Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[CH:3]1[C:16]2[NH:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[O:8][C:7]=2[CH:6]=[CH:5][CH:4]=1.Br[CH2:18][CH2:19][O:20][C:21]1[CH:28]=[CH:27][C:24]([CH:25]=[O:26])=[CH:23][CH:22]=1.O>CN(C)C=O>[CH:13]1[C:14]2[N:15]([CH2:18][CH2:19][O:20][C:21]3[CH:28]=[CH:27][C:24]([CH:25]=[O:26])=[CH:23][CH:22]=3)[C:16]3[C:7](=[CH:6][CH:5]=[CH:4][CH:3]=3)[O:8][C:9]=2[CH:10]=[CH:11][CH:12]=1
Reactant: c1ccc2c(c1)Nc1ccccc1O2
Reactant: O=Cc1ccc(OCCBr)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: O=Cc1ccc(OCCN2c3ccccc3Oc3ccccc32)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 58.1 %

Procedure:
To a suspension of sodium hydride (60% mineral oil, 0.13 g, 3.24 mmol) in dimethyl formamide (3 ml) was added phenoxazine (0.5 g, 2.7 mmol) in dimethyl formamide (5 mL). The reaction mixture was stirred at 25° C. for 0.5 h and a solution of 4-(2-bromoethoxy)benzaldehyde (0.74 g, 3.24 mmol) in dimethyl formamide (3 mL) was added. The reaction mixture was stirred at 25° C. for 6 h. Water (25 ml) was added and the mixture was extracted with ethyl acetate (2×50 ml). The combined organic layers were washed with water (50 ml), brine solution (50 ml) and dried (Na2SO4). The solvent was evaporated and the residue was chromatographed over silica gel using a mixture of ethyl acetate and pet. ether (3:7) as eluent to afford the title compound (0.52 g, 57%) as a syrupy liquid.
Reaction SMILES: [C:1]1([CH3:35])[CH:6]=[CH:5][C:4]([C:7]2[N:8]=[C:9]3[CH2:23][CH2:22][CH2:21][N:20]([CH2:24][CH2:25][CH2:26][CH2:27][CH:28]([OH:34])[CH2:29][C:30]([O:32]C)=[O:31])[C:10]3=[N:11][C:12]=2[C:13]2[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=2)=[CH:3][CH:2]=1.[OH-].[Na+]>CCO.O>[C:1]1([CH3:35])[CH:2]=[CH:3][C:4]([C:7]2[N:8]=[C:9]3[CH2:23][CH2:22][CH2:21][N:20]([CH2:24][CH2:25][CH2:26][CH2:27][CH:28]([OH:34])[CH2:29][C:30]([OH:32])=[O:31])[C:10]3=[N:11][C:12]=2[C:13]2[CH:14]=[CH:15][C:16]([CH3:19])=[CH:17][CH:18]=2)=[CH:5][CH:6]=1
Reactant: COC(=O)CC(O)CCCCN1CCCc2nc(-c3ccc(C)cc3)c(-c3ccc(C)cc3)nc21
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: Cc1ccc(-c2nc3c(nc2-c2ccc(C)cc2)N(CCCCC(O)CC(=O)O)CCC3)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of methyl 7-(2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-3-hydroxy heptanoate (step 3)(43 mg, 0.091 mmol) in EtOH (908 μL) was treated with sodium hydroxide (136 μL, 0.272 mmol) and stirred at room temperature for 1 hour. The resulting mixture was diluted with water (2 ml) and acidified to pH 2. The mixture was extracted with EtOAc and the combined organic extracts were washed with brine, dried by passing through a phase separator and concentrated under reduced pressure to give an oil. The oil was purified by flash column chromatography using the ISCO combiflash Rf, eluting with 0-50% EtOAc (containing 10% MeOH) in iso-hexane on a 4 g silca cartridge. The product fractions were combined and the solvent removed under reduced pressure to yield the titled compound as a colourless oil;
Reaction SMILES: [F:1][C:2]1[CH:9]=[CH:8][C:7]([Cl:10])=[CH:6][C:3]=1[CH:4]=[O:5].[C-:11]#[N:12].[K+].OS([O-])=O.[Na+]>C(OCC)(=O)C.O>[F:1][C:2]1[CH:9]=[CH:8][C:7]([Cl:10])=[CH:6][C:3]=1[CH:4]([OH:5])[C:11]#[N:12]
Reactant: [C-]#N
Reactant: O=Cc1cc(Cl)ccc1F
Agent: O=S([O-])O
Agent: [K+]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Product: N#CC(O)c1cc(Cl)ccc1F
Reaction time: 8 h
Yield: 98.3 %

