Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([S:13]([CH3:16])(=[O:15])=[O:14])=[C:11]([C:17]([O:19]C(C)(C)C)=[O:18])[N:10]=[C:9]2[C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=2[Cl:31])=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O.[SiH](CC)(CC)CC>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([S:13]([CH3:16])(=[O:15])=[O:14])=[C:11]([C:17]([OH:19])=[O:18])[N:10]=[C:9]2[C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=2[Cl:31])=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)c1nc(-c2ccc(Cl)cc2Cl)n(-c2ccc(Cl)cc2)c1S(C)(=O)=O
Agent: CC[SiH](CC)CC
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CS(=O)(=O)c1c(C(=O)O)nc(-c2ccc(Cl)cc2Cl)n1-c1ccc(Cl)cc1

Procedure:
To a magnetically stirred solution of tert-butyl 1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-methylsulfonyl-1H-imidazole-4-carboxylate (4.76 g, 9.49 mmol) in CH2Cl2 (60 ml) was added excess TFA (9.40 ml, 0.2124 mol) and Et3SiH (3.8 ml, 0.0238 mol). The solution was reacted at room temperature for 16 h and concentrated in vacuo. Water was added and the formed precipitate was collected by filtration and subsequently dried to give 1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-methylsulfonyl-1H-imidazole-4-carboxylic acid in quantitative yield, mp˜130° C. (dec); 1H-NMR (400 MHz, CDCl3) δ 3.45 (s, 3H), 3.50 (br s, 1H), 7.40 (br d, J˜8 Hz, 2H), 7.42 (dd, J=8 and 2 Hz, 1H), 7.50 (br d, J˜8 Hz, 2H), 7.59 (d, J=2 Hz, 1H), 7.61 (d, J=8 Hz, 1H).
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[C:5]([CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[N:6]=1.[Cl:13][C:14]1[S:15][C:16]([S:20](Cl)(=[O:22])=[O:21])=[CH:17][C:18]=1[Cl:19]>>[Cl:19][C:18]1[CH:17]=[C:16]([S:20]([NH:1][C:2]2[S:3][CH:4]=[C:5]([CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[N:6]=2)(=[O:22])=[O:21])[S:15][C:14]=1[Cl:13]
Reactant: O=S(=O)(Cl)c1cc(Cl)c(Cl)s1
Reactant: CCOC(=O)Cc1csc(N)n1
Product: CCOC(=O)Cc1csc(NS(=O)(=O)c2cc(Cl)c(Cl)s2)n1

Procedure:
The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 2,3-dichlorothiophene-5-sulfonyl chloride as described in the synthetic METHOD B to give a white-yellow solid (36.9 mg) with purity >90%. MS (pos) m/z 401.1, 403.1.
Reaction SMILES: C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[K+].[CH2:9]([O:11][C:12](=[O:26])[CH:13]([O:23][CH2:24][CH3:25])[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][C:16]=1[CH3:22])[CH3:10].Cl[CH2:28][C:29]1[N:30]=[C:31]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=2[Cl:41])[O:32][C:33]=1[CH3:34].ClC1C=CC=CC=1C=O.O=P(Cl)(Cl)Cl>CC(C)=O>[CH2:9]([O:11][C:12](=[O:26])[CH:13]([O:23][CH2:24][CH3:25])[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH2:28][C:29]2[N:30]=[C:31]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[Cl:41])[O:32][C:33]=2[CH3:34])=[CH:17][C:16]=1[CH3:22])[CH3:10]
Reactant: Cc1oc(-c2ccccc2Cl)nc1CCl
Reactant: CCOC(=O)C(Cc1ccc(O)cc1C)OCC
Agent: O=C([O-])[O-]
Agent: O=Cc1ccccc1Cl
Agent: [Cs+]
Solvent: O=P(Cl)(Cl)Cl
Solvent: CC(C)=O
Product: CCOC(=O)C(Cc1ccc(OCc2nc(-c3ccccc3Cl)oc2C)cc1C)OCC
Yield: 79 %

