Diisopropylethylamine → 2-[(2-Methylsulfonylbenzen-1-carbonyl)-amino]-indan-2-carboxylic acid ethyl ester

HRID 1047819Notes

Reaction equation

HRID 1047819 reaction equation
[CH3:1][S:2]([C:5]1[CH:13]=[CH:12][CH:11]=[CH:10][C:6]=1[C:7]([OH:9])=O)(=[O:4])=[O:3].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>CO.C(Cl)Cl.C(Cl)Cl>[CH2:38]([O:40][C:41]([C:43]1([NH:52][C:7]([C:6]2[CH:10]=[CH:11][CH:12]=[CH:13][C:5]=2[S:2]([CH3:1])(=[O:3])=[O:4])=[O:9])[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 2843422-Methanesulfonylbenzoic 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 593141392-[(2-Methylsulfonylbenzen-1-carbonyl)-amino]-indan-2-carboxylic acid ethyl esterYield 139.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

To a 40 mL vial containing a stirring bar, 2-(methylsulfonyl)benzoic acid (0.4 g, 2.88 mmol) is charged with dry DCM (7 mL). Stirring is initiated. HBTU (922 mg, 2.43 mmol). The 2-aminoindane-2-carboxylic acid ethyl ester (500 mg, 2.44 mmol) is added followed by the DIPEA (0.95 mL, 8 mmol). The reaction is allowed to stir for 36 h. Analysis by tlc of the reaction mixture (silica, 10% MeOH/DCM) 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 1.32 g of white solid. This material is dissolved in 10 mL of DCM and 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 50% over 8 column volumes and then 90% EtOAc for 2 column volumes with a ramp of 1 column volume. 25 mL fractions are collected. Fractions 5 through 8 are combined and evaporated in vacuo. Pumping to a constant weight gives amorphous white solid 0.71 g.

Workup

  1. additionTo a 40 mL vial containing a stirring bar
  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-f652abca2de14303b99d1e923c4cd934
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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