1,2-Dichloroethane → N1-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N3,N3-dipropyl-5-(3-thienyl)isophthalamide hydrochloride

HRID 14037Notes

Reaction equation

HRID 14037 reaction equation
[CH2:1]([N:4]([CH2:21][CH2:22][CH3:23])[C:5]([C:7]1[CH:8]=[C:9]([CH:13]=[C:14]([C:16]2[CH:20]=[CH:19][S:18][CH:17]=2)[CH:15]=1)[C:10]([OH:12])=O)=[O:6])[CH2:2][CH3:3].FC(F)(F)C(O)=O.[NH2:31][C@@H:32]([CH2:46][C:47]1[CH:52]=[C:51](F)[CH:50]=[C:49](F)[CH:48]=1)[C@H:33]([OH:45])[CH2:34][NH:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([O:43][CH3:44])[CH:38]=1.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.C(Cl)C[Cl:74]>CN(C=O)C.O>[ClH:74].[CH2:46]([C@H:32]([NH:31][C:10](=[O:12])[C:9]1[CH:13]=[C:14]([C:16]2[CH:20]=[CH:19][S:18][CH:17]=2)[CH:15]=[C:7]([C:5]([N:4]([CH2:21][CH2:22][CH3:23])[CH2:1][CH2:2][CH3:3])=[O:6])[CH:8]=1)[C@H:33]([OH:45])[CH2:34][NH:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([O:43][CH3:44])[CH:38]=1)[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 210857863-[(Dipropylamino)carbonyl]-5-(3-thienyl)benzoic acidHCID 69869154(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanol Trifluoroacetate

Product 1

HCID 68608779N1-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-N3,N3-dipropyl-5-(3-thienyl)isophthalamide hydrochloride

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
22.5 °C

Procedure

A mixture of 3-[(dipropylamino)carbonyl]-5-(3-thienyl)benzoic acid (IX-L, step 4, 0.26 g, 0.79 mmol), (2R,3S)-3-amino-1-[(3-methoxybenzyl)amino]-4-phenyl-2-butanol dihydrochloride (VIII, 0.26 g, 0.71 mmol), HOBt (0.16 g, 1.18 mmol), and triethylamine (0.44 mL, 3.15 mmol) in DMF (4 mL) is stirred at 20-25 degrees C. for 10 minutes EDC (0.23 g, 1.18 mmol) is added and the reaction mixture is stirred for 4 hours. The reaction mixture is diluted with water and extracted with ethyl acetate. The organic phase is washed with hydrochloric acid (1 N), water, and saline, dried over magnesium sulfate and concentrated under reduced pressure. Recrystallization (methylene chloride/hexanes, 1/1) gives the title compound, mp=199-201 degrees C.; IR (KBr): 3278, 2961, 2874 and 2837 cm−1; ESI-MS (m/z) [M+H]+=614.

Workup

  1. stirringthe reaction mixture is stirred for 4 hours
  2. extractionextracted with ethyl acetate
  3. washThe organic phase is washed with hydrochloric acid (1 N), water, and saline
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customRecrystallization (methylene chloride/hexanes, 1/1)

Sources & evidence

ORD record
ord-f8f74105d6ed4c458fc2e6a9b60c1d1c
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Reaction notes

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