Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][CH2:2][C@H:3]([NH:6][C:7]1[N:12]=[C:11]([NH:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=3)=[CH:17][CH:16]=2)[N:10]2[N:27]=[CH:28][C:29]([CH:30]([CH3:32])[CH3:31])=[C:9]2[N:8]=1)CC.NC[C@@H](O)[CH2:36][OH:37]>>[OH:37][CH2:36][C@H:2]([OH:1])[CH2:3][NH:6][C:7]1[N:12]=[C:11]([NH:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=3)=[CH:17][CH:16]=2)[N:10]2[N:27]=[CH:28][C:29]([CH:30]([CH3:32])[CH3:31])=[C:9]2[N:8]=1
Reactant: NC[C@@H](O)CO
Reactant: CC[C@H](CO)Nc1nc(NCc2ccc(-c3ccccn3)cc2)n2ncc(C(C)C)c2n1
Product: CC(C)c1cnn2c(NCc3ccc(-c4ccccn4)cc3)nc(NC[C@@H](O)CO)nc12
Yield: 35 %

Procedure:
According to the same conditions resulting in the preparation of the compound 2, the compound 10 is prepared from IIa.2 by oxidation reaction of the sulfur atom and then introduction of commercial (R)-3-amino-1,2-propanediol. Yield=35%. Oil. 1H NMR (300 MHz, CDCl3): δ 8.69 (d, 1H, J=4.5 Hz, Harom), 7.98 (d, 2H, J=8.3 Hz, Harom), 7.79-7.70 (m, 2H, Harom) 7.66 (s, 1H, Harom), 7.45 (d, 2H, J=8.3 Hz, Harom), 7.27.28-7.22 (m, 1H, Harom), 6.80 (bs, 1H, NB), 4.78 (d, 2H, J=5.8 Hz, CH2), 3.83-3.79 (m, 1H, CH), 3.65-3-3.55 (m, 4H, 2 CH2), 3.03 (hept, 1H, J=7.0 Hz, CH), 1.28 (d, 6H, J=7.0 Hz, 2 CH3). MS (BSI): m/z 434 (MH+).
Reaction SMILES: CCN(C(C)C)C(C)C.[F:10][C:11]([F:28])([F:27])[O:12][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[O:21][C:20](=[O:23])[C:19]([C:24]([OH:26])=O)=[CH:18]2.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:53]([O:55][C:56]1[CH:61]=[CH:60][C:59]([C:62]2[CH:67]=[CH:66][CH:65]=[C:64]([NH2:68])[CH:63]=2)=[CH:58][C:57]=1[CH3:69])[CH3:54]>CN(C=O)C>[CH2:53]([O:55][C:56]1[CH:61]=[CH:60][C:59]([C:62]2[CH:67]=[CH:66][CH:65]=[C:64]([NH:68][C:24]([C:19]3[C:20](=[O:23])[O:21][C:22]4[C:17]([CH:18]=3)=[CH:16][CH:15]=[CH:14][C:13]=4[O:12][C:11]([F:10])([F:28])[F:27])=[O:26])[CH:63]=2)=[CH:58][C:57]=1[CH3:69])[CH3:54]
Reactant: O=C(O)c1cc2cccc(OC(F)(F)F)c2oc1=O
Reactant: CCOc1ccc(-c2cccc(N)c2)cc1C
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCOc1ccc(-c2cccc(NC(=O)c3cc4cccc(OC(F)(F)F)c4oc3=O)c2)cc1C
Temperature: 25 °C
Yield: 52.5 %

