Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([C:8]([CH2:11][C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:10])[CH3:9])[CH:5]=[CH:4][C:3]=1[OH:16].[C:17](OC(=O)C)(=[O:19])[CH3:18]>C(#N)C>[C:17]([NH:1][C:2]1[CH:7]=[C:6]([C:8]([CH2:11][C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:9])[CH3:10])[CH:5]=[CH:4][C:3]=1[OH:16])(=[O:19])[CH3:18]
Reactant: CC(C)(C)CC(C)(C)c1ccc(O)c(N)c1
Reactant: CC(=O)OC(C)=O
Solvent: CC#N
Product: CC(=O)Nc1cc(C(C)(C)CC(C)(C)C)ccc1O
Yield: 70 %

Procedure:
2-Amino-4-tert-octylphenol was refluxed by heating in a mixture of acetonitrile and acetic anhydride to synthesize Intermediate B having the melting point of 176° to 177° C. in a yield of 70%. 26.3 g of 2-acetamido-4-tert-octylphenol thus obtained was dissolved in 200 ml of chloroform, the solution was cooled to 0° to 5° C. to which was added 8.1 g of sulfur monochloride (S2Cl2) and the mixture was stirred for 2 hours. Water was added to the reaction solution, and the chloroform layer was thoroughly washed with water and then concentrated. The residue was dissolved in 50 ml of dimethylformamide without purification and isolation, to the solution were added 16.6 g of anhydrous potassium carbonate and 23 g of butyl bromide and the mixture was heated at 100° C. for 3 hours. After the reaction, 300 ml of ethyl acetate and 200 ml of water were added to the reaction mixture and extracted. The ethyl acetate layer was concentrated and the residue was crystallized from acetonitrile to obtain 15.8 g of Intermediate D having the melting point of 150° to 153° C. 15.8 g of Intermediate D thus obtained was dissolved in a mixture of 100 ml of ethanol and 10 ml of 6N hydrochloric acid and the mixture was stirred at 40° to 50° C. for 1 hour whereby the acetyl group of Intermediate D was quantitatively hydrolized. The reaction solution was poured into ice water and the precipitate thus formed was collected by filtration and dried to obtain 14 g of Intermediate E. 14 g of Intermediate E thus obtained was dissolved in 100 ml of pyridine, to the solution was added 5.7 g of methanesulfonyl chloride in a nitrogen atmosphere and the mixture was stirred at room temperature for 2 hours. The reaction solution was poured into ice water, the oily product thus precipitated was separated by decantation and dissolved in 200 ml of ethyl acetate. The solution was thoroughly washed with an aqueous acidic solution of acetic acid. The ethyl acetate was concentrated and the residue was crystallized from a mixture of hexane and ethyl acetate to obtain 9.3 g of Intermediate F having a melting point of 102° to 103° C.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].COCCOC.[N:13]([N:15]1[CH2:20][CH2:19][N:18]([CH2:21][C:22]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[NH:24][CH:23]=2)[CH2:17][CH2:16]1)=O>O>[NH2:13][N:15]1[CH2:20][CH2:19][N:18]([CH2:21][C:22]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[NH:24][CH:23]=2)[CH2:17][CH2:16]1
Reactant: O=NN1CCN(Cc2c[nH]c3ccccc23)CC1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: COCCOC
Product: NN1CCN(Cc2c[nH]c3ccccc23)CC1
Temperature: 0 °C

