Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(O[N:4]1[CH2:9][CH2:8][CH:7]([NH:10][CH:11]2[CH2:20][CH2:19][C:18]3[C:13](=[C:14]([O:21][CH3:22])[CH:15]=[CH:16][CH:17]=3)[CH2:12]2)[CH2:6][C:5]1=C=O)C.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+].[CH3:34]COCC>>[CH3:22][O:21][C:14]1[CH:15]=[CH:16][CH:17]=[C:18]2[C:13]=1[CH2:12][CH:11]([NH:10][CH:7]1[CH2:6][CH2:5][N:4]([CH3:34])[CH2:9][CH2:8]1)[CH2:20][CH2:19]2
Reactant: CCOCC
Reactant: CCON1CCC(NC2CCc3cccc(OC)c3C2)CC1=C=O
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Product: COc1cccc2c1CC(NC1CCN(C)CC1)CC2
Temperature: 25 °C
Reaction time: 15 h
Yield: 91 %

Procedure:
A solution of 1.20 g (3.6 mmol) of 2-(1-ethoxy-carbonyl-piperidin-4-yl)amino-8-methoxy-1,2,3,4-tetrahydronaphthalene in 10 ml of ether was added dropwise at room temperature to the suspension of 0.27 g (7.2 mmol) of lithium aluminum hydride in 10 ml of ether. After stirring &for 15 hours at room temperature, the mixture was diluted with 30 ml of ether. 0.3 ml of water, 0.25 ml of 20% strength sodium hydroxide solution and 1 ml of water were subsequently carefully added dropwise. For drying, 3 g of potassium carbonate were added, and the mixture was stirred for 20 minutes. By filtration and concentration (finally high vacuum), U.90 g (91%) of the title compound was obtained as an oil.
Reaction SMILES: C([O:8][CH2:9][C:10]1[N:11]([CH2:27][CH2:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=2)[C:12]([S:18][C:19]2[CH:24]=[C:23]([Cl:25])[CH:22]=[C:21]([Cl:26])[CH:20]=2)=[C:13]([CH:15]([CH3:17])[CH3:16])[N:14]=1)C1C=CC=CC=1.Cl>C(O)C>[Cl:25][C:23]1[CH:24]=[C:19]([S:18][C:12]2[N:11]([CH2:27][CH2:28][CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=3)[C:10]([CH2:9][OH:8])=[N:14][C:13]=2[CH:15]([CH3:17])[CH3:16])[CH:20]=[C:21]([Cl:26])[CH:22]=1
Reactant: CC(C)c1nc(COCc2ccccc2)n(CCCc2ccccn2)c1Sc1cc(Cl)cc(Cl)c1
Agent: Cl
Solvent: CCO
Product: CC(C)c1nc(CO)n(CCCc2ccccn2)c1Sc1cc(Cl)cc(Cl)c1
Temperature: 90 °C
Reaction time: 2 h
Yield: 51.1 %

Procedure:
To 300 mg of 2-benzyloxymethyl-5-(3,5-dichlorophenylthio)-4-isopropyl-1-(3-(2-pyridyl)propyl)-imidazole was added 10 ml of ethanol and 20 ml of 36% hydrochloric acid, and the mixture was stirred at 90° C. for 2 hours. After completion of the reaction, the solvent was distilled off under reduced pressure, an aqueous sodium hydrogen carbonate solution was added, and extracted with ethyl acetate. The extract was dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate:methanol=10:1) to give 127 mg of 5-(3,5-dichlorophenylthio)-4-isopropyl-2-hydroxymethyl-1-(3-(2-pyridyl)propyl)-1H-imidazole (yield 51%).
Reaction SMILES: [Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([CH2:12]Br)=[CH:7]2.[C-:14]#[N:15].[Na+]>CC#N.O>[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([CH2:12][C:14]#[N:15])=[CH:7]2
Reactant: [C-]#N
Reactant: BrCc1ccc2c(Br)cccc2c1
Agent: [Na+]
Solvent: O
Solvent: CC#N
Product: N#CCc1ccc2c(Br)cccc2c1
Temperature: 25 °C
Yield: 99.1 %

