Tetrahydrofuran → HCID 58137757, compound

HRID 2189463Notes

Reaction equation

HRID 2189463 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:32]=[CH:31][C:12]([C:13]([NH:15][NH:16][C:17]2[N:18]=[N:19][C:20]([Cl:30])=[CH:21][C:22]=2[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=O)=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1COCC1.P(CC)(CC)CC.CCN(C(C)C)C(C)C>C(Cl)(Cl)(Cl)Cl>[C:1]([O:5][C:6]([NH:8][C:9]1[CH:32]=[CH:31][C:12]([C:13]2[N:18]3[N:19]=[C:20]([Cl:30])[CH:21]=[C:22]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C:17]3=[N:16][N:15]=2)=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 27365TriethylphosphineHCID 81531DiisopropylethylamineHCID 58137759HCID 58137759, compound

Product 1

HCID 58137757HCID 58137757, compoundYield 71.5%

Reagents, catalysts & solvents 1

HCID 5943Carbon TetrachlorideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl 3-(2-(4-(tert-butoxycarbonylamino)benzoyl)hydrazinyl)-6-chloropyridazine-4-carboxylate (66C) (1.49 g, 3.20 mmol) in a mixed solvent of THF (10 mL) and CCl4 (5 mL) at 0° C. under argon was added Et3P (3.35 mL, 19.2 mmol), followed by DIPEA (3.35 mL, 19.2 mmol). The reaction mixture was stirred at 0° C. for 10 min. Analysis by LC/MS indicated the starting material was consumed. The reaction mixture was partitioned between EtOAc and water, the separated EtOAc layer washed with water, saturated aqueous NaHCO3, saturated aqueous NaCl (2×), dried (anhydrous Na2SO4), and concentrated. The crude residue was purified using a silica gel cartridge (40 g) which was pretreated with 1% Et3N in hexanes for 10 min at 10 mL/min, eluting with a gradient of EtOAc (0-50%) in hexanes to afford 1.02 g (71%) of the title compound as a yellow solid. HPLC/MS (Method B): retention time=3.78 min, [M+H]+=446.3.

Workup

  1. customwas consumed
  2. customThe reaction mixture was partitioned between EtOAc and water
  3. washthe separated EtOAc layer washed with water, saturated aqueous NaHCO3, saturated aqueous NaCl (2×)
  4. dry with materialdried (anhydrous Na2SO4)
  5. concentrationconcentrated
  6. customThe crude residue was purified
  7. waitwas pretreated with 1% Et3N in hexanes for 10 min at 10 mL/min
  8. washeluting with a gradient of EtOAc (0-50%) in hexanes

Sources & evidence

ORD record
ord-221eac93e8bc43c990dd2317065a71dd
Source dataset
uspto-grants-2012_12
Patent number
US08324241B2

Reaction notes

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