Dimethylamine → HCID 10295563, compound

HRID 2183505Notes

Reaction equation

HRID 2183505 reaction equation
S(Cl)(C)(=O)=O.[CH3:6][C:7]1[O:11][N:10]=[C:9]([C:12]2[N:16]3[N:17]=[C:18]([O:25][CH2:26][C:27]4[N:28]=[N:29][N:30]([CH2:32][CH2:33]O)[CH:31]=4)[C:19]4[C:24]([C:15]3=[N:14][N:13]=2)=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH:8]=1.C[CH2:36][N:37](CC)[CH2:38]C.N(C)C>C(Cl)Cl.C1COCC1.O>[CH3:36][N:37]([CH3:38])[CH2:33][CH2:32][N:30]1[CH:31]=[C:27]([CH2:26][O:25][C:18]2[C:19]3[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:15]3=[N:14][N:13]=[C:12]([C:9]4[CH:8]=[C:7]([CH3:6])[O:11][N:10]=4)[N:16]3[N:17]=2)[N:28]=[N:29]1

Participants

8

Reactant 4

HCID 674DimethylamineHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 131724939HCID 131724939, compound

Product 1

HCID 10295563HCID 10295563, compoundYield 8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Mesyl chloride (349 μl, 4.5 mmol) was added to a stirred suspension of 2-{4-[3-(5-methylisoxazol-3-yl)-[1,2,4]triazolo[3,4-α]phthalazin-6-yloxymethyl]-[1,2,3]triazol-1-yl}ethanol (354 mg, 0.9 mmol) in Et3N (629 μl, 4.5 mmol) and CH2Cl2 (50 ml) at 0° C. under N2. The reaction was stirred overnight slowly warming to room temperature. H2O (20 ml) was added and the organics separated, dried and concentrated under reduced pressure. The crude residue was taken up in DMF (5 ml) in a sealed tube and a solution of Me2NH (8 mmol) in THF (2.0 M, 4 ml) was added. The reaction was heated at 80° C. for 4 h. The reaction mixture was concentrated under reduced pressure and then taken up in MeOH/CH2Cl2 and dry loaded onto silica. The mixture was purified by column chromatography on silica using 1.5% MeOH/CH2Cl2 containing 1% NH3 as eluent to yield the desired phthalazine (30 mg, 8%). 1H NMR (360 MHz, CDCl3) δ 8:85 (1H, s), 8.64 (1H, d, J=7.4 Hz), 8.24 (1H, d, J=7.4 Hz), 7.93 (1H, t, J=7.4 Hz), 7.80 (1H, t, J=7.4 Hz), 6.90 (1H, s), 5.77 (2H, s), 4.46 (2H, t, J=6.5 Hz), 2.92 (2H, t, J=6.5 Hz), 2.60 (3H, s), 2.24 (6H, s). m/z (ES+) 420 (M+H+).

Workup

  1. customthe organics separated, dried
  2. concentrationconcentrated under reduced pressure
  3. customThe crude residue was taken up in DMF (5 ml) in a sealed tube
  4. temperatureThe reaction was heated at 80° C. for 4 h
  5. concentrationThe reaction mixture was concentrated under reduced pressure
  6. customdry
  7. customThe mixture was purified by column chromatography on silica using 1.5% MeOH/CH2Cl2 containing 1% NH3 as eluent

Sources & evidence

ORD record
ord-2776970453d3499f9b909f7db992e627
Source dataset
uspto-grants-2005_05
Patent number
US06900209B2

Reaction notes

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