Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]([C:20]3[CH:25]=[CH:24][C:23]([S:26]([CH3:29])(=[O:28])=[O:27])=[CH:22][CH:21]=3)[S:11][C:12]=2[C:13]2[CH:18]=[CH:17][N+:16]([O-])=[CH:15][CH:14]=2)[CH:5]=[CH:6][CH:7]=1.F[B-](F)(F)F.[CH3:35][O+:36](C)C.S(OOS([O-])(=O)=O)([O-])(=O)=O.[NH4+].[NH4+]>C(Cl)Cl.O>[CH3:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]([C:20]3[CH:25]=[CH:24][C:23]([S:26]([CH3:29])(=[O:28])=[O:27])=[CH:22][CH:21]=3)[S:11][C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[C:15]([CH2:35][OH:36])[CH:14]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: Cc1cccc(-c2nc(-c3ccc(S(C)(=O)=O)cc3)sc2-c2cc[n+]([O-])cc2)c1
Reactant: C[O+](C)C
Agent: F[B-](F)(F)F
Agent: O=S(=O)([O-])OOS(=O)(=O)[O-]
Agent: [NH4+]
Solvent: O
Solvent: ClCCl
Product: Cc1cccc(-c2nc(-c3ccc(S(C)(=O)=O)cc3)sc2-c2ccnc(CO)c2)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 59.6 %

Procedure:
To a solution of 4-[4-(3-methylphenyl)-2-(4-methylsulfonylphenyl)-1,3-thiazol-5-yl]pyridine N-oxide (0.43 g, 1.0 mmol) in methylene chloride (10 mL) was added trimethyloxonium tetrafluoroborate (0.17 g, 1.2 mmol), and the mixture was stirred for 2 hours. The reaction mixture was concentrated under reduced pressure, and methanol (15 mL) was added to the residue. To the mixture was added a solution of ammonium persulfate (0.05 g, 0.22 mmol) in water (1 mL) under reflux, and the mixture was heated to reflux for 30 minutes. A solution of ammonium persulfate (0.03 g, 0.11 mmol) in water. (1 mL) was added to the reaction mixture, and the mixture was further heated to reflux for 13 hours. The reaction mixture was cooled to room temperature, then, concentrated under reduced pressure. To the residue was added an aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The extracts were washed with brine, dried over magnesium sulfate, and filtrated and concentrated under reduced pressure. The residued was purified by column chromatography (filler: Chromatorex NH DM1020 (trade name, manufactured by Fuji Silysia Chemical Ltd.), ethyl acetate) to obtain a title compound (0.26 g, yield 61%).
Reaction SMILES: CN(C)C=O.[CH3:6][C:7]1[CH:8]=[C:9]([CH:12]=[C:13]([CH3:16])[C:14]=1[OH:15])[C:10]#[N:11].[Br:17][C:18]1[C:19]([NH:34][C:35](=[O:42])[C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[N:20][C:21]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[CH:28][CH:27]=2)=[N:22][C:23]=1Cl>O>[Br:17][C:18]1[C:19]([NH:34][C:35](=[O:42])[C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)=[N:20][C:21]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[CH:28][CH:27]=2)=[N:22][C:23]=1[O:15][C:14]1[C:13]([CH3:16])=[CH:12][C:9]([C:10]#[N:11])=[CH:8][C:7]=1[CH3:6]
Reactant: Cc1cc(C#N)cc(C)c1O
Reactant: N#Cc1ccc(Nc2nc(Cl)c(Br)c(NC(=O)c3ccccc3)n2)cc1
Solvent: O
Solvent: CN(C)C=O
Product: Cc1cc(C#N)cc(C)c1Oc1nc(Nc2ccc(C#N)cc2)nc(NC(=O)c2ccccc2)c1Br
Temperature: 25 °C

