Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:10]=[CH:9][C:5]=1[C:6]([OH:8])=O)([O-:3])=[O:2].C(Cl)(=O)C(Cl)=O.[Cl:23][C:24]1[CH:25]=[CH:26][C:27]([NH2:30])=[N:28][CH:29]=1.N1C=CC=CC=1>C(Cl)(Cl)Cl.CN(C)C=O>[Cl:23][C:24]1[CH:25]=[CH:26][C:27]([NH:30][C:6](=[O:8])[C:5]2[CH:9]=[CH:10][C:11]([C:13]([F:16])([F:15])[F:14])=[CH:12][C:4]=2[N+:1]([O-:3])=[O:2])=[N:28][CH:29]=1
Reactant: Nc1ccc(Cl)cn1
Reactant: O=C(O)c1ccc(C(F)(F)F)cc1[N+](=O)[O-]
Agent: O=C(Cl)C(=O)Cl
Solvent: ClC(Cl)Cl
Solvent: c1ccncc1
Solvent: CN(C)C=O
Product: O=C(Nc1ccc(Cl)cn1)c1ccc(C(F)(F)F)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 3 h
Yield: 112.8 %

Procedure:
2-Nitro-4-(trifluoromethyl)benzoic acid (3.0 g) is suspended in chloroform (25 ml), and thereto are added oxalyl chloride (1.67 ml) and N,N-dimethylformamide (2 drops) followed by stirring at room temperature for 3 hours. The reaction solution is concentrated under reduced pressure, and to the residue is poured chloroform (20 ml) to obtain a suspension. Chloroform (30 ml) is added to 5-chloro-2-aminopyridine (1.56 g) and pyridine (1.55 ml), and the solution is ice-cooled. To the solution is added dropwise the suspension prepared above. The reaction solution is stirred at room temperature for 8 hours and concentrated under reduced pressure. The residue is diluted with ethyl acetate, washed successively with 10% aqueous potassium hydrogen sulfate solution, saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over magnesium sulfate, and evaporated to remove the solvent under reduced pressure. The resulting residue is suspended into n-hexane, filtered and dried to give N-(5-chloropyridin-2-yl)-2-nitro-4-(trifluoromethyl)-benzamide (4.73 g). APCI-MS M/Z: 346/348[M+H]+
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([C:13]([OH:15])=[O:14])[CH:7]=[C:8]([CH:12]=1)[C:9]([OH:11])=[O:10])([O-:3])=[O:2].Br[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30].C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[CH2:17]([O:14][C:13]([C:6]1[CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[CH:12]=[C:8]([C:9]([O:11][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH3:17])=[O:10])[CH:7]=1)=[O:15])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30]
Reactant: CCCCCCCCCCCCCCBr
Reactant: O=C(O)c1cc(C(=O)O)cc([N+](=O)[O-])c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCCCCCCCCCCCCCOC(=O)c1cc(C(=O)OCCCCCCCCCCCCCC)cc([N+](=O)[O-])c1
Yield: 74 %

Procedure:
A mixture of 1.0 g (4.7 mmol) of 5-nitroisophthalic acid, 3.1 ml (10.3 mmol) of 1-bromotetradecane and 2.0 g (15 mmol) of potassium carbonate in 40 ml of anhydrous DMF was stirred and heated at 100° for 20 hours. Water was added to the cooled reaction mixture and the resultant solid was filtered and recrystallized from methylene chloride-methanol to give 2.1 g (74% yield, mp 60°-61°) of 5-nitro-1,3-benzenedicarboxylic acid ditetradecyl ester.
Reaction SMILES: [CH2:1]([O:5][C:6]([C:8]1[N:9]=[C:10]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=2)[C:11]2[C:16]([C:17]=1[O:18]CC1C=CC=CC=1)=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4].C1C=CC(C([C@@H]2OC[C@H](NCC3C=CC(F)=CC=3)C(O)C2)C2C=CC=CC=2)=CC=1>>[CH2:1]([O:5][C:6]([C:8]1[N:9]=[C:10]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=2)[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCOC(=O)c1nc(-c2ccccn2)c2ccccc2c1OCc1ccccc1
Agent: OC1C[C@H](C(c2ccccc2)c2ccccc2)OC[C@@H]1NCc1ccc(F)cc1
Product: CCCCOC(=O)c1nc(-c2ccccn2)c2ccccc2c1O

