Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[C:24]([CH3:25])=[C:23]([CH3:26])[C:5]2[O:6][C:7]([CH3:22])([CH2:9][N:10]3[CH2:15][CH2:14][CH:13]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)[CH2:12][CH2:11]3)[CH2:8][C:4]=2[C:3]=1[CH3:27].[C:28]([OH:38])(=[O:37])[C@H:29]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[OH:30]>C(Cl)(Cl)Cl.CO>[C:28]([OH:38])(=[O:37])[C@H:29]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[OH:30].[NH2:1][C:2]1[C:24]([CH3:25])=[C:23]([CH3:26])[C:5]2[O:6][C@:7]([CH3:22])([CH2:9][N:10]3[CH2:15][CH2:14][CH:13]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)[CH2:12][CH2:11]3)[CH2:8][C:4]=2[C:3]=1[CH3:27]
Reactant: Cc1c(C)c2c(c(C)c1N)CC(C)(CN1CCC(c3ccccc3)CC1)O2
Agent: O=C(O)[C@@H](O)c1ccccc1
Solvent: CO
Solvent: ClC(Cl)Cl
Product: Cc1c(C)c2c(c(C)c1N)C[C@@](C)(CN1CCC(c3ccccc3)CC1)O2
Yield: 39.7 %

Procedure:
To a solution of 35.4 g of (±)-5-amino-2,4,6,7-tetramethyl-2-(4-phenylpiperidinomethyl)-2,3-dihydrobenzo[b]furan in 500 ml of chloroform was added a solution of 14.78 g of (S)--(+)--mandelic acid in 300 ml of methanol, followed by concentration. To the residue was added about 500 ml of ether; the resulting precipitate was collected by filtration and washed with ether. The resulting 35.4 g crude crystal was subjected to the following recrystallizing procedure. Specifically, the crude crystal was dissolved in methanol-acetonitrile (2:1) (1 liter). After the solution was concentrated to about 100 ml volume, about 500 ml of ether was added, and the mixture was kept standing at 20° C. The resulting precipitate was finely milled, then filtered and washed witch ether. The above procedure was repeated in two cycles (first yield 21.96 g) to yield 19.90 g of (S)--(+)-5-amino-2,4,6,7-tetramethyl-2-(4-phenylpiperidinomethyl)-2,3-dihydrobenzo[b]furan (S)--(+)--mandelate.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[CH:6][C:7]([O:10][CH3:11])=[N:8][CH:9]=1)(=[O:3])[CH3:2].[CH3:12][C:13]1[N:14]=[CH:15][S:16][C:17]=1[CH:18]=O.[OH-].[K+]>>[CH3:11][O:10][C:7]1[N:8]=[CH:9][C:4]([C:1](=[O:3])/[CH:2]=[CH:18]/[C:17]2[S:16][CH:15]=[N:14][C:13]=2[CH3:12])=[CH:5][CH:6]=1
Reactant: Cc1ncsc1C=O
Reactant: COc1ccc(C(C)=O)cn1
Agent: [K+]
Agent: [OH-]
Product: COc1ccc(C(=O)/C=C/c2scnc2C)cn1

Procedure:
In analogy to example 170, step 1, 5-acetyl-2-methoxypyridine was reacted with 4-methylthiazole-5-carbaldehyde in the presence of potassium hydroxide to give the title compound as an off-white solid. MS (ESI+): m/z=261.1 [M+H]+.
Reaction SMILES: [CH:1]([Mg]Cl)([CH3:3])[CH3:2].[Br:6][C:7]1[CH:14]=[CH:13][C:10]([CH:11]=[O:12])=[CH:9][CH:8]=1>O1CCCC1>[Br:6][C:7]1[CH:14]=[CH:13][C:10]([CH:11]([OH:12])[CH:1]([CH3:3])[CH3:2])=[CH:9][CH:8]=1
Reactant: CC(C)[Mg]Cl
Reactant: O=Cc1ccc(Br)cc1
Solvent: C1CCOC1
Product: CC(C)C(O)c1ccc(Br)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 24 %

