1,2-Dichloroethane → N1-((1S,2R)-1-[4-(benzyloxy)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N3,N3-dipropylisophthalamide

HRID 14046Notes

Reaction equation

HRID 14046 reaction equation
C(OC[CH2:10][CH2:11][CH2:12][N:13]([CH2:26][CH2:27][CH3:28])[C:14]([C:16]1[CH:17]=[C:18]([CH:22]=[C:23]([CH3:25])[CH:24]=1)[C:19]([OH:21])=O)=[O:15])C1C=CC=CC=1.F[C:30](F)(F)[C:31]([OH:33])=O.[NH2:36][C@@H:37]([CH2:51][C:52]1[CH:57]=[C:56](F)[CH:55]=[C:54](F)[CH:53]=1)[C@H:38]([OH:50])[CH2:39][NH:40][CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[C:44]([O:48][CH3:49])[CH:43]=1.C(N(CC)C(C)C)(C)C.[CH:69]1[CH:70]=[CH:71]C2N(O)N=N[C:73]=2[CH:74]=1.C(Cl)CCl>ClCCl>[CH2:31]([O:33][C:55]1[CH:56]=[CH:57][C:52]([CH2:51][C@H:37]([NH:36][C:19](=[O:21])[C:18]2[CH:22]=[C:23]([CH3:25])[CH:24]=[C:16]([C:14]([N:13]([CH2:12][CH2:11][CH3:10])[CH2:26][CH2:27][CH3:28])=[O:15])[CH:17]=2)[C@H:38]([OH:50])[CH2:39][NH:40][CH2:41][C:42]2[CH:47]=[CH:46][CH:45]=[C:44]([O:48][CH3:49])[CH:43]=2)=[CH:53][CH:54]=1)[C:30]1[CH:71]=[CH:70][CH:69]=[CH:74][CH:73]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 210856863-{[[4-(Benzyloxy)butyl](propyl)amino]carbonyl)-5-methylbenzoic acidHCID 69869154(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanol Trifluoroacetate

Product 1

HCID 68609943N1-((1S,2R)-1-[4-(benzyloxy)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N3,N3-dipropylisophthalamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
22.5 °C

Procedure

To a stirred mixture of 3-[(dipropylamino)-carbonyl]-5-methylbenzoic acid (IX, 150 mg, 0.570 mmol), (2R,3S)-3-amino-4-[4-(benzyloxy)phenyl]-1-[(3-methoxybenzyl)amino]-2-butanol hydrochloride (VIII, 274 mg, 0.571 mmol), N,N-diisopropylethylamine (400 microliter, 2.28 mmol), and HOBt (116 mg, 0.857 mmol) in dichloromethane (10 mL) is added EDC (165 mg, 0.857 mmol). The resulting mixture is stirred at 20-25 degrees C. for 16 hours. The reaction mixture is partitioned between dichloromethane and water. The aqueous phase is separated and extracted with dichloromethane (3×15 mL). The combined organic phases are washed with water, dried (magnesium sulfate), and concentrated under reduced pressure. Purification by flash column chromatography (silica; dichloromethane/methanol/ammonium hydroxide, 97/3/0.05) gives N1-{(1S,2R)-1-[4-(benzyloxy)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N3,N3-dipropylisophthalamide, ESI-MS (m/z) [M+H]+=652.

Workup

  1. customThe reaction mixture is partitioned between dichloromethane and water
  2. customThe aqueous phase is separated
  3. extractionextracted with dichloromethane (3×15 mL)
  4. washThe combined organic phases are washed with water
  5. dry with materialdried (magnesium sulfate)
  6. concentrationconcentrated under reduced pressure
  7. customPurification by flash column chromatography (silica; dichloromethane/methanol/ammonium hydroxide, 97/3/0.05)

Sources & evidence

ORD record
ord-5b5210b2db3e418d93d6001e78fc5de1
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Reaction notes

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