1,2-Dichloroethane → N1-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl)-N3,N3-dipropyl-1,3,5-benzenetricarboxamide

HRID 14014

Reaction equation

HRID 14014 reaction equation
[NH2:1][C:2]([C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([C:13]([N:15]([CH2:19][CH2:20][CH3:21])[CH2:16][CH2:17][CH3:18])=[O:14])[CH:12]=1)[C:7](O)=[O:8])=[O:3].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.FC(F)(F)C(O)=O.[NH2:50][C@@H:51]([CH2:65][C:66]1[CH:71]=[C:70](F)[CH:69]=[C:68](F)[CH:67]=1)[C@H:52]([OH:64])[CH2:53][NH:54][CH2:55][C:56]1[CH:61]=[CH:60][CH:59]=[C:58]([O:62][CH3:63])[CH:57]=1>CN(C=O)C>[CH2:65]([C@H:51]([NH:50][C:7]([C:6]1[CH:5]=[C:4]([C:2]([NH2:1])=[O:3])[CH:12]=[C:11]([C:13]([N:15]([CH2:19][CH2:20][CH3:21])[CH2:16][CH2:17][CH3:18])=[O:14])[CH:10]=1)=[O:8])[C@H:52]([OH:64])[CH2:53][NH:54][CH2:55][C:56]1[CH:61]=[CH:60][CH:59]=[C:58]([O:62][CH3:63])[CH:57]=1)[C:66]1[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 223948913-Carbamoyl-5-dipropylcarbamoyl-benzoic acidHCID 69869154(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanol Trifluoroacetate

Product 1

HCID 44426032N1-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl)-N3,N3-dipropyl-1,3,5-benzenetricarboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
22.5 °C

Procedure

To a mixture of 3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoic acid (IX, PREPARATION 6, 0.18 g, 0.616 mmol) in dry DMF (16 mL) is added EDC (0.182 g, 0.9 mmol), HOBT (0.127 g, 0.9 mmol), triethylamine (0.062 g, 0.616 mol), and (2R,3S)-3-amino-1-[(3-methoxybenzyl)amino]-4-phenyl-2-butanol (VIII, EXAMPLE 175, 0.185 g, 0.616 mmol). The mixture is stirred at 20-25 degrees C. for 3 days. The mixture is partitioned between water and ethyl acetate. The phases are separated and the organic phase is washed three times with water. The organic phase is dried over anhydrous magnesium sulfate, filtered and concentrated. Column chromatography (silica gel, 75 mL; methanol/methylene chloride, 10/90) gives the title compound, IR (diffuse reflectance) 3306, 3301, 3270, 2962, 1676, 1667, 1663, 1645, 1638, 1627, 1615, 1550, 1537, 1450 and 1439 cm−1; NMR (CDCl3) δ 0.645, 0.968, 1.20, 1.43, 1.67, 2.8, 2.97, 3.38, 3.47, 3.73, 3.87, 4.31, 6.78, 6.91, 7.23, 7.72, 7.87, 8.22 and 8.43.

Workup

  1. customThe mixture is partitioned between water and ethyl acetate
  2. customThe phases are separated
  3. washthe organic phase is washed three times with water
  4. dry with materialThe organic phase is dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-82f4803aa6514f62ba3dc9893e2e51d8
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Linked notes

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