Procedure:
A solution of isopropylmagnesium chloride (17.0 L, 1M in tetrahydrofuran) was added dropwise to the solution of 4-bromobenzaldehyde (2.1 g, 11.4 mol) in tetrahydrofuran (30 mL) at −10° C. Then the mixture was stirred at 25° C. for 4 hours. The resultant reaction was quenched with saturated ammonium chloride aqueous (20 mL). The organic phase was separated, dried over sodium sulfate, filtered and concentrated to give a residue. The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=2:1) to give 1-(4-bromophenyl)-2-methylpropan-1-ol (620 mg, 24%). 1H NMR (300 MHz, CDCl3): δ 7.98-7.85 (m, 2H), 7.48-7.35 (m, 2H), 5.17 (s, 1H), 4.49 (d, J=6.6 Hz, 1H), 2.35-2.30 (m, 1H), 1.01 (d, J=6.6 Hz, 6H).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[N:11]=[C:12]([NH2:15])[S:13][CH:14]=1)([O-:3])=[O:2].Br[CH2:17][C:18](=O)[C:19]([O:21][CH2:22][CH3:23])=[O:20]>C(C(C)=O)C>[CH2:22]([O:21][C:19]([C:18]1[N:15]=[C:12]2[N:11]([CH:17]=1)[C:10]([C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=1[N+:1]([O-:3])=[O:2])=[CH:14][S:13]2)=[O:20])[CH3:23]
Reactant: Nc1nc(-c2ccccc2[N+](=O)[O-])cs1
Reactant: CCOC(=O)C(=O)CBr
Solvent: CCC(C)=O
Product: CCOC(=O)c1cn2c(-c3ccccc3[N+](=O)[O-])csc2n1
Temperature: 25 °C
Yield: 52.5 %

Procedure:
4-(2-Nitro-phenyl)-thiazol-2-ylamine (1.60 g, 7.2 mmol) was mixed with 50 mL of methyl ethyl ketone along 0.90 mL of ethyl bromopyruvate (7.2 mmol) and stirred under reflux for 24 hours. Another equivalent of ethyl bromopyruvate (0.90 mL, 7.2 mmol) was added and the reaction mixture was stirred under reflux for another 8 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The resulting residue was purified by chromatography (Isco, gradient elution, CH2Cl2 to 95% CH2Cl2, 5% MeOH) to afford 1.2 g of 3-(2-nitro-phenyl)-imidazo[2,1-b]thiazole-6-carboxylic acid ethyl ester (52% yield).
Reaction SMILES: O[CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([C:15]2[C:16](=[O:32])[NH:17][C:18](=[O:31])[C:19]=2[C:20]2[C:28]3[O:27][CH:26]=[CH:25][C:24]=3[C:23]([O:29][CH3:30])=[CH:22][CH:21]=2)=[CH:7]1.C(Br)(Br)(Br)[Br:34].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[Br:34][CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([C:15]2[C:16](=[O:32])[NH:17][C:18](=[O:31])[C:19]=2[C:20]2[C:28]3[O:27][CH:26]=[CH:25][C:24]=3[C:23]([O:29][CH3:30])=[CH:22][CH:21]=2)=[CH:7]1
Reactant: BrC(Br)(Br)Br
Reactant: COc1ccc(C2=C(c3cn(CCCCO)c4ccccc34)C(=O)NC2=O)c2occc12
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: COc1ccc(C2=C(c3cn(CCCCBr)c4ccccc34)C(=O)NC2=O)c2occc12
Reaction time: 0.17 h

