Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC([N:8]1[CH:12]=[CH:11][CH:10]=[C:9]1[C:13]1[CH:14]=[N:15][C:16]([NH2:29])=[C:17]([O:19][CH2:20][C:21]2[C:26]([Cl:27])=[CH:25][CH:24]=[CH:23][C:22]=2[Cl:28])[CH:18]=1)=O)(C)(C)C.C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.O>[Cl:27][C:26]1[CH:25]=[CH:24][CH:23]=[C:22]([Cl:28])[C:21]=1[CH2:20][O:19][C:17]1[C:16]([NH2:29])=[N:15][CH:14]=[C:13]([C:9]2[NH:8][CH:12]=[CH:11][CH:10]=2)[CH:18]=1
Reactant: CC(C)(C)OC(=O)n1cccc1-c1cnc(N)c(OCc2c(Cl)cccc2Cl)c1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: Nc1ncc(-c2ccc[nH]2)cc1OCc1c(Cl)cccc1Cl
Temperature: 25 °C

Procedure:
To a mixture of 2-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl]-pyrrole-1-carboxylic acid tert-butyl ester (Example 6, 30 mg, 0.069 mmol) in ethanol/water (2:1, 10 mL) was added sodium carbonate (100 mg, 0.95 mmol). The mixture was refluxed overnight. The reaction was cooled to ambient temperature and extracted with ethyl acetate. The mixture was washed with water, brine, dried over Na2SO4, and purified on a silica gel column to afford 3-(2,6-dichloro-benzyloxy)-5-(1H-pyrrol-2-yl)-pyridin-2-ylamine.
Reaction SMILES: [CH3:1][C:2]1[CH:6]=[C:5]([NH2:7])[NH:4][N:3]=1.[F:8][C:9]1[CH:10]=[C:11]([C:16](=O)[CH2:17][C:18](OCC)=[O:19])[CH:12]=[C:13]([F:15])[CH:14]=1>N1C=CC=CC=1>[F:8][C:9]1[CH:10]=[C:11]([C:16]2[N:4]3[N:3]=[C:2]([CH3:1])[CH:6]=[C:5]3[NH:7][C:18](=[O:19])[CH:17]=2)[CH:12]=[C:13]([F:15])[CH:14]=1
Reactant: Cc1cc(N)[nH]n1
Reactant: CCOC(=O)CC(=O)c1cc(F)cc(F)c1
Solvent: c1ccncc1
Product: Cc1cc2[nH]c(=O)cc(-c3cc(F)cc(F)c3)n2n1
Temperature: 25 °C
Yield: 36.8 %

Procedure:
3-Methylpyrazol-5-amine (526 mg) and ethyl 3-(3,5-difluorophenyl)-3-oxopropanoate (879 g) are stirred overnight in a pyridine (30 mL) solvent at 85° C. After cooling to room temperature, the reaction solvent is removed by distillation under reduced pressure. The remainder is extracted with ethyl acetate and water. The extracted organic layer is washed with brine and dehydrated with anhydrous MgSO4. The dehydrated organic layer is distilled under reduced pressure and purified by column chromatography to yield the target compound (521 mg).
Reaction SMILES: [CH:1]1([NH:4][C:5]([C@@H:7]2[C@H:11]([CH2:12][OH:13])[CH2:10][N:9]([C@H:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH3:15])[CH2:8]2)=[O:6])[CH2:3][CH2:2]1.N1C=CN=C1.[C:27]([Si:31](Cl)([CH3:33])[CH3:32])([CH3:30])([CH3:29])[CH3:28]>CN(C)C=O>[CH:1]1([NH:4][C:5]([C@@H:7]2[C@H:11]([CH2:12][O:13][Si:31]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:33])[CH3:32])[CH2:10][N:9]([C@H:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH3:15])[CH2:8]2)=[O:6])[CH2:2][CH2:3]1
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: C[C@@H](c1ccccc1)N1C[C@@H](CO)[C@@H](C(=O)NC2CC2)C1
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: C[C@@H](c1ccccc1)N1C[C@@H](CO[Si](C)(C)C(C)(C)C)[C@@H](C(=O)NC2CC2)C1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 67 %

