Diisopropylethylamine → HCID 178512775, compound

HRID 708386Notes

Reaction equation

HRID 708386 reaction equation
[NH2:1][CH2:2][C:3]1[CH:7]=[N:6][N:5]([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])[N:4]=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])[CH2:25][CH2:26]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:5]2[N:4]=[C:3]([CH2:2][NH:1][C:42]([NH2:43])=[NH:37])[CH:7]=[N:6]2)=[O:30])[N:17]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 2734672Pyrazole-1-carboxamidine monohydrochlorideHCID 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 acid

Product 1

HCID 178512775HCID 178512775, compoundYield 38.2%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(((Z)-(2-(((2R,3S)-2-((4-(aminomethyl)-2H-1,2,3-triazol-2-yl)methyl)-4-oxo-1-sulfoazetidin-3-yl)amino)-1-(2-aminothiazol-4-yl)-2-oxoethylidene)amino)oxy)-cyclopropanecarboxylic acid (582 mg, 1.10 mmol) in DMF (12 mL) at 0° C. was added pyrazole-1-carboxamidine hydrochloride (322 mg, 2.20 mmol) and DIPEA (1.54 mL, 8.80 mmol). After 16 h of stirring at rt, the solution was diluted with toluene (60 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, 37%) as an off-white powder. LCMS: Rt=0.31 min, m/z=572.2 (M+H) Method 2m_acidic; 1H NMR (400 MHz, D2O) δ 7.59 (s, 1H), 6.99 (br s, 1H), 5.43 (d, J=5.5 Hz, 1H), 4.91-4.75 (m, 2H assumed; obscured by solvent residual peak), 4.70 (dd, J=8.2, 6.3 Hz, 1H), 4.41-4.34 (m, 2H), 1.20 (br s, 2H), 1.05 (br s, 2H). E-isomer was also obtained. LCMS: Rt=0.33 min, m/z=572.2 (M+H) Method 2m_acidic; 1H NMR (400 MHz, D2O) δ 7.58 (s, 1H), 7.46 (br. s., 1H), 5.45 (br. s., 1H), 4.84 (s, 3H), 4.37 (s, 2H), 1.33-1.08 (m, 4H).

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-a27a84125ee643ee9ccf87fc084244f0
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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