Diisopropylethylamine → HCID 59314316, compound

HRID 1047825Notes

Reaction equation

HRID 1047825 reaction equation
[CH3:1][C:2]1[O:3][C:4]2[C:10]([C:11]([OH:13])=O)=[CH:9][CH:8]=[CH:7][C:5]=2[CH:6]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:38]([O:40][C:41]([C:43]1([NH2:52])[CH2:51][C:50]2[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=2)[CH2:44]1)=[O:42])[CH3:39].CCN(C(C)C)C(C)C>CCO.ClCCl.C(Cl)Cl>[CH2:38]([O:40][C:41]([C:43]1([NH:52][C:11]([C:10]2[C:4]3[O:3][C:2]([CH3:1])=[CH:6][C:5]=3[CH:7]=[CH:8][CH:9]=2)=[O:13])[CH2:51][C:50]2[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=2)[CH2:44]1)=[O:42])[CH3:39]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2731742-methylbenzofuran-7-carboxylic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10921653Ethyl 2-amino-2,3-dihydro-1H-indene-2-carboxylate

Product 1

HCID 59314316HCID 59314316, compoundYield 136.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21584144Dichloromethane ethanolSolvent

Procedure

To a 25 mL vial containing a stirring bar, 2-methylbenzofuran-7-carboxylic acid (0.343 g, 1.95 mmol) is charged with dry DCM (6 mL). Stirring is initiated. HBTU (738 mg, 1.95 mmol) is added. The 2-aminoindane-2-carboxylic acid ethyl ester (400 mg, 1.95 mmol) is added followed by DIPEA (0.75 mL, 4.31 mmol). The reaction is allowed to stir for 16 h. Analysis by tlc of the reaction mixture (silica, 10% EtOH/dichloromethane) indicates complete consumption of the starting amine. The contents of the reaction flask are diluted with EtOAc (50 mL) and transferred to a separatory funnel. This is washed consecutively with dilute aqueous HCl (3%, 25 mL), saturated aqueous NaHCO3 (25 mL) and brine (25 mL), dried over MgSO4, filtered and evaporated in vacuo to provide 0.97 g of yellow oil. This material is dissolved in 10 mL of DCM. This is purified utilizing an ISCO Companion with a 40 g cartridge of silica. The gradient is 15% EtOAc in heptanes for 3 column volumes followed by a linear gradient to 90% over 15 column volumes and then 100% EtOAc for 2 column volumes with a ramp of 1 column volume. 25 mL fractions are collected. Fractions 2 through 7 are combined and evaporated in vacuo to a constant weight to give 0.63 g of amorphous white solid.

Workup

  1. additionTo a 25 mL vial containing a stirring bar
  2. stirringto stir for 16 h
  3. customconsumption of the starting amine
  4. additionThe contents of the reaction flask are diluted with EtOAc (50 mL)
  5. customtransferred to a separatory funnel
  6. washThis is washed consecutively with dilute aqueous HCl (3%, 25 mL), saturated aqueous NaHCO3 (25 mL) and brine (25 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated in vacuo

Sources & evidence

ORD record
ord-29a2fd9cca344cb182f931adbeea198c
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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