Procedure:
To 2-fluoro-5-chloro-benzaldehyde (12.7 g, 17 mmol) in ethyl acetate (50 mL) was added a solution of KCN (3.3 g) and NaHSO3 (5.3 g) dissolved in H2O (25 mL). It was left stirring overnight before extracted with ethyl acetate (3×50 mL). The combined organic extracts were dried and concentrated. The crude product was purified by silica gel chromatography to give 121A (3.1 g, 99% yield) as an oil.
Reaction SMILES: [OH:1][C@H:2]([CH2:13]O)[CH2:3][NH:4][C:5]([C:7]1[S:8][C:9]([Cl:12])=[CH:10][CH:11]=1)=[O:6].BrC[C@@H](O)CNC(C1SC(Cl)=CC=1)=O.[NH2:29][C:30]1[CH:35]=[CH:34][C:33]([N:36]2[CH2:41][CH2:40][O:39][CH2:38][C:37]2=[O:42])=[CH:32][CH:31]=1>>[OH:1][C@H:2]([CH2:13][NH:29][C:30]1[CH:31]=[CH:32][C:33]([N:36]2[CH2:41][CH2:40][O:39][CH2:38][C:37]2=[O:42])=[CH:34][CH:35]=1)[CH2:3][NH:4][C:5]([C:7]1[S:8][C:9]([Cl:12])=[CH:10][CH:11]=1)=[O:6]
Reactant: O=C(NC[C@H](O)CO)c1ccc(Cl)s1
Reactant: Nc1ccc(N2CCOCC2=O)cc1
Agent: O=C(NC[C@H](O)CBr)c1ccc(Cl)s1
Product: O=C(NC[C@H](O)CNc1ccc(N2CCOCC2=O)cc1)c1ccc(Cl)s1

Procedure:
In this case, 5-chlorothiophene-2-carbonyl chloride (IV) is reacted with (28)-3-aminopropane-1,2-diol hydrochloride (VII) to give 5-chlorothiophene-2-carboxylic acid ((S)-2,3-dihydroxypropyl)-amide (IX). Subsequently, (IX) is converted into 5-chlorothiophene-2-carboxylic acid ((S)-3-bromo-2-hydroxypropyl)amide (X), which is then reacted with 4-(4-aminophenyl)-3-morpholinone (III) to give 5-chlorothiophene-2-carboxylic acid {(R)-2-hydroxy-3-[4-(3-oxomorpholin-4-yl)phenylamino]-propyl}amide (XI). Finally, (XI) is reacted with phosgene or a phosgene equivalent to give 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide (I).
Reaction SMILES: I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([CH:12]2[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]2)[N:3]=1.[CH3:19][O:20][C:21]1[CH:26]=[C:25](B2OC(C)(C)C(C)(C)O2)[CH:24]=[CH:23][C:22]=1[NH:36][C:37](=[O:43])[O:38][C:39]([CH3:42])([CH3:41])[CH3:40].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([CH:12]3[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]3)[N:3]=[C:2]([C:25]3[CH:24]=[CH:23][C:22]([NH:36][C:37](=[O:43])[O:38][C:39]([CH3:40])([CH3:41])[CH3:42])=[C:21]([O:20][CH3:19])[CH:26]=3)[C:10]=12
Reactant: CN1CCC(n2nc(I)c3c(N)ncnc32)CC1
Reactant: COc1cc(B2OC(C)(C)C(C)(C)O2)ccc1NC(=O)OC(C)(C)C
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: COCCOC
Product: COc1cc(-c2nn(C3CCN(C)CC3)c3ncnc(N)c23)ccc1NC(=O)OC(C)(C)C
Yield: 73.1 %

