Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:15]([S:16]([C:19]2[CH:24]=[CH:23][C:22]3[O:25][CH2:26][O:27][C:21]=3[CH:20]=2)(=[O:18])=[O:17])=[CH:14][C:5]2[O:6][CH:7]([C:9]([O:11]CC)=[O:10])[O:8][C:4]=2[CH:3]=1.[OH-].[Na+].Cl>>[Cl:1][C:2]1[C:15]([S:16]([C:19]2[CH:24]=[CH:23][C:22]3[O:25][CH2:26][O:27][C:21]=3[CH:20]=2)(=[O:17])=[O:18])=[CH:14][C:5]2[O:6][CH:7]([C:9]([OH:11])=[O:10])[O:8][C:4]=2[CH:3]=1
Reactant: CCOC(=O)C1Oc2cc(Cl)c(S(=O)(=O)c3ccc4c(c3)OCO4)cc2O1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: O=C(O)C1Oc2cc(Cl)c(S(=O)(=O)c3ccc4c(c3)OCO4)cc2O1

Procedure:
10.9 g (0.0264 mole) of ethyl 5-chloro-6-(3,4-methylenedioxyphenylsulfonyl)-1,3-benzodioxole-2-carboxylate are covered with 40 ml of 2-n sodium hydroxide solution and the batch is heated for half an hour in a boiling water bath, cooled, acidified with hydrochloric acid and then extracted with ethyl acetate, affording 5-chloro-6-(3,4-methylenedioxyphenylsulfonyl)-1,3-benzodioxole-2-carboxylic acid. Melting point 182°-184° C. (crystallisation from ethyl acetate/toluene).
Reaction SMILES: C1C2C(CO[C:16]([N:18](C)[C:19]([CH3:69])([C:21]([NH:23][C@H:24]([C:28]([N:30]([C@@H:32]([C@@H:65]([CH3:68])[CH2:66][CH3:67])[C@H:33]([O:63][CH3:64])[CH2:34][C:35]([N:37]3[CH2:41][CH2:40][CH2:39][C@H:38]3[C@H:42]([O:61][CH3:62])[C@@H:43]([CH3:60])[C:44]([NH:46][C@H:47]([C:55]3[S:56][CH:57]=[CH:58][N:59]=3)[CH2:48][C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)=[S:45])=[O:36])[CH3:31])=[O:29])[CH:25]([CH3:27])[CH3:26])=[O:22])[CH3:20])=O)C3C(=CC=CC=3)C=2C=CC=1>ClCCl.C(NCC)C.CO>[CH3:16][NH:18][C:19]([CH3:69])([C:21]([NH:23][C@H:24]([C:28]([N:30]([C@@H:32]([C@@H:65]([CH3:68])[CH2:66][CH3:67])[C@H:33]([O:63][CH3:64])[CH2:34][C:35]([N:37]1[CH2:41][CH2:40][CH2:39][C@H:38]1[C@H:42]([O:61][CH3:62])[C@@H:43]([CH3:60])[C:44]([NH:46][C@H:47]([C:55]1[S:56][CH:57]=[CH:58][N:59]=1)[CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)=[S:45])=[O:36])[CH3:31])=[O:29])[CH:25]([CH3:27])[CH3:26])=[O:22])[CH3:20]
Reactant: CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=S)N[C@@H](Cc1ccccc1)c1nccs1)OC)N(C)C(=O)[C@@H](NC(=O)C(C)(C)N(C)C(=O)OCC1c2ccccc2-c2ccccc21)C(C)C
Solvent: CO
Solvent: CCNCC
Solvent: ClCCl
Product: CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=S)N[C@@H](Cc1ccccc1)c1nccs1)OC)N(C)C(=O)[C@@H](NC(=O)C(C)(C)NC)C(C)C
Yield: 94.6 %

