Lithium Chloride → HCID 86700380, compound

HRID 879556Notes

Reaction equation

HRID 879556 reaction equation
Br[C:2]1[C:7]([NH:8][C:9](=[O:14])[C:10]([F:13])([F:12])[F:11])=[CH:6][CH:5]=[C:4]([C:15]2[CH:16]=[C:17]3[C:21](=[CH:22][CH:23]=2)[N:20]([CH3:24])[N:19]=[CH:18]3)[N:3]=1.[Li+].[Cl-].Br[C:28]1[S:29][C:30]2[C:36]([C:37]3[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][CH:38]=3)=[C:35]([C@H:44]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])[C:45]([O:47][CH2:48][CH3:49])=[O:46])[C:34]([CH3:55])=[CH:33][C:31]=2[N:32]=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:51]([O:50][C@@H:44]([C:35]1[C:34]([CH3:55])=[CH:33][C:31]2[N:32]=[C:28]([C:2]3[C:7]([NH:8][C:9](=[O:14])[C:10]([F:13])([F:12])[F:11])=[CH:6][CH:5]=[C:4]([C:15]4[CH:16]=[C:17]5[C:21](=[CH:22][CH:23]=4)[N:20]([CH3:24])[N:19]=[CH:18]5)[N:3]=3)[S:29][C:30]=2[C:36]=1[C:37]1[CH:38]=[CH:39][C:40]([Cl:43])=[CH:41][CH:42]=1)[C:45]([O:47][CH2:48][CH3:49])=[O:46])([CH3:52])([CH3:53])[CH3:54]

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 86700379HCID 86700379, compound

Product 1

HCID 86700380HCID 86700380, 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, N-(2-bromo-6-(1-methyl-1H-indazol-5-yl)pyridin-3-yl)-2,2,2-trifluoroacetamide (24 mg, 0.06 mmol) was dissolved in dioxane (3 mL) at room temperature. The solution was bubbled with argon for 5 min. Then Sn2(n-Bu)6 (0.057 mL, 0.108 mmol), LiCl (30 mg, 0.7 mmol), Pd(PPh3)2Cl2 (6.3 mg, 0.009 mmol) and Pd(PPh3)4 (10 mg, 0.009 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 (44 mg, 0.09 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: C37H33ClF3N5O4S: 736.2, 737.2, 738.2 (M+H+); found: 736.1, 737.1, 738.1 (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-1c6b7e98ee46474d8132f873f0c95130
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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