Procedure:
Synthesized from 4-Benzyloxy-1-pyridin-2-yl-isoquinoline-3-carboxylic acid butyl ester in analogy to example D-153 b); MS-(−)-ion M−1=321.4.
Reaction SMILES: O=[C:2]1[CH2:11][CH2:10][CH2:9][C:8]2[CH:7]=[C:6]([C:12]([NH2:14])=[O:13])[CH:5]=[CH:4][C:3]1=2.Cl.[CH2:16]([C:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([NH:32]N)[CH:27]=2)=[CH:22][CH:21]=1)[CH2:17][CH2:18][CH3:19]>>[CH2:16]([C:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:27]=[C:28]3[C:29]([C:11]4[CH2:10][CH2:9][C:8]5[CH:7]=[C:6]([C:12]([NH2:14])=[O:13])[CH:5]=[CH:4][C:3]=5[C:2]=4[NH:32]3)=[CH:30][CH:31]=2)=[CH:22][CH:21]=1)[CH2:17][CH2:18][CH3:19]
Reactant: NC(=O)c1ccc2c(c1)CCCC2=O
Reactant: CCCCc1ccc(-c2cccc(NN)c2)cc1
Agent: Cl
Product: CCCCc1ccc(-c2ccc3c4c([nH]c3c2)-c2ccc(C(N)=O)cc2CC4)cc1

Procedure:
The 5-Oxo-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid amide and (4′-Butyl-biphenyl-3-yl)-hydrazine hydrochloride (example 70, step 1) are reacted in the same manner and similar yield as example 1, step 3.11H NMR (400 MHz, d6-DMSO) δ 11.60 (s, 1H), 7.83 (m, 2H), 7.70 (d, J=8.3 Hz, 1H), 7.59 (m, 3H), 7.27-7.35 (m, 4H), 3.05 (m, 2H), 2.96 (m, 2H), 2.62 (m, 2H), 1.60 (m, 2H), 1.35 (m, 2H), 0.92 (m, 3H); LC/MS calculated for [M+H]+ C27H27N2O: 395.5, found: 395.1.
Reaction SMILES: [OH-].[Na+].C[O:4][C:5]([C:7]1[CH:11]=[C:10]([Br:12])[N:9]([CH:13]([CH3:15])[CH3:14])[C:8]=1[CH:16]([NH:24][C:25]1[CH:30]=[CH:29][C:28]([F:31])=[C:27]([Cl:32])[CH:26]=1)[C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=1)=[O:6]>C1COCC1.CO>[Br:12][C:10]1[N:9]([CH:13]([CH3:15])[CH3:14])[C:8]([CH:16]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([F:31])=[C:27]([Cl:32])[CH:26]=2)[C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)=[C:7]([C:5]([OH:6])=[O:4])[CH:11]=1
Reactant: COC(=O)c1cc(Br)n(C(C)C)c1C(Nc1ccc(F)c(Cl)c1)c1ccc(Cl)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: CC(C)n1c(Br)cc(C(=O)O)c1C(Nc1ccc(F)c(Cl)c1)c1ccc(Cl)cc1
Temperature: 80 °C
Reaction time: 10 h

