Water → HCID 69200205, compound

HRID 746415Notes

Reaction equation

HRID 746415 reaction equation
O.[C:2](Cl)(=[O:6])[C:3](Cl)=O.Cl.[F:9][C:10]([F:22])([F:21])[C:11]1[N:20]=[CH:19][C:14]2[CH2:15][NH:16][NH:17]C[C:13]=2[CH:12]=1.C([N:25](CC)CC)C>C(Cl)Cl.CN(C=O)C>[F:9][C:10]([F:22])([F:21])[C:11]1[N:20]=[CH:19][C:14]2[CH2:15][NH:16][NH:17][CH:3]([C:2]([NH2:25])=[O:6])[C:13]=2[CH:12]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 69203803HCID 69203803, compound

Product 1

HCID 69200205HCID 69200205, compoundYield 10.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×

Procedure

To a solution of Intermediate 2 (250 mg, 0.712 mmol) in DCM (100 mL), was added 2M oxalyl chloride in DCM (0.427 μL, 0.854 mmol) and DMF (˜50 μL). The reaction mixture was stirred for 4 hr, and concentrated. The residue was put on high vacuum for 2 hr and dissolved in DCM (10 mL). The formed acid chloride was added into a solution of the product from Step D (267 mg, 0.854 mmol) and triethylamine (456 L, 3.28 mmol) in DCM (10 mL) at 0° C. The reaction mixture was stirred for 16 hr and concentrated. The residue was purified by flash column chromatography (silica gel, 8% [aq. NH4OH/MeOH 1/9]/DCM ) first and then by preparative TLC (100 micron) (developed by 5% MeOH/DCM) to yield the 7-(trifluoromethyl)-1,2,3,4-tetrahydropyrido[3,4-d]pyridazine amide (39.5 mg, 10.3%) and another structural isomer (42.3 mg, 11.1%). LC-MS calc. For C24H30F6N4O3: 536.22; Found: 537 (M+H).

Workup

  1. concentrationconcentrated
  2. waitThe residue was put on high vacuum for 2 hr
  3. dissolutiondissolved in DCM (10 mL)
  4. stirringThe reaction mixture was stirred for 16 hr
  5. concentrationconcentrated
  6. customThe residue was purified by flash column chromatography (silica gel, 8% [aq. NH4OH/MeOH 1/9]/DCM ) first

Sources & evidence

ORD record
ord-d8f355911bcf473496be9a869e9cf0f2
Source dataset
uspto-grants-2008_07
Patent number
US07393844B2

Reaction notes

Loading…