Procedure:
DIEA (0.013 mL, 0.072 mmol) was added to 8-trifluoromethoxy-3-carboxy-coumarin (0.020 g, 0.067 mmol) and HATU (0.028 g, 0.072 mmol) in 0.37 mL of DMF with constant stirring at room temperature until a clear solution resulted. Subsequently, 4′-ethoxy-3′-methyl-biphenyl-3-ylamine (0.015 g, 0.067 mmol) was added and allowed to react overnight when a solid precipitated out of solution. The resulting precipitate was filtered, dried under suction, and finally dried overnight in vacuo to give 0.017 g of product in 53% yield: LCMS (ESI) m/z 484 (MH+).
Reaction SMILES: C([C:3]1[CH:8]=[CH:7][C:6]([N:9]=[N:10][C:11]2[CH:23]=[CH:22][C:14]([O:15][CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:13][CH:12]=2)=[CH:5][CH:4]=1)#N.[N+:24](C1C=CC(N=NC2C=CC(O)=CC=2)=CC=1)([O-:26])=[O:25].BrCC(OCC)=O>>[N+:24]([C:3]1[CH:8]=[CH:7][C:6]([N:9]=[N:10][C:11]2[CH:23]=[CH:22][C:14]([O:15][CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:13][CH:12]=2)=[CH:5][CH:4]=1)([O-:26])=[O:25]
Reactant: CCOC(=O)COc1ccc(N=Nc2ccc(C#N)cc2)cc1
Reactant: O=[N+]([O-])c1ccc(N=Nc2ccc(O)cc2)cc1
Agent: CCOC(=O)CBr
Product: CCOC(=O)COc1ccc(N=Nc2ccc([N+](=O)[O-])cc2)cc1

Procedure:
Ethyl 2-[4-(4-nitrophenylazo)phenoxy]-ethanoate was prepared in a manner similar to ethyl 2-[4-(4-cyanophenylazo)phenoxy]-ethanoate starting from 4-(4-nitrophenylazo)phenol and ethyl bromoacetate.
Reaction SMILES: [OH:1][C@@H:2]1[C@H:7]2[C@H:8]3[C@H:18]([CH2:19][CH2:20][C@:5]2([CH3:6])[C:4](=[O:22])[CH2:3]1)[C@:16]1([CH3:17])[C:11](=[CH:12][C:13](=[O:21])[CH2:14][CH2:15]1)[CH2:10][CH2:9]3.[C:23]1([SH:29])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C=O.[CH3:32]CCCCC.C(OCC)(=O)C>N(CCO)(CCO)CCO>[OH:1][C@@H:2]1[C@H:7]2[C@H:8]3[C@H:18]([CH2:19][CH2:20][C@:5]2([CH3:6])[C:4](=[O:22])[CH2:3]1)[C@:16]1([CH3:17])[C:11](=[C:12]([CH2:32][S:29][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:13](=[O:21])[CH2:14][CH2:15]1)[CH2:10][CH2:9]3
Reactant: Sc1ccccc1
Reactant: CCCCCC
Reactant: C[C@]12CCC(=O)C=C1CC[C@H]1[C@@H]3[C@@H](O)CC(=O)[C@@]3(C)CC[C@@H]12
Agent: C=O
Solvent: OCCN(CCO)CCO
Solvent: CCOC(C)=O
Product: C[C@]12CCC(=O)C(CSc3ccccc3)=C1CC[C@H]1[C@@H]3[C@@H](O)CC(=O)[C@@]3(C)CC[C@@H]12

Procedure:
15 g of 15α-hydroxyandrost-4ene-3,17-dione is reacted analogously to Example 6(a) with thiophenol and formaldehyde in triethanolamine. Chromatography of the crude product on silica gel with a hexane-ethyl acetate gradient yields 11 g of 15α-hydroxy-4-(phenylthiomethyl)androst-4ene-3,17-dione as a foam.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([CH:8]([CH3:10])[CH3:9])[C:5]([NH:11]S(C2C=CC(C)=CC=2)(=O)=O)=[C:4]([CH:22]([CH3:24])[CH3:23])[CH:3]=1.Br[CH2:26][CH2:27][O:28][CH2:29][CH2:30]Br.C(N(CC)C(C)C)(C)C.CN1CCCC1>C(OCC)(=O)C>[CH:22]([C:4]1[CH:3]=[C:2]([N:1]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)[CH:7]=[C:6]([CH:8]([CH3:9])[CH3:10])[C:5]=1[NH2:11])([CH3:23])[CH3:24]
Reactant: Cc1ccc(S(=O)(=O)Nc2c(C(C)C)cc(N)cc2C(C)C)cc1
Reactant: BrCCOCCBr
Agent: CN1CCCC1
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)c1cc(N2CCOCC2)cc(C(C)C)c1N
Temperature: 180 °C
Reaction time: 3 h
Yield: 99 %

