1-Hydroxybenzotriazole → HCID 178423900, compound

HRID 1169424Notes

Reaction equation

HRID 1169424 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10](/[CH:13]=[CH:14]/[C:15]([OH:17])=O)[O:11][CH:12]=2)=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.Cl.Cl.[CH3:42][N:43]([CH2:50][C@H:51]1[CH2:56][CH2:55][C@H:54]([NH2:57])[CH2:53][CH2:52]1)[CH:44]1[CH2:49][CH2:48][O:47][CH2:46][CH2:45]1.C1CCN2C(=NCCC2)CC1>C(#N)C.C(N(CC)CC)C>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:9]=[C:10](/[CH:13]=[CH:14]/[C:15]([NH:57][C@H:54]3[CH2:53][CH2:52][C@H:51]([CH2:50][N:43]([CH3:42])[CH:44]4[CH2:49][CH2:48][O:47][CH2:46][CH2:45]4)[CH2:56][CH2:55]3)=[O:17])[O:11][CH:12]=2)=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11817032HCID 11817032, compoundHCID 178484107HCID 178484107, compound

Product 1

HCID 178423900HCID 178423900, compoundYield 47.7%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 8471TriethylamineSolvent

Procedure

Into a suspension of (E)-3-[4-(4-methylphenyl) furan-2-yl]acrylic acid (150 mg) and 1-hydroxybenzotriazole (133 mg) in acetonitrile (15 ml) was added at room temperature 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (189 mg), and the resulting mixture was stirred for 2 hours. Into the reaction mixture was added a solution of trans-4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]cyclohexylamine dihydrochloride (295 mg), 1,8-diazabicyclo[5,4,0]-7-undecene (0.3 g) and triethylamine (0.18 ml) in acetonitrile (15 ml), and the resulting mixture was stirred for 4 days. After the reaction mixture was concentrated under reduced pressure, water was added to the residue, and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with an aqueous saturated solution of sodium chloride and was dried with magnesium sulfate. After the resulting organic layer was concentrated under reduced pressure to remove the solvent, the residue was subjected to purification using column chromatography (ethanol/ethyl acetate 1:3→1:2) and to recrystallization (ethyl acetate/hexane) to obtain (trans, E)-3-[4-(4-methylphenyl)furan-2-yl]-N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]cyclohexyl]acrylamide (compound 74) (137 mg) as light yellow crystals.

Workup

  1. stirringthe resulting mixture was stirred for 4 days
  2. concentrationAfter the reaction mixture was concentrated under reduced pressure, water
  3. additionwas added to the residue
  4. extractionthe resulting mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with an aqueous saturated solution of sodium chloride
  6. dry with materialwas dried with magnesium sulfate
  7. concentrationAfter the resulting organic layer was concentrated under reduced pressure
  8. customto remove the solvent
  9. customthe residue was subjected to purification
  10. customto recrystallization (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-3dde94af77da4bd8afdad99535a640e4
Source dataset
uspto-grants-2003_09
Patent number
US06627651B1

Reaction notes

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