Procedure:
A suspension of 5-bromo-2-bromomethylnaphthalene (4.50 g, 15 mmol) and NaCN (784 mg, 16 mmol) in 9:1 CH3CN/H2O (150 mL) was heated to reflux for 1 hour during which time the reaction mixture became homogeneous. The solution was cooled to room temperature and the volatiles removed in vacuo. The aqueous residue was partitioned between H2O (200 mL) and CH2Cl2 (200 mL). The aqueous phase was further washed with CH2Cl2 (1×200 mL) and the combined organic layers dried (Na2SO4) and concentrated in vacuo to give the product as a white solid (3.66 g, 99%). This material was of sufficient purity to be used as such without purification.
Reaction SMILES: [Cl:1][C:2]1[CH:12]=[CH:11][C:5]([CH2:6][NH:7][C:8](=O)[CH3:9])=[CH:4][CH:3]=1.B.CSC.Cl>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][CH2:8][CH3:9])=[CH:11][CH:12]=1
Reactant: CC(=O)NCc1ccc(Cl)cc1
Agent: B
Agent: Cl
Solvent: CSC
Solvent: C1CCOC1
Product: CCNCc1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 43.4 %

Procedure:
N-(4-chlorobenzyl)acetamide (2.337 g, 12.726 mmol) was dissolved in THF (100 ml) and was cooled to zero degrees under argon atmosphere. (Methylthio)methane compound with borane (1:1) (2.417 g, 31.815 mmol) was added and the mixture was refluxed overnight at RT. HCl (15 ml, 10%) was gently added and was stirred overnight. The solvent was removed by evaporation. Diethyl ether (20 ml) was added and the product was extracted to the water phase by K2CO3 (3×15 ml). The aqueous phase was acidified by HCl (10 ml, 10%) and the product was extracted to the organic phase by EtOAc (3×15 ml). The organic phase was dried (MgSO4) and the solvent was removed by evaporation to give 0.938 g of N-(4-chlorobenzyl)-N-ethylamine (yield 43.4%).
Reaction SMILES: [OH:1][CH:2]1[CH:18]2[CH:10]([CH2:11][CH:12]([OH:27])[C:13]3([CH3:26])[CH:17]2[CH2:16][CH2:15][CH:14]3[CH:19]([CH3:25])[CH2:20][CH2:21][C:22]([OH:24])=[O:23])[C:9]2([CH3:28])[CH:4]([CH2:5][CH:6]([O:29][CH2:30][CH2:31][NH:32][C:33](=[O:42])[CH2:34][C:35]3[CH:40]=[CH:39][C:38]([OH:41])=[CH:37][CH:36]=3)[CH2:7][CH2:8]2)[CH2:3]1.[CH3:43][C:44](=[CH:50][C:51]1[CH:56]=[C:55]([F:57])[C:54](F)=[C:53]([F:59])[CH:52]=1)[C:45]([O:47][CH2:48][CH3:49])=[O:46].C([O-])([O-])=O.[K+].[K+].Cl>CN(C=O)C>[C:22]([CH2:21][CH2:20][CH:19]([CH:14]1[C:13]2([CH3:26])[CH:17]([CH:18]3[CH:10]([CH2:11][CH:12]2[OH:27])[C:9]2([CH3:28])[CH:4]([CH2:5][CH:6]([O:29][CH2:30][CH2:31][NH:32][C:33]([CH2:34][C:35]4[CH:36]=[CH:37][C:38]([O:41][C:54]5[C:53]([F:59])=[CH:52][C:51]([CH:50]=[C:44]([CH3:43])[C:45]([O:47][CH2:48][CH3:49])=[O:46])=[CH:56][C:55]=5[F:57])=[CH:39][CH:40]=4)=[O:42])[CH2:7][CH2:8]2)[CH2:3][CH:2]3[OH:1])[CH2:16][CH2:15]1)[CH3:25])([OH:24])=[O:23]
Reactant: CC(CCC(=O)O)C1CCC2C3C(O)CC4CC(OCCNC(=O)Cc5ccc(O)cc5)CCC4(C)C3CC(O)C12C
Reactant: CCOC(=O)C(C)=Cc1cc(F)c(F)c(F)c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)C(C)=Cc1cc(F)c(Oc2ccc(CC(=O)NCCOC3CCC4(C)C(C3)CC(O)C3C4CC(O)C4(C)C(C(C)CCC(=O)O)CCC34)cc2)c(F)c1
Temperature: 150 °C
Reaction time: 2.67 h
Yield: 62.4 %

