Triethylsilane → HCID 118379687, compound

HRID 708408Notes

Reaction equation

HRID 708408 reaction equation
C([O:5][C:6](=[O:54])[C:7]([O:10]/[N:11]=[C:12](/[C:41]1[N:42]=[C:43]([NH:46]C(OC(C)(C)C)=O)[S:44][CH:45]=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][CH2:32][NH:33]C(OC(C)(C)C)=O)[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>[NH2:33][CH2:32][CH2:31][C:29]1[N:28]=[N:27][N:26]([CH2:25][C@@H:17]2[C@H:16]([NH:15][C:13](=[O:14])/[C:12](=[N:11]\[O:10][C:7]([CH3:9])([CH3:8])[C:6]([OH:54])=[O:5])/[C:41]3[N:42]=[C:43]([NH2:46])[S:44][CH:45]=3)[C:19](=[O:20])[N:18]2[S:21]([OH:24])(=[O:22])=[O:23])[CH:30]=1

Participants

5

Reactant 3

HCID 12052TriethylsilaneHCID 21863450Trifluoroacetic acid methylene chlorideHCID 118379397HCID 118379397, compound

Product 1

HCID 118379687HCID 118379687, compoundYield 7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution 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-((tert-butoxycarbonyl)amino)ethyl)-1H-1,2,3-triazol-1-yl)methyl)-4-oxoazetidine-1-sulfonic acid (110 mg, 0.137 mmol) in DCM (1.4 mL) at 0° C. added TFA: DCM (1:1, 4.2 mL) followed by triethylsilane (65 μL, 0.411 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, acetonitrile: water solvent system with 0.1% formic acid modifier) to afford the title compound (5 mg, 7%); LCMS: m/z=543.9 (M−1); 1H NMR (400 MHz, MeOH-d4) δ 8.06 (s, 1H), 6.95 (s, 1H), 5.44 (d, J=5.8 Hz, 1H), 4.66 (q, J=6.0 Hz, 1H), 4.95-4.83 (m, 2H assumed; obscured by water), 3.29-3.24 (m, 2H), 3.07 (t, J=6.5 Hz, 2H), 1.54 (s, 3H), 1.52 (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, acetonitrile: water solvent system with 0.1% formic acid modifier)

Sources & evidence

ORD record
ord-2f8f68c49b6d41dd9a15acecf18e7455
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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