Tetrahydrofuran → 1-(4-Methoxybenzyl)-6-vinyl-1H-indazole

HRID 1410337Notes

Reaction equation

[H-].[Na+].[CH3:3][O:4][C:5]1[CH:22]=[CH:21][C:8]([CH2:9][N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([CH:19]=O)[CH:17]=3)[CH:12]=[N:11]2)=[CH:7][CH:6]=1.[CH2:23]1COCC1>C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Br-]>[CH3:3][O:4][C:5]1[CH:22]=[CH:21][C:8]([CH2:9][N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([CH:19]=[CH2:23])[CH:17]=3)[CH:12]=[N:11]2)=[CH:7][CH:6]=1

Participants

Conditions

Temperature: 0 °C

Procedure

An oven-dried flask under N2 (g) was charged with NaH (60% wt) (592 mg, 14.8 mmol) and THF (30 mL) and the suspension cooled to 0° C. CH3PPh3Br (5.29 g, 14.8 mmol) was added and stirred for 30 min at which time 1-(4-methoxybenzyl)-1H-indazole-6-carbaldehyde (1.97 g, 7.40 mmol) was added and the reaction was allowed to slowly warm to room temperature. After 2.5 h quenched with NH4Cl and extracted with Et2O. The organic layers were washed with brine (2×) and dried over MgSO4. The solvent was removed and the residue purified using Biotage Isolera (silica gel, 10-20% EtOAc in hexane) to give the title compound as a white solid (1.20 g, 61%); 1H NMR (400 MHz, CDCl3) δ 7.99 (s, 1H), 7.67 (d, J=8.8 Hz, 1H), 7.30-7.26 (m, 2H), 7.16 (d, J=8.3 Hz, 2H), 6.84-6.76 (m, 3H), 5.80 (d, J=17.5 Hz, 1H), 5.53 (s, 2H), 5.30 (d, J=10.9 Hz, 1H), 3.76 (s, 3H); MS ESI 264.9 [M+H]+, calcd for [C17H16N2O+H]+ 265.1.

Workup

additionwas added
temperatureto slowly warm to room temperature
customAfter 2.5 h quenched with NH4Cl
extractionextracted with Et2O
washThe organic layers were washed with brine (2×)
dry with materialdried over MgSO4
customThe solvent was removed
customthe residue purified

Sources & evidence

ORD record: ord-16a3eae9e3624130b8a629fc589872a3
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08921545B2

Reaction notes

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