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

HRID 348840Notes

Reaction equation

HRID 348840 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

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-ab0ff06d0f5e4305824e291ca02fb3a4
Source dataset
uspto-grants-2007_02
Patent number
US07176242B2

Reaction notes

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