Triethylamine → HCID 86591643, compound

HRID 2212970Notes

Reaction equation

HRID 2212970 reaction equation
C(O[C:4]([C@@H:6]1[CH2:10][CH2:9][CH2:8][C@@H:7]1[C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:20]#[N:21])[CH:18]=2)[NH:13][CH:12]=1)=[O:5])C.O.[OH-].[Li+].C(N(CC)CC)C.Cl.[CH3:33][NH:34][O:35][CH3:36].CCN=C=NCCCN(C)C.Cl>C(O)C.O.C(Cl)Cl>[CH3:36][O:35][N:34]([CH3:33])[C:4]([C@@H:6]1[CH2:10][CH2:9][CH2:8][C@H:7]1[C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:20]#[N:21])[CH:18]=2)[NH:13][CH:12]=1)=[O:5]

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 168937Lithium hydroxide, monohydrateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 69658351HCID 69658351, compound

Product 1

HCID 86591643HCID 86591643, compoundYield 41.3%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Procedure

A solution of cis-2-(5-cyano-1H-indol-3-yl)-cyclopentanecarboxylic acid ethyl ester (1.06 g, 3.75 mMol) and lithium hydroxide monohydrate (1.54 g, 37.5 mMol) in ethanol (50 mL) and water (10 mL) was heated to reflux for 3 h. The solution was concentrated in vacuo, and the residue was dissolved in water (20 mL) and HCl was added to pH<2. The reaction was extracted with ethyl acetate (4×10 mL), dried with magnesium sulfate, and evaporated in vacuo. The residue was suspended in methylene chloride with triethylamine (2.62 mL, 18.8 mMol). To this was added N,O-dimethylhydroxylamine hydrochloride (733 mg, 7.5 mMol) and EDC hydrochloride (1.58 g, 8.26 mMol) and the reaction was stirred for 2 h. Water (20 mL) was added and the reaction was extracted with methylene chloride (10 mL). The organic layers were dried with magnesium sulfate and the solvent was evaporated in vacuo. The residue was purified by chromatography on silica gel with ethyl acetate/hexanes (60%) to provide the product as a clear oil (460 mg, 41%). 1H NMR (400 MHz, CDCl3) δ 8.36 (1H, bs), 8.01 (1H, s), 7.28–7.41 (2H, m), 7.13 (1H, d, J=1.9 Hz), 3.74 (1H, m), 3.38 (3H, s), 3.38 (1H, buried), 3.11 (3H, s), 1.84–2.32 (5H, m), 1.37 (1H, sextet, J=7.6 Hz); MS m/e 320.2 (M+Na).

Workup

  1. temperatureto reflux for 3 h
  2. concentrationThe solution was concentrated in vacuo
  3. dissolutionthe residue was dissolved in water (20 mL)
  4. additionHCl was added to pH<2
  5. extractionThe reaction was extracted with ethyl acetate (4×10 mL)
  6. dry with materialdried with magnesium sulfate
  7. customevaporated in vacuo
  8. extractionthe reaction was extracted with methylene chloride (10 mL)
  9. dry with materialThe organic layers were dried with magnesium sulfate
  10. customthe solvent was evaporated in vacuo
  11. customThe residue was purified by chromatography on silica gel with ethyl acetate/hexanes (60%)

Sources & evidence

ORD record
ord-ba05f30956354f3ca2d78455a5bb14f2
Source dataset
uspto-grants-2006_09
Patent number
US07105516B2

Reaction notes

Loading…