Procedure:
Cesium carbonate (97 mg, 300 μmol, 1.5 eq.) and a trace of potassium iodide were added to a solution of [rac]-2-ethoxy-3-(4-hydroxy-2-methyl-phenyl)-propionic acid ethyl ester (50 mg, 200 μmol, 1 eq., example 129 c]) and 4-chloromethyl-2-(2-chloro-phenyl)-5-methyl-oxazole (72 mg, 300 μmol, 1.5 eq., prepared from 2-chloro-benzaldehyde and diacetyl monoxyme followed by treatment with POCl3 in analogy to the procedures described in examples 21 a] and b]) in acetone (4 ml). The mixture was heated under reflux for 12 h, filtered off and the filtrate evaporated in vacuo. The residue was taken up in ethyl acetate and ice cold 1 M hydrochloric acid. The organic layer was washed two times with brine and dried over sodium sulfate. Removal of the solvent under reduced pressure gave a yellow oil which was purified by column chromatography (silica gel, hexane/AcOEt=9/1) to give 72 mg (160 μmol, 79%) of the title compound as colorless oil.
Reaction SMILES: C(OC([N:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:24][CH2:23][C:22]4[CH:25]=[C:26]([C:28]5[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=5)[S:27][C:21]=4[C:20]3=[O:35])=[CH:15][C:14]=2[O:36][CH3:37])[CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[NH:8]1[CH2:9][CH:10]([O:12][C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:24][CH2:23][C:22]4[CH:25]=[C:26]([C:28]5[CH:29]=[CH:30][C:31]([Cl:34])=[CH:32][CH:33]=5)[S:27][C:21]=4[C:20]3=[O:35])=[CH:15][C:14]=2[O:36][CH3:37])[CH2:11]1
Reactant: COc1cc(N2CCc3cc(-c4ccc(Cl)cc4)sc3C2=O)ccc1OC1CN(C(=O)OC(C)(C)C)C1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COc1cc(N2CCc3cc(-c4ccc(Cl)cc4)sc3C2=O)ccc1OC1CNC1
Yield: 78.5 %

Procedure:
Dissolve 3-{4-[2-(4-chloro-phenyl)-7-oxo-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl]-2-methoxy-phenoxy}-azetidine-1-carboxylic acid tert-butyl ester (924 μmol, 500 mg) in dichloromethane (10 mL), add trifluoroacetic acid (5 mL), and stir the reaction at room temperature for 2 h. Concentrate the material in vacuo and partition the residue between 1N NaOH (10 mL) and CH2Cl2 (15 mL). Separate the organic portion and extract the aqueous portion with CH2Cl2 (3×10 mL). Dry the combined organics over Na2SO4, filter, and concentrate to dryness to afford 320 mg of 6-[4-(azetidin-3-yloxy)-3-methoxy-phenyl]-2-(4-chloro-phenyl)-5,6-dihydro-4H-thieno[2,3-c]pyridin-7-one as a white solid.
Reaction SMILES: [CH3:1][C:2]1([CH3:16])[CH2:7][C:6](=[O:8])[CH2:5][C:4](=[O:9])[CH:3]1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[CH3:17][CH2:18][CH2:19][C:20](Cl)=[O:21].C(OC1CC(C)(C)C(C2C=CC=CC=2)C(=O)C=1)(=O)CCC.C(OC1C(C2C=CC=CC=2)C(C)(C)CC(=O)C=1)(=O)CCC>C(Cl)Cl.C1(C)C=CC=CC=1.C(N(CC)CC)C>[C:20]([C:5]1[C:6](=[O:8])[CH2:7][C:2]([CH3:16])([CH3:1])[CH:3]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:4]=1[OH:9])(=[O:21])[CH2:19][CH2:18][CH3:17]
Reactant: CC1(C)CC(=O)CC(=O)C1c1ccccc1
Reactant: CCCC(=O)Cl
Agent: CCCC(=O)OC1=CC(=O)C(c2ccccc2)C(C)(C)C1
Agent: CCCC(=O)OC1=CC(=O)CC(C)(C)C1c1ccccc1
Solvent: ClCCl
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: CCCC(=O)C1=C(O)C(c2ccccc2)C(C)(C)CC1=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 42.1 %

