Dichloromethane → HCID 178511586, compound

HRID 1623265Notes

Reaction equation

HRID 1623265 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]([NH2:15])[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+]>C(OCC)(=O)C.CO.CS(C)=O.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].C(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]([NH2:15])[CH2:11][CH2:10]2)=[N:6][CH:7]=1

Participants

11

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 426145762-Fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 178511614HCID 178511614, compound

Product 1

HCID 178511586HCID 178511586, compoundYield 73.1%

Reagents, catalysts & solvents 6

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 679Dimethyl SulfoxideSolventHCID 702EthanolSolventHCID 887MethanolSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of trans-N1-(5-chloro-4-iodopyridin-2-yl)cyclohexane-1,4-diamine (from step 1 above, 300 mg, 0.853 mmol), 2-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (285 mg, 1.280 mmol), PdCl2(dppf).CH2Cl2 adduct (84 mg, 0.102 mmol), DME (4 ml), Ethanol (1 ml), and 2M sodium carbonate (1.706 ml, 3.41 mmol) reaction mixture was stirred at about 90° C. until done by LCMS. The reaction mixture was cooled, then diluted with 25 ml of ethyl acetate and 10 ml of methanol, filtered, and concentrated to yield a crude solid. The crude solid was dissolved in DMSO, filtered and purified by prep LC. After lyapholization, 200 mg of the title compound was obtained as a TFA salt. LCMS (m/z): 321.0 (MH+), retention time=0.48 min.

Workup

  1. temperatureThe reaction mixture was cooled
  2. filtrationfiltered
  3. concentrationconcentrated
  4. customto yield a crude solid
  5. filtrationfiltered
  6. custompurified by prep LC

Sources & evidence

ORD record
ord-3a3a41d07bba4cdab491814c0d109f5f
Source dataset
uspto-grants-2014_07
Patent number
US08778951B2

Reaction notes

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