Procedure:
1000 ml of dimethylformamide, 51.52 g of 3,5-dimethyl-4-hydroxybenzonitrile, 106.9 g of diazabicyclo undecene were added to a reaction vessel and stirred at RT. The reaction mixture was maintained at same temperature for 1 hr and 100 g of N-[5-bromo-6-chloro-2-(4-cyanophenylamino)-pyrimidin-4-yl]benzamide added with continued stirring for 30 mins. The reaction mixture was heated to 100-110° C. and further maintained at same temperature for 24 hr. After completion of the reaction, the reaction mixture was cooled to RT and 2000 ml of water added and stirred at RT for 1 hr. The reaction mixture was filtered. The obtained solid was dried under vacuum (0.5 kg/cm2) at 55-60° C. overnight.
Reaction SMILES: [CH:1]1[CH:6]=[C:5]2[C:7]([N:9]([CH2:12][C:13]([OH:15])=O)[C:10](=[O:11])[C:4]2=[CH:3][CH:2]=1)=[O:8].C(N1C=CN=C1)(N1C=CN=C1)=O.[CH:28]1([C:31](=[N:33]O)[NH2:32])[CH2:30][CH2:29]1.O>CN(C=O)C>[CH:28]1([C:31]2[N:33]=[C:13]([CH2:12][N:9]3[C:7](=[O:8])[C:5]4=[CH:6][CH:1]=[CH:2][CH:3]=[C:4]4[C:10]3=[O:11])[O:15][N:32]=2)[CH2:30][CH2:29]1
Reactant: O=C(O)CN1C(=O)c2ccccc2C1=O
Reactant: NC(=NO)C1CC1
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: O
Solvent: CN(C)C=O
Product: O=C1c2ccccc2C(=O)N1Cc1nc(C2CC2)no1
Temperature: 80 °C
Reaction time: 0.25 h

Procedure:
N-Phthaloylglycine (90.7 g, 442 mmol) was dissolved in portions (because of clumping) in DMF (500 mL). 1,1′-Carbonyldiimidazole (78.9 g, 486 mmrol) was added in portions (attention CO evolution). The resulting suspension was heated at 80° C. for 20 min. and then cooled to rt, then cyclopropanecarboxamidoxime 1 added and then heated at 110° C. for 2 h. The solution was cooled to rt, then poured into water (4 L), stirred for 15 min, filtered, washed with water (400 mL) and (fried. Yield: 104 g (87%). Mp 115° C. m/z 269 (M).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][C:2]1=[O:7].[C:8]1([CH:14]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:15][C:16](O)=[O:17])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C(Cl)CCl>ClCCl>[C:19]1([CH:14]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH2:15][C:16]([N:4]2[CH2:5][CH2:6][NH:1][C:2](=[O:7])[CH2:3]2)=[O:17])[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1
Reactant: O=C(O)CC(c1ccccc1)c1ccccc1
Reactant: O=C1CNCCN1
Solvent: ClCCCl
Solvent: ClCCl
Product: O=C1CN(C(=O)CC(c2ccccc2)c2ccccc2)CCN1
Temperature: 25 °C
Reaction time: 8 h
Yield: 79.8 %

Procedure:
To a solution of piperazin-2-one (100 m g, 1 mmol), 3,3-diphenylpropanoic acid (226 mg, 1 mmol) was added EDC (382 mg, 2 mmol) in dichloromethane (5 mL). The solution was stirred at room temperature overnight and concentrated in vacuo. The residue was diluted with EtOAc, and the mixture was washed consecutively with saturated aqueous NaHCO3 and brine. The organic layer was dried (Na2SO4), filtered, and concentrated in vacuo. The crude material was purified by flash column chromatography (2:98 MeOH/DCM) to give the desired 4-(3,3-diphenylpropanoyl)piperazin-2-one product (compound 4) (246 mg, 80%) as a white powder.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][CH:7]=1.Cl.[CH3:14][C:15]1([NH:21][C:22](=[O:24])[CH3:23])[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1.C(N(CC)CC)C>[I-].[K+].CN(C)C=O>[F:12][C:9]1[CH:10]=[CH:11][C:6]([O:5][CH2:4][CH2:3][CH2:2][N:18]2[CH2:19][CH2:20][C:15]([NH:21][C:22](=[O:24])[CH3:23])([CH3:14])[CH2:16][CH2:17]2)=[CH:7][CH:8]=1
Reactant: Fc1ccc(OCCCCl)cc1
Reactant: CC(=O)NC1(C)CCNCC1
Agent: Cl
Agent: [I-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CC(=O)NC1(C)CCN(CCCOc2ccc(F)cc2)CC1
Temperature: 70 °C
Yield: 39.6 %

