Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([O:7][NH2:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:9][C:10]1[N:14]([CH2:15][C:16]([N:18]2[CH2:23][CH2:22][CH:21]([C:24]3[S:25][CH:26]=[C:27]([CH:29]=O)[N:28]=3)[CH2:20][CH2:19]2)=[O:17])[N:13]=[C:12]([C:31]([F:34])([F:33])[F:32])[CH:11]=1>C(O)C>[C:1]1([O:7][N:8]=[CH:29][C:27]2[N:28]=[C:24]([CH:21]3[CH2:20][CH2:19][N:18]([C:16](=[O:17])[CH2:15][N:14]4[C:10]([CH3:9])=[CH:11][C:12]([C:31]([F:32])([F:34])[F:33])=[N:13]4)[CH2:23][CH2:22]3)[S:25][CH:26]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: NOc1ccccc1
Reactant: Cc1cc(C(F)(F)F)nn1CC(=O)N1CCC(c2nc(C=O)cs2)CC1
Solvent: CCO
Product: Cc1cc(C(F)(F)F)nn1CC(=O)N1CCC(c2nc(C=NOc3ccccc3)cs2)CC1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
At room temperature, O-phenylhydroxylamine (41 mg) and Amberlyst A21 (200 mg) are added to a solution of 2-(1-{[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazole-4-carbaldehyde (100 mg) in ethanol. The reaction mixture is stirred at room temperature for 24 hours. The solvent is then removed under reduced pressure. The residue is purified by column chromatography (silica gel, ethyl acetate:hexane 0%-100% elution gradient). This gives 2-(1-{[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazole-4-carbaldehyde O-phenyl oxime (50 mg, 40%) which consists of an about 9:1 mixture of cis and trans isomers (log P(pH2.7)=3.74 (93%), 3.94 (7%)).
Reaction SMILES: C[O:2][C:3]([C:5]1[N:6]=[CH:7][N:8]([C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH:11]=2)[CH:9]=1)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-]>>[CH:11]1[C:12]2[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:18]=[CH:19][C:10]=1[N:8]1[CH:9]=[C:5]([CH2:3][OH:2])[N:6]=[CH:7]1
Reactant: COC(=O)c1cn(-c2ccc3ccccc3c2)cn1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Product: OCc1cn(-c2ccc3ccccc3c2)cn1

Procedure:
Following the general method described in example 298, 1-naphthalen-2-yl-1H-imidazole-4-carboxylic acid methyl ester was reacted with lithium aluminum hydride followed by hydrolytic workup and chromatography. The title compound was obtained as a light brown gum. MS: m/e=225 (M+).
Reaction SMILES: [CH3:1][CH:2]([N:4]1[C:12](/[CH:13]=[CH:14]/[C@H:15]([OH:24])[CH2:16][C@H:17]([OH:23])[CH2:18][C:19]([O:21]C)=[O:20])=[C:11]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)[C:10]2[C:5]1=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH3:3].[OH-].[Na+:33]>ClCCl>[CH3:3][CH:2]([N:4]1[C:12](/[CH:13]=[CH:14]/[CH:15]([OH:24])[CH2:16][CH:17]([OH:23])[CH2:18][C:19]([O-:21])=[O:20])=[C:11]([C:25]2[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=2)[C:10]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]1=2)[CH3:1].[Na+:33]
Reactant: COC(=O)C[C@@H](O)C[C@@H](O)/C=C/c1c(-c2ccc(F)cc2)c2ccccc2n1C(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Product: CC(C)n1c(/C=C/C(O)CC(O)CC(=O)[O-])c(-c2ccc(F)cc2)c2ccccc21
Yield: 61.8 %

