Dichloromethane → HCID 66937030, compound

HRID 1963954Notes

Reaction equation

HRID 1963954 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)[CH:5]=[N:4][CH:3]=1.[Cl:16][C:17]1[C:18](B(O)O)=[CH:19][C:20]([F:23])=[N:21][CH:22]=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].CO.C(OCC)(=O)C.COCCOC>[Cl:16][C:17]1[C:18]([C:2]2[N:7]=[C:6]([NH:8][CH2:9][CH:10]3[CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)[CH:5]=[N:4][CH:3]=2)=[CH:19][C:20]([F:23])=[N:21][CH:22]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 44754822(5-Chloro-2-fluoropyridin-4-yl)boronic acidHCID 534102886-Chloro-N-[(tetrahydro-2H-pyran-4-yl)methyl]-2-pyrazinamine

Product 1

HCID 66937030HCID 66937030, compoundYield 49.8%

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 6-chloro-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine (1390 mg, 6.10 mmol), 5-chloro-2-fluoropyridin-4-ylboronic acid (2141 mg, 12.21 mmol), PdCl2(dppf).CH2Cl2 adduct (399 mg, 0.488 mmol), DME (24 ml) and 2M sodium carbonate (9.16 ml, 18.31 mmol) was stirred atl 10-115° C. for 90 min and the reaction progress was followed by LCMS. The reaction mixture was cooled, 30 ml of ethyl acetate and 20 ml of methanol were added, filtered and concentrated to crude product. The crude was purified by silica gel chromatography using 80 g column eluting with 20-75% ethyl acetate in heptane. The desired fractions were concentrated to constant mass, giving 980 mg of titled compound as free base. LCMS (m/z): 323.0 (MH+), retention time=0.81 min.

Workup

  1. temperatureThe reaction mixture was cooled
  2. filtrationfiltered
  3. concentrationconcentrated to crude product
  4. customThe crude was purified by silica gel chromatography
  5. washeluting with 20-75% ethyl acetate in heptane
  6. concentrationThe desired fractions were concentrated to constant mass

Sources & evidence

ORD record
ord-369d8ccd879141338a284083dd4b3a02
Source dataset
uspto-grants-2013_04
Patent number
US08415381B2

Reaction notes

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