2-Pyridinecarboxaldehyde → HCID 66790920, compound

HRID 1678263Notes

Reaction equation

HRID 1678263 reaction equation
[S:1]1[C:5]([C:6]2[C:14]3[C:10](=[CH:11][N:12]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[N:13]=3)[CH:9]=[C:8](Br)[CH:7]=2)=[CH:4][C:3]2[CH:24]=[CH:25][CH:26]=[CH:27][C:2]1=2.C([Li])CCC.[N:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[CH:39]=[O:40]>O1CCCC1>[S:1]1[C:5]([C:6]2[C:14]3[C:10](=[C:11]([CH:39]([C:34]4[CH:35]=[CH:36][CH:37]=[CH:38][N:33]=4)[OH:40])[N:12]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[N:13]=3)[CH:9]=[CH:8][CH:7]=2)=[CH:4][C:3]2[CH:24]=[CH:25][CH:26]=[CH:27][C:2]1=2

Participants

5

Reactant 3

HCID 142732-PyridinecarboxaldehydeHCID 59023903HCID 59023903, compoundHCID 178418339Butyllithium

Product 1

HCID 66790920HCID 66790920, compoundYield 31.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-65 °C

Procedure

A mixture of 7-benzo[b]thiophen-2-yl-5-bromo-2-(2-trimethylsilanyl-ethoxymethyl)-2H-indazole (Preparation #23, 0.15 g, 0.326 mmol) in tetrahydrofuran (2 mL) was cooled to about −65° C. then a solution of n-butyllithium (1.6 M, 0.36 mL, 0.36 mmol) was added dropwise. After about 30 minutes, 2-pyridinecarboxaldehyde (0.042 g, 0.39 mmol) was added. The mixture was quenched with methanol (1 mL) then warmed to room temperature. The solvent was removed in vacuo and the residue was purified by preparative reverse phase HPLC chromatography (RP-HPLC (Rainin C18, 8 mm, 300 Å, 35 cm; 5-100% acetonitrile/0.1 M ammonium acetate over 20 min, 100% acetonitrile hold 10 minutes, 21 mL/min) to give the intermediate [7-benzo[b]thiophen-2-yl-2-(2-trimethylsilanyl-ethoxymethyl)-2H-indazol-3-yl-pyridin-2-yl-methanol (50 mg) which was suspended in a mixture of 1,4-dioxane (2 mL) and manganese dioxide (90 mg, 31%). The mixture was heated to about 90° C. for 15 minutes then filtered and evaporated. The residue was purified by reverse phase HPLC (RP-HPLC (Rainin C18, 8 mm, 300 Å, 35 cm; 5-100% acetonitrile/0.1 M ammonium acetate over 20 min, 100% acetonitrile hold 10 minutes, 21 mL/min) to give (7-Benzo[b]thiophen-2-yl-1H-indazol-3-yl)-pyridin-2-yl-methanone (22 mg, 44%); (DMSO-d6, 400 MHz) δ 8.8 (bs, 1H), 8.31 (d, 1H), 8.09 (m, 4H), 7.93 (d, 1H), 7.78 (bs, 1H), 6.96 (bs, 1H), 7.51 (t, 1H), 7.43 (m, 2H); RP-HPLC (Table 1, Method e) Rt 2.60 min; m/z: (M−H)− 353.8.

Workup

  1. customThe mixture was quenched with methanol (1 mL)
  2. temperaturethen warmed to room temperature
  3. customThe solvent was removed in vacuo
  4. customthe residue was purified by preparative reverse phase HPLC chromatography (RP-HPLC (Rainin C18, 8 mm, 300 Å, 35 cm; 5-100% acetonitrile/0.1 M ammonium acetate over 20 min, 100% acetonitrile hold 10 minutes, 21 mL/min)

Sources & evidence

ORD record
ord-a32a644630944d8189310eab71201408
Source dataset
uspto-grants-2011_08
Patent number
US08008481B2

Reaction notes

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