Trifluoroacetic acid → HCID 131724941, compound

HRID 2183513Notes

Reaction equation

HRID 2183513 reaction equation
FC(F)(F)C(O)=O.[OH:8][C:9]1([C:22]2[CH:27]=[CH:26][C:25]([CH2:28][O:29][C:30]3[C:39]4[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=4)[C:33]4=[N:40][N:41]=[C:42]([C:43]5[CH:47]=[C:46]([CH3:48])[O:45][N:44]=5)[N:32]4[N:31]=3)=[CH:24][N:23]=2)[CH2:14][CH2:13][N:12](C(OC(C)(C)C)=O)[CH2:11][CH2:10]1>C(Cl)Cl>[CH3:48][C:46]1[O:45][N:44]=[C:43]([C:42]2[N:32]3[N:31]=[C:30]([O:29][CH2:28][C:25]4[CH:26]=[CH:27][C:22]([C:9]5([OH:8])[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]5)=[N:23][CH:24]=4)[C:39]4[C:34]([C:33]3=[N:40][N:41]=2)=[CH:35][CH:36]=[CH:37][CH:38]=4)[CH:47]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58298364HCID 58298364, compound

Product 1

HCID 131724941HCID 131724941, compoundYield 62.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (3 ml) was added to a stirred solution of 1,1-dimethylethyl 4-hydroxy-4-[5-({[3-(5-methylisoxazol-3-yl){1,2,4]triazolo[3,4-α]phthalazin-6-yl]oxy}methyl)pyridin-2-yl]-1-piperidine carboxylate(707 mg, 1.27 mmol) in CH2Cl2 (30 ml) at room temperature and the reaction stirred for 6 h. The reaction mixture was concentrated under reduced pressure, 2N NaOH solution (30 ml) was added and the resulting precipitate was filtered off. After dissolving in MeOH/CH2Cl2 (60 ml) and dry loading onto alumina, the crude residue was purified by column chromatography on alumina using 5-7% MeOH/CH2Cl2 containing 1% NH3 to yield the desired phthalazine (361 mg, 62%). 1H NMR (360 MHz, d6-DMSO) δ 8.80 (1H, s), 8.55 (1H, d, J=7.1 Hz), 8.23 (1H, d, J=7.1 Hz), 8.15-8.03 (2H, m), 7.93 (1H, t, J=7.1 Hz), 7.71 (1H, d, J=7.4 Hz), 7.07 (1H, s), 5.67 (2H, s), 5.06 (2H, s), 2.91 (2H, t, J=11.2 Hz), 2.74 (2H, d, J=11.2 Hz), 2.60 (3H, s), 2.04 (2H, td, J=12.4, 4.0 Hz), 1.44 (2H, d, J=12.4 Hz). m/z (ES+) 458 (M+H+).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure, 2N NaOH solution (30 ml)
  2. additionwas added
  3. filtrationthe resulting precipitate was filtered off
  4. dissolutionAfter dissolving in MeOH/CH2Cl2 (60 ml)
  5. customdry loading onto alumina
  6. customthe crude residue was purified by column chromatography on alumina using 5-7% MeOH/CH2Cl2 containing 1% NH3

Sources & evidence

ORD record
ord-81df27fde90f4fa1b85bffe0a9ce0516
Source dataset
uspto-grants-2005_05
Patent number
US06900209B2

Reaction notes

Loading…