Procedure:
A mixture of 35.84 g of 1-(3-chloropropoxy)-4-fluorobenzene, 33 g of N-(4-methyl-4-piperidinyl)acetamide monohydrochloride, 54 ml of N,N-diethylethanamine, 0.1 g of potassium iodide and 1000 ml of N,N-dimethylformamide was stirred and heated for 1.5 hours at 70° C. The reaction mixture was cooled and the solvent was evaporated. The residue was taken up in a sodium carbonate solution in water and the product was extracted with dichloromethane. The extract was washed successively twice with water, twice with a sodium carbonate solution in water and again with water, dried, filtered and evaporated. The residue was purified by column chromatography (CHCl3 :CH3OH 95:5 by volume). The pure fractions were collected and the eluent was evaporated. The residue was crystallized from 2,2'-oxybispropane. The product was filtered off and dried in vacuo at 50° C., yielding 20.93 g of N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]acetamide; mp. 103.4° C. (interm. 2).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[C:6](B(O)O)[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:25]([O:27][C:28](=[O:42])[C:29]1[C:34]([CH3:35])=[CH:33][CH:32]=[C:31]([C:36]2[CH2:40][CH2:39][CH2:38][C:37]=2Br)[CH:30]=1)[CH3:26].O>C1(C)C(CCO)=CC=CC=1>[CH2:25]([O:27][C:28](=[O:42])[C:29]1[CH:30]=[C:31]([C:36]2[CH2:40][CH:39]=[CH:38][C:37]=2[C:6]2[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=2[O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:32]=[CH:33][C:34]=1[CH3:35])[CH3:26]
Reactant: OB(O)c1cc(Cl)ccc1OCc1ccccc1
Reactant: CCOC(=O)c1cc(C2=C(Br)CCC2)ccc1C
Agent: Cc1ccccc1CCO
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Product: CCOC(=O)c1cc(C2=C(c3cc(Cl)ccc3OCc3ccccc3)C=CC2)ccc1C
Yield: 61 %

Procedure:
(5-chloro-2-benzyloxyphenyl)boronic acid (150 mg, 0.5 mmol), Pd(0)[PPh3]4 (25 mg, 0.021 mmol), potassium carbonate (483 mg, 3.36 mmol) and (3-(2-bromo-cyclopent-1-enyl)-6-methylbenzoic acid ethyl ester (130 mg, 0.42 mmol) in toluene-ethanol (1:1 10 mL) were stirred at 90° C., under nitrogen, for 2 hrs. Upon cooling, the reaction mixture was poured into water and extracted with ethyl acetate (3×20 mL). The combined organic layers were dried (MgSO4), filters and concentrated. The residue was purified on a Biotage® using 5% of ethyl acetate in iso-hexane to give the required product as white solid (114 mg, 61%). 1HNMR (CDCl3):1.27(3H,t, J=12 Hz), 2.01–2.08(2H, m), 2.51(3H, s), 2.83(2H, t, J=6 Hz), 2.90(2H, t, J=6 Hz), 4.94(2H, s), 6.80(1H, d, J=Hz), 6.97–7.70 (9H, m), 7.70(1H, s). LC/MS; Rt=4.22 [M+H] 447 (1 Cl)
Reaction SMILES: [Br:1][C:2]1[S:6][C:5]([C:7]2([S:11]([NH2:14])(=[O:13])=[O:12])[CH2:10][CH2:9][CH2:8]2)=[N:4][CH:3]=1.[C:15](OC(=O)C)(=[O:17])[CH3:16]>N1C=CC=CC=1>[Br:1][C:2]1[S:6][C:5]([C:7]2([S:11]([NH:14][C:15](=[O:17])[CH3:16])(=[O:13])=[O:12])[CH2:8][CH2:9][CH2:10]2)=[N:4][CH:3]=1
Reactant: CC(=O)OC(C)=O
Reactant: NS(=O)(=O)C1(c2ncc(Br)s2)CCC1
Solvent: c1ccncc1
Product: CC(=O)NS(=O)(=O)C1(c2ncc(Br)s2)CCC1
Temperature: 70 °C
Reaction time: 8 h
Yield: 95.6 %

