Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br.[F:2][C:3]([F:19])([CH2:14][C:15]([F:18])([F:17])[F:16])[C:4]([F:13])([F:12])[O:5][CH2:6][C:7]1([CH3:11])[CH2:10][O:9][CH2:8]1.[OH-:20].[Na+]>O>[F:19][C:3]([F:2])([CH2:14][C:15]([F:17])([F:18])[F:16])[C:4]([F:12])([F:13])[O:5][CH2:6][C:7]1([CH2:11][O:20][C:4]([F:12])([F:13])[C:3]([F:2])([F:19])[CH2:14][C:15]([F:16])([F:17])[F:18])[CH2:10][O:9][CH2:8]1
Reactant: [OH-]
Reactant: CC1(COC(F)(F)C(F)(F)CC(F)(F)F)COC1
Agent: Br
Agent: [Na+]
Solvent: O
Product: FC(F)(F)CC(F)(F)C(F)(F)OCC1(COC(F)(F)C(F)(F)CC(F)(F)F)COC1
Temperature: 5 °C
Reaction time: 8 h
Yield: 93.5 %

Procedure:
A 2-L, 3-neck, jacketed flask fitted with a mechanical stirrer, thermocouple probe, and an addition funnel was charged with 48% hydrobromic acid (208.0 g, 1.23 mole). The flask was cooled to 5° C. by circulating coolant through the jacket, and 3-heptafluorobutoxymethyl-3-methyloxetane was added at a rate to maintain the temperature below 12° C. The addition was complete after 11/4 hours. GC analysis indicated 98% conversion of the starting material to product. Additional 48% HBr (14.9 g, 0.088 mole) was added, and the mixture was stirred overnight at room temperature. The mixture was poured into 200-ml water, and the pH of the aqueous layer was adjusted to a pH of about 5 with 1N NaOH. The layers were separated, and the organic layer was washed with water (250 ml), dried (MgSO4), and filtered to give 300.4 g (93.5%) of 3-bromo-2-heptafluorobutoxymethyl-2-methyl-1-propanol (2), a clear oil: 1H NMR (CDCl3) 1.00 (s), 3.43 and 3.52 (AB, J=10.4 Hz), 3.53 and 3.59 (AB, J=11.1 Hz), 3.58 (s), and 3.95 (t, J=13.4 Hz); Anal. Calcd for C9H12BrF7O2 : C, 29.60; H, 3.32; Br, 21.88; Found: C, 29.15; H, 3.27; Br, 21.09.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]([CH2:22][OH:23])[S:12][C:13]=2[C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)=[CH:5][CH:4]=1>C(OCC)(=O)C.[O-2].[O-2].[Mn+4]>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[N:10]=[C:11]([CH:22]=[O:23])[S:12][C:13]=2[C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)=[CH:7][CH:8]=1
Reactant: COc1ccc(-c2nc(CO)sc2-c2ccc(OC)cc2)cc1
Agent: [Mn+4]
Agent: [O-2]
Solvent: CCOC(C)=O
Product: COc1ccc(-c2nc(C=O)sc2-c2ccc(OC)cc2)cc1
Temperature: 25 °C
Reaction time: 5.5 h
Yield: 64.9 %

Procedure:
A mixture of 4,5-bis(4-methoxyphenyl)-2-hydroxymethylthiazole (5.04 g) and manganese dioxide (35.0 g) in ethyl acetate (250 ml) was stirred at ambient temperature for 5.5 hours. After filtration, the filtrate was evaporated in vacuo, and the resulting residue was washed with hexane to give 4,5-bis(4-methoxyphenyl)-2-formylthiazol (3.25 g).
Reaction SMILES: [C:1]([CH2:3][C:4]([OH:6])=[O:5])#[N:2].[CH:7]([N:20]1[CH2:23][CH:22](O)[CH2:21]1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1>[C:1]([CH2:3][C:4]([O:6][CH:22]1[CH2:23][N:20]([CH:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:21]1)=[O:5])#[N:2]
Reactant: OC1CN(C(c2ccccc2)c2ccccc2)C1
Reactant: N#CCC(=O)O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: C1CCOC1
Product: N#CCC(=O)OC1CN(C(c2ccccc2)c2ccccc2)C1