Procedure:
(3R,4S)-N-Cyclopropyl-4-hydroxymethyl-1-[(1S)-1-phenylethyl]pyrrolidine-3-carboxamide (7.54 g) was dissolved in N,N-dimethylformamide (180 mL). While this solution was cooled on an ice bath, imidazole (2.67 g) and tert-butylchlorodimethylsilane (4.72 g) were sequentially added. The mixture was stirred at room temperature for 90 min and was subsequently concentrated under reduced pressure. The resulting residue was dissolved in ethyl acetate (300 mL) and the solution was washed with water (2×100 mL), followed by drying over anhydrous sodium sulfate and concentration under reduced pressure. The resulting residue was purified on a silica gel column (eluant=ethyl acetate) to give 7.05 g of (3R,4S)-N-cyclopropyl-4-(tert-butyldimethylsilyl)oxymethyl-1-[(1S)-1-phenylethyl]pyrrolidine-3-carboxamide as a pale yellow tar-like product.
Reaction SMILES: [CH3:1][S:2][C:3]1[C:4]([NH:13][C:14](=[O:25])[CH:15](Br)[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[CH:6]2.[CH2:26]([NH2:32])[CH2:27][CH2:28][CH2:29][CH2:30][CH3:31].C(OCC)(=O)C>CCCCCC>[CH3:1][S:2][C:3]1[C:4]([NH:13][C:14](=[O:25])[CH:15]([NH:32][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[CH:6]2
Reactant: CCCCCCN
Reactant: CCCCCCCCC(Br)C(=O)Nc1c(SC)ccc2ncccc12
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: CCCCCCCCC(NCCCCCC)C(=O)Nc1c(SC)ccc2ncccc12
Temperature: 120 °C
Yield: 88 %

Procedure:
A mixture of N-(6-methylthioquinolin-5-yl)-2-bromodecanamide (200 mg, 0.47 mmol) and n-hexylamine (10 ml) was heated at 120° C. for 1 hour, cooled to room temperature, and chromatographed using 1:24:25/triethylamine:ethyl acetate:hexane as eluants to give the title compound as a pink oil (184 mg, 88% yield).
Reaction SMILES: Br[C:2]1[C:3]([C:12]2[C:13]([F:22])=[CH:14][C:15]([Cl:21])=[C:16]([CH:20]=2)[C:17]([OH:19])=[O:18])=[N:4][N:5]([CH3:11])[C:6]=1[C:7]([F:10])([F:9])[F:8].[H-].[Na+].C([Li])CCC.CN(C)[CH:32]=[O:33]>O1CCCC1>[Cl:21][C:15]1[CH:14]=[C:13]([F:22])[C:12]([C:3]2[C:2]([CH:32]=[O:33])=[C:6]([C:7]([F:10])([F:9])[F:8])[N:5]([CH3:11])[N:4]=2)=[CH:20][C:16]=1[C:17]([OH:19])=[O:18]
Reactant: CN(C)C=O
Reactant: Cn1nc(-c2cc(C(=O)O)c(Cl)cc2F)c(Br)c1C(F)(F)F
Agent: [H-]
Agent: [Li]CCCC
Agent: [Na+]
Solvent: C1CCOC1
Product: Cn1nc(-c2cc(C(=O)O)c(Cl)cc2F)c(C=O)c1C(F)(F)F
Temperature: 60 °C

Procedure:
To a mechanically stirred solution of 10 g of 5-[4-bromo-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]-2-chloro-4-fluorobenzoic acid in 400 ml of anhydrous tetrahydrofuran under a nitrogen atmosphere was added 1.0 g of 95% sodium hydride. After the foaming subsided, the reaction was stirred and heated to 60° C. for one hour to ensure complete anion formation of the acid. The reaction was cooled to -110° C. with vigorous stirring and a 10.8 mL of 2.5M n-butyl lithium in hexanes was added maintaining the temperature below -100° C. As soon as the addition of n-butyl lithium was completed, 10 mL of dimethyl formamide was added and the solution was allowed to warm to -20° C. The reaction was then quenched with 3N HCl, and most of the volatiles were removed from the reaction mixture. The precipitate was filtered and recrystalized from carbon tetrachloride to give-3.0 g of 2-chloro-4-fluoro-5-[4-formyl-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]benzoic acid: mp 163° C.; 1HNMR (CDCl3) ppm: 9.82 (s, 1H), 7.89 (d, 1H, J=7.6), 7.07 (d, 1H, J=9.2), 3.39 (s, 3H). 19FNMR (CDCl3) ppm: -57.78, -107.41.
Reaction SMILES: C(N(CC)CC)C.[CH:8]1([NH:14][S:15]([C:18]([Cl:22])=[C:19]([Cl:21])[Cl:20])(=[O:17])=[O:16])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1.[Cl:23][C:24]([Cl:30])([S:28]Cl)[CH:25]([Cl:27])[Cl:26]>ClCCl>[CH:8]1([N:14]([S:28][C:24]([Cl:30])([Cl:23])[CH:25]([Cl:27])[Cl:26])[S:15]([C:18]([Cl:22])=[C:19]([Cl:20])[Cl:21])(=[O:17])=[O:16])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]1
Reactant: ClSC(Cl)(Cl)C(Cl)Cl
Reactant: O=S(=O)(NC1CCCCC1)C(Cl)=C(Cl)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=S(=O)(C(Cl)=C(Cl)Cl)N(SC(Cl)(Cl)C(Cl)Cl)C1CCCCC1
Temperature: 25 °C
Reaction time: 3 h
Yield: 72 %