Procedure:
3-Iodo-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (270 mg, 0.754 mmol), tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (290 mg, 0.829 mmol), palladium tetrakistriphenyphosphine (52 mg, 0.045 mmol) and sodium carbonate (192 mg, 1.81 mmol) were mixed in ethylene glycol dimethyl ether (8 mL) and water (4 mL). The reaction mixture was heated at reflux overnight under nitrogen. Organic solvent was removed under reduced pressure and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol (90:10 to 70:30) as mobile phase to give tert-butyl N-{4-[4-amino-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}carbamate (250 mg, 73%). 1H NMR (DMSO-d6) δ 1.48 (s, 9H), 1.88 (m, 2H), 2.10 (m, 2H), 2.24 (m, 5H), 2.92 (m, 2H), 3.69 (s, 3H), 4.64 (m, 1H), 7.21 (m, 2H), 7.91 (d, J=8.16 Hz, 1H), 8.04 (s, 1H), 8.23 (s, 1H). LCMS (Thermoquest AQA single Quad MS, Finnigan HPLC-Column: Genesis, C18, 3 um, 33×4.6 mm. Eluents: 30% B/A to 95% B/A in 4.5 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, pH 4.5), 0.8 mL/min.): MH+=454.2, Rt=1.67 min.
Reaction SMILES: C([O:8][C:9]1[C:14]2[CH:15]=[C:16]([C:18]3[N:19]=[C:20]4[CH:25]=[CH:24][C:23]([CH3:26])=[N:22][N:21]4[CH:27]=3)[O:17][C:13]=2[CH:12]=[C:11]([O:28][CH3:29])[CH:10]=1)C1C=CC=CC=1.[H][H]>ClCCl.CO.[Pd]>[CH3:29][O:28][C:11]1[CH:12]=[C:13]2[O:17][C:16]([C:18]3[N:19]=[C:20]4[CH:25]=[CH:24][C:23]([CH3:26])=[N:22][N:21]4[CH:27]=3)=[CH:15][C:14]2=[C:9]([OH:8])[CH:10]=1
Reactant: COc1cc(OCc2ccccc2)c2cc(-c3cn4nc(C)ccc4n3)oc2c1
Reactant: [H][H]
Agent: [Pd]
Solvent: ClCCl
Solvent: CO
Product: COc1cc(O)c2cc(-c3cn4nc(C)ccc4n3)oc2c1
Reaction time: 18 h
Yield: 99.4 %

Procedure:
A solution of 2-(4-(benzyloxy)-6-methoxybenzofuran-2-yl)-6-methylimidazo[1,2-b]pyridazine (Example 39A, 1.00 g, 2.59 mmol) in a mixture of dichloromethane (420 mL) and methanol (150 mL) in a 1 L flask was hydrogenated over 10% Palladium over carbon (0.30 g, i.e., 30 mg Pd) and under 1 atm of hydrogen for 6 h. The reaction mixture was maintained under vacuum for 2 min and then flushed with nitrogen. The catalyst was filtered and washed with warm dichloromethane-methanol (8:2, 100 mL) and the combined filtrate was concentrated under reduced pressure. The yellow residue was boiled with 1,2-dichloroethane (30 mL) and allowed to stand at room temperature for 18 h. The solid was filtered (contains methanol by NMR) and dried in vacuo at 120° C. for 12 h to give the title material (0.760 g, 99% yield) of a yellow solid. LC (Method A): 1.844 min. 1H NMR (DMSO-d6, 400 MHz) δ ppm: 2.54 (s, 3H), 3.77 (s, 3H), 6.28 (d, J=1.96 Hz, 1H), 6.70 (dd, J=1.96, 1.17 Hz, 1H), 7.20 (d, J=9.39 Hz, 1H), 7.24 (d, J=0.78 Hz, 1H), 8.03 (d, J=9.78 Hz, 1H), 8.50 (s, 1H), 10.10 (br s, 1H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:27]=[CH:26][C:6]([CH2:7][N:8]([CH2:15][CH2:16][N:17]([CH3:25])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][NH2:24])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)=[CH:5][CH:4]=1.CS[C:30]([NH:35][CH2:36][CH2:37][CH2:38][O:39][C:40]1[CH:45]=[CH:44][CH:43]=[C:42]([CH2:46][N:47]2[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]2)[CH:41]=1)=[CH:31][N+:32]([O-:34])=[O:33]>>[CH3:1][O:2][C:3]1[CH:27]=[CH:26][C:6]([CH2:7][N:8]([CH2:15][CH2:16][N:17]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][NH:24][C:30]([NH:35][CH2:36][CH2:37][CH2:38][O:39][C:40]2[CH:45]=[CH:44][CH:43]=[C:42]([CH2:46][N:47]3[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]3)[CH:41]=2)=[CH:31][N+:32]([O-:34])=[O:33])[CH3:25])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)=[CH:5][CH:4]=1
Reactant: CSC(=C[N+](=O)[O-])NCCCOc1cccc(CN2CCCCC2)c1
Reactant: COc1ccc(CN(CCN(C)CCCCCCN)c2ccccn2)cc1
Product: COc1ccc(CN(CCN(C)CCCCCCNC(=C[N+](=O)[O-])NCCCOc2cccc(CN3CCCCC3)c2)c2ccccn2)cc1