Procedure:
According to general procedure A, from #83 (552 mg, 0.555 mmol, 1 eq.) in dichloromethane (10 mL, 0.05 M) and diethylamine (10 mL) was synthesized the crude desired material, which was diluted with methanol, concentrated in vacuo onto silica, and purified by silica gel chromatography (Gradient: 0% to 10% methanol in dichloromethane) to give #84 (406 mg, 95%) as a white solid. LC-MS: m/z 772.8 [M+H+], retention time=1.35 minutes; HPLC (Protocol A): 774.4 [M+H+], retention time=7.390 minutes; 1H NMR (400 MHz, DMSO-d6), presumed to be a mixture of rotamers, characteristic signals: δ [10.54 (br d, J=8 Hz) and 10.81 (br d, J=8 Hz), total 1H], 7.78-7.84 (m, 2H), [7.65 (d, J=3.1 Hz) and 7.69 (d, J=3.3 Hz), total 1H], 7.29-7.34 (m, 2H), 7.20-7.28 (m, 2H), 7.14-7.19 (m, 1H), 6.27-6.35 and 6.40-6.48 (2 m, total 1H), [4.51 (dd, J=9, 8 Hz) and 4.57 (dd, J=9, 8 Hz), total 1H], 3.24 and 3.25 (2 s, total 3H), 3.16 and 3.21 (2 s, total 3H), 2.94 and 3.00 (2 br s, total 3H), 2.09 and 2.10 (2 s, total 3H), 1.08 and 1.09 (2 s, total 3H), 0.73-0.80 (m, 3H).
Reaction SMILES: [N+:1]([C:4]1[CH:24]=[CH:23][C:7]([O:8][CH:9]([C:14]2[CH:19]=[CH:18][C:17]3[O:20][CH2:21][O:22][C:16]=3[CH:15]=2)[C:10]([O:12][CH3:13])=[O:11])=[C:6]([CH2:25][CH:26]=[CH2:27])[CH:5]=1)([O-])=O>CO.[Pd]>[NH2:1][C:4]1[CH:24]=[CH:23][C:7]([O:8][CH:9]([C:14]2[CH:19]=[CH:18][C:17]3[O:20][CH2:21][O:22][C:16]=3[CH:15]=2)[C:10]([O:12][CH3:13])=[O:11])=[C:6]([CH2:25][CH2:26][CH3:27])[CH:5]=1
Reactant: C=CCc1cc([N+](=O)[O-])ccc1OC(C(=O)OC)c1ccc2c(c1)OCO2
Agent: [Pd]
Solvent: CO
Product: CCCc1cc(N)ccc1OC(C(=O)OC)c1ccc2c(c1)OCO2
Temperature: 25 °C
Reaction time: 6 h
Yield: 108.1 %

Procedure:
To a solution of the product of Step B (0.5 g) in methanol (6 mL) was added Pd-C(10%)(0.05g), and the reaction mixture was stirred at room temperature for 6 h under an atmosphere of hydrogen gas. The catalyst was filtered off and the filtrate was concentrated in vacuo to give the desired methyl α-(4-amino-2-n-propylphenoxy)-2-(3,4-methylenedioxyphenyl)acetate (0.5 g) as a solid. This material without further purification was dissolved in dry THF (5 mL) and reacted with N-iso-propylisocyanate (0.1 mL) at room temperature for 12 h. Purification of the crude product by flash chromatography using EtOAc-hexanes (1:2) gave the titled compound as white solid (0.36 g).
Reaction SMILES: [CH2:1](Cl)/[CH:2]=[C:3](/[CH2:5][CH2:6][CH2:7][C@@H:8]([CH2:10][CH2:11][CH2:12][C@@H:13]([CH2:15][CH2:16][CH2:17][CH:18]([CH3:20])[CH3:19])[CH3:14])[CH3:9])\[CH3:4].[CH3:22][O-:23].[Na+]>CO.C(OCC)(=O)C>[CH2:1]([O:23][CH3:22])/[CH:2]=[C:3](/[CH2:5][CH2:6][CH2:7][C@@H:8]([CH2:10][CH2:11][CH2:12][C@@H:13]([CH2:15][CH2:16][CH2:17][CH:18]([CH3:20])[CH3:19])[CH3:14])[CH3:9])\[CH3:4]
Reactant: C[O-]
Reactant: C/C(=C\CCl)CCC[C@H](C)CCC[C@H](C)CCCC(C)C
Agent: [Na+]
Solvent: CO
Solvent: CCOC(C)=O
Product: COC/C=C(\C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C
Temperature: 60 °C
Reaction time: 4 h
Yield: 95.3 %