Procedure:
Fluvastatin methyl ester (3.0 g) was dissolved in dichloromethane (35 ml). NaOH (0.29 g) was added and the mixture was stirred at room over night. The product was isolated by filtration under nitrogen, washed with dichloromethane (20 ml) and dried at 50EC in a vacuum oven for 24 h to obtain 1.89 g (62%) of fluvastatin sodium Form C.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[C:5]([N:10]3[CH2:15][CH2:14][N:13]([CH2:16][C@H:17]([NH:25][CH3:26])[CH2:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=4)[CH2:12][CH2:11]3)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.C(=O)([O-])[O-].[K+].[K+].[CH3:33][C:34]1([C:40](Cl)=[O:41])[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1>ClCCl.O>[NH:1]1[C:9]2[C:4](=[C:5]([N:10]3[CH2:15][CH2:14][N:13]([CH2:16][C@H:17]([N:25]([CH3:26])[C:40]([C:34]4([CH3:33])[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]4)=[O:41])[CH2:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=4)[CH2:12][CH2:11]3)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1
Reactant: CN[C@H](Cc1ccccn1)CN1CCN(c2cccc3[nH]ccc23)CC1
Reactant: CC1(C(=O)Cl)CCCCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: O
Product: CN(C(=O)C1(C)CCCCC1)[C@H](Cc1ccccn1)CN1CCN(c2cccc3[nH]ccc23)CC1
Temperature: 25 °C

Procedure:
To a solution of (2R)-1-[4-(1H-indol-4-yl)piperazin-1-yl]-N-methyl-3-pyridin-2-ylpropan-2-amine (349 mg.; 1 mmol, from Example 20) in dichloromethane (10 mL) at 0° C. is added a solution of potassium carbonate (690 mg.; 5 mmol) in water (1.6 mL), followed by a solution of 1-methyl-1-cyclohexanecarbonyl chloride (160 mg.; 1 mmol) in dichloromethane (1.6 mL). The reaction mixture is stirred while allowing to warm to ambient temperature over 1 hour, diluted with dichloromethane (20 mL), and the layers allowed to separate. The organic layer is dried over MgSO4, filtered, and the solvent removed in vacuo. The crude residue is purified by flash chromatography on silica gel (10% methanol/ethyl acetate) to yield the free base of the title compound. The fumarate salt is prepared by treatment with an equimolar amount of fumaric acid in ethanol.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=13)[NH:8][CH2:7][N:6]([C@H:16]1[CH2:21][CH2:20][O:19][CH2:18][C@@H:17]1[O:22][Si](C(C)(C)C)(C)C)[C:5]2=[O:30].Cl.[C:32]([O-])(O)=O.[Na+]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=13)[N:8]([CH3:32])[CH2:7][N:6]([C@@H:16]1[C@@H:17]([OH:22])[CH2:18][O:19][CH2:20][CH2:21]1)[C:5]2=[O:30]
Reactant: CC(C)(C)[Si](C)(C)O[C@H]1COCC[C@@H]1N1CNc2c(cc(Br)c3ccccc23)C1=O
Reactant: O=C([O-])O
Agent: Cl
Agent: [Na+]
Solvent: C1CCOC1
Product: CN1CN([C@H]2CCOC[C@@H]2O)C(=O)c2cc(Br)c3ccccc3c21
Reaction time: 8 h

Procedure:
To a solution of 1,5-anhydro-3-(6-bromo-4-oxo-1,4-dihydrobenzo[h]quinazolin-3(2H)-yl)-2-O-[tert-butyl(dimethyl)silyl]-3,4-dideoxy-L-threo-pentitol (0.89 g, 1.8 mmol) in THF (17.5 mL) was added hydrochloric acid (1 N, 10 mL). Additional concentrated hydrochloric acid (2 mL) was added. After stirring overnight, the solution was basified by addition of saturated, aqueous NaHCO3, then extracted 2× with EtOAc. The organics were washed with brine, dried over MgSO4, filtered, concentrated, and dried to provide 1,5-anhydro-3-(6-bromo-1-methyl-4-oxo-1,4-dihydrobenzo[h]quinazolin-3(2H)-yl)-2,3-dideoxy-L-threo-pentitol that gave a mass ion (ES+) of 392.9 for [M+H]+.
Reaction SMILES: C(OC([NH:8][C:9]1([C:18]([OH:20])=[O:19])[CH2:16][CH:15]2[NH:17][CH:11]([CH2:12][O:13][CH2:14]2)[CH2:10]1)=O)(C)(C)C.Br[CH2:22][C:23]1[NH:28][C:27]([C:29]2[S:30][CH:31]=[CH:32][N:33]=2)=[N:26][C@@H:25]([C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[C:35]=2[F:41])[C:24]=1[C:42]([O:44][CH2:45][CH3:46])=[O:43]>>[NH2:8][C:9]1([C:18]([OH:20])=[O:19])[CH2:10][CH:11]2[N:17]([CH2:22][C:23]3[NH:28][C:27]([C:29]4[S:30][CH:31]=[CH:32][N:33]=4)=[N:26][C@@H:25]([C:34]4[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[C:35]=4[F:41])[C:24]=3[C:42]([O:44][CH2:45][CH3:46])=[O:43])[CH:15]([CH2:14][O:13][CH2:12]2)[CH2:16]1
Reactant: CC(C)(C)OC(=O)NC1(C(=O)O)CC2COCC(C1)N2
Reactant: CCOC(=O)C1=C(CBr)NC(c2nccs2)=N[C@H]1c1cccc(F)c1F
Product: CCOC(=O)C1=C(CN2C3COCC2CC(N)(C(=O)O)C3)NC(c2nccs2)=N[C@H]1c1cccc(F)c1F
Yield: 8.4 %

