Trifluoroacetic acid → HCID 178464616, compound

HRID 708526Notes

Reaction equation

HRID 708526 reaction equation
C([O:14][C:15]([C:17]1([O:20]/[N:21]=[C:22](/[C:72]2[N:73]=[C:74]([NH:77]C(OC(C)(C)C)=O)[S:75][CH:76]=2)\[C:23]([NH:25][C@@H:26]2[C:29](=[O:30])[N:28]([S:31]([OH:34])(=[O:33])=[O:32])[C@@H:27]2[CH2:35][N:36]2[N:40]=[C:39]([CH:41]([N:43](C(OC(C)(C)C)=O)/[C:44](=[N:57]/C(OC(C)(C)C)=O)/[NH:45][CH2:46][CH2:47][CH2:48][NH:49]C(=O)OC(C)(C)C)[CH3:42])[CH:38]=[N:37]2)=[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>[NH2:49][CH2:48][CH2:47][CH2:46][NH:45][C:44](=[NH:57])[NH:43][CH:41]([C:39]1[CH:38]=[N:37][N:36]([CH2:35][C@@H:27]2[C@H:26]([NH:25][C:23](=[O:24])/[C:22](=[N:21]\[O:20][C:17]3([C:15]([OH:16])=[O:14])[CH2:19][CH2:18]3)/[C:72]3[N:73]=[C:74]([NH2:77])[S:75][CH:76]=3)[C:29](=[O:30])[N:28]2[S:31]([OH:34])(=[O:32])=[O:33])[N:40]=1)[CH3:42]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 178437238HCID 178437238, compound

Product 1

HCID 178464616HCID 178464616, compoundYield 39.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Followed the general procedure for the acid mediated deprotection using (2R,3S)-3-((Z)-2-((1-((benzhydryloxy)carbonyl)cyclopropoxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetamido)-2-((4-((E)-3-(tert-butoxycarbonyl)-4-((tert-butoxycarbonyl)imino)-12,12-dimethyl-10-oxo-11-oxa-3,5,9-triazatridecan-2-yl)-2H-1,2,3-triazol-2-yl)methyl)-4-oxoazetidine-1-sulfonic acid (0.133 mmol), TFA (410 μl, 5.32 mmol) anisole (29 μL, 0.27 mmol) and DCM (1.33 mL). The reaction mixture was cooled to 0° C. and diluted with DCM and ice water, Whereupon the layers were separated. The aqueous layer was purified by reverse phase preparative HPLC (XSELECT, C18 5 um 30×100 mm; ACN-water with 0.1% formic acid), affording the title compound (34 mg, 39%) as a white powder. LCMS: Rt=0.52 min, m/z=643.2 (M+1) Method 2m_acidic_polar. 1H NMR (400 MHz, D2O, reported as a 1:1 mixture of diastereomers) δ 7.79 (s, 1H) 7.77 (s, 1H), 7.12 (s, 1H), 7.12 (s, 1H), 5.64 (d, J=5.6 Hz, 1H), 5.61 (d, J=5.6 Hz, 1H), 5.05-4.73 (m, 8H assumed; partially obscured by solvent residual peak), 3.39-3.32 (m, 4H), 3.13-3.05 (m, 4H), 2.00 (p, J=7.0 Hz, 4H), 1.64 (d, J=3.6 Hz, 3H), 1.63 (d, J=3.7 Hz, 3H), 1.37-1.28 (m, 4H), 1.21-1.12 (m, 4H).

Workup

  1. customwere separated
  2. customThe aqueous layer was purified by reverse phase preparative HPLC (XSELECT

Sources & evidence

ORD record
ord-eff3614447084711a04824bf19204608
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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