Dichloromethane → N-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[butyryl(propyl)amino]-5-methylbenzamide

HRID 348813Notes

Reaction equation

HRID 348813 reaction equation
C(P(=O)(O[CH2:8][CH3:9])OCC)#N.NC([C:14]1[CH:15]=[C:16]([CH:20]=[C:21]([C:23](N(CCC)CCC)=O)[CH:22]=1)[C:17]([OH:19])=O)=O.F[C:33](F)(F)[C:34]([OH:36])=O.[NH2:39][C@@H:40]([CH2:54][C:55]1[CH:60]=[C:59](F)[CH:58]=[C:57](F)[CH:56]=1)[C@H:41]([OH:53])[CH2:42][NH:43][CH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[C:47]([O:51][CH3:52])[CH:46]=1.C([N:65]([CH2:68][CH3:69])CC)C.Cl[CH2:71]Cl>>[CH2:54]([C@H:40]([NH:39][C:17](=[O:19])[C:16]1[CH:20]=[C:21]([CH3:23])[CH:22]=[C:14]([N:65]([C:34](=[O:36])[CH2:33][CH2:8][CH3:9])[CH2:68][CH2:69][CH3:71])[CH:15]=1)[C@H:41]([OH:53])[CH2:42][NH:43][CH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[C:47]([O:51][CH3:52])[CH:46]=1)[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1

Participants

6

Reactant 5

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 76257Diethyl cyanophosphonateHCID 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 68611790N-{(1S,2R)-1-Benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-[butyryl(propyl)amino]-5-methylbenzamide

Procedure

Following the procedure of EXAMPLE 570 and making non-critical variations, diethyl cyanophosphonate (0.0760 mL, 0.550 mmol) is added to a mixture of 3-[butyryl(propyl)amino]-5-methylbenzoic acid (IX, 0.120 g, 0.460 mmol), (2R,3S)-3-amino-1-[(3-methoxybenzyl)amino]-4-phenyl-2-butanol (VIII, 0.137 g, 0.460 mmol), and triethylamine (0.0760 mL, 0.550 mmol) in dichloromethane (5 mL). The mixture is stirred for 1 hour at 20–25 degrees C. Dichloromethane is then removed under reduced pressure. The residue is partitioned between ethyl acetate and water. The organic is separated, is washed with saline, dried over anhydrous sodium sulfate, filtered and concentrated. The concentrate is column chromatographed (silica gel; methanol/dichloromethane, 5/95) to give the title compound, NMR (400 MHz, CDCl3) δ 7.09, 4.15, 3.80, 3.79, 3.60, 3.02, 2.84, 2.36, 1.94, 1.56, 1.49, 0.87 and 0.81; . MS (ESI+) for C33H43N3O4 m/z (M+H)+=546.3; HRMS (FAB) calculated for C33H43N3O4+H=546.3331, found=546.3331.

Workup

  1. customDichloromethane is then removed under reduced pressure
  2. customThe residue is partitioned between ethyl acetate and water
  3. customThe organic is separated
  4. washis washed with saline
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customchromatographed (silica gel; methanol/dichloromethane, 5/95)

Sources & evidence

ORD record
ord-ee35a87a148c43caa4d765d0b3b73f8e
Source dataset
uspto-grants-2007_02
Patent number
US07176242B2

Reaction notes

Loading…