Procedure:
10.0 g of phytyl chloride was dropped into a solution of 2.0 g of sodium methoxide dissolved in 70 ml of methanol. The resulting mixture was stirred for 4 hours at 60° C. After the completion of the reaction, the reaction mixture was concentrated under reduced pressure. The residue obtained was dissolved in 30 ml of ethyl acetate, and the resulting solution was washed with water. The solution was dried over anhydrous magnesium sulfate and the solvent was removed by distillation under reduced pressure. The residue thus obtained was subjected to distillation (b.p.: 148°-150° C., 1.5 mmHg) to obtain 9.4 g (yield: 95%) of oily methyl phytyl ether.
Reaction SMILES: [NH:1]=[C:2]1[N:6]([OH:7])[C:5]([CH2:8][C:9]([NH:11][CH:12]2[C:27](=[O:28])[N:14]3[C:15]([C:24]([OH:26])=[O:25])=[C:16]([CH2:19]OC(=O)C)[CH2:17][S:18][C@H:13]23)=[O:10])=[CH:4][S:3]1.[OH:29][CH2:30][C:31]1[N:35]([CH3:36])[C:34]([SH:37])=[N:33][N:32]=1.C(=O)([O-])O.[Na+:42].O>P([O-])([O-])([O-])=O>[NH:1]=[C:2]1[N:6]([OH:7])[C:5]([CH2:8][C:9]([NH:11][CH:12]2[C:27](=[O:28])[N:14]3[C:15]([C:24]([O-:26])=[O:25])=[C:16]([CH2:19][S:37][C:34]4[N:35]([CH3:36])[C:31]([CH2:30][OH:29])=[N:32][N:33]=4)[CH2:17][S:18][C@H:13]23)=[O:10])=[CH:4][S:3]1.[Na+:42]
Reactant: CC(=O)OCC1=C(C(=O)O)N2C(=O)C(NC(=O)Cc3csc(=N)n3O)[C@H]2SC1
Reactant: Cn1c(S)nnc1CO
Agent: O=C([O-])O
Agent: O=P([O-])([O-])[O-]
Agent: [Na+]
Solvent: O
Product: Cn1c(CO)nnc1SCC1=C(C(=O)[O-])N2C(=O)C(NC(=O)Cc3csc(=N)n3O)[C@H]2SC1
Temperature: 70 °C
Reaction time: 2 h

Procedure:
In 20 ml of phosphate buffer (pH 6.4) is dissolved 1.0 g of 7-[2-(2-imino-3-hydroxy-4-thiazolin-4-yl)acetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid together with 0.3 g of 3-hydroxymethyl-4-methyl-1,2,4-triazole-5-thiol and 0.336 g of sodium hydrogen carbonate and the solution is stirred at 70° C. for 2 hours. This reaction mixture is subjected to column chromatography on polystyrene resin (Amberlite XAD-2) with water as the developer and the fractions containing the contemplated product are pooled. This solution contains 3-hydroxymethyl-4-methyl-1,2,4-triazole-5-thiol together with the desired compound. The solution is lyophilized and the resultant powder is redissolved in water. The solution is then subjected to column chromatography on dextran gel (Sephadex LH-20®, Pharmacia) with water as the developer. The fractions containing the contemplated compound are pooled and lyophilized. By the above procedure is obtained the captioned compound. Yield 0.28 g.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:10]2[O:20][C:19]3[CH:18]=[C:17]([OH:21])[CH:16]=[C:15]([OH:22])[C:14]=3[C:12](=[O:13])[CH:11]=2)=[CH:7][C:8]=1[OH:9].[CH2:23](Br)[CH:24]=[CH2:25]>CO.[K]>[OH:22][C:15]1[C:14]2[C:12](=[O:13])[CH:11]=[C:10]([C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[C:8]([O:9][CH2:25][CH:24]=[CH2:23])[CH:7]=3)[O:20][C:19]=2[CH:18]=[C:17]([OH:21])[CH:16]=1
Reactant: COc1ccc(-c2cc(=O)c3c(O)cc(O)cc3o2)cc1O
Reactant: C=CCBr
Agent: [K]
Solvent: CO
Product: C=CCOc1cc(-c2cc(=O)c3c(O)cc(O)cc3o2)ccc1OC
Temperature: 25 °C
Reaction time: 48 h
Yield: 83.8 %

