Sodium Sulfate → (4-[1-(3-Fluoro-benzyl)-1H-indazol-5-ylamino]-pyrrolo[2,1-f][1,2,4]triazin-5-yl}-methanol

HRID 1072092Notes

Reaction equation

HRID 1072092 reaction equation
Br[CH2:2][C:3]1[CH:4]=[CH:5][N:6]2[C:11]=1[C:10](Cl)=[N:9][CH:8]=[N:7]2.C([O-])(O)=O.[Na+].[O-:18]S([O-])(=O)=O.[Na+].[Na+].[F:25][C:26]1[CH:27]=[C:28]([CH:40]=[CH:41][CH:42]=1)[CH2:29][N:30]1[C:38]2[C:33](=[CH:34][C:35]([NH2:39])=[CH:36][CH:37]=2)[CH:32]=[N:31]1>C(#N)C.O>[F:25][C:26]1[CH:27]=[C:28]([CH:40]=[CH:41][CH:42]=1)[CH2:29][N:30]1[C:38]2[C:33](=[CH:34][C:35]([NH:39][C:10]3[C:11]4=[C:3]([CH2:2][OH:18])[CH:4]=[CH:5][N:6]4[N:7]=[CH:8][N:9]=3)=[CH:36][CH:37]=2)[CH:32]=[N:31]1

Participants

7

Reactant 4

HCID 24436Sodium SulfateHCID 516892Sodium Bicarbonate2×HCID 71470731-(3-Fluorobenzyl)-1H-indazol-5-amineHCID 218743865-(Bromomethyl)-4-chloropyrrolo[2,1-f][1,2,4]triazine

Product 1

HCID 22390542(4-[1-(3-Fluoro-benzyl)-1H-indazol-5-ylamino]-pyrrolo[2,1-f][1,2,4]triazin-5-yl}-methanolYield 65%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of crude 5-bromomethyl-4-chloro-pyrrolo[2,1-f][1,2,4]triazine (3.69 gm, 0.015 moles and NaHCO3 (2.51 gm, 2 equiv) in a mixture of acetonitrile (50 mL) and water (5 mL) was stirred under a N2 atmosphere for 3 days. This was treated with Na2SO4 and then with 1-(3-flurobenzyl)-1H-indazol-5-ylamine (3.24 gm, 0.90 equiv) and NaHCO3 (1 gm) and left stirring for 18 hr at RT. The reaction was filtered and the filter cake was washed with DCM (100 mL). The filtrate was concentrated and silica gel chromatography (elution with 30% EtOAc in hexane) of the residue gave the title compound as a tan solid (3.78 gm, 65% yield): 1H NMR (CDCl3) δ 3.03 (t, J=5.9 Hz, 1H), 4.98 (d, J=5.7 Hz, 2H), 5.55 (s, 2H), 6.76 (d, J=2.7 Hz, 1H), 6.83 (d, J=9.0 Hz, 1H), 6.98-6.90 (m, 3H), 7.43 (d, J=2.5 Hz, 1H), 7.51 (dd, J=2.1, 8.8 Hz, 1H), 7.96 (s, 1H), 8.03 (s, 1H), 8.22 (s, 1H), 9.91 (s, 1H); MS: (M+H+); HPLC Ret Time: 2.38 min (YMC C18 S5, 3.0×50 mm, 4 min gradient, 4 mL/min.

Workup

  1. stirringstirring for 18 hr at RT
  2. filtrationThe reaction was filtered
  3. washthe filter cake was washed with DCM (100 mL)
  4. concentrationThe filtrate was concentrated
  5. washsilica gel chromatography (elution with 30% EtOAc in hexane) of the residue

Sources & evidence

ORD record
ord-5cd3ebb762a24326966c6cd8c2733dab
Source dataset
uspto-grants-2005_06
Patent number
US06908916B2

Reaction notes

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