Diisopropylethylamine → N-[(1S,2R)-1-Benzyl-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl]-1-oxo-2-(1-propylbutyl)isoindoline-4-carboxamide

HRID 387617Notes

Reaction equation

HRID 387617 reaction equation
[O:1]=[C:2]1[C:10]2[CH:9]=[CH:8][CH:7]=[C:6]([C:11]([OH:13])=O)[C:5]=2[CH2:4][N:3]1[CH:14]([CH2:18][CH2:19][CH3:20])[CH2:15][CH2:16][CH3:17].Cl.[NH2:22][C@@H:23]([CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[C@H:24]([OH:38])[CH2:25][NH:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([C:34]([F:37])([F:36])[F:35])[CH:29]=1.OC1C2N=NNC=2C=CC=1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C>ClCCl.O>[CH2:39]([C@H:23]([NH:22][C:11]([C:6]1[C:5]2[CH2:4][N:3]([CH:14]([CH2:15][CH2:16][CH3:17])[CH2:18][CH2:19][CH3:20])[C:2](=[O:1])[C:10]=2[CH:9]=[CH:8][CH:7]=1)=[O:13])[C@H:24]([OH:38])[CH2:25][NH:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([C:34]([F:35])([F:36])[F:37])[CH:29]=1)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57514512(2R,3S)-3-amino-4-phenyl-1-{[3-(trifluoromethyl)benzyl]amino}butan-2-ol hydrochlorideHCID 68474849HCID 68474849, compoundHCID 178418300HCID 178418300, compound

Product 1

HCID 25206129N-[(1S,2R)-1-Benzyl-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl]-1-oxo-2-(1-propylbutyl)isoindoline-4-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

136.4 mg of 1-oxo-2-(1-propylbutyl)isoindoline-4-carboxylic acid are dissolved in 8 cm3 of dichloromethane under an inert atmosphere at a temperature close to 20° C. 195 mg of ((2R,3S)-3-amino-4-phenyl-1-{[3-(trifluoromethyl)benzyl]amino}butan-2-ol hydrochloride (2:1), 9.6 mg of hydroxybenzotriazole, and 108.7 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride are added to the solution. 0.308 cm3 of N,N-diisopropylethylamine is poured into the reaction medium. This is kept stirring for 20 h at 20° C. 10 cm3 of water are added to the reaction medium. The organic phase is washed with 10 cm3 of a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and concentrated using a rotary evaporator under reduced pressure (5 kPa). The 310 mg of beige gum obtained are purified by flash chromatography over silica (column: 15 g; particle size: 20-40 μm, spherical; flow rate: 20 cm3/min; eluent: 95% dichloromethane/5% methanol). After concentrating the fractions under reduced pressure, 110 mg of N-[(1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl]-1-oxo-2-(1-propylbutyl)isoindoline-4-carboxamide are obtained in the form of a beige foam.

Workup

  1. customclose to 20° C
  2. washThe organic phase is washed with 10 cm3 of a saturated aqueous solution of sodium chloride
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. customa rotary evaporator under reduced pressure (5 kPa)

Sources & evidence

ORD record
ord-2f2c96976a63444e893c8bb355191878
Source dataset
uspto-grants-2013_02
Patent number
US08372864B2

Reaction notes

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