Procedure:
20 g of diosmetin are dissolved in a mixture of 400 ml of anhydrous methanol and 13.3 g of potassium pellets. The reaction mixture is maintained at room temperature and then 16 g of allyl bromide dissolved in 40 ml of methanol are added dropwise with stirring. Stirring is then continued for 48 hours, and the solvents and volatile products are subsequently distilled off under reduced pressure at room temperature. The residue is taken up in 400 ml of CH2Cl2, and the insoluble material is collected by filtration and then recrystallised from 440 ml of isopropanol to yield 19 g of the expected compound, m.p.: 219° C.
Reaction SMILES: [CH2:1]([C:5]1[C:6]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:35]=[CH:34][C:21]([CH2:22][N:23]4[CH2:26][CH:25]([C:27]([O:29]C(C)(C)C)=[O:28])[CH2:24]4)=[CH:20][CH:19]=3)[N:14]=2)=[N:7][O:8][C:9]=1[CH2:10][CH2:11][CH3:12])[CH:2]([CH3:4])[CH3:3].[C:36]([OH:42])([C:38]([F:41])([F:40])[F:39])=[O:37]>>[CH2:1]([C:5]1[C:6]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:19]=[CH:20][C:21]([CH2:22][N:23]4[CH2:26][CH:25]([C:27]([OH:29])=[O:28])[CH2:24]4)=[CH:34][CH:35]=3)[N:14]=2)=[N:7][O:8][C:9]=1[CH2:10][CH2:11][CH3:12])[CH:2]([CH3:4])[CH3:3].[C:36]([OH:42])([C:38]([F:41])([F:40])[F:39])=[O:37]
Reactant: CCCc1onc(-c2nc(-c3ccc(CN4CC(C(=O)OC(C)(C)C)C4)cc3)no2)c1CC(C)C
Solvent: O=C(O)C(F)(F)F
Product: CCCc1onc(-c2nc(-c3ccc(CN4CC(C(=O)O)C4)cc3)no2)c1CC(C)C
Reaction time: 2.5 h

Procedure:
A solution of tert-butyl 1-(4-(5-(4-isobutyl-5-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate (21 mg, 0.044 mmol) in TFA (0.5 mL) was allowed to stand at rt for 2.5 hr. The volatiles were removed in vacuo and the residue was triturated with Et2O and dried to afford 1-(4-(5-(4-isobutyl-5-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylic acid, TFA (21 mg, 0.038 mmol, 88% yield) as a light yellow glassy solid. HPLC retention time=3.20 minutes (YMC Combi 4.6×50 mm S-5 ODS column) eluting with 10-90% aqueous methanol+0.2% phosphoric acid over a 4 minute gradient. MS: (M+H)=425.20. 1H NMR (400 MHz, MeOD) δ ppm 0.96 (d, J=6.5 Hz, 6H) 1.03 (t, J=7.3 Hz, 3H) 1.75-1.86 (m, 2H) 1.94 (m, 1H) 2.68 (d, J=7.3 Hz, 2H) 2.85 (t, J=7.5 Hz, 2H) 3.61-3.71 (m, 1H) 4.29-4.40 (m, 4H) 4.50 (s, 2H) 7.68 (d, J=8.0 Hz, 2H) 8.24 (d, J=8.3 Hz, 2H).
Reaction SMILES: [CH2:1]([C:4]1[C:13]([NH:14][C:15](=[O:17])[CH3:16])=[CH:12][CH:11]=[C:6]([C:7]([O:9][CH3:10])=[O:8])[C:5]=1[OH:18])[CH:2]=[CH2:3].C(N(CC)CC)C.[CH3:26][O:27][CH2:28]Cl>C(Cl)Cl.C(OCC)(=O)C>[CH3:26][O:27][CH2:28][O:18][C:5]1[C:4]([CH2:1][CH:2]=[CH2:3])=[C:13]([NH:14][C:15](=[O:17])[CH3:16])[CH:12]=[CH:11][C:6]=1[C:7]([O:9][CH3:10])=[O:8]
Reactant: COCCl
Reactant: C=CCc1c(NC(C)=O)ccc(C(=O)OC)c1O
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: C=CCc1c(NC(C)=O)ccc(C(=O)OC)c1OCOC
Reaction time: 24 h

