Potassium Iodide → HCID 66898762, compound

HRID 2168501Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([O:13][CH3:14])=[O:12])[CH:10]=1)[NH:7][N:6]=[CH:5]2.[CH3:15][O:16][CH:17]([O:20][CH3:21])[CH2:18]Br.[I-].[K+].N12CCCN=C1CCCCC2.[NH4+].[Cl-]>CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([O:13][CH3:14])=[O:12])[CH:10]=1)[N:7]([CH2:18][CH:17]([O:20][CH3:21])[O:16][CH3:15])[N:6]=[CH:5]2

Participants

Conditions

Temperature: 80 °C

Procedure

Methyl 5-chloro-1H-indazole-7-carboxylate (2.65 g, 12.6 mmol; 1 eq) from Step A above was stirred in DMSO (25 mL) at room temperature while bromoacetaldehyde dimethyl acetal (3 mL, 25.2 mmol) pre-mixed with potassium iodide (209 mg, 1.3 mmol) was added. 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU; 2 mL, 12.6 mmol) was then added dropwise. The reaction mixture was stirred at 80° C. (external temperature) overnight. The reaction mixture was neutralized with sat. NH4Cl then partitioned between H2O and ethyl acetate. The ethyl acetate layers were combined, dried (Na2SO4), filtered, concentrated and purified by column chromatography (silica gel, 1:1 ethyl acetate/hexanes) to afford methyl 5-chloro-1-(2,2-dimethoxyethyl)-1H-indazole-7-carboxylate as a light yellow oil (404 mg, 11%, regioisomer confirmed by NOE): 1H NMR (300 MHz, CDCl3) δ 8.04 (s, 1H), 8.84 (s, 2H), 4.93 (d, J=5.1 Hz, 2H), 4.50 (t, J=5.1 Hz, 1H), 3.99 (s, 3H), 3.27 (s, 6H). [1.29 g starting material recovered; 846 mg, 22% undesired regioisomer methyl 5-chloro-2-(dimethoxymethyl)-2H-indazole-7-carboxylate collected as side product, dark yellow solid]

Workup

additionwas added
customthen partitioned between H2O and ethyl acetate
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated
custompurified by column chromatography (silica gel, 1:1 ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-f249037506fb4af296e56be3f5d9afb5
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09045501B2

Reaction notes

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