1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 3-((R)-3-((S)-3,3-dimethylbutan-2-yl)-6-(4-fluorophenyl)-2-oxo-1,3-oxazinan-6-yl)propanamide

HRID 403584Notes

Reaction equation

HRID 403584 reaction equation
[CH3:1][C:2]([CH3:25])([CH3:24])[C@@H:3]([N:5]1[CH2:10][CH2:9][C@:8]([CH2:18][CH2:19][C:20](O)=[O:21])([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[O:7][C:6]1=[O:23])[CH3:4].CC[N:28]=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH3:1][C:2]([CH3:25])([CH3:24])[C@@H:3]([N:5]1[CH2:10][CH2:9][C@:8]([CH2:18][CH2:19][C:20]([NH2:28])=[O:21])([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[O:7][C:6]1=[O:23])[CH3:4]

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 584852693-((R)-3-((S)-3,3-dimethylbutan-2-yl)-6-(4-fluorophenyl)-2-oxo-1,3-oxazinan-6-yl)propanoic acid

Product 1

HCID 426422863-((R)-3-((S)-3,3-dimethylbutan-2-yl)-6-(4-fluorophenyl)-2-oxo-1,3-oxazinan-6-yl)propanamideYield 30%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-((R)-3-((S)-3,3-dimethylbutan-2-yl)-6-(4-fluorophenyl)-2-oxo-1,3-oxazinan-6-yl)propanoic acid (50 mg, 0.144 mmol), EDCI (55 mg, 0.28 mmol), HOBt (38 mg, 0.28 mmol), and DIEA (90 mg, 0.07 mmol) were dissolved in CH2Cl2 (10 mL) under ice bath. The mixture was stirred under an NH3 atmosphere overnight. The reaction mixture was concentrated to give the crude product, which was purified by preparative TLC to give 3-((R)-3-((S)-3,3-dimethylbutan-2-yl)-6-(4-fluorophenyl)-2-oxo-1,3-oxazinan-6-yl)propanamide (15 mg, 30%). LC-MS Method 1 tR=2.027, min, m/z=351.1; 1H NMR (CDCl3) 0.73 (s, 9H), 1.12 (d, 3H), 1.89-1.98 (m, 1H), 2.01-2.12 (m, 1H), 2.22-2.38 (m, 3H), 2.48-2.52 (m, 1H), 2.71 (m, 1H), 3.18 (m, 1H), 4.46 (m, 1H), 5.29 (s, 1H), 5.53 (s, 1H), 7.07 (m, 2H), 7.29 (m, 2H)

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customto give the crude product, which
  3. customwas purified by preparative TLC

Sources & evidence

ORD record
ord-4ca6af5c05b847d8b5bdffa0233e6012
Source dataset
uspto-grants-2014_06
Patent number
US08748444B2

Reaction notes

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