Procedure:
Triethylamine (5.2 g) was added dropwise to a stirred solution of 5,5-dimethyl-4-phenyl cyclohexane-1,3-dione (10.8 g) and n-butyryl chloride (5.3 g) in methylene chloride (100 ml). After stirring at ambient temperature for a further 2 hours, the reaction solution was washed with water and brine and dried over anhydrous magnesium sulphate. The methylene chloride was removed in vacuo to give a mixture of 1-butyryloxy-5,5-di-methyl-4-phenyl cyclohex-1-ene-3-one and 1-butyryloxy-5,5-dimethyl-6-phenyl cyclohex-1-ene-3-one. Toluene (100 ml) was added, followed by 4-(N-dimethylamino) pyridine (1 g) and the mixture was refluxed for 3 hours. Evaporation of the toluene in vacuo gave a red oil which was purified on a silica gel column using 5% (v/v) diethyl ethermethylene chloride as eluant to give the title compound (6 g) as a pale yellow oil.
Reaction SMILES: C([O:8][C:9](=[O:44])[CH:10]([O:41][CH2:42][CH3:43])[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][C:19](=[O:33])[CH2:20][C:21]2[N:22]=[C:23]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[O:24][C:25]=2[CH3:26])=[C:14]([CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH:13]=1)C1C=CC=CC=1.CCO>CCOC(C)=O>[CH2:34]([C:14]1[CH:13]=[C:12]([CH2:11][CH:10]([O:41][CH2:42][CH3:43])[C:9]([OH:44])=[O:8])[CH:17]=[CH:16][C:15]=1[O:18][C:19](=[O:33])[CH2:20][C:21]1[N:22]=[C:23]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[O:24][C:25]=1[CH3:26])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1
Reactant: CCOC(Cc1ccc(OC(=O)Cc2nc(-c3ccccc3)oc2C)c(Cc2ccccc2)c1)C(=O)OCc1ccccc1
Solvent: CCO
Solvent: CCOC(C)=O
Product: CCOC(Cc1ccc(OC(=O)Cc2nc(-c3ccccc3)oc2C)c(Cc2ccccc2)c1)C(=O)O

Procedure:
The title compound was prepared from 3-{3-benzyl-4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-acetoxy]-phenyl}-2-ethoxy-propionic acid benzyl ester (0.054 g, 0.09 mmol) in the same manner as described for example 1 with the difference that EtOH was used as the solvent instead of EtOAc. The crude product was purified by column chromatography using DCM/MeOH (95:5) as the eluent and the desired compound was obtained as an oil (0.019 g, 41.3%). 1H NMR (400 MHz, CDCl3): δ 7.93-7.96 (m, 2H), 7.39-7.41 (m, 3H), 7.02-7.19 (m, 8H), 3.99 (m, 1H), 3.86 (s, 2H), 3.69 (s, 2H), 3.48 (m, 1H), 3.32 (m, 1H), 3.03-3.09 (dd, 1H), 2.90-2.93 (dd, 1H), 2.29 (s, 3H), 1.04-1.07 (t, 3H).
Reaction SMILES: [Si]([O:8][C@@H:9]1[C@@:34]2([CH3:35])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:33]2[CH2:32][CH2:31][C@@:30]2([CH3:36])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C@@H:21]([S:23][CH2:24][CH2:25][C:26]([OH:29])([CH3:28])[CH3:27])[CH3:22])[CH2:12][C@@H:11]([OH:37])[CH2:10]1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.C(OCC)(=O)C>[OH:8][C@@H:9]1[C@@:34]2([CH3:35])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:33]2[CH2:32][CH2:31][C@@:30]2([CH3:36])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C@@H:21]([S:23][CH2:24][CH2:25][C:26]([OH:29])([CH3:27])[CH3:28])[CH3:22])[CH2:12][C@@H:11]([OH:37])[CH2:10]1
Reactant: C[C@H](SCCC(C)(C)O)C1=CC[C@H]2C3=CC=C4C[C@@H](O)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: C[C@H](SCCC(C)(C)O)C1=CC[C@H]2C3=CC=C4C[C@@H](O)C[C@H](O)[C@]4(C)[C@H]3CC[C@]12C
Yield: 90.3 %

