1-Hydroxybenzotriazole → HCID 87558202, compound

HRID 2354307Notes

Reaction equation

HRID 2354307 reaction equation
[CH2:1]([O:8][C@@H:9]1[C@@H:14]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@H:13]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@@H:12]([CH2:31][O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[O:11][C@H:10]1[C:40]1[C:48]2[C:43](=[C:44]([CH3:49])[CH:45]=[CH:46][CH:47]=2)[N:42]([CH2:50][C:51]2[CH:56]=[CH:55][C:54](/[CH:57]=[CH:58]/[CH2:59][C:60](O)=[O:61])=[CH:53][CH:52]=2)[CH:41]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:63][C:64]([CH3:77])([CH3:76])[C:65]([N:67]1[CH2:72][CH2:71][N:70]([CH:73]([CH3:75])[CH3:74])[CH2:69][CH2:68]1)=[O:66].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.O.C(N(CC)CC)C>[CH2:1]([O:8][C@@H:9]1[C@@H:14]([O:15][CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C@H:13]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@@H:12]([CH2:31][O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[O:11][C@H:10]1[C:40]1[C:48]2[C:43](=[C:44]([CH3:49])[CH:45]=[CH:46][CH:47]=2)[N:42]([CH2:50][C:51]2[CH:56]=[CH:55][C:54](/[CH:57]=[CH:58]/[CH2:59][C:60](=[O:61])[NH:63][C:64]([C:65]([N:67]3[CH2:72][CH2:71][N:70]([CH:73]([CH3:74])[CH3:75])[CH2:69][CH2:68]3)=[O:66])([CH3:76])[CH3:77])=[CH:53][CH:52]=2)[CH:41]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57616312HCID 57616312, compoundHCID 59363440HCID 59363440, compound

Product 1

HCID 87558202HCID 87558202, compoundYield 89%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
50 °C

Procedure

A suspension of 3-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)-1-[4-((1E)-3-carboxyprop-1-enyl)benzyl]-7-methyl-1H-indole (0.10 g), 1-(2-amino-2-methylpropionyl)-4-isopropylpiperazine (31 mg), 1-hydroxybenzotriazole (18 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (35 mg) and triethylamine (0.034 mL) in N,N-dimethylformamide (2 mL) was stirred at 50° C. overnight. The reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with an aqueous potassium carbonate solution and brine successively, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: dichloromethane/methanol=20/1-12/1) to give 3-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)-1-[4-((1E)-3-{1-[(4-isopropylpiperazin-1-yl)carbonyl]-1-(methyl)ethylcarbamoyl}prop-1-enyl)benzyl]-7-methyl-1H-indole (0.11 g). This material was dissolved in a mixed solvent of methanol (3 mL) and tetra hydrofuran (3 mL). To the solution was added 10% palladium-carbon powder (0.50 g), and the mixture was stirred at room temperature under a hydrogen atmosphere for 4 hours. The insoluble material was removed by filtration, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: dichloromethane/methanol=5/1-3/1) to give the title compound (19 mg).

Workup

  1. extractionthe resulting mixture was extracted with ethyl acetate
  2. washThe extract was washed with an aqueous potassium carbonate solution and brine successively
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was removed under reduced pressure
  5. customthe residue was purified by column chromatography on silica gel (eluent: dichloromethane/methanol=20/1-12/1)

Sources & evidence

ORD record
ord-c9601244222a4877baa3bb2a095fcf62
Source dataset
uspto-grants-2010_07
Patent number
US07750145B2

Reaction notes

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