1-Hydroxybenzotriazole → HCID 18472370, compound

HRID 2228139Notes

Reaction equation

HRID 2228139 reaction equation
[N:1]1([C:6]2[CH:11]=[CH:10][C:9]([C:12]3[CH:13]=[CH:14][C:15]4[O:21][CH2:20][CH2:19][C:18]([C:22]([OH:24])=O)=[CH:17][C:16]=4[CH:25]=3)=[CH:8][CH:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:26][N:27]([CH2:34][C:35]1[CH:41]=[CH:40][C:38]([NH2:39])=[CH:37][CH:36]=1)[CH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C1CCN2C(=NCCC2)CC1>CN(C)C=O.CN(C)C1C=CN=CC=1>[N:1]1([C:6]2[CH:7]=[CH:8][C:9]([C:12]3[CH:13]=[CH:14][C:15]4[O:21][CH2:20][CH2:19][C:18]([C:22]([NH:39][C:38]5[CH:40]=[CH:41][C:35]([CH2:34][N:27]([CH:28]6[CH2:33][CH2:32][O:31][CH2:30][CH2:29]6)[CH3:26])=[CH:36][CH:37]=5)=[O:24])=[CH:17][C:16]=4[CH:25]=3)=[CH:10][CH:11]=2)[CH2:2][CH2:3][CH2:4][CH2:5]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 9877845(4-Amino-benzyl)-methyl-(tetrahydro-pyran-4-yl)-amineHCID 18472261HCID 18472261, compound

Product 1

HCID 18472370HCID 18472370, compoundYield 33.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 7—(4—(pyrrolidin-1-yl)phenyl)-2,3-dihydro-1-benzoxepine-4-carboxylic acid (0.15 g), 4—(N-methyl-N-(tetrahydropyran-4-yl)aminomethyl)aniline (0.1 g) and l-hydroxybenzotriazole (0.07 g) in dimethylformamide (10 ml) was added 1-ethyl-3—(3-dimethylaminopropyl)carbodiimide hydro-chloride (0.13 g) under ice-cooling, and the mixture was stirred under nitrogen atmosphere at room temperature for 3 hours. To the mixture were added 4-dimethylaminopyridine (catalytic amount) and 1,8-diazabicyclo[5.4.0]-7-undecene (0.2 ml), and the mixture was stirred overnight. The solvent was evaporated, and the residue was purified with silica gel column (methanol/ethyl acetate/triethylamine) to give crude crystals, which were recrystallized from ethanol-hexane to give 7—(4—(pyrrolidin-1-yl)phenyl)-N-(4—((N-tetrahydropyran-4-yl-N-methylamino)-methyl)phenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (Compound 150) (0.08 g) as colorless crystals.

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred overnight
  3. customThe solvent was evaporated
  4. customthe residue was purified with silica gel column (methanol/ethyl acetate/triethylamine)
  5. customto give crude crystals, which
  6. customwere recrystallized from ethanol-hexane

Sources & evidence

ORD record
ord-7795cb0c142147148e0a68433c3d79ef
Source dataset
uspto-grants-2002_07
Patent number
US06413947B1

Reaction notes

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