Trifluoroacetic acid → HCID 118379957, compound

HRID 708530Notes

Reaction equation

HRID 708530 reaction equation
C([O:14][C:15]([C:17]1([O:20]/[N:21]=[C:22](/[C:62]2[N:63]=[C:64]([NH:67]C(OC(C)(C)C)=O)[S:65][CH:66]=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]([C@@H:41]([N:43](C(OC(C)(C)C)=O)[CH2:44][CH2:45][CH2:46][NH:47]C(OC(C)(C)C)=O)[CH3:42])[CH:38]=[N:37]2)=[O:24])[CH2:19][CH2:18]1)=[O:16])(C1C=CC=CC=1)C1C=CC=CC=1.C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:47][CH2:46][CH2:45][CH2:44][NH:43][C@H: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:62]3[N:63]=[C:64]([NH2:67])[S:65][CH:66]=3)[C:29](=[O:30])[N:28]2[S:31]([OH:34])(=[O:32])=[O:33])[N:40]=1)[CH3:42]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 118380190HCID 118380190, compound

Product 1

HCID 118379957HCID 118379957, compoundYield 25.8%

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-((S)-1-((tert-butoxycarbonyl)(3-((tert-butoxycarbonyl)amino)propyl)amino)ethyl)-2H-1,2,3-triazol-2-yl)methyl)-4-oxoazetidine-1-sulfonic acid (0.709 mmol), anisole (153 mg, 1.42 mmol), TFA (273 μl, 35.5 mmol) and DCM (7.1 mL). The reaction mixture was cooled to 0° C. and diluted with DCM and ice water. After vigorous stirring the two layers were separated and aqueous layer was purified by reverse phase prepatory HPLC (XSELECT, C18, 5 um 30×100 mm ACN-water with 0.1 formic acid), affording title compound (110 mg, 25%) as a white solid. LCMS: Rt=0.50 min, m/z=601.3 (M+1) Method 2m_acidic_polar; 1H NMR (400 MHz, D2O) δ 7.87 (s, 1H) 7.04 (s, 1H) 5.61 (d, J=5.6 Hz, 1H) 5.04-4.97 (m, 1H) 4.89 (d, J=5.4 Hz, 2H) 4.69-4.62 (m, 1H) 3.13-3.00 (m, 4H) 2.04 (t, J=4.0 Hz, 2H) 1.68 (d, J=6.9 Hz, 3H) 1.23 (t, J=3.9 Hz, 2H) 1.11-1.02 (m, 2H).

Workup

  1. customwere separated
  2. customaqueous layer was purified by reverse phase prepatory HPLC (XSELECT, C18, 5 um 30×100 mm ACN-water with 0.1 formic acid)

Sources & evidence

ORD record
ord-588aa91c7d1641bbbb8743aac5372d2e
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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