Procedure:
1-(5-Bromo-1,3-thiazol-2-yl)cyclobutanesulfonamide (110 mg, 0.370 mmol, prepared according to Example 70, Steps 1-5) was taken up in pyridine (5 mL), and acetic anhydride (524 μL, 5.55 mmol) was added. The reaction was stirred at 70° C. overnight. The reaction was concentrated to dryness, diluted with water, acidified with 2 N HCl, and extracted with CH2Cl2 (2×). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated to give N-{[1-(5-bromo-1,3-thiazol-2-yl)cyclobutyl]sulfonyl}acetamide (120 mg, 96%) as a beige solid. MS ESI: [M+H]+ m/z 338.9/340.9.
Reaction SMILES: C(OC(C#CCNCC=CCOC(=O)C)=O)(C)(C)C.[C:20]([O:24][C:25]([N:27]1[CH2:31][CH:30]2[CH:32]([CH2:36][O:37][C:38](=[O:40])[CH3:39])[CH:33]([NH2:35])[CH2:34][CH:29]2[CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21].[CH2:41]([O:48][C:49]([NH:51][CH2:52][C:53](O)=[O:54])=[O:50])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>C(#N)C>[C:20]([O:24][C:25]([N:27]1[CH2:31][CH:30]2[CH:32]([CH2:36][O:37][C:38](=[O:40])[CH3:39])[CH:33]([NH:35][C:53](=[O:54])[CH2:52][NH:51][C:49]([O:48][CH2:41][C:42]3[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=3)=[O:50])[CH2:34][CH:29]2[CH2:28]1)=[O:26])([CH3:23])([CH3:21])[CH3:22]
Reactant: O=C(O)CNC(=O)OCc1ccccc1
Reactant: CC(=O)OCC1C(N)CC2CN(C(=O)OC(C)(C)C)CC21
Agent: CC(=O)OCC=CCNCC#CC(=O)OC(C)(C)C
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: CC(=O)OCC1C(NC(=O)CNC(=O)OCc2ccccc2)CC2CN(C(=O)OC(C)(C)C)CC21
Temperature: 25 °C

Procedure:
By sequentially following the procedures of Example 3, Parts B and C, and Example 1, Parts A and B, acetic acid 4-(tert-butoxy-carbonylprop-2-ynylamino)-but-2-enyl ester is converted to 4-acetoxymethyl-5-aminooctahydrocyclopenta[c]pyrrole-2-carboxylic acid tert-butyl ester. A solution of this material and benzyloxycarbonyl glycine in acetonitrile is treated sequentially with diisopropylethylamine and TBTU, and the resulting mixture is stirred at room temperature until the reaction is complete. The mixture is concentrated under vacuum yielding a residue. The residue is purified by flash column chromatography providing the title product.
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[C:12]2[C:11]([NH:13][CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([OH:22])=[C:18]([O:23][CH3:24])[CH:17]=3)=[N:10][CH:9]=[N:8][C:7]=2[S:6][CH:5]=1.Cl[C:26]1[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[CH:28][N:27]=1>CS(C)=O.O>[Cl:3][C:4]1[C:12]2[C:11]([NH:13][CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][C:26]4[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[CH:28][N:27]=4)=[C:18]([O:23][CH3:24])[CH:17]=3)=[N:10][CH:9]=[N:8][C:7]=2[S:6][CH:5]=1
Reactant: FC(F)(F)c1ccnc(Cl)c1
Reactant: COc1cc(CCNc2ncnc3scc(Cl)c23)ccc1O
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: COc1cc(CCNc2ncnc3scc(Cl)c23)ccc1Oc1cc(C(F)(F)F)ccn1
Temperature: 80 °C
Reaction time: 0.5 h
Yield: 33 %

