Trifluoroacetic acid → HCID 118379967, compound

HRID 708422Notes

Reaction equation

HRID 708422 reaction equation
C([O:5][C:6](=[O:53])[C:7]([O:10]/[N:11]=[C:12](/[C:40]1[N:41]=[C:42]([NH:45]C(OC(C)(C)C)=O)[S:43][CH:44]=1)\[C:13]([NH:15][C@@H:16]1[C:19](=[O:20])[N:18]([S:21]([OH:24])(=[O:23])=[O:22])[C@@H:17]1[CH2:25][N:26]1[N:30]=[C:29]([CH2:31][NH:32]C(OC(C)(C)C)=O)[CH:28]=[N:27]1)=[O:14])([CH3:9])[CH3:8])(C)(C)C.C(O)(C(F)(F)F)=O>C(O)=O>[NH2:32][CH2:31][C:29]1[CH:28]=[N:27][N:26]([CH2:25][C@@H:17]2[C@H:16]([NH:15][C:13](=[O:14])/[C:12](=[N:11]\[O:10][C:7]([CH3:9])([CH3:8])[C:6]([OH:53])=[O:5])/[C:40]3[N:41]=[C:42]([NH2:45])[S:43][CH:44]=3)[C:19](=[O:20])[N:18]2[S:21]([OH:24])(=[O:23])=[O:22])[N:30]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 118379727(2R,3S)-3-[[(2Z)-2-[2-methyl-1-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]oxyimino-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]acetyl]amino]-2-[[4-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]triazol-2-yl]methyl]-4-oxoazetidine-1-sulfonic acid

Product 1

HCID 118379967HCID 118379967, compoundYield 31.1%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Conditions

Temperature
0 °C

Procedure

(2R,3S)-3-((Z)-2-(((1-(tert-butoxy)-2-methyl-1-oxopropan-2-yl)oxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetamido)-2-((4-(((tert-butoxycarbonyl)amino)methyl)-2H-1,2,3-triazol-2-yl)methyl)-4-oxoazetidine-1-sulfonic acid (82 mg, 0.104 mmol) was stirred with formic acid (2.0 mL) at rt for 5 h, which removed both Boc groups. After concentration in vacuo, the material was dissolved in DCM (1.5 mL), cooled to 0° C. and treated with TFA (0.5 mL, 6.5 mmol) for 1 h, whereupon it was concentrated in vacuo. The crude residue was purified by reverse phase prep HPLC (T3, 30×150 mm, 5 μm, C18 column; ACN-water with 0.1% formic acid modifier, 1 mL/min), affording the title compound (17.2 mg, 31%) as a white solid. LCMS: m/z=529.9 (M−1); 1H NMR (400 MHz, D2O): δ 7.67 (s, 1H), 6.92 (s, 1H), 5.39 (d, J=5.6 Hz, 1H), 4.86-4.74 (m, 3H assumed; obscured by solvent residual peak), 4.16 (s, 2H), 1.25 (s, 3H), 1.23 (3H, s).

Workup

  1. customwhich removed both Boc groups
  2. concentrationAfter concentration in vacuo
  3. dissolutionthe material was dissolved in DCM (1.5 mL)
  4. concentrationwas concentrated in vacuo
  5. customThe crude residue was purified by reverse phase prep HPLC (T3, 30×150 mm, 5 μm, C18 column; ACN-water with 0.1% formic acid modifier, 1 mL/min)

Sources & evidence

ORD record
ord-548fe4b803ef431787b42aeef36a39cf
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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