Dichloromethane → HCID 178521575, compound

HRID 1623284Notes

Reaction equation

HRID 1623284 reaction equation
[Cl:1][C:2]1[C:3](I)=[CH:4][C:5]([NH:8][C@H:9]2[CH2:14][CH2:13][C@H:12]([OH:15])[CH2:11][CH2:10]2)=[N:6][CH:7]=1.[F:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20](B2OC(C)(C)C(C)(C)O2)[N:19]=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>[Cl:1][C:2]1[C:3]([C:20]2[CH:21]=[CH:22][CH:23]=[C:18]([F:17])[N:19]=2)=[CH:4][C:5]([NH:8][C@H:9]2[CH2:14][CH2:13][C@H:12]([OH:15])[CH2:11][CH2:10]2)=[N:6][CH:7]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 426145762-Fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 178521587HCID 178521587, compound

Product 1

HCID 178521575HCID 178521575, compoundYield 83.8%

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
95 °C

Procedure

A mixture of trans-4-(5-chloro-4-iodopyridin-2-yl-amino)cyclohexanol (575 mg, 1.631 mmol), 2-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (655 mg, 2.94 mmol), PdCl2(dppf).CH2Cl2 adduct (133 mg, 0.163 mmol), DME (15 ml), and t 2M sodium carbonate (4.48 ml, 8.97 mmol) reaction mixture was stirred at 95° C. for 2 hr, followed by LCMS. The reaction mixture was cooled to room temperature, mixed with 20 ml of ethyl acetate, 15 ml of methanol, filtered and concentrated to yield a crude product. The crude was purified by silica gel chromatography using a 40 g column, eluting from 35%-85% ethyl acetate with hexane. The desired fractions were combined and concentrated to constant mass, giving 440 mg of titled compound as free base. LCMS (m/z): 322.2 (MH+), retention time=0.53 min.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered
  3. concentrationconcentrated
  4. customto yield a crude product
  5. customThe crude was purified by silica gel chromatography
  6. washeluting from 35%-85% ethyl acetate with hexane
  7. concentrationconcentrated to constant mass

Sources & evidence

ORD record
ord-18356223de5d41e7b9345a3689312bb3
Source dataset
uspto-grants-2014_07
Patent number
US08778951B2

Reaction notes

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