Procedure:
To a solution of 60 percent sodium hydride / oil dispersion (31 mg, 0.78 mmol) in DMSO (3 mL) was added 4-{2-[(5-chlorothieno[2,3-d]pyrimidin-4-yl)amino]ethyl}-2-methoxyphenol (250 mg, 0.75 mmol). After stirring for 30 min, 2-chloro-4-(trifluoromethyl)pyridine (141 mg, 0.78 mmol) was added and the reaction heated at 80° C. overnight. The reaction mixture was diluted with H2O and the precipitate collected by filtration. The filter cake washed with H2O and then dissolved in CH2Cl2. The organics were dried with (Na2SO4), filtered and the stripped in vacuo. The solid residue was triturated with a mixture of ether and pentane leaving a brown solid, 120 mg, 0.25 mmol, 33 percent yield.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH2:13][CH:14]([OH:19])[C:15]([F:18])([F:17])[F:16])[C:11](=[O:20])[N:10]([CH2:21]C3C=CC(C(OC)=O)=CC=3)[N:9]=2)=[CH:4][CH:3]=1.ClC1C=CC(C2N(CC(O)C(F)(F)F)C(=O)NN=2)=CC=1.BrC[C:54]1[CH:55]=[C:56]([CH:61]=[CH:62][CH:63]=1)[C:57]([O:59][CH3:60])=[O:58]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:12]([CH2:13][CH:14]([OH:19])[C:15]([F:18])([F:16])[F:17])[C:11](=[O:20])[N:10]([CH2:21][C:54]3[CH:55]=[C:56]([CH:61]=[CH:62][CH:63]=3)[C:57]([O:59][CH3:60])=[O:58])[N:9]=2)=[CH:6][CH:7]=1
Reactant: COC(=O)c1cccc(CBr)c1
Reactant: COC(=O)c1ccc(Cn2nc(-c3ccc(Cl)cc3)n(CC(O)C(F)(F)F)c2=O)cc1
Agent: O=c1[nH]nc(-c2ccc(Cl)cc2)n1CC(O)C(F)(F)F
Product: COC(=O)c1cccc(Cn2nc(-c3ccc(Cl)cc3)n(CC(O)C(F)(F)F)c2=O)c1

Procedure:
In the same way as for the compound from Example 24A, 267 mg (0.87 mmol) of the compound from Example 19A were reacted with 199 mg (0.87 mmol) of methyl 3-(bromomethyl)benzoate. This gave 302 mg (76% of theory) of the target compound.
Reaction SMILES: Br[C:2]1[S:3][C:4]([NH:32]C(=O)OC(C)(C)C)=[C:5]([C:7](=[O:31])[NH:8][C:9]2[CH:10]=[N:11][N:12]([CH3:30])[C:13]=2[C@@H:14]2[CH2:20][CH2:19][C@@H:18]([NH:21]C(OC(C)(C)C)=O)[C@@H:17]([F:29])[CH2:16][O:15]2)[N:6]=1.[CH:40]([N:43]1[CH:47]=[C:46](B(O)O)[CH:45]=[N:44]1)([CH3:42])[CH3:41]>>[NH2:32][C:4]1[S:3][C:2]([C:46]2[CH:45]=[N:44][N:43]([CH:40]([CH3:42])[CH3:41])[CH:47]=2)=[N:6][C:5]=1[C:7]([NH:8][C:9]1[CH:10]=[N:11][N:12]([CH3:30])[C:13]=1[C@@H:14]1[CH2:20][CH2:19][C@@H:18]([NH2:21])[C@@H:17]([F:29])[CH2:16][O:15]1)=[O:31]
Reactant: Cn1ncc(NC(=O)c2nc(Br)sc2NC(=O)OC(C)(C)C)c1[C@@H]1CC[C@@H](NC(=O)OC(C)(C)C)[C@@H](F)CO1
Reactant: CC(C)n1cc(B(O)O)cn1
Product: CC(C)n1cc(-c2nc(C(=O)Nc3cnn(C)c3[C@@H]3CC[C@@H](N)[C@@H](F)CO3)c(N)s2)cn1

