Triethylamine → HCID 44409596, compound

HRID 914794Notes

Reaction equation

HRID 914794 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]([CH3:15])=[C:7]2[N:12]([CH:13]=1)[N:11]=[CH:10][N:9]=[C:8]2Cl)=[O:4].[CH3:16][C:17]1[NH:18][C:19]2[C:24]([CH:25]=1)=[CH:23][C:22]([OH:26])=[CH:21][CH:20]=2.C(N(CC)CC)C>C(#N)C>[CH3:1][O:2][C:3]([C:5]1[C:6]([CH3:15])=[C:7]2[N:12]([CH:13]=1)[N:11]=[CH:10][N:9]=[C:8]2[O:26][C:22]1[CH:23]=[C:24]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17]([CH3:16])=[CH:25]2)=[O:4]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 833362-methyl-1H-indol-5-olHCID 21945969Methyl 4-chloro-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate

Product 1

HCID 44409596HCID 44409596, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of 4-chloro-5-methyl-pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid methyl ester (0.5 g, 2.22 inmol) and 2-methyl-5-hydroxyindole (424 mg, 2.9 mmol) under argon in acetonitrile (10.0 mL) was added triethylamine (6.65 mmol, 0.93 mL). After stirring the mixture at room temperature for 17 h. solvent was removed under vacuum and the residue was chromatographed on silica gel eluting with 20-30% ethyl acetate (gradient) in hexanes. The solvent was removed in vacuo to obtain 5-methyl-4-(2-methyl-1H-indol-5-yloxy)-pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid methyl ester as a white solid (0.58 g, 85%). LC/MS; (M+H)+=337.2 B. To a solution of compound A (575 mg, 1.71 mmol) in pyridine (20 mL) was added lithium iodide (17 mmol, 2.3 g). The mixture was stirred at reflux for 45 h. The mixture was allowed to cool and the pyridine was then removed in vacuo. The remaining solid material was purified by preparative HPLC. Removal of the eluent in vacuo afforded 5-methyl-4-(2-methyl-1H-indol-5-yloxy)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid (228 mg, 41%) as a brown solid. LC/MS; (M+H)+=323.1 C. To a solution of compound B (35 mg, 0.11 mmol) in dioxane (7 mL) was added ca. 5 mg of crushed 4 Å molecular sieves, triethylamine (0.13 mmol, 18 EL), and DPPA (0.13 mmol, 28 mL). The mixture was heated under argon at 50° C. for 6 h, followed by addition of the 3-piperidinepropanol (1.1 mmol, 156 mg) in dioxane (2.0 mL), warmed to 76° C., then allowed to stir for ca. 16 h. The reaction mixture was purified on preparative HPLC. The product obtained was then dissolved in ethyl acetate (100 mL) and washed with 30 mL of saturated aqueous sodium bicarbonate, dried, filtered and concentrated in vacuo. The oil was then chromatographed using silica gel eluting with 1% triethylamine, 10% methanol in chloroform. Removal of the solvent in vacuo afforded the title compound (9.2 mg, 18%) as an orange oil. LC/MS; (M+H)+=323.2

Workup

  1. customwas removed under vacuum
  2. customthe residue was chromatographed on silica gel eluting with 20-30% ethyl acetate (gradient) in hexanes
  3. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-4a5a306a07a64ce29e9b2aa3878d382d
Source dataset
uspto-grants-2007_09
Patent number
US07265113B2

Reaction notes

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