Trifluoroacetic acid → HCID 67076742, compound

HRID 521473

Reaction equation

HRID 521473 reaction equation
[NH2:1][C:2]1([C:11]([OH:13])=[O:12])[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3]1.[OH:14][C:15]1[CH:16]=[C:17]([CH:21]=[CH:22][C:23]=1[O:24][CH3:25])[C:18]([OH:20])=O.N1CCCCC1.Br[CH2:33][C:34]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1[F:42])=[O:35].N12CCCN=C1CCCCC2.C(O)(C(F)(F)F)=O>CN(C=O)C.C(Cl)Cl>[F:42][C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=1[CH:34]([OH:35])[CH2:33][O:14][C:15]1[CH:16]=[C:17]([CH:21]=[CH:22][C:23]=1[O:24][CH3:25])[C:18]([NH:1][C:2]1([C:11]([OH:13])=[O:12])[CH2:3][C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH2:10]1)=[O:20]

Participants

9

Reactant 6

HCID 6422Trifluoroacetic acidHCID 8082PiperidineHCID 12575Isovanillic AcidHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 2509362-Aminoindane-2-carboxylic acidHCID 27374492-Bromo-2'-fluoroacetophenone

Product 1

HCID 67076742HCID 67076742, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

The title compound was prepared according to the general procedure described in example 125 using 0.25 g of resin (0.5 mmol/g). Attachment of the 2-amino-indane-2-carboxylic acid moiety to the resin was followed by acylation with 3-hydroxy-4-methoxy-benzoic acid and treatment with 50% piperidine in DMF for 2 h. After extensive washing with DMF and DCM the resin was reacted with 2-bromo-1-(2-fluoro-phenyl)-ethanone (3 equivalents) in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU; 3 equivalents) in 3 ml of DCM overnight at room temperature. The compound was cleaved from the resin with neat TFA for 2 h, and TFA was evaporated in vacuo. The crude intermediate product was dissolved in 4 ml of THF, 10 mg of lithium borohydride were added and the reaction mixture was shaken for 3 h. Then the reaction mixture was quenched with acetic acid, evaporated to dryness, and the residue was purified by preparative RP HPLC (water/ACN gradient). Yield: 3.7 mg.

Workup

  1. washAfter extensive washing with DMF and DCM the resin
  2. customTFA was evaporated in vacuo
  3. dissolutionThe crude intermediate product was dissolved in 4 ml of THF
  4. addition10 mg of lithium borohydride were added
  5. customThen the reaction mixture was quenched with acetic acid
  6. customevaporated to dryness
  7. customthe residue was purified by preparative RP HPLC (water/ACN gradient)

Sources & evidence

ORD record
ord-a62538756ee9488696788acccde78f5e
Source dataset
uspto-grants-2016_05
Patent number
US09328071B2

Linked notes

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