Lithium Chloride → HCID 86700382, compound

HRID 879558Notes

Reaction equation

HRID 879558 reaction equation
Br[C:2]1[N:3]=[C:4]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[N:13]([CH3:17])[N:12]=[CH:11]3)[N:5]([CH3:7])[CH:6]=1.[Li+].[Cl-].Br[C:21]1[S:22][C:23]2[C:29]([C:30]3[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=3)=[C:28]([C@H:37]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])[C:38]([O:40][CH2:41][CH3:42])=[O:39])[C:27]([CH3:48])=[CH:26][C:24]=2[N:25]=1>O1CCOCC1.CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.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>[C:44]([O:43][C@@H:37]([C:28]1[C:27]([CH3:48])=[CH:26][C:24]2[N:25]=[C:21]([C:2]3[N:3]=[C:4]([C:8]4[CH:9]=[C:10]5[C:14](=[CH:15][CH:16]=4)[N:13]([CH3:17])[N:12]=[CH:11]5)[N:5]([CH3:7])[CH:6]=3)[S:22][C:23]=2[C:29]=1[C:30]1[CH:31]=[CH:32][C:33]([Cl:36])=[CH:34][CH:35]=1)[C:38]([O:40][CH2:41][CH3:42])=[O:39])([CH3:45])([CH3:46])[CH3:47]

Participants

8

Reactant 3

HCID 433294Lithium ChlorideHCID 86700141(S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetateHCID 86700381HCID 86700381, compound

Product 1

HCID 86700382HCID 86700382, compound

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
90 °C

Procedure

In a 10 mL reaction vial, 5-(4-bromo-1-methyl-1H-imidazol-2-yl)-1-methyl-1H-indazole (50 mg, 0.172 mmol) was dissolved in dioxane (3 mL) at rt. The solution was bubbled with argon for 5 min. Then Sn2(n-Bu)6 (0.136 mL, 0.259 mmol), LiCl (60 mg, 1.4 mmol), Pd(PPh3)2Cl2 (24 mg, 0.034 mmol) and Pd(PPh3)4 (40 mg, 0.0344 mmol) were added sequentially. The resulting reaction mixture was sealed and heated to 90° C. in oil bath. To this mixture, a solution of (S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate (128 mg, 0.259 mmol) in dioxane (1.5 mmol) was added slowly through syringe pump over 1.5 h. The resulting reaction mixture was stirred at 100° C. in oil bath for 16 h. The reaction was then diluted with EtOAc (20 mL) and filtered to remove solid. The filtrate was concentrated and purified on silica gel column with 0-20% EtOAc/Hex to afford product. LCMS-ESI+: calc'd for: C34H34ClN5O3S: 628.2, 629.2, 630.2 (M+H+); found: 628.1, 629.1, 630.1 (M+H+)

Workup

  1. customIn a 10 mL reaction vial
  2. customThe solution was bubbled with argon for 5 min
  3. customThe resulting reaction mixture
  4. customwas sealed
  5. customThe resulting reaction mixture
  6. filtrationfiltered
  7. customto remove solid
  8. concentrationThe filtrate was concentrated
  9. custompurified on silica gel column with 0-20% EtOAc/Hex
  10. customto afford product

Sources & evidence

ORD record
ord-b36109c56bd5434f89dc63ff7443df99
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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