Diisopropylethylamine → N-[(1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl]-1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxamide

HRID 387628Notes

Reaction equation

HRID 387628 reaction equation
[O:1]=[C:2]1[C:11]2[CH:10]=[CH:9][CH:8]=[C:7]([C:12]([OH:14])=O)[C:6]=2[CH2:5][CH2:4][N:3]1[CH:15]([CH2:19][CH2:20][CH3:21])[CH2:16][CH2:17][CH3:18].Cl.[NH2:23][C@@H:24]([CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[C@H:25]([OH:39])[CH2:26][NH:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:38])([F:37])[F:36])[CH:30]=1.OC1C2N=NNC=2C=CC=1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C>ClCCl.O>[CH2:40]([C@H:24]([NH:23][C:12]([C:7]1[C:6]2[CH2:5][CH2:4][N:3]([CH:15]([CH2:19][CH2:20][CH3:21])[CH2:16][CH2:17][CH3:18])[C:2](=[O:1])[C:11]=2[CH:10]=[CH:9][CH:8]=1)=[O:14])[C@H:25]([OH:39])[CH2:26][NH:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:36])([F:37])[F:38])[CH:30]=1)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=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 68470583HCID 68470583, compoundHCID 178418300HCID 178418300, compound

Product 1

HCID 25206291N-[(1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl]-1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxamideYield 110.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

43 mg of 1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxylic acid are dissolved in 2.5 cm3 of dichloromethane under an inert atmosphere at a temperature close to 20° C. 62 mg of (2R,3S)-3-amino-4-phenyl-1-{[3-(trifluoromethyl)benzyl]amino}butan-2-ol hydrochloride (2:1), 3 mg of hydroxybenzotriazole and 34 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride are added to the solution. 0.124 cm3 of N,N-diisopropylethylamine is poured into the reaction medium. This medium is kept stirring for 20 h at a temperature close to 20° C. 10 cm3 of dichloromethane are added to the reaction mixture, then 10 cm3 of water. After decantation, the organic phase is washed with 5 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 100 mg of colorless oil obtained are purified by flash chromatography over silica (column: 7 g; particle size: 20-40 μm spherical; flow rate: 20 cm3/min; eluent: 100% ethyl acetate). After concentrating the fractions under reduced pressure, 40 mg of N-[(1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl]-1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxamide are obtained in the form of a colorless oil.

Workup

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

Sources & evidence

ORD record
ord-bfafa699f61a43cd9e8521395a2b6d9b
Source dataset
uspto-grants-2013_02
Patent number
US08372864B2

Reaction notes

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