Trifluoroacetic acid → HCID 59471836, compound

HRID 78668Notes

Reaction equation

HRID 78668 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:35]2[O:39][C:38]([C:40]3[CH:55]=[CH:54][C:43]([CH2:44][N:45](C)[C:46](=O)OC(C)(C)C)=[CH:42][CH:41]=3)=[N:37][N:36]=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][C:23]=2[F:34])=[CH:20][N:21]=1)=O)(C)(C)C>C(Cl)Cl>[F:34][C:23]1[CH:24]=[C:25]([S:28]([CH:31]([CH3:33])[CH3:32])(=[O:29])=[O:30])[CH:26]=[CH:27][C:22]=1[C:19]1[N:18]=[C:17]([C:35]2[O:39][C:38]([C:40]3[CH:41]=[CH:42][C:43]([CH2:44][NH:45][CH3:46])=[CH:54][CH:55]=3)=[N:37][N:36]=2)[C:16]([NH2:15])=[N:21][CH:20]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59472421Tert-butyl 4-(5-(3-bis(tert-butoxycarbonyl)amino-6-(2-fluoro-4-(isopropylsulfonyl)phenyl)pyrazin-2-yl)-1,3,4-oxadiazol-2-yl)benzyl(methyl)carbamate

Product 1

HCID 59471836HCID 59471836, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (1 mL, 12.98 mmol) was added to a solution of tert-butyl 4-(5-(3-bis(tert-butoxycarbonyl)amino-6-(2-fluoro-4-(isopropylsulfonyl)phenyl)pyrazin-2-yl)-1,3,4-oxadiazol-2-yl)benzyl(methyl)carbamate (114 mg, 0.1456 mmol) in CH2Cl2 (5 mL). The reaction was stirred at room temperature for 2 h. The solvent was removed in vacuo and the residue azeotroped with CH2Cl2 (×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: CH3 CN) over 16 minutes at 25 mL/min]. The product fractions were collected, passed through a sodium bicarbonate cartridge and freeze-dried to give the title compound as a yellow solid (43.5 mg, 62% yield); 1H NMR (400.0 MHz, DMSO) d 1.23 (d, 6H), 2.29 (s, 3H), 3.58 (m, 1H), 3.76 (s, 2H), 7.60 (d, 2H), 7.88 (d, 2H), 8.00 (br s, 2H), 8.10 (d, 2H), 8.32 (t, 1H) and 8.80 (s, 1H) ppm; MS (ES+) 483.3

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue azeotroped with CH2Cl2 (×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: CH3 CN) over 16 minutes at 25 mL/min]
  4. customThe product fractions were collected
  5. customfreeze-dried

Sources & evidence

ORD record
ord-fe088beaaf6342ef9c748b6c3a48383f
Source dataset
uspto-grants-2014_09
Patent number
US08841308B2

Reaction notes

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