Procedure:
Following the procedure for Example 101 starting from tert-butyl N-[2-bromo-4-[[5-[(2S,5R,6R)-5-(tert-butoxycarbonylamino)-6-fluoro-oxepan-2-yl]-1-methyl-pyrazol-4-yl]carbamoyl]thiazol-5-yl]carbamate (Intermediate 88), and replacing 3,6-dihydro-2H-pyran-4-boronic acid pinacol ester with (1-isopropyl-1H-pyrazol-4-yl)boronic acid gave 256. 1H NMR (400 MHz, DMSO-d6) δ 9.37 (s, 1H), 8.15 (s, 1H), 7.83 (s, 1H), 7.77 (s, 1H), 7.25 (s, 2H), 5.12-4.80 (m, 2H), 4.60-4.45 (m, 1H), 4.18-3.95 (m, 2H), 3.72 (s, 3H), 3.38-3.26 (m, 1H), 2.33-2.22 (m, 1H), 1.83-1.56 (m, 5H), 1.44 (d, J=6.7 Hz, 6H). LCMS (ES+) m/z 463 (M+1).
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[O:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[C:17]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C[CH:18]=1.C(O)C.[N+](C(OCC)=O)(C(OCC)=O)=[N-]>C(OCC)(=O)C>[CH2:17]([O:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[O:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[CH3:18]
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: N#Cc1ccc(O)c(Oc2ccccc2)c1
Agent: CCOC(=O)[N+](=[N-])C(=O)OCC
Solvent: CCOC(C)=O
Solvent: CCO
Product: CCOc1ccc(C#N)cc1Oc1ccccc1
Yield: 88.6 %

Procedure:
To a stirred solution of the product of step 2 (0.742 g, 3.51 mmol), triphenylphosphine (1.01 g, 3.85 mmol) and ethanol (0.25 mL, 4.29 mmol) in ethyl acetate (12 mL) was added, dropwise, diethyl diazodicarboxylate (0.61 mL, 3.87 mmol). After 4 hours the reaction solution was diluted with ethyl acetate and washed with aqueous sodium bicarbonate solution. The organic layer was dried (sodium sulfate) and concentrated. The resulting gum was purified by flash chromatography over silica (hexanes/ethyl acetate) to afford 0.744 g (89%) of product as a white solid: 1H NMR (CDCl3) δ7.40 (dd, J=8.4, 2.0 Hz, 1H), 7.37-7.31 (m, 2H), 7.17 (d, J=2.0 Hz, 1H), 7.13 (t, J=7.4 Hz, 1H), 7.03-6.92 (m, 3H), 4.13 (q, J=7.1 Hz, 2H), 1.37 (t, J=7.1 Hz, 3H) ppm.
Reaction SMILES: [CH:1]([C:3]1[CH:22]=[CH:21][C:6]([O:7][CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([NH:16][S:17]([CH3:20])(=[O:19])=[O:18])=[CH:12][CH:11]=2)=[CH:5][CH:4]=1)=O.[S:23]1[CH2:27][C:26](=[O:28])[NH:25][C:24]1=[O:29].C([O-])(=O)C.[Na+]>O.CC(C)=O>[CH3:20][S:17]([NH:16][C:13]1[CH:14]=[CH:15][C:10]([CH2:9][CH2:8][O:7][C:6]2[CH:21]=[CH:22][C:3]([CH:1]=[C:27]3[S:23][C:24](=[O:29])[NH:25][C:26]3=[O:28])=[CH:4][CH:5]=2)=[CH:11][CH:12]=1)(=[O:19])=[O:18]
Reactant: CS(=O)(=O)Nc1ccc(CCOc2ccc(C=O)cc2)cc1
Reactant: O=C1CSC(=O)N1
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: O
Solvent: CC(C)=O
Product: CS(=O)(=O)Nc1ccc(CCOc2ccc(C=C3SC(=O)NC3=O)cc2)cc1
Temperature: 140 °C
Reaction time: 0.33 h
Yield: 39.7 %