Procedure:
610 mg of 4-(7,12-dihydroxy-3-{2-[2-(4-hydroxyphenyl)acetylamino]ethoxy}-10,13-dimethylhexadecahydrocyclopenta[a]phenanthren-17-yl)pentanoic acid, 232 mg of ethyl 2-methyl-3-(3,4,5-trifluorophenyl)acrylate and 393 mg of K2CO3 are suspended in 5 ml of DMF (anhydrous) and the suspension is stirred at 150° C. for 160 minutes. After cooling, the reaction mixture is taken up using 150 ml of a 2N aqueous HCl solution and extracted three times using 100 ml of EA each time. The extract is dried over Na2SO4 and the solvent is removed in vacuo. Chromatography on silica gel using EA/MeOH 10:1 yields 480 mg of resinous product.
Reaction SMILES: Cl[Si](C)(C)C.CO[C:8]([CH:10]1[CH2:14][CH2:13][CH2:12][C:11]1=O)=[O:9].[NH2:16][C:17]([NH2:19])=[O:18].[OH-].[Na+].Cl>CN(C=O)C.O>[N:16]1[C:11]2[CH2:12][CH2:13][CH2:14][C:10]=2[C:8]([OH:9])=[N:19][C:17]=1[OH:18]
Reactant: NC(N)=O
Reactant: COC(=O)C1CCCC1=O
Agent: C[Si](C)(C)Cl
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: Oc1nc(O)c2c(n1)CCC2
Reaction time: 48 h
Yield: 79.2 %

Procedure:
Chlorotrimethylsilane (20.9 g, 193.6 mmol) was added drop wise under nitrogen to a solution of 2-oxo-cyclopentanecarboxylic acid methyl ester (25 g, 176 mmol) and urea (19.01 g, 316 mmol) in anhydrous DMF (200 mL) at 0° C. After addition, the mixture was warmed to a temperature in the range of 15° C. to 40° C. and stirred for 48 hours. Water was added to the mixture and the resultant precipitate was filtered, washed with water followed by petroleum ether and dried in vacuo. The solid was suspended to a solution of sodium hydroxide (19.9 g, 499 mmol) in water (280 mL) and stirred at 70° C. for 1 hour. After cooling to a temperature in the range of 15° C. to 40° C., concentrated hydrochloric acid was added drop wise to adjust the pH to ˜2. The resultant precipitate was filtered, washed with water and dried in vacuo to afford the title compound as a white solid (21.2 g, 79% yield).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[C:10]([C:12]([OH:14])=O)[CH:11]=1)[NH:8][C:7](=[O:15])[CH2:6]2.O1CCCC1.[C:21]1([Li])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[C:10]([C:12](=[O:14])[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH:11]=1)[NH:8][C:7](=[O:15])[CH2:6]2
Reactant: [Li]c1ccccc1
Reactant: COc1cc2c(c(C(=O)O)c1)NC(=O)C2
Solvent: C1CCOC1
Solvent: O
Product: COc1cc2c(c(C(=O)c3ccccc3)c1)NC(=O)C2
Reaction time: 2 h

