrystallization from dichloromethane-hexanes

Sources & evidence

ORD record
ord-c0e7ad5a1f40418ba46cc6a9a061bb72
Source dataset
uspto-grants-1998_07
Patent number
US05776940

Reaction notes

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