Trifluoroacetic acid → HCID 54673362, compound

HRID 509554Notes

Reaction equation

HRID 509554 reaction equation
C(O)(C(F)(F)F)=O.C(OC([N:15](C(OC(C)(C)C)=O)[C:16]1[C:21]([C:22]2[O:26][N:25]=[C:24]([C:27]3[CH:32]=[CH:31][C:30]([CH2:33][N:34](C)[C:35](=O)OC(C)(C)C)=[CH:29][C:28]=3[F:43])[CH:23]=2)=[CH:20][C:19]([C:44]2[CH:49]=[CH:48][C:47]([S:50]([CH:53]([CH3:55])[CH3:54])(=[O:52])=[O:51])=[CH:46][N:45]=2)=[CH:18][N:17]=1)=O)(C)(C)C>C(Cl)Cl>[F:43][C:28]1[CH:29]=[C:30]([CH2:33][NH:34][CH3:35])[CH:31]=[CH:32][C:27]=1[C:24]1[CH:23]=[C:22]([C:21]2[C:16]([NH2:15])=[N:17][CH:18]=[C:19]([C:44]3[CH:49]=[CH:48][C:47]([S:50]([CH:53]([CH3:54])[CH3:55])(=[O:51])=[O:52])=[CH:46][N:45]=3)[CH:20]=2)[O:26][N:25]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67480116HCID 67480116, compound

Product 1

HCID 54673362HCID 54673362, compoundYield 7.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (1.724 g, 1.165 mL, 15.12 mmol) was added to a stirred solution of tert-butyl N-[[4-[5-[2-[bis(tert-butoxycarbonyl)amino]-5-(5-isopropylsulfonyl-2-pyridyl)-3-pyridyl]isoxazol-3-yl]-3-fluoro-phenyl]methyl]-N-methyl-carbamate (198.7 mg, 0.1652 mmol) in DCM (7 mL) and the reaction stirred at ambient temperature for 16 hours. The solvent was removed in vacuo and the residue azeotroped with DCM (×2) and ether (×2). The material 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]. The fractions were collected, passed through a sodium bicarbonate cartridge and freeze-dried to give the title compound as a white solid (6 mg, 7% Yield). 1H NMR (400.0 MHz, DMSO) δ 1.22 (d, J=6.8 Hz, 6H), 2.20-2.30 (m, 3H), 3.50-3.60 (m, 1H), 3.75 (s, 2H), 7.05 (br s, 2H), 7.35-7.45 (m, 2H), 7.50 (s, 1H), 7.90-8.00 (m, 1H), 8.25-8.40 (m, 2H) and 8.80 (s, 1H) ppm; MS (ES+) 482.0.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue azeotroped with DCM (×2) and ether (×2)
  3. customThe material 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]
  4. customThe fractions were collected
  5. customfreeze-dried

Sources & evidence

ORD record
ord-26d738f08bc74794aae7191ff24f17c9
Source dataset
uspto-grants-2015_08
Patent number
US09096584B2

Reaction notes

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