Reaction SMILES: C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[O:43]1[CH2:47][CH2:46][O:45][CH:44]1[C:48]1[S:52][C:51]([C:53]([OH:55])=O)=[CH:50][C:49]=1[CH3:56].[CH2:57]([O:64][C:65]1[C:74]([CH3:75])=[CH:73][C:68]([C:69]([NH:71][NH2:72])=[O:70])=[CH:67][C:66]=1[CH2:76][CH3:77])[C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1>CN(C=O)C>[CH2:57]([O:64][C:65]1[C:74]([CH3:75])=[CH:73][C:68]([C:69]([NH:71][NH:72][C:53]([C:51]2[S:52][C:48]([CH:44]3[O:43][CH2:47][CH2:46][O:45]3)=[C:49]([CH3:56])[CH:50]=2)=[O:55])=[O:70])=[CH:67][C:66]=1[CH2:76][CH3:77])[C:58]1[CH:59]=[CH:60][CH:61]=[CH:62][CH:63]=1
Reactant: CCc1cc(C(=O)NN)cc(C)c1OCc1ccccc1
Reactant: Cc1cc(C(=O)O)sc1C1OCCO1
Agent: F[P-](F)(F)(F)(F)F
Agent: c1ccc2c(c1)nnn2O[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CCc1cc(C(=O)NNC(=O)c2cc(C)c(C3OCCO3)s2)cc(C)c1OCc1ccccc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 49.8 %

Procedure:
PyBOP (4.10 g, 7.88 mmol) and DIPEA (2.17 g, 16.8 mmol) is added to a cooled solution (0° C.) of 5-[1,3]dioxolan-2-yl-4-methyl-thiophene-2-carboxylic acid (1.42 g, 5.26 mmol) in DMF (20 mL). 4-Benzyloxy-3-ethyl-5-methyl-benzoic acid hydrazide (1.20 g, 5.26 mmol) is then added and the mixture is stirred at 0° C. for 30 min, then at rt for 1 h. The mixture is concentrated in vacuo, diluted with EA and washed with aq. sat. NaHCO3 followed by water. The organic extract is dried over Na2SO4, filtered and concentrated. The crude product is purified by prep. HPLC (XBridge Rp C18, 50×50 +50×100 mm, eluting with a gradient of acetonitrile in water containing 0.5% of formic acid) and the product containing fractions are neutralised by adding aq. Na2CO3 solution. The organic solvent is evaporated and the remaining aq. solution is extracted twice with EA. The organic extracts are concentrated. The product is further purified by prep. HPLC (XBridge Rp C18 50×50 +50×100 mm, eluting with a gradient of acetonitrile in water containing 0.5% of aq. ammonia) to give 5-[1,3]dioxolan-2-yl-4-methyl-thiophene-2-carboxylic acid N′-(4-benzyloxy-3-ethyl-5-methyl-benzoyl)-hydrazide (1.26 g) as a beige solid; LC-MS*: tR=0.77 min; [M+1]+=481.05. To a solution of this material (1.14 g, 2.37 mmol) in THF (40 mL), Lawesson's reagent (1.92 g, 4.74 mmol) is added. The resulting suspension is heated to 70° C. with microwave irradiation (200 W, with concomitant cooling). The clear solution is concentrated, dissolved in DMF and separated by prep. HPLC (XBridge, RP C18, 30×75 mm, eluting with a gradient of acetonitrile in water containing 0.5% of formic acid) to give 5-[5-(4-benzyloxy-3-ethyl-5-methyl-phenyl)-[1,3,4]thiadiazol-2-yl]-3-methyl-thiophene-2-carbaldehyde (294 mg) as a beige resin, LC-MS: tR=0.95 min; [M+1]+=435.07; 1H NMR (D6-DMSO): δ 1.22 (t, J=7.5 Hz, 3H), 2.38 (s, 3H), 2.63 (s, 3H), 2.73 (q, J=7.5 Hz, 2H), 4.91 (s, 2H), 7.37-7.48 (m, 3H), 7.50-7.54 (m, 2H), 7.75-7.78 (m, 2H), 7.82 (s, 1H), 10.13 (s, 1H). The above benzyl ether (284 mg, 0.654 mmol) is dissolved in acetic acid (10 mL) and 33% HBr in acetic acid (11 mL). The mixture is stirred at rt for 10 min before the solvent is removed in vacuo. The residue is dissolved in DMF and separated by prep. HPLC (XBridge, RP C18, 30×75 mm, eluting with a gradient of acetonitrile in water containing 0.5% of formic acid) to give the title compound (74 mg) as a pale yellow powder; LC-MS: tR=0.77 min; [M+1]+=345.07; 1H NMR (D6-DMSO): δ 1.19 (t, J=7.5 Hz, 3H), 2.27 (s, 3H), 2.62 (s, 3H), 2.68 (q, J=7.3 Hz, 2H), 7.60-7.64 (m, 2H), 7.77 (s, 1H), 9.12 (s, 1H), 10.12 (s, 1H).