Benzyl mercaptan → 5-(Benzylsulfanyl)-6-methyl-1H-indazole

HRID 1051412Notes

Reaction equation

HRID 1051412 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[CH3:11])[NH:7][N:6]=[CH:5]2.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CCN(C(C)C)C(C)C.[CH2:63]([SH:70])[C:64]1[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=1>C(Cl)Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[CH2:63]([S:70][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[CH3:11])[NH:7][N:6]=[CH:5]2)[C:64]1[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=1

Participants

8

Reactant 4

HCID 7509Benzyl mercaptanHCID 81531DiisopropylethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 247292595-Bromo-6-methyl-1H-indazole

Product 1

HCID 901091435-(Benzylsulfanyl)-6-methyl-1H-indazole

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

5-Bromo-6-methyl-1H-indazole (4-1, 2 g, 9.48 mmol), XANTPHOS (0.548 g, 0.948 mmol), and Pd2(dba)3 (0.868 g, 0.948 mmol) were added to an oven-dried sealed tube followed by anhydrous Dioxane (31.6 ml), DIPEA (3.31 ml, 18.95 mmol) and BENZYL MERCAPTAN (1.177 ml, 9.95 mmol). Placed in 120° C. bath. After 2 h, UPLC showed >52% P1 at 1.25 min, 15% R1 at 1.07 min, 16% byproduct at 1.56 min and several minor peaks each less than 7%. After an additional 2 h, UPLC showed no change. Cooled to RT, filtered through Celite, washed with EtOAc, concentrated to give a clear, orange oil. Dissolved in 5 mL DCM, purified by normal-phase ISCO (80 g column, 0-50% EtOAc:Hex) to give 4-3 as a yellow solid.

Workup

  1. customsealed tube
  2. customPlaced in 120° C.
  3. customat 1.25 min
  4. waitAfter an additional 2 h
  5. filtrationfiltered through Celite
  6. washwashed with EtOAc
  7. concentrationconcentrated
  8. customto give a clear, orange oil
  9. custompurified by normal-phase ISCO (80 g column, 0-50% EtOAc:Hex)

Sources & evidence

ORD record
ord-ca1f364953f6488abc3223504519c811
Source dataset
uspto-grants-2016_07
Patent number
US09388179B2

Reaction notes

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