Procedure:
To a solution of 10 g (40.2 mmol) of methyl 3-allyl-4-acetylaminosalicylate in 50 ml of CH2Cl2 is added 7.9 ml (56.3 mmol) of triethylamine in one portion at room temperature, followed by 3.3 ml (44.2 mmol) of chloromethyl methyl ether dropwise at room temperature. Stirring is continued for 24 hours at room temperature. The reaction mixture is diluted with ethyl acetate and washed with water. The organic layer is dried over MgSO4, filtered and concentrated. Flash chromatography (10% EtOAc/hexanes) affords pure methyl 2-methoxymethyloxy-3-allyl-4-acetylaminobenzoate.
Reaction SMILES: [CH3:1][C:2]1([C:7]2[S:11][CH:10]=[C:9]([CH2:12][N:13]3[CH:17]=[C:16]([NH2:18])[CH:15]=[N:14]3)[CH:8]=2)[O:6]CCO1.[C:19]1([C:25]2[O:29][CH:28]=[N:27][C:26]=2[C:30](O)=[O:31])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>>[C:2]([C:7]1[S:11][CH:10]=[C:9]([CH2:12][N:13]2[CH:17]=[C:16]([NH:18][C:30]([C:26]3[N:27]=[CH:28][O:29][C:25]=3[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)=[O:31])[CH:15]=[N:14]2)[CH:8]=1)(=[O:6])[CH3:1]
Reactant: CC1(c2cc(Cn3cc(N)cn3)cs2)OCCO1
Reactant: O=C(O)c1ncoc1-c1ccccc1
Product: CC(=O)c1cc(Cn2cc(NC(=O)c3ncoc3-c3ccccc3)cn2)cs1

Procedure:
Following general procedure B followed by C, starting from 1-[5-(2-methyl-[1,3]dioxolan-2-yl)-thiophen-3-ylmethyl]-1H-pyrazol-4-ylamine and 5-phenyl-oxazole-4-carboxylic acid. LC-MS-conditions 02: tR=0.98 min; [M+H]+=393.24.
Reaction SMILES: [CH2:1]([C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[C:18]1[CH:19]=[C:20]([CH:29]=[CH:30][CH:31]=1)[O:21][C:22]1[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=1)=[CH:15][CH:14]=[CH:13][C:12]=2[C:32]([F:35])([F:34])[F:33])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:36][O:37][C:38](=[O:47])[C:39]1[CH:44]=[CH:43][C:42]([CH2:45]Br)=[CH:41][CH:40]=1>>[CH3:36][O:37][C:38](=[O:47])[C:39]1[CH:44]=[CH:43][C:42]([CH2:45][O:28][C:25]2[CH:26]=[CH:27][C:22]([O:21][C:20]3[CH:29]=[CH:30][CH:31]=[C:18]([C:17]4[C:16]5[C:11](=[C:12]([C:32]([F:35])([F:33])[F:34])[CH:13]=[CH:14][CH:15]=5)[N:10]=[CH:9][C:8]=4[CH2:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)[CH:19]=3)=[CH:23][CH:24]=2)=[CH:41][CH:40]=1
Reactant: Oc1ccc(Oc2cccc(-c3c(Cc4ccccc4)cnc4c(C(F)(F)F)cccc34)c2)cc1
Reactant: COC(=O)c1ccc(CBr)cc1
Product: COC(=O)c1ccc(COc2ccc(Oc3cccc(-c4c(Cc5ccccc5)cnc5c(C(F)(F)F)cccc45)c3)cc2)cc1

Procedure:
The title compound was prepared from 4-{3-[3-benzyl-8-(trifluoromethyl)quinolin-4-yl]-phen-oxy}phenol (0.1 g, 0.0002 mole) and 4-Bromomethyl-benzoic acid methyl ester (0.057 g, 0.00024 mole) following the procedure of Example 478: MS (ESI) [M+H]+), 620.0.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH:4]([OH:7])[CH2:3][CH2:2]1.N1C=CN=C1.[CH3:13][Si:14](Cl)([CH3:16])[CH3:15]>C(Cl)Cl>[CH3:13][Si:14]([CH3:16])([CH3:15])[O:7][CH:4]1[CH2:5][CH2:6][O:1][CH2:2][CH2:3]1
Reactant: OC1CCOCC1
Reactant: C[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: ClCCl
Product: C[Si](C)(C)OC1CCOCC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 93.7 %