Procedure:
Preparation is effected analogously to Example 22, using 0.54 g (1.45 mmol) of N-[2-[N-(4-methoxybenzyl)-N-(2-pyridyl)amino]ethyl]-N-methyl-1,6-hexanediamine and the equimolar amount of 1-methylthio-1-[3-[3-(piperidinomethyl)phenoxy]propyl]amino-2-nitroethene as starting materials. Working up by chromatography analogously to Example 22 yields the purified title compound in the form of a viscous oil; MS (+FAB method): m/z (rel. int. [%])=688 ([M+H]+, 5), 121 (100). For further analysis, a portion of the compound is converted into the tartaric acid salt in an ethanol/ether solvent mixture; m.p.: 73° C. (ethanol/ether).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH:6]=[CH:5]2.C(=O)([O-])[O-].[K+].[K+].[CH:19]1([N:25]2[C:29]([CH2:30][CH2:31][CH2:32]Cl)=[N:28][N:27]=[N:26]2)[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1>CN(C)C=O>[CH:19]1([N:25]2[C:29]([CH2:30][CH2:31][CH2:32][O:1][C:2]3[CH:3]=[C:4]4[C:9](=[CH:10][CH:11]=3)[NH:8][C:7](=[O:12])[CH:6]=[CH:5]4)=[N:28][N:27]=[N:26]2)[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]1
Reactant: ClCCCc1nnnn1C1CCCCC1
Reactant: O=c1ccc2cc(O)ccc2[nH]1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=c1ccc2cc(OCCCc3nnnn3C3CCCCC3)ccc2[nH]1
Reaction time: 4 h
Yield: 50.4 %

Procedure:
Into 200 ml of dimethylformamide, 3.2 g of 6-hydroxycarbostyril, 3.3 g of potassium carbonate and 7.7 g of 1-cyclohexyl-5-γ-chloropropyltetrazole are added and stirred for 4 hours at 70° to 80° C. After the reaction is completed, dimethylformamide is removed by distillation under reduced pressure. The residue thus obtained is then extracted with 300 ml of chloroform and the chloroform layer is washed with a diluted NaOH aqueous solution and with water and next dried with Na2SO4. After removal of the drying agent by filtration, then the mother liquor is concentrated and the residue is recrystallized from chloroform to obtain 3.54 g of 6-[3-(1-cyclohexyltetrazol-5-yl)propoxy]carbostyril, in the form of colorless needle-like crystals. Melting point: 211° to 212° C.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([C:7](=O)[CH3:8])=[CH:3][CH:2]=1.[CH:10]([NH2:12])=[O:11].[OH-].[Na+]>C(O)=O.O>[N:1]1[CH:6]=[CH:5][C:4]([CH:7]([NH:12][CH:10]=[O:11])[CH3:8])=[CH:3][CH:2]=1
Reactant: CC(=O)c1ccncc1
Reactant: NC=O
Agent: [Na+]
Agent: [OH-]
Solvent: O=CO
Solvent: O
Product: CC(NC=O)c1ccncc1
Reaction time: 1.5 h