Procedure:
The title compound was prepared in analogy to Example 133 by using 7-(tert-butoxycarbonylamino)-3-oxa-9-azabicyclo[3.3.1]nonane-7-carboxylic acid 139a (49 mg) and ethyl (4R)-6-(bromomethyl)-4-(2,3-difluoro-phenyl)-2-thiazol-2-yl-1,4-dihydropyrimidine-5-carboxylate 140a (48 mg). 5 mg of the title compound was isolated.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3](B(O)O)[CH:2]=1.C([O-])([O-])=O.[Na+].[Na+].Cl[C:17]1[N:22]2[N:23]=[C:24]([NH2:26])[N:25]=[C:21]2[CH:20]=[C:19]([C:27]2[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=2)[CH:18]=1.C(Cl)Cl>C1(C)C=CC=CC=1>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:17]2[N:22]3[N:23]=[C:24]([NH2:26])[N:25]=[C:21]3[CH:20]=[C:19]([C:27]3[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=3)[CH:18]=2)[CH:2]=1
Reactant: OB(O)c1cccnc1
Reactant: Nc1nc2cc(-c3cccnc3)cc(Cl)n2n1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: Nc1nc2cc(-c3cccnc3)cc(-c3cccnc3)n2n1

Procedure:
A mixture of 3-pyridine boronic acid pinacolate ester (500 mg, 2.44 mmol), Na2CO3 (649 mg, 6.12 mmol) and 5-chloro-7-pyridin-3-yl-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine, which may be produced as in Example 1A, (500 mg, 2.04 mmol) in toluene (30 mL), ethanol (15 mL) and water (15 mL) was degassed by purging with N2 for 10 min. [PdCl2(dppf)].CH2Cl2 (56 mg, 0.082 mmol) was added and the mixture was brought to reflux for 36 h. The solvent was evaporated and the residue was extracted into hot EtOH/MeOH, filtered through Celite, and pre-adsorbed onto SiO2. Column chromatography (0-10% MeOH in CH2Cl2) afforded the product 5,7-di-pyridin-3-yl-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine as a solid. MS m/z 289 (M+H+).
Reaction SMILES: [CH3:1][C@H:2]([NH:6][C:7]([O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:8])[C:3]([OH:5])=O.Cl.[NH2:18][CH2:19][C:20]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:21].CN1CCOCC1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>ClCCl>[CH2:10]([O:9][C:7](=[O:8])[NH:6][CH:2]([C:3](=[O:5])[NH:18][CH2:19][C:20](=[O:21])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH3:1])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: C[C@H](NC(=O)OCc1ccccc1)C(=O)O
Reactant: NCC(=O)c1ccccc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCl
Solvent: CN1CCOCC1
Product: CC(NC(=O)OCc1ccccc1)C(=O)NCC(=O)c1ccccc1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