Procedure:
To a stirred mixture of 10.5 g of lithium aluminum hydride in 100 ml. of 1,2-dimethoxyethane is added slowly 38 g (0.16 mol) of 3-(4-nitrosopiperazin-1-yl) methylindole while maintaining the temperature below 35° C. After total addition of the material, the mixture is refluxed for four hours. The reaction mixture is cooled to 0° C. and a solution of 50 ml. of water and 50 ml. of 1,2-dimethoxyethane is added slowly maintaining the temperature below 20° C. and an additional 50 ml. of water is added. The mixture is filtered and the solvent is removed from the filtrate. The residual solid is recrystallized from ethanol and water (2:1) to produce pure flakes of 3-(4-aminopiperazin-1-yl) methylindole, m.p. 147°-149° C. Analysis: Calculated for C13H18N4 :67.80% C; 7.88% H; 24.33% N Found: 67.69% C; 7.94% H; 24.28% N.
Reaction SMILES: [CH2:1]([Se:8][C:9]1[C:17]2[O:18][CH2:19][O:20][C:16]=2[CH:15]=[CH:14][C:10]=1[C:11]([OH:13])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1.[NH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>ClCCl>[CH2:1]([Se:8][C:9]1[C:17]2[O:18][CH2:19][O:20][C:16]=2[CH:15]=[CH:14][C:10]=1[C:11]([NH:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)=[O:13])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Nc1ccccc1
Reactant: O=C(O)c1ccc2c(c1[Se]Cc1ccccc1)OCO2
Agent: O=C1OCCN1P(=O)(Cl)N1CCOC1=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(Nc1ccccc1)c1ccc2c(c1[Se]Cc1ccccc1)OCO2

Procedure:
To a solution of 1.6 g (0.0048 mol) 2-benzylseleno-3,4-methylenedioxybenzoic acid and 0.48 g triethylamine in 50 ml dichloromethane at 0° C. is added in one portion 1.22 g (0.0048 mol) solid bis[2-oxo-3-oxazolidinyl]phosphoryl chloride. After stirring for 30 min 0.44 g (0.44 ml) aniline in 5 ml dichloromethane are added at 0° C. dropwise with stirring followed after 1 hour by a solution of 0.48 g (0.66 ml) triethylamine in 10 ml dichloromethane. After 90 minutes at room temperature the reaction mixture is extracted successively with 50 ml 1N HCl and 50 ml water. The organic phase is dried over sodium sulfate and the solvent removed in vacuum. The crude product is purified by recrystallization from 2-propanol.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([OH:11])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].CCN(C(C)C)C(C)C.[CH3:21][O:22][CH2:23]Cl>C(Cl)Cl>[CH3:10][O:9][C:8]1[CH:7]=[CH:6][C:5]([O:11][CH2:21][O:22][CH3:23])=[CH:4][C:3]=1[O:2][CH3:1]
Reactant: COCCl
Reactant: COc1ccc(O)cc1OC
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COCOc1ccc(OC)c(OC)c1
Reaction time: 17 h

Procedure:
To a stirred solution of 3,4-bis(methyloxy)phenol (Commercial eg Alfa Aesar) (1.0 g) and DIPEA (2.28 ml) in DCM (15 ml) was added chloromethyl methyl ether (0.74 ml) at 0 C. After stirring at 25-30 C for 17 h, the reaction was washed with dilute hydrochloric acid and saturated aqueous sodium bicarbonate. This was dried over sodium sulphate and purified through silica eluting with 0-5% ethyl acetate in hexane, to give the title compound, 0.80 g
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[C:9]([CH3:11])[C:5]2[C:6](=O)[CH2:7][C:4]=2[CH:3]=1.C1(P(=[CH:31][C:32](=[O:34])[CH3:33])(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>>[CH:31](=[C:6]1[C:5]2=[C:9]([CH3:11])[CH:10]=[C:2]([CH3:1])[CH:3]=[C:4]2[CH2:7]1)[C:32]([CH3:33])=[O:34]
Reactant: Cc1cc(C)c2c(c1)CC2=O
Reactant: CC(=O)C=P(c1ccccc1)(c1ccccc1)c1ccccc1
Product: CC(=O)C=C1Cc2cc(C)cc(C)c21
Temperature: 180 °C
Reaction time: 0.5 h
Yield: 80.5 %