Procedure:
2N aqueous NaOH (32 mmol) was added to a solution of 5-bromo-2-[(3-chloro-4-fluoro-phenylamino)-(4-chloro-phenyl)-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid methyl ester (Step D2) (1.517 mmol) in 1:1 THF/MeOH (32 mL) and the mixture was stirred at 80° C. for 10 h. After evaporation of MeOH, the pH was adjusted to 5 with addition of 10% w/w aqueous citric acid (35 mL) and extracted with EtOAc. The organic phase was dried (Na2SO4), filtered and concentrated to afford a light brown solid. tR: 8.05 min (HPLC 2); ESI-MS: tR=1.38 min, [M−H] 497/499/501 (LC-MS 2).
Reaction SMILES: C(N(CC)CC)C.[N:8]1[C:17]2[C:12](=[CH:13][C:14]([C:18]3([C:21]4[N:25]5[CH:26]=[C:27]([C:30]([OH:32])=O)[CH:28]=[N:29][C:24]5=[N:23][CH:22]=4)[CH2:20][CH2:19]3)=[CH:15][CH:16]=2)[CH:11]=[CH:10][CH:9]=1.F[P-](F)(F)(F)(F)F.[N:40]1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)[C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][C:43]=2N=N1.C1(N)CCCCC1>CN(C)C=O.CO>[CH:44]1([NH:40][C:30]([C:27]2[CH:28]=[N:29][C:24]3[N:25]([C:21]([C:18]4([C:14]5[CH:13]=[C:12]6[C:17](=[CH:16][CH:15]=5)[N:8]=[CH:9][CH:10]=[CH:11]6)[CH2:20][CH2:19]4)=[CH:22][N:23]=3)[CH:26]=2)=[O:32])[CH2:45][CH2:46][CH2:47][CH2:48][CH2:43]1
Reactant: O=C(O)c1cnc2ncc(C3(c4ccc5ncccc5c4)CC3)n2c1
Reactant: c1ccc2c(c1)nnn2O[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Agent: F[P-](F)(F)(F)(F)F
Solvent: CO
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: O=C(NC1CCCCC1)c1cnc2ncc(C3(c4ccc5ncccc5c4)CC3)n2c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Triethylamine (13.9 μL, 0.1 mmol) was added to a mixture of 3-(1-quinolin-6-ylcyclopropyl)imidazo[1,2-a]pyrimidine-6-carboxylic acid (8.26 mg, 0.025 mmol), (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (14.3 mg, 0.0275 mmol) and cyclohexanamine (5.7 μL, 0.05 mmol) in N,N-dimethylformamide (0.5 mL) at RT. The mixture was stirred at RT for 2 h, and diluted with methanol (1.3 mL). The resulting solution was purified by RP-HPLC to give the desired product. LCMS: (M+H)=412.1.
Reaction SMILES: [CH2:1]([C@@:4]1([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16](B3OC(C)(C)C(C)(C)O3)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1)[CH:2]=[CH2:3].Br[C:36]1[C:37]([OH:42])=[N:38][CH:39]=[CH:40][CH:41]=1.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCOCC1>[CH2:1]([C@@:4]1([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([C:36]3[C:37](=[O:42])[NH:38][CH:39]=[CH:40][CH:41]=3)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1)[CH:2]=[CH2:3]
Reactant: Oc1ncccc1Br
Reactant: C=CC[C@]1(c2ccc(F)cc2)CCN([C@@H](C)c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)C(=O)O1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Product: C=CC[C@]1(c2ccc(F)cc2)CCN([C@@H](C)c2ccc(-c3ccc[nH]c3=O)cc2)C(=O)O1
Temperature: 85 °C
Yield: 42.7 %

