1-Hydroxybenzotriazole → HCID 178423871, compound

HRID 1169423Notes

Reaction equation

HRID 1169423 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10](/[CH:14]=[CH:15]/[C:16]([OH:18])=O)[CH:11]=[N:12][CH:13]=2)=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.Cl.Cl.[CH3:43][N:44]([CH2:51][C@H:52]1[CH2:57][CH2:56][C@H:55]([NH2:58])[CH2:54][CH2:53]1)[CH:45]1[CH2:50][CH2:49][O:48][CH2:47][CH2:46]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:14]=[CH:15]/[C:16]([NH:58][C@H:55]3[CH2:54][CH2:53][C@H:52]([CH2:51][N:44]([CH3:43])[CH:45]4[CH2:50][CH2:49][O:48][CH2:47][CH2:46]4)[CH2:57][CH2:56]3)=[O:18])[CH:11]=[N:12][CH:13]=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 18472468HCID 18472468, compoundHCID 178484107HCID 178484107, compound

Product 1

HCID 178423871HCID 178423871, compoundYield 80.5%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 8471TriethylamineSolvent

Procedure

Into a suspension of (E)-3-[5-(4-methylphenyl)pyridin-3-yl]acrylic acid (150 mg) and 1-hydroxybenzotriazole (134 mg) in acetonitrile (15 ml) was added at room temperature 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (0.19 g), 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 (198 mg), 1,8-diazabicyclo[5,4,0]-7-undecene (0.2 g) and triethylamine (0.18 ml) in acetonitrile (20 ml), and the resulting mixture was stirred for 64 hours. After the reaction mixture was concentrated under reduced pressure, water was added to the residue, and the resulting mixture was extracted with chloroform. 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 precipitated crystals were purified by recrystallization (ethanol/ethyl acetate) to obtain (trans, E)-3-[5-(4-methylphenyl)pyridin-3-yl]-N-[4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]cyclohexyl]acrylamide (compound 73) (226 mg) as colorless crystals.

Workup

  1. stirringthe resulting mixture was stirred for 64 hours
  2. concentrationAfter the reaction mixture was concentrated under reduced pressure, water
  3. additionwas added to the residue
  4. extractionthe resulting mixture was extracted with chloroform
  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 precipitated crystals were purified by recrystallization (ethanol/ethyl acetate)

Sources & evidence

ORD record
ord-012bec3e63db44069360045a6bbaf7bf
Source dataset
uspto-grants-2003_09
Patent number
US06627651B1

Reaction notes

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