Sodium Iodide → HCID 58529552, compound

HRID 1972967Notes

Reaction equation

HRID 1972967 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]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:30]([N:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1)(=[O:32])[CH3:31].C(N(CC)CC)C.[I-].[Na+]>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:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH:16]=4)[CH:18]=[C:19]([CH2:27][CH2:28][N:36]3[CH2:37][CH2:38][N:33]([C:30](=[O:32])[CH3:31])[CH2:34][CH2:35]3)[N:20]2[N:21]=[CH:22][N:23]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 8471TriethylamineHCID 837951-AcetylpiperazineHCID 58529284HCID 58529284, compound

Product 1

HCID 58529552HCID 58529552, compoundYield 65.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 5-(2-benzyl-2H-indazol-6-yl)-7-(2-bromo-ethyl)-pyrrolo[2,1-f][1,2,4]-triazin-4-ylamine (70 mg, 0.156 mmol), 1-acetyl-piperazine (40.1 mg, 0.313 mmol, 2.0 eq), triethylamine (20.6 mg, 0.20 mmol, 1.3 eq), and sodium iodide (2.3 mg, 0.016 mmol, 0.1 eq) in anhydrous DMF (1.6 mL) was stirred at 50° C. for 15 h. The reaction mixture was partitioned between EtOAc and water, and the organic layer was washed with 50% aqueous brine (3×), dried over 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 elided with 2M NH3 in MeOH. The filtrate was concentrated and the residue was crystallized from DCM-hexane to provide the title compound (50.3 mg, 65%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.54 (s, 1H), 7.89 (s, 1H), 7.80 (dd, 1H), 7.57 (s, 1H), 7.36 to 7.30 (m, 5H), 7.13 (dd, 1H), 6.65 (s, 1H), 5.65 (s, 2H), 3.40 (q, 4H), 3.07 (t, 2H), 2.68 (t, 2H), 2.45 (t, 2H), 2.38 (t, 2H), 1.97 (s, 3H); ES-MS m/z 495.3 [M+H]+, RT (min) 2.02.

Workup

  1. customThe reaction mixture was partitioned between EtOAc and water
  2. washthe organic layer was washed with 50% aqueous brine (3×)
  3. dry with materialdried over 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. concentrationThe filtrate was concentrated
  12. customthe residue was crystallized from DCM-hexane

Sources & evidence

ORD record
ord-9fa937a263334628aa58a25cdfca709b
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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