Procedure:
Dissolve 3-[1-(4-hydroxybutyl)-1H-indol-3-yl]-4-(4-methoxybenzofur-7-yl)pyrrole-2,5-dione (0.1 g, 0.232 mmol) in 10 mL dichloromethane. Add carbon tetrabromide (0.077 g, 1 equivalent) and triphenyl phosphine (0.061 g, 1 equivalent). Stir for 10 min, add another equivalent of both reagents. Stir 10 min then dilute with dichloromethane and wash with water followed by brine. Dry over magnesium sulfate then filter and concentrate. Purification by column chromatography (2% methanol: dichloromethane) affords the title compound. MS (ES, m/z): 493.0 (M−1).
Reaction SMILES: [F:1][C:2]1[CH:25]=[CH:24][C:5]([O:6][C:7]2[N:23]=[CH:22][CH:21]=[CH:20][C:8]=2[C:9]([NH:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=2)=[O:10])=[CH:4][CH:3]=1.[CH3:26][C:27]([CH3:32])([CH3:31])[C:28](Cl)=[O:29].C(N(CC)CC)C>C(Cl)Cl.[OH-].[Na+]>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][C:7]2[C:8]([C:9]([NH:11][CH2:12][C:13]3[CH:18]=[CH:17][C:16]([O:19][C:28](=[O:29])[C:27]([CH3:32])([CH3:31])[CH3:26])=[CH:15][CH:14]=3)=[O:10])=[CH:20][CH:21]=[CH:22][N:23]=2)=[CH:24][CH:25]=1
Reactant: CC(C)(C)C(=O)Cl
Reactant: O=C(NCc1ccc(O)cc1)c1cccnc1Oc1ccc(F)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)C(=O)Oc1ccc(CNC(=O)c2cccnc2Oc2ccc(F)cc2)cc1
Yield: 68.8 %

Procedure:
A solution 2-(4-Fluoro-phenoxy)-N-(4-hydroxy-benzyl)-nicotinamide (0.050 grams, 0.148 mmole), trimethylacetyl chloride (0.019 grams, 0.163 mmole) and triethyl amine (0.022 grams, 0.222 mmole) in methylene chloride (5 ml) was stirred for 30 minutes. The mixture was diluted with 50 ml 1N sodium hydroxide and extracted with ethyl acetate. The combined organics were washed with water and brine, dried over Na2SO4, filtered and concentrated to give an oil that was purified by chromatography on silica gel eluting with 40% ethyl acetate/hexane. Recrystalization from ethyl acetate/hexane gave a solid (0.043 g). M.P. 91-93° C.; Anal. calcd. for C24H23N2O4F: C, 68.24; H, 5.49; N, 6.63. Found: C, 66.07; H, 5.24; N, 6.42.
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([CH2:9][CH3:10])[C:4]=1[NH:11][C:12]([C:14]1[C:18]2[CH2:19][CH2:20][C:21]3[CH:22]=[N:23][C:24]([NH:27][C:28]4[CH:33]=[CH:32][C:31]([CH:34]=O)=[CH:30][C:29]=4[O:36][CH3:37])=[N:25][C:26]=3[C:17]=2[N:16]([CH3:38])[N:15]=1)=[O:13])[CH3:2].[CH3:39][N:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].CC(O)=O>C(Cl)Cl>[CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([CH2:9][CH3:10])[C:4]=1[NH:11][C:12]([C:14]1[C:18]2[CH2:19][CH2:20][C:21]3[CH:22]=[N:23][C:24]([NH:27][C:28]4[CH:33]=[CH:32][C:31]([CH2:34][N:43]5[CH2:44][CH2:45][N:40]([CH3:39])[CH2:41][CH2:42]5)=[CH:30][C:29]=4[O:36][CH3:37])=[N:25][C:26]=3[C:17]=2[N:16]([CH3:38])[N:15]=1)=[O:13])[CH3:2]
Reactant: CCc1cccc(CC)c1NC(=O)c1nn(C)c2c1CCc1cnc(Nc3ccc(C=O)cc3OC)nc1-2
Reactant: CN1CCNCC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Solvent: CC(=O)O
Product: CCc1cccc(CC)c1NC(=O)c1nn(C)c2c1CCc1cnc(Nc3ccc(CN4CCN(C)CC4)cc3OC)nc1-2
Temperature: 25 °C
Reaction time: 3 h
Yield: 75 %

