Triethylsilane → HCID 118380122, compound

HRID 708411Notes

Reaction equation

HRID 708411 reaction equation
C([O:5][C:6](=[O:53])[C:7]([O:10]/[N:11]=[C:12](/[C:40]1[N:41]=[C:42]([NH:45]C(OC(C)(C)C)=O)[S:43][CH:44]=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(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>[NH2:32][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:53])=[O:5])/[C:40]3[N:41]=[C:42]([NH2:45])[S:43][CH:44]=3)[C:19](=[O:20])[N:18]2[S:21]([OH:24])(=[O:23])=[O:22])[CH:30]=1

Participants

5

Reactant 3

HCID 12052TriethylsilaneHCID 21863450Trifluoroacetic acid methylene chlorideHCID 118379507HCID 118379507, compound

Product 1

HCID 118380122HCID 118380122, compoundYield 14.2%

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-(((tert-butoxycarbonyl)amino)methyl)-1H-1,2,3-triazol-1-yl)methyl)-4-oxoazetidine-1-sulfonic acid (120 mg, 0.15 mmol) In DCM (1.5 mL) at 0° C. was added TFA: DCM (1:1, 4.5 mL) followed by triethylsilane (72 μL, 0.45 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 (11.3 mg, 14%). LCMS: m/z=528.9 (M−1); 1H NMR (400 MHz, DMSO-d6) δ 9.47 (d, J=8.5 Hz, 1H), 8.25 (s, 1H), 7.30 (s, 2H), 6.75 (s, 1H), 5.27 (dd, J=8.6, 5.6 Hz, 1H), 4.82 (qd, J=14.9, 5.0 Hz, 2H), 4.23 (q, J=5.1 Hz, 1H), 4.09 (s, 2H), 1.37 (s, 3H), 1.32 (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-acb521bc81cc4d2a8bae691c98a91786
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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