Procedure:
A mixture of N-(4-amino-2,6-diisopropyl-phenyl)-4-methyl-benzenesulfonamide (346 mg), bis-(2-bromoethyl)ether (151 μL), N,N-diisopropyl-ethylamine (0.53 mL) and N-methylpyrrolidine (1.0 mL) was heated to 180° C. for 20 minutes in a sealed microwave process vial. The mixture was diluted with ethyl acetate (20 mL), washed with brine (30 mL) and saturated aqueous potassium carbonate (30 mL) and dried over sodium sulfate. The organic phase was concentrated in vacuo and redissolved in a mixture of sulfuric acid (1.9 mL) and water (0.1 mL) and stirred at 40° C. for 3 hours. Ice (30 mL) and water (30 mL) were added and the mixture was basified with solid potassium carbonate. The mixture was extracted with ethyl acetate (3×20 mL) and the combined organic phases were dried over sodium sulfate and concentrated in vacuo to furnish 260 mg (99%) of the title compound as a white solid. 1H NMR (500 MHz, CDCl3): 1.26 (d, 12H), 2.95 (m, 2H), 3.06 (m, 4H), 3.49 (b, 2H), 3.87 (m, 4H), 6.69 (s, 2H).
Reaction SMILES: [Cl:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=[O:20])[C:18]3[C:13]4=[C:14]([CH2:22][CH:23]([CH2:24][OH:25])[N:12]4[CH:11]=2)[CH:15]=[C:16](I)[CH:17]=3)=[O:9])=[CH:4][CH:3]=1.CN([CH:31]=[O:32])C.[CH2:33](N(CC)CC)[CH3:34]>>[Cl:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=[O:20])[C:18]3[C:13]4=[C:14]([CH2:22][CH:23]([CH2:24][OH:25])[N:12]4[CH:11]=2)[CH:15]=[C:16]([C:33]#[C:34][CH2:31][OH:32])[CH:17]=3)=[O:9])=[CH:4][CH:3]=1
Reactant: CN(C)C=O
Reactant: CCN(CC)CC
Reactant: O=C(NCc1ccc(Cl)cc1)c1cn2c3c(cc(I)cc3c1=O)CC2CO
Product: O=C(NCc1ccc(Cl)cc1)c1cn2c3c(cc(C#CCO)cc3c1=O)CC2CO
Temperature: 65 °C
Yield: 70 %

Procedure:
A solution containing N-(4-chlorobenzyl)-2-(hydroxymethyl)-8-iodo-6-oxo-1,2-dihydro-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide (Preparation 10, 0.15 g), anhydrous DMF (6 mL), and triethylamine (0.8 mL) is purged with nitrogen three times before adding propargyl alcohol (19 μL), copper(I)iodide (14 mg), and PdCl2(PPh3)2 (8 mg). The solution is heated to 65° C. and then is cooled, diluted with CH2Cl2 (25 mL), and poured into water (30 mL). The organic layer is washed with brine, dried (Na2SO4), filtered, and concentrated to give a brown residue. The crude product is chromatographed eluting with 0-6% methanol in CH2Cl2 (250 mL each) to give 90 mg (70%) of the title compound as a white solid. Physical characteristics: M.p. 224-225° C.; MS (ESI+) m/z 423 (M+H)+.
Reaction SMILES: [H-].[Na+].C(O)(C)(C)C.[H][H].[CH3:10][C:11]1[C:16]([C:17]([O:19]CC)=[O:18])=[CH:15][N:14]=[CH:13][CH:12]=1.[Br:22][C:23]1[CH:30]=[CH:29][C:26]([CH:27]=O)=[CH:25][CH:24]=1>CN(C=O)C>[Br:22][C:23]1[CH:30]=[CH:29][C:26]([CH:27]=[CH:10][C:11]2[C:16]([C:17]([OH:19])=[O:18])=[CH:15][N:14]=[CH:13][CH:12]=2)=[CH:25][CH:24]=1
Reactant: [H][H]
Reactant: O=Cc1ccc(Br)cc1
Reactant: CCOC(=O)c1cnccc1C
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CC(C)(C)O
Product: O=C(O)c1cnccc1C=Cc1ccc(Br)cc1
Temperature: 0 °C
Yield: 40.2 %

