Diisopropylethylamine → HCID 59314205, compound

HRID 1047811Notes

Reaction equation

HRID 1047811 reaction equation
[Cl:1][C:2]1[CH:14]=[CH:13][C:5]2[S:6][C:7]([C:10]([OH:12])=O)=[C:8]([CH3:9])[C:4]=2[CH:3]=1.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.[CH2:48]([O:50][C:51]([C:53]1([NH2:62])[CH2:61][C:60]2[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=2)[CH2:54]1)=[O:52])[CH3:49]>CO.C(Cl)Cl.C(Cl)Cl>[CH2:48]([O:50][C:51]([C:53]1([NH:62][C:10]([C:7]2[S:6][C:5]3[CH:13]=[CH:14][C:2]([Cl:1])=[CH:3][C:4]=3[C:8]=2[CH3:9])=[O:12])[CH2:61][C:60]2[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=2)[CH2:54]1)=[O:52])[CH3:49]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27946145-Chloro-3-methyl-1-benzothiophene-2-carboxylic acidHCID 10921653Ethyl 2-amino-2,3-dihydro-1H-indene-2-carboxylate

Product 1

HCID 59314205HCID 59314205, compoundYield 53.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

To a 40 mL vial containing a stirring bar, 5-chloro3-methyl-benzo[b]thiophene-2-carboxylic acid ([50451-84-8], 0.81 g, 3.53 mmol) is charged with dry DCM (10 mL). Stirring is initiated. HBTU (1.34 g, 3.54 mmol) and the DIPEA (1.4 mL, 8.0 mmol) are added. The 2-aminoindane-2-carboxylic acid ethyl ester (0.725 g, 3.53 mmol) is added. The reaction is allowed to stir for 240 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 (80 mL) and transferred to a reparatory 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 1.26 g of a off white solid. This material is purified utilizing an ISCO Companion with a 40 g cartridge of silica. The gradient is 20% EtOAc in heptanes over 3 column volumes followed by a step gradient to 30% and then 50% and then 70% EtOAc for 2 column volumes each with a ramp of 1 column volume. 25 mL fractions are collected. Fractions 22 through 60 are combined and evaporated in vacuo. Pumping to a constant weight gives amorphous white solid 0.78 g.

Workup

  1. additionTo a 40 mL vial containing a stirring bar
  2. stirringto stir for 240 h
  3. customconsumption of the starting amine
  4. additionThe contents of the reaction flask are diluted with EtOAc (80 mL)
  5. customtransferred to a reparatory 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 1.26 g of a off white solid
  11. customThis material is purified
  12. custom25 mL fractions are collected
  13. customevaporated in vacuo

Sources & evidence

ORD record
ord-10b0de4e9df04399b42b39b18b4991c2
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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