Diisopropylethylamine → (1-(2-(4-benzyl-4-(N',N'-dimethylhydrazinocarbonyl)piperidine-1-yl)-1-(1H-indol-3-ylmethyl)-2-oxoethylcarbamoyl)-1-methylethyl)carbamic acid tert-butyl ester

HRID 380664Notes

Reaction equation

HRID 380664 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]([CH3:14])([CH3:13])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2N=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[CH3:37][N:38]([CH3:69])[NH:39][C:40]([C:42]1([CH2:62][C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=2)[CH2:47][CH2:46][N:45]([C:48](=[O:61])[CH:49]([NH2:60])[CH2:50][C:51]2[C:59]3[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=3)[NH:53][CH:52]=2)[CH2:44][CH2:43]1)=[O:41].C(N(C(C)C)CC)(C)C>C(Cl)Cl>[C:1]([O:5][C:6](=[O:7])[NH:8][C:9]([C:10](=[O:12])[NH:60][CH:49]([CH2:50][C:51]1[C:59]2[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=2)[NH:53][CH:52]=1)[C:48]([N:45]1[CH2:44][CH2:43][C:42]([CH2:62][C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=2)([C:40]([NH:39][N:38]([CH3:69])[CH3:37])=[O:41])[CH2:47][CH2:46]1)=[O:61])([CH3:14])[CH3:13])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2733845N-((1,1-dimethylethoxy)carbonyl)-2-methyl-alanineHCID 206947011-(2-amino-3-(1H-indol-3-yl)propionyl)-4-benzylpiperidine-4-carboxylic acid N',N'-dimethylhydrazide

Product 1

HCID 69019306(1-(2-(4-benzyl-4-(N',N'-dimethylhydrazinocarbonyl)piperidine-1-yl)-1-(1H-indol-3-ylmethyl)-2-oxoethylcarbamoyl)-1-methylethyl)carbamic acid tert-butyl esterYield 67.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-tert-butoxycarbonylamino-2-methylpropionic acid (0.18 g, 0.88 mmol) in methylene chloride (10 ml) was added 1-hydroxy-7-azabenzotriazole (0.12 mg, 0.88 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.12 g, 0.88 mmol) and the mixture was stirred for 30 min. Then 1-(2-amino-3-(1H-indol-3-yl)propionyl)-4-benzylpiperidine-4-carboxylic acid N′,N′-dimethylhydrazide (0.46 g, 0.73 mmol) and diisopropylethylamine (0.50 ml, 2.92 mmol) was added and the mixture was stirred overnight. Methylene chloride (100 ml) was added and the mixture was washed with saturated aqueous sodium hydrogencarbonate (20 ml), water (20 ml), dried (MgSO4), filtered and concentrated in vacuo. The obtained oil was chromatographed on silica (40 g) with methylene chloride/(10% ammonia in methanol) (9:1) to give 0.31 g of (1-(2-(4-benzyl-4-(N′,N′-dimethylhydrazinocarbonyl)piperidine-1-yl)-1-(1H-indol-3-ylmethyl)-2-oxoethylcarbamoyl)-1-methylethyl)carbamic acid tert-butyl ester as a colorless oil.

Workup

  1. stirringthe mixture was stirred overnight
  2. washthe mixture was washed with saturated aqueous sodium hydrogencarbonate (20 ml), water (20 ml)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe obtained oil was chromatographed on silica (40 g) with methylene chloride/(10% ammonia in methanol) (9:1)

Sources & evidence

ORD record
ord-1841cb8f0cf84605801068482b5c9c9f
Source dataset
uspto-grants-2001_10
Patent number
US06303620B1

Reaction notes

Loading…