Procedure:
0.9 g (22.5 mmol) of a 60% suspension of sodium hydride in paraffin are added to a solution of 2.25 g (30.40 mmol) of tertbutanol in 27.5 ml of DMF. The whole is heated in a water bath for 30′ till the evolution of hydrogen ends. The system is cooled at 0° C. and 2.5 g (15.13 mmol) of ethyl 4-methylnicotinate in 2.5 ml of DMF are dropped with stirring. After 1.5 hr stirring at the same temperature, 3.4 g (18.37 mmol) of 4-bromobenzaldehyde in 2.5 ml DMF are dropped. The system is stirred at room temperature overnight. The solution is poured over 100 g of ice and is filtered. The filtrate is acidified with acetic acid and the solid is filtered, washed with water and dried, yielding 1.85 g (40%) of a product that is used directly in the next step.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[OH:11])(=[O:4])=[O:3].C([O-])([O-])=O.[K+].[K+].Br[CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21]>CC#N.O>[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[O:11][CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])(=[O:3])=[O:4]
Reactant: CS(=O)(=O)c1ccccc1O
Reactant: CCOC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: O
Product: CCOC(=O)COc1ccccc1S(C)(=O)=O
Temperature: 80 °C
Yield: 94 %

Procedure:
To a solution of 2-(methylsulfonyl)phenol (100 mg, 0.58 mmol) and K2CO3 (276 mg, 2 mmol) in CH3CN (10 mL) was added ethyl 2-bromoacetate (115.2 mg, 0.69 mmol) at 25° C. The mixture was heated at 80° C. for 4 h, diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated. The crude product was used in the next step without further purification. (140 mg, yield 94%).
Reaction SMILES: [CH:1]([O:4][CH2:5][CH2:6][CH:7]=[CH:8][CH2:9][OH:10])([CH3:3])[CH3:2].[CH2:11]1[O:19][C:18]2[CH:17]=[CH:16][C:15](O)=[CH:14][C:13]=2[O:12]1.C1(N=C=NC2CCCCC2)CCCCC1>CCOCC>[CH:1]([O:4][CH2:5][CH2:6][CH:7]=[CH:8][CH2:9][O:10][C:16]1[CH:15]=[CH:14][C:13]2[O:12][CH2:11][O:19][C:18]=2[CH:17]=1)([CH3:3])[CH3:2]
Reactant: Oc1ccc2c(c1)OCO2
Reactant: CC(C)OCCC=CCO
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: CCOCC
Product: CC(C)OCCC=CCOc1ccc2c(c1)OCO2
Reaction time: 16 h

Procedure:
A mixture of 7.2 g (0.05 mol) of 5-isopropoxy-2-penten-1-ol, 6.9 g (0.05 mol) of 3,4-methylendioxy-phenol, and 10.3 g (0.05 mol) of dicyclohexyl-carbodiimide is stirred at 105° for 16 hours. After cooling 50 cc of ether are added, the mixture is filtered and the filtrate is evaporated. The residue is chromatographed on silica gel with hexane/ethyl acetate 9 : 1 and 5-(5-isopropoxy-2-pentenyloxy)-1,3-benzodioxol is obtained as colourless oil which is identical with the product produced in accordance with Example 39.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[C:9]([SH:11])[CH:8]=[C:7]([C:12]([CH3:15])([CH3:14])[CH3:13])[C:6]=1[OH:16])([CH3:4])([CH3:3])[CH3:2].[C:17]1(=[O:23])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1>CO>[C:1]([C:5]1[CH:10]=[C:9]([S:11][C:9]2([S:11][C:20]3[CH:21]=[C:22]([C:1]([CH3:3])([CH3:2])[CH3:4])[C:17]([OH:23])=[C:18]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH:19]=3)[CH2:10][CH2:5][CH2:6][CH2:7][CH2:8]2)[CH:8]=[C:7]([C:12]([CH3:15])([CH3:14])[CH3:13])[C:6]=1[OH:16])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)c1cc(S)cc(C(C)(C)C)c1O
Reactant: O=C1CCCCC1
Solvent: CO
Product: CC(C)(C)c1cc(SC2(Sc3cc(C(C)(C)C)c(O)c(C(C)(C)C)c3)CCCCC2)cc(C(C)(C)C)c1O
Yield: 92.9 %