Procedure:
4.25 g (0.05 mole) of cyanoacetic acid and 11.95 g (0.05 mole) of 1-benzhydryl-3-hydroxyazetidine were dissolved in 400 ml of tetrahydrofuran. 12.38 g (0.06 mole) of 1,3-dicyclohexylcarbodiimide were then added to the solution, whilst stirring, after which the mixture was stirred at 55° C. for 11 hours. At the end of this time, the mixture was cooled, precipitated crystals were removed and the solvent was removed by distillation under reduced pressure. The residue was dissolved in ethyl acetate and the resulting solution was washed with water and then dried over anhydrous sodium sulfate.
Reaction SMILES: [C:1]([CH:4]([CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH:19]([C:24](=[O:26])[CH3:25])C(OC)=O)C(OC)=O)(=[O:3])[CH3:2].[Cl-].[Na+].O>CS(C)=O>[CH3:2][C:1](=[O:3])[CH2:4][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][C:24](=[O:26])[CH3:25]
Reactant: COC(=O)C(CCCCCCCCCCC(C(C)=O)C(=O)OC)C(C)=O
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: CC(=O)CCCCCCCCCCCCC(C)=O

Procedure:
0.37 g (1 mmol) of dimethyl 2,13-bisacetyl-1,14-tetradecanedioate were dissolved in 20 ml of DMSO and refluxed with 0.06 g (0.1 mmol) of sodium chloride and 0.04 g (2 mmol) of water for 3 h at 155 to 160° C. For work-up, the DMSO is firstly distilled off under reduced pressure, and the residue is distilled using a bulb tube. This gives 0.21 g of hexadecane-1,15-dione. Accordingly, the yield of 1,15-hexadecanedione is 82%, based on 1,9-decadiene.
Reaction SMILES: [CH2:1]([C:5]1[NH:6][C:7]2[C:8]([N:14]=1)=[N:9][CH:10]=[CH:11][C:12]=2[CH3:13])[CH2:2][CH2:3][CH3:4].[C:15]1([C:21]([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[N:22]2[C:26]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[C:33]3[CH:38]=[CH:37][C:36]([CH2:39]Br)=[CH:35][CH:34]=3)=[N:25][N:24]=[N:23]2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[H-].[Na+]>>[CH2:1]([C:5]1[N:14]([CH2:39][C:36]2[CH:35]=[CH:34][C:33]([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=3[C:26]3[N:22]([C:21]([C:47]4[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=4)([C:41]4[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=4)[C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=4)[N:23]=[N:24][N:25]=3)=[CH:38][CH:37]=2)[C:8]2=[N:9][CH:10]=[CH:11][C:12]([CH3:13])=[C:7]2[N:6]=1)[CH2:2][CH2:3][CH3:4]
Reactant: BrCc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Reactant: CCCCc1nc2nccc(C)c2[nH]1
Agent: [H-]
Agent: [Na+]
Product: CCCCc1nc2c(C)ccnc2n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1

Procedure:
2-Butyl-7-methyl-3-(2'-(N-triphenylmethyltetrazol-5-yl)biphen-4-yl)methyl-3H-imidazo[4,5-b]pyridine was prepared according to the procedure described in Example 7, Part A from 2-butyl-7-methylimidazo[4,5-b]pyridine (28 mg, 0.148 mmol), N-triphenylmethyl-5-(4'-bromomethylbiphenyl-2-yl)tetrazole (62 mg, 0.135 mmol), and NaH (0.296 mmol).
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl:20]C(Cl)(Cl)C(Cl)(Cl)Cl.[CH3:28][O:29][C:30](=[O:42])[C@H:31]([CH2:40]O)[NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34]>ClCCl>[CH3:28][O:29][C:30](=[O:42])[CH:31]([NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:40][Cl:20]
Reactant: ClC(Cl)(Cl)C(Cl)(Cl)Cl
Reactant: COC(=O)[C@H](CO)NC(=O)OC(C)(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: COC(=O)C(CCl)NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 77.5 %