Procedure:
1.6 g (5 mmole) N-{4-[2-(4-formylphenoxy)ethyl]phenyl}methanesulfonamide, 0.73 g (6.25 mmole) 2,4-thiazolidinedione and 1.025 g (12.5 mmole) sodium acetate were mixed and heated to 140° C. on an oil bath under vacuum (it melted at 130° C.). It was kept at 140° C. for 20 minutes and thereafter taken off the heat. When the temperature was low enough water:acetone (2:1) was added to dissolve the reaction product. Acetone was evaporated in vacuo, acetic acid was added and the obtained crystals were filtered off and recrystallized in dichloromethane to give 0.83 g (yield 40%) of 5-(4-[2-(4-methanesulfonylamino-phenyl)ethoxy]benzylidene)thiazolidine-2,4-dione.
Reaction SMILES: [Na].[CH:2]1([N:7]2[C:11]([NH2:12])=[C:10]([C:13]([NH2:15])=[O:14])[C:9]([CH2:16][CH3:17])=[N:8]2)[CH2:6][CH2:5][CH2:4][CH2:3]1.[CH3:18][O:19][C:20]1[CH:21]=[C:22]([CH2:26][C:27](OCC)=O)[CH:23]=[CH:24][CH:25]=1.Cl>C(O)C.O>[CH:2]1([N:7]2[C:11]3=[N:12][C:27]([CH2:26][C:22]4[CH:23]=[CH:24][CH:25]=[C:20]([O:19][CH3:18])[CH:21]=4)=[N:15][C:13](=[O:14])[C:10]3=[C:9]([CH2:16][CH3:17])[NH:8]2)[CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: CCc1nn(C2CCCC2)c(N)c1C(N)=O
Reactant: CCOC(=O)Cc1cccc(OC)c1
Agent: Cl
Agent: [Na]
Solvent: O
Solvent: CCO
Product: CCc1[nH]n(C2CCCC2)c2nc(Cc3cccc(OC)c3)nc(=O)c1-2
Temperature: 25 °C
Yield: 55.4 %

Procedure:
Sodium (1.19 g) was dissolved in ethanol (85 mL) and 1-cyclopentyl-3-ethyl-5-amino-1H-pyrazole-4-carboxamide (5.7 g, 26 mmol) and then ethyl 3-methoxyphenylacetate (10 g) were added. The reaction mixture was refluxed overnight, cooled to room temperature and the solvent was stripped. Water was added to the residue, followed by 2N HCl and the precipitate which formed was collected by filtration and recrystallized from ethyl acetate to afford 5.08 g of 1-cyclopentyl-3-ethyl-6-(3-methoxyphenylmethyl)pyrazolo[3,4-d]pyrimidin-4-one, m.p. 148°-150° C.
Reaction SMILES: [CH:1]([O:10][CH:11]([CH3:13])[CH3:12])(OC(C)C)OC(C)C.[C:14]1(=O)[CH2:19][CH2:18]C[CH2:16][CH2:15]1.C(O)(C)C>[Fe](Cl)(Cl)Cl>[CH:11]([O:10][C:1]1[CH2:18][CH2:19][CH2:14][CH2:15][CH:16]=1)([CH3:12])[CH3:13]
Reactant: CC(C)OC(OC(C)C)OC(C)C
Reactant: O=C1CCCCC1
Agent: Cl[Fe](Cl)Cl
Solvent: CC(C)O
Product: CC(C)OC1=CCCCC1
Temperature: 5 °C
Yield: 92 %