Procedure:
A 4.0 g (0.04 mol) sample of triethylamine was added dropwise to a cooled (-10° to 0° C.) solution of 9.5 g (0.0324 mol) N-(cyclohexyl)trichlorovinylsulfonamide, m.p. 152°-153° C., and 7.6 g (0.0324 mol) 1,1,2,2-tetrachloroethylsulfenyl chloride in 200 ml dichloromethane. The reaction mixture was then stirred at about 25° C. for 3 hours, washed with water, dried over magnesium sulfate and evaporated to give an oil. The oil was chromatographed on silica gel. The N-cyclohexyl-N-(1,1,2,2-tetrachloroethylthio)trichlorovinylsulfonamide product, 11 g (72% yield), was eluted from the silica gel with 30% ether/20% hexane. The infrared spectrum of the product showed strong absorption bands at 1385 cm-1 and 1160 cm-1. The elemental analysis for the product is tabulated in Table I under Compound No. 6.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]([C:11](=O)[CH3:12])[C:8]([C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[C:16]([F:21])[CH:15]=2)=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2.C([O-])(=O)C.[NH4+].C([BH3-])#[N:28].[Na+]>CO.C(#N)C>[Cl:1][C:2]1[CH:10]=[C:9]([CH:11]([NH2:28])[CH3:12])[C:8]([C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[C:16]([F:21])[CH:15]=2)=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2
Reactant: [BH3-]C#N
Reactant: CC(=O)c1cc(Cl)c2cn[nH]c2c1-c1cc(F)cc(F)c1
Agent: CC(=O)[O-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CC#N
Solvent: CO
Product: CC(N)c1cc(Cl)c2cn[nH]c2c1-c1cc(F)cc(F)c1
Temperature: 65 °C

Procedure:
A mixture of 1-[4-chloro-7-(3,5-difluorophenyl)-1H-indazol-6-yl]ethanone (0.20 g, 0.65 mmol) and ammonium acetate (0.50 g, 6.5 mmol) and sodium cyanoborohydride (0.082 g, 1.3 mmol) in methanol (2 mL) and acetonitrile (2 mL) was heated at 65° C. overnight in a sealed tube. The mixture was then cooled to room temperature and quenched with sat. sodium bicarbonate and then extracted with dichloromethane. The combined extracts were dried over magnesium sulfate and evaporated to dryness to give the crude amine which was used directly in the next step. LCMS calculated for C15H10ClF2N2 (M−NH2)+: m/z=291.0; Found: 291.0.
Reaction SMILES: C([O-])(=O)C.[K+].Cl[C:7]1[C:8]([O:13][C:14]2[CH:23]=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][CH:15]=2)=[N:9][CH:10]=[CH:11][N:12]=1.CC1(C)C(C)(C)OB([C:32]2[CH2:33][CH2:34][CH2:35][N:36]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH:37]=2)O1>CC#N>[CH3:21][O:20][C:18]([C:17]1[CH:22]=[CH:23][C:14]([O:13][C:8]2[C:7]([C:34]3[CH2:33][CH2:32][CH2:37][N:36]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH:35]=3)=[N:12][CH:11]=[CH:10][N:9]=2)=[CH:15][CH:16]=1)=[O:19]
Reactant: COC(=O)c1ccc(Oc2nccnc2Cl)cc1
Reactant: CC(C)(C)OC(=O)N1C=C(B2OC(C)(C)C(C)(C)O2)CCC1
Agent: CC(=O)[O-]
Agent: [K+]
Solvent: CC#N
Product: COC(=O)c1ccc(Oc2nccnc2C2=CN(C(=O)OC(C)(C)C)CCC2)cc1
Temperature: 80 °C

