Diisopropylethylamine → 2-[(Benzo[b]thiophene-5-carbonyl)-amino]-indane-2-carboxylic acid ethyl ester

HRID 1047817Notes

Reaction equation

HRID 1047817 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[C:7]([C:10]([OH:12])=O)[CH:8]=[CH:9][C:2]1=2.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH2:46]([O:48][C:49]([C:51]1([NH2:60])[CH2:59][C:58]2[C:53](=[CH:54][CH:55]=[CH:56][CH:57]=2)[CH2:52]1)=[O:50])[CH3:47]>CO.C(Cl)Cl.C(Cl)Cl>[CH2:46]([O:48][C:49]([C:51]1([NH:60][C:10]([C:7]2[CH:8]=[CH:9][C:2]3[S:1][CH:5]=[CH:4][C:3]=3[CH:6]=2)=[O:12])[CH2:59][C:58]2[C:53](=[CH:54][CH:55]=[CH:56][CH:57]=2)[CH2:52]1)=[O:50])[CH3:47]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27954441-Benzothiophene-5-carboxylic acidHCID 10921653Ethyl 2-amino-2,3-dihydro-1H-indene-2-carboxylate

Product 1

HCID 593140832-[(Benzo[b]thiophene-5-carbonyl)-amino]-indane-2-carboxylic acid ethyl esterYield 88.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

To a 40 mL vial containing a stirring bar, benzo[b]thiophene-5-carboxylic acid (434 g, 2.44 mmol) is charged with dry DCM (7 mL). Stirring is initiated. HBTU (922 mg, 2.43 mmol) and DIPEA (0.95 mL, 8 mmol) are added. The 2-aminoindane-2-carboxylic acid ethyl ester (500 mg, 2.44 mmol) is added. The reaction is allowed to stir for 64 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 1.4 g of an off white solid. 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 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 4 through 16 are combined and evaporated in vacuo. Pumping to a constant weight gives amorphous white solid 0.79 g.

Workup

  1. additionTo a 40 mL vial containing a stirring bar
  2. stirringto stir for 64 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
  10. customto provide 1.4 g of an off white solid
  11. customThis material is purified
  12. custom25 mL fractions are collected
  13. customevaporated in vacuo

Sources & evidence

ORD record
ord-6c339960b4104f839816c3cb4be7c864
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

Loading…