Procedure:
The procedure of Example 1 was repeated using 28.71 grams of 2.6-di-tert-butyl-4-mercaptophenol, 5.91 grams of cyclohexanone, and 150 ml of methyl alcohol. The product is triturated with methyl alcohol to give 31.17 grams (93.3% yield) of white solid, mp 195°-197° C.
Reaction SMILES: [Cl:1][C:2]1[C:11]([CH3:12])=[N:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.C.[NH2:14][C:15]([NH2:17])=[S:16]>CC(C)=O>[ClH:1].[CH3:12][C:11]1[C:2]([S:16][C:15](=[NH:14])[NH2:17])=[N:3][C:4]2[C:9]([N:10]=1)=[CH:8][CH:7]=[CH:6][CH:5]=2
Reactant: Cc1nc2ccccc2nc1Cl
Reactant: NC(N)=S
Agent: C
Solvent: CC(C)=O
Product: Cc1nc2ccccc2nc1SC(=N)N
Product: Cl

Procedure:
2-Chloro-3-methylquinoxaline (10.72 g., 0.06 mole) was dissolved in 150 ml. of acetone, treated with Norit and filtered. The filtrate was added to 4.56 g. (0.06 mole) of thiourea in 150 ml. acetone. The solution was stirred at reflux under nitrogen for 2 hours. The precipitate which began to form after 5 minutes, was filtered while the reaction mixture was hot. The solid was collected, washed with hot acetone and dried to give 11.85 g. of a pink solid, m.p. 156°-157° C.
Reaction SMILES: [OH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]2[C@H:8]3[C@H:19]([CH2:20][CH2:21][C@:3]12[CH3:4])[C@:16]1([CH2:17][OH:18])[C:11](=[C:12]([CH3:23])[C:13](=[O:22])[CH2:14][CH2:15]1)[CH2:10][C@H:9]3[CH3:24].[OH:25][C@@:26]1([C:48]#[C:49][CH3:50])[CH2:31][CH2:30][C@H:29]2[C@H:32]3[C@H:43]([CH2:44][CH2:45][C@:27]12[CH3:28])[C@:40]1([CH2:41][OH:42])[C:35](=[CH:36][C:37](=[O:46])[CH2:38][CH2:39]1)[CH2:34][C@H:33]3[CH3:47].O[C@H]1CC[C@H]2[C@H]3[C@H](CC[C@]12C)[C@]1(CO)C(=CC(=O)CC1)C[C@H]3C>>[OH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]2[C@H:8]3[C@H:19]([CH2:20][CH2:21][C@:3]12[CH3:4])[C@:16]1([CH2:17][OH:18])[C:11]([C@H:12]([CH3:23])[C:13](=[O:22])[CH2:14][CH2:15]1)=[CH:10][C@H:9]3[CH3:24].[OH:25][C@@:26]1([C:48]#[C:49][CH3:50])[CH2:31][CH2:30][C@H:29]2[C@H:32]3[C@H:43]([CH2:44][CH2:45][C@:27]12[CH3:28])[C@:40]1([CH2:41][OH:42])[C:35]([CH2:36][C:37](=[O:46])[CH2:38][CH2:39]1)=[CH:34][C@H:33]3[CH3:47]
Reactant: CC1=C2C[C@@H](C)[C@@H]3[C@H](CC[C@]4(C)[C@@H](O)CC[C@@H]34)[C@@]2(CO)CCC1=O
Reactant: CC#C[C@]1(O)CC[C@H]2[C@@H]3[C@H](C)CC4=CC(=O)CC[C@]4(CO)[C@H]3CC[C@@]21C
Agent: C[C@@H]1CC2=CC(=O)CC[C@]2(CO)[C@H]2CC[C@]3(C)[C@@H](O)CC[C@H]3[C@H]12
Product: CC#C[C@]1(O)CC[C@H]2[C@@H]3[C@H](C)C=C4CC(=O)CC[C@]4(CO)[C@H]3CC[C@@]21C
Product: C[C@@H]1C(=O)CC[C@@]2(CO)C1=C[C@@H](C)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](O)CC[C@@H]12

