Binap, (A+-)- → 6-Bromo-N-[4-(1-fluoroethyl)-2-pyridinyl]-4-methyl-2-pyridinamine

HRID 595276Notes

Reaction equation

HRID 595276 reaction equation
[F:1][CH:2]([C:4]1[CH:9]=[CH:8][N:7]=[C:6](I)[CH:5]=1)[CH3:3].[Br:11][C:12]1[N:17]=[C:16]([NH2:18])[CH:15]=[C:14]([CH3:19])[CH:13]=1.CC([O-])(C)C.[K+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[Br:11][C:12]1[N:17]=[C:16]([NH:18][C:6]2[CH:5]=[C:4]([CH:2]([F:1])[CH3:3])[CH:9]=[CH:8][N:7]=2)[CH:15]=[C:14]([CH3:19])[CH:13]=1

Participants

7

Reactant 4

HCID 634876Binap, (A+-)-HCID 221765076-Bromo-4-methylpyridin-2-amineHCID 23665647Potassium tert-butoxideHCID 1182089034-(1-Fluoroethyl)-2-iodopyridine

Product 1

HCID 901351346-Bromo-N-[4-(1-fluoroethyl)-2-pyridinyl]-4-methyl-2-pyridinamine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

4-(1-Fluoroethyl)-2-iodopyridine (90 g, 359 mmol, 1.05 equiv), 6-bromo-4-methylpyridin-2-amine (63.7 g, 341 mmol, 1.00 equiv), toluene (900 mL), t-BuOK (57.6 g, 1.50 equiv), BINAP (10.8 g, 17.3 mmol, 0.05 equiv) and Pd2(dba)3 (15.7 g, 17.1 mmol, 0.05 equiv) were combined into a 2000-mL 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen. The reaction mixture was stirred overnight at 90° C. in an oil bath and then cooled to r.t, diluted with DCM (500 mL). The solid was filtered out, washed with DCM and the filtrate was concentrated under vacuum. The residue was purified by column chromatography on silica gel column (1:15 ethyl acetate/petroleum ether) to afford 6-bromo-N-[4-(1-fluoroethyl)pyridin-2-yl]-4-methylpyridin-2-amine as a light yellow solid. ESI calc'd for C13H14BrFN3 [M+H]+ 309. found 309. 1H NMR (CD3OD, 400 MHz, ppm): δ 8.23-8.22 (m, 1H), 7.66 (s, 1H), 7.45 (s, 1H), 6.934-6.91 (m, 2H), 5.72-5.51 (m, 1H), 2.32 (s, 3H), 1.68-1.61 (m, 3H).

Workup

  1. custompurged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. temperaturecooled
  4. additiondiluted with DCM (500 mL)
  5. filtrationThe solid was filtered out
  6. washwashed with DCM
  7. concentrationthe filtrate was concentrated under vacuum
  8. customThe residue was purified by column chromatography on silica gel column (1:15 ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-55bcbfd5b6cd4363a6896e79c3cf970f
Source dataset
uspto-grants-2016_01
Patent number
US09242984B2

Reaction notes

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