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

HRID 14018

Reaction equation

HRID 14018 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

Conditions

Temperature
22.5 °C

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-9316884b2ab24f57a4e0af3289abebf1
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Linked notes

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