Procedure:
Substituting 17β,19-dihydroxy-4,7α-dimethyl-4-androsten-3-one, 17β,19-dihydroxy-7α,17α-dimethyl-4-androsten-3-one, 17β,19-dihydroxy-7α-methyl-17α-propinyl-4-androsten-3-one and 7α-methyl-17β,19-di(2'-tetrahydropyranyloxy)-4-androsten-3-one for the 17β,19-dihydroxy-7α-methyl-4-androsten-3-one above results in the formation of 17β,19-dihydroxy-4α,7α-dimethyl-5-androsten-3-one, 17β, 19-dihydroxy-7α,17α-dimethyl-5-androsten-3-one, 17β,19-dihydroxy-7α-methyl-17α-propinyl-5-androsten-3-one and 7α-methyl-17β,19-di(2'-tetrahydropyranyloxy)-5-androsten-3-one, respectively.
Reaction SMILES: [H-].[Na+].[CH:3]([C:5]1[S:9][C:8]([C:10]2[S:11][C:12]([CH3:15])=[CH:13][CH:14]=2)=[CH:7][CH:6]=1)=O.[Cl:16][C:17]1[CH:31]=[CH:30][C:20]([CH2:21]P(=O)(OCC)OCC)=[CH:19][CH:18]=1>CN(C)C=O>[Cl:16][C:17]1[CH:31]=[CH:30][C:20]([CH:21]=[CH:3][C:5]2[S:9][C:8]([C:10]3[S:11][C:12]([CH3:15])=[CH:13][CH:14]=3)=[CH:7][CH:6]=2)=[CH:19][CH:18]=1
Reactant: CCOP(=O)(Cc1ccc(Cl)cc1)OCC
Reactant: Cc1ccc(-c2ccc(C=O)s2)s1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1ccc(-c2ccc(C=Cc3ccc(Cl)cc3)s2)s1
Temperature: 25 °C

Procedure:
Under a nitrogen atmosphere, 0.12 gram (0.0050 mole) of sodium hydride was added to a stirred solution of 1.2 gram (0.0057 mole) of 5-formyl-5'-methyl[2,2'-bithienyl] and 1.7 gram (0.0064 mole) of diethyl 4-chlorobenzylposphonate in 20 mL of N,N-dimethylformamide. The reaction mixture was stirred at room temperature for about three huurs. Analysis of the reaction mixture by thin layer chromatography indicated starting materials remained. Additional sodium hydride was added, and the mixture was stirred at room temperature for several hours. The reaction mixture was quenched with an aqueous solution saturated with ammonium chloride. This mixture was extracted several times with diethyl ether. The extracts were combined and washed with an aqueous solution saturated with sodium chloride. The washed extract was dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure leaving a residue. This residue was purified by column chromatography on silica gel to yield 2-(4-chlorophenyl)-1-(5'-methyl[2,2'-bithienyl]-5-yl)ethene as a solid, m.p. 157°-162° C.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC([O-])(C)C.[K+].Br[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32]>C1COCC1>[CH2:25]([N:14]1[C:15]2[C:11](=[CH:10][C:9]([O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[CH:17][CH:16]=2)[CH:12]=[CH:13]1)[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32]
Reactant: CCCCCCCCBr
Reactant: c1ccc(COc2ccc3[nH]ccc3c2)cc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CCCCCCCCn1ccc2cc(OCc3ccccc3)ccc21
Reaction time: 3 h

Procedure:
N-Octyl-5-benzyloxyindole was prepared by general method A. 5-Benzyloxyindole (500 mg, 2.24 mmol) was dissolved in THF (20 mL) and treated with 1M KOtBu in THF (3.81 mL, 3.8 mmol). After stirring for 3 hours, 1-bromooctane (0.39 mL, 2.24 mmol) was added and the reaction mixture was stirred for an additional 24 hrs. Standard aqueous workup and purification by silica gel chromatography, eluting with 3:1 hexane/ethyl acetate, provided N-octyl-5-benzyloxyindole. 1H NMR (200 MHz, CDCl3) δ 7.68 (m, 7H), 7.35 (m, 2H), 6.78 (d, J=2.9 Hz, 1H), 5.40 (s, 2H), 4.23 (t, J=7.0 Hz, 2H), 2.05 (broad t, J=6.5 Hz, 2H), 1.62 (broad s, 10H), 1.31 (t, J=6.2 Hz, 3H)
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([C:13]([OH:15])=O)[CH:10]([CH3:12])[CH3:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.C(OC(Cl)=O)C(C)C.Cl.[CH3:32][O:33][C:34](=[O:45])[C@H:35]([CH2:37][C:38]1[CH:43]=[CH:42][C:41]([OH:44])=[CH:40][CH:39]=1)[NH2:36]>C(Cl)Cl>[CH3:32][O:33][C:34](=[O:45])[C@H:35]([CH2:37][C:38]1[CH:39]=[CH:40][C:41]([OH:44])=[CH:42][CH:43]=1)[NH:36][C:13](=[O:15])[C@H:9]([CH:10]([CH3:11])[CH3:12])[NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7]
Reactant: COC(=O)[C@@H](N)Cc1ccc(O)cc1
Reactant: CC(C)[C@H](NC(=O)OC(C)(C)C)C(=O)O
Agent: CC(C)COC(=O)Cl
Agent: Cl
Solvent: ClCCl
Solvent: CN1CCOCC1
Product: COC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)C
Temperature: -70 °C
Reaction time: 16 h

