Hydrochloric Acid → HCID 67439351, compound

HRID 1664826Notes

Reaction equation

HRID 1664826 reaction equation
Cl.CN(C)CCCN=C=NCC.[Na].[F:14][C:15]1[C:20]([F:21])=[CH:19][CH:18]=[CH:17][C:16]=1[CH:22]([CH2:29][NH:30][CH2:31][C:32]1[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][C:33]=1[O:40][CH3:41])[CH2:23][CH2:24][CH2:25][C:26](O)=[O:27].Cl.O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>C(#N)C>[F:14][C:15]1[C:20]([F:21])=[CH:19][CH:18]=[CH:17][C:16]=1[CH:22]1[CH2:29][N:30]([CH2:31][C:32]2[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][C:33]=2[O:40][CH3:41])[C:26](=[O:27])[CH2:25][CH2:24][CH2:23]1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 27960291-Hydroxybenzotriazole hydrateHCID 5360545SodiumHCID 67439941HCID 67439941, compound

Product 1

HCID 67439351HCID 67439351, compoundYield 72.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (3.65 g, 19.1 mmol) was added to a solution of the sodium salt of 5-(2,3-difluorophenyl)-6-[(2,4-dimethoxybenzyl)amino]hexanoic acid (8.58 g, 17.3 mmol) in acetonitrile (346 mL). After 2 h, hydrochloric acid (4.0 M in dioxane; 13.0 mL; 52.0 mmol) was added. After 16 h, additional N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (3.24 g, 16.9 mmol), 1-hydroxybenzotriazole hydrate (1.0 g, 6.53 mmol) and triethylamine (4.83 mL, 34.6 mmol) were added. After 16 h, the reaction mixture was concentrated. The mixture was diluted with saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The organic extracts were washed with saturated brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% dichloromethane→96% dichloromethane/methanol) gave the title compound (4.72 g). MS 376.1 (M+1).

Workup

  1. waitAfter 16 h
  2. waitAfter 16 h
  3. concentrationthe reaction mixture was concentrated
  4. additionThe mixture was diluted with saturated aqueous sodium bicarbonate
  5. extractionextracted with ethyl acetate
  6. washThe organic extracts were washed with saturated brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by silica gel chromatography (100% dichloromethane→96% dichloromethane/methanol)

Sources & evidence

ORD record
ord-49b59f90904641babbdfbf86fedcf79c
Source dataset
uspto-grants-2011_10
Patent number
US08039460B2

Reaction notes

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