Procedure:
(R)-6-allyl-6-(4-fluorophenyl)-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one (18 mg, 0.039 mmol), 3-bromo-2-hydroxypyridine (14 mg, 2 equiv), Pd(dppf)Cl2 (3 mg, 10% mol), 2M aq Na2CO3 solution (800 μL) and 1,4-dioxane (1.5 mL) were mixed. The mixture was evacuated and refilled with N2 gas (3×) before being heated overnight at 85° C. After being cooled to rt, the mixture was filtered and acidified with 5% aq HCl solution before being purified by prep HPLC to afford (R)-6-allyl-6-(4-fluorophenyl)-3-((S)-1-(4-(2-oxo-1,2-dihydropyridin-3-yl)phenyl)ethyl)-1,3-oxazinan-2-one (7.2 mg, 43% yield). LC-MS
Reaction SMILES: [Br:1][C:2]1[C:7]([O:8][CH2:9][C:10]([O:12]CC)=[O:11])=[C:6]([O:15][CH3:16])[C:5]([O:17][CH:18]([F:20])[F:19])=[CH:4][CH:3]=1.[OH-].[Li+]>O1CCCC1.O>[Br:1][C:2]1[C:7]([O:8][CH2:9][C:10]([OH:12])=[O:11])=[C:6]([O:15][CH3:16])[C:5]([O:17][CH:18]([F:19])[F:20])=[CH:4][CH:3]=1
Reactant: CCOC(=O)COc1c(Br)ccc(OC(F)F)c1OC
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: COc1c(OC(F)F)ccc(Br)c1OCC(=O)O
Temperature: 25 °C
Reaction time: 1 h
Yield: 65.1 %

Procedure:
To a stirring solution of ethyl 2-(6-bromo-3-(difluoromethoxy)-2-methoxyphenoxy)acetate (300 mg, 0.845 mmol) in tetrahydrofuran was added lithium hydroxide in water and the reaction mixture was stirred at RT for 1 h. The reaction mixture was concentrated under reduced pressure and the obtained residue was acidified to pH 2 and then extracted with ethyl acetate. The combined ethyl acetate layers were dried over sodium sulphate and concentrated under reduced pressure to afford 2-(6-Bromo-3-(difluoromethoxy)-2-methoxyphenoxy)acetic acid as a solid (180 mg, 66%).
Reaction SMILES: Br[C:2]1[N:6]2[C:7]3[C:12]([N:13]=[C:14]([NH:15][CH2:16][CH:17]([CH3:19])[CH3:18])[C:5]2=[N:4][CH:3]=1)=[CH:11][CH:10]=[CH:9][CH:8]=3.[O:20]1[C:25]2[CH:26]=[CH:27][C:28](B(O)O)=[CH:29][C:24]=2[O:23][CH2:22][CH2:21]1.C([O-])([O-])=O.[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[O:20]1[C:25]2[CH:26]=[CH:27][C:28]([C:2]3[N:6]4[C:7]5[C:12]([N:13]=[C:14]([NH:15][CH2:16][CH:17]([CH3:19])[CH3:18])[C:5]4=[N:4][CH:3]=3)=[CH:11][CH:10]=[CH:9][CH:8]=5)=[CH:29][C:24]=2[O:23][CH2:22][CH2:21]1
Reactant: OB(O)c1ccc2c(c1)OCCO2
Reactant: CC(C)CNc1nc2ccccc2n2c(Br)cnc12
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Product: CC(C)CNc1nc2ccccc2n2c(-c3ccc4c(c3)OCCO4)cnc12
Temperature: 130 °C
Yield: 21.6 %