Procedure:
A suspension of 1.0 g. (4.9 mmole) of 5-methoxy-7-carboxyindolin-2-one in 20 ml. of tetrahydrofuran was treated dropwise with 12 ml. of commercially prepared phenyllithium solution (2.3 molar ether: benzene; 0.28 moles). After stirring for two hours the reaction mixture was poured into water and extracted several times with ethyl ether and benzene. The combined extracts were washed with water, dried over sodium sulfate and concentrated using a rotary evaporator to a solid residue which on recrystallization from acetone-water gave 259 mg. (21%) of a yellow powder which melted at 154° C.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[C:6]([C:12](=[O:15])[CH2:13]Br)[CH:5]=1.C(=O)([O-])[O-].[K+].[K+].[CH:23]1[C:28]([OH:29])=[CH:27][CH:26]=[CH:25][C:24]=1[CH3:30]>CN(C=O)C>[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[C:6]([C:12](=[O:15])[CH2:13][O:29][C:28]2[CH:23]=[C:24]([CH3:30])[CH:25]=[CH:26][CH:27]=2)[CH:5]=1
Reactant: COC(=O)c1ccc(OC)c(C(=O)CBr)c1
Reactant: Cc1cccc(O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(OC)c(C(=O)COc2cccc(C)c2)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 37.8 %

Procedure:
The compound of step 1 (1.18 g, 4.12 mmol) and potassium carbonate (1.72 g, 12.4 mmol) were suspended in DMF (10 ml), m-cresol (450 mg, 4.12 mmol) was added, and the mixture was stirred at room temperature for 2 h. The volatiles were evaporated in vacuo, the residue was partitioned between EA and water, and the aqueous phase extracted with EA. The combined organic extracts were washed with a sodium chloride solution, dried over sodium sulfate, filtered and evaporated to dryness. The residue was purified by preparative RP HPLC (water/ACN gradient) to give 0.49 g of the title compound.
Reaction SMILES: [NH2:1][C:2]1[C:3]([F:11])=[C:4]([CH:7]=[CH:8][C:9]=1[F:10])[CH2:5][NH2:6].[C:12](Cl)(=[O:17])[C:13]([CH3:16])([CH3:15])[CH3:14]>C1COCC1.CCOC(C)=O>[NH2:1][C:2]1[C:3]([F:11])=[C:4]([CH:7]=[CH:8][C:9]=1[F:10])[CH2:5][NH:6][C:12](=[O:17])[C:13]([CH3:16])([CH3:15])[CH3:14]
Reactant: CC(C)(C)C(=O)Cl
Reactant: NCc1ccc(F)c(N)c1F
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(C)(C)C(=O)NCc1ccc(F)c(N)c1F
Reaction time: 8 h

Procedure:
TEA (1.92 mL, 13.8 mmol) was added to a mixture of 3-amino-2,4-difluoro-benzylamine (0.58 g, 2.5 mmol) in THF (40 ml) followed by pivaloyl chloride (0.31 mL, 2.5 mmol) and it was stirred overnight. The mixture was diluted with EtOAc, washed successively with satd. NaHCO3 and brine. The organic phase was dried with Na2SO4, filtered and concentrated.
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6]Br)=[CH:4][CH:3]=1.C(N(CC)CC)C.C[C@@:18]1([OH:24])[CH2:23][CH2:22][CH2:21][NH:20][CH2:19]1>C1COCC1>[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][N:20]2[CH2:21][CH2:22][CH2:23][C@@H:18]([OH:24])[CH2:19]2)=[CH:4][CH:3]=1
Reactant: C[C@@]1(O)CCCNC1
Reactant: BrCc1ccc(Br)cc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: O[C@@H]1CCCN(Cc2ccc(Br)cc2)C1
Temperature: 25 °C
Reaction time: 16 h
Yield: 69.4 %

