Diisopropylethylamine → HCID 59913952, compound

HRID 990393Notes

Reaction equation

HRID 990393 reaction equation
[CH:1]1([N:7]([CH3:15])[C@@H:8]([CH:12]([CH3:14])[CH3:13])[C:9]([OH:11])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)C(C)C)(C)C.Cl.[F:26][C:27]1[CH:32]=[CH:31][C:30]([CH:33]([C:38]2[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=2)[CH2:34][CH2:35][CH2:36][NH2:37])=[CH:29][CH:28]=1>CN(C=O)C.C(OCC)C>[F:26][C:27]1[CH:32]=[CH:31][C:30]([CH:33]([C:38]2[CH:39]=[CH:40][C:41]([F:44])=[CH:42][CH:43]=2)[CH2:34][CH2:35][CH2:36][NH:37][C:9](=[O:11])[C@@H:8]([N:7]([CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]2)[CH3:15])[CH:12]([CH3:14])[CH3:13])=[CH:29][CH:28]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 15458711HCID 15458711, compoundHCID 18418679HCID 18418679, compound

Product 1

HCID 59913952HCID 59913952, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 358 mg (1.68 mmol) (S)-2-(cyclohexyl-methyl-amino)-3-methylbutyric 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 50 minutes at which time it was diluted with 20 mL diethyl ether, and washed with 20 mL saturated aqueous sodiumbicarbonate 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 40% ethyl acetate in hexanes as eluant, followed by conversion to the hydrochloride salt by treatment with excess diethyl ether which had been saturated with hydrogen chloride gas to give 577 mg (68%) mp 82-86° C. APCI-MS m/z 457.4 (MH+).

Workup

  1. additionwas added
  2. washwashed with 20 mL saturated aqueous sodiumbicarbonate 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. customto give 577 mg (68%) mp 82-86° C

Sources & evidence

ORD record
ord-012fc01975fe43929f5469affd822cee
Source dataset
uspto-grants-2002_10
Patent number
US06458781B1

Reaction notes

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