Procedure:
A solution of triphenylphosphine (65.8 g, 0.251 mol)) and hexachloroethane (59.4 g, 0.251 mol) in dichloromethane (850 mL) was added in one portion to a solution of N-Boc-serine methyl ester (50 g, 0.228 mol) in dichloromethane (170 mL) under argon atmosphere. The reaction mixture was stirred at room temperature for 2 h and then the reaction was quenched with a saturated solution of NaHCO3 (150 mL). The organic product was extracted with dichloromethane (2×300 mL) and the combined organic layers was washed with brine (300 mL) and dried over anhydrous sodium sulphate. The solution was concentrated under reduced pressure and then triturated with Et2O (500 mL). After filtration and evaporation of the solvent, the crude product was purified by chromatography on a silica column eluted with 6-8% EtOAc in pet. ether) which gave the title compound (42 g, 78%).
Reaction SMILES: Cl[C:2]1[C:3]([C:8]2[CH:19]=[CH:18][C:11]3[C:12](O)=[N:13][S:14](=[O:16])(=[O:15])[C:10]=3[CH:9]=2)=[N:4][CH:5]=[CH:6][CH:7]=1.[F:20][C:21]([F:31])([F:30])[O:22][C:23]1[CH:29]=[CH:28][C:26]([NH2:27])=[CH:25][CH:24]=1.C(C1C=CC(N)=CC=1)(C)(C)C>>[F:20][C:21]([F:30])([F:31])[O:22][C:23]1[CH:29]=[CH:28][C:26]([NH:27][C:12]2[C:11]3[CH:18]=[CH:19][C:8]([C:3]4[C:2]([C:21]([F:31])([F:30])[F:20])=[CH:7][CH:6]=[CH:5][N:4]=4)=[CH:9][C:10]=3[S:14](=[O:16])(=[O:15])[N:13]=2)=[CH:25][CH:24]=1
Reactant: O=S1(=O)N=C(O)c2ccc(-c3ncccc3Cl)cc21
Reactant: Nc1ccc(OC(F)(F)F)cc1
Agent: CC(C)(C)c1ccc(N)cc1
Product: O=S1(=O)N=C(Nc2ccc(OC(F)(F)F)cc2)c2ccc(-c3ncccc3C(F)(F)F)cc21