Procedure:
A mixture of 4-bromobenzyl bromide (1.0 g, 4.0 mmol), triethylamine (0.84 mL, 6.0 mmol) and (R)-3-methyl-piperidin-3-ol (1.11 g, 8.0 mmol) in THF (20 mL) was stirred at ambient temperature for 16 h. The solvent was evaporated and the resultant residue diluted with saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate (2×50 mL). The combined organic layer was dried over sodium sulfate, filtered and evaporated. The material was purified by flash chromatography (silica, Biotage 50 g column, 50-100% ethyl acetate in cyclohexane) to afford the title compound (0.75 g, 69%). 1H NMR (CDCl3, 300 MHz): 7.46-7.40 (m, 2H), 7.21-7.14 (m, 2,H), 3.85-3.76 (m, 1H), 3.45 (s, 2H), 2.45 (s, 3H), 2.29-2.16 (m, 1H), 1.86-1.70 (m, 1H) 1.67-1.45 (m, 3H) plus 1 exchangeable not observed. LCMS (Method G): RT=2.00 min, M+H+=270.
Reaction SMILES: [C:1]1([CH:6]=O)[CH2:5][CH2:4][CH2:3][CH:2]=1.[C:8]([NH:11][CH:12]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:13]([O:15][CH2:16][CH3:17])=[O:14])(=[O:10])[CH3:9]>>[C:8]([N:11]1[CH2:6][CH:1]2[CH2:5][CH2:4][CH2:3][CH:2]2[C:12]1([C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:13]([O:15][CH2:16][CH3:17])=[O:14])(=[O:10])[CH3:9]
Reactant: O=CC1=CCCC1
Reactant: CCOC(=O)C(NC(C)=O)C(=O)OCC
Product: CCOC(=O)C1(C(=O)OCC)C2CCCC2CN1C(C)=O

Procedure:
The title compound was prepared from cyclopenten-1-aldehyde (1 equiv.) and diethyl 2-acetamidomalonate using the procedure by Chung et al (J. Org. Chem. 1990, 55, 270). MS (ESI) 298 (M+H).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][OH:7].[NH:8]1[C:16]2[C:11](=[CH:12][C:13]([NH:17][C:18]3[CH:23]=[CH:22][N:21]=[C:20]4[CH:24]=[C:25]([C:27]5[CH:34]=[CH:33][C:30]([CH:31]=O)=[CH:29][CH:28]=5)[S:26][C:19]=34)=[CH:14][CH:15]=2)[CH:10]=[CH:9]1>>[NH:8]1[C:16]2[C:11](=[CH:12][C:13]([NH:17][C:18]3[CH:23]=[CH:22][N:21]=[C:20]4[CH:24]=[C:25]([C:27]5[CH:34]=[CH:33][C:30]([CH2:31][NH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][OH:7])=[CH:29][CH:28]=5)[S:26][C:19]=34)=[CH:14][CH:15]=2)[CH:10]=[CH:9]1
Reactant: NCCOCCO
Reactant: O=Cc1ccc(-c2cc3nccc(Nc4ccc5[nH]ccc5c4)c3s2)cc1
Product: OCCOCCNCc1ccc(-c2cc3nccc(Nc4ccc5[nH]ccc5c4)c3s2)cc1

Procedure:
The title compound was prepared from 2-(2-amino-ethoxy)-ethanol and 4-[7-(1H-indol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]-benzaldehyde by a procedure analogous to example 17. LC-MS: 459 (MH+); HPLC RT: 3.48 minutes.
Reaction SMILES: [CH3:1][O:2][CH2:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH2:6][N:7](C(OC(C)(C)C)=O)[CH2:8]2.C(OCC)(=O)C.Cl.[OH-].[Na+]>C(OCC)(=O)C>[CH3:1][O:2][CH2:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH2:6][NH:7][CH2:8]2
Reactant: COCc1cccc2c1CN(C(=O)OC(C)(C)C)C2
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Product: COCc1cccc2c1CNC2
Temperature: 25 °C
Reaction time: 8 h
Yield: 80.7 %

