Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[N:12]=[C:11]2[C:6]([CH:7]=[CH:8][C:9](=[O:16])[N:10]2[CH2:13][CH:14]=O)=[CH:5][CH:4]=1.[NH:17]1[CH2:22][CH2:21][CH:20]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:19][CH2:18]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.O>[CH3:1][O:2][C:3]1[N:12]=[C:11]2[C:6]([CH:7]=[CH:8][C:9](=[O:16])[N:10]2[CH2:13][CH2:14][N:17]2[CH2:18][CH2:19][CH:20]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:28])([CH3:27])[CH3:29])[CH2:21][CH2:22]2)=[CH:5][CH:4]=1
Reactant: COc1ccc2ccc(=O)n(CC=O)c2n1
Reactant: CC(C)(C)OC(=O)NC1CCNCC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Solvent: CC(=O)O
Product: COc1ccc2ccc(=O)n(CCN3CCC(NC(=O)OC(C)(C)C)CC3)c2n1
Reaction time: 0.33 h
Yield: 94.9 %

Procedure:
To a solution of 1.6 g of (7-methoxy-2-oxo-1,8-naphthyridin-1(2H)-yl)acetaldehyde in 70 mL of dichloromethane, 1.5 g of tert-butyl (piperidin-4-yl)carbamate and 0.42 mL of acetic acid were added, the mixture was stirred for 20 minutes, then 2.3 g of sodium triacetoxyborohydride was added to the reaction mixture and the mixture was stirred at room temperature for 2 hours 10 minutes. Thereto were added water, a saturated aqueous sodium hydrogen carbonate solution and chloroform, the organic layer was separated, and the aqueous layer was extracted with chloroform. The organic layer and the extract were combined, the resultant solution was washed with a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel column chromatography using an eluent of chloroform:methanol=50:1 to obtain 2.8 g of tert-butyl (1-(2-(7-methoxy-2-oxo-1,8-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)carbamate as a white foam.
Reaction SMILES: [CH2:1]([S:3][C:4]([CH3:8])([CH3:7])[C:5]#[N:6])[CH3:2].[Cl:9]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl>[Cl:9][CH:1]([S:3][C:4]([CH3:8])([CH3:7])[C:5]#[N:6])[CH3:2]
Reactant: O=C1CCC(=O)N1Cl
Reactant: CCSC(C)(C)C#N
Solvent: ClC(Cl)(Cl)Cl
Product: CC(Cl)SC(C)(C)C#N
Reaction time: 4 h
Yield: 101.5 %

Procedure:
In 10 ml of carbon tetrachloride were placed 1.4 g of 2-(ethylthio)-2-methylpropanenitrile and 1.5 g of N-chlorosuccinimide and the mixture was refluxed with stirring for four hours. Solid was filtered and the filtrate was evaporated to give 1.8 g of product as a yellow liquid. This product was used without purification.
Reaction SMILES: [CH3:1][O:2][C:3]([CH:5]1[CH:9]([C:10]([CH2:12][CH2:13][CH2:14][CH2:15][NH:16][C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])=[CH2:11])[O:8][CH:7]=[N:6]1)=[O:4].[O:27]1CCCC1>O.C(N(CC)CC)C>[CH3:1][O:2][C:3](=[O:4])[CH:5]([NH:6][CH:7]=[O:27])[CH:9]([OH:8])[C:10](=[CH2:11])[CH2:12][CH2:13][CH2:14][CH2:15][NH:16][C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18]
Reactant: C=C(CCCCNC(=O)OCc1ccccc1)C1OC=NC1C(=O)OC
Reactant: C1CCOC1
Solvent: O
Solvent: CCN(CC)CC
Product: C=C(CCCCNC(=O)OCc1ccccc1)C(O)C(NC=O)C(=O)OC