Procedure:
0.1 mmol (1-bromo-imidazo[1,2-a]quinoxalin-4-yl)-isobutyl-amine (intermediate example 2.1, 1 mL, 0.1 M in NMP), 0.15 mmol 2,3-dihydro-1,4-benzodioxin-6-ylboronic acid (0.3 mL, 0.5 M in NMP, 1.5 eq), 0.02 mmol Pd(dppf)Cl2 (0.533 mL, 0.0375M in NMP, 0.2 eq) and 0.3 mmol K2CO3 (0.3 mL, 1M in water, 3 eq) were combined in a sealed vial and heated at 130° C. under microwave irradiation for 60 min. After cooling, the solution was filtered and subjected to preparative HPLC to give 8.1 mg (22%) 1-(2,3-dihydro-1,4-benzodioxin-6-yl)-N-(2-methylpropyl)imidazo[1,2-a]quinoxalin-4-amine. UPLC-MS: RT==1.26 min; m/z (ES+) 375.4 [MH+]; required MW=374.4.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][C:5]2[C:8]([O:30][CH2:31][CH2:32][OH:33])=[N:9][N:10]([C:11]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:4]=2[CH:3]=1.[F:34][C:35]([F:43])(S(F)(=O)=O)C(O)=O>C(#N)C.[Cu]I>[Cl:1][C:2]1[N:7]=[CH:6][C:5]2[C:8]([O:30][CH2:31][CH2:32][O:33][CH:35]([F:43])[F:34])=[N:9][N:10]([C:11]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:4]=2[CH:3]=1
Reactant: OCCOc1nn(C(c2ccccc2)(c2ccccc2)c2ccccc2)c2cc(Cl)ncc12
Reactant: O=C(O)C(F)(F)S(=O)(=O)F
Agent: [Cu]I
Solvent: CC#N
Product: FC(F)OCCOc1nn(C(c2ccccc2)(c2ccccc2)c2ccccc2)c2cc(Cl)ncc12
Temperature: 80 °C
Yield: 55.4 %

Procedure:
A mixture of 2-((6-chloro-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-yl)oxy)ethanol (58B, 500 mg, 0.987 mmol) and copper(I) iodide (282 mg, 1.480 mmol) in acetonitrile (2861 μl) were degassed (evacuated and back filled w/Argon). 2,2-difluoro-2-(fluorosulfonyl)acetic acid (153 μl, 1.480 mmol) was added, degassed, and heated at 80° C. for 30 min. Reaction was quenched with water (1 mL), diluted with EtOAc and filtered through a celite pug. The solution was concentrated in vacuo on silica. Material was purified by normal phase column chromotography eluting with Hex/EtOAc (0-20%) affording 6-chloro-3-(2-(difluoromethoxy)ethoxy)-1-trityl-1H-pyrazolo[4,3-c]pyridine (59B, 277 mg, 0.547 mmol, 55.5% yield) as a white crystalline solid. MS: [M+H]+ m/z 506.
Reaction SMILES: [NH2:1][C@@H:2]([CH3:30])[C@@H:3]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([C:14]1[CH:23]=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][CH:15]=1)[N:9]=[CH:8]2.C(N(CC)CC)C.[O:38]1[CH:42]=[CH:41][CH:40]=[C:39]1[C:43](Cl)=[O:44]>ClCCl>[O:38]1[CH:42]=[CH:41][CH:40]=[C:39]1[C:43]([NH:1][C@@H:2]([CH3:30])[C@@H:3]([C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)[O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([C:14]1[CH:23]=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][CH:15]=1)[N:9]=[CH:8]2)=[O:44]
Reactant: O=C(Cl)c1ccco1
Reactant: COC(=O)c1ccc(-n2ncc3cc(O[C@H](c4ccccc4)[C@H](C)N)ccc32)cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)c1ccc(-n2ncc3cc(O[C@H](c4ccccc4)[C@H](C)NC(=O)c4ccco4)ccc32)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 48.2 %

Procedure:
Methyl 4-{5-[(1R,2S)-2-amino-1-phenylpropoxy]-1H-indazole-1-yl}benzoate (64.3 mg, 0.16 mmol) is dissolved in 6.1 mL of dichloromethane. Triethylamine (0.053 mL, 0.38 mmol) and 2-furoylchloride (20.9 mg, 0.16 mmol) are added. After 4 h stirring at r.t. the reaction mixture is diluted with dichloromethane, washed with water and brine and dried over Na2SO4. The reaction mixture is filtered, the solvent evaporated and the residue purified by chromatography (silicagel, eluents: ethyl acetate/hexane). 38.2 mg (48.1%) of the title compound are obtained.
Reaction SMILES: [CH2:1]=CC1C=CC=CC=1.C1C=CC=CC=1.C1(C(C2C=CC=CC=2)C)C=CC=CC=1.[C:29]1([CH:35]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=2[CH3:43])[CH3:36])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>C1(C)C(C)=CC=CC=1.C1(C)C=CC=CC=1>[C:29]1([C:35]2([CH2:36][CH3:1])[CH:41]=[CH:40][CH:39]=[C:38]([CH3:43])[CH:37]2[CH3:42])[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1
Reactant: C=Cc1ccccc1
Reactant: Cc1ccccc1C(C)c1ccccc1
Agent: CC(c1ccccc1)c1ccccc1
Solvent: Cc1ccccc1
Solvent: Cc1ccccc1C
Solvent: c1ccccc1
Product: CCC1(c2ccccc2)C=CC=C(C)C1C