Procedure:
To a solution of 200 mg of tert-butyl 4-(methoxymethyl)-1,3-dihydro-2H-isoindole-2-carboxylate in 2 mL of ethyl acetate was added 2.3 mL of a 4 M hydrogen chloride-ethyl acetate solution under ice-cooling, followed by stirring at room temperature overnight. Under ice-cooling, to the reaction mixture was added a 1 M aqueous sodium hydroxide solution to adjust the pH to about 7. The aqueous layer was separated, the organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to obtain 100 mg of 4-(methoxymethyl)isoindoline as a brown oil.
Reaction SMILES: C[N+](CC)(CC)CC.[C:9]([C:11]([F:19])([F:18])[C:12]([F:17])([F:16])[C:13]([O-])=[O:14])#[N:10].S(F)(OC(F)(F)C(F)=C(F)[F:27])(=O)=O>COCCOCCOC>[C:9]([C:11]([F:19])([F:18])[C:12]([F:17])([F:16])[C:13]([F:27])=[O:14])#[N:10]
Reactant: O=S(=O)(F)OC(F)(F)C(F)=C(F)F
Reactant: N#CC(F)(F)C(F)(F)C(=O)[O-]
Agent: CC[N+](C)(CC)CC
Solvent: COCCOCCOC
Product: N#CC(F)(F)C(F)(F)C(=O)F
Reaction time: 1 h
Yield: 28.9 %

Procedure:
A solution of 53.9 g (0.2 mole) of methyltriethylammonium-3-cyanotetrafluoropropionate prepared as in Part A in 300 ml of diglyme was stirred at -10° to -5° while 46.0 g (0.20 mole) of perfluoroallyl fluorosulfate was rapidly added. The mixture was then stirred at -10° to -5° for 1 hr., and then at -5° to 0° for 4 hr. Removal of volatiles at 35° (5 mm, 6.7×10-1 kPa) through a liquid N2 trap and fractionation gave 10.0 g (29%) of 3-cyanotetrafluoropropionyl fluoride, bp 19°-20°. IR (gas phase): 2265 (CN), 1888 (COF), and 1300-1100 cm-1 (CF) with traces of CO2, SO2F2 and SiF4 present. NMR (CCl4 ; 0°); 19F 25.8 (t of t, JFF 10.1, 5.0 Hz, 1F, COF), -106.7 (d of t, JFF 5.0, 4.6 Hz, 2F, CF2CN), and -118.5 ppm (d of t, JFF 10.1, 4.6 Hz, 2F, CF2C=O).
Reaction SMILES: [CH2:1]([CH:8]([C:19]([O-])=[O:20])[C:9]([O:11]CC1C=CC=CC=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[OH:20][CH2:19][CH:8]([CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:9]([OH:11])=[O:10]
Reactant: O=C([O-])C(Cc1ccccc1)C(=O)OCc1ccccc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: O=C(O)C(CO)Cc1ccccc1
Temperature: 25 °C

Procedure:
benzyl 2-benzyl malonate (75) is treated with lithium aluminum hydride in THF at -78° C. The reaction is allowed to warm to room temperature and then is quenched with aqueous HCl. The reaction mixture is diluted with water and extracted with ethyl acetate. After drying over Na2SO4, the ethyl acetate is evaporated and the product purified by flash chromatography over silica gel to give (76).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[S:5][C:6]=1[NH:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].CCN(C(C)C)C(C)C.P(C(C)(C)C)(C(C)(C)C)C(C)(C)C.[C:42]1([C:48]#[CH:49])[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1>CCOC(C)=O.C1C=CC(C#N)=CC=1.C1C=CC(C#N)=CC=1.Cl[Pd]Cl.[Cu]I>[C:11]([O:10][C:8]([NH:7][C:6]1[S:5][C:4]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:3][C:2]=1[C:49]#[C:48][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)=[O:9])([CH3:14])([CH3:13])[CH3:12]
Reactant: C#Cc1ccccc1
Reactant: CCOC(=O)c1cc(Br)c(NC(=O)OC(C)(C)C)s1
Agent: Cl[Pd]Cl
Agent: [Cu]I
Agent: CC(C)(C)P(C(C)(C)C)C(C)(C)C
Solvent: CCN(C(C)C)C(C)C
Solvent: N#Cc1ccccc1
Solvent: CCOC(C)=O
Product: CCOC(=O)c1cc(C#Cc2ccccc2)c(NC(=O)OC(C)(C)C)s1
Temperature: 25 °C
Reaction time: 8 h
Yield: 96 %

