Trifluoroacetic acid → HCID 58529924, compound

HRID 1972962Notes

Reaction equation

HRID 1972962 reaction equation
C(OC([N:8]1[CH2:11][CH:10]([CH2:12][NH:13][CH2:14][CH2:15][CH2:16][C:17]2[N:25]3[C:20]([C:21]([NH2:26])=[N:22][CH:23]=[N:24]3)=[C:19]([C:27]3[CH:28]=[CH:29][C:30]4[C:34]([CH:35]=3)=[N:33][N:32]([CH2:36][C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[CH:31]=4)[CH:18]=2)[CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[NH:8]1[CH2:11][CH:10]([CH2:12][NH:13][CH2:14][CH2:15][CH2:16][C:17]2[N:25]3[C:20]([C:21]([NH2:26])=[N:22][CH:23]=[N:24]3)=[C:19]([C:27]3[CH:28]=[CH:29][C:30]4[C:34]([CH:35]=3)=[N:33][N:32]([CH2:36][C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[CH:31]=4)[CH:18]=2)[CH2:9]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 69326681HCID 69326681, compound

Product 1

HCID 58529924HCID 58529924, compoundYield 9.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 3-({3-[4-amino-5-(2-benzyl-2H-indazol-6-yl)-pyrrolo[2,1-f][1,2,4]triazin-7-yl]-propylamino}-methyl)-azetidine-1-carboxylic acid tert-butyl ester (80 mg, 0.14 mmol) in anhydrous DCM (2.8 mL) was added trifluoroacetic acid (1.4 mL). The mixture was stirred at rt under N2 for 3 days. The reaction mixture was concentrated and the crude was dissolved in EtOAc. The organic layer was washed with aqueous, saturated NaHCO3 solution, water and brine, dried (Na2SO4), filtered and concentrated in vacuo. The crude was purified via preparative HPLC [gradient 15 to 90% ACN/H2O+0.1% TFA]. The product containing fractions were collected, and the TFA was removed via filtration through an acidic resin followed by washing with acetonitrile. The product was then eluted with 2M NH3 in MeOH. The filtrate was concentrated and the residue was crystallized from DCM-ether to provide the title compound (6 mg, 9%) as a white solid. 1H NMR (300 MHz, MeOD). 8.39 (s, 1H), 7.85 to 7.82 (m, 2H), 7.65 (s, 1H), 7.36 to 7.33 (m, 5H), 7.24 (d, 1H), 6.56 (s, 1H), 5.67 (s, 2H), 4.02 (t, 2H), 3.78 to 3.75 (m, 2H), 3.05 (t, 3H), 2.87 (d, 2H), 2.70 (t, 2H), 2.02 to 1.98 (m, 2H); ES-MS m/z 467.3 [M+H]+, RT (min) 2.82.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe crude was dissolved in EtOAc
  3. washThe organic layer was washed with aqueous, saturated NaHCO3 solution, water and brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude was purified via preparative HPLC [gradient 15 to 90% ACN/H2O+0.1% TFA]
  8. additionThe product containing fractions
  9. customwere collected
  10. customthe TFA was removed via filtration through an acidic resin
  11. washby washing with acetonitrile
  12. washThe product was then eluted with 2M NH3 in MeOH
  13. concentrationThe filtrate was concentrated
  14. customthe residue was crystallized from DCM-ether

Sources & evidence

ORD record
ord-73af10c35d064643bf98e95d86492b03
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

Loading…