Cesium carbonate → 1-(3-fluorobenzyl)-5-nitro-1H-indazole

HRID 2212497Notes

Reaction equation

[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][N:8]=[CH:7]2)([O-:3])=[O:2].C(=O)([O-])[O-].[Cs+].[Cs+].[F:19][C:20]1[CH:21]=[C:22]([CH:25]=[CH:26][CH:27]=1)[CH2:23]Br.[N+](C1C2C(=CC=CC=2)NN=1)([O-])=O>CN(C=O)C>[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH2:23][C:22]1[CH:25]=[CH:26][CH:27]=[C:20]([F:19])[CH:21]=1)[N:8]=[CH:7]2)([O-:3])=[O:2]

Participants

Conditions

Temperature: 20 °C

Procedure

5-nitro indazole (1 equiv.), cesium carbonate (1.1 equiv.) and DMF (5 volumes) were charged to a vessel. The mixture was heated to 70–80° C. and 3-fluoro benzyl bromide was added over 75 mins. The reaction was assayed by HPLC for completion (<2 AP of nitro indazole vs combined isomers) and then cooled to 20° C. The salts were filtered and the cake was washed with DMF (2.7 volumes). The product was crystallized by charging water (1.35 to 1.45 volumes) between 15–21° C. The crystal slurry was held for 4 h, crystals were filtered and washed with 2:1 DMF:water mix (2.1 volumes), water (2 volumes) and finally 3:1 cold ACN:water mix (1.5 volumes). The wet cake was dried <45° C. to LOD <1% and the yield was about 49%

Workup

temperatureThe mixture was heated to 70–80° C.
filtrationThe salts were filtered
washthe cake was washed with DMF (2.7 volumes)
customThe product was crystallized
custombetween 15–21° C
filtrationcrystals were filtered
washwashed with 2:1 DMF
additionwater mix (2.1 volumes), water (2 volumes) and finally 3:1 cold ACN
additionwater mix (1.5 volumes)
customThe wet cake was dried <45° C. to LOD <1%

Sources & evidence

ORD record: ord-ccf7a374430f41a4987253d7e87aaa88
Source dataset: uspto-grants-2006_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07102001B2

Reaction notes

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