To a solution of commercially available N-α-CBZ-L-alanine (2.11 g, 9.5 mmol) in dichloromethane (50 mL) was added 2-aminoacetophenone hydrochloride (1.62 g, 9.5 mmol). The resulting solution was cooled to 0° C. and N-methylmorpholine (1.15 g, 11 mmol), 1-hydroxybenzotriazole (2.55 g, 18.9 mmol) and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (2.35 g, 12.3 mmol), in that order, were added under an Argon atmosphere. The reaction mixture was warmed to room temperature and stirred overnight. The reaction was quenched by addition of saturated aqueous NaHCO3 solution; the separated organic phase was washed with 2N citric acid, saturated NaHCO3 solution and brine, then dried over MgSO4 overnight. After filtration and concentration, the residue was purified by column chromatography on silica gel (eluent, EtOAc:hexane-1:1) to yield the title compound, [1-(2-oxo-2-phenyl-ethylcarbamoyl)-ethyl]-carbamic acid benzyl ester.
Reaction SMILES: [CH3:1][N:2](S(C1C=CC(C)=CC=1)(=O)=O)[N:3]=[C:4](Cl)[C:5]1[C:10]([F:11])=[CH:9][CH:8]=[CH:7][C:6]=1[Cl:12].[Cl:24][C:25]1[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[CH:27][C:26]=1[O:33][CH2:34][CH2:35][CH2:36][CH2:37][CH3:38].ClC1C=CC=CC=1Cl>C(Cl)(Cl)Cl.[Fe](Cl)(Cl)Cl>[Cl:12][C:6]1[CH:7]=[CH:8][CH:9]=[C:10]([F:11])[C:5]=1[C:4]1[N:30]=[C:29]([C:28]2[CH:31]=[CH:32][C:25]([Cl:24])=[C:26]([O:33][CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])[CH:27]=2)[N:2]([CH3:1])[N:3]=1
Reactant: CCCCCOc1cc(C#N)ccc1Cl
Reactant: Cc1ccc(S(=O)(=O)N(C)N=C(Cl)c2c(F)cccc2Cl)cc1
Agent: Cl[Fe](Cl)Cl
Solvent: ClC(Cl)Cl
Solvent: Clc1ccccc1Cl
Product: CCCCCOc1cc(-c2nc(-c3c(F)cccc3Cl)nn2C)ccc1Cl
Temperature: 140 °C
Reaction time: 0.5 h
Yield: 41.8 %

Procedure:
A mixture of N-methyl-N-(p-toluenesulfonyl)-2-chloro-6-fluorobenzohydrazonoyl chloride (1.10 g), 4-chloro-3-pentyloxybenzonitrile (0.70 g), anhydrous iron (III) chloride (0.60 g) and o-dichlorobenzene (5 ml) is stirred at an oil bath temperature of 140° C. for 30 minutes. After cooling, the reaction mixture is dissolved in chloroform (100 ml), washed with dilute hydrochloric acid, dilute aqueous solution of sodium hydroxide and saline in this order, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate is purified by silica gel column chromatography using mixed solvent of hexane-ethyl acetate as eluent to give 0.50 g of desired compound.
Reaction SMILES: [Br:1][C:2]1[C:11]([CH3:12])=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][C:6](=[O:13])[NH:7]2.[N-]=[N+]=[N-].[Na+].[C:18]([O-])(O)=O.[Na+]>CS(O)(=O)=O>[Br:1][C:2]1[C:3]2[CH2:18][CH2:4][CH2:5][C:6](=[O:13])[NH:7][C:8]=2[CH:9]=[CH:10][C:11]=1[CH3:12]
Reactant: O=C([O-])O
Reactant: Cc1ccc2c(c1Br)CCC(=O)N2
Agent: CS(=O)(=O)O
Agent: [N-]=[N+]=[N-]
Agent: [Na+]
Product: Cc1ccc2c(c1Br)CCCC(=O)N2