Procedure:
9.4 g (26.1 mmol) of 5-[6-(N-benzyloxycarbonylamino)hex-1-en-2-yl]-oxazoline-4-carboxylic acid methyl ester are dissolved in 40 ml of tetrahydrofuran and 20 ml of water, a few drops of triethylamine are added and the mixture is heated under reflux for 18 hours. The solvent is removed under reduced pressure and the oil that remains is taken up in a total of 125 ml of methylene chloride, dried over magnesium sulfate and concentrated to dryness by evaporation. 8-(N-benzyloxycarbonylamino)-2-formylamino-3-hydroxy-4-methylene-octanoic acid methyl ester is obtained.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:12][CH:11]([CH2:13][O:14][C:15]3[CH:20]=[CH:19][C:18]([S:21][CH:22]([CH3:25])[CH2:23][CH3:24])=[CH:17][CH:16]=3)[CH2:10][O:9]2)=[CH:4][CH:3]=1.[O-:26]I(=O)(=O)=O.[Na+]>CO.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:12][CH:11]([CH2:13][O:14][C:15]3[CH:20]=[CH:19][C:18]([S:21]([CH:22]([CH3:25])[CH2:23][CH3:24])=[O:26])=[CH:17][CH:16]=3)[CH2:10][O:9]2)=[CH:4][CH:3]=1
Reactant: [O-][I+3]([O-])([O-])[O-]
Reactant: CCC(C)Sc1ccc(OCC2COC(c3ccc(Cl)cc3)O2)cc1
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CCC(C)S(=O)c1ccc(OCC2COC(c3ccc(Cl)cc3)O2)cc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of 2-(4-chlorophenyl)-4-[4-(1-methylpropylthio)phenoxymethyl]-1,3-dioxolane (7.1 mmol) in 10 ml of methanol at 0° is added, dropwise over 5 min., sodium m-periodate (1.67 g, 7.8 mmol) in 13 ml of water. The mixture is stirred for 3 hours while warming to RT. The reaction mixture is poured into water and extracted with ether. The combined organic extracts are washed with saturated sodium thiosulfate, with water and with brine, dried and rotoevaporated to give 2-(4-chlorophenyl)-4-[4-(1-methylpropylsulfinyl)phenoxymethyl]-1,3-dioxolane.
Reaction SMILES: Cl.[C:2]1([CH3:10])[CH:7]=[CH:6][C:5]([NH:8][NH2:9])=[CH:4][CH:3]=1.[C:11]([CH2:17][C:18]#[N:19])(=O)[C:12]([CH3:15])([CH3:14])[CH3:13]>CO>[C:12]([C:11]1[CH:17]=[C:18]([NH2:19])[N:8]([C:5]2[CH:6]=[CH:7][C:2]([CH3:10])=[CH:3][CH:4]=2)[N:9]=1)([CH3:15])([CH3:14])[CH3:13]
Reactant: Cc1ccc(NN)cc1
Reactant: CC(C)(C)C(=O)CC#N
Agent: Cl
Solvent: CO
Product: Cc1ccc(-n2nc(C(C)(C)C)cc2N)cc1
Temperature: 25 °C
Yield: 116 %

Procedure:
A solution of p-tolyl-hydrazine hydrochloride (15.86 g, 100 mmol) and pivaloylacetonitrile (17.9 g, 143 mmol) dissolved in MeOH (65 mL) was heated to reflux for 18 hours under N2 atmosphere. The mixture was cooled to room temperature and concentrated under reduced pressure. The residue was triturated with ether and collected by filtration. The solid was dried under high vacuum to provide 26.6 g of white solid (99% yield).
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:15]=[C:14]([OH:16])[C:13]2[C:8](=[CH:9][C:10]([CH3:17])=[CH:11][CH:12]=2)[N:7]=1)=[O:5])C.[OH-].[Na+].Cl>C1COCC1>[OH:16][C:14]1[C:13]2[C:8](=[CH:9][C:10]([CH3:17])=[CH:11][CH:12]=2)[N:7]=[C:6]([C:4]([OH:5])=[O:3])[CH:15]=1
Reactant: CCOC(=O)c1cc(O)c2ccc(C)cc2n1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: Cc1ccc2c(O)cc(C(=O)O)nc2c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of 9.7 g of 4-Hydroxy-7-methyl-quinoline-2-carboxylic acid ethyl ester in 200 ml of THF, 84 ml of a 1M aqueous sodium hydroxide solution was added and stirred for 16 h at RT. The reaction mixture was acidified with 1M hydrochloric acid to pH 1 to precipitate the product, which was then collected by filtration. The residue was co-distilled additional two times with toluene. After drying under reduced pressure the product was pure enough for the next reaction step. Yield: 7.7 g.
Reaction SMILES: Cl.[NH2:2][CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][N:8]([CH3:11])[C:7](=[O:12])[CH:6]=1.[CH3:13][C:14]1([CH3:30])[C:18]([CH3:20])([CH3:19])[O:17][B:16]([C:21]2[CH:29]=[CH:28][C:24]([C:25](O)=[O:26])=[CH:23][CH:22]=2)[O:15]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C=O)C>[CH3:11][N:8]1[CH:9]=[CH:10][C:5]([CH2:4][CH2:3][NH:2][C:25](=[O:26])[C:24]2[CH:23]=[CH:22][C:21]([B:16]3[O:17][C:18]([CH3:19])([CH3:20])[C:14]([CH3:30])([CH3:13])[O:15]3)=[CH:29][CH:28]=2)=[CH:6][C:7]1=[O:12]
Reactant: Cn1ccc(CCN)cc1=O
Reactant: CC1(C)OB(c2ccc(C(=O)O)cc2)OC1(C)C
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: Cn1ccc(CCNC(=O)c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)cc1=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 150.4 %

