Trifluoroacetic acid → HCID 178434056, compound

HRID 708520Notes

Reaction equation

HRID 708520 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:57]/[O:58][C:59]2([C:62]([OH:64])=[O:63])[CH2:61][CH2:60]2)/[C:8]([NH:10][C@@H:11]2[C:14](=[O:15])[N:13]([S:16]([OH:19])(=[O:18])=[O:17])[C@@H:12]2[CH2:20][N:21]2[N:25]=[C:24]([CH2:26][NH:27]/[C:28](=[N:48]/C(OC(C)(C)C)=O)/[N:29](C(OC(C)(C)C)=O)[CH2:30][CH2:31][CH2:32][NH:33]C(=O)OC(C)(C)C)[C:23]([CH3:56])=[N:22]2)=[O:9])[N:6]=1.C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:33][CH2:32][CH2:31][CH2:30][NH:29][C:28](=[NH:48])[NH:27][CH2:26][C:24]1[C:23]([CH3:56])=[N:22][N:21]([CH2:20][C@@H:12]2[C@H:11]([NH:10][C:8](=[O:9])/[C:7](=[N:57]\[O:58][C:59]3([C:62]([OH:64])=[O:63])[CH2:61][CH2:60]3)/[C:5]3[N:6]=[C:2]([NH2:1])[S:3][CH:4]=3)[C:14](=[O:15])[N:13]2[S:16]([OH:19])(=[O:18])=[O:17])[N:25]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 178434055HCID 178434055, compound

Product 1

HCID 178434056HCID 178434056, compoundYield 47.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Followed the general procedure for the acid mediated deprotection using 1-(((Z)-(1-(2-aminothiazol-4-yl)-2-(((2R,3S)-2-((4-((Z)-4-(tert-butoxycarbonyl)-3-((tert-butoxycarbonyl)imino)-11,11-dimethyl-9-oxo-10-oxa-2,4,8-triazadodecyl)-5-methyl-2H-1,2,3-triazol-2-yl)methyl)-4-oxo-1-sulfoazetidin-3-yl)amino)-2-oxoethylidene)amino)oxy)cyclopropanecarboxylic acid (58.5 mg, 0.062 mmol), DCM (621 μL), anisole (20.4 μL, 0.186 mmol) and TFA (427 μL, 4.55 mmol). The reaction mixture was diluted with ice-cold water (1 mL) and the layers were separated. The organic layer was extracted with water (1 mL) and the combined aqueous layers were washed with DCM (1 mL) and then purified by reverse phase preparative HPLC (XSELECT C18, 5μ, 30×100 mm, 1-20% ACN/H2O w/0.1% formic acid buffer over 18 min, 60 mL/min), affording the title compound (19 mg, 44%) as an off-white solid. LCMS: Rt=0.54 min, m/z=643.2 (M+1) Method 2m_acidic_polar. 1H NMR (400 MHz, D2O) δ 7.11 (s, 1H), 5.62 (d, J=5.6 Hz, 1H), 5.01-4.94 (m, 1H), 4.91-4.74 (m, 2H assumed; obscured by solvent residual peak), 4.50 (br s, 2H), 3.36 (t, J=6.9 Hz, 2H), 3.11 (t, J=7.8 Hz, 2H), 2.29 (s, 3H), 2.01 (p, J=7.2 Hz, 2H), 1.35-1.25 (m, 2H), 1.21-1.05 (m, 2H).

Workup

  1. customthe layers were separated
  2. extractionThe organic layer was extracted with water (1 mL)
  3. washthe combined aqueous layers were washed with DCM (1 mL)
  4. custompurified by reverse phase preparative HPLC (XSELECT C18, 5μ, 30×100 mm, 1-20% ACN/H2O w/0.1% formic acid buffer over 18 min, 60 mL/min)

Sources & evidence

ORD record
ord-40ba0421b4eb486c8e8536f5342f2ed2
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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