Procedure:
5-Bromo-6-methyl-3,4-dihydroquinolin-2(1H)-one (477.7 mg, 1.998 mmol) was treated with NaN3 (194.8 mg, 0.938 mmol, 1.5 equiv) in MeSO3H (3 g) at 0° C. to room temperature for 1 h. The mixture was neutralized with NaHCO3 and extracted with EtOAc (30 mL×3). The organic layer was washed with brine (30 mL) and dried over Na2SO4. The solvent was removed under a reduced pressure and the crude product was recrystallized from EtOAc (10 mL) to give 6-bromo-7-methyl-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[C:12]3[C:19]([CH3:22])=[N:20][O:21][C:11]=3[C@H:10]([CH2:23][C:24]([O:34]C)([O:29][Si](C)(C)C)[C:25]([F:28])([F:27])[F:26])[N:9]=2)=[CH:4][CH:3]=1.[F-].[Cs+]>CO.CC(OC)(C)C.Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[C:12]3[C:19]([CH3:22])=[N:20][O:21][C:11]=3[C@H:10]([CH2:23][C:24]([OH:29])([OH:34])[C:25]([F:28])([F:27])[F:26])[N:9]=2)=[CH:4][CH:3]=1
Reactant: COC(C[C@@H]1N=C(c2ccc(Cl)cc2)c2ccccc2-c2c(C)noc21)(O[Si](C)(C)C)C(F)(F)F
Agent: Cl
Agent: [Cs+]
Agent: [F-]
Solvent: CO
Solvent: COC(C)(C)C
Product: Cc1noc2c1-c1ccccc1C(c1ccc(Cl)cc1)=N[C@H]2CC(O)(O)C(F)(F)F

Procedure:
To a cooled (0° C.) solution of crude (4S)-6-(4-chlorophenyl)-1-methyl-4-(3,3,3-trifluoro-2-methoxy-2-((trimethylsilyl)oxy)propyl)-4H-benzo[c]isoxazolo[4,5-e]azepine in MeOH (3 mL) was added CsF (0.048 g, 0.316 mmol). The reaction was maintained at 0° C. for 30-60 min or until complete conversion of starting material to the desired ketone/di-hydrate was observed. The reaction mixture was diluted with MTBE and aqueous 1 N HCl was added until a phase cut was observed. The aqueous phase was extracted with MTBE (3×), the combined organic phases were washed with water, dried over Na2SO4, and concentrated to give the desired product as an orange oil. The product 3-((4S)-6-(4-chlorophenyl)-1-methyl-4H-benzo[c]isoxazolo[4,5-e]azepin-4-yl)-1,1,1-trifluoropropane-2,2-diol (0.121 g, 0.277 mmol, 96% yield) was used without further purification. LC/MS m/z 437 [M+H]+.
Reaction SMILES: Cl.[NH2:2][C:3]1[NH:4][CH:5]=[CH:6][N:7]=1.N1C=CC=CC=1.[C:14](Cl)(=[O:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>O>[C:15]1([C:14]([NH:2][C:3]2[NH:4][CH:5]=[CH:6][N:7]=2)=[O:21])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: Nc1ncc[nH]1
Agent: Cl
Solvent: c1ccncc1
Solvent: O
Product: O=C(Nc1ncc[nH]1)c1ccccc1
Temperature: 25 °C

Procedure:
To a suspension of 6.8 g. of 2-aminoimidazole hydrochloride in 100 ml. of pyridine at -20°C. there is added 6.8 ml. of benzoyl chloride. The thus-obtained reaction mixture is allowed to warm slowly to between 20°-30°C. (room temperature), and maintained at this temperature for 12 hours, diluted with water and filtered to give a residue which is recrystallized from methanol to yield 2-phenylcarbonylaminoimidazole [(III), R = phenyl].
Reaction SMILES: [NH2:1][C:2]([C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:8][CH:7]=1)=[CH:3][C:4]#[N:5].[N+:19]([C:22]1[CH:27]=[CH:26][C:25]([C:28](=O)[CH2:29][C:30](OCC)=[O:31])=[CH:24][CH:23]=1)([O-:21])=[O:20]>CN(C)C(=O)C>[N+:19]([C:22]1[CH:23]=[CH:24][C:25]([C:28]2[NH:1][C:2]([C:6]3[CH:11]=[CH:10][C:9]([O:12][C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)=[CH:8][CH:7]=3)=[C:3]([C:4]#[N:5])[C:30](=[O:31])[CH:29]=2)=[CH:26][CH:27]=1)([O-:21])=[O:20]
Reactant: N#CC=C(N)c1ccc(Oc2ccccc2)cc1
Reactant: CCOC(=O)CC(=O)c1ccc([N+](=O)[O-])cc1
Solvent: CC(=O)N(C)C
Product: N#Cc1c(-c2ccc(Oc3ccccc3)cc2)[nH]c(-c2ccc([N+](=O)[O-])cc2)cc1=O
Temperature: 25 °C
Yield: 120.7 %