Procedure:
To a solution of N-(2,6-diethylphenyl)-8-[(4-formyl-2-methoxyphenyl)amino]-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (50 mg, 0.097 mmol) and N-methyl-piperazine (49 mg, 0.49 mmol) in 1 ml of dry DCM, NaBH(AcO)3 (123 mg, 0.58 mmol) and AcOH (25 μl) were added. The mixture was stirred at room temperature for 3 h, washed with aqueous NaHCO3, dried over Na2SO4 and evaporated to dryness. The crude was purified by flash column chromatography (DCM/MeOH 9:1) affording the title compound in 75% yield.
Reaction SMILES: [C:1]([NH:4][C@@H:5]1[CH2:8][C@H:7]([C:9]([O:11]CC2C=CC=CC=2)=[O:10])[C:6]1([CH3:20])[CH3:19])(=[O:3])[CH3:2]>CCOC(C)=O.[Pd]>[C:1]([NH:4][C@@H:5]1[CH2:8][C@H:7]([C:9]([OH:11])=[O:10])[C:6]1([CH3:20])[CH3:19])(=[O:3])[CH3:2]
Reactant: CC(=O)N[C@@H]1C[C@H](C(=O)OCc2ccccc2)C1(C)C
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CC(=O)N[C@@H]1C[C@H](C(=O)O)C1(C)C
Temperature: 25 °C
Reaction time: 1 h
Yield: 54.9 %

Procedure:
A stirred solution of (1S,3R)-benzyl 3-acetamido-2,2-dimethylcyclobutanecarboxylate (0.650 g, 2.36 mmol) in EtOAc (10 ml) at room temperature, 10% Pd/C (catalytic amount) were added and the reaction mixture was stirred under H2 gas atmosphere at room temperature for about 1 hour. After completion of the reaction (monitored by TLC), the reaction mixture was filtered through celite bed. The obtained filtrate was concentrated under reduced pressure to afford title compound as an off white solid. Wt: 0.240 g; Yield: 54.9%; 1H NMR (300 MHZ, CD3OD): δ 8.09 (d, J=3.0 Hz, 1H), 4.08-3.96 (m, 1H), 2.62-2.58 (m, 1H), 2.20-2.15 (m, 2H), 1.93 (s, 3H), 1.26 (s, 3H), 0.92 (s, 3H); Mass: [M+1]+ 186 (70%), [M+Na]+ 208 (93%). IR (KBr, cm−1): 3349, 2962, 1697, 1624, 1557, 1428, 1377, 1257, 1075, 988, 920, 736; M.R: 194.7° C.-216.2° C.
Reaction SMILES: C([O:4][C:5]1[CH:38]=[CH:37][CH:36]=[CH:35][C:6]=1[C:7]([NH:9][CH:10]1[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][CH2:18][O:19][C:20]2[CH:21]=[CH:22][C:23]3[C:28]4[CH2:29][CH2:30][CH2:31][CH2:32][C:27]=4[C:26](=[O:33])[O:25][C:24]=3[CH:34]=2)[CH2:12][CH2:11]1)=[O:8])(=O)C.Cl>O1CCOCC1>[OH:4][C:5]1[CH:38]=[CH:37][CH:36]=[CH:35][C:6]=1[C:7]([NH:9][CH:10]1[CH2:11][CH2:12][N:13]([CH2:16][CH2:17][CH2:18][O:19][C:20]2[CH:21]=[CH:22][C:23]3[C:28]4[CH2:29][CH2:30][CH2:31][CH2:32][C:27]=4[C:26](=[O:33])[O:25][C:24]=3[CH:34]=2)[CH2:14][CH2:15]1)=[O:8]
Reactant: CC(=O)Oc1ccccc1C(=O)NC1CCN(CCCOc2ccc3c4c(c(=O)oc3c2)CCCC4)CC1
Agent: Cl
Solvent: C1COCCO1
Product: O=C(NC1CCN(CCCOc2ccc3c4c(c(=O)oc3c2)CCCC4)CC1)c1ccccc1O