Procedure:
4,6-Dimethylbenzocyclobut-en-1-one (5.5 g, 38 mmol) and triphenylphosphoranylidene-2-propanone (15.0 g, 47 mmol) were heated together with stirring at 180° C. for 0.5 hours. After cooling the mixture was triturated with ether, filtered and the filtrate evaporated to give 1-acetonylidene-4,6-dimethylbenzocyclobutene as a pale brown solid (5.7 g, 81%). Pmr spectrum (CDCl3, δ in ppm): 2.30 (6H, s); 2.35 (3H,s); 3.94 (2H, s); 6.25 (1H, s); 6.86 (2H, s).
Reaction SMILES: [NH2:1][C:2]1[C:10]([OH:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[CH:12](OC)(OC)OC>>[O:11]1[C:10]2=[CH:9][CH:8]=[CH:7][C:3]([C:4]([OH:6])=[O:5])=[C:2]2[N:1]=[CH:12]1
Reactant: COC(OC)OC
Reactant: Nc1c(O)cccc1C(=O)O
Product: O=C(O)c1cccc2ocnc12
Temperature: 25 °C

Procedure:
A solution of 2-amino-3-hydroxy-benzoic acid (13.1 mmol) in trimethyl orthoformate (20.0 mL) is refluxed for 4 h, cooled to RT and concentrated in vacuo to give a crude product which is used without further purification.
Reaction SMILES: [C:1](OC(=O)C)(=[O:3])[CH3:2].[NH2:8][C:9]1[CH:30]=[CH:29][CH:28]=[CH:27][C:10]=1[CH2:11][O:12][C:13]1[C:14]2[N:15]([C:19]([CH2:23][N:24]([CH3:26])[CH3:25])=[C:20]([CH3:22])[N:21]=2)[CH:16]=[CH:17][CH:18]=1>C(Cl)Cl>[C:1]([NH:8][C:9]1[CH:30]=[CH:29][CH:28]=[CH:27][C:10]=1[CH2:11][O:12][C:13]1[C:14]2[N:15]([C:19]([CH2:23][N:24]([CH3:26])[CH3:25])=[C:20]([CH3:22])[N:21]=2)[CH:16]=[CH:17][CH:18]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)OC(C)=O
Reactant: Cc1nc2c(OCc3ccccc3N)cccn2c1CN(C)C
Solvent: ClCCl
Product: CC(=O)Nc1ccccc1COc1cccn2c(CN(C)C)c(C)nc12
Temperature: 25 °C
Reaction time: 5 h
Yield: 77.5 %

Procedure:
Acetic anhydride (0.43 g) was added dropwise to a solution of 8-(2-aminobenzyloxy)-3-dimethylaminomethyl-2-methylimidazo[1,2 a]pyridine (1 g) in methylene chloride (13 ml) with ice cooling. After being stirred for 5 hours at room temperature the reaction solution was washed successively with aqueous sodium bicarbonate, water, and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by column chromatography on silica gel (20 g) with a mixture of methylene chloride and methanol (50:1-20:1) as an eluent to give 8-(2-acetamidobenzyloxy)-3-dimethylaminomethyl-2-methylimidazo[1,2-a]pyridine (0.88 g)
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([C:10]2[O:11][C:12]3[CH:17]=[CH:16][N:15]=[CH:14][C:13]=3[N:18]=2)[CH:7]=[CH:8][CH:9]=1)([O-])=O.[NH4+].[Cl-]>CO.O.[Fe]>[O:11]1[C:12]2[CH:17]=[CH:16][N:15]=[CH:14][C:13]=2[N:18]=[C:10]1[C:6]1[CH:5]=[C:4]([NH2:1])[CH:9]=[CH:8][CH:7]=1
Reactant: O=[N+]([O-])c1cccc(-c2nc3cnccc3o2)c1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CO
Product: Nc1cccc(-c2nc3cnccc3o2)c1
Yield: 84.5 %