Procedure:
A mixture of 3-amino-3-(4-phenoxyphenyl)acrylonitrile (101 mg, 0.427 mmol) and ethyl 3-(4-nitrophenyl)-3-oxopropanoate (312.8 mg, 1.319 mmol) in N,N-dimethylacetamide (1 mL) was microwaved at 230° C. for 20 min, cooled to room temperature, and concentrated. Silica gel chromatography, eluting with 0-5% methanol in dichloromethane, gave 6-(4-nitrophenyl)-4-oxo-2-(4-phenoxyphenyl)-1,4-dihydropyridine-3-carbonitrile as brown solid (211 mg, 100% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.31 (2H, δ, J=8.78 Hz), 8.19 (2H, br. s), 7.96 (2H, br. s), 7.39 (2H, t, J=7.91 Hz), 7.18 (1H, t, J=7.40 Hz), 7.06-7.13 (3H, m); MS (ES+) m/z: 410 (M+H); LC retention time: 4.275 min (analytical HPLC Method A).
Reaction SMILES: [O-:1]Cl=O.[Na+].[CH2:5]([O:12][C:13]1[CH:20]=[CH:19][C:16]([CH:17]=[O:18])=[C:15]([CH2:21][CH3:22])[CH:14]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1>CS(C)=O>[CH2:5]([O:12][C:13]1[CH:20]=[CH:19][C:16]([C:17]([OH:1])=[O:18])=[C:15]([CH2:21][CH3:22])[CH:14]=1)[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1
Reactant: [O-][Cl+][O-]
Reactant: CCc1cc(OCc2ccccc2)ccc1C=O
Agent: [Na+]
Solvent: CS(C)=O
Product: CCc1cc(OCc2ccccc2)ccc1C(=O)O
Temperature: 25 °C
Reaction time: 3 h

