Dichloromethane → HCID 58127300, compound

HRID 1963834Notes

Reaction equation

HRID 1963834 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[C:5]([C:16]([F:19])([F:18])[F:17])=[CH:4][CH:3]=1.[Cl:20][C:21]1[C:22](B(O)O)=[CH:23][C:24]([F:27])=[N:25][CH:26]=1.C(Cl)Cl.COCCOC>CCOC(C)=O.CO.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]>[Cl:20][C:21]1[C:22]([C:2]2[CH:3]=[CH:4][C:5]([C:16]([F:19])([F:18])[F:17])=[C:6]([NH:8][CH2:9][CH:10]3[CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)[N:7]=2)=[CH:23][C:24]([F:27])=[N:25][CH:26]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 80711,2-DimethoxyethaneHCID 44754822(5-Chloro-2-fluoropyridin-4-yl)boronic acidHCID 58127318HCID 58127318, compound

Product 1

HCID 58127300HCID 58127300, compoundYield 77.2%

Reagents, catalysts & solvents 3

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

Procedure

A mixture of 6-chloro-N-((tetrahydro-2H-pyran-4-yl)methyl)-3-(trifluoromethyl)pyridin-2-amine (100 mg, 0.339 mmol), 5-chloro-2-fluoropyridin-4-ylboronic acid (89 mg, 0.509 mmol), PdCl2(dppf). CH2Cl2 adduct (27.7 mg, 0.034 mmol), DME (1.5 mL) and 2M aqueous Na2CO2 (0.5 mL, 1 mmol) was stirred in a sealed glass vessel at about 100° C. for about 3 hours. After cooling to ambient temperature the mixture was diluted with EtOAc (25 mL) and MeOH (20 mL), filtered and concentrated in vacuo. The resulting crude material was purified by column chromatography [silica gel, 12 g, EtOAc/hexane=5/100 to 50/50] to yield 5′-chloro-2′-fluoro-N-((tetrahydro-2H-pyran-4-yl)methyl)-5-(trifluoromethyl)-2,4′-bipyridin-6-amine (Intermediate T, 102 mg, 77%). LCMS (m/z): 390.2 [M+H]+; Retention time=1.12 min.

Workup

  1. filtrationfiltered
  2. concentrationconcentrated in vacuo
  3. customThe resulting crude material was purified by column chromatography [silica gel, 12 g, EtOAc/hexane=5/100 to 50/50]

Sources & evidence

ORD record
ord-57606b5b3d7e449da4b916cd23a4439f
Source dataset
uspto-grants-2013_04
Patent number
US08415381B2

Reaction notes

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