Sodium bis(trimethylsilyl)amide → 6-Chloro-4-[(R)-1-(5-fluoro-2-methoxy-phenyl)-ethoxy]-pyridazin-3-ylamine

HRID 1406276Notes

Reaction equation

HRID 1406276 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][CH3:12])=[C:6]([C@H:8]([OH:10])[CH3:9])[CH:7]=1.N[N:14]1[CH:19]=[C:18](Br)[CH:17]=[C:16]([Cl:21])[NH:15]1.C[Si](C)(C)[N-:24][Si](C)(C)C.[Na+]>O1CCCC1>[Cl:21][C:16]1[N:15]=[N:14][C:19]([NH2:24])=[C:18]([O:10][C@@H:8]([C:6]2[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=2[O:11][CH3:12])[CH3:9])[CH:17]=1

Participants

5

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 26597266(1R)-1-(5-fluoro-2-methoxyphenyl)ethan-1-olHCID 674671712-Amino-4-bromo-6-chloro-pyridazine

Product 1

HCID 866910956-Chloro-4-[(R)-1-(5-fluoro-2-methoxy-phenyl)-ethoxy]-pyridazin-3-ylamineYield 54%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
66 °C

Procedure

To a solution of (R)-1-(5-fluoro-2-methoxy-phenyl)-ethanol (4.78 g, 28 mmol, 1.5 eq.) in tetrahydrofuran (40 mL) was added 2-amino-4-bromo-6-chloro-pyridazine (3.9 g, 18.7 mmol) followed by a solution of sodium hexamethyldisilazide (1M in tetrahydrofuran, 28.1 mL, 1.5 eq.). This mixture was then heated to 66° C. for 18 hr before cooling and evaporating under reduced pressure. The residue was purified by chromatography on silica gel (150 g) eluting with a gradient of ethyl acetate in heptane (10:90 to 50:50) to give the title compound as a yellow solid (3.0 g, 54%).

Workup

  1. temperaturebefore cooling
  2. customevaporating under reduced pressure
  3. customThe residue was purified by chromatography on silica gel (150 g)
  4. washeluting with a gradient of ethyl acetate in heptane (10:90 to 50:50)

Sources & evidence

ORD record
ord-167e7b9864614f0084cde8f97e331ce5
Source dataset
uspto-grants-2014_12
Patent number
US08916593B2

Reaction notes

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