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

HRID 348828Notes

Reaction equation

HRID 348828 reaction equation
[CH2:1]([N:4]([CH2:22][CH2:23][CH3:24])[C:5]([C:7]1[CH:8]=[C:9]([C:19](O)=[O:20])[CH:10]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:12]=1)=[O:6])[CH2:2][CH3:3].FC(F)(F)C(O)=O.[NH2:32][C@@H:33]([CH2:47][C:48]1[CH:53]=[C:52]([F:54])[CH:51]=[C:50]([F:55])[CH:49]=1)[C@H:34]([OH:46])[CH2:35][NH:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([O:44][CH3:45])[CH:39]=1.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.C(Cl)C[Cl:75]>C(Cl)Cl.CN(C)C=O>[ClH:75].[F:55][C:50]1[CH:49]=[C:48]([CH:53]=[C:52]([F:54])[CH:51]=1)[CH2:47][C@H:33]([NH:32][C:19]([C:9]1[CH:10]=[C:11]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:12]=[C:7]([C:5]([N:4]([CH2:22][CH2:23][CH3:24])[CH2:1][CH2:2][CH3:3])=[O:6])[CH:8]=1)=[O:20])[C@H:34]([OH:46])[CH2:35][NH:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([O:44][CH3:45])[CH:39]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 21085975HCID 21085975, compoundHCID 69869154(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanol Trifluoroacetate

Product 1

HCID 68611811N3-{(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N5,N5-dipropyl[1,1'-biphenyl]-3,5-dicarboxamide hydrochloride

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 5-[(dipropylamino)carbonyl][1,1′-biphenyl]-3-carboxylic acid (IX, 188 mg, 0.56 mmol), (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanol dihydrochloride (VIII, Step 2, 230 mg, 0.56 mmol), HOBt (114 mg, 0.84 mmol), and N-methylmorpholine (0.23 g, 2.24 mmol) in methylene chloride (6 mL) and dimethylformamide (1 mL) is stirred at 20–25 degrees C. for 15 minutes EDC (161 mg, 0.84 mmol) is added and the reaction mixture is stirred at 20–25 degrees C. overnight. The reaction mixture is washed with water, 1 N hydrochloric acid, water, and saline, dried (sodium sulfate), and concentrated under reduced pressure to give the title compound, mp 230–233 degrees C.; IR (ATR): 2965, 1651, 1596 and 1267 cm−1; ESI-MS (m/z) [M+H]+=644.

Workup

  1. stirringthe reaction mixture is stirred at 20–25 degrees C
  2. customovernight
  3. washThe reaction mixture is washed with water, 1 N hydrochloric acid, water, and saline
  4. dry with materialdried (sodium sulfate)
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a4124b0dea604bbf81f7e8510aae7a0b
Source dataset
uspto-grants-2007_02
Patent number
US07176242B2

Reaction notes

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