Procedure:
To a mixture of (amphos)2PdCl2 (0.145 g, 0.205 mmol), potassium acetate (1.045 g, 10.65 mmol), methyl 4-(3-chloropyrazin-2-yloxy)benzoate (1.084 g, 4.10 mmol), and tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydropyridine-1(2H)-carboxylate (1.900 g, 6.14 mmol) under N2 was added MeCN (7.0 mL) and Ar degassed water (0.70 mL). The reaction mixture was degassed with Ar (10 min) then heated to 80° C. for 20 h. The reaction mixture was diluted with H2O (20 mL) and extracted with Teac (2×10 mL). The combined organic extracts were washed with brine (10 mL), dried (MgSO4), and concentrated. Purification by ISCO (120 g SiO2, 10-100% Teac/hexanes) gave tert-butyl 5-(3-(4-(methoxycarbonyl)phenoxy)pyrazin-2-yl)-3,4-dihydropyridine-1(2H)-carboxylate as a yellow oil.
Reaction SMILES: [CH3:1][S:2][C:3]1[C:11]([OH:12])=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[N:6][NH:7]2.O[C@H:14]1[CH2:19][CH2:18][C@H:17]([N:20]2[C:28](=[O:29])[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:21]2=[O:30])[CH2:16][CH2:15]1.CS(C1C(OC2CCCN(C(OC(C)(C)C)=O)CC2)=CC=C2C=1C=NN2)(=O)=O.C(C=P(CCCC)(CCCC)CCCC)#N>C1(C)C=CC=CC=1>[CH3:1][S:2][C:3]1[C:11]([O:12][C@@H:14]2[CH2:15][CH2:16][C@H:17]([N:20]3[C:21](=[O:30])[C:22]4[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:28]3=[O:29])[CH2:18][CH2:19]2)=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[N:6][NH:7]2
Reactant: CSc1c(O)ccc2[nH]ncc12
Reactant: O=C1c2ccccc2C(=O)N1[C@H]1CC[C@H](O)CC1
Agent: CC(C)(C)OC(=O)N1CCCC(Oc2ccc3[nH]ncc3c2S(C)(=O)=O)CC1
Agent: CCCCP(=CC#N)(CCCC)CCCC
Solvent: Cc1ccccc1
Product: CSc1c(O[C@H]2CC[C@@H](N3C(=O)c4ccccc4C3=O)CC2)ccc2[nH]ncc12
Temperature: 100 °C
Reaction time: 7 h
Yield: 57.9 %

Procedure:
The 4-(methylthio)-1H-indazol-5-ol (0.166 g, 0.92 mmol) obtained in Example 607 and the trans-2-(4-hydroxycyclohexyl)-1H-isoindole-1,3(2H)-dione (0.151 g, 0.61 mmol) obtained in Example 323, (a) were added to a solution of cyanomethylenetri-n-butylphosphorane (0.247 g, 0.92 mmol) in toluene (6 ml), and the resulting mixture was heated at 100° C. and stirred for 7 hours. The reaction solution was concentrated and then diluted with chloroform, and a 1N-aqueous sodium hydroxide solution was added thereto, followed by extraction with chloroform (three times). The extract solution was dried over anhydrous magnesium sulfate. The solvent was distilled off and the residue was purified by a silica gel chromatography (hexane/ethyl acetate=2/1˜1/1) to obtain 2-(cis-4-{[4-(methylthio)-1H-indazol-5-yl]oxy}cyclohexyl)-1H-isoindole-1,3(2H)-dione (0.144 g: 58%).
Reaction SMILES: O=[C:2]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[CH2:3][CH2:4][C:5]([OH:7])=[O:6].Cl.[NH2:15][OH:16].C([O-])(=O)C.[Na+].O>CCO>[N:15](=[C:2]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[CH2:3][CH2:4][C:5]([OH:7])=[O:6])[OH:16]
Reactant: O=C(O)CCC(=O)c1ccccc1
Reactant: NO
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: O=C(O)CCC(=NO)c1ccccc1
Temperature: 80 °C