Procedure:
A mixture of 4-(2-aminoethyl)-1-methylpyridin-2(1H)-one hydrochloride (76 mg, 0.4 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid (100 mg, 0.4 mmol), HATU (190 mg, 0.5 mmol) and DIEA (260 mg, 2 mmol) in 25 mL of DCM and 5 mL of DMF was stirred at room temperature overnight. The solution was washed with sat NaHCO3 (2×20 mL), brine (2×20 mL), dried over anhydrous sodium sulfate, concentrated under reduce pressure to give crude N-(2-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)ethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (230 mg) and used for next step without further purification. LC-MS: 383 [M+H]+, tR=1.41 min.
Reaction SMILES: [C:1](Cl)(=[O:5])[C:2]([CH3:4])=[CH2:3].[CH2:7]([NH:11][S:12]([C:15]1[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=1)(=[O:14])=[O:13])[CH2:8][CH2:9][CH3:10].C(N(CC)CC)C>C(Cl)Cl>[CH2:7]([NH:11][S:12]([C:15]1[CH:16]=[CH:17][C:18]([O:21][C:1](=[O:5])[C:2]([CH3:4])=[CH2:3])=[CH:19][CH:20]=1)(=[O:14])=[O:13])[CH2:8][CH2:9][CH3:10]
Reactant: CCCCNS(=O)(=O)c1ccc(O)cc1
Reactant: C=C(C)C(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: C=C(C)C(=O)Oc1ccc(S(=O)(=O)NCCCC)cc1
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 65.4 %

Procedure:
A solution of 20.91 g (0.20 mol) of methacryloyl chloride in 80 ml of methylene chloride was added to a solution of 45.86 g (0.20 mol) of N-butyl-4-hydroxybenzenesulfonamide, 20.24 g (0.20 mol) of triethylamine and 320 ml of methylene chloride and cooled to 0° C. over a period of approximately 20 minutes. The mixture was then stirred for another 1.5 hours with cooling, washed three times with water, dried over magnesium sulfate and concentrated in vacuo in a warm bath. The resultant oil (Note 1) was cooled and crystallized to an oily solid. Removal of residual solvent with high vacuum caused this material to completely solidify. This solid was recrystallized from 600 ml of cyclohexane with filtering. Collection of the white solid and drying at room temperature in vacuo gave 38.9 g of N-butyl-4-methacryloyloxybenzenesulfonamide; m.p.=59° to 60° C.
Reaction SMILES: [OH-].[Na+].[N+:3]([C:6]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:7]=1[C:8](=[O:21])[C:9]1[CH2:10][CH2:11][CH2:12][CH2:13][C:14]=1[C:15]2=[O:20])([O-])=O.C1(O)CCCCC1.[H][H]>[Ni]>[NH2:3][C:6]1[C:7]2[C:8](=[O:21])[C:9]3[C:14](=[CH:13][CH:12]=[CH:11][CH:10]=3)[C:15](=[O:20])[C:16]=2[CH:17]=[CH:18][CH:19]=1
Reactant: O=C1C2=C(CCCC2)C(=O)c2c1cccc2[N+](=O)[O-]
Reactant: [H][H]
Agent: [Ni]
Agent: [Na+]
Agent: [OH-]
Solvent: OC1CCCCC1
Product: Nc1cccc2c1C(=O)c1ccccc1C2=O
Temperature: 100 °C
Reaction time: 1 h
Yield: 82.8 %

