1H-Pyrrolo(2,3-b)pyridine → HCID 16662994, compound

HRID 885034Notes

Reaction equation

[NH:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[CH:2]1.[H-].[Na+].Cl[C:13]1[CH:18]=[CH:17][C:16]([C:19]#[C:20][C:21]2[N:22]=[C:23]([CH3:26])[S:24][CH:25]=2)=[CH:15][N:14]=1>CN(C=O)C>[CH3:26][C:23]1[S:24][CH:25]=[C:21]([C:20]#[C:19][C:16]2[CH:17]=[CH:18][C:13]([N:1]3[C:5]4=[N:6][CH:7]=[CH:8][CH:9]=[C:4]4[CH:3]=[CH:2]3)=[N:14][CH:15]=2)[N:22]=1

Participants

Conditions

Temperature: 75 °C

Procedure

To a stirred solution of 1H-pyrrolo[2,3-b]pyridine (2.0 mmol, 236 mg) in DMF (20 mL) at 60° C. was added sodium hydride (2.5 mmol, 100 mg of 60% wt dispersion in mineral oil). After 30 min, 2-chloro-5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (0.5 mmol, 117 mg) was added and the reaction was warmed to 75° C. and stirred overnight under nitrogen. The reaction was then partitioned with EtOAc:hexanes (1:1, 100 mL) and water (50 mL). The organic layer was washed with 5% NaCl (4×50 mL), then dried over MgSO4, filtered, and concentrated in vacuo. The crude residue was chromatographed on SiO2, eluting with 3% MeOH in DCM, to afford the title compound as a white solid that was dissolved in ether and precipitated as the hydrochloride salt with 1N HCl in ether. 1H-NMR (CD3OD, 500 MHz) δ 8.88 (m, 2H), 8.65 (d, 1H), 8.54 (d, 1H), 8.30 (dd, 1H), 8.05 (d, 1H), 7.94 (s, 1H), 7.83 (dd, 1H), 7.24 (d, 1H), 2.82 (s, 3H). MS (ESI) 317.4 (M+H+).

Workup

customThe reaction was then partitioned with EtOAc:hexanes (1:1, 100 mL) and water (50 mL)
washThe organic layer was washed with 5% NaCl (4×50 mL)
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude residue was chromatographed on SiO2
washeluting with 3% MeOH in DCM

Sources & evidence

ORD record: ord-fc51c9bbfe874d37af19718e4f555472
Source dataset: uspto-grants-2012_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08242143B2

Reaction notes

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