1,2-Dichloroethane → N1-((1S,2R)-1-benzyl-3-{[3-(2,4-dimethylphenyl)propyl]amino}-2-hydroxypropyl)-5-methyl-N3,N3-dipropylisophthalamide

HRID 14048Notes

Reaction equation

HRID 14048 reaction equation
F[C:2](F)(F)C(O)=O.[NH2:8][C@@H:9]([CH2:23][C:24]1[CH:29]=[C:28](F)[CH:27]=[C:26](F)[CH:25]=1)[C@H:10]([OH:22])[CH2:11][NH:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16](OC)[CH:15]=1.C(OC[CH2:41][CH2:42][CH2:43][N:44]([CH2:57][CH2:58][CH3:59])[C:45]([C:47]1[CH:48]=[C:49]([CH:53]=[C:54]([CH3:56])[CH:55]=1)[C:50](O)=[O:51])=[O:46])C1C=CC=CC=1.[CH:60]1[CH:61]=CC2N(O)N=NC=2[CH:65]=1.CN1CCOCC1.C(Cl)CCl>C(Cl)Cl>[CH2:23]([C@H:9]([NH:8][C:50](=[O:51])[C:49]1[CH:53]=[C:54]([CH3:56])[CH:55]=[C:47]([C:45]([N:44]([CH2:57][CH2:58][CH3:59])[CH2:43][CH2:42][CH3:41])=[O:46])[CH:48]=1)[C@H:10]([OH:22])[CH2:11][NH:12][CH2:13][CH2:14][CH2:19][C:18]1[CH:17]=[CH:16][C:15]([CH3:2])=[CH:65][C:60]=1[CH3:61])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 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 68608870N1-((1S,2R)-1-benzyl-3-{[3-(2,4-dimethylphenyl)propyl]amino}-2-hydroxypropyl)-5-methyl-N3,N3-dipropylisophthalamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred mixture of (2R,3S)-3-amino-1-{[3-(2,4-dimethylphenyl)propyl]amino}-4-phenyl-2-butanol hydrochloride (VIII, 163 mg, 0.411 mmol), 3-[(dipropylamino)carbonyl]-5-methylbenzoic acid (IX, 108 mg, 0.411 mmol), HOBt (55 mg, 0.411 mmol), and N-methylmorpholine (133 mg, 1.32 mmol) in methylene chloride (5 mL) is added EDC (142 mg, 0.740 mmol). The reaction mixture is stirred overnight and then partitioned between ethyl acetate and water. The organic phase is washed with hydrochloric acid (1 N), saturated sodium bicarbonate, saline, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica; methylene chloride/methanol/ammonium hydroxide, 95/5/1) gives the title compound, IR (ATR): 3299, 2930 and 1614 cm−1; APCI-MS (m/z) [M+H]+=572.

Workup

  1. custompartitioned between ethyl acetate and water
  2. washThe organic phase is washed with hydrochloric acid (1 N), saturated sodium bicarbonate, saline
  3. dry with materialdried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by flash column chromatography (silica; methylene chloride/methanol/ammonium hydroxide, 95/5/1)

Sources & evidence

ORD record
ord-6cfa202a0fa44ed39e779d76f10cbf95
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Reaction notes

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