Triethylsilane → HCID 118380238, compound

HRID 708410Notes

Reaction equation

HRID 708410 reaction equation
[Br-].C([O:6][C:7](=[O:54])[C:8]([O:11]/[N:12]=[C:13](/[C:41]1[N:42]=[C:43]([NH:46]C(OC(C)(C)C)=O)[S:44][CH:45]=1)\[C:14]([NH:16][C@@H:17]1[C:20](=[O:21])[N:19]([S:22]([OH:25])(=[O:24])=[O:23])[C@@H:18]1[CH2:26][N:27]1[CH:31]=[C:30]([CH2:32][NH:33][C:34](=[O:40])[CH2:35][N+:36]([CH3:39])([CH3:38])[CH3:37])[N:29]=[N:28]1)=[O:15])([CH3:10])[CH3:9])(C)(C)C.C(O)(C(F)(F)F)=O.C(Cl)Cl.C([SiH](CC)CC)C>C(Cl)Cl>[NH2:46][C:43]1[S:44][CH:45]=[C:41](/[C:13](=[N:12]/[O:11][C:8]([C:7]([OH:54])=[O:6])([CH3:9])[CH3:10])/[C:14]([NH:16][C@H:17]2[C@@H:18]([CH2:26][N:27]3[CH:31]=[C:30]([CH2:32][NH:33][C:34](=[O:40])[CH2:35][N+:36]([CH3:37])([CH3:38])[CH3:39])[N:29]=[N:28]3)[N:19]([S:22]([O-:25])(=[O:24])=[O:23])[C:20]2=[O:21])=[O:15])[N:42]=1

Participants

5

Reactant 3

HCID 12052TriethylsilaneHCID 21863450Trifluoroacetic acid methylene chlorideHCID 118380283HCID 118380283, compound

Product 1

HCID 118380238HCID 118380238, compoundYield 27.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a slurry of 2-(((1-(((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)-4-oxo-1-sulfoazetidin-2-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl)amino)-N,N,N-trimethyl-2-oxoethanaminium bromide (50 mg, 0.0635 mmol) In DCM (640 μL) at 0° C. was added TFA: DCM (1:1, 1.92 mL) followed by triethylsilane (31 μL, 0.19 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 mg, 27%). LCMS: m/z=630.9 (M−1); 1H NMR (400 MHz, DMSO-d6) δ 9.40 (d, J=8.6 Hz, 1H), 9.06 (t, J=5.6 Hz, 1H), 8.06 (s, 1H), 7.32 (s, 2H), 6.71 (s, 1H), 5.28 (dd, J=8.6, 5.5 Hz, 1H), 4.89-4.64 (m, 2H), 4.38 (t, J=5.1 Hz, 2H), 4.22 (q, J=5.3 Hz, 1H), 4.08 (s, 2H), 3.22 (s, 9H), 1.33 (s, 3H), 1.26 (s, 3H).

Workup

  1. temperatureslowly warmed to room temperature
  2. waitAfter 2 h at rt
  3. concentrationit was concentrated in vacuo
  4. customtriturated with MTBE:Heptane (1:2) whereupon a solid
  5. 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-a191f01474e24be7bb18c60467185c70
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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