Procedure:
To a solution of 4-oxo-4-phenylbutyric acid (1.0 g, 5.3 mmol) in 50 mL of EtOH was added hydroxylamine hydrochloride (742 mg, 11 mmol) and sodium acetate (1.8 g, 21 mmol). The reaction flask was heated at 80° C. for 4 h and was then cooled to room temperature. Addition of water and filtration of the resultant precipitate afforded, after recrystallization (10:1 chloroform:hexane), 620 mg (60%) of the title compound.
Reaction SMILES: [CH:1]([N:4]1[C:9](=[O:10])[CH:8]=[CH:7][C:6]([C:11](=[N:20]O)[C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:13])=[N:5]1)([CH3:3])[CH3:2].[C:22](OC(=O)C)(=[O:24])[CH3:23].CC(O)=O>CCOC(C)=O.[Zn]>[CH:1]([N:4]1[C:9](=[O:10])[CH:8]=[CH:7][C:6]([CH:11]([NH:20][C:22](=[O:24])[CH3:23])[C:12](=[O:13])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[N:5]1)([CH3:3])[CH3:2]
Reactant: CC(=O)OC(C)=O
Reactant: CC(C)n1nc(C(=NO)C(=O)c2ccccc2)ccc1=O
Agent: [Zn]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: CC(=O)NC(C(=O)c1ccccc1)c1ccc(=O)n(C(C)C)n1
Reaction time: 4 h

Procedure:
Zinc dust (1.57 g) was added in portions to a suspension of 1-(1-isopropyl-6-oxo-1,6-dihydro-3-pyridazinyl)-2-phenyl-1,2-ethanedione 1-oxime (856 mg) in a mixture acetic anhydride (1.7 ml) and AcOH (10 ml) under ambient temperature and the mixture was stirred at the same temperature for 4 hours. An insoluble material was filtered off and a filtrate was concentrated under reduced pressure to give a residue. The residue was dissolved in EtOAc, washed with sat. aq. NaHCO3 solution, dried over MgSO4 and subjected to column chromatography on silica gel eluting with a mixture of MeOH and EtOAc (2:98 v/v) to give N-[1-(1-isopropyl-6-oxo-1,6-dihydro-3-pyridazinyl)-2-oxo-2-phenylethyl]acetamide as a solid (724 mg).
Reaction SMILES: Cl.[NH2:2][OH:3].C(=O)(O)[O-].[Na+].[C:9](#[N:18])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17].C1(C)C=CC=CC=1>C(O)(C)C>[OH:3][NH:2][C:9](=[NH:18])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17]
Reactant: NO
Reactant: CCCCCCCCC#N
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(C)O
Solvent: Cc1ccccc1
Product: CCCCCCCCC(=N)NO
Reaction time: 0.21 h

Procedure:
To a solution of 0.74 g (10.7 mmol) of hydroxylamine hydrochloride in 11 mL of isopropyl alcohol, 1.327 g (17.8 mmol) of sodium bicarbonate was added. The resulting mixture was stirred at 25° C. to 30° C. for 10-15 min. 1.0 g (7.1 mmol) of nonanenitrile was added and stirred at 80° C. to 85° C. for 3-4 h. After the reaction period, the reaction mixture was cooled to 25° C. to 30° C., filtered and washed with 2 mL of isopropyl alcohol. The filtrate was collected and distilled out completely to obtain a crude residue. The residue with chased with 5 mL of toluene below 45° C., under vacuum, to yield the title compound.
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:6]=[C:7]([CH:11]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12]2)[CH:8]=[CH:9][CH:10]=1)=[O:4].[OH-].[Na+]>CCO.O>[C:19]([O:18][C:16]([N:13]1[CH2:14][CH2:15][CH:11]([C:7]2[CH:6]=[C:5]([CH:10]=[CH:9][CH:8]=2)[C:3]([OH:4])=[O:2])[CH2:12]1)=[O:17])([CH3:22])([CH3:20])[CH3:21]
Reactant: COC(=O)c1cccc(C2CCN(C(=O)OC(C)(C)C)C2)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CC(C)(C)OC(=O)N1CCC(c2cccc(C(=O)O)c2)C1
Temperature: 29 °C
Reaction time: 0.5 h
Yield: 98 %