Procedure:
1-Pyridin-4-yl-ethanone (24.2 g, 199.77 mmol) and 10 ml of formic acid were heated to 180° C. and formamide (126 g, 2.797 mol) in 10 ml of formic acid was added within 30 min. The mixture was stirred for 90 min., cooled and poured in 100 ml of water. After addition of conc. sodium hydroxide solution until pH13 the product was extracted with diethyl-ether. The organic layer was dried with MgSO4 and evaporated. Purification by distillation (165° C./4 mbar) yields pure product.
Reaction SMILES: C([O:4][C@@H:5]1[C@@H:10]([O:11]C(=O)C)[C@H:9]([O:15]C(=O)C)[C@@H:8]([CH2:19][O:20]C(=O)C)[O:7][C@H:6]1[C:24]1[CH:29]=[CH:28][C:27]([F:30])=[C:26]([CH2:31][C:32]2[S:33][C:34](Br)=[CH:35][CH:36]=2)[CH:25]=1)(=O)C.C([Sn](CCCC)(CCCC)[C:43]1[S:44][CH:45]=[CH:46][N:47]=1)CCC>>[C@@H:6]1([C:24]2[CH:29]=[CH:28][C:27]([F:30])=[C:26]([CH2:31][C:32]3[S:33][C:34]([C:43]4[S:44][CH:45]=[CH:46][N:47]=4)=[CH:35][CH:36]=3)[CH:25]=2)[O:7][C@H:8]([CH2:19][OH:20])[C@@H:9]([OH:15])[C@H:10]([OH:11])[C@H:5]1[OH:4]
Reactant: CCCC[Sn](CCCC)(CCCC)c1nccs1
Reactant: CC(=O)OC[C@H]1O[C@@H](c2ccc(F)c(Cc3ccc(Br)s3)c2)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Product: OC[C@H]1O[C@@H](c2ccc(F)c(Cc3ccc(-c4nccs4)s3)c2)[C@H](O)[C@@H](O)[C@@H]1O

Procedure:
1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-3-(5-bromo-2-thienylmethyl)-4-fluorobenzene obtained in Example 189-(3) and tri-n-butyl(2-thiazolyl)tin were used and treated in a manner similar to Example 128 to give the title compound as colorless crystals. APCI-Mass m/z 438 (M+NH4). mp 161.5-162° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH2:15])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.I.CS[C:19]1[NH:20][CH2:21][CH2:22][N:23]=1.[OH-].[Na+]>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([N:15]=[C:19]2[NH:23][CH2:22][CH2:21][NH:20]2)[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:6][CH:7]=1
Reactant: CSC1=NCCN1
Reactant: NC(c1ccccc1)c1ccc(Cl)cc1
Agent: I
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: Clc1ccc(C(N=C2NCCN2)c2ccccc2)cc1

Procedure:
A mixture of 3.37 g of α-(p-chlorophenyl)benzylamine and 4.54 g of 2-methylmercapto-2-imidazoline-hydroiodide was heated at 150°-160° C. for 20 minutes. After cooling, the reaction mixture was dissolved in methanol and the solution rendered basic with sodium hydroxide to give 2-(α-(p-chlorophenyl)benzyl)iminoimidazolidine having a melting point of 187°-189° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]([C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)=[C:11]([C:19]2[O:23][N:22]=[C:21]([C:24]3[CH:31]=[CH:30][C:27]([CH:28]=O)=[CH:26][CH:25]=3)[N:20]=2)[N:10]=[N:9]1.[NH2:32][CH2:33][CH2:34][C:35]([OH:37])=[O:36]>>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]([C:13]2[CH:14]=[CH:15][N:16]=[CH:17][CH:18]=2)=[C:11]([C:19]2[O:23][N:22]=[C:21]([C:24]3[CH:25]=[CH:26][C:27]([CH2:28][NH:32][CH2:33][CH2:34][C:35]([OH:37])=[O:36])=[CH:30][CH:31]=3)[N:20]=2)[N:10]=[N:9]1
Reactant: O=Cc1ccc(-c2noc(-c3nnn(-c4ccccc4F)c3-c3ccncc3)n2)cc1
Reactant: NCCC(=O)O
Product: O=C(O)CCNCc1ccc(-c2noc(-c3nnn(-c4ccccc4F)c3-c3ccncc3)n2)cc1

