Diisopropylethylamine → HCID 59314190, compound

HRID 1047939Notes

Reaction equation

HRID 1047939 reaction equation
[F:1][C:2]1[C:3]([C:8]([OH:10])=O)=[N:4][CH:5]=[CH:6][CH:7]=1.[CH2:11]([O:13][C:14]([C:16]1([NH2:25])[CH2:24][C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:17]1)=[O:15])[CH3:12].CCN(C(C)C)C(C)C.CC(O)C.C(Cl)Cl>C(Cl)Cl>[CH2:11]([O:13][C:14]([C:16]1([NH:25][C:8]([C:3]2[C:2]([F:1])=[CH:7][CH:6]=[CH:5][N:4]=2)=[O:10])[CH2:24][C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:17]1)=[O:15])[CH3:12]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27627863-Fluoropyridine-2-carboxylic acidHCID 10921653Ethyl 2-amino-2,3-dihydro-1H-indene-2-carboxylateHCID 21966342Isopropanol methylene chloride

Product 1

HCID 59314190HCID 59314190, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A 40 mL reaction vial which contains a stirring bar is charged with 3-Fluoropyridine-2-carboxylic acid (997 mg, 7.07 mmol) and dry DCM (15 mL). Stirring is initiated. After 2 min, the HTBU (2.7 g, 7.07 mmol) is added. After 5 min, 2-Amino-indan-2-carboxylic acid ethyl ester (1.45 g, 7.07 mmol) is added followed by DIPEA (2.50 mL, 14.5 mmol). The reaction is allowed to stir for 18 h. 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 water (3%, 25 mL), saturated aqueous NaHCO3 (2×25 mL) and brine (25 mL), and then dried over MgSO4, filtered and evaporated in vacuo to provide 4.15 g of light orange solid. This material is dissolved in 20 mL of DCM. This material is purified utilizing an ISCO Companion with an 80 g cartridge of silica. The gradient is 5% EtOAc in heptanes for 4 column volumes followed by a linear gradient to 60% EtOAc in heptanes over 10 column volumes. 14 mL fractions of UV active elutant are collected. Fractions 6 through 14 are combined and evaporated in vacuo. This yields 2.04 g white solid (2.04 g, 88%).

Workup

  1. customA 40 mL reaction vial which
  2. additionthe HTBU (2.7 g, 7.07 mmol) is added
  3. waitAfter 5 min
  4. stirringto stir for 18 h
  5. customconsumption of the starting amine
  6. customThe contents of the reaction flask are transferred to a separatory funnel
  7. additiondiluted with EtOAc (50 mL)
  8. washThis is washed consecutively with water (3%, 25 mL), saturated aqueous NaHCO3 (2×25 mL) and brine (25 mL)
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. customevaporated in vacuo
  12. customto provide 4.15 g of light orange solid
  13. customThis material is purified
  14. custom14 mL fractions of UV active elutant are collected
  15. customevaporated in vacuo

Sources & evidence

ORD record
ord-4570608a5e824a9da1c9a0d94d355ef4
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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