تفاعل #42310

معادلة التفاعل

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

المذيبات

methylene chloride

dimethylformamide

ظروف التفاعل

المعالجة

1. 1
   workup.ADDITIONis added
2. 2
   أخرىThe reaction mixture is partitioned between methylene chloride and water
3. 3
   غسيلThe organic phase is washed with hydrochloric acid (1N), water, and saline
4. 4
   تجفيفdried (magnesium sulfate)
5. 5
   تركيزconcentrated
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
    أخرىto precipitate the rest of the product
11. 11
    ترشيحThe precipitate is collected by filtration
12. 12
    أخرىdried in the vacuum oven at 50 degrees C

الإجراء التجريبي

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.

المصدر