Procedure:
When styrene is reacted with, for example, benzene, toluene or xylene according to the method of the present invention, 1,1-diaryl-ethane such as 1,1-diphenyl-ethane, 1-phenyl-1-tolyl-ethane, or 1-phenyl-1-xylyl-ethane is obtained, respectively, as an aralkylation product.
Reaction SMILES: C(OC([N:8]1[C:17]2[C:16]([F:18])=[CH:15][CH:14]=[CH:13][C:12]=2[CH:11]2[CH2:19][CH2:20][CH2:21][C:10]2([F:22])[C:9]1=[O:23])=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl.O.C(OCC)(=O)C>[F:22][C:10]12[CH2:21][CH2:20][CH2:19][CH:11]1[C:12]1[CH:13]=[CH:14][CH:15]=[C:16]([F:18])[C:17]=1[NH:8][C:9]2=[O:23]
Reactant: CC(C)(C)OC(=O)N1C(=O)C2(F)CCCC2c2cccc(F)c21
Solvent: O
Solvent: CCOC(C)=O
Solvent: O=C(O)C(F)(F)F
Product: O=C1Nc2c(F)cccc2C2CCCC12F
Reaction time: 0.5 h
Yield: 44.8 %

Procedure:
A solution of 200 mg (0.6 mmol) of 5-tert-butoxycarbonyl-3a,6-difluoro-1,2,3,3a,5,9b-hexahydrocyclopenta[c]quinolin-4-one in 2 ml of dichloromethane is mixed with 2 ml of trifluoroacetic acid at room temperature. After 30 minutes, the batch is diluted with water and ethyl acetate. The organic phase is separated, washed with water, saturated NaHCO3 and saturated NaCl, dried (Na2SO4) and concentrated by evaporation in a vacuum. Column chromatography of the residue on silica gel with hexane-ethyl acetate yields 60 mg of product.
Reaction SMILES: [ClH:1].[C:2]([N:6]1[CH2:11][CH2:10][N:9]([CH:12]2[CH2:29][CH2:28][C:15]3([CH2:20][CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17][CH2:16]3)[CH2:14][CH2:13]2)[CH2:8][CH2:7]1)([CH3:5])([CH3:4])[CH3:3]>CO>[ClH:1].[ClH:1].[ClH:1].[C:2]([N:6]1[CH2:11][CH2:10][N:9]([CH:12]2[CH2:29][CH2:28][C:15]3([CH2:16][CH2:17][NH:18][CH2:19][CH2:20]3)[CH2:14][CH2:13]2)[CH2:8][CH2:7]1)([CH3:5])([CH3:3])[CH3:4]
Reactant: CC(C)(C)OC(=O)N1CCC2(CCC(N3CCN(C(C)(C)C)CC3)CC2)CC1
Agent: Cl
Solvent: CO
Product: CC(C)(C)N1CCN(C2CCC3(CCNCC3)CC2)CC1
Reaction time: 0.25 h