Procedure:
The title compound was prepared following the procedure described for Example 94, but starting from 4-(5-(1-(2-fluorophenyl)-5-(pyridin-4-yl)-1H-1,2,3-triazol-4-yl)-1,2,4-oxadiazol-3-yl)benzaldehyde, obtained as described in Example 113, Step 1, (100 mg; 0.24 mmol) and β-alanine (43.2 mg; 0.48 mmol) to give Example 127 as a white solid. 1H NMR: (DMSO-d6, 400 MHz) δ 8.75 (2H, dd, J=4.5, 1.6 Hz), 7.97 (2H, d, J=8.1 Hz), 7.91 (1H, td, J=7.6, 1.7 Hz), 7.76-7.69 (1H, m), 7.61 (2H, dd, J=4.5, 1.7 Hz), 7.58 (2H, d, J=8.1 Hz), 7.55-7.45 (2H, m), 3.87 (2H, s), 2.81-2.68 (2H, m), 2.39 (2H, t, J=6.7 Hz). LC/MS (Method C): 484 (M+H)+. HPLC (Method F) Rt 2.83 min (Purity: 99.2%).
Reaction SMILES: [NH2:1][CH:2]([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([S:19][C:20]([F:23])([F:22])[F:21])[CH:14]=1)[CH:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=1)[OH:4].[C:24]1([C:35](O)=[O:36])[CH:25]=[CH:26][CH:27]=[C:28]2[CH2:34][CH2:33][CH2:32][CH:31]=[CH:30][C:29]=12.Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1>C(#N)C.O>[F:11][C:8]1[CH:9]=[CH:10][C:5]([CH:3]([OH:4])[CH:2]([NH:1][C:35]([C:24]2[CH:25]=[CH:26][CH:27]=[C:28]3[CH2:34][CH2:33][CH2:32][CH:31]=[CH:30][C:29]=23)=[O:36])[CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([S:19][C:20]([F:23])([F:22])[F:21])[CH:14]=2)=[CH:6][CH:7]=1
Reactant: NC(Cc1cccc(SC(F)(F)F)c1)C(O)c1ccc(F)cc1
Reactant: O=C(O)c1cccc2c1C=CCCC2
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CC#N
Product: O=C(NC(Cc1cccc(SC(F)(F)F)c1)C(O)c1ccc(F)cc1)c1cccc2c1C=CCCC2
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of (1RS,2SR)-2-amino-1-(4-fluorophenyl)-3-{3-[(trifluoromethyl)thio]phenyl}propan-1-ol (450 mg, 1.51 mmol) in acetonitrile (20 ml) were added 6,7-dihydro-5H-benzo[a]cycloheptene-1-carboxylic acid (284 mg, 1.51 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (435 mg, 2.27 mmol) and 1-hydroxybenzotriazole hydrate (231 mg, 1.51 mmol), and the mixture was stirred overnight at room temperature. The reaction solution was diluted with water (100 ml) and extracted with ethyl acetate (100 ml×2). The extract was washed successively with water and saturated brine, dried (anhydrous magnesium sulfate) and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1-ethyl acetate). Recrystallization from ethyl acetate-hexane gave the objective substance (396 mg, 51%).
Reaction SMILES: [CH3:1][N:2]1[C:11](=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[Br:13])[NH:4][C:3]1=O.[CH:15]1([C:18]2[O:22][N:21]=[C:20]([CH2:23][N+:24]#[C-:25])[N:19]=2)[CH2:17][CH2:16]1>>[CH:15]1([C:18]2[O:22][N:21]=[C:20]([C:23]3[N:24]=[CH:25][N:4]4[C:5]5[C:10](=[C:9]([Br:13])[CH:8]=[CH:7][CH:6]=5)[C:11](=[O:12])[N:2]([CH3:1])[C:3]=34)[N:19]=2)[CH2:17][CH2:16]1
Reactant: Cn1c(=O)[nH]c2cccc(Br)c2c1=O
Reactant: [C-]#[N+]Cc1noc(C2CC2)n1
Product: Cn1c(=O)c2c(Br)cccc2n2cnc(-c3noc(C4CC4)n3)c12

Procedure:
M.p. 206,6° C. by reaction between 3-methyl-5-bromo-1,2,3,4-tetrahydro-2,4-dioxo-quinazoline an 5-cyclopropyl-3-isocyanomethyl-1,2,4oxadiazole.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][CH:12]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6].C(N(CC)CC)C.FC(F)(F)S(O[Si:26]([CH3:29])([CH3:28])[CH3:27])(=O)=O>C1(C)C=CC=CC=1>[CH3:27][Si:26]([N:1]([Si:26]([CH3:29])([CH3:28])[CH3:27])[C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][CH:12]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6])([CH3:29])[CH3:28]
Reactant: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Reactant: CCOC(=O)c1cccc(N)c1
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: CCOC(=O)c1cccc(N([Si](C)(C)C)[Si](C)(C)C)c1
Yield: 92.4 %

