Reaktion #42310

Reaktionsgleichung

5-[(dipropylamino)carbonyl]-4′-methoxy[1,1′-biphenyl]-3-carboxylic acid

(2R,3S)-3-amino-1-[(3-methoxybenzyl)amino]-4-phenyl-2-butanol dihydrochloride

(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanol trifluoroacetate

HOBt

N-methylmorpholine

EDC

→

title compound

N3-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4′-methoxy-N5,N5-dipropyl[1,1′-biphenyl]-3,5-dicarboxamide hydrochloride

Lösungsmittel

methylene chloride

dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONis added
2. 2
   SonstigeThe reaction mixture is partitioned between methylene chloride and water
3. 3
   WaschenThe organic phase is washed with hydrochloric acid (1N), water, and saline
4. 4
   Trocknendried (magnesium sulfate)
5. 5
   Einengenconcentrated
6. 6
   workup.DISSOLUTIONThe concentrate is dissolved in a minimum of methanol
7. 7
   workup.ADDITIONtreated with hydrochloric acid (3 mL of a 1.0 M mixture in ether, 3 mmol), and
8. 8
   workup.STIRRINGstirred for 10 minutes
9. 9
   workup.ADDITIONMore ether is added
10. 10
    Sonstigeto precipitate the rest of the product
11. 11
    FiltrationThe precipitate is collected by filtration
12. 12
    Sonstigedried in the vacuum oven at 50 degrees C

Vorschrift

A mixture of 5-[(dipropylamino)carbonyl]-4′-methoxy[1,1′-biphenyl]-3-carboxylic acid (IX-L, step 1, 316 mg, 0.89 mmol), (2R,3S)-3-amino-1-[(3-methoxybenzyl)amino]-4-phenyl-2-butanol dihydrochloride (VIII, 332 mg, 0.89 mmol), HOBt (181 mg, 1.34 mmol), and N-methylmorpholine (0.37 g, 3.56 mmol) in methylene chloride (8 mL) and dimethylformamide (2 mL) is stirred at 20-25 degrees for 15 minutes EDC (257 mg, 1.34 mmol) is added and the reaction mixture is stirred for 4.5 hours. The reaction mixture is partitioned between methylene chloride and water. The organic phase is washed with hydrochloric acid (1N), water, and saline, dried (magnesium sulfate), and concentrated. The concentrate is dissolved in a minimum of methanol, treated with hydrochloric acid (3 mL of a 1.0 M mixture in ether, 3 mmol), and stirred for 10 minutes. More ether is added to precipitate the rest of the product. The precipitate is collected by filtration and dried in the vacuum oven at 50 degrees C. to give the title compound, mp=205-209 degrees C.; IR (ATR): 2964 and 1649 cm−1; APCI-MS (m/z) [M+H]+=638.

Quelle