Procedure:
21.7 g of t-butoxycarbonylvaline is dissolved in 200 ml of methylene chloride. 22.2 ml of N-methylmorpholine is added to the solution. The solution is cooled to -70° C. 13.1 ml of isobutylchloroformate is then added. The reaction mixture is again cooled to -70° C. 23.2 g of tyrosine methyl ester hydrochloride is added to the reaction mixture. The reaction mixture is allowed to warm to room temperature, and then is stirred for 16 hours. The reaction mixture is extracted three times with 0.5 M potassium bisulfate and once with brine. The methylene chloride solution is dried over anhydrous sodium sulfate, filtered and stripped of solvent. The residue is dissolved in 200 ml of ethyl ether. The ether solution is added to cold rapidly stirring Skellysolve B. The white precipitate is filtered and dried to afford the product t-butoxycarbonylvalyltyrosine methyl ester.
Reaction SMILES: [N:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:15]=[CH:14][CH:13]=[N:12][C:11]2=[O:16])=[CH:6][CH:5]=1)=[N+:2]=[N-:3].[Cl:17][C:18]1[S:22][C:21]([C:23]([NH:25][CH2:26][C:27]#[CH:28])=[O:24])=[CH:20][CH:19]=1.C1CCN2C(=NCCC2)CC1>CO.C(#N)C.[Cu]I>[Cl:17][C:18]1[S:22][C:21]([C:23]([NH:25][CH2:26][C:27]2[N:3]=[N:2][N:1]([C:4]3[CH:9]=[CH:8][C:7]([N:10]4[CH:15]=[CH:14][CH:13]=[N:12][C:11]4=[O:16])=[CH:6][CH:5]=3)[CH:28]=2)=[O:24])=[CH:20][CH:19]=1
Reactant: [N-]=[N+]=Nc1ccc(-n2cccnc2=O)cc1
Reactant: C#CCNC(=O)c1ccc(Cl)s1
Agent: [Cu]I
Solvent: C1CCC2=NCCCN2CC1
Solvent: CO
Solvent: CC#N
Product: O=C(NCc1cn(-c2ccc(-n3cccnc3=O)cc2)nn1)c1ccc(Cl)s1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
1-(4-Azidophenyl)pyrimidin-2(1H)-one (2.4, 20 mg, 0.09 mmol) was dissolved in 5 mL methanol. To it were added 5-chloro-N-(prop-2-ynyl)thiophene-2-carboxamide (compound 1.4, 18 mg, 0.09 mmol), DBU (26 μL, 0.18 mmol) and CuI (17 mg, 0.09 mmol). The mixture was stirred for 2 hrs at RT, diluted with 30 mL acetonitrile, filtered through celite, concentrated in vacuo and subjected to prep HPLC to isolate the title compound. MS found for C18H13ClN6O2S (M+H)+ 413.0, 415.0 (Cl pattern).
Reaction SMILES: [OH:1][N:2]=[CH:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[C:14](=[O:15])[CH:13]([CH3:16])[NH:12][C:11]2=[O:17])=[CH:6][CH:5]=1.[H-].[Na+].[H][H].[CH2:22](Br)[CH:23]=[CH:24][CH3:25]>C(OCC)C.O>[CH2:22]([O:1][N:2]=[CH:3][C:4]1[CH:5]=[CH:6][C:7]([N:10]2[C:14](=[O:15])[CH:13]([CH3:16])[NH:12][C:11]2=[O:17])=[CH:8][CH:9]=1)[CH:23]=[CH:24][CH3:25]
Reactant: [H][H]
Reactant: CC=CCBr
Reactant: CC1NC(=O)N(c2ccc(C=NO)cc2)C1=O
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CCOCC
Product: CC=CCON=Cc1ccc(N2C(=O)NC(C)C2=O)cc1
Reaction time: 2 h

