Triethylsilane → HCID 118379871, compound

HRID 708414Notes

Reaction equation

HRID 708414 reaction equation
C([O:5][C:6](=[O:56])[C:7]([O:10]/[N:11]=[C:12](/[C:43]1[N:44]=[C:45]([NH:48]C(OC(C)(C)C)=O)[S:46][CH:47]=1)\[C:13]([NH:15][C@@H:16]1[C:19](=[O:20])[N:18]([S:21]([OH:24])(=[O:23])=[O:22])[C@@H:17]1[CH2:25][N:26]1[CH:30]=[C:29]([CH2:31][NH:32][C:33](=[O:42])[CH2:34][N:35]2[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][CH2:36]2)[N:28]=[N:27]1)=[O:14])([CH3:9])[CH3:8])(C)(C)C.C(O)(C(F)(F)F)=O.C(Cl)Cl.C([SiH](CC)CC)C>C(Cl)Cl>[NH2:48][C:45]1[S:46][CH:47]=[C:43](/[C:12](=[N:11]/[O:10][C:7]([CH3:9])([CH3:8])[C:6]([OH:56])=[O:5])/[C:13]([NH:15][C@@H:16]2[C:19](=[O:20])[N:18]([S:21]([OH:24])(=[O:22])=[O:23])[C@@H:17]2[CH2:25][N:26]2[CH:30]=[C:29]([CH2:31][NH:32][C:33](=[O:42])[CH2:34][N:35]3[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][CH2:36]3)[N:28]=[N:27]2)=[O:14])[N:44]=1

Participants

5

Reactant 3

HCID 12052TriethylsilaneHCID 21863450Trifluoroacetic acid methylene chlorideHCID 118379608HCID 118379608, compound

Product 1

HCID 118379871HCID 118379871, compoundYield 10.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a slurry of (2R,3S)-3-((Z)-2-(((1-(tert-butoxy)-2-methyl-1-oxopropan-2-yl)oxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetamido)-2-((4-((2-(4-methylpiperazin-1-yl)acetamido)methyl)-1H-1,2,3-triazol-1-yl)methyl)-4-oxoazetidine-1-sulfonic acid (120 mg, 0.13 mmol) In DCM (1.3 mL) at 0° C. was added TFA: DCM (1:1, 3.9 mL) followed by triethylsilane (62 μL, 0.39 mmol). The reaction mixture was stirred at 0° C. for 30 min and slowly warmed to room temperature. After 2 h at rt it was concentrated in vacuo and triturated with MTBE: Heptane (1:2) whereupon a solid was observed. The crude solid was purified by reverse phase prep HPLC (C18 column, ACN-water solvent system with 0.1% formic acid modifier) to afford the title compound (9 mg). LCMS: m/z=669.75 (M−1); 1H NMR (400 MHz, DMSO-d6) δ 9.40 (d, J=8.7 Hz, 1H), 8.25 (s, 1H), 8.00 (s, 1H), 7.33 (s, 2H), 6.71 (s, 1H), 5.29 (dd, J=8.7, 5.6 Hz, 1H), 4.88-4.60 (m, 2H), 4.34 (d, J=5.7 Hz, 2H), 4.24 (q, J=5.3 Hz, 1H), 3.20-2.87 (m, 8H), 2.77 (s, 3H), 1.34 (s, 3H), 1.30 (s, 3H).

Workup

  1. temperatureslowly warmed to room temperature
  2. concentrationAfter 2 h at rt it was concentrated in vacuo
  3. customtriturated with MTBE: Heptane (1:2) whereupon a solid
  4. customThe crude solid was purified by reverse phase prep HPLC (C18 column, ACN-water solvent system with 0.1% formic acid modifier)

Sources & evidence

ORD record
ord-685d8761cd584126a40171decb9dbe9e
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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