Dichloromethane → HCID 58127273, compound

HRID 1963931Notes

Reaction equation

HRID 1963931 reaction equation
[Cl:1][C:2]1[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=3)[N:10]=2)=[CH:4][C:5](F)=[N:6][CH:7]=1.BrC1N=C([NH:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=C(F)C=2)C=CC=1.ClC1C(B(O)O)=C[C:44](F)=[N:45][CH:46]=1.C(Cl)Cl.[C:54](=[O:57])([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:9]2[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=3)[N:10]=2)=[CH:4][C:5]([NH:31][C@@H:32]2[CH2:33][CH2:38][C@H:37]([C:54]([N:45]([CH3:46])[CH3:44])=[O:57])[CH2:36]2)=[N:6][CH:7]=1

Participants

10

Reactant 5

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 44754822(5-Chloro-2-fluoropyridin-4-yl)boronic acidHCID 58127193HCID 58127193, compoundHCID 581273766-bromo-N-(3-fluorobenzyl)pyridin-2-amine

Product 1

HCID 58127273HCID 58127273, compound

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
100 °C

Procedure

Preparation of 5′-chloro-2′-fluoro-N-(3-fluorobenzyl)-2,4′-bipyridin-6-amine: To 6-bromo-N-(3-fluorobenzyl)pyridin-2-amine (2.0 g, 7.11 mmol) was added 5-chloro-2-fluoropyridin-4-ylboronic acid (1.996 g, 11.38 mmol), PdCl2(dppf).CH2Cl2 adduct (0.465 g, 0.569 mmol), DME (27 ml) and last 2M sodium carbonate (9.25 ml, 18.50 mmol). The crude reaction mixture was stirred at 100° C. for 3 hr, followed by LCMS. The crude mixture was cooled, 25 ml of ethyl acetate and 20 ml of methanol was added, filtered and concentrated to crude product. The crude was purified by silica gel chromatography using a 120 g column, eluting from 0%-20% ethyl acetate with hexane. The desired fractions were concentrated to constant mass, giving 1.259 grams of title compound as free base use with out further purification. LCMS (m/z): 332.2 (MH+), retention time=0.92 min.

Workup

  1. customThe crude reaction mixture
  2. filtrationfiltered
  3. concentrationconcentrated to crude product
  4. customThe crude was purified by silica gel chromatography
  5. washeluting from 0%-20% ethyl acetate with hexane
  6. concentrationThe desired fractions were concentrated to constant mass

Sources & evidence

ORD record
ord-5e41e1c2386b483a9a753cb6406bc002
Source dataset
uspto-grants-2013_04
Patent number
US08415381B2

Reaction notes

Loading…