Procedure:
About 8.37 g of ethyl 3-aminobenzoate, 11.80 g of triethylamine, and 10 ml of toluene were mixed in a round-bottom reaction flask cooled with an ice bath. To this mixture was added, in a dropwise fashion, a solution of 25.91 g of trimethylsilyl trifluoromethanesulfonate in 50 ml of toluene. The resulting mixture was heated to reflux for 30 hours to give a biphasic mixture. The top layer was transferred to another flask, and the bottom layer was extracted with 40 ml of toluene. The combined toluene solution was evaporated under vacuum. The residue was extracted with 100 ml of hexane, and the hexane layer was evaporated under vacuum, yielding ethyl 3-[bis(trimethylsilyl)amino]benzoate (3-BTMSAEBz) as a yellow oil (14.50 g, 92% yield). The 1H NMR data (C6D6, 25° C., referenced to tetramethylsilane) of the product are listed as follows: δ 7.95 (multiplet, 1 H, aromatic proton), 7.91 (multiplet, 1 H, aromatic proton), 6.98 (multiplet, 1 H, aromatic proton), 6.91 (multiplet, 1 H, aromatic proton), 4.07 (quartet, 2 H, CH2 protons), 0.95 (triplet, 3 H, CH3 protons), 0.04 (singlet, 18 H, Si—CH3 protons). From the 1H NMR data, the structure of the product was determined to be as follows:
Reaction SMILES: [F:1][C:2]1[C:12](I)=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[C:4]([OH:14])[CH:3]=1.[C:15]([C:17]1[CH:22]=[CH:21][C:20]([S:23]([NH:26][C:27]2[C:32]([CH3:33])=[CH:31][CH:30]=[CH:29][N:28]=2)(=[O:25])=[O:24])=[CH:19][CH:18]=1)#[CH:16].C(N(CC)CC)C>O1CCCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[F:1][C:2]1[C:12]([C:16]#[C:15][C:17]2[CH:18]=[CH:19][C:20]([S:23]([NH:26][C:27]3[C:32]([CH3:33])=[CH:31][CH:30]=[CH:29][N:28]=3)(=[O:24])=[O:25])=[CH:21][CH:22]=2)=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[C:4]([OH:14])[CH:3]=1
Reactant: C#Cc1ccc(S(=O)(=O)Nc2ncccc2C)cc1
Reactant: CCOC(=O)c1cc(I)c(F)cc1O
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CCOC(=O)c1cc(C#Cc2ccc(S(=O)(=O)Nc3ncccc3C)cc2)c(F)cc1O
Temperature: 50 °C
Reaction time: 3 h

Procedure:
Ethyl 4-fluoro-2-hydroxy-5-iodobenzoate (3.6 g, 80%, 10 mmol), 4-ethynyl-N-(3-methyl-2-pyridinyl)benzenesulfonamide (2.7 g, 10 mmol) and triethylamine (5 g, 50 mmol) were suspended in tetrahydrofuran (20 ml) and the mixture heated to 50° C. Dichlorobis(triphenylphosphine)palladium (45 mg, 0.06 mmol) and copper(I)iodide (76 mg, 0.4 mmol) were added with stirring. After about 15 min a practically clear solution had formed. After 3 h at 50° C. the solution was taken to dryness and triturated with isobutylmethylketone and dilute hydrochloric acid. The organic phase was separated and the solvent evaporated. The oily residue was triturated with a small amount of acetonitrile to form crystals. These were recrystallized from acetic acid. The product was dissolved in a small amount of chloroform and the solution applied on top of a short silica gel column and eluted with 25% isobutylmethylketone in toluene. The pure product resulted after evaporation of the solvent Yield 2.0 g, 44%.
Reaction SMILES: [C:1]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:15]([SH:18])[CH2:16][SH:17].C1(C)C=CC(S(O)(=O)=O)=CC=1.C1C=CC=CC=1>O>[C:2]1([C:1]2([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[S:18][CH2:15][CH2:16][S:17]2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(c1ccccc1)c1ccccc1
Reactant: SCCS
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: c1ccccc1
Product: c1ccc(C2(c3ccccc3)SCCS2)cc1

Procedure:
A solution containing benzophenone (45.5 grams; 0.25 mole), 1,2-ethanedithiol (23.5 grams; 0.25 mole), and p-toluenesulfonic acid (1 gram) in 150 mls. of dry benzene was heated at reflux until no more water was azeotroped off. The remaining benzene was then evaporated and the residue was dissolved in diethyl ether. The ethereal solution was then washed with water, dried over anhydrous magnesium sulfate, filtered and evaporated to obtain 2,2-diphenyl-1,3-dithiolane, a white crystalline solid which melted at 104°-105° C. A different preparation of this same compound is described in Fasbender, Berichte 21, 1473-7, (1888), wherein the melting point is reported as 106° C.