Triethylsilane → HCID 118379634, compound

HRID 708409Notes

Reaction equation

HRID 708409 reaction equation
C([O:5][C:6](=[O:59])[C:7]([O:10]/[N:11]=[C:12](/[C:46]1[N:47]=[C:48]([NH:51]C(OC(C)(C)C)=O)[S:49][CH:50]=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][N:33]2[CH2:38][CH2:37][N:36](C(OC(C)(C)C)=O)[CH2:35][CH2:34]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>[NH2:51][C:48]1[S:49][CH:50]=[C:46](/[C:12](=[N:11]/[O:10][C:7]([CH3:9])([CH3:8])[C:6]([OH:59])=[O:5])/[C:13](=[O:14])[NH:15][C@H:16]2[C@@H:17]([CH2:25][N:26]3[CH:30]=[C:29]([CH2:31][CH2:32][N:33]4[CH2:34][CH2:35][NH:36][CH2:37][CH2:38]4)[N:28]=[N:27]3)[N:18]([S:21]([OH:24])(=[O:22])=[O:23])[C:19]2=[O:20])[N:47]=1

Participants

5

Reactant 3

HCID 12052TriethylsilaneHCID 21863450Trifluoroacetic acid methylene chlorideHCID 118379533HCID 118379533, compound

Product 1

HCID 118379634HCID 118379634, compoundYield 11%

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-(4-(tert-butoxycarbonyl)piperazin-1-yl)ethyl)-1H-1,2,3-triazol-1-yl)methyl)-4-oxoazetidine-1-sulfonic acid (120 mg, 0.138 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 (9.3 mg, 11%); LCMS: m/z=612.8 (M−1); 1H NMR (400 MHz, DMSO-d6) δ 9.67 (s, 1H), 7.99 (s, 1H), 7.30 (s, 2H), 6.66 (s, 1H), 5.27 (dd, J=8.8, 5.5 Hz, 1H), 4.82 (dd, J=14.7, 4.0 Hz, 1H), 4.68 (dd, J=14.7, 6.6 Hz, 1H), 4.24 (td, J=5.9, 4.2 Hz, 1H), 3.10 (t, J=5.2 Hz, 4H), 2.76 (t, J=7.0 Hz, 2H), 2.64-2.54 (m, 6H), 1.37 (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, acetonitrile: water solvent system with 0.1% formic acid modifier)

Sources & evidence

ORD record
ord-f159bdf8aa5346f9918cd3261d8b5c4d
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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