Procedure:
A mixture of 5.18 g. (0.01 mole) 3-{3-[4-(2-acetoxybenzamido)-piperidino]-propoxy}-7,8,9,10-tetrahydro-6H-dibenzo[b,d]pyran-6-one (compound of Example 47), 20 ml. dioxane and 20 ml. 6 N hydrochloric acid is heated under reflux for 10 hours, cooled and filtered. There are obtained 3.0 g. (63% of theory) of the desired compound in the form of its hydrochloride; m.p. 232°-234° C. The corresponding free base melts at 209°-211° C.
Reaction SMILES: Br[C:2]1[CH:7]=[N:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)=[CH:4][N:3]=1.[Li]CCCC.CCCCCC.[N:26]1[CH:31]=[CH:30][C:29]([C:32](=[O:34])[CH3:33])=[CH:28][CH:27]=1>C1COCC1>[F:14][C:11]1[CH:12]=[CH:13][C:8]([C:5]2[N:6]=[CH:7][C:2]([C:32]([C:29]3[CH:30]=[CH:31][N:26]=[CH:27][CH:28]=3)([OH:34])[CH3:33])=[N:3][CH:4]=2)=[CH:9][CH:10]=1
Reactant: Fc1ccc(-c2cnc(Br)cn2)cc1
Reactant: CC(=O)c1ccncc1
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CC(O)(c1ccncc1)c1cnc(-c2ccc(F)cc2)cn1
Temperature: -78 °C
Reaction time: 0.17 h
Yield: 27.1 %

Procedure:
2-bromo-5-(4-fluorophenyl)pyrazine (115 mg, 0.4 mmol) in THF (10 mL) was cooled to −78° C., 1.6 M n-BuLi in hexane (0.56 mL, 0.8 mmol) added slowly at −78° C., the reaction mixture was stirred for 10 min at −78° C., and 1-(pyridin-4-yl)ethanone (54 mg, 0.4 mmol) in THF (3 mL) was added. The resulting mixture was stirred at −78° C. for 1 h. The reaction mixture was quenched with saturated NH4Cl solution (10 mL) and extracted with ethyl acetate (2×200 mL). The combined extracts were washed with brine solution (20 mL), dried over Na2SO4, filtered and concentrated under vacuum to obtain crude product. The crude product was purified by preparative TLC (mobile phase: 60% ethyl acetate in hexane) to afford 1-(5-(4-fluorophenyl)pyrazin-2-yl)-1-(pyridin-4-yl)ethanol as off-white solid (32 mg, 24% yield) in 98.7% HPLC purity. 1H NMR (400 MHz, DMSO-d6): δ 9.13 (s, 1H), 8.93 (s, 1H), 8.48 (d, 2H), 8.16-8.13 (m, 2H), 7.49 (d, 2H), 7.34 (t, 2H), 6.43 (s, 1H), 1.90 (s, 3H); LC-MS m/z calculated for [M+H]+ 296.11, found 296.1.
Reaction SMILES: Br[C:2]1[N:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:15][CH2:14][N:13]([C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][C:17]=3[CH3:23])[CH2:12][CH2:11]2)=[O:9])=[CH:4][CH:3]=1.[I-:24].[Na+]>[Cu]I>[CH3:23][C:17]1[CH:18]=[C:19]([CH3:22])[CH:20]=[CH:21][C:16]=1[N:13]1[CH2:14][CH2:15][N:10]([C:8]([C:5]2[CH:6]=[N:7][C:2]([I:24])=[CH:3][CH:4]=2)=[O:9])[CH2:11][CH2:12]1
Reactant: Cc1ccc(N2CCN(C(=O)c3ccc(Br)nc3)CC2)c(C)c1
Reactant: [I-]
Agent: [Cu]I
Agent: [Na+]
Product: Cc1ccc(N2CCN(C(=O)c3ccc(I)nc3)CC2)c(C)c1
Yield: 62.1 %