Procedure:
3 Grams of a Raney nickel catalyst and 100 grams of a 20% aqueous sodium hydroxide solution were added to a mixture of 128 grams of 5-nitrotetrahydroanthraquinone and 1,700 grams of cyclohexanol, into which was fed hydrogen while agitating at 100° C. for having hydrogen absorbed in the starting 5-nitro compound in an amount of 2 mols per mol of the 5-nitro compound. After completion of hydrogenation, the catalyst was separated by filtration and air was passed into the resultant filtrate at 30° C. for 1 hour. The resultant solution was cooled to 10° C. to precipitate crystals, which were then separated by filtration, washed with water and dried to obtain 92 grams of 1-aminoanthraquinone having a purity of 98.2%.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][N:7]=[C:6]([O:10][C:11]2[CH:12]=[C:13]([CH3:27])[C:14]3[CH:18]([CH2:19][C:20]([O:22]CC)=[O:21])[O:17][B:16]([OH:25])[C:15]=3[CH:26]=2)[CH:5]=1)(=[NH:3])[NH2:2]>[OH-].[Na+]>[C:1]([C:4]1[CH:9]=[CH:8][N:7]=[C:6]([O:10][C:11]2[CH:12]=[C:13]([CH3:27])[C:14]3[CH:18]([CH2:19][C:20]([OH:22])=[O:21])[O:17][B:16]([OH:25])[C:15]=3[CH:26]=2)[CH:5]=1)(=[NH:2])[NH2:3]
Reactant: CCOC(=O)CC1OB(O)c2cc(Oc3cc(C(=N)N)ccn3)cc(C)c21
Agent: [Na+]
Agent: [OH-]
Product: Cc1cc(Oc2cc(C(=N)N)ccn2)cc2c1C(CC(=O)O)OB2O
Temperature: 25 °C
Reaction time: 2 h

Procedure:
The crude ethyl 2-(6-(4-carbamimidoylpyridin-2-yloxy)-1-hydroxy-4-methyl-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acetate was treated with aqueous NaOH solution (500 mg in 20 mL water). After stirring at room temperature for two hours, the reaction mixture was evaporated, acidified with 1N HCl to pH 3 and then concentrated. HPLC purification gave desired product as white solid. 1H NMR (400 MHz, DMSO-d6) δ 12.4 (b, 1H), 9.54 (m, 3H), 9.20 (b, 1H), 8.38 (d, J=4.8 Hz, 1H), 7.45 (m, 2H), 7.22 (d, J=4.8 Hz, 1H), 7.05 (d, J=2 Hz, 1H), 5.52 (dd, J=9.6, 2.4 Hz, 1H), 3.09 (dd, J=15.6, 2.4 Hz, 1H), 2.30 (s, 3H), 2.13 (dd, J=15.6, 9.6 Hz, 1H). MS (ESI) m/z=42 [M+H]+.
Reaction SMILES: C(OC([NH:11][C@H:12]([C:25]([N:27]([CH3:29])[CH3:28])=[O:26])[CH2:13][CH2:14][CH2:15][CH2:16][NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=O)C1C=CC=CC=1.[H][H]>CCO.[Pd]>[C:21]([O:20][C:18](=[O:19])[NH:17][CH2:16][CH2:15][CH2:14][CH2:13][C@H:12]([NH2:11])[C:25]([N:27]([CH3:28])[CH3:29])=[O:26])([CH3:22])([CH3:24])[CH3:23]
Reactant: CN(C)C(=O)[C@H](CCCCNC(=O)OC(C)(C)C)NC(=O)OCc1ccccc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: CN(C)C(=O)[C@@H](N)CCCCNC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 106.8 %

Procedure:
Under nitrogen atmosphere, palladium-activated carbon (10% Pd, 0.30 g) was added to a solution of 2.75 g of the compound obtained in Step 78-1 in EtOH (30 ml) and the inside of the reaction system was displaced with hydrogen gas. The solution was stirred at room temperature for two hours, then, the reaction solution was filtered, and the solvent was filtered out under reduced pressure to obtain 1.97 g of residue (pale yellow oil). The present compound was used in the next reaction without purification.
Reaction SMILES: I[C:2]1[CH:10]=[CH:9][C:8]([S:11]([CH3:14])(=[O:13])=[O:12])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[F:15][C:16]1[CH:17]=[C:18](B(O)O)[CH:19]=[CH:20][CH:21]=1>>[F:15][C:16]1[CH:21]=[C:20]([C:2]2[C:3]([C:4]([OH:6])=[O:5])=[CH:7][C:8]([S:11]([CH3:14])(=[O:13])=[O:12])=[CH:9][CH:10]=2)[CH:19]=[CH:18][CH:17]=1
Reactant: CS(=O)(=O)c1ccc(I)c(C(=O)O)c1
Reactant: OB(O)c1cccc(F)c1
Product: CS(=O)(=O)c1ccc(-c2cccc(F)c2)c(C(=O)O)c1