Procedure:
To a solution of 1α-(tert-butyldimethylsilyloxy)-3β-hydroxy-20(S)-(3-hydroxy-3-methylbutylthio)pregna-5,7,16-triene (58.5 mg, 0.107 mmol) in tetrahydrofuran (3 ml) was added 1M tetra-n-butylammonium fluoride solution in tetrahydrofuran (2 ml), and the mixed solution was heated under reflux for 4 hours. After completion of the reaction, the reaction solution was diluted with ethyl acetate, and washed with ice-cooled 0.5 N hydrochloric acid, saturated aqueous sodium bicarbonate solution and brine successively, and the organic layer was dried over magnesium sulfate. The solvent was removed under reduced pressure, and the resulting residue was purified by preparative thin layer chromatography (0.5 mm×2, dichloromethane:ethanol=7:1, developed once) to give the title compound as a pale yellow oil (41.8 mg, 90%).
Reaction SMILES: [F:1][C:2]1[C:15]([N:16]=[C:17]=[O:18])=[CH:14][C:5]2[N:6]([CH2:11][C:12]#[CH:13])[C:7](=[O:10])[CH2:8][O:9][C:4]=2[CH:3]=1.[OH:19][CH:20]([C:25]([CH3:27])=[CH2:26])[C:21]([O:23][CH3:24])=[O:22].C(N(CC)CC)C.O>C1C=CC=CC=1>[F:1][C:2]1[C:15]([NH:16][C:17]([O:19][CH:20]([C:21]([O:23][CH3:24])=[O:22])[C:25]([CH3:27])=[CH2:26])=[O:18])=[CH:14][C:5]2[N:6]([CH2:11][C:12]#[CH:13])[C:7](=[O:10])[CH2:8][O:9][C:4]=2[CH:3]=1
Reactant: C=C(C)C(O)C(=O)OC
Reactant: C#CCN1C(=O)COc2cc(F)c(N=C=O)cc21
Solvent: c1ccccc1
Solvent: CCN(CC)CC
Solvent: O
Product: C#CCN1C(=O)COc2cc(F)c(NC(=O)OC(C(=C)C)C(=O)OC)cc21
Temperature: 25 °C

Procedure:
To a solution of 7-fluoro-6-isocyanato-4-propargyl-2H-1,4-benzoxazin-3(4H)-one (2.5 g) and methyl 2-hydroxy-3-methyl-3-butenoate (1.3 g) in benzene (50 ml), triethylamine (0.5 g) was added at room temperature. The resulting mixture was refluxed for 1 hour, cooled to room temperature, combined with water and extracted with ethyl acetate. The organic layer was washed with water, dried over magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography using a mixture of toluene and ethyl acetate as the eluent to give Compound No. 72 (2.9 g). nD25.0 1.4868
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][C:8]([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH:12]2[O:24][CH2:25][C:26]2[CH:35]=[CH:34][C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH:27]=2)=[CH:7][CH:6]=1.[C:36](Cl)(=[O:43])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>>[C:36]([O:1][CH2:2][CH2:3][CH2:4][C:5]1[CH:6]=[CH:7][C:8]([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[O:18])[CH2:13][CH:12]2[O:24][CH2:25][C:26]2[CH:35]=[CH:34][C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH:27]=2)=[CH:9][CH:10]=1)(=[O:43])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: CC(C)(C)OC(=O)N1CCC(c2ccc(CCCO)cc2)C(OCc2ccc3ccccc3c2)C1
Product: CC(C)(C)OC(=O)N1CCC(c2ccc(CCCOC(=O)c3ccccc3)cc2)C(OCc2ccc3ccccc3c2)C1