Procedure:
Pd(PhCN)2Cl2 (0.03 eq.) and CuI (0.02 eq.) were added to a dry septum-capped vial, which was then sparged with argon and charged with ethyl 4-bromo-5-[(tert-butoxycarbonyl)amino]thiophene-2-carboxylate (prepared as described in example 14, step 4) (1 M solution in dioxane), DIEA (1.2 eq.), P(t-Bu)3 (0.06 eq., 0.8 M solution in dioxane) and phenylacetylene (1.2 eq.). The reaction was stirred overnight at RT, then diluted with AcOEt and filtered trough a small pad of silica gel. The filtrate was concentrated giving a residue that was purified by flash chromatography on silica gel (1:5 AcOEt/petroleum ether) to afford the title compound (96%) as a solid.
Reaction SMILES: [C:1]([O-:4])(=[S:3])[CH3:2].[K+].Cl[CH2:7][C:8]1[C:16]2[S:15][N:14]=[N:13][C:12]=2[CH:11]=[CH:10][CH:9]=1>CS(C)=O>[C:1]([S:3][CH2:7][C:8]1[C:16]2[S:15][N:14]=[N:13][C:12]=2[CH:11]=[CH:10][CH:9]=1)(=[O:4])[CH3:2]
Reactant: ClCc1cccc2nnsc12
Reactant: CC([O-])=S
Agent: [K+]
Solvent: CS(C)=O
Product: CC(=O)SCc1cccc2nnsc12
Temperature: 0 °C
Reaction time: 8 h

Procedure:
A solution of 2.2 g of potassium thioacetate in 20 ml of absolute dimethyl sulfoxide, stirred at 20° C., is treated dropwise with stirring with a solution of 2.8 g of 7-chloromethylbenzo-1,2,3-thiadiazole in 10 ml of dimethyl sulfoxide, during which process the internal temperature rises to 37° C. The mixture is subsequently stirred overnight at room temperature and, on the following day, poured into ice-water and extracted using ethyl acetate. The extracts are washed five times with water, dried over sodium sulfate and evaporated. The residue which remains is distilled in vacuo, resulting in an oil of refractive index nD27 =1.6478.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=O)=[CH:2]1.Cl.[NH2:20][OH:21].C([O-])(=O)C.[K+]>C(O)C.O>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[N:20][OH:21])=[CH:2]1
Reactant: NO
Reactant: O=C(Cc1c[nH]c2ccccc12)c1ccccc1
Agent: CC(=O)[O-]
Agent: Cl
Agent: [K+]
Solvent: O
Solvent: CCO
Product: ON=C(Cc1c[nH]c2ccccc12)c1ccccc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 96 %

Procedure:
2-(1H-indol-3-yl)-1-phenylethanone (0.97 g, 4.12 mmol) dissolved in absolute ethanol (20 ml) was added to a solution of hydroxylamine hydrochloride (0.97 g, 13.95 mmol) and potassium acetate (1.54 g, 15.74 mmol) in absolute ethanol (20 ml). This reaction mixture was stirred for 24 h at room temperature. The batch was then boiled for 3 h with reflux. The batch was then dissolved in water (20 ml) at 70° C. The batch was then left to stand for 5 h at 4° C. Since no solid separated out, the volatile constituents were removed completely in a vacuum. The residue was mixed with water (10 ml) and the pH value of the solution adjusted to pH 11 with 5N sodium hydroxide solution. The mixture was then extracted with ethyl acetate (5×30 ml). The combined organic phases were dried with sodium sulphate, filtered and all the volatile constituents removed in a vacuum. Yield: 90% (990 mg) yellow-brown oil
Reaction SMILES: [CH2:1]([N:3]([CH2:12][CH3:13])[C:4]1[CH:11]=[CH:10][C:7]([CH:8]=O)=[CH:6][CH:5]=1)[CH3:2].[C:14]1(=[O:19])[CH2:18][CH2:17][CH2:16][CH2:15]1>[OH-].[K+].CO>[CH2:1]([N:3]([CH2:12][CH3:13])[C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[C:15]2[CH2:16][CH2:17][C:18](=[CH:8][C:7]3[CH:10]=[CH:11][C:4]([N:3]([CH2:1][CH3:2])[CH2:12][CH3:13])=[CH:5][CH:6]=3)[C:14]2=[O:19])=[CH:6][CH:5]=1)[CH3:2]
Reactant: CCN(CC)c1ccc(C=O)cc1
Reactant: O=C1CCCC1
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: CCN(CC)c1ccc(C=C2CCC(=Cc3ccc(N(CC)CC)cc3)C2=O)cc1