Procedure:
Prepared in analogy to Example B25 from 2-Iodo-5-methanesulfonyl-benzoic acid (example B19(b)) and 3-fluorobenzeneboronic acid. Yellow solid. MS (m/e): 293.2 ([M−H], 100%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]([NH:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([OH:32])=[C:27]([O:30][CH3:31])[CH:28]=3)[N:23]=[CH:22][CH:21]=2)=[CH:15][C:14]=1[F:33])=[O:11].C(=O)([O-])[O-].[K+].[K+].Cl.Cl[CH2:42][CH2:43][N:44]1[CH2:49][CH2:48][O:47][CH2:46][CH2:45]1.C(=O)([O-])O.[Na+]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]([NH:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:32][CH2:42][CH2:43][N:44]4[CH2:49][CH2:48][O:47][CH2:46][CH2:45]4)=[C:27]([O:30][CH3:31])[CH:28]=3)[N:23]=[CH:22][CH:21]=2)=[CH:15][C:14]=1[F:33])=[O:11]
Reactant: ClCCN1CCOCC1
Reactant: COc1cc2c(Oc3ccc(NC(=O)Nc4ccc(F)cc4F)c(F)c3)ccnc2cc1O
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: Cl
Agent: O=C([O-])O
Solvent: CN(C)C=O
Product: COc1cc2c(Oc3ccc(NC(=O)Nc4ccc(F)cc4F)c(F)c3)ccnc2cc1OCCN1CCOCC1
Temperature: 70 °C
Reaction time: 8 h
Yield: 56.1 %

Procedure:
N-(2,4-Difluorophenyl)-N′-{2-fluoro-4-[(7-hydroxy-6-methoxy-4-quinolyl)oxy)phenyl}urea (20 mg), potassium carbonate (7 mg), tetra-n-butylammonium iodide (2 mg), and N-(2-chloroethyl)morpholine hydrochloride (10 mg) were dissolved in N,N-dimethylformamide (1 ml), and the solution was stirred at 70° C. overnight. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with chloroform. The chloroform layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation under the reduced pressure. The residue was purified by thin-layer chromatography on silica gel by development with chloroform/methanol (30/1) to give 14 mg (yield 57%) of the title compound.
Reaction SMILES: C1N=CN(C(N2C=NC=C2)=O)C=1.[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:21]=[CH:22][C:23]([C:26]#[C:27][C:28]3[CH:39]=[CH:38][C:31]4[S:32][C:33]([C:35](O)=[O:36])=[CH:34][C:30]=4[CH:29]=3)=[N:24][CH:25]=2)=[CH:16][CH:15]=1.[BH4-].[Na+].OS([O-])(=O)=O.[K+].C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.O>[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([C:20]2[CH:21]=[CH:22][C:23]([C:26]#[C:27][C:28]3[CH:39]=[CH:38][C:31]4[S:32][C:33]([CH2:35][OH:36])=[CH:34][C:30]=4[CH:29]=3)=[N:24][CH:25]=2)=[CH:18][CH:19]=1
Reactant: O=C(O)c1cc2cc(C#Cc3ccc(-c4ccc(Cl)cc4)cn3)ccc2s1
Agent: O=C([O-])[O-]
Agent: O=C(n1ccnc1)n1ccnc1
Agent: O=S(=O)([O-])O
Solvent: CN(C)C=O
Solvent: O
Product: OCc1cc2cc(C#Cc3ccc(-c4ccc(Cl)cc4)cn3)ccc2s1
Temperature: 50 °C
Reaction time: 2 h

