Water → 7-Chloro-5-methyl-2-phenyl-1H-pyrrolo[3,2-b]pyridine

HRID 1371123Notes

Reaction equation

HRID 1371123 reaction equation
[NH2:1][C:2]1[C:3]([C:10]#[C:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[N:4][C:5]([CH3:9])=[CH:6][C:7]=1[Cl:8].O>CN(C=O)C.[Cu]I>[Cl:8][C:7]1[CH:6]=[C:5]([CH3:9])[N:4]=[C:3]2[CH:10]=[C:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[NH:1][C:2]=12

Participants

5

Reactant 2

HCID 962WaterHCID 10752718HCID 10752718, compound

Product 1

HCID 108477767-Chloro-5-methyl-2-phenyl-1H-pyrrolo[3,2-b]pyridineYield 48.5%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

3-Amino-4-chloro-6-methyl-2-(2-phenylethynyl)pyridine (1.24 g, 5.1 mmol) was dissolved in anhydrous DMF (90 mL), CuI (150 mg, 0.8 mmol) was added and the mixture was heated at 110° C. for 18 h. The cooled mixture was poured into H2O (125 mL) and extracted with EtOAc (2×100 mL). The combined extracts were washed with H2O and brine, dried over MgSO4 and filtered through a plug of silica using CHCl3. The crude product was triturated with 20:1 hexanes:EtOAc, filtered, and dried under high vacuum to afford 600 mg (48%) of 7-chloro-5-methyl-2-phenylpyrrolo-[3,2-b]pyridine. 1H NMR (DMSO-d6; 500 MHz): δ 2.40 (s, 3), 7.05 (s, 1), 7.16 (s, 1), 7.38 (t, 1, J=5.2), 7.49 (m, 2), 8.02 (d, 2, J=7.2). MS m/z: 243 (M+H). This intermediate chloride (273 mg, 1.1 mmol) was taken up in 4:1 o-xylene/piperidine (10 mL) and heated to 140° C. in a Teflon-capped pressure tube for 7 d. The mixture was cooled to room temperature, diluted with H2O (125 mL) and extracted with EtOAc (2×100 mL). The combined organic layers were washed with H2O and brine, dried over MgSO4 filtered, and concentrated in vacuo. Chromatography on silica gel eluting with 10:1 CHCl3:MeOH afforded 244 mg (75%, 36% overall) of the title compound as a pale yellow solid. The product's 1H-NMR was identical to that obtained using Method A.

Workup

  1. extractionextracted with EtOAc (2×100 mL)
  2. washThe combined extracts were washed with H2O and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered through a plug of silica
  5. customThe crude product was triturated with 20:1 hexanes
  6. filtrationEtOAc, filtered
  7. customdried under high vacuum

Sources & evidence

ORD record
ord-aaa1e82048264fc899da2b4a3ac2e00b
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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