Lithium Chloride → HCID 86700433, compound

HRID 879624Notes

Reaction equation

HRID 879624 reaction equation
Br[C:2]1[S:3][C:4]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=3)=[C:9]([C@H:18]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[C:19]([O:21][CH3:22])=[O:20])[C:8]([CH3:28])=[CH:7][C:5]=2[N:6]=1.[Cl-].[Li+].[CH:31]([N:34]1[CH2:39][CH2:38][N:37]([C:40]2[CH:45]=[N:44][CH:43]=[C:42]([Sn](CCCC)(CCCC)CCCC)[N:41]=2)[CH2:36][CH2:35]1)([CH3:33])[CH3:32]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[C:24]([O:23][C@@H:18]([C:9]1[C:8]([CH3:28])=[CH:7][C:5]2[N:6]=[C:2]([C:42]3[CH:43]=[N:44][CH:45]=[C:40]([N:37]4[CH2:38][CH2:39][N:34]([CH:31]([CH3:33])[CH3:32])[CH2:35][CH2:36]4)[N:41]=3)[S:3][C:4]=2[C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=1)[C:19]([O:21][CH3:22])=[O:20])([CH3:27])([CH3:26])[CH3:25]

Participants

7

Reactant 3

HCID 433294Lithium ChlorideHCID 86699809Methyl (S)-2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-(tert-butoxy)acetateHCID 86700434HCID 86700434, compound

Product 1

HCID 86700433HCID 86700433, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

(S)-methyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate (60.0 mg, 0.124 mmol), tetrakis(triphenylphosphine)palladium(0) (21.5 mg, 0.019 mmol), lithium chloride (15.8 mg, 0.373 mmol), and copper(I) iodide (7.1 mg, 0.037 mmol) were taken in a microwave vial and the vial vacuum pumped and flushed with argon three times. To this mixture was added 2-(4-isopropylpiperazin-1-yl)-6-(tributylstannyl)pyrazine (73.9 mg, 0.149 mmol) in dioxane (1.5 mL), and the resulting mixture was stirred at 100° C. for 4.5 h. The reaction mixture was cooled, filtered through Celite (ethyl acetate eluent), and concentrated. Purification by flash column chromatography on silica gel using 79:20:1 DCM/MeOH/NH3 (0 to 100%) in DCM provided the product. LCMS-ESI+ calc'd for C32H39ClN5O3S (M+H+): 608.2; Found: 608.3 (M+H+).

Workup

  1. customflushed with argon three times
  2. temperatureThe reaction mixture was cooled
  3. filtrationfiltered through Celite (ethyl acetate eluent)
  4. concentrationconcentrated
  5. customPurification by flash column chromatography on silica gel using 79:20:1 DCM/MeOH/NH3 (0 to 100%) in DCM
  6. customprovided the product

Sources & evidence

ORD record
ord-803fd529094f4d40a2939e09a8fdca45
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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