Dichloromethane → HCID 178453634, compound

HRID 1963856Notes

Reaction equation

HRID 1963856 reaction equation
[C:1]([O:5][C:6](=[O:24])[NH:7][CH2:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([NH:15][C:16]2[CH:21]=[C:20](I)[C:19]([Cl:23])=[CH:18][N:17]=2)[CH2:11][CH2:10]1)([CH3:4])([CH3:3])[CH3:2].[F:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28](B2OC(C)(C)C(C)(C)O2)[N:27]=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].C(OCC)(=O)C.COCCOC>[C:1]([O:5][C:6](=[O:24])[NH:7][CH2:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([NH:15][C:16]2[CH:21]=[C:20]([C:28]3[CH:29]=[CH:30][CH:31]=[C:26]([F:25])[N:27]=3)[C:19]([Cl:23])=[CH:18][N:17]=2)[CH2:11][CH2:10]1)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 426145762-Fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 178453635HCID 178453635, compound

Product 1

HCID 178453634HCID 178453634, compoundYield 83.1%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

A mixture of tert-butyl(trans-4-(5-chloro-4-iodopyridin-2-yl-amino)cyclohexyl)methylcarbamate (510 mg, 1.095 mmol), 2-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (440 mg, 1.971 mmol), PdCl2(dppf).CH2Cl2 adduct (89 mg, 0.109 mmol), DME (7.5 ml), and 2M sodium carbonate (2.464 ml, 4.93 mmol) reaction mixture was stirred at about 100° C. for about 2 hours. The reaction mixture mixture was cooled to room temperature, mixed with 20 ml ethyl acetate, filtered and concentrated to yield a crude solid. The crude solid was purified by silica gel chromatography using 40 g column, eluting from 0%-45% ethyl acetate with hexane. The desired fractions were concentrated to constant mass, yielding 396 mg of titled compound as a free base. LCMS (m/z): 435.2 (MH+), retention time=0.85 min.

Workup

  1. temperatureThe reaction mixture mixture was cooled to room temperature
  2. filtrationfiltered
  3. concentrationconcentrated
  4. customto yield a crude solid
  5. customThe crude solid was purified by silica gel chromatography
  6. washeluting from 0%-45% ethyl acetate with hexane
  7. concentrationThe desired fractions were concentrated to constant mass

Sources & evidence

ORD record
ord-3a9e43d24cc24c50ac9719a10186947d
Source dataset
uspto-grants-2013_04
Patent number
US08415381B2

Reaction notes

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