Formic Acid → HCID 60054145, compound

HRID 488360Notes

Reaction equation

HRID 488360 reaction equation
[CH2:1]1[C:10]2[C:5](=[CH:6][C:7]([N:11]3[CH2:15][C@H:14]([CH2:16][NH:17][C:18](=[O:20])[CH3:19])[O:13][C:12]3=[O:21])=[CH:8][CH:9]=2)[CH2:4][CH2:3][NH:2]1.CCN=C=NCCCN(C)C.Cl.[CH:34](O)=[O:35]>C1COCC1.O>[CH:34]([N:2]1[CH2:3][CH2:4][C:5]2[C:10](=[CH:9][CH:8]=[C:7]([N:11]3[CH2:15][C@H:14]([CH2:16][NH:17][C:18](=[O:20])[CH3:19])[O:13][C:12]3=[O:21])[CH:6]=2)[CH2:1]1)=[O:35]

Participants

6

Reactant 3

HCID 284Formic AcidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 69734604HCID 69734604, compound

Product 1

HCID 60054145HCID 60054145, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of N-[[(5S)-3-[1,2,3,4-tetrahydro-6-isoquinolinyl]-2-oxo-5-oxazolidinyl]methyl]acetamide (Example 1, Step 6, 200 mg, 0.691 mmol) in THF is treated with EDC.HCl (172 mg, 0.899 mmol) and formic acid (34 μL, 0.899 mmol) to give a white slurry which is then diluted with H2O (approx. 2 mL) to give a homogeneous mixture. The mixture is stirred at ambient temperature for 1.25 hrs and is then diluted with H2O (10 mL) and extracted with CH2Cl2 (4×20 mL). The combined organic phase is washed with brine (10 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure, and the crude product is chromatographed on a Flash 40S silica gel (40 g, 32-63 μm) cartridge, eluting with a gradient of MeOH/CH2Cl2 (1/99-5/95). Those fractions with an Rf=0.41 by TLC (MeOH/CHCl3, 10/90) are pooled and concentrated and the resulting glassy solid is triturated with Et2O and filtered to give 161 mg (74%) of the title compound as a white solid, mp 139-141° C. (dec.). [α]25D=−22° (c 0.92, DMSO).

Workup

  1. customto give a white slurry which
  2. customto give a homogeneous mixture
  3. extractionextracted with CH2Cl2 (4×20 mL)
  4. washThe combined organic phase is washed with brine (10 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customthe crude product is chromatographed on a Flash 40S silica gel (40 g, 32-63 μm) cartridge
  8. washeluting with a gradient of MeOH/CH2Cl2 (1/99-5/95)
  9. concentrationconcentrated
  10. customthe resulting glassy solid is triturated with Et2O
  11. filtrationfiltered

Sources & evidence

ORD record
ord-4132e80fd8c046dd836aa6555aca648c
Source dataset
uspto-grants-2005_12
Patent number
US06972286B2

Reaction notes

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