Procedure:
(aa) In an analogous manner to that described in Example 22(k), by acylating tert-butyl (3RS,4RS)-4-[4-(3-hydroxy-propyl)-phenyl]-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate [Example 24(t)] with benzoyl chloride there was obtained tert-butyl (3RS,4RS)-4-[4-(3-benzoyloxy-propyl)-phenyl]-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate as an almost colourless solid; MS: 580 (M+H)+.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:10][C:9](=[O:11])[CH2:8][O:7][C:6]=2[CH:12]=1.Cl[C:14]1[S:18][C:17]([C:19]([O:21][CH3:22])=[O:20])=[CH:16][C:15]=1[N+:23]([O-:25])=[O:24]>>[N+:23]([C:15]1[CH:16]=[C:17]([C:19]([O:21][CH3:22])=[O:20])[S:18][C:14]=1[O:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:10][C:9](=[O:11])[CH2:8][O:7][C:6]=2[CH:12]=1)([O-:25])=[O:24]
Reactant: COC(=O)c1cc([N+](=O)[O-])c(Cl)s1
Reactant: O=C1COc2cc(O)ccc2N1
Product: COC(=O)c1cc([N+](=O)[O-])c(Oc2ccc3c(c2)OCC(=O)N3)s1

Procedure:
Prepared according to the procedure described for step A of example 18 from 7-hydroxy-2H-benzo[b][1,4]oxazin-3(4H)-one (826 mg, 5.0 mmol) and methyl 5-chloro-4-nitro-thiophene-2-carboxylate (1.1 g, 5.0 mmol). The title compound was obtained as a white solid (400 mg, 23% yield). 1H NMR (400 MHz, d6-DMSO) δ: 10.92 (1H, S), 8.04 (1H, S), 7.22 (1H, M), 7.10 (2H, S), 7.03 (1H, M), 4.66 (2H, S), 3.80 (3H, S). MS m/z: 349.20 [M+H]+.
Reaction SMILES: [CH:1](=[N:8][N:9]([C:11]1[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[CH2:14][O:13][N:12]=1)[CH3:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl>C(O)C>[OH:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[C:11]1[N:9]([CH3:10])[N:8]=[C:1]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[N:12]=1
Reactant: CN(N=Cc1ccccc1)C1=NOCc2ccccc21
Agent: Cl
Solvent: CCO
Product: Cn1nc(-c2ccccc2)nc1-c1ccccc1CO
Temperature: 0 °C
Yield: 96 %

Procedure:
A suspension of 1.2 g. of 4-(2-benzylidene-1-methylhydrazino)-1H-2,3-benzoxazine in 12 ml. of ethanol and 12 ml. of aqueous 5% HCl is heated on a water bath for 3 hours. The ethanol is removed by distillation and the residue, neutralized with aqueous NaHCO3, is cooled to about 0° C. The precipitate is filtered and crystallized from ethanol. M.p. 122° C. Yield 96%.
Reaction SMILES: C([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C:15]1[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=1)C1C=CC=CC=1>CO>[N:17]1[CH:18]=[CH:19][CH:20]=[C:15]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[OH:8])[CH:16]=1
Reactant: c1ccc(COc2ccccc2-c2cccnc2)cc1
Solvent: CO
Product: Oc1ccccc1-c1cccnc1
Reaction time: 16 h
Yield: 81 %

Procedure:
2-(3-pyridyl)phenyl benzyl ether (6.67 g, 25.52 mmol) was dissolved in MeOH (100 mL). Argon was bubbled through this solution for 10 min to remove oxygen. Then Pd/C (350 mg 5 w %) was added, and the reaction mixture was put into the Parr-reactor and shaken for 16 hr under a hydrogen atmosphere at 80 psi. After the hydrogenation, the mixture was filtered over diatomaceous earth, and the colourless solution was evaporated to dryness. The crude product was recrystallized from 2-propanol to yield a white crystalline material (3.54 g, 79%). M.p.=185° C. 1H-NMR (CDCl3/MeOD):δ=8.76 (d, 1H), 8.43 (dd, 1H), 8.02 (dt, 1H), 7.39 (m, 1H), 7.21-7.29 (m, 2H), 6.95 (m, 2H).
Reaction SMILES: C([Si](C)(C)[O:6][C:7]([C:10]1[NH:11][C:12]2[C:17]([C:18]=1[S:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([N+:26]([O-:28])=[O:27])[CH:21]=1)=[CH:16][C:15]([C:29]#[N:30])=[C:14]([C:31]([F:34])([F:33])[F:32])[CH:13]=2)([CH3:9])[CH3:8])(C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[OH:6][C:7]([C:10]1[NH:11][C:12]2[C:17]([C:18]=1[S:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([N+:26]([O-:28])=[O:27])[CH:21]=1)=[CH:16][C:15]([C:29]#[N:30])=[C:14]([C:31]([F:33])([F:34])[F:32])[CH:13]=2)([CH3:9])[CH3:8]
Reactant: CC(C)(O[Si](C)(C)C(C)(C)C)c1[nH]c2cc(C(F)(F)F)c(C#N)cc2c1Sc1cccc([N+](=O)[O-])c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: CC(C)(O)c1[nH]c2cc(C(F)(F)F)c(C#N)cc2c1Sc1cccc([N+](=O)[O-])c1
Reaction time: 8 h
Yield: 67.2 %

