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 14033Notes

Reaction equation

HRID 14033 reaction equation
C([N:4]([CH2:22][CH2:23][CH3:24])[C:5]([C:7]1[CH:8]=[C:9]([C:19]([OH:21])=O)[CH:10]=[C:11](C2C=CC=CC=2)[CH:12]=1)=[O:6])CC.F[C:26](F)(F)[C:27](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.[CH:56]1[CH:57]=[CH:58][C:59]2N(O)N=N[C:60]=2[CH:61]=1.[CH3:66]N1CCOCC1.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:61]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[CH:12]=[C:7]([C:5]([N:4]([CH2:22][CH2:23][CH3:24])[CH2:66][CH2:26][CH3:27])=[O:6])[CH:8]=1)=[O:21])[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

Conditions

Temperature
22.5 °C

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 230-233degrees C.; IR (ATR): 2965, 1651, 1596 and 1267 cm1; 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-3ff2f073c8d64b2bba2f15ee54dd7fe8
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Reaction notes

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