Procedure:
The title compound was prepared using the procedure as described in Example 1C, substituting the product of Example 7B for the product of Example 1B, and substituting 4-trifluoromethoxy aniline for 4-tert-butylaniline. MS (DCI+) m/z 488 (M+H)+ (50%), m/z 309 (M-177)+ (100%); 1H NMR (DMSO-d6) δ 7.53 (d, J 8.5, 2H), 7.78 (dd, J 5.1, 7.2, 1H), 8.01 (m, 3H), 8.15 (s, 1H), 8.42 (d, J 8.1, 1H), 8.57 (d, J 7.1, 1H), 8.99 (d, J 4.7, 1H), 11.11 (s, 1H).
Reaction SMILES: N[C:2]1[C:3]([Cl:23])=[CH:4][C:5]([F:22])=[C:6]([N:8]2[C:13](=[O:14])[CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[N:10]3[CH:19]=[CH:20][N:21]=[C:9]23)[CH:7]=1.[ClH:24].[C:25]([O:29][CH2:30][CH3:31])(=[O:28])[CH:26]=[CH2:27].N([O-])=O.[Na+]>O.[Cu]Cl.CC(C)=O>[Cl:23][C:3]1[C:2]([CH2:27][CH2:26][C:25]([O:29][CH:30]([Cl:24])[CH3:31])=[O:28])=[CH:7][C:6]([N:8]2[C:13](=[O:14])[CH:12]=[C:11]([C:15]([F:16])([F:17])[F:18])[N:10]3[CH:19]=[CH:20][N:21]=[C:9]23)=[C:5]([F:22])[CH:4]=1
Reactant: Nc1cc(-n2c(=O)cc(C(F)(F)F)n3ccnc23)c(F)cc1Cl
Reactant: Cl
Reactant: C=CC(=O)OCC
Agent: Cl[Cu]
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Solvent: CC(C)=O
Product: CC(Cl)OC(=O)CCc1cc(-n2c(=O)cc(C(F)(F)F)n3ccnc23)c(F)cc1Cl
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a mixture of 8-(5-amino-4-chloro-2-fluorophenyl)-7,8-dihydro-5-trifluoromethylimidazo[1,2-a]pyrimidin-7-one (1.5 g), copper(I) chloride (0.06 g) and acetone (30 ml) was added concentrated hydrochloric acid (1.13 g) and ethyl acrylate (5.0 g) under ice-cooled condition. Sodium nitrite (0.38 g) dissolved in water was added slowly under ice-cooled condition to the mixture, which was then stirred for 3 hours at room temperature. The reaction solution was poured into water and extracted with ethyl acetate. The extract layer was washed with diluted hydrochloric acid and water in this order, and dried on anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by a preparative thin-layer plate of silica gel (developing solvent: ethyl acetate/hexane=3/7) to give the compound of interest (0.5 g) as a pale yellow oil.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][NH:4][C:3]2[CH:7]=[CH:8][C:9]([O:11][C:12]3[C:21]4[C:16](=[CH:17][C:18]([OH:24])=[C:19]([O:22][CH3:23])[CH:20]=4)[N:15]=[CH:14][CH:13]=3)=[CH:10][C:2]1=2.[CH3:25][C:26]1[O:30][N:29]=[C:28]([NH:31][C:32](=O)[O:33]C2C=CC([N+]([O-])=O)=CC=2)[CH:27]=1.C(N(CC)CC)C>C1COCC1>[OH:24][C:18]1[CH:17]=[C:16]2[C:21]([C:12]([O:11][C:9]3[CH:8]=[CH:7][C:3]4[N:4]([C:32]([NH:31][C:28]5[CH:27]=[C:26]([CH3:25])[O:30][N:29]=5)=[O:33])[CH2:5][CH2:6][O:1][C:2]=4[CH:10]=3)=[CH:13][CH:14]=[N:15]2)=[CH:20][C:19]=1[O:22][CH3:23]
Reactant: Cc1cc(NC(=O)Oc2ccc([N+](=O)[O-])cc2)no1
Reactant: COc1cc2c(Oc3ccc4c(c3)OCCN4)ccnc2cc1O
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: COc1cc2c(Oc3ccc4c(c3)OCCN4C(=O)Nc3cc(C)on3)ccnc2cc1O
Temperature: 50 °C
Reaction time: 16 h
Yield: 15.3 %

