Carbamoylphosphonates part 7. An efficient method for the synthesis of hindered carbamoylphosphonates using 4-nitrophenoxycarbonylphosphonate diesters

Orally Active, Antimetastatic, Nontoxic Diphenyl Ether‐Derived Carbamoylphosphonate Matrix Metalloproteinase Inhibitors

“…[25] Step 3 was the bromotrimethylsilane-mediated dealkylation. For some diaminoalkanes it was preferable to start by protecting one of the amine groups as the tert-butoxycarbonyl (Boc) derivative before sulfonylation of the second amine group.…”

Synthesis of Enantiomeric Aminoalkylcarbamoylphosphonates and Their Evaluation as Dual‐Action Anticancer MMP and Carbonic Anhydrase Inhibitors

“…According to the retro synthetic strategy (Scheme , carbamoylphosphonic acid V can be obtained by the deprotection of trityl and 2‐propyl ester groups of the corresponding carbamoylphosphonate IV using (CH 3 ) 3 SiBr or Trimethyl‐Silyl‐Bromide (TMSBr), which in turn can be obtained by the reaction of amine derivative (obtained by the Staudinger reduction of the azide derivative with trimethylphosphine) followed by treatment with 4‐nitrophenoxycarbonyl phosphonoformate diisopropyl ester (NPPF‐iPr) . This azide derivative III can be obtained by the Mitsunobu reaction of the corresponding alcohol II using triphenylphosphine and hydrazoic acid .…”

“…Heteroatom Chemistry DOI 10.1002/hc Synthesis of Enantiomeric Aminoalkylcarbamoylphosphonates and Their Evaluation 259 SCHEME 2 Synthesis of (R)-N-[2-amino-3-(4-phenoxybenzenesulfonamido)propyl]carbamoyl phosphonic acid (6). SCHEME 3 Synthesis of (S)-N-[2-amino-3-(4-phenoxybenzenesulfonamido)propyl]carbamoylphosphonic acid (12). by trifluoroacetic acid (TFA) and the amino group had to be reprotected with the electron-withdrawing benzyloxycarbonyl group as shown in Scheme 2 to compound 3 [15], and then successfully transformed to azide 4 by the Mitsunobu reaction using Ph 3 P, followed by the Staudinger reduction and the reaction with NPPF-iPr to provide compound 5, which was deprotected using TMSBr in CHCl 3 to afford the R enantiomer, 6.…”

“…[α] D = -6.78 (c 1.99, CH 3 OH); mp 106-108°C; NMR (CDCl 3 ) 31 P, δ -4.06 ppm; 1 (12). To a stirred solution of diisopropyl (S)-2-benzy loxycarbonylamino-3-(4-phenoxybenzenesulfona mido)propylcarbamoylphosphonate (0.10 g, 0.15 mmol) in CHCl 3 (2 mL), TMSBr (0.20 mL, 1.5 mmol) was added dropwise.…”

“…Methanol was added to the reaction mixture and stirred at RT for 1 h. Solvents were evaporated, and the product was solidified using MeOH. Mother liquor was evaporated, and the product was solidified from residue using EtOH, to get the second crop of the product (12) (20) N,N'-di-Boc-2-hydroxy-1, 3-diaminopropane (14) To a solution of 2-hydroxy-1,3-diaminopropane (13) (5.1 g, 56.6 mmol) in 25 mL water, Boc-anhydride (24.6 g, 113 mmol) was added in 50 mL dioxane followed by Na 2 CO 3 (13.76 g, 141 mmol) at 0°C and stirred for 2 h. The reaction mixture was allowed to warm to room temperature and was then stirred for an addi-tional 16 h. Then the solvents were evaporated; the residue was diluted with water and extracted with EtOAc (3 × 50 mL). The organic phase was dried over Na 2 SO 4 , and the solvent was evaporated.…”