Dichloromethane → HCID 66936842, compound

HRID 1963874Notes

Reaction equation

HRID 1963874 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=2)[CH:5]=[C:4]([C:17]([F:20])([F:19])[F:18])[CH:3]=1.[F:21][C:22]1[CH:27]=[C:26](B(O)O)[CH:25]=[CH:24][N:23]=1.C(Cl)Cl.C(=O)([O-])[O-].[Na+].[Na+]>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].CO.C(OCC)(=O)C.COCCOC>[F:21][C:22]1[CH:27]=[C:26]([C:2]2[CH:3]=[C:4]([C:17]([F:20])([F:19])[F:18])[CH:5]=[C:6]([NH:8][CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=3)[N:7]=2)[CH:25]=[CH:24][N:23]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 27833962-Fluoropyridine-4-boronic acidHCID 86650609HCID 86650609, compound

Product 1

HCID 66936842HCID 66936842, compoundYield 41.7%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 887MethanolSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
105 °C

Procedure

To 6-chloro-N-(3-fluorobenzyl)-4-(trifluoromethyl)pyridin-2-amine (70 mg, 0.230 mmol) was added 2-fluoropyridin-4-ylboronic acid (58.3 mg, 0.414 mmol), PdCl2(dppf).CH2Cl2 adduct (22.52 mg, 0.028 mmol), DME (1.2 ml), and 2M sodium carbonate (0.460 ml, 0.919 mmol). The resulting reaction mixture was stirred at 105° C. until completion as indicated by LCMS, about 6 hours. The reaction mixture was cooled, 15 ml of ethyl acetate and 5 ml of methanol was added, filtered and concentrated to yield a crude solid. The solid was purified by prep LC. The product was free-based using 200 ml of ethyl acetate and washed with saturated sodium bicarbonate (1×), water (2×), saturated salt solution (1×), dried sodium sulfate, filtered and concentrated to a constant mass, yielding 35 mg of titled compound as free base. LCMS (m/z): 366.2 (MH+), retention time=1.20 min.

Workup

  1. customThe resulting reaction mixture
  2. customas indicated by LCMS, about 6 hours
  3. temperatureThe reaction mixture was cooled
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto yield a crude solid
  7. customThe solid was purified by prep LC
  8. washwashed with saturated sodium bicarbonate (1×), water (2×), saturated salt solution (1×), dried sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated to a constant mass

Sources & evidence

ORD record
ord-71bb082d07b644e18b1747617c8c6913
Source dataset
uspto-grants-2013_04
Patent number
US08415381B2

Reaction notes

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