Procedure:
A suspension of 2-(3-nitrophenyl)oxazolo[4,5-c]pyridine (1.50 g, 6.2 mmol), iron powder (1.867 g, 31.8 mmol) and NH4Cl (2.86 g, 53.5 mmol) in CH3OH/H2O (4: 1, 311.2 mL) was refluxed for 6 h. The mixture was filtered and the filtrate was evaporated in vacuo. The residue was purified by chromatography on silica gel (eluted with petroleum ether: EtOAc : Et3N=160:40:1) to afford 3-(oxazolo[4,5-c]pyridin-2-yl)benzenamine as a white solid (1.107 g, yield: 85%). 1H NMR (400 MHz, DMSO-d6) δ: 5.54 (2H, s), 6.82 (1H, d, J=8.0 Hz), 7.24 (1H, t, J=8.0 Hz), 7.35 (1H, d, J=8.0 Hz), 7.44 (1H, s), 7.86 (1H, d, J=5.6 Hz), 8.56 (1H, d, J=5.6 Hz), 9.07 (1H, s); MS (ESI) calcd. for C12H9N3O (m/z): 211, found: 212 [M+1]+.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([O:11][CH:12]([CH3:14])[CH3:13])[C:5]([CH3:10])=[C:6]([CH:9]=1)[CH:7]=O.[CH3:15][O:16][CH:17]([O:20][CH3:21])[CH2:18][NH2:19].[BH3-]C#N.[Na+].CC(O)=O>CO>[Br:1][C:2]1[CH:3]=[C:4]([O:11][CH:12]([CH3:14])[CH3:13])[C:5]([CH3:10])=[C:6]([CH:9]=1)[CH2:7][NH:19][CH2:18][CH:17]([O:20][CH3:21])[O:16][CH3:15]
Reactant: Cc1c(C=O)cc(Br)cc1OC(C)C
Reactant: COC(CN)OC
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: COC(CNCc1cc(Br)cc(OC(C)C)c1C)OC
Temperature: 25 °C
Reaction time: 8 h
Yield: 56.2 %

Procedure:
To a solution of 5-bromo-2-methyl-3-(propan-2-yloxy)benzaldehyde (108b, 4.5 g, 18 mmol) and 2,2-dimethoxyethanamine (2.2 g, 21 mmol) in MeOH (50 mL) was added NaBH3CN (1.4 g, 22 mmol) and HOAc (1 mL) at 0° C. The reaction mixture was stirred at room temperature overnight. The reaction mixture was quenched with water (50 mL). The reaction mixture was concentrated under vacuum. The residue was extracted with EtOAc (3×30 mL). The combined organic layers were washed with brine (2×30 mL), dried over Na2SO4, filtered, and concentrated under vacuum. The residue was purified by column chromatography (petroleum ether/EtOAc=5:1) to obtain N-[5-bromo-2-methyl-3-(propan-2-yloxy)benzyl]-2,2-dimethoxyethanamine (108c, 3.5 g, 58%) as a colorless oil.
Reaction SMILES: [C:1]([NH:4][C:5](=[O:8])[CH2:6][SH:7])(=[O:3])[CH3:2].[C:9]1([CH2:15][C:16](Cl)=[O:17])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C(N(CC)CC)C>C(Cl)(Cl)Cl>[C:1]([NH:4][C:5](=[O:8])[CH2:6][S:7][C:16](=[O:17])[CH2:15][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)NC(=O)CS
Reactant: O=C(Cl)Cc1ccccc1
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: CC(=O)NC(=O)CSC(=O)Cc1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To 0.10 mole of N-acetyl-2-mercapto acetamide in 150 ml. of chloroform is added 0.1 mole of phenyl acetylchloride followed by 0.1 mole of triethylamine. The reaction mixture is stirred at ambient temperature for 1 hour and then concentrated to dryness. Chromatograph of the residue on 500 g. of silica gel eluting with ethylacetate in hexane (25-75%) gives N-acetyl-2-(phenylacetylthio) acetamide.
Reaction SMILES: Cl[C:2](=[N:8][NH:9][C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4].[CH2:17]=[CH:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(N(CC)CC)C>C1C=CC=CC=1>[Cl:16][C:13]1[CH:14]=[CH:15][C:10]([N:9]2[CH:18]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:17][C:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])=[N:8]2)=[CH:11][CH:12]=1
Reactant: C=Cc1ccccc1
Reactant: CCOC(=O)C(Cl)=NNc1ccc(Cl)cc1
Solvent: CCN(CC)CC
Solvent: c1ccccc1
Product: CCOC(=O)C1=NN(c2ccc(Cl)cc2)C(c2ccccc2)C1
Temperature: 25 °C
Yield: 94 %