Procedure:
A 25-mL round bottomed flask was charged with 4-(3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yloxy)-6-methoxyquinolin-7-ol (0.124 g, 0.38 mmol), 4-nitrophenyl 5-methylisoxazol-3-ylcarbamate (0.11 g, 0.40 mmol), and THF (5.0 mL). Triethylamine (0.160 mL, 1.1 mmol) was added, the system was purged with argon, and the tube was sealed. The mixture stirred at 50° C. for 16 h. The reaction mixture was concentrated and the residue was purified via column chromatography on silica gel (RediSep 40 g column, 100% ethyl acetate for 10 min, followed by 5% methanol/dichloromethane for 20 min) to afford 7-(7-hydroxy-6-methoxyquinolin-4-yloxy)-N-(5-methylisoxazol-3-yl)-2,3-dihydrobenzo[b][1,4]oxazine-4-carboxamide (0.026 g, 15% yield) as a yellow solid.
Reaction SMILES: [NH2:1][C@H:2]([C:4]1[N:5]=[C:6]2[CH:11]=[CH:10][CH:9]=[C:8]([C:12]([O:14][CH3:15])=[O:13])[N:7]2[C:16]=1[C:17]1[CH:18]=[N:19][CH:20]=[C:21]([F:23])[CH:22]=1)[CH3:3].[NH2:24][C:25]1[C:30]([C:31]#[N:32])=[C:29](Cl)[N:28]=[CH:27][N:26]=1.CCN(C(C)C)C(C)C>C(O)CCC>[NH2:24][C:25]1[N:26]=[CH:27][N:28]=[C:29]([NH:1][C@H:2]([C:4]2[N:5]=[C:6]3[CH:11]=[CH:10][CH:9]=[C:8]([C:12]([O:14][CH3:15])=[O:13])[N:7]3[C:16]=2[C:17]2[CH:18]=[N:19][CH:20]=[C:21]([F:23])[CH:22]=2)[CH3:3])[C:30]=1[C:31]#[N:32]
Reactant: COC(=O)c1cccc2nc([C@H](C)N)c(-c3cncc(F)c3)n12
Reactant: N#Cc1c(N)ncnc1Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CCCCO
Product: COC(=O)c1cccc2nc([C@H](C)Nc3ncnc(N)c3C#N)c(-c3cncc(F)c3)n12

Procedure:
A solution of (S)-methyl 2-(1-aminoethyl)-3-(5-fluoropyridin-3-yl)imidazo[1,2-a]pyridine-5-carboxylate (0.151 g, 0.480 mmol), 4-amino-6-chloropyrimidine-5-carbonitrile (0.089 g, 0.576 mmol) and DIEA (0.252 mL, 1.441 mmol) in n-butanol (2.40 mL) was stirred at 110° C. for 2 h. The mixture was loaded onto silica gel and purified by MPLC (eluted with a gradient of 0-7% MeOH in DCM) to afford the methyl 2-((1S)-1-((6-amino-5-cyano-4-pyrimidinyl)amino)ethyl)-3-(5-fluoro-3-pyridinyl)imidazo[1,2-a]pyridine-5-carboxylate as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.55 (d, J=6.65 Hz, 3H) 3.33 (s, 3H) 5.41 (quin, J=6.65 Hz, 1H) 7.16 (d, J=7.24 Hz, 1H) 7.23 (br. s., 2H) 7.38-7.50 (m, 2H) 7.75-7.90 (m, 2H) 7.95 (dd, J=8.61, 1.57 Hz, 1H) 8.42 (br. s., 1H) 8.62 (d, J=2.74 Hz, 1H). LC-MS (ESI) m/z 433.1 [M+H]+.
Reaction SMILES: [C:1]1([C:7](=O)[CH:8]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:9][C:10]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1(C)C(C)=CC=CC=1.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:36].S>C(O)C>[C:1]1([C:7]2[S:36][C:10]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)=[CH:9][C:8]=2[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: COc1ccc(C(=O)CC(C(=O)c2ccccc2)c2ccccc2)cc1
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Agent: S
Solvent: Cc1ccccc1C
Solvent: CCO
Product: COc1ccc(-c2cc(-c3ccccc3)c(-c3ccccc3)s2)cc1
Yield: 142.8 %