Procedure:
2.37 g (14.62 mmol) CDI was added to a suspension of 1.9 g (4.87 mmol) of 5-[5-(4-chlorophenyl)pyridin-2-ylethynyl]benzo[b]thiophene-2-carboxylic acid in 40 mL of DMF and the reaction mixture was heated to 50° C. overnight. After cooling to RT, the reaction solution was added to a solution of 552 mg (14.62 mmol) NaBH4 in 5 mL of water in such a way that the temperature did not exceed 30° C. The mixture was stirred for 2 hours at RT, carefully mixed with KHSO4 solution until an acidic reaction was obtained, made basic with saturated sodium carbonate solution, extracted exhaustively with DCM, the combined organic phases were washed twice with water and dried over magnesium sulfate. After the desiccant and solvent had been eliminated, the residue was triturated with PE, suction filtered, and dried in the air. Yield: 1.1 g (60% of theoretical); C22H14ClNOS (M=375.871); calc.: molpeak (M+H)+: 376/378 (Cl); found: molpeak (M+H)+: 376/378 (Cl); HPLC-MS: 6.2 minutes (method B).
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([F:19])[CH:18]=[C:13]3[CH:12]=[C:11]2[CH:20]([OH:25])[CH2:21][CH:22]([CH3:24])[CH3:23])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>ClCCl>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([F:19])[CH:18]=[C:13]3[CH:12]=[C:11]2[C:20](=[O:25])[CH2:21][CH:22]([CH3:23])[CH3:24])(=[O:9])=[O:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CC(C)CC(O)c1cc2cc(F)cnc2n1S(=O)(=O)c1ccccc1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Product: CC(C)CC(=O)c1cc2cc(F)cnc2n1S(=O)(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 88.6 %

Procedure:
To a solution of 1-(1-benzenesulfonyl-5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methyl-butan-1-ol (9.4 g, 26 mmol) in dichloromethane (400 mL) was added Dess-Martin periodinane (16.6 g, 39 mmol) at 25° C. The reaction mixture was stirred at 25° C. for 1 h and then quenched with a saturated aqueous sodium bicarbonate solution (200 mL). The mixture was extracted with dichloromethane (100 mL), washed with a saturated aqueous sodium bicarbonate solution (3×100 mL), brine, dried over anhydrous sodium sulfate and then concentrated in vacuo. Purification by flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company, 25% ethyl acetate/hexanes) afforded 1-(1-benzenesulfonyl-5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methyl-butan-1-one (8.3 g, 84%) as a light yellow solid: LC/MS m/e calcd for C18H17FN2O3S [M+H]+ 361.41, observed 360.8.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1F.[CH3:12][S:13]([O-:15])=[O:14].[Na+].O>CS(C)=O>[F:1][C:2]1[CH:3]=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[S:13]([CH3:12])(=[O:15])=[O:14]
Reactant: CS(=O)[O-]
Reactant: O=[N+]([O-])c1ccc(F)c(F)c1
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: CS(=O)(=O)c1ccc([N+](=O)[O-])cc1F
Temperature: 60 °C
Reaction time: 3 h
Yield: 79 %

Procedure:
8 g of 3,4-difluoronitrobenzene and 1.01 eq of sodium methanesulfinate (95%) was dissolved in 10 ml of DMSO. The solution was stirred at 60° C. for 3 hours. When the reaction was completed, the solution was added to 100 ml of water to form pale yellow solid, followed by filtration and washing with 50 ml of cool water and 30 ml of n-hexane separately to give 8.8 g of the title compound as a pale yellow solid (yield 79%).
Reaction SMILES: [CH3:1][C:2]1[N:11]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:9]=[CH:8][C:3]=1[C:4](OC)=[O:5].[H-].[Al+3].[Li+].[H-].[H-].[H-].[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+].CCOC(C)=O>C1COCC1.O>[CH3:1][C:2]1[C:3]([CH2:4][OH:5])=[CH:8][CH:9]=[C:10]([C:12]([F:14])([F:13])[F:15])[N:11]=1
Reactant: COC(=O)c1ccc(C(F)(F)F)nc1C
Agent: O=C([O-])[C@H](O)[C@@H](O)C(=O)[O-]
Agent: [Al+3]
Agent: [H-]
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: Cc1nc(C(F)(F)F)ccc1CO
Temperature: 25 °C
Yield: 98.1 %

