Hydrochloric Acid → HCID 86727229, compound

HRID 1471425Notes

Reaction equation

HRID 1471425 reaction equation
Br[C:2]1[CH:20]=[CH:19][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]([C:16]([OH:18])=[O:17])=[CH:8]2)=[C:4]([F:21])[CH:3]=1.[CH3:22][N:23]1[CH:27]=[C:26](B2OC(C)(C)C(C)(C)O2)[CH:25]=[N:24]1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl>O.ClCCl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1COCC1.O>[F:21][C:4]1[CH:3]=[C:2]([C:26]2[CH:25]=[N:24][N:23]([CH3:22])[CH:27]=2)[CH:20]=[CH:19][C:5]=1[CH2:6][N:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]([C:16]([OH:18])=[O:17])=[CH:8]1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 43438759HCID 43438759, compound

Product 1

HCID 86727229HCID 86727229, compound

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
150 °C

Procedure

In a 5 mL microwave vial, 1-(4-bromo-2-fluorobenzyl)-1H-indole-3-carboxylic acid (70 mg, 0.20 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (90 mg, 0.43 mmol), cesium carbonate (250 mg, 0.77 mmol), and Pd(dppf)Cl2 (20 mg, 0.02 mmol) was massed. The vial was then charged with a stir bar and 3 mL of 5:1 THF/H2O. The vial was capped and heated to 150° C. for 30 min. The reaction was cooled to ambient temperature and deemed to be complete by LCMS. The reaction mixture was diluted with H2O (20 mL) and dichloromethane (20 mL), and the organic layer was acidified to pH 1 with 1M HCl. The aqueous layer was extracted with dichloromethane (3×20 mL). The organic layers were combined, dried over MgSO4, filtered, and concentrated in vacuo. The crude material was purified by silica gel chromatography eluting with hexanes/ethyl acetate (0 to 100%) to afford 1-(2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)benzyl)-1H-indole-3-carboxylic acid (LCMS: M+H=350, RT=0.687 min).

Workup

  1. additionThe vial was then charged with a stir bar
  2. customThe vial was capped
  3. temperatureThe reaction was cooled to ambient temperature
  4. extractionThe aqueous layer was extracted with dichloromethane (3×20 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by silica gel chromatography
  9. washeluting with hexanes/ethyl acetate (0 to 100%)

Sources & evidence

ORD record
ord-d566ff3ea15a4b39a76455180c6fa66f
Source dataset
uspto-grants-2015_04
Patent number
US09012445B2

Reaction notes

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