Procedure:
To a solution of tert-butyl 3-(3-(methoxycarbonyl)phenyl)pyrrolidine-1-carboxylate (210 mg, 0.7 mmol) in EtOH (4 ml) was added a solution of NaOH (56 mg, 1.4 mmol) in H2O (1 ml) at 29° C. The mixture was stirred for 30 min at 29° C. The mixture was concentrated and the residue was treated with water and extracted with EA. The water layer was treated with 2N HCl until pH=3, extracted with EA and the combined organic layers were washed with brine, dried over Na2SO4 and concentrated to give the title compound which was used in next step without further purification (200 mg, Yield 98.0%).
Reaction SMILES: [CH2:1]([CH:11]1[CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[C:16]([C:20]3[N:25]=[CH:24][C:23]([OH:26])=[CH:22][N:21]=3)[CH:17]=2)[CH2:12]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].C1(C)C=CC(S(O[CH2:37][CH2:38][CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)(=O)=O)=CC=1.[OH-].[K+].O>C(O)C>[CH2:1]([CH:11]1[CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[C:16]([C:20]3[N:25]=[CH:24][C:23]([O:26][CH2:37][CH2:38][CH2:39][C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=4)=[CH:22][N:21]=3)[CH:17]=2)[CH2:12]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: Cc1ccc(S(=O)(=O)OCCCc2ccccc2)cc1
Reactant: CCCCCCCCCCC1Cc2ccc(-c3ncc(O)cn3)cc2C1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CCCCCCCCCCC1Cc2ccc(-c3ncc(OCCCc4ccccc4)cn3)cc2C1
Yield: 56.3 %

Procedure:
0.443 g of 2-(2-decylindan-5-yl)pyrimidine-5-ol, 0.343 g of phenylpropyl p-toluenesulfonate and 0.1 g of potassium hydroxide were dissolved in 2 ml of ethanol, followed by heat-refluxing for 4 hours. After the reaction, the reaction mixture was poured into water and subjected to extraction with toluene. The resultant organic layer was washed with water and dried with anhydrous sodium sulfate, followed by distilling-off of the solvent and purification by silica gel column chromatography to obtain 0.313 g of an objective product (Yield: 53.2%).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Br:8])[CH:3]=1.[C:9]1(B(O)O)[C:22]2[C:23]3=[C:24]4[C:19](=[CH:20][CH:21]=2)[CH:18]=[CH:17][CH:16]=[C:15]4[CH:14]=[CH:13][C:12]3=[CH:11][CH:10]=1.C([O-])([O-])=O.[Na+].[Na+].CCO>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1>[Br:8][C:4]1[CH:3]=[C:2]([C:16]2[C:15]3[C:24]4=[C:23]5[C:12](=[CH:13][CH:14]=3)[CH:11]=[CH:10][CH:9]=[C:22]5[CH:21]=[CH:20][C:19]4=[CH:18][CH:17]=2)[CH:7]=[CH:6][CH:5]=1
Reactant: OB(O)c1ccc2ccc3cccc4ccc1c2c34
Reactant: Brc1cccc(Br)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCO
Product: Brc1cccc(-c2ccc3ccc4cccc5ccc2c3c45)c1
Temperature: 90 °C
Yield: 48.9 %

