Diisopropylethylamine → HCID 178512774, compound

HRID 708397Notes

Reaction equation

HRID 708397 reaction equation
[NH2:1][CH2:2][C:3]1[N:4]=[N:5][N:6]([CH2:8][C@@H:9]2[C@H:12]([NH:13][C:14](=[O:30])/[C:15](=[N:22]\[O:23][C:24]3([C:27]([OH:29])=[O:28])[CH2:26][CH2:25]3)/[C:16]3[N:17]=[C:18]([NH2:21])[S:19][CH:20]=3)[C:11](=[O:31])[N:10]2[S:32]([OH:35])(=[O:34])=[O:33])[CH:7]=1.Cl.[N:37]1([C:42](N)=[NH:43])C=CC=N1.CCN(C(C)C)C(C)C>CN(C=O)C.C1(C)C=CC=CC=1>[NH2:21][C:18]1[S:19][CH:20]=[C:16](/[C:15](=[N:22]/[O:23][C:24]2([C:27]([OH:29])=[O:28])[CH2:26][CH2:25]2)/[C:14]([NH:13][C@@H:12]2[C:11](=[O:31])[N:10]([S:32]([OH:35])(=[O:34])=[O:33])[C@@H:9]2[CH2:8][N:6]2[CH:7]=[C:3]([CH2:2][NH:1][C:42]([NH2:43])=[NH:37])[N:4]=[N:5]2)=[O:30])[N:17]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 2734672Pyrazole-1-carboxamidine monohydrochlorideHCID 118379301HCID 118379301, compound

Product 1

HCID 178512774HCID 178512774, compoundYield 39.6%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(((Z)-(2-(((2R,3S)-2-((4-(aminomethyl)-1H-1,2,3-triazol-1-yl)methyl)-4-oxo-1-sulfoazetidin-3-yl)amino)-1-(2-aminothiazol-4-yl)-2oxoethylidene)amino)oxy)cyclopropane-carboxylic acid (559 mg, 1.06 mmol) and Pyrazole-1-carboxamidine hydrochloride (310 mg, 2.12 mmol) in DMF (12 mL) was added DIPEA (1.48 mL, 8.45 mmol). After 16 h of stirring at rt, the solution was diluted with toluene (20 mL), causing a dense oil to separate out. The top layer was decanted and the remaining oil was 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 (240 mg, 39%) as a white powder. LCMS: Rt=0.28 min, m/z=572.0 (M+H) Method 2m_acidic; 1H NMR (400 MHz, D2O) δ 8.09 (s, 1H), 7.18 (s, 1H), 5.52 (d, J=5.4 Hz, 1H), 4.97 (dd, J=14.1, 5.5 Hz, 1H), 4.91 (q, J=5.5 Hz, 1H), 4.84-4.76 (m, 1H assumed; partially obscured by solvent residual peak), 4.55 (s, 2H), 1.49-1.36 (m, 2H), 1.34-1.23 (m, 2H). E-isomer was also obtained. LCMS: Rt=0.32 min, m/z=572.0 (M+H) Method 2m_acidic. 1H NMR (400 MHz, DMSO-d6) δ 9.37 (d, J=9.6 Hz, 1H), 8.11 (s, 1H), 7.41 (s, 1H), 7.13 (s, 2H), 6.50 (s, 1H), 5.18 (dd, J=9.6, 5.3 Hz, 1H), 4.97 (d, J=13.5 Hz, 1H), 4.76-4.58 (m, 1H), 4.52 (dd, J=16.11, 7.70 Hz, 1H), 4.26-4.05 (m, 2H), 1.86-2.08 (m, 1H), 1.34-1.07 (m, 6H).

Workup

  1. customto separate out
  2. customThe top layer was decanted
  3. customthe remaining oil was 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-169e239c232b46e980ab236fef9012e6
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

Loading…