Ethyl Acetate → HCID 15598548, compound

HRID 594189Notes

Reaction equation

HRID 594189 reaction equation
Cl.[C:2]([O:6][C:7](=[O:13])[C@@H:8]1[CH2:12][CH2:11][CH2:10][NH:9]1)([CH3:5])([CH3:4])[CH3:3].CC[N:16]([CH:20]([CH3:22])[CH3:21])[CH:17]([CH3:19])C.CN(C([O:30]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(OCC)(=O)C>ClCCl>[NH:16]1[CH2:17][CH2:19][CH2:22][C@H:20]1[C:21]([N:9]1[CH2:10][CH2:11][CH2:12][C@H:8]1[C:7]([O:6][C:2]([CH3:5])([CH3:3])[CH3:4])=[O:13])=[O:30]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 6453107tert-Butyl L-prolinate hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 15598548HCID 15598548, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of L-proline-tert-butyl ester hydrogen chloride salt 75 (0.5 g, 2.9 mmol) in dichloromethane (50 mL) was added 76 (0.98 g, 2.99 mmol), DIPEA (756 mg, 4.35 mmol) and HATU (1.3 g, 3.5 mmol). The reaction mixture was allowed to stir at an ambient temperature for 16 h. The mixture was poured into ethyl acetate (100 mL) and was washed with 0.2 N HCl (50 mL), water (50 mL), brine (50 mL) and dried over MgSO4. Chromatography was conducted on a 2 mm radial chromatotron plate eluting with 10% ethyl acetate in hexanes. Product-containing fractions were concentrated under reduced pressure, dissolved in dichloromethane (8 mL) and treated with piperidine (2 mL). The mixture was stirred for 1 h, concentrated under reduced pressure and purified on a 2 mm radial chromatotron plate eluting with 5% methanol/dichloromethane. This gave 200 mg (26%) of the dipeptide 74: 1H-NMR (400 MHz, CDCl3) δ 4.41 (m, 1H), 4.17 (m, 1H), 3.82 (m, 1H), 3.57 (m, 4H), 3.2 (m, 1H), 2.82 (m, 1H), 2.83-1.65 (m, 5H), 1.44 (m, 9H).

Workup

  1. washwas washed with 0.2 N HCl (50 mL), water (50 mL), brine (50 mL)
  2. dry with materialdried over MgSO4
  3. washeluting with 10% ethyl acetate in hexanes
  4. concentrationProduct-containing fractions were concentrated under reduced pressure
  5. dissolutiondissolved in dichloromethane (8 mL)
  6. additiontreated with piperidine (2 mL)
  7. stirringThe mixture was stirred for 1 h
  8. concentrationconcentrated under reduced pressure
  9. custompurified on a 2 mm radial chromatotron plate
  10. washeluting with 5% methanol/dichloromethane

Sources & evidence

ORD record
ord-1a9f673ed5a84357a61ad031be4f32e6
Source dataset
uspto-grants-2016_01
Patent number
US09242013B2

Reaction notes

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