Diisopropylamine → 3-(Tributylstannanyl)pyridazine

HRID 638817Notes

Reaction equation

HRID 638817 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[N:13]1[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=1.[CH2:19]([Sn:23](Cl)([CH2:28][CH2:29][CH2:30][CH3:31])[CH2:24][CH2:25][CH2:26][CH3:27])[CH2:20][CH2:21][CH3:22].[NH4+].[Cl-]>O1CCCC1>[CH2:28]([Sn:23]([C:18]1[N:13]=[N:14][CH:15]=[CH:16][CH:17]=1)([CH2:19][CH2:20][CH2:21][CH3:22])[CH2:24][CH2:25][CH2:26][CH3:27])[CH2:29][CH2:30][CH3:31]

Participants

7

Reactant 5

HCID 7912DiisopropylamineHCID 9259PyridazineHCID 15096Tributyltin ChlorideHCID 25517Ammonium ChlorideHCID 178418339Butyllithium

Product 1

HCID 27632603-(Tributylstannanyl)pyridazineYield 8.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

n-Butyllithium (2.76 mL, 6.9 mmol, 2.5 M in hexane) was added dropwise to a cooled (0° C.) solution of diisopropylamine (0.97 mL, 6.9 mmol) in tetrahydrofuran (2 mL) under a nitrogen atmosphere. After stirring for 30 minutes the reaction mixture was cooled to −78° C. and a solution of pyridazine (452 μL, 6.3 mmol) and tributyltin chloride (1.9 mL, 6.9 mmol) were added simultaneously while the temperature was kept below −70° C. The reaction mixture was stirred for 2 hours at −78° C.; subsequently, a saturated aqueous NH4Cl solution was added and the reaction mixture was extracted three times with ethyl acetate. The combined organic layers were dried (MgSO4) and evaporated to dryness. The crude product was purified by LCMS to give tributylstannylpyridazine (197 mg, 0.53 mmol, 8% yield). This stannylpyridazine (183 mg, 0.49 mmol), (11β,16α,17β)-11-(4-bromophenyl)-17-cyclopropylcarbonyl-16-methylestra-4,9-dien-3-one (100 mg, 0.20 mmol) and bis(triphenylphosphine)palladium(II) chloride (3 mg, 0.004 mmol) were dissolved in dioxane (3 mL) under a nitrogen atmosphere. The reaction mixture was stirred overnight at 110° C. and then cooled to room temperature. Water was added and the mixture was extracted three times with dichloromethane. The combined organic layers were dried through a phase separate filter and evaporated to dryness. Purification by LCMS followed by lyophilisation gave (11β,16α,17β)-17-cyclopropylcarbonyl-16-methyl-11-[4-(4-pyridazinyl)phenyl]estra-4,9-dien-3-one (78 mg, 0.16 mmol, 79% yield). 1H NMR (400 MHz, CDCl3): δ 0.33 (s, 3H), 0.85-2.84 (m, 26H), 4.48 (d, J=7 Hz, 1H), 5.81 (s, 1H), 7.33-7.37 (m, 2H), 7.60-7.64 (m, 3H), 9.21 (dd, J=5 and 1 Hz, 1H), 9.46 (dd, J=3 and 1 Hz, 1H).

Workup

  1. customwas kept below −70° C
  2. stirringThe reaction mixture was stirred for 2 hours at −78° C.
  3. extractionthe reaction mixture was extracted three times with ethyl acetate
  4. dry with materialThe combined organic layers were dried (MgSO4)
  5. customevaporated to dryness
  6. customThe crude product was purified by LCMS

Sources & evidence

ORD record
ord-8e1b27ee17174dec936848ba0b0842dd
Source dataset
uspto-grants-2010_04
Patent number
US07691836B2

Reaction notes

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