Procedure:
Using (6-bromopyridin-3-yl)[4-(2,4-dimethylphenyl)piperazin-1-yl]methanone (487 mg) described in Preparation Example 115, sodium iodide (389 mg) and copper(I) iodide (123 mg) and by the reaction and treatment in the same manner as in Preparation Example 154, the title compound (340.6 mg) was obtained.
Reaction SMILES: [CH:1]1[CH:2]=[CH:3][N:4]2[C:10](=[O:11])[C:9]3[CH:12]=[CH:13][CH:14]=[CH:15][C:8]=3[NH:7][CH2:6][C:5]=12.C(N(CC)CC)C.[CH3:23][C:24]1[CH:41]=[CH:40][CH:39]=[CH:38][C:25]=1[C:26]([NH:28][C:29]1[CH:37]=[CH:36][C:32]([C:33](Cl)=[O:34])=[CH:31][CH:30]=1)=[O:27]>C(Cl)Cl>[CH3:23][C:24]1[CH:41]=[CH:40][CH:39]=[CH:38][C:25]=1[C:26]([NH:28][C:29]1[CH:37]=[CH:36][C:32]([C:33]([N:7]2[C:8]3[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=3[C:10](=[O:11])[N:4]3[CH:3]=[CH:2][CH:1]=[C:5]3[CH2:6]2)=[O:34])=[CH:31][CH:30]=1)=[O:27]
Reactant: Cc1ccccc1C(=O)Nc1ccc(C(=O)Cl)cc1
Reactant: O=C1c2ccccc2NCc2cccn21
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1ccccc1C(=O)Nc1ccc(C(=O)N2Cc3cccn3C(=O)c3ccccc32)cc1
Reaction time: 6 h

Procedure:
To a stirred solution of 107 mg of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one in 3 ml of methylene chloride containing 0.084 ml of triethylamine is added 165 mg of 4-[(2-methylbenzoyl)amino]benzoyl chloride and stirring continued for 6 hours. The volatiles are removed in vacuo to a residue which is purified on thick layer chromatography plates with 7:3 hexane-ethyl acetate to afford the desired product as a foam.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:15]([CH3:25])([O:20][Si](C)(C)C)[C:16]([F:19])([F:18])[F:17])=[C:7]([CH2:9][CH2:10][O:11][C:12](=[O:14])[CH3:13])[CH:8]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O>O1CCCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:15]([OH:20])([CH3:25])[C:16]([F:18])([F:19])[F:17])=[C:7]([CH2:9][CH2:10][O:11][C:12](=[O:14])[CH3:13])[CH:8]=1
Reactant: COc1ccc(C(C)(O[Si](C)(C)C)C(F)(F)F)c(CCOC(C)=O)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: O
Solvent: C1CCOC1
Product: COc1ccc(C(C)(O)C(F)(F)F)c(CCOC(C)=O)c1
Reaction time: 1 h

Procedure:
To the crude reaction mixture described in example 2 containing a solution of acetic acid 2-[5-methoxy-2-(2,2,2-trifluoro-1-methyl-1-trimethylsilanyloxy-ethyl)-phenyl]-ethyl ester was added tetrabutylammonium fluoride (52.9 mL of a 1.0M solution in tetrahydrofuran, 52.9 mmol). The reaction mixture was stirred one hour after which GC/MS and HPLC analysis showed no starting material. For characterization purposes, the reaction mixture was poured into water and extracted with methyl tert-butyl ether (75 mL). The organic layer was washed with water (75 mL) and brine (50 mL), dried over magnesium sulfate, filtered and concentrated to provide a crude oil. 1H NMR (400 MHz, CDCl3) δ1.82 (s, 3), 2.01 (s, 3), 2.98-3.06 (m, 2), 3.55 (dt, 1, J=13.7, 6.8), 3.79 (s, 3), 4.27-4.34 (m, 2), 6.73-6.77 (m, 2), 7.28 (d, 1, J=8.5). 13C NMR (100 MHz, CDCl3) δ20.92, 25.50, 34.16, 55.10, 66.49, 76.67 (q, J=30.3), 111.55, 118.25, 126.02 (q, J=286), 128.67, 129.56, 139.70, 159.20, 171.32. IR 3453, 1720, 1610, 1249, 1161, 1134, 1038 cm−1. Analysis calculated for C14H17F3O4: C, 54.90; H, 5.59. Found: C, 55.03; H, 5.85.
Reaction SMILES: [O:1]1CCOCC1.[CH3:7][O:8][C:9]1[CH:26]=[CH:25][C:12]([CH2:13][C:14]2[CH:22]=[CH:21][CH:20]=[C:19]3[C:15]=2[CH2:16][CH2:17][CH:18]3[C:23]#[N:24])=[CH:11][CH:10]=1.[Se](=O)=O>O>[CH3:7][O:8][C:9]1[CH:10]=[CH:11][C:12]([C:13]([C:14]2[CH:22]=[CH:21][CH:20]=[C:19]3[C:15]=2[CH2:16][CH2:17][CH:18]3[C:23]#[N:24])=[O:1])=[CH:25][CH:26]=1
Reactant: C1COCCO1
Reactant: COc1ccc(Cc2cccc3c2CCC3C#N)cc1
Agent: O=[Se]=O
Solvent: O
Product: COc1ccc(C(=O)c2cccc3c2CCC3C#N)cc1

