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

HRID 14032Notes

Reaction equation

HRID 14032 reaction equation
[CH2:1]([N:4]([CH2:24][CH2:25][CH3:26])[C:5]([C:7]1[CH:8]=[C:9]([C:21]([OH:23])=O)[CH:10]=[C:11]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[CH:12]=1)=[O:6])[CH2:2][CH3:3].FC(F)(F)C(O)=O.[NH2:34][C@@H:35]([CH2:49][C:50]1[CH:55]=[C:54](F)[CH:53]=[C:52](F)[CH:51]=1)[C@H:36]([OH:48])[CH2:37][NH:38][CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[C:42]([O:46][CH3:47])[CH:41]=1.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.C(Cl)C[Cl:77]>C(Cl)Cl.CN(C)C=O>[ClH:77].[CH2:49]([C@H:35]([NH:34][C:21]([C:9]1[CH:10]=[C:11]([C:13]2[CH:14]=[CH:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=2)[CH:12]=[C:7]([C:5]([N:4]([CH2:24][CH2:25][CH3:26])[CH2:1][CH2:2][CH3:3])=[O:6])[CH:8]=1)=[O:23])[C@H:36]([OH:48])[CH2:37][NH:38][CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[C:42]([O:46][CH3:47])[CH:41]=1)[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 21085976HCID 21085976, compoundHCID 69869154(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanol Trifluoroacetate

Product 1

HCID 68608068N3-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-4'-methoxy-N5,N5-dipropyl[1,1'-biphenyl]-3,5-dicarboxamide hydrochloride

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

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.

Workup

  1. additionis added
  2. customThe reaction mixture is partitioned between methylene chloride and water
  3. washThe organic phase is washed with hydrochloric acid (1N), water, and saline
  4. dry with materialdried (magnesium sulfate)
  5. concentrationconcentrated
  6. dissolutionThe concentrate is dissolved in a minimum of methanol
  7. additiontreated with hydrochloric acid (3 mL of a 1.0 M mixture in ether, 3 mmol), and
  8. stirringstirred for 10 minutes
  9. additionMore ether is added
  10. customto precipitate the rest of the product
  11. filtrationThe precipitate is collected by filtration
  12. customdried in the vacuum oven at 50 degrees C

Sources & evidence

ORD record
ord-b3e01b3b0ed34daeb91b5633e8e9c229
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Reaction notes

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