Diisopropylethylamine → HCID 57216102, compound

HRID 990391Notes

Reaction equation

HRID 990391 reaction equation
[CH:1]([N:4]([CH3:13])[CH:5]([CH2:9][CH:10]([CH3:12])[CH3:11])[C:6]([OH:8])=O)([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.Cl.[F:24][C:25]1[CH:30]=[CH:29][C:28]([CH:31]([C:36]2[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=2)[CH2:32][CH2:33][CH2:34][NH2:35])=[CH:27][CH:26]=1>CN(C=O)C.C(OCC)C>[F:24][C:25]1[CH:30]=[CH:29][C:28]([CH:31]([C:36]2[CH:37]=[CH:38][C:39]([F:42])=[CH:40][CH:41]=2)[CH2:32][CH2:33][CH2:34][NH:35][C:6](=[O:8])[C@@H:5]([N:4]([CH:1]([CH3:2])[CH3:3])[CH3:13])[CH2:9][CH:10]([CH3:12])[CH3:11])=[CH:27][CH:26]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 18418679HCID 18418679, compoundHCID 18418729HCID 18418729, compound

Product 1

HCID 57216102HCID 57216102, compoundYield 89.6%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 297 mg (1.68 mmol) 2-(isopropyl-methyl-amino)-4-methyl-pentanoic acid, 0.88 mL (5 mmol) N,N-diisopropylethylamine, and 636 mg (1.68 mmol) O-Benzotriazol-1-yl-N,N,N′,N′-bis(tetramethylene)uronium hexafluorophosphate in 4 mL dry DMF was stirred at 3° for 60 minutes, at which time 500 mg (1.68 mmol) 4,4-bis-(4-fluoro-phenyl)-butylamine monohydrochloride was added and the reaction stirred an additional 10 minutes at 3°, then warmed to 25° C. for 40 minutes at which time it was diluted with 20 mL diethyl ether and washed with 20 mL saturated aqueous sodium bicarbonate solution and twice with 20 mL brine, dried over anhydrous sodium sulfate and concentrated at reduced pressure. The residue thus obtained was further purified by silica gel chromatography using 60% ethyl acetate in hexanes as eluant, followed by conversion to the hydrochloride salt by treating with excess diethyl ether which had been saturated with hydrogen chloride gas to give 648 mg (83%) of titled compound: mp 155-156° C. APCI-MS m/z 431.4 (MH+).

Workup

  1. additionwas added
  2. washwashed with 20 mL saturated aqueous sodium bicarbonate solution and twice with 20 mL brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated at reduced pressure
  5. customThe residue thus obtained
  6. customwas further purified by silica gel chromatography
  7. additionby treating with excess diethyl ether which

Sources & evidence

ORD record
ord-15f059c4e9844511a1188b3ba695de1b
Source dataset
uspto-grants-2002_10
Patent number
US06458781B1

Reaction notes

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