Diisopropylethylamine → HCID 59314253, compound

HRID 1047926Notes

Reaction equation

HRID 1047926 reaction equation
[CH2:1]([O:4][C:5]1[C:6]([C:11]([OH:13])=O)=[N:7][CH:8]=[CH:9][CH:10]=1)[CH2:2][CH3:3].[CH2:14]([O:16][C:17]([CH:19]1[CH2:27][C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:20]1)=[O:18])[CH3:15].CC[N:30](C(C)C)C(C)C.CC(O)C.C(Cl)Cl>C(Cl)Cl>[CH2:14]([O:16][C:17]([C:19]1([NH:30][C:11]([C:6]2[C:5]([O:4][CH2:1][CH2:2][CH3:3])=[CH:10][CH:9]=[CH:8][N:7]=2)=[O:13])[CH2:27][C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:20]1)=[O:18])[CH3:15]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 15280733ethyl 2,3-dihydro-1H-indene-2-carboxylateHCID 197561423-Propoxypyridine-2-carboxylic acidHCID 21966342Isopropanol methylene chloride

Product 1

HCID 59314253HCID 59314253, compoundYield 99%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A 40 mL reaction vial which contains a stirring bar is charged with 3-n-propoxypicolinic acid (397 mg, 2.19 mmol) and dry DCM (6 mL). Stirring is initiated. After 2 min, the HTBU (831 mg, 2.195 mmol) is added. After 5 min, the 2-amino)-indane-2-carboxylic acid ethyl ester (450 mg, 2.19 mmol is added followed by DIPEA (0.96 mL, 5.48 mmol). The reaction is allowed to stir at ambient temperature. After 20 days, analysis by tlc of the reaction mixture (silica, 5% iPrOH/DCM) indicates complete consumption of the starting amine. The contents of the reaction flask are transferred to a separatory funnel and diluted with EtOAc (50 mL). This is washed consecutively with dilute aqueous HCl (3%, 25 mL), saturated aqueous NaHCO3 (25 mL) and brine (25 mL), and dried over MgSO4, filtered and evaporated in vacuo to give 1.23 g of light orange solid. This material is dissolved in 10 mL of DCM. This material is purified utilizing an ISCO Companion with a 40 g cartridge of silica. The gradient is 10% EtOAc in heptanes over 3 column volumes followed by a linear gradient to 60% EtOAc in heptanes over 10 column volumes. 17 mL fractions eluent are collected. Fractions 57 through 67 are combined and evaporated in vacuo by pumping to constant weight to give white solid (0.8 g, 99%).

Workup

  1. customA 40 mL reaction vial which
  2. additionthe HTBU (831 mg, 2.195 mmol) is added
  3. waitAfter 5 min
  4. stirringto stir at ambient temperature
  5. waitAfter 20 days
  6. customconsumption of the starting amine
  7. customThe contents of the reaction flask are transferred to a separatory funnel
  8. additiondiluted with EtOAc (50 mL)
  9. washThis is washed consecutively with dilute aqueous HCl (3%, 25 mL), saturated aqueous NaHCO3 (25 mL) and brine (25 mL)
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. customevaporated in vacuo
  13. customto give 1.23 g of light orange solid
  14. customThis material is purified
  15. custom17 mL fractions eluent are collected
  16. customevaporated in vacuo

Sources & evidence

ORD record
ord-c1a9c36b7a6e4ca9ab0067885fcf3356
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

Loading…