Procedure:
A mixture of 10 g (42.4 mmol) of 1,3-dibromobenzene, 10.43 g (42.4 mmol) of Pyren-1-ylboronic acid, 0.5 g (0.424 mmol) of Tetrakis(triphenylphosphine)palladium, 32 ml of 2M Na2CO3, 80 ml of EtOH and 160 ml toluene was degassed and placed under nitrogen, and then heated at 90° C. for 24 h. After the reaction finish, the mixture was allowed to cool to room temperature. The organic layer was extracted with ethyl acetate and water, dried with anhydrous magnesium sulfate, the solvent was removed and the residue was purified by column chromatography on silica (hexane-dichloromethane) to give product 7.4 g (49%) as a white solid.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:16])[C@H:4]([CH2:14][OH:15])[NH:5][O:6][Si:7]([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8].C(N(C(C)C)CC)(C)C.[C:26](Cl)([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:16])[C@H:4]([CH2:14][OH:15])[N:5]([O:6][Si:7]([C:10]([CH3:13])([CH3:11])[CH3:12])([CH3:8])[CH3:9])[C:26]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1)[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: COC(=O)[C@H](CO)NO[Si](C)(C)C(C)(C)C
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)[C@H](CO)N(O[Si](C)(C)C(C)(C)C)C(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To t-butyldimethylsilyloxyserine methyl ester (27.5 g; 0.118 mol) dissolved in CH2Cl2 (125 ml) and diisopropylethylamine (25 ml; 0.14 mol) and cooled to 0° C. is added tritylchloride (33. g; 0.118 mol) portionwise over 2 minutes. The reaction is stirred for 4 hours at 25° C., diluted with CH2Cl2 and washed with H2O 3×. The organic phase is dried (MgSO4) and concentrated to dryness to give N-trityl-t-butyldimethylsilyloxy serine methyl ester as a tan solid which is used directly next Step C.
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[O:9][CH3:10].[CH:11]1([CH2:16][C:17](Cl)=[O:18])[CH2:15][CH2:14][CH2:13][CH2:12]1.[Cl-].[Al+3].[Cl-].[Cl-].Cl>ClCCl>[Cl:8][C:7]1[C:2]([Cl:1])=[C:3]([O:9][CH3:10])[CH:4]=[CH:5][C:6]=1[C:17](=[O:18])[CH2:16][CH:11]1[CH2:15][CH2:14][CH2:13][CH2:12]1
Reactant: COc1cccc(Cl)c1Cl
Reactant: O=C(Cl)CC1CCCC1
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: COc1ccc(C(=O)CC2CCCC2)c(Cl)c1Cl
Temperature: 0 °C
Reaction time: 16 h

Procedure:
2,3-Dichloroanisole (57.8 g., 0.327 mole) is dissolved in dichloromethane (300 ml.) and cyclopentylacetyl chloride (52.7 g., 0.367 mole) is added. The solution is cooled to +5° C. and aluminum chloride (48.0 g., 0.36 mole) is added gradually over a one-hour period at +5° C. The mixture is stirred for 2 hours at +5° C. and at 20°-25° C. for 16 hours and then poured into 1 liter of ice water containing 150 ml. of 12N hydrochloric acid. The organic phase is separated and the aqueous phase is extracted with dichloromethane. The combined organic phases are washed with sodium chloride solution, 10% sodium hydroxide and again with sodium chloride solution and dried over magnesium sulfate. On evaporation of the solvent a brown solid is obtained which is crystallized from hexane to obtain 53.2 of 2',3'-dichloro-4'-methoxy-2-cyclopentylacetophenone, m.p. 60°-61.5° C.
Reaction SMILES: [Cl:1][C:2]1[C:7]([CH3:9])([CH3:8])[C:6](=[O:10])[C:5]([CH3:12])([CH3:11])[C:4](=[O:13])[C:3]=1[C:14]([C:16]1[C:17]([CH3:26])=[N:18][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:20][CH:21]=1)=[O:15].[Br:27]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[Br:27][CH2:26][C:17]1[C:16]([C:14]([C:3]2[C:4](=[O:13])[C:5]([CH3:12])([CH3:11])[C:6](=[O:10])[C:7]([CH3:9])([CH3:8])[C:2]=2[Cl:1])=[O:15])=[CH:21][CH:20]=[C:19]([C:22]([F:23])([F:24])[F:25])[N:18]=1
Reactant: Cc1nc(C(F)(F)F)ccc1C(=O)C1=C(Cl)C(C)(C)C(=O)C(C)(C)C1=O
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: CC1(C)C(=O)C(C(=O)c2ccc(C(F)(F)F)nc2CBr)=C(Cl)C(C)(C)C1=O

Procedure:
0.39 g (1 mmol) of 5-chloro-2,2,6,6-tetramethyl-4-(2-methyl-6-trifluoromethylpyridine-3-carbonyl)cyclohex-4-ene-1,3-dione and 0.20 g (1.1 mmol) of N-bromsuccinimide are refluxed in the presence of a catalytic amount of dibenzoyl peroxide in 10 ml of carbon tetrachloride. After the reaction has subsided, the resulting succinimide is removed by filtration and the crude product is purified by column chromatography (mobile phase: ethyl acetatelhexane 1:4). This gives pure 4-(2-bromomethyl-6-trifluoromethylpyridine-3-carbonyl)-5-chloro-2,2,6,6-tetramethylcyclohex-4-ene-1,3-dione of melting point 94.5-95° C.