Trifluoroacetic acid → Lys 228)

HRID 708388Notes

Reaction equation

HRID 708388 reaction equation
C([O:14][C:15]([C:17]1([O:20]/[N:21]=[C:22](/[C:42]2[N:43]=[C:44]([NH:47]C(OC(C)(C)C)=O)[S:45][CH:46]=2)\[C:23]([NH:25][C@H:26]2[C@@H:29]([CH2:30][N:31]3[CH2:35][CH2:34][O:33][C:32]3=[O:36])[N:28]([S:37]([OH:40])(=[O:39])=[O:38])[C:27]2=[O:41])=[O:24])[CH2:19][CH2:18]1)=[O:16])(C1C=CC=CC=1)C1C=CC=CC=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:47][C:44]1[S:45][CH:46]=[C:42](/[C:22](=[N:21]/[O:20][C:17]2([C:15]([OH:16])=[O:14])[CH2:18][CH2:19]2)/[C:23](=[O:24])[NH:25][C@H:26]2[C@@H:29]([CH2:30][N:31]3[CH2:35][CH2:34][O:33][C:32]3=[O:36])[N:28]([S:37]([OH:40])(=[O:39])=[O:38])[C:27]2=[O:41])[N:43]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 118379616HCID 118379616, compound

Product 1

HCID 118379834Lys 228)Yield 24.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Followed the general procedure for the acid mediated deprotection using (3S,4R)-3-((Z)-2-((1-((benzhydryloxy)carbonyl)cyclopropoxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetamido)-2-oxo-4-((2-oxooxazolidin-3-yl)methyl)azetidine-1-sulfonic acid (1.10 g, 1.40 mmol), DCM (7.0 mL) and TFA (5.39 mL, 70.0 mmol). Additional TFA (3.24 mL, 42.0 mmol) was added after 1 h at rt and the solution was diluted with DCM and concentrated in vacuo after an additional 30 min. The crude residue purified by reverse phase prep HPLC (XSelect CSH, 30×100 mm, 5 μm, C18 column; ACN-water with 0.1% formic acid modifier, 60 mL/min), affording the title compound (178 mg, 23%) as a white powder. LCMS: Rt=0.30 min, m/z=518.9 (M+1) Method 2m_acidic; 1H NMR (400 MHz, DMSO-d6) δ 9.27 (d, J=9.0 Hz, 1H) 6.92 (s, 1H) 5.23 (dd, J=9.1, 5.7 Hz, 1H) 4.12-4.23 (m, 3H) 3.72-3.62 (m, 2H assumed; obscured by water) 3.61-3.52 (m, 1H assumed; obscured by water) 3.26 (dd, J=14.5, 5.9 Hz, 1H) 1.36 (s, 4H). 1H NMR (400 MHz, D2O) δ 7.23 (s, 1H), 5.48 (d, J=5.8 Hz, 1H), 4.71-4.65 (m, 1H), 4.44 (t, J=8.2 Hz, 2H), 3.89-3.73 (m, 3H), 3.54 (dd, J=14.9, 4.9 Hz, 1H), 1.65-1.56 (m, 2H), 1.56-1.46 (m, 2H).

Workup

  1. concentrationconcentrated in vacuo after an additional 30 min
  2. customThe crude residue purified by reverse phase prep HPLC (XSelect CSH, 30×100 mm, 5 μm, C18 column; ACN-water with 0.1% formic acid modifier, 60 mL/min)

Sources & evidence

ORD record
ord-a5a3fce0dc5e4ecabbcfe818eed142fd
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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