Procedure:
A solution of 0.01 mol of 3-[4-(hydroxyiminomethyl)phenyl]-5-methylhydantoin in diethyl ether is treated with 0.01 mol of sodium hydride. After hydrogen evolution stops, 0.011 mol of crotyl bromide is added. The reaction mixture is stirred for 2 hours. The reaction mixture is then poured into cold water, the layers are separated, and the aqueous layer is extracted with diethyl ether. The combined ether solutions are dried over MgSO4 and filtered, and the solvent is removed by rotary evaporator to yield 3-[4-(crotyloxyiminomethyl)phenyl]-5-methylhydantoin.
Reaction SMILES: C([Li])(C)(C)C.CCCCC.[CH3:11][O:12][C:13]1[CH:26]=[CH:25][C:16]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:15][CH:14]=1.[B:27](OC)([O:30]C)[O:28]C>CCOCC>[B:27]([C:15]1[CH:14]=[C:13]([O:12][CH3:11])[CH:26]=[CH:25][C:16]=1[NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:21])[CH3:22])([OH:30])[OH:28]
Reactant: COc1ccc(NC(=O)OC(C)(C)C)cc1
Reactant: COB(OC)OC
Agent: [Li]C(C)(C)C
Solvent: CCCCC
Solvent: CCOCC
Product: COc1ccc(NC(=O)OC(C)(C)C)c(B(O)O)c1
Temperature: -20 °C
Reaction time: 5 h
Yield: 54.8 %

Procedure:
A solution of t-butyllithium in pentane (1.70M, 200 mL, 340 mmol, 2.50 equiv) was added via cannula to a solution of tert-butyl 4-methoxycarbanilate (30.4 g, 136 mmol, 1 equiv) in ether (500 mL) at -20° C., producing a cloudy yellow solution. After stirring at -20° C. for 5 h, trimethyl borate (46.3 mL, 408 mmol, 3.00 equiv) was added. The resulting viscous solution was swirled by hand for 5 min, then was allowed to warm to 23° C. and was held at that temperature for 12 h. The product solution was partitioned between saturated aqueous ammonium chloride solution (500 mL) and ethyl acetate (500 mL). The aqueous layer was separated and further extracted with ethyl acetate (2×500 mL). The combined organic layers were dried over sodium sulfate and were concentrated. The product was purified by flash column chromatography (2.5% methanol-dichloromethane initially, grading to 10% methanol-dichloromethane) to provide the tert-Butyl 2-Borono-4-methoxycarbanilate (8) as a yellow powder (19.9 g, 55%). ##STR20##
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[CH:22]=[CH:21][C:17]([C:18]([OH:20])=[O:19])=[CH:16][CH:15]=1.[C:23](O)(=[O:26])[CH:24]=[CH2:25].C1(C=CC(O)=CC=1)O>C1C=CC=CC=1>[C:23]([O:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[CH:15]=[CH:16][C:17]([C:18]([OH:20])=[O:19])=[CH:21][CH:22]=1)(=[O:26])[CH:24]=[CH2:25]
Reactant: C=CC(=O)O
Reactant: O=C(O)c1ccc(OCCCCCCCCCCCO)cc1
Agent: Oc1ccc(O)cc1
Solvent: c1ccccc1
Product: C=CC(=O)OCCCCCCCCCCCOc1ccc(C(=O)O)cc1
Yield: 38.6 %

Procedure:
6.4 g of 4-(11-hydroxyundecanyloxy)benzoic acid and 5.8 g of acrylic acid were heat-refluxed in the pressure of hydroquinone in benzene for 80 hours. After distilling off the solvent, the product was purified by column chromatography to obtain 2.9 g of the objective product (yield: 38%).