Procedure:
An aqueous solution (750 ml) of 85 g of NaClO2 and 90 g of NaH2PO4 is added dropwise with cooling and stirring to 120 g of 4-benzyloxy-2-ethylbenzaldehyde, dissolved in 1 l of DMSO, during which the temperature should not rise above 35° C. The mixture is stirred at RT for a further 3 h, and the precipitate formed is filtered off with suction. The solid is then dissolved in 600 ml of EtOAc, dried and re-evaporated. The residue is crystallised from (Me2CH)2O, giving 4-benzyloxy-2-ethylbenzoic acid; yield 96.2 g (75%); m.p. 132-133°.
Reaction SMILES: [CH2:1]([C:3]1[S:7][C:6]([C:8]2[O:12][N:11]=[C:10]([C:13]3[CH:18]=[C:17]([CH3:19])[C:16]([OH:20])=[C:15]([CH3:21])[CH:14]=3)[N:9]=2)=[CH:5][CH:4]=1)[CH3:2].Cl[CH2:23][C@H:24]([OH:27])[CH2:25][OH:26]>C(O)(C)C.[OH-].[Na+].O>[CH2:1]([C:3]1[S:7][C:6]([C:8]2[O:12][N:11]=[C:10]([C:13]3[CH:18]=[C:17]([CH3:19])[C:16]([O:20][CH2:23][C@H:24]([OH:27])[CH2:25][OH:26])=[C:15]([CH3:21])[CH:14]=3)[N:9]=2)=[CH:5][CH:4]=1)[CH3:2]
Reactant: CCc1ccc(-c2nc(-c3cc(C)c(O)c(C)c3)no2)s1
Reactant: OC[C@@H](O)CCl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(C)O
Product: CCc1ccc(-c2nc(-c3cc(C)c(OC[C@H](O)CO)c(C)c3)no2)s1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 4-[5-(5-ethyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethyl-phenol (79 mg, 0.263 mmol) in isopropanol (3 mL) and 3 N aq. NaOH (0.6 mL), (R)-3-chloro-propane-1,2-diol (148 mg, 1.31 mmol) is added. The mixture is stirred at rt for 2 h, then at 65° C. for 16 h before another portion of (R)-3-chloro-propane-1,2-diol (119 mg, 1.05 mmol) is added. Stirring is continued at 65° C. for 24 h. The reaction mixture is diluted with water and extracted with diethyl ether. The org. extract is dried over MgSO4, filtered and evaporated. The crude product is purified by chromatography on prep. TLC plates with DCM containing 4% of 7 N NH3 in methanol to give (2R)-3-{4-[5-(5-ethyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethyl-phenoxy}-propane-1,2-diol as an off-white solid; LC-MS: tR=0.99 min; [M+1]+=375.13; 1H NMR (CDCl3): δ 7.83 (s, 2H), 7.80 (d, J=3.8 Hz, 1H), 6.93 (d, J=3.8 Hz, 1H), 4.20-4.11 (m, 1H), 3.97-3.93 (m, 1H), 3.91 (dd, J=11.5, 4.3 Hz, 1H), 3.85 (dd, J=11.5, 5.5 Hz, 1H), 2.97 (q, J=7.5 Hz, 2H), 2.39 (s, 6H), 1.41 (t, J=7.5 Hz, 3H).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:19])[C:5]([CH:7]1[CH2:16][CH2:15][C:14]2[CH:13]=[N:12][C:11]([Cl:17])=[CH:10][C:9]=2[C:8]1=O)=O)[CH3:2].[NH2:20][NH2:21].O>CCO>[CH2:1]([O:3][C:4]([C:5]1[NH:20][N:21]=[C:8]2[C:9]3[C:14](=[CH:13][N:12]=[C:11]([Cl:17])[CH:10]=3)[CH2:15][CH2:16][C:7]=12)=[O:19])[CH3:2]
Reactant: CCOC(=O)C(=O)C1CCc2cnc(Cl)cc2C1=O
Reactant: NN
Solvent: O
Solvent: CCO
Product: CCOC(=O)c1[nH]nc2c1CCc1cnc(Cl)cc1-2

Procedure:
(3-Chloro-5-oxo-5,6,7,8-tetrahydro-isoquinolin-6-yl)-oxo-acetic acid ethyl ester (1.4 g; 4.8 mmol) in EtOH (15 ml) is combined with H2NNH2.H2O (242 mg; 4.8 mmol) and refluxed for 1 hour. The mixture is left over night at room temperature and delivers the title compound as yellowish crystals. 1H-NMR (400 MHz; DMSO-d6): 8.37 (s, 1H); 7.68 (s, 1H); 4.36 (q, 2H); 3.5 (bs, 1H); 2.99 (m, 2H); 2.97 (m, 2H); 1.35 (t, 3H). MS (m/z) ES+: 278 (MH+).
Reaction SMILES: [Br-:1].[Br-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:22]([Si:25]([CH2:37][CH:38]=[CH2:39])([CH2:34][CH:35]=[CH2:36])[CH2:26][CH2:27][CH2:28][Si:29](OC)([CH3:31])[CH3:30])[CH:23]=[CH2:24]>ClCCl>[CH2:22]([Si:25]([CH2:37][CH:38]=[CH2:39])([CH2:34][CH:35]=[CH2:36])[CH2:26][CH2:27][CH2:28][Si:29]([Br:1])([CH3:31])[CH3:30])[CH:23]=[CH2:24]
Reactant: C=CC[Si](CC=C)(CC=C)CCC[Si](C)(C)OC
Reactant: [Br-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: C=CC[Si](CC=C)(CC=C)CCC[Si](C)(C)Br
Temperature: 25 °C
Reaction time: 5 h

