Cesium carbonate → 1-{5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridin-2-yl}-1H-pyrrolo[2,3-c]pyridine

HRID 885035Notes

Reaction equation

Br.[NH:2]1[C:10]2[C:5](=[CH:6][CH:7]=[N:8][CH:9]=2)[CH:4]=[CH:3]1.Cl[C:12]1[CH:17]=[CH:16][C:15]([C:18]#[C:19][C:20]2[N:21]=[C:22]([CH3:25])[S:23][CH:24]=2)=[CH:14][N:13]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[CH3:25][C:22]1[S:23][CH:24]=[C:20]([C:19]#[C:18][C:15]2[CH:16]=[CH:17][C:12]([N:2]3[C:10]4=[CH:9][N:8]=[CH:7][CH:6]=[C:5]4[CH:4]=[CH:3]3)=[N:13][CH:14]=2)[N:21]=1

Participants

Conditions

Temperature: 120 °C

Procedure

6-azaindole hydrobromide (198 mg, 1.0 mmol), 2-chloro-5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (1.0 mmol, 234 mg), and cesium carbonate (3.2 mmol, 1.04 g) were combined in DMF (15 mL) and heated at 120° C. for 18 hrs. The reaction was cooled to room temperature and partitioned in a separatory funnel with 1:1 hexanes:EtOAc (100 mL) and water (50 mL). The organic layer was washed with 5% NaCl (4×25 mL), then dried over MgSO4, filtered, and concentrated in vacuo. The crude residue was purified on SiO2, elution with a 0% to 6% iPrOH gradient in DCM to afford the title compound as a white solid which was dissolved in ether and precipitated as the hydrochloride salt with 1M HCl in ether. 1H-NMR (CD3OD, 500 MHz) δ 10.1 (s, 1H), 8.83 (m, 2H), 8.43 (d, 1H), 8.27 (d, 1H), 8.22 (d, 1H), 7.99 (d, 1H), 7.92 (s, 1H), 7.26 (d, 1H), 2.79 (s, 3H). MS (ESI) 317.2 (M+H+).

Workup

temperatureThe reaction was cooled to room temperature
custompartitioned in a separatory funnel with 1:1 hexanes
washThe organic layer was washed with 5% NaCl (4×25 mL)
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude residue was purified on SiO2, elution with a 0% to 6% iPrOH gradient in DCM

Sources & evidence

ORD record: ord-7e99f7ae78d44cab8cff9c71dd3e821e
Source dataset: uspto-grants-2012_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08242143B2

Reaction notes

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