Procedure:
Hydrogen chloride in methanol (1.25 mol/l, 5.3 ml) was added to tert-butyl 9-(4-tert-butylpiperazin-1-yl)-3-azaspiro[5.5]undecane-3-carboxylate (0.26 g, 0.661 mmol) and the mixture was refluxed for 1 h. The solvent was removed in vacuo, the residue was taken up in ethanol (10 ml) and the mixture was stirred for 15 min. Diethyl ether (50 ml) was added and the mixture was then stirred at room temperature. The precipitate was filtered out with suction, washed with diethyl ether and dried in vacuo. Yield: 0.23 g (86%)
Reaction SMILES: [OH:1][CH:2]1[CH2:6][CH2:5][CH:4]([CH:7]=O)[CH:3]1[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][OH:16].[CH2:17]([CH:19]([CH2:42][CH2:43][CH2:44][CH3:45])[C:20]([CH:22]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)=[O:21])[CH3:18]>O1CCCC1>[OH:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH:3]1[CH:4]([CH:7]=[CH:22][C:20](=[O:21])[CH:19]([CH2:17][CH3:18])[CH2:42][CH2:43][CH2:44][CH3:45])[CH2:5][CH2:6][CH:2]1[OH:1]
Reactant: O=CC1CCC(O)C1CCCCCCCO
Reactant: CCCCC(CC)C(=O)C=P(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: C1CCOC1
Product: CCCCC(CC)C(=O)C=CC1CCC(O)C1CCCCCCCO
Temperature: 0 °C

Procedure:
A mixture of 3-hydroxy-2-(7-hydroxyheptyl)-cyclopentanecarbaldehyde (6 g.) [prepared as described in Example 1]and 2-ethylhexanoylmethylenetriphenylphosphorane (9g.) in dry tetrahydrofuran (70 ml.) was heated under refux under nitrogen for 6 hours. The solvent was removed in vacuo and the residue was triturated with petrol (b.p. 40°-α°C.) with cooling to 0°C. and filtered to remove triphenylphosphine oxide. Evaporation of the filtrate then gave crude 2-(7-hydroxyheptyl)-3-(4-ethyl-3-oxo-1-octenyl)cyclopentanol (4.4 g.), ν max 1620 cm-1, 1655 cm-1 (liquid film), which was used in the next step without further purification.
Reaction SMILES: [C:1]([C:3]1[C:8](=[O:9])[N:7]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[C:12]([CH3:17])[CH:11]=2)[C:6]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[N:5][C:4]=1[S:24][CH3:25])#[N:2].[Cl:26][S:27](O)(=[O:29])=[O:28]>CO>[C:1]([C:3]1[C:8](=[O:9])[N:7]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[C:12]([CH3:17])[CH:11]=2)[C:6]([C:18]2[CH:19]=[CH:20][C:21]([S:27]([Cl:26])(=[O:29])=[O:28])=[CH:22][CH:23]=2)=[N:5][C:4]=1[S:24][CH3:25])#[N:2]
Reactant: CSc1nc(-c2ccccc2)n(-c2ccc(C)c(C)c2)c(=O)c1C#N
Reactant: O=S(=O)(O)Cl
Solvent: CO
Product: CSc1nc(-c2ccc(S(=O)(=O)Cl)cc2)n(-c2ccc(C)c(C)c2)c(=O)c1C#N
Yield: 13 %

