Lithium Chloride → (1R,2R)-2-methyl-cyclopropane carboxylic acid [4-bromo-3-(2-methyl-2H-indazol-5-yl)-isothiazol-5-yl]-amide

HRID 2079746Notes

Reaction equation

HRID 2079746 reaction equation
Br[C:2]1[C:6]([Br:7])=[C:5]([NH:8][C:9]([C@@H:11]2[CH2:13][C@H:12]2[CH3:14])=[O:10])[S:4][N:3]=1.[CH3:15][N:16]1[CH:24]=[C:23]2[C:18]([CH:19]=[CH:20][C:21]([Sn](C)(C)C)=[CH:22]2)=[N:17]1.[Cl-].[Li+]>O1CCOCC1>[CH3:20][CH2:19][CH2:18][CH:23]([CH3:24])[CH3:22].[Br:7][C:6]1[C:2]([C:21]2[CH:20]=[CH:19][C:18]3[C:23](=[CH:24][N:16]([CH3:15])[N:17]=3)[CH:22]=2)=[N:3][S:4][C:5]=1[NH:8][C:9]([C@@H:11]1[CH2:13][C@H:12]1[CH3:14])=[O:10]

Participants

6

Reactant 3

HCID 433294Lithium ChlorideHCID 668384392-Methyl-5-(trimethylstannyl)-2H-indazoleHCID 67103560(R,R)-N-[3,4-dibromoisothiazol-5-yl]-2-methylcyclopropanecarboxamide

Product 2

HCID 78922-MethylpentaneHCID 67103132(1R,2R)-2-methyl-cyclopropane carboxylic acid [4-bromo-3-(2-methyl-2H-indazol-5-yl)-isothiazol-5-yl]-amideYield 43%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

Charge a round bottom flask with (1R,2R)-2-methyl-cyclopropanecarboxylic acid (3,4-dibromo-isothiazol-5-yl)-amide (2.55; g, 7.49; mmol), 2-methyl-5-trimethylstannanyl-2H-indazole (2.21; g, 7.49; mmol) and lithium chloride (0.95; g, 22.48; mmol) in 1,4-dioxane (19.2; mL). Purge with nitrogen for 20; min, add tetrakis(triphenylphosphine) palladium (1.31; g, 1.12; mmol) and heat at 105° C. for 48; h. Directly load reaction mixture onto a silica gel column and purify by gradient eluting from 0:100; to 100:0; ethyl acetate:iso-hexane to give the title compound (1.25; g, 43%). MS (m/z): 391, 393; (M+1).

Workup

  1. customPurge with nitrogen for 20
  2. additionmin, add tetrakis(triphenylphosphine) palladium (1.31; g, 1.12; mmol)
  3. customDirectly load reaction mixture onto a silica gel column
  4. custompurify
  5. washby gradient eluting from 0:100

Sources & evidence

ORD record
ord-0eee5c15b07b4e6092a4e2a81bdacc08
Source dataset
uspto-grants-2011_04
Patent number
US07932274B2

Reaction notes

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