Dichloromethane → HCID 66937071, compound

HRID 1623377Notes

Reaction equation

HRID 1623377 reaction equation
Br[C:2]1[N:7]=[C:6]([NH:8][C@H:9]2[C:11]3([CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[CH2:10]2)[CH:5]=[CH:4][CH:3]=1.[Cl:17][C:18]1[C:19](B(O)O)=[CH:20][C:21]([F:24])=[N:22][CH:23]=1.C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>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:17][C:18]1[C:19]([C:2]2[CH:3]=[CH:4][CH:5]=[C:6]([NH:8][C@H:9]3[C:11]4([CH2:16][CH2:15][O:14][CH2:13][CH2:12]4)[CH2:10]3)[N:7]=2)=[CH:20][C:21]([F:24])=[N:22][CH:23]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 44754822(5-Chloro-2-fluoropyridin-4-yl)boronic acidHCID 86650634HCID 86650634, compound

Product 1

HCID 66937071HCID 66937071, compoundYield 89.9%

Reagents, catalysts & solvents 4

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

Procedure

A mixture of (R)-6-bromo-N-(6-oxaspiro[2.5]octan-1-yl)pyridin-2-amine (C, 100 mg, 0.35 mmol), 5-chloro-2-fluoropyridin-4-ylboronic acid (136 mg, 0.77 mmol), PdCl2(dppf).CH2Cl2 adduct (23 mg, 0.028 mmol) in DME (1 mL) and 2M Na2CO3 (97 mg, 0.92 mmol) in a sealed tube was heated at 103° C. for 2 hr. The mixture was allowed to cool to ambient temperature and was diluted with EtOAc (˜25 mL) and MeOH (˜5 mL), filtered off and concentrated in vacuo. The resulting residue was purified by column chromatography [SiO2, 12 g, EtOAc/heptane=10/90 to 50/50]. Fractions were combined and concentrated in vacuo giving 105 mg of titled compound. LCMS (m/z): 334.0/336.0 [M+H]+, retention time=0.64 min.

Workup

  1. filtrationfiltered off
  2. concentrationconcentrated in vacuo
  3. customThe resulting residue was purified by column chromatography [SiO2, 12 g, EtOAc/heptane=10/90 to 50/50]
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f9b92c5907274224847df2a533da1836
Source dataset
uspto-grants-2014_07
Patent number
US08778951B2

Reaction notes

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