Trifluoroacetic acid → HCID 59471817, compound

HRID 2204880Notes

Reaction equation

HRID 2204880 reaction equation
[NH2:1][C:2]1[C:3]([C:20]2[O:24][C:23]([C:25]3[CH:30]=[CH:29][C:28]([CH2:31][N:32](C)[C:33](=O)OC(C)(C)C)=[CH:27][C:26]=3[CH3:41])=[N:22][N:21]=2)=[N:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH:17]([CH3:19])[CH3:18])(=[O:16])=[O:15])=[CH:10][CH:9]=2)=[CH:6][N:7]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH:17]([S:14]([C:11]1[CH:10]=[CH:9][C:8]([C:5]2[N:4]=[C:3]([C:20]3[O:24][C:23]([C:25]4[CH:30]=[CH:29][C:28]([CH2:31][NH:32][CH3:33])=[CH:27][C:26]=4[CH3:41])=[N:22][N:21]=3)[C:2]([NH2:1])=[N:7][CH:6]=2)=[CH:13][CH:12]=1)(=[O:15])=[O:16])([CH3:19])[CH3:18]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59472405HCID 59472405, compound

Product 1

HCID 59471817HCID 59471817, compoundYield 48.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl N-[[4-[5-[3-amino-6-(4-isopropylsulfonylphenyl)pyrazin-2-yl]-1,3,4-oxadiazol-2-yl]-3-methyl-phenyl]methyl]-N-methyl-carbamate (120 mg, 0.2074 mmol) in CH2Cl2 (10 mL) was added TFA (709.5 mg, 479.4 μL, 6.222 mmol) and the resulting solution stirred at room temperature for 1 h. The reaction mixture was concentrated in vacuo and redissolved in CH2Cl2 (20 ml) and concentrated. The residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. Product fractions were combined and lypholised to give the product as a yellow solid (48.0 mg, 39%); 1H NMR (400 MHz, DMSO) d 1.2 (d, 6H), 2.6 (s, 3H), 2.75 (s, 3H), 3.4-3.5 (m, 1H), 4.25 (s, 2H), 7.7 (d, 1H), 7.72 (s, 1H), 8.0-8.1 (m, 3H), 8.2 (d, 1H), 8.4 (d, 2H), 8.8 (br s, 2H) and 9.2 (s, 1H) ppm; MS (ES+) 479.4

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionredissolved in CH2Cl2 (20 ml)
  3. concentrationconcentrated
  4. customThe residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]

Sources & evidence

ORD record
ord-8b0495f8aba648d98a82e31ad99944f8
Source dataset
uspto-grants-2016_06
Patent number
US09365557B2

Reaction notes

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