Procedure:
To the solution of methyl 2-methyl-6-(trifluoromethyl)nicotinate (8.8 g, 40 mmol) in 40 mL dry THF at 0° C. under argon was added 1.0 M lithium aluminum hydride in THF solution (40 mL, 40 mmol) drop-wise over 15 min. The reaction mixture was allowed to warm to room temperature over 1 h. HPLC/MS analysis indicated that the reaction was complete. Rochelle's salt, 10% aqueous solution (20 mL) was carefully added to the stirring reaction mixture over a period of 10 min. After 1 h of subsequent stirring, 50 mL EtOAc and water were added. The layers were separated. The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated to obtain 7.5 g of the title compound as a colorless oil, which was greater than 98% pure. HPLC/MS: retention time=2.1 min, [M+H]30 =192.
Reaction SMILES: [CH:1]([C@H:3]1[CH2:7][O:6][C:5]([CH3:9])([CH3:8])[N:4]1[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])=[O:2].[CH:17]1([Mg]Br)[CH2:19][CH2:18]1>C1COCC1>[CH:17]1([CH:1]([OH:2])[C@H:3]2[CH2:7][O:6][C:5]([CH3:9])([CH3:8])[N:4]2[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:19][CH2:18]1
Reactant: Br[Mg]C1CC1
Reactant: CC(C)(C)OC(=O)N1[C@@H](C=O)COC1(C)C
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1[C@@H](C(O)C2CC2)COC1(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 84.7 %

Procedure:
To a solution of (R)-tert-butyl 4-formyl-2,2-dimethyloxazolidine-3-carboxylate (Aldrich, 12.44 g, 54.26 mmol) in THF (150 mL) at −78° C. was added cyclopropylmagnesium bromide (217 mL, 108.52 mmol) dropwise. The reaction mixture was allowed to warm to room temperature and stir overnight. The reaction was quenched with water and diluted with ethyl acetate and brine. The resulting emulsion was filtered through celite and the layers separated. The organics were dried over magnesium sulfate, filtered and concentrated. Silica gel chromatography (0%-20% ethyl acetate/hexanes) afforded the title compound as a light yellow oil (12.47 g, 85%).
Reaction SMILES: C[O:2][C:3]([C:5]1[C:19]2=[C:20]3[C:12]([C:13]4[C:18]2=[CH:17][CH:16]=[CH:15][CH:14]=4)=[CH:11][CH:10]=[CH:9][C:8]3=[CH:7][CH:6]=1)=O.[Li+].[BH4-].C1COCC1.Cl>O>[OH:2][CH2:3][C:5]1[C:19]2=[C:20]3[C:12]([C:13]4[C:18]2=[CH:17][CH:16]=[CH:15][CH:14]=4)=[CH:11][CH:10]=[CH:9][C:8]3=[CH:7][CH:6]=1
Reactant: COC(=O)c1ccc2cccc3c2c1-c1ccccc1-3
Agent: Cl
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: OCc1ccc2cccc3c2c1-c1ccccc1-3
Yield: 85.7 %

Procedure:
To a RB flask equipped with magnetic stirrer, condenser, and N2 inlet line with bubbler was added methyl-1-fluoranthenecarboxylate (3A, 71.54 g, 0.275 mol), LiBH4 (Aldrich, 100 g, 0.459 mol) and dry THF (1 L). The mixture was refluxed overnight, cooled and poured into H2O (2 L). The mixture was cautiously acidified with 1N HCl, filtered and the resulting solid washed with H2O (2×300 mL). After recrystallization (CH2Cl2 /hexane) and drying, 54.75 g (86%) of 1-hydroxymethylfluoranthene was obtained, mp 147°-185°, (C,H).
Reaction SMILES: [CH3:1][C:2]([C:10]#[N:11])([CH3:9])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[CH2:12](OCC)C>>[CH3:1][C:2]([CH3:9])([CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])[C:10](=[NH:11])[CH3:12]
Reactant: CCOCC
Reactant: CCCCCCC(C)(C)C#N
Product: CCCCCCC(C)(C)C(C)=N
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of dimethyl heptylcyanide (1.00 g, 6.53 mmol) in anhydrous diethyl ether (5 mL) was added under argon 1.6 M methyl lithium in diethyl ether (25 mL, 39.00 mmol), and the mixture was stirred for 3 hours at room temperature. After quenching with water, the mixture was extracted with diethyl ether. The extracts were dried over anhydrous Na2SO4 and the solvent was evaporated under reduced pressure to get a colorless oil which was pure enough to carry out for further reactions based on analytical data. (1.03 g, 94%). 1H NMR (300 MHz, CDCl3): ∂ 0.80-0.85 (m, 3H), 0.92-1.05 (m, 3H), 1.15-1.28 (m, 14H), 1.54-1.6 (m, 2H), 3.4 (s, 1H). (ESI, Pos) m/z 170.2