Procedure:
2-[1-(tert-Butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-3-(3-nitro-phenylsulfanyl)-6-trifluoromethyl-1H-indole-5-carbonitrile (33 mg, 0.060 mmole) was stirred in THF (1 mL) with TBAF (1 M in THF) (0.1 mL, 0.1 mmol). The reaction was allowed to proceed overnight and purified by column chromatography eluting with 0 and 1% methanol/dichloromethane. Obtained 17 mg (71%) of desired product. 1H NMR (acetone-d6) δ 11.75 (s, 1H), 8.19 (s, 1H), 8.08 (s, 1H), 7.98-7.96 (m, 1H), 7.81 (t, J=2.0 Hz, 1H), 7.54 (t. J=8.0 Hz, 1H), 7.48-7.45 (m, 1H), 2.83 (s, 1H), 1.75 (s, 6H). MS (m/z): 444 (MNa+), 420 (MH−).
Reaction SMILES: I[C:2]1[C:10]2[S:9][C:8]([NH:11][C:12]([C:14]3[S:15][C:16]([CH3:19])=[CH:17][CH:18]=3)=[O:13])=[N:7][C:6]=2[C:5]([O:20][CH3:21])=[CH:4][CH:3]=1.[Cl:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1B(O)O>>[Cl:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[C:2]1[C:10]2[S:9][C:8]([NH:11][C:12]([C:14]3[S:15][C:16]([CH3:19])=[CH:17][CH:18]=3)=[O:13])=[N:7][C:6]=2[C:5]([O:20][CH3:21])=[CH:4][CH:3]=1
Reactant: OB(O)c1ccccc1Cl
Reactant: COc1ccc(I)c2sc(NC(=O)c3ccc(C)s3)nc12
Product: COc1ccc(-c2ccccc2Cl)c2sc(NC(=O)c3ccc(C)s3)nc12
Yield: 80 %

Procedure:
5-Methyl-thiophene-2-carboxylic acid [7-(2-chloro-phenyl)-4-methoxy-benzothiazol-2-yl]-amide is synthesized from 5-methyl-thiophene-2-carboxylic acid (7-iodo-4-methoxy-benzothiazol-2-yl)-amide (100 mg, 0.23 mmol) and 2-chlorophenylboronic acid (54 mg, 0.35 mmol) using the general procedure A as a light yellow solid in 80% yield. MS: m/e=415 (M+H+).
Reaction SMILES: CI.[CH3:3][N:4]([CH3:35])[C:5]1[CH:6]=[C:7]([CH:32]=[CH:33][CH:34]=1)[C:8]([NH:10][C:11]1[CH:12]=[CH:13][C:14]([CH3:31])=[C:15]([NH:17][C:18](=[O:30])[C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([NH:25][S:26]([CH3:29])(=[O:28])=[O:27])[CH:20]=2)[CH:16]=1)=[O:9].[C:36](=O)([O-])[O-].[Cs+].[Cs+].CN(C=O)C>O>[CH3:35][N:4]([CH3:3])[C:5]1[CH:6]=[C:7]([CH:32]=[CH:33][CH:34]=1)[C:8]([NH:10][C:11]1[CH:12]=[CH:13][C:14]([CH3:31])=[C:15]([NH:17][C:18](=[O:30])[C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([N:25]([S:26]([CH3:29])(=[O:28])=[O:27])[CH3:36])[CH:20]=2)[CH:16]=1)=[O:9]
Reactant: O=C([O-])[O-]
Reactant: Cc1ccc(NC(=O)c2cccc(N(C)C)c2)cc1NC(=O)c1cccc(NS(C)(=O)=O)c1
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Solvent: CI
Product: Cc1ccc(NC(=O)c2cccc(N(C)C)c2)cc1NC(=O)c1cccc(N(C)S(C)(=O)=O)c1
Yield: 74.4 %