Procedure:
In a 1-liter steel autoclave fitted with a mechanical stirrer, a thermometer and a pressure gauge were placed 32 g (0.09 mole) of 1,2-diphenyl-4-p-methoxyphenylbutane-1,4-dione, 100 ml of xylene, 20 g (0.045 mole) of phosphorus pentasulfide and 130 g of hydrogen sulfide. The mixture was stirred and heated 3 hours at 157°-162° C. (1190-1220 psig). The vessel was cooled and the hydrogen sulfide vented into an aqueous sodium hydroxide trap. The semisolid residue was stirred with 150 ml of absolute ethanol. Filtration gave 23 g (72%) of crude product, m.p. 130°-132° C. and a second crop of 3.7 g (11.6%) m.p. 124°-126° C. The two crops were combined and recrystallized from a mixture of 30 ml of dioxane and 60 ml of absolute ethanol to give 22 g (69%) of pure product m.p. 133°-134° C.
Reaction SMILES: [NH2:1][C:2]1[CH:34]=[CH:33][C:5]([C:6]([O:8][CH2:9][CH2:10][O:11][C:12](=[O:32])[CH2:13][CH2:14][C@H:15]([N:19]2[C:31]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[C:25]3[C:20]2=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:16]([OH:18])=[O:17])=[O:7])=[CH:4][CH:3]=1.Cl.N([O-])=O.[Na+].[N-:40]=[N+:41]=[N-].[Na+]>CC(C)=O.O>[N:1]([C:2]1[CH:3]=[CH:4][C:5]([C:6]([O:8][CH2:9][CH2:10][O:11][C:12](=[O:32])[CH2:13][CH2:14][C@H:15]([N:19]2[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:25]=3[C:26]3[C:31]2=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:16]([OH:18])=[O:17])=[O:7])=[CH:33][CH:34]=1)=[N+:40]=[N-:41]
Reactant: [N-]=[N+]=[N-]
Reactant: Nc1ccc(C(=O)OCCOC(=O)CC[C@@H](C(=O)O)n2c3ccccc3c3ccccc32)cc1
Agent: Cl
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Solvent: CC(C)=O
Product: [N-]=[N+]=Nc1ccc(C(=O)OCCOC(=O)CC[C@@H](C(=O)O)n2c3ccccc3c3ccccc32)cc1
Reaction time: 0.08 h
Yield: 84.2 %

Procedure:
To a stirred solution of 25 (0.38 g, 0.83 mmol) in acetone (8 mL) was added 5% HCl (8 mL) at 0° C. and the solution was stiffed for 5 min NaNO2 (0.70 g, 1.0 mmol) in 1 mL water was added dropwise to the above solution causing an immediate color change from colorless to orange. After 20 min of stiffing at 0° C., NaN3 (0.107 g, 1.65 mmol) in 1 mL water was added dropwise to the reaction mixture causing an immediate color changed from orange to colorless to pale yellow. The reaction mixture was stiffed for additional 30 min and extracted with ethyl acetate (100 mL), washed with water (30 mL) and brine (30 mL). The final organic layer was dried over anhydrous Na2SO4, filtrated and concentrated under reduced pressure to obtain (S)-5-(2-(4-azidobenzoyloxy)ethoxy)-2-(9H-carbazol-9-yl)-5-oxopentanoic acid 26 (0.34 g, 85%) as an off white gummy solid.
Reaction SMILES: [F:1][C:2]1[C:3]([CH3:17])=[CH:4][CH:5]=[C:6]2[C:11]=1[NH:10][C:9]([C:12]([O:14][CH3:15])=[O:13])=[CH:8][C:7]2=O.O=P(Cl)(Cl)[Cl:20]>>[Cl:20][C:7]1[C:6]2[C:11](=[C:2]([F:1])[C:3]([CH3:17])=[CH:4][CH:5]=2)[N:10]=[C:9]([C:12]([O:14][CH3:15])=[O:13])[CH:8]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: COC(=O)c1cc(=O)c2ccc(C)c(F)c2[nH]1
Product: COC(=O)c1cc(Cl)c2ccc(C)c(F)c2n1
Yield: 75 %