Procedure:
To 60 ml. of dioxane are added 8.0 g. of 4-(p-methoxybenzyl)indan-1-carbonitrile and 2.8 g. of selenium dioxide and the mixture is refluxed for 12 hours. After cooling, water is added, followed by extraction with chloroform. The extract is washed with water and dried. Then, the solvent is distilled off under reduced pressure and the residue is purified by column chromatography (500 g. silica gel; eluted with chloroform). The crude crystals thus obtained are recrystallized from benzene. The procedure gives 4-(p-methoxybenzoyl)indan-1-carbonitrile as crystals melting at 115.5°-117.5° C.
Reaction SMILES: C(O)(=O)C.C(N)CC.C([O-])(=O)C.C([NH3+])CC.[Cl:17][C:18]1[CH:19]=[C:20]([C:25]2[O:31][C:28]([CH:29]=O)=[CH:27][CH:26]=2)[CH:21]=[CH:22][C:23]=1[Cl:24].[N+:32]([CH3:35])([O-:34])=[O:33]>CO>[Cl:17][C:18]1[CH:19]=[C:20]([C:25]2[O:31][C:28](/[CH:29]=[CH:35]/[N+:32]([O-:34])=[O:33])=[CH:27][CH:26]=2)[CH:21]=[CH:22][C:23]=1[Cl:24]
Reactant: O=Cc1ccc(-c2ccc(Cl)c(Cl)c2)o1
Reactant: C[N+](=O)[O-]
Agent: CC(=O)[O-]
Agent: CCC[NH3+]
Solvent: CO
Solvent: CCCN
Solvent: CC(=O)O
Product: O=[N+]([O-])/C=C/c1ccc(-c2ccc(Cl)c(Cl)c2)o1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 97 %

Procedure:
A stirred solution of acetic acid (1.4 ml, 1.46 g, 24.3 mmol) in methanol (3.5 ml) under nitrogen atmosphere at 0° C. was treated dropwise with n-propylamine (2.0 ml, 1.42 g, 24.0 mmol). The resulting n-propylammonium acetate solution was stirred at 0° C. for 5 min, then added dropwise to a stirred solution of 5-(3,4-dichlorophenyl)furfural (10.04 g, 41.6 mmol) in nitromethane (6.8 ml, 7.61 g, 124.7 mmol) at 0° C. The resulting mixture was stirred at 0° C. for 30 min. Then the cooling bath was removed, and stirring was continued at RT. From time to time, 10 ml of THF was added five times. After stirring overnight THF was evaporated and water was added. A solid was filtrated, washed with water and heptane to afford 11.46 g of 2-(3,4-dichlorophenyl)-5-((E)-2-nitrovinyl)furan. 1H NMR (400 MHz, DMSO-d6): 7.38 (1H, d), 7.43 (1H, d), 7.76 (1H, d), 7.95 (1H, dd), 8.03 (1H, d), 8.19 (1H, d), 8.31 (1H, d)
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=1.[I:9]N1C(=O)CCC1=O.CC(OCC1C2C(=CC=CC=2)C(COC(C)=O)=C2C=1C=CC=C2)=O.C(=O)([O-])O.[Na+]>CS(C)=O>[F:8][C:5]1[CH:6]=[C:7]([I:9])[C:2]([NH2:1])=[N:3][CH:4]=1
Reactant: Nc1ccc(F)cn1
Reactant: O=C1CCC(=O)N1I
Agent: CC(=O)OCc1c2ccccc2c(COC(C)=O)c2ccccc12
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CS(C)=O
Product: Nc1ncc(F)cc1I
Temperature: 25 °C
Reaction time: 1 h
Yield: 17.7 %