Procedure:
Tetrahydro-4-pyranol (1 g, 9.8 mmol) was dissolved in 30 mL of methylene chloride. To it was added imidazole (1.7 g, 24.5 mmol) followed by TMSCl (1.5 mL, 11.76 mmol). The reaction was allowed to stir at room temperature overnight. Insoluble material was removed by filtration, and the filtrate was washed with half saturated aqueous sodium bicarbonate and brine, and dried over MgSO4. The solids were filtered and solvent removed under reduced pressure to afford 1.6 g of trimethyl(tetrahydro-2H-pyran-4-yloxy)silane as a clear liquid.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([CH:8]([O:11][CH3:12])[O:9][CH3:10])[CH:5]=[C:4]([CH3:13])[N:3]=1.[Cl:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[S:21]([N:24]=[C:25]=[O:26])(=[O:23])=[O:22]>CCOCC>[Cl:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[S:21]([NH:24][C:25]([NH:1][C:2]1[N:7]=[C:6]([CH:8]([O:11][CH3:12])[O:9][CH3:10])[CH:5]=[C:4]([CH3:13])[N:3]=1)=[O:26])(=[O:23])=[O:22]
Reactant: O=C=NS(=O)(=O)c1ccccc1Cl
Reactant: COC(OC)c1cc(C)nc(N)n1
Solvent: CCOCC
Product: COC(OC)c1cc(C)nc(NC(=O)NS(=O)(=O)c2ccccc2Cl)n1
Yield: 76.2 %

Procedure:
A solution of 0.3 g of 2-amino-4-dimethoxymethyl-6-methylpyrimidine in 50 ml of ether was stirred overnight at room temperature with 0.46 g of o-chlorobenzenesulfonyl isocyanate. The product was filtered and washed with hexane to provide 0.5 g of the title compound, m.p. 150°-153°.
Reaction SMILES: [CH:1]1([C:5]2[N:6]=[C:7]([CH2:10][CH2:11][C:12]3[CH:30]=[CH:29][N:15]4[C:16](=[O:28])[C:17]([CH:26]=O)=[C:18]([N:20]5[CH2:25][CH2:24][O:23][CH2:22][CH2:21]5)[N:19]=[C:14]4[CH:13]=3)[S:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.[C:31]([CH2:36][CH:37]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([O:33][CH2:34][CH3:35])=[O:32]>C1(C)C=CC=CC=1>[CH:1]1([C:5]2[N:6]=[C:7]([CH2:10][CH2:11][C:12]3[CH:30]=[CH:29][N:15]4[C:16](=[O:28])[C:17](/[CH:26]=[C:36](\[CH3:37])/[C:31]([O:33][CH2:34][CH3:35])=[O:32])=[C:18]([N:20]5[CH2:25][CH2:24][O:23][CH2:22][CH2:21]5)[N:19]=[C:14]4[CH:13]=3)[S:8][CH:9]=2)[CH2:2][CH2:3][CH2:4]1
Reactant: CCOC(=O)CC=P(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: O=Cc1c(N2CCOCC2)nc2cc(CCc3nc(C4CCC4)cs3)ccn2c1=O
Solvent: Cc1ccccc1
Product: CCOC(=O)/C(C)=C/c1c(N2CCOCC2)nc2cc(CCc3nc(C4CCC4)cs3)ccn2c1=O
Temperature: 130 °C
Reaction time: 96 h
Yield: 369.1 %

Procedure:
8-[2-(4-Cyclobutyl-1,3-thiazol-2-yl)ethyl]-2-morpholino-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-carbaldehyde (100 mg, 0.236 mmol) dissolved in toluene (2 ml) was added with (carbethoxyethylidene)triphenylphosphorane (102 mg, 0.283 mmol) and refluxed by heating at 130° C. Then the regent was added until the reaction was completed, and 7 equivalents of the regent was finally added. After the reaction mixture was stirred for 4 days, the solvent was evaporated under reduced pressure, and the resulting residue was purified by thin layer silica gel chromatography (chloroform:methanol=40:1) to obtain 443 mg of yellow crystals in a mixture with triphenylphosphine oxide.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:7]([C:10]1[CH:15]=[CH:14][C:13]([C@H:16]2[CH2:21][CH2:20][C@H:19]([CH:22]=[O:23])[CH2:18][CH2:17]2)=[CH:12][CH:11]=1)[CH2:8][CH3:9].C(OCC)(=O)C.N>C1COCC1>[CH2:7]([C:10]1[CH:11]=[CH:12][C:13]([C@H:16]2[CH2:21][CH2:20][C@H:19]([CH2:22][OH:23])[CH2:18][CH2:17]2)=[CH:14][CH:15]=1)[CH2:8][CH3:9]
Reactant: CCCc1ccc([C@H]2CC[C@H](C=O)CC2)cc1
Agent: N
Agent: [Al+3]
Agent: [H-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CCCc1ccc([C@H]2CC[C@H](CO)CC2)cc1
Reaction time: 2 h