Procedure:
Methyl iodide (0.1 g) was added to a mixture of N-[5-(3-dimethylaminobenzamido)-2-methylphenyl]-3-methanesulphonylaminobenzamide (0.3 g), caesium carbonate (0.23 g) and DMF (20 ml) and the resultant mixture was stirred at ambient temperature for 18 hours. The reaction mixture was poured into water (250 ml). The precipitate was isolated, washed in turn with water and diethyl ether and dried under vacuum at 60° C. There was thus obtained the title compound (0.23 g); m.p. 168-169° C.; NMR Spectrum: (DMSOd6) 2.19 (s, 3H), 2.95 (s, 6H), 3.0 (s, 3H), 6.9 (d, 1H), 7.21 (m, 3H), 7.29 (t, 1H), 7.58 (m, 3H), 7.81 (d, 1H), 7.9 (d, 1H), 7.98 (d, 1H) 9.97 (br s, 1H), 10.09 (br s, 1 H); Mass Spectrum: M+H+ 481.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][N:5]2[C:8]([CH2:14][C:15]3[CH:38]=[CH:37][C:18]4/[C:19](=[C:29](\[C:31]5[NH:32][O:33][C:34](=[O:36])[N:35]=5)/[CH3:30])/[C:20]5[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:21]=5[O:22][CH2:23][C:17]=4[CH:16]=3)=[C:9]([C:11]([NH2:13])=O)[N:10]=[C:4]2[CH:3]=1.C(N(CC)CC)C.FC(F)(F)C(OC(=O)C(F)(F)F)=O.O>C1COCC1>[C:11]([C:9]1[N:10]=[C:4]2[CH:3]=[C:2]([F:1])[CH:7]=[CH:6][N:5]2[C:8]=1[CH2:14][C:15]1[CH:38]=[CH:37][C:18]2/[C:19](=[C:29](\[C:31]3[NH:35][C:34](=[O:36])[O:33][N:32]=3)/[CH3:30])/[C:20]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:21]=3[O:22][CH2:23][C:17]=2[CH:16]=1)#[N:13]
Reactant: C/C(=C1/c2ccc(Cc3c(C(N)=O)nc4cc(F)ccn34)cc2COc2cc(F)ccc21)c1nc(=O)o[nH]1
Solvent: O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: C/C(=C1/c2ccc(Cc3c(C#N)nc4cc(F)ccn34)cc2COc2cc(F)ccc21)c1noc(=O)[nH]1
Temperature: 25 °C
Reaction time: 2 h
Yield: 13.7 %

Procedure:
[step 2] (E)-7-fluoro-3-({3-fluoro-11-[1-(5-oxo-1,2,4-oxadiazol-3-yl)ethylidene]dibenzo[b,e]oxepin-8-yl}methyl)imidazo[1,2-a]pyridine-2-carboxamide (113 mg, 0.22 mmol) obtained in step 1 was dissolved in THF (2 mL), triethylamine (67 mg, 0.66 mmol) and trifluoroacetic anhydride (138 mg, 0.66 mmol) were added and the mixture was stirred at room temperature for 2 hr. Furthermore, triethylamine (89 mg, 0.88 mmol) and trifluoroacetic anhydride (184 mg, 0.88 mmol) were added, and the mixture was stirred at room temperature for 8 hr. Water was added to the reaction mixture, and the mixture was extracted 3 times with chloroform. The combined organic layers were dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform/methanol=9/1 v/v) to give the title compound (compound 14i) (15 mg, 14%).
Reaction SMILES: [N:1]([CH2:4][CH2:5][O:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[O:13][CH:12]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:11][CH2:10]2)=[N+:2]=[N-:3].[OH:23]C1C=C2C(=CC=1)OC(C1C=CC=CC=1)CC2=O>>[N:1]([CH2:4][CH2:5][O:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[O:13][CH:12]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:11][C:10]2=[O:23])=[N+:2]=[N-:3]
Reactant: [N-]=[N+]=NCCOc1ccc2c(c1)CCC(c1ccccc1)O2
Reactant: O=C1CC(c2ccccc2)Oc2ccc(O)cc21
Product: [N-]=[N+]=NCCOc1ccc2c(c1)C(=O)CC(c1ccccc1)O2