Procedure:
To triphenylphosphine dibromide (2.3 g, 5.5 mmol), distilled dichloromethane (15 ml) was added under a nitrogen atmosphere, to dissolve. Then, a solution, in which {3-(triallylsilyl)propyl}(methoxy)dimethylsilane (32) (1.5 g, 5.0 mmol) is dissolved in distilled dichloromethane (5 ml), was added and stirred at room temperature for 5 hours to obtain {3-(triallylsilyl)propyl}(bromo)dimethylsilane (33). After stirring, glass beads which was treated with Piranha solution was added and stirred further at room temperature for 4 hours. Water was added to the reaction mixture to stop the reaction, then 10% hydrochloric acid was added until the salt was dissolved. After that, glass beads were filtered out and washed each three times with toluene, ethanol and diethyl ether, dried, obtaining a functional material (34) represented by the following chemical reaction equation.
Reaction SMILES: Cl.[CH2:2]([O:5][C:6]1[CH:7]=[C:8]([CH:11]=[CH:12][C:13]=1[O:14][CH3:15])[CH2:9][NH2:10])[CH2:3][CH3:4].[Cl:16][C:17]1[C:18](=[O:27])[N:19]([CH:24]([CH3:26])[CH3:25])[N:20]=[CH:21][C:22]=1Cl.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1>O>[Cl:16][C:17]1[C:18](=[O:27])[N:19]([CH:24]([CH3:25])[CH3:26])[N:20]=[CH:21][C:22]=1[NH:10][CH2:9][C:8]1[CH:11]=[CH:12][C:13]([O:14][CH3:15])=[C:6]([O:5][CH2:2][CH2:3][CH3:4])[CH:7]=1
Reactant: CC(C)n1ncc(Cl)c(Cl)c1=O
Reactant: CCCOc1cc(CN)ccc1OC
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1COCCO1
Product: CCCOc1cc(CNc2cnn(C(C)C)c(=O)c2Cl)ccc1OC
Reaction time: 8 h

Procedure:
A mixture comprising 1.34 g of 3-n-propoxy-4-methoxybenzylamine hydrochloride, 0.4 g of 4,5-dichloro-2-i-propyl-3(2H)pyridazinone, 1.08 g of potassium carbonate, 6 ml of 1,4-dioxane and 18 ml of water was refluxed under stirring for 8 hours. The solvent was distilled off under reduced pressure, and water was added to the the residue thereby obtained, and then the mixture was extracted with ethyl acetate. The extract was washed successively with diluted hydrochloric acid, water and a saturated sodium chloride aqueous solution, and dried over sodium sulfate, and then the solvent was distilled off. The product was crystallized from ethyl acetate-diethyl ether-n-hexane to obtain 230 mg of the above identified compound having a melting point of from 120° to 122° as colorless crystals.
Reaction SMILES: [Br:1][C:2]1[CH:8]=[C:7]([Cl:9])[CH:6]=[C:5]([CH3:10])[C:3]=1[NH2:4].[N:11]([O-])=O.[Na+]>C(O)(=O)C.O>[Br:1][C:2]1[CH:8]=[C:7]([Cl:9])[CH:6]=[C:5]2[C:3]=1[NH:4][N:11]=[CH:10]2
Reactant: Cc1cc(Cl)cc(Br)c1N
Reactant: O=N[O-]
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: Clc1cc(Br)c2[nH]ncc2c1
Temperature: 25 °C
Reaction time: 4 h
Yield: 88.1 %

Procedure:
2.20 g (10 mmol) of 2-bromo-4-chloro-6-methyl aniline were dissolved in 125 ml acetic acid. 0.69 g (10 mmol) of sodium nitrite dissolved in 2 ml water were added dropwise. The reaction mixture was stirred at rt for 4 h. Acetic acid was evaporated and the residue dissolved in EtOAc. The organic layer was washed with water, dried over sodium sulfate, filtered and the solvent was evaporated. The residue was several times evaporated with heptane to yield 2.04 g (88%) of 7-bromo-5-chloro-1H-indazol as a light brown solid. 1H NMR (DMSO-d6, 300 MHz): δ 8.23 (s, 1H), 7.91 (s, 1H), 7.67 (s, 1H).