Procedure:
Lithium aluminum hydride (2.4 g) was suspended in THF (200 ml). trans-4-(4-propylphenyl)-cyclohexanecarboxaldehyde (s17) (24.4 g) was added dropwise to the suspension in the temperature range of −20° C. to −10° C., and the mixture was stirred at the same temperature range for 2 hours. After the completion of reaction had been confirmed by means of GC analysis, ethyl acetate and a saturated aqueous solution of ammonia were added successively to the reaction mixture under ice-cooling, and the deposits were removed by filtration through Celite. The filtrate was extracted with ethyl acetate. The combined organic layers were washed successively with water and brine, and then dried over anhydrous magnesium sulfate. The products were purified by recrystallization from heptane to give trans-4-(4-propylphenyl)-hydroxymethylcyclohexane (s18) (22.9 g). The yield based on the compound (s17) was 93.0%.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[C:8]([C:10]2[CH:14]=[CH:13][NH:12][N:11]=2)[CH:7]=[C:6]([F:15])[C:3]=1[C:4]#[N:5].O[C@@H:17]([CH3:27])[CH2:18][NH:19]C(=O)OC(C)(C)C>>[NH2:19][CH2:18][C@H:17]([N:12]1[CH:13]=[CH:14][C:10]([C:8]2[CH:7]=[C:6]([F:15])[C:3]([C:4]#[N:5])=[C:2]([Cl:1])[CH:9]=2)=[N:11]1)[CH3:27]
Reactant: C[C@H](O)CNC(=O)OC(C)(C)C
Reactant: N#Cc1c(F)cc(-c2cc[nH]n2)cc1Cl
Product: C[C@H](CN)n1ccc(-c2cc(F)c(C#N)c(Cl)c2)n1

Procedure:
The title compound was prepared using the procedure described in Example 3(g) starting from 2-chloro-6-fluoro-4-(1H-pyrazol-3-yl)benzonitrile (14.9 mmol, 3.3 g) and (S)-tert-butyl (2-hydroxypropyl)carbamate (29.8 mmol, 5.23 g). Yield 2.2 g. 1H-NMR (400 MHz; CDCl3): δ 1.53 (d, 3H), 3.44-3.61 (m, 2H), 4.48-4.54 (m, 1H), 6.59 (d, 1H), 7.48 (d, 1H), 7.55 (d, 1H), 7.75 (s, 1H). LC-MS: [M+1]=279.12.
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[C:8]([OH:14])=[C:7]([OH:15])[CH:6]=1)=O.[NH2:16][C:17]1[S:18][CH:19]=[N:20][N:21]=1>C(O)CCC>[S:18]1[CH:19]=[N:20][N:21]2[CH:2]=[C:3]([C:5]3[CH:6]=[C:7]([OH:15])[C:8]([OH:14])=[C:9]([N+:11]([O-:13])=[O:12])[CH:10]=3)[N:16]=[C:17]12
Reactant: Nc1nncs1
Reactant: O=C(CBr)c1cc(O)c(O)c([N+](=O)[O-])c1
Solvent: CCCCO
Product: O=[N+]([O-])c1cc(-c2cn3ncsc3n2)cc(O)c1O
Temperature: 25 °C