Procedure:
Methyl 8-fluoro-7-methyl-4-oxo-1,4-dihydroquinoline-2-carboxylate (7-7, 1.23 g, 5.23 mmol) in POCl3 (11 ml) was heated at 100° C. for 1 hour. The excess POCl3 was removed in vacuo. The resulting residue was triturated with ether, then filtered and washed with ether till no brown color remained in the ether. The remaining solid was Methyl 4-chloro-8-fluoro-7-methylquinoline-2-carboxylate (7-8, 993 mg, 75% yield) 100% pure by LCMS, LRMS m/z (M+H)+ 254.0 found, 254.1 required.
Reaction SMILES: Br[CH2:2][C:3]1[C:12]([C:13]([O:15][CH2:16][CH2:17][CH3:18])=[O:14])=[C:11]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH3:28])[CH:20]=2)[C:10]2[C:5](=[CH:6][C:7]([O:31][CH3:32])=[C:8]([O:29][CH3:30])[CH:9]=2)[N:4]=1.[NH:33]1[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1>ClCCl>[CH3:30][O:29][C:8]1[CH:9]=[C:10]([C:11]2[C:19]3[C:24](=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH3:28])[CH:20]=3)[N:4]=[C:3]([CH2:2][N:33]3[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]3)[C:12]=2[C:13]([O:15][CH2:16][CH2:17][CH3:18])=[O:14])[CH:5]=[CH:6][C:7]=1[O:31][CH3:32]
Reactant: CCCOC(=O)c1c(CBr)nc2cc(OC)c(OC)cc2c1-c1ccc(OC)c(OC)c1
Reactant: C1CCNCC1
Solvent: ClCCl
Product: CCCOC(=O)c1c(CN2CCCCC2)nc2cc(OC)c(OC)cc2c1-c1ccc(OC)c(OC)c1
Temperature: 25 °C
Reaction time: 48 h
Yield: 52.9 %

Procedure:
A mixture of propyl 2-bromomethyl-4-(3,4-dimethoxyphenyl)-6,7-dimethoxyquinoline-3-carboxylate (1.5 g), piperidine (1.27 g) and dichloromethane (30 ml) was stirred at room temperature for 2 days. The reaction mixture was washed with water and dried over magnesium sulfate, and the solvent was evaporated. The residue was subjected to column chromatography on silica gel. The fractions eluted with chloroform-ethyl acetate (10:1, v/v) gave propyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-piperidinomethylquinoline-3-carboxylate (0.8 g, 53%). This compound was recrystallized from ethyl acetate - hexane. Colorless prisms, mp. 129°-131° C.
Reaction SMILES: [Cl:1][C:2]1[CH:19]=[CH:18][C:5]2[N:6]([C:11]3[CH:12]=[N:13][C:14]([Cl:17])=[CH:15][CH:16]=3)[C:7]([CH2:9]Cl)=[N:8][C:4]=2[CH:3]=1.CS(N1C2C(=CC=CC=2)C=N1)(=O)=O.[CH3:33][S:34]([C:37]1[C:45]2[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=2)[NH:39][N:38]=1)(=[O:36])=[O:35]>>[Cl:1][C:2]1[CH:19]=[CH:18][C:5]2[N:6]([C:11]3[CH:12]=[N:13][C:14]([Cl:17])=[CH:15][CH:16]=3)[C:7]([CH2:9][N:39]3[C:40]4[C:45](=[CH:44][CH:43]=[CH:42][CH:41]=4)[C:37]([S:34]([CH3:33])(=[O:35])=[O:36])=[N:38]3)=[N:8][C:4]=2[CH:3]=1
Reactant: CS(=O)(=O)c1n[nH]c2ccccc12
Reactant: ClCc1nc2cc(Cl)ccc2n1-c1ccc(Cl)nc1
Agent: CS(=O)(=O)n1ncc2ccccc21
Product: CS(=O)(=O)c1nn(Cc2nc3cc(Cl)ccc3n2-c2ccc(Cl)nc2)c2ccccc12