Procedure:
To a mixture of 2-amino-5-fluoropryidine (2.0 g, 17.8 mmol) and dimethyl sulfoxide (50 mL) was added N-iodosuccinimide (4.8 g, 21.4 mmol), which was stirred for 1 hour at room temperature. A suitable amount of acetic add was added to this mixture, which was stirred for 1 hour at the same temperature, and then stirred for another 3 hours at 55° C. This reaction mixture was cooled to room temperature, after which a saturated sodium hydrogencarbonate aqueous solution was added, and the mixture was extracted with ethyl acetate. The organic layer was separated, washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue thus obtained was purified by NH silica gel column chromatography (ethyl acetate) to obtain the title compound (751 mg, 18%).
Reaction SMILES: [H-].[Na+].[CH3:3][S:4]([NH2:7])(=[O:6])=[O:5].[CH3:8][C:9]1([CH3:34])[C:18]2[C:13](=[C:14]([C:19](O)=[O:20])[CH:15]=[CH:16][CH:17]=2)[NH:12][CH:11]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[CH:23]=2)[CH2:10]1.C(N1C=CN=C1)(N1C=CN=C1)=O>CN(C)C=O.O>[CH3:8][C:9]1([CH3:34])[C:18]2[C:13](=[C:14]([C:19]([NH:7][S:4]([CH3:3])(=[O:6])=[O:5])=[O:20])[CH:15]=[CH:16][CH:17]=2)[NH:12][CH:11]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[CH:23]=2)[CH2:10]1
Reactant: CC1(C)CC(c2cccc(N3CCOCC3)c2)Nc2c(C(=O)O)cccc21
Reactant: CS(N)(=O)=O
Agent: O=C(n1ccnc1)n1ccnc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CC1(C)CC(c2cccc(N3CCOCC3)c2)Nc2c(C(=O)NS(C)(=O)=O)cccc21
Temperature: 25 °C
Reaction time: 1 h
Yield: 30 %

Procedure:
To a suspension of 60% sodium hydride (535.0 mg, 13.7 mmol) in N,N-dimethylformamide (2.5 mL) was added methanesulfonamide (1.3 g, 13.8 mmol) at room temperature. The resulting mixture was stirred at 25° C. for 1 h to afford Solution A10. A solution of 4,4-dimethyl-2-(3-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid (300.0 mg, 0.82 mmol) and 1,1′-carbonyldiimidazole (442.0 mg, 2.76 mmol) in N,N-dimethylformamide (2.0 mL) was stirred at 70° C. for 1 h and cooled to room temperature to afford Solution B10. Solution B10 was added to Solution A10 and the resulting mixture was stirred at 25° C. for 1 h. To the reaction mixture was added water (0.5 mL). The mixture was filtered to remove the insoluble solid, and the filtrate was purified by Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water) afforded N-[4,4-dimethyl-2-(3-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-8-carbonyl]-methanesulfonamide (109.0 mg, 30%) as a white solid: MS (ESI) M+1=444.2.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:11])=[C:6]([CH:10]=1)[C:7](O)=[O:8].CN(C)C=O.C(Cl)(=O)C([Cl:20])=O>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:11])=[C:6]([CH:10]=1)[C:7]([Cl:20])=[O:8]
Reactant: O=C(Cl)C(=O)Cl
Reactant: O=C(O)c1cc(Br)ccc1Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: O=C(Cl)c1cc(Br)ccc1Cl
Temperature: 20 °C

Procedure:
5-bromo-2-chlorobenzoic acid (270 g, 1.15 mol) was suspended in methylene chloride (2700 mL). To the resulting mixture was added N,N-dimethylformamide (1 mL), and then added dropwise oxalyl chloride (288 mL, 3.46 mol) at 0° C. After the completion of dropwise addition, the mixture was warmed up to 20° C. and reacted for 3 h. The reaction mixture became clear, and TLC (Thin layer chromatography) indicated the completion of reaction. The reaction mixture was evaporated by rotation at 30-35° C. to produce a product, which was directly used in the next reaction.