Water → HCID 58529944, compound

HRID 1972963Notes

Reaction equation

HRID 1972963 reaction equation
[CH2:1]([N:8]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([C:17]3[CH:18]=[C:19]([CH2:27][CH2:28][CH2:29]Br)[N:20]4[C:25]=3[C:24]([NH2:26])=[N:23][CH:22]=[N:21]4)[CH:13]=[CH:14]2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C-:31]#[N:32].[Na+].[I-].[Na+].O>CN(C=O)C>[NH2:26][C:24]1[C:25]2=[C:17]([C:12]3[CH:13]=[CH:14][C:15]4[C:10]([CH:11]=3)=[N:9][N:8]([CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH:16]=4)[CH:18]=[C:19]([CH2:27][CH2:28][CH2:29][C:31]#[N:32])[N:20]2[N:21]=[CH:22][N:23]=1

Participants

6

Reactant 4

HCID 962WaterHCID 5238Sodium IodideHCID 8929Sodium CyanideHCID 58529276HCID 58529276, compound

Product 1

HCID 58529944HCID 58529944, compoundYield 67.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 5-(2-benzyl-2H-indazol-6-yl)-7-(3-bromopropyl)pyrrolo[2,1-f][1,2,4]triazin-4-ylamine (80 mg, 0.173 mmol), sodium cyanide (17 mg, 0.35 mmol, 2.0 eq.), and sodium iodide (2.6 mg, 0.017 mmol, 0.1 eq.) in anhydrous DMF (1.7 mL) was stirred at 100° C. for 16 h. The reaction mixture was cooled to rt and poured into water. The aqueous layer was extracted with 3×25 mL of EtOAc and the combined organic phases were washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. The crude was purified via preparative HPLC. The product containing fractions were collected, and the TFA from the eluent 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 (47.5 mg, 67%) as a white solid. 1H NMR (300 MHz, DMSO-d6) 8.54 (s, 1H), 7.91 (s, 1H), 7.80 (d, 1H), 7.59 (s, 1H), 7.36 to 7.30 (m, 5H), 7.15 (dd, 1H), 6.65 (s, 1H), 5.65 (s, 2H), 3.00 (t, 2H), 2.59 (t, 2H), 2.04 to 1.96 (m, 2H); ES-MS m/z 408.3 [M+H]+, RT (min) 2.95.

Workup

  1. extractionThe aqueous layer was extracted with 3×25 mL of EtOAc
  2. washthe combined organic phases were washed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude was purified via preparative HPLC
  7. additionThe product containing fractions
  8. customwere collected
  9. customthe TFA from the eluent was removed via filtration through an acidic resin
  10. washby washing with acetonitrile
  11. washThe product was then eluted with 2M NH3 in MeOH
  12. concentrationThe filtrate was concentrated
  13. customthe residue was crystallized from DCM-ether

Sources & evidence

ORD record
ord-4e8cf54a919c465b9c898c73f053069e
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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