Procedure:
6-(2-Azidoethoxy)-2-phenylchroman-4-one was prepared as described for 6-(2-azidoethoxy)-2-phenylchroman in example 4(a) starting from 1.0 g of 6-hydroxy-flavanone. 1H NMR (400 MHz, CD3OD) δ: 7.53-7.51 (m, 2H), 7.44-7.35 (m, 4H), 7.22 (dd, 1H, J 9.0, 3.1 Hz), 7.04 (d, 1H, J 9.0 Hz), 5.51 (dd, 1H, J 13.1, 3.0 Hz), 4.17 (t, 2H, J 4.9 Hz), 3.60 (t, 2H, J 4.9 Hz), 3.11 (dd, 1H, J −16.9, 13.1 Hz), 2.85 (dd, 1H, J −16.9, 3.0 Hz).
Reaction SMILES: C([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:13]([O:15][CH3:16])=[O:14])[CH:11]=2)[C:6](=[C:17](OCC)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:5]1=[O:27])(=O)C.[CH3:28][N:29]([CH3:44])[CH2:30][CH2:31][N:32]([C:36]1[CH:42]=[CH:41][C:39]([NH2:40])=[CH:38][C:37]=1[Br:43])[C:33](=[O:35])[CH3:34]>>[CH3:44][N:29]([CH3:28])[CH2:30][CH2:31][N:32]([C:36]1[CH:42]=[CH:41][C:39]([NH:40]/[C:17](=[C:6]2\[C:5](=[O:27])[NH:4][C:12]3[C:7]\2=[CH:8][CH:9]=[C:10]([C:13]([O:15][CH3:16])=[O:14])[CH:11]=3)/[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:38][C:37]=1[Br:43])[C:33](=[O:35])[CH3:34]
Reactant: CCOC(=C1C(=O)N(C(C)=O)c2cc(C(=O)OC)ccc21)c1ccccc1
Reactant: CC(=O)N(CCN(C)C)c1ccc(N)cc1Br
Product: COC(=O)c1ccc2c(c1)NC(=O)/C2=C(\Nc1ccc(N(CCN(C)C)C(C)=O)c(Br)c1)c1ccccc1

Procedure:
Prepared from 1-acetyl-3-(1-ethoxy-1-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(N-(2-dimethylamino-ethyl)-N-acetyl-amino)-3-bromo-aniline Rf value: 0.6 (silica gel, methylene chloride/methanol=5:1) C29H29BrN4O4
Reaction SMILES: [C:1](OCC)(=[O:5])[C:2]([CH3:4])=O.[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[C:18]([NH2:26])=[CH:19][C:20]([C:23](=[O:25])[CH3:24])=[CH:21][CH:22]=2)=[CH:12][CH:11]=1>>[Cl:9][C:10]1[CH:11]=[CH:12][C:13]([N:16]2[C:17]3[C:18](=[CH:19][C:20]([C:23](=[O:25])[CH3:24])=[CH:21][CH:22]=3)[N:26]=[C:2]([CH3:4])[C:1]2=[O:5])=[CH:14][CH:15]=1
Reactant: CCOC(=O)C(C)=O
Reactant: CC(=O)c1ccc(Nc2ccc(Cl)cc2)c(N)c1
Product: CC(=O)c1ccc2c(c1)nc(C)c(=O)n2-c1ccc(Cl)cc1

Procedure:
Preparation as in Example 1 but using ethyl pyruvate and N-(4-chlorophenyl)-4-acetylbenzene-1,2-diamine.