Trifluoroacetic acid → HCID 59471824, compound

HRID 78669Notes

Reaction equation

HRID 78669 reaction equation
C(O)(C(F)(F)F)=O.C(OC([N:15](C(OC(C)(C)C)=O)[C:16]1[C:17]([C:34]2[O:38][N:37]=[C:36]([C:39]3[CH:44]=[CH:43][C:42]([CH2:45][N:46](C)[C:47](=O)OC(C)(C)C)=[CH:41][C:40]=3[CH3:55])[CH:35]=2)=[N:18][C:19]([C:22]2[CH:27]=[CH:26][C:25]([S:28]([CH:31]([CH3:33])[CH3:32])(=[O:30])=[O:29])=[CH:24][CH:23]=2)=[CH:20][N:21]=1)=O)(C)(C)C>ClCCl>[CH:31]([S:28]([C:25]1[CH:24]=[CH:23][C:22]([C:19]2[N:18]=[C:17]([C:34]3[O:38][N:37]=[C:36]([C:39]4[CH:44]=[CH:43][C:42]([CH2:45][NH:46][CH3:47])=[CH:41][C:40]=4[CH3:55])[CH:35]=3)[C:16]([NH2:15])=[N:21][CH:20]=2)=[CH:27][CH:26]=1)(=[O:29])=[O:30])([CH3:33])[CH3:32]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59471981HCID 59471981, compound

Product 1

HCID 59471824HCID 59471824, compoundYield 82.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (556.9 mg, 376.3 μL, 4.884 mmol) was added to a solution of tert-butyl N-[[4-[5-[3-[bis(tert-butoxycarbonyl)amino]-6-(4-isopropylsulfonylphenyl)pyrazin-2-yl]isoxazol-3-yl]-3-methyl-phenyl]methyl]-N-methyl-carbamate (190 mg, 0.2442 mmol) in dichloromethane (4.750 mL) and the resulting yellow solution stirred overnight at room temperature. The reaction mixture was concentrated in vacuo and the residue taken up in methanol (2 mL) and dichloromethane (1 mL) and passed through an SCX cartridge and the product eluted with 2M ammonia in methanol and concentrated in vacuo. The filtrate was purified further 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: CH3 CN) over 16 minutes at 25 mL/min]. The product fractions were collected and lypholised to give the product as a yellow solid (96.4 mg, 69% yield); 1H NMR (400.0 MHz, DMSO) d 1.18 (d, 6H), 2.61 (s, 3H), 2.62 (m, 3H), 3.48 (m, 1H), 4.20 (m, 2H), 7.24 (br s, 2H), 7.48-7.52 (m, 2H), 7.63 (s, 1H), 7.84 (m, 1H), 7.93 (m, 2H), 8.37 (m, 2H), 8.81 (br s, 2H) and 8.97 (s, 1H) ppm; MS (ES+) 478.3

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. washthe product eluted with 2M ammonia in methanol
  3. concentrationconcentrated in vacuo
  4. customThe filtrate was purified further 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: CH3 CN) over 16 minutes at 25 mL/min]
  5. customThe product fractions were collected

Sources & evidence

ORD record
ord-1765c960cdff4357ae00b7ca0144379d
Source dataset
uspto-grants-2014_09
Patent number
US08841308B2

Reaction notes

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