Procedure:
About 110 g of p-diethylaminobenzaldehyde were dissolved in a solution of 80 g of potassium hydroxide in 1000 mL of methanol. About 26 g of cyclopentanone were added with stirring and the reaction mixture was heated under reflux on a steam bath for 3 hr. After chilling in the freezer, a solid precipitate was collected, washed with alcohol and recrystallized from a mixture of alcohol and acetonitrile. The title compound was confirmed by its NMR spectrum. This dye has an ε488 /MW of 188.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:11]3[O:31][C@H:30]([CH2:32][O:33]CC4C=CC=CC=4)[C@@H:21]([O:22]CC4C=CC=CC=4)[C@H:12]3[O:13]CC3C=CC=CC=3)[N:9]=[CH:10][C:3]=12.[Na+].[Cl-]>>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:11]3[O:31][C@H:30]([CH2:32][OH:33])[C@@H:21]([OH:22])[C@H:12]3[OH:13])[N:9]=[CH:10][C:3]=12
Reactant: Nc1ncnc2c1cnn2[C@@H]1O[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Agent: [Cl-]
Agent: [Na+]
Product: Nc1ncnc2c1cnn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O

Procedure:
1.45 g (2.7 mmoles) of 4-amino-1-(2,3,5-tri-O-benzyl-β -D-ribofuranosyl)pyrazolo[ 3,4-d]pyrimidine are hydrogenated in a manner similar to that of Example 6. The 4-amino- 1-(β-D-ribofuranosyl)pyrazolo[ 3,4-d] pyrimidine precipitates; however, during the reaction so that in this case the preparation is modified. The reaction mixture is filtered off (vacuum filter funnel) from the catalyst and the reaction product which has been partially precipitated. The obtained solution is neutralized with diluted NaHCO3 solution. The catalyst with the remainder of the product is washed in a pointed funnel with the application of vacuum using hot water. The solution so obtained is neutralised and combined with the above solution. It is freed of solvent and the product, which is contaminated with a little NaCl, is recrystallised from H2O. White needles are obtained. Yield: 350 mg (48 %), Melting point: 253° C.(4).
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:20]=[CH:19][C:7]2[S:8][C:9]3[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[C:10]=3[CH2:11][C:12](=[O:13])[C:6]=2[CH:5]=1)[CH3:2].O>CO.C(Cl)(Cl)Cl>[CH2:1]([O:3][C:4]1[CH:20]=[CH:19][C:7]2[S:8][C:9]3[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[C:10]=3[CH2:11][CH:12]([OH:13])[C:6]=2[CH:5]=1)[CH3:2]
Reactant: CCOc1ccc2c(c1)C(=O)Cc1c(Cl)cccc1S2
Solvent: CO
Solvent: O
Solvent: ClC(Cl)Cl
Product: CCOc1ccc2c(c1)C(O)Cc1c(Cl)cccc1S2
Temperature: 25 °C
Reaction time: 2 h

Procedure:
An amount of 31.8 g of 2-ethoxy-9-chloro-10,11 -dihydrodibenzo[b,f]thiepin-11-one was dissolved in 200 ml of a mixed solvent of methanol and chloroform (5/1) and the mixture was stirred at room temperature for 2 hours and freed of the solvent to obtain the residue. To the resulting residue was added 100 ml of water and the mixture was extracted with chloroform. The extract was washed with water, dried over anhydrous sodium sulfate and freed of the solvent to obtain the residue.