Nitrogen → HCID 86710714, compound

HRID 1027287Notes

Reaction equation

HRID 1027287 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[C:4]([F:11])[CH:3]=1.Cl[C:13]1[N:18]=[N:17][C:16]([N:19]([CH3:30])[CH:20]2[CH2:25][C:24]([CH3:27])([CH3:26])[NH:23][C:22]([CH3:29])([CH3:28])[CH2:21]2)=[CH:15][CH:14]=1.C([O-])([O-])=O.[Na+].[Na+].N#N>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:13]2[N:18]=[N:17][C:16]([N:19]([CH3:30])[CH:20]3[CH2:25][C:24]([CH3:26])([CH3:27])[NH:23][C:22]([CH3:29])([CH3:28])[CH2:21]3)=[CH:15][CH:14]=2)=[C:4]([F:11])[CH:3]=1

Participants

5

Reactant 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 4193595(4-Chloro-2-fluorophenyl)boronic acidHCID 867105396-chloro-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine

Product 1

HCID 86710714HCID 86710714, compoundYield 95.2%

Conditions

Temperature
90 °C

Procedure

(4-Chloro-2-fluorophenyl)boronic acid (4.29 g, 24.6 mmol), Intermediate 1-1 (6.63 g, 23.4 mmol) and Na2CO3 (7.45 g, 70.3 mmol) were degassed for 10 minutes with N2, then PdCl2(dppf)CH2Cl2 (0.96 g, 1.17 mmol) was added. The reaction mixture was heated at 90° C. for 2 h. The reaction mixture was concentrated in vacuo then CH2Cl2 and 1 M HCl were added. The aqueous phase was washed with CH2Cl2, then basified to pH 14 with a 6 M NaOH solution. The aqueous phase was then extracted with CH2Cl2 (3×). The combined organic phases were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford 6-(4-chloro-2-fluorophenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine as a brown solid (8.40 g, 95%). [M+H]: 377.2; 1H NMR (400 MHz, MeOD) δ 7.87 (t, J=8.5 Hz, 1H), 7.76 (dd, J=9.5, 2.4 Hz, 1H), 7.32-7.40 (m, 2H), 7.17 (d, J=9.5 Hz, 1H), 5.13-5.36 (m, 1H), 1.69 (dd, J=12.5, 3.5 Hz, 2H), 1.57 (t, J=12.5 Hz, 2H), 1.38 (s, 6H), 1.23 (s, 6H).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additionCH2Cl2 and 1 M HCl were added
  3. washThe aqueous phase was washed with CH2Cl2
  4. extractionThe aqueous phase was then extracted with CH2Cl2 (3×)
  5. dry with materialThe combined organic phases were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-48d32af319e947808843e811cdb1608b
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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