Procedure:
A solution of 1.38 g of 2-bromo-3',4'-dihydroxy-5'-nitroacetophenone and 505.7 mg of 2-amino-1,3,4-thiadiazole in 25 ml of n-butanol is heated to boiling under reflux for 7 hours. The reaction mixture is then cooled to room temperature and the separated crystals are filtered under suction. There is obtained 5-(imidazo-[2,1-b]-1,3,4-thiadiazol-6-yl)-3-nitropyrocatechol of m.p. 278°-280° (from methanol).
Reaction SMILES: [C:1]([NH:8][C@@H:9]([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C@@H:10]([OH:25])[CH2:11][C@@H:12]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=1[F:24])[C:13]([OH:15])=[O:14])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[C:33]([Si:37]([CH3:40])([CH3:39])Cl)([CH3:36])([CH3:35])[CH3:34].N1C=CN=C1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.CO.C1COCC1.O.CCCCCC.C(OCC)(=O)C>[C:1]([NH:8][C@@H:9]([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C@@H:10]([O:25][Si:37]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:40])[CH3:39])[CH2:11][C@@H:12]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=1[F:24])[C:13]([OH:15])=[O:14])([O:3][C:4]([CH3:6])([CH3:7])[CH3:5])=[O:2]
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)[C@@H](O)C[C@@H](Cc1ccc(F)cc1F)C(=O)O
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: c1c[nH]cn1
Solvent: C1CCOC1
Solvent: CO
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)[C@H](C[C@@H](Cc1ccc(F)cc1F)C(=O)O)O[Si](C)(C)C(C)(C)C

Procedure:
Analogously to Example 1j), 3.2 g (7.12 mmol) of 5(S)-(Boc-amino)-4(S)-hydroxy-6-phenyl-2(R)-[(2,4-difluorophenyl)methyl]-hexanoic acid in 67 ml of DMF are silylated with 4.93 g (32.7 mmol) of tert-butyldimethylchlorosilane and 3.97 g (58.4 mmol) of imidazole. Hydrolysis of the silyl ester function with 5.9 g of potassium carbonate in 77 ml of methanol, 20 ml of THF and 20 ml of water yields the title compound after column chromatography (SiO2, hexane/ethyl acetate 2:1): TLC Rf (D)=0.22; tRet (I)=20.8 min.
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[CH3:12][C:13]1[CH:14]=[N:15][C:16]2[CH:17]([S:23]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[O:24])[CH2:18][CH2:19][CH2:20][C:21]=2[CH:22]=1.FC(F)(F)C(O)=O>ClCCl>[CH3:12][C:13]1[CH:14]=[N:15][C:16]2[CH:17]([S:23]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)(=[O:9])=[O:24])[CH2:18][CH2:19][CH2:20][C:21]=2[CH:22]=1
Reactant: Cc1cnc2c(c1)CCCC2S(=O)c1ccccc1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cc1cnc2c(c1)CCCC2S(=O)(=O)c1ccccc1

Procedure:
A solution of m-chloroperbenzoic acid (1.4g) in dichloromethane (25ml) was added to a stirred solution of 5,6,7,8-tetrahydro-3-methyl-8-phenylsulphinylquinoline (1.87g) and trifluoroacetic acid (1.2ml) in dichloromethane (25ml). After stirring at ambient temperature for 1h, the reaction mixture was washed with 2M sodium hydroxide, dried over magnesium sulphate and evaporated to a solid. After chromatography on silica eluting with ether the product was recrystallised from diisopropylether affording white crystals, mp 84°-86° C.
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[C:7]([O:9][C:10]2[S:14][N:13]=[C:12]([C:15]3([Cl:18])[CH2:17][CH2:16]3)[N:11]=2)[C:6]([CH3:19])=[CH:5][C:3]=1[NH2:4].CO[CH:22](OC)[N:23]([CH2:25][CH3:26])[CH3:24]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:8]=[C:7]([O:9][C:10]2[S:14][N:13]=[C:12]([C:15]3([Cl:18])[CH2:16][CH2:17]3)[N:11]=2)[C:6]([CH3:19])=[CH:5][C:3]=1[N:4]=[CH:22][N:23]([CH2:25][CH3:26])[CH3:24]
Reactant: Cc1cc(N)c(Cl)cc1Oc1nc(C2(Cl)CC2)ns1
Reactant: CCN(C)C(OC)OC
Solvent: Cc1ccccc1
Product: CCN(C)C=Nc1cc(C)c(Oc2nc(C3(Cl)CC3)ns2)cc1Cl
Yield: 86.5 %

Procedure:
0.63 g (1.86 mmol) of 2-chloro-4-{[3-(1-chlorocyclopropyl)-1,2,4-thiadiazol-5-yl]oxy}-5-methylaniline is dissolved in 5 ml of toluene and treated with 0.50 g (3.71 mmol) of N-ethyl-N-methylformamide dimethyl acetal. The reaction mixture is refluxed for 12 h, subsequently cooled, freed from solvent under vacuum and purified by column chromatography. 0.62 g of product is obtained (82.0% purity, 71.3% yield; log P (pH 2.3)=1.62).