Procedure:
A mixture of 190.3 g (1 mol) triisopropyl orthoformate, 98.15 g (1 mol) of cyclohexanone and 6.00 g (0.10 mol) of isopropanol was placed in a three-neck round bottom flask and cooled to about 5° C. in an ice bath. The mixture was stirred and 0.4 g (2 mmol) of reagent grade iron (III) chloride was added. Upon addition of the FeCl3 catalyst, the temperature of the mixture rose to about 15-20° C., indicating that the reaction was proceeding. The mixture was stirred at 20° C. until gas-chromatographic (“GC”) analysis indicated completion of the reaction. The by-products isopropyl formate and isopropanol were removed by distillation under reduced pressure. The remaining residue was subsequently distilled to provide 1-isopropoxy-1-cyclohexene (bp 34° C. @3 mm Hg) as a colorless liquid; the yield was 92% with a purity exceeding 99%.
Reaction SMILES: [CH:1]1([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:13]=[CH:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>S(=O)(=O)(O)O>[CH:7]1([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][C:6]=2[CH:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH3:13])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12]1
Reactant: C=Cc1ccccc1
Reactant: c1ccc(C2CCCCC2)cc1
Agent: O=S(=O)(O)O
Product: CC(c1ccccc1)c1ccccc1C1CCCCC1

Procedure:
In a reactor, 1 liter or cyclohexylbenzene and 200 ml of concentrated sulfuric acid were introduced and the resultant mixture was kept at 15° C. Then, 800 ml of a 1:1 mixture of cyclohexylbenzene and styrene was added dropwise to the resultant mixture over a period of two hours, while the temperature of the mixture was kept in the range of from 15° to 20° C. At the end of the dropwise addition of the mixture, 200 ml of concentrated sulfuric acid was added to continue the reaction further for 30 minutes. Then, the reaction mixture was washed repeatedly with water to remove residual sulfuric acid and then distilled to isolate 1-(cyclohexylphenyl)-1-phenylethane (a mixture of structural isomers). Then, 1 liter of 1-(cyclohexylphenyl)-1-phenylethane was introduced in the autoclave and, in the presence of a nickel catalyst, subjected to hydrogenation under the conditions of 100 kg/cm2G of initial hydrogen pressure and 140° to 170° C. temperature for two hours, to afford hydrogenated 1-(biphenylyl)-1-phenylethane (a mixture of structural isomers). The general attributes of this hydrogenation product were as shown in Table 4.
Reaction SMILES: [Li]CCCC.CCCCCC.Br[C:13]1[C:26]2[C:27]3=[C:28]4[C:23](=[CH:24][CH:25]=2)[CH:22]=[CH:21][CH:20]=[C:19]4[CH:18]=[CH:17][C:16]3=[CH:15][CH:14]=1.[B:29](OC)([O:32]C)[O:30]C.Cl>O1CCCC1>[C:13]1([B:29]([OH:32])[OH:30])[C:26]2[C:27]3=[C:28]4[C:23](=[CH:24][CH:25]=2)[CH:22]=[CH:21][CH:20]=[C:19]4[CH:18]=[CH:17][C:16]3=[CH:15][CH:14]=1
Reactant: COB(OC)OC
Reactant: Brc1ccc2ccc3cccc4ccc1c2c34
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: OB(O)c1ccc2ccc3cccc4ccc1c2c34
Temperature: 0 °C
Reaction time: 24 h
Yield: 70 %

Procedure:
An excess of 1.6 M n-BuLi in hexane (50 mL, 80 mmol) was added to a solution of 1-bromopyrene (20.4 g, 72.6 mmol) in 500 ml dry tetrahydrofuran at −78° C. under N2. The reaction mixture was then maintained at 0° C. for 1 h before cooling to −78° C. Trimethyl borate (10.4 g, 100 mmol) was added dropwise; the solution was then warmed slowly to room temperature and stirred for 24 h. 2N HCl (150 ml) was added and then the mixture was stirred for a further 1 h. The reaction mixture was extracted with ethyl acetate and water, dried with anhydrous magnesium sulfate, the solvent was evaporated in vacuo, and the residue was crystallized (n-hexane) to give the pyren-1-ylboronic acid 12.5 g as a yellow solid (70%)