Lithium Chloride → (S)-methyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(2-(1-methyl-1H-indazol-5-yl)pyrimidin-4-yl)benzo[d]thiazol-6-yl)acetate

HRID 879295Notes

Reaction equation

HRID 879295 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+].[CH3:31][N:32]1[C:40]2[C:35](=[CH:36][C:37]([C:41]3[N:46]=[C:45]([Sn](CCCC)(CCCC)CCCC)[CH:44]=[CH:43][N:42]=3)=[CH:38][CH:39]=2)[CH:34]=[N:33]1>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:43]3[CH:44]=[CH:45][N:46]=[C:41]([C:37]4[CH:36]=[C:35]5[C:40](=[CH:39][CH:38]=4)[N:32]([CH3:31])[N:33]=[CH:34]5)[N:42]=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 866998151-methyl-5-(4-(tributylstannyl)pyrimidin-2-yl)-1H-indazole

Product 1

HCID 86699814(S)-methyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(2-(1-methyl-1H-indazol-5-yl)pyrimidin-4-yl)benzo[d]thiazol-6-yl)acetate

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 (17.4 mg, 0.036 mmol), Pd(PPh3)4 (2.1 mg, 0.002 mmol), lithium chloride (2.3 mg, 0.054 mmol), and copper(I) iodide (1.0 mg, 0.005 mmol) were taken in a microwave vial and the vial was vacuum pumped and flushed with argon three times. To this mixture was added 1-methyl-5-(4-(tributylstannyl)pyrimidin-2-yl)-1H-indazole (9.0 mg, 0.018 mmol) in degassed 1,4-dioxane (0.5 mL). The reaction mixture was heated at 100° C. for 5 h, cooled, filtered through celite (ethyl acetate eluent), and concentrated. Purification by flash column chromatography on silica gel (hexanes/ethyl acetate eluent) provided the product. LCMS-ESI+: calc'd for C33H31ClN5O3S: 612.2 (M+H+); Found: 611.9 (M+H+).

Workup

  1. customflushed with argon three times
  2. temperaturecooled
  3. filtrationfiltered through celite (ethyl acetate eluent)
  4. concentrationconcentrated
  5. customPurification by flash column chromatography on silica gel (hexanes/ethyl acetate eluent)
  6. customprovided the product

Sources & evidence

ORD record
ord-031710bcfdc74c1e91d036665289755a
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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