2-Fluoroethyl bromide → HCID 57404829, compound

HRID 1520077Notes

Reaction equation

Br[CH2:2][CH2:3][F:4].[NH:5]1[CH2:10][CH2:9][CH:8]([C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH:21]=[C:20]([C:22]4[C:30]5[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=5)[NH:24][N:23]=4)[N:19]=[N:18]3)=[CH:13][CH:12]=2)[CH2:7][CH2:6]1.C([O-])(O)=O.[Na+]>CN(C=O)C.O>[F:4][CH2:3][CH2:2][N:5]1[CH2:10][CH2:9][CH:8]([C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH:21]=[C:20]([C:22]4[C:30]5[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=5)[NH:24][N:23]=4)[N:19]=[N:18]3)=[CH:13][CH:12]=2)[CH2:7][CH2:6]1

Participants

Conditions

Temperature: 100 °C

Procedure

1-bromo-2-fluoroethane (30 mg; 0.24 mmol; 0.9 eq.) was added to a suspension of 3-[1-(4-piperidin-4-ylphenyl)-1H-1,2,3-triazol-4-yl]-1H-indazole (100 mg; 0.26 mmol; 1.0 eq.) and NaHCO3 (331 mg; 3.94 mmol; 15 eq.) in dry DMF (2 mL). The reaction mixture was heated in MW at 100° C. for 3 h. It was then diluted with water and extracted with EtOAc. Combined organic phases were washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by flash chromatography on silica (DCM: MeOH, gradient from 100:0 to 90:10) gave the title compound as a white solid (40 mg, 39%). 1H NMR (300 MHz, DMSO-d6) δ 13.36 (brs, 1H), 9.27 (s, 1H), 8.41-8.31 (m, 1H), 8.01-7.92 (m, 2H), 7.64-7.58 (m, 1H), 7.55-7.38 (m, 3H), 7.30-7.20 (m, 1H), 4.56 (dt, J=47.8, 4.9 Hz, 2H), 3.09-2.96 (m, 2H), 2.75-2.54 (m, 3H), 2.22-2.07 (m, 2H), 1.88-1.61 (m, 4H). HPLC (max plot) 99.8%; Rt 2.64 min. UPLC/MS: (MS+) 391.1, (MS−) 389.2

Workup

extractionextracted with EtOAc
washCombined organic phases were washed with brine
dry with materialdried over magnesium sulfate
filtrationfiltered
concentrationconcentrated
customPurification by flash chromatography on silica (DCM: MeOH, gradient from 100:0 to 90:10)

Sources & evidence

ORD record: ord-51dbb72a78184b24969b3e1c535bab4b
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09073892B2

Reaction notes

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