Procedure:
A solution of 5-cyano-1-(3,4-dimethylphenyl)-4-(methylthio)-2-phenyl-6-oxo-1,6-dihydropyrimidine (3 g, 8.6 mmol) (obtained according to example 57) in chlorosulfonic acid (50.37 g, 432 mmol) was stirred at 0° C. for 2 hr and at ambient temperature for 24 hr and then poured onto ice and extracted with chloroform. The collected chloroform layer was dried over anhydrous Na2SO4 and concentrated in vacuo to yield crude compound, which was further purified by column chromatography using chloroform:methanol mixture as eluent to yield title compound (0.5 g, yield 13%). 1H-NMR (CDCl3):δ 2.37 (s, 3H), 2.65 (s, 3H), 2.68 (s, 3H), 7.26-7.55 (m, 7H). MS m/z:446.1 (M+).
Reaction SMILES: Br[CH2:2][C:3]1[CH:7]=[N:6][N:5]([C:8]2[C:13]([Cl:14])=[CH:12][C:11]([C:15]([F:18])([F:17])[F:16])=[CH:10][C:9]=2[Cl:19])[N:4]=1.[CH2:20]([SH:22])[CH3:21].[H-].[Na+].O>O1CCCC1>[Cl:19][C:9]1[CH:10]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:12]=[C:13]([Cl:14])[C:8]=1[N:5]1[N:4]=[C:3]([CH2:2][S:22][CH2:20][CH3:21])[CH:7]=[N:6]1
Reactant: FC(F)(F)c1cc(Cl)c(-n2ncc(CBr)n2)c(Cl)c1
Reactant: CCS
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CCSCc1cnn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)n1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
4-Bromomethyl-2-(2,6-dichloro-4-trifluoromethylphenyl) 2H-1,2,3-triazole (2.9 g) was added portionwise to a stirred mixture of ethanethiol (0.5 g) and sodium hydride (0.25 g) in tetrahydrofuran (30 ml) and the mixture stirred at room temperature for 3 hours. The mixture was added to water and extracted with ether. The extract was worked up to give 2-(2,6-dichloro-4-trifluoromethylphenyl)-4-(ethylthiomethyl)-2H-1,2,3-triazole, m.p. 53°-54°. (Compound 19)
Reaction SMILES: [N:1]([C@H:4]1[C@@H:8]([N:9]=[N+]=[N-])[CH2:7][N:6]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:5]1)=[N+]=[N-]>CO.[OH-].[OH-].[Pd+2]>[NH2:1][C@H:4]1[C@@H:8]([NH2:9])[CH2:7][N:6]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:5]1
Reactant: CC(C)(C)OC(=O)N1C[C@H](N=[N+]=[N-])[C@H](N=[N+]=[N-])C1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CO
Product: CC(C)(C)OC(=O)N1C[C@@H](N)[C@@H](N)C1
Reaction time: 21 h

Procedure:
To the product from Step B (1.6 g) in methanol (50 mL) was added 20% palladium hydroxide on carbon (100 mg). The reaction mixture was purged with hydrogen gas and held under 1 atmosphere of hydrogen for 21 h. The mixture was filtered through a pad of Celite and the filter cake was successively washed with methanol (3×20 mL). The combined filtrate and washings were concentrated and used without further purification. LC/MS 103.0 (M+1-100).
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.FC(F)(F)S(O[C:18]1[CH:22]=[CH:21][N:20]([CH3:23])[N:19]=1)(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+].C(O)C>C1(C)C=CC=CC=1.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl.O>[CH3:23][N:20]1[CH:21]=[CH:22][C:18]([C:6]2[CH:7]=[CH:8][C:3]([CH2:2][OH:1])=[CH:4][CH:5]=2)=[N:19]1
Reactant: OCc1ccc(B(O)O)cc1
Reactant: Cn1ccc(OS(=O)(=O)C(F)(F)F)n1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: CCO
Solvent: Cc1ccccc1
Solvent: O
Product: Cn1ccc(-c2ccc(CO)cc2)n1
Yield: 27.2 %

Procedure:
A mixture of [4-(hydroxymethyl)phenyl]boronic acid (4.46 g), 1-methyl-1H-pyrazol-3-yl trifluoromethanesulfonate (4.50 g), cesium carbonate (19.1 g) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane adduct (0.80 g) in toluene (15.0 mL)-ethanol (1.00 mL)-water (1.00 mL) was subjected to microwave irradiation at 150° C. for 1 hr. The reaction mixture was diluted with ethyl acetate, and the insoluble substance was removed by filtration. The filtrate was washed successively with saturated aqueous sodium bicarbonate solution and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (1.00 g).