Trifluoroacetic acid → 1-[(Z)-[2-[[(2R,3S)-2-[[4-(aminomethyl)triazol-2-yl]methyl]-4-oxo-1-sulfoazetidin-3-yl]amino]-1-(2-amino-1,3-thiazol-4-yl)-2-oxoethylidene]amino]oxycyclopropane-1-carboxylic acid

HRID 708385Notes

Reaction equation

HRID 708385 reaction equation
C([O:14][C:15]([C:17]1([O:20]/[N:21]=[C:22](/[C:50]2[N:51]=[C:52]([NH:55]C(OC(C)(C)C)=O)[S:53][CH:54]=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]([CH2:41][NH:42]C(OC(C)(C)C)=O)[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>[NH2:42][CH2:41][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])[CH2:18][CH2:19]3)/[C:50]3[N:51]=[C:52]([NH2:55])[S:53][CH:54]=3)[C:29](=[O:30])[N:28]2[S:31]([OH:34])(=[O:33])=[O:32])[N:40]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 118379914(2R,3S)-3-[[(2Z)-2-(1-benzhydryloxycarbonylcyclopropyl)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 1183794851-[(Z)-[2-[[(2R,3S)-2-[[4-(aminomethyl)triazol-2-yl]methyl]-4-oxo-1-sulfoazetidin-3-yl]amino]-1-(2-amino-1,3-thiazol-4-yl)-2-oxoethylidene]amino]oxycyclopropane-1-carboxylic acidYield 50%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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-(((tert-butoxycarbonyl)amino)methyl)-2H-1,2,3-triazol-2-yl)methyl)-4-oxoazetidine-1-sulfonic acid (1.98 g, 2.21 mmol), DCM (18.4 mL) and TFA (10.2 mL, 133 mmol). Half of 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 (300 mg, ca 50%) as an off-white powder. LCMS: Rt=0.29 min, m/z=530.1 (M+1) Method 2m_acidic; 1H NMR (400 MHz, D2O) δ 7.69 (s, 1H), 7.04 (br s, 1H), 5.43 (d, J=5.5 Hz, 1H), 4.93-4.78 (m, 2H), 4.74-4.67 (m, 1H), 4.22-4.12 (m, 2H), 1.36-1.20 (m, 2H), 1.20-1.00 (m, 2H).

Workup

  1. customHalf of 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)

Sources & evidence

ORD record
ord-a591548ce0fe4bb5bab9f7bf106e2469
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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