1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → tert-butyl 4-((1S)-1-{[(2,5-dichloropyridin-3-yl)carbonyl]amino}ethyl)benzoate

HRID 1293183

Reaction equation

HRID 1293183 reaction equation
[Cl:1][C:2]1[N:10]=[CH:9][C:8]([Cl:11])=[CH:7][C:3]=1[C:4]([OH:6])=O.[NH2:12][C@H:13]([C:15]1[CH:27]=[CH:26][C:18]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[CH:17][CH:16]=1)[CH3:14].Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1>ClCCl.C(N(CC)CC)C>[Cl:1][C:2]1[C:3]([C:4]([NH:12][C@H:13]([C:15]2[CH:27]=[CH:26][C:18]([C:19]([O:21][C:22]([CH3:24])([CH3:23])[CH3:25])=[O:20])=[CH:17][CH:16]=2)[CH3:14])=[O:6])=[CH:7][C:8]([Cl:11])=[CH:9][N:10]=1

Participants

7

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27360852,5-Dichloropyridine-3-carboxylic acidHCID 27960291-Hydroxybenzotriazole hydrateHCID 51358470tert-butyl 4-[(1S)-1-aminoethyl]benzoate

Product 1

HCID 57572256tert-butyl 4-((1S)-1-{[(2,5-dichloropyridin-3-yl)carbonyl]amino}ethyl)benzoateYield 70%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To a stirred solution of 2,5-dichloronicotinic acid (Syn. Commun. 1989, 19, 553–9, 1.92 g, 10 mmol) and tert-butyl 4-[(1S)-1-aminoethyl]benzoate (example 44 step 3, 2.02 g, 9.1 mmol) in dichloromethane (20 mL) were successively added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) (2.59 g, 13.5 mmol), 1-hydroxybenzotriazole hydrate (HOBT) (2.07 g, 13.5 mmol), and triethylamine (4 mL). After being stirred overnight, the reaction was quenched by the addition of saturated sodium bicarbonate aqueous solution (100 mL). The aqueous layer was extracted with dichloromethane (50 mL×3) and the combined organic layers were washed with brine (100 mL), dried (sodium sulfate), and evaporated. The remaining residue was purified by flush column chromatography on silica gel (100 g) eluting with dichloromethane/ethyl acetate (20/1) to afford 2.51 g (70%) of the title compounds as white solids: 1H-NMR (CDCl3) δ 8.41 (1H, d, J=2.6 Hz), 8.09 (1H, d, J=2.6 Hz), 7.99 (2H, d, J=8.3 Hz), 7.43 (2H, d, J=8.3 Hz), 6.81 (1H, d, J=7.2 Hz), 5.33 (1H, dq, J=7.2, 7.0 Hz), 1.62 (3H, d, J=7.0 Hz), 1.58 (9H, s).

Workup

  1. customthe reaction was quenched by the addition of saturated sodium bicarbonate aqueous solution (100 mL)
  2. extractionThe aqueous layer was extracted with dichloromethane (50 mL×3)
  3. washthe combined organic layers were washed with brine (100 mL)
  4. dry with materialdried (sodium sulfate)
  5. customevaporated
  6. customThe remaining residue was purified
  7. customby flush column chromatography on silica gel (100 g)
  8. washeluting with dichloromethane/ethyl acetate (20/1)

Sources & evidence

ORD record
ord-197a03deed514e97bd29a962f9aa3629
Source dataset
uspto-grants-2007_07
Patent number
US07238714B2

Linked notes

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