Procedure:
The title compound was prepared in analogy to Example 3-1 by using 5-chloro-2-chloromethyl-1-(6-chloro-pyridin-3-yl)-1H-benzoimidazole and methanesulfonyl-1H-indazole instead of 5-chloro-2-chloromethyl-1-(4,4,4-trifluoro-butyl)-1H-benzoimidazole and 3-methanesulfonyl-1H-indazole.
Reaction SMILES: [CH2:1](Cl)[CH2:2][CH2:3][CH2:4][CH3:5].[Mg].Cl[SiH:9]1[CH2:14][CH2:13][CH:12]([CH2:15][CH2:16][C@H:17]2[CH2:22][CH2:21][C@H:20]([C:23]3[CH:28]=[CH:27][C:26]([C:29]4[CH:34]=[CH:33][C:32]([Cl:35])=[C:31]([F:36])[CH:30]=4)=[CH:25][CH:24]=3)[CH2:19][CH2:18]2)[CH2:11][CH2:10]1>C1COCC1>[CH2:1]([Si@H:9]1[CH2:10][CH2:11][C@H:12]([CH2:15][CH2:16][C@H:17]2[CH2:18][CH2:19][C@H:20]([C:23]3[CH:28]=[CH:27][C:26]([C:29]4[CH:34]=[CH:33][C:32]([Cl:35])=[C:31]([F:36])[CH:30]=4)=[CH:25][CH:24]=3)[CH2:21][CH2:22]2)[CH2:13][CH2:14]1)[CH2:2][CH2:3][CH2:4][CH3:5]
Reactant: Fc1cc(-c2ccc([C@H]3CC[C@H](CCC4CC[SiH](Cl)CC4)CC3)cc2)ccc1Cl
Reactant: CCCCCCl
Agent: [Mg]
Solvent: C1CCOC1
Product: CCCCC[Si@H]1CC[C@H](CC[C@H]2CC[C@H](c3ccc(-c4ccc(Cl)c(F)c4)cc3)CC2)CC1

Procedure:
10.7 g (0.1 mol) of n-pentyl chloride was dripped into a mixture of 2.5 g (0.1 mol) of magnesium and 300 ml of THF to obtain a Grignard's reagent. This solution was then dripped into a 300 ml THF solution of 45 g (0.1 mol) of 4-(trans-4-(2-(4-chloro-4-silacyclohexyl)ethyl)cyclohexyl)-3'-fluoro-4'-chlorobiphenyl to obtain 4-(trans-4-(2-(trans-4-n-pentyl-4-silacyclohexyl)ethyl)cyclohexyl)-3'-fluoro-4'-chlorobiphenyl. The silacyclohexane rings of the product were a mixture of trans isomers and cis isomers. They were separated by means of chromatography to obtain 31.3 g (yield 69.9%) of the trans isomer.
Reaction SMILES: [C:1]1([CH2:7][N:8]2[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N:15]1[CH:20]=[CH:19][CH:18]=[C:17]([NH2:21])[CH:16]=1.CC1C=CC=CC=1.CC1C=CC(S(O)(=O)=O)=CC=1>O>[C:1]1([CH2:7][N:8]2[CH2:13][CH2:12][C:11](=[N:21][C:17]3[CH:16]=[N:15][CH:20]=[CH:19][CH:18]=3)[CH2:10][CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C1CCN(Cc2ccccc2)CC1
Reactant: Nc1cccnc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: Cc1ccccc1
Product: c1ccc(CN2CCC(=Nc3cccnc3)CC2)cc1

Procedure:
A mixture of 19 parts of 1-(phenylmethyl)-4-piperidinone, 11.8 parts of 3-pyridinamine, 120 parts of methylbenzene and a small volume of 4-methylbenzenesulfonic acid is stirred and refluxed for 5 hours. (The reaction vessel is provided with reflux-condensor and water-separator). After the calculated amount of water is separated, the solvent is evaporated. The oily residue is dissolved in 800 parts of 2,2'-oxybispropane and evaporated again, yielding 27 parts of N-[1-(phenylmethyl)-4-piperidinylidene]-3-pyridinamine as a yellow-brown oil.