Diisopropylethylamine → HCID 59314241, compound

HRID 1047807Notes

Reaction equation

HRID 1047807 reaction equation
[CH2:1]([O:3][C:4]([C:6]1([NH2:15])[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7]1)=[O:5])[CH3:2].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:40][C:41]1[C:49]([O:50][CH3:51])=[CH:48][CH:47]=[CH:46][C:42]=1[C:43](O)=[O:44].CCN(C(C)C)C(C)C>C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1([NH:15][C:43](=[O:44])[C:42]2[CH:46]=[CH:47][CH:48]=[C:49]([O:50][CH3:51])[C:41]=2[CH3:40])[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7]1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 70214833-Methoxy-2-MethylBenzoic AcidHCID 10921653Ethyl 2-amino-2,3-dihydro-1H-indene-2-carboxylate

Product 1

HCID 59314241HCID 59314241, compoundYield 85.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A 100 mL round bottom flask is charged with 2-amino-indane-2-carboxylic acid ethyl ester (750 mg, 3.65 mmol) and dry DCM (10 mL). A stirring bar is added and stirring is initiated. The HBTU (1.38 g, 3.65 mmol) is added. After 2 min, the 2-methyl-3-methoxy-benzoic acid (0.61 g, 3.65 mmol) and DIPEA (1.5 mL, 8.6 mmol) are added. The reaction is allowed to stir for 36 h. Analysis by tlc of the reaction mixture (silica, 50% EtOAc/heptanes) 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 NaHCO3 (25 mL) and brine (25 mL), dried over MgSO4, filtered and evaporated in vacuo to provide 1.1 g of thick brownish gum. This material is purified utilizing an ISCO Companion with a 40 g cartridge of silica. The gradient is 15% EtOAc in heptanes over 2 column volumes followed by a step gradient to 30% EtOAc then 50% and then 70% EtOAc for 3 column volumes each with ramp of 1 column volume. 35 mL fractions are collected. Fractions 15 through 21 are combined and evaporated in vacuo. Pumping to a constant weight gives a white solid (1.15 g).

Workup

  1. additionA stirring bar is added
  2. stirringto stir for 36 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 NaHCO3 (25 mL) and brine (25 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated in vacuo

Sources & evidence

ORD record
ord-275d7c1eef9048db90e0bdacae6bea7f
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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