Procedure:
Part B: To a stirred boiling solution of ethyl 2-chloro[(4-chlorophenyl) hydrazono]acetate (22.95 gram, 0.088 mol) and styrene (30.3 ml, 0.264 mol) in benzene (140 ml) is added triethylamine (34.3 ml, 0.247 mol) and the resulting solution is heated at reflux temperature for 1 hour. The resulting solution is cooled to room temperature and the formed precipitate is removed by filtration and washed with toluene. The filtrate is concentrated in vacuo and purified by flash chromatography (silica gel, dichloromethane) to give ethyl 1-(4-chlorophenyl)-5-phenyl-4,5-dihydro-(1H)-pyrazole-3-carboxylate (27.2 gram, 94% yield) as a syrup which slowly solidifies on standing. 1H-NMR (200 MHz, CDCl3): 1.38 (t, J=7 Hz, 3H), 3.06 (dd, J=18 and 7 Hz, 1H), 3.73 (dd, J=18 and 13 Hz, 1H), 4.33 (q, J=7 Hz, 2H), 5.38 (dd, J=13 and 7 Hz, 1H), 7.02 (br d, J=8 Hz, 2H), 7.08-7.40 (m, 7H).
Reaction SMILES: [CH:1]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:2]=1[C:3](=[O:18])[N:4]1[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[NH:11][C:5]1=[N:6]2.[CH2:19](Br)[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30]>>[CH2:30]([N:11]1[C:5]2=[N:6][C:7]3[C:2]([C:3](=[O:18])[N:4]2[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]1=2)=[CH:1][CH:10]=[CH:9][CH:8]=3)[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH3:19]
Reactant: O=c1c2ccccc2nc2[nH]c3ccccc3n12
Reactant: CCCCCCCCCCCCBr
Product: CCCCCCCCCCCCn1c2ccccc2n2c(=O)c3ccccc3nc12

Procedure:
6-(n-Dodecyl)benzimidazo[2,1-b]quinazolin-12(6H)one is prepared with benzimidazo[2,1-b]quinazolin-12(6H)one and n-dodecyl bromide.
Reaction SMILES: CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.[CH2:34]([O:41][C:42]([NH:44][C@@H:45]([CH2:50][CH2:51][CH2:52][NH:53][C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH2:46][C:47]([OH:49])=O)=[O:43])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.Cl.[NH2:62][CH2:63][CH2:64][NH:65][C:66](=[O:75])[O:67][CH2:68][C:69]1[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=1>CN(C=O)C>[CH2:68]([O:67][C:66](=[O:75])[NH:65][CH2:64][CH2:63][NH:62][C:47](=[O:49])[CH2:46][C@@H:45]([NH:44][C:42]([O:41][CH2:34][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)=[O:43])[CH2:50][CH2:51][CH2:52][NH:53][C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[C:69]1[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=1
Reactant: NCCNC(=O)OCc1ccccc1
Reactant: CC(C)(C)OC(=O)NCCC[C@@H](CC(=O)O)NC(=O)OCc1ccccc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)NCCC[C@@H](CC(=O)NCCNC(=O)OCc1ccccc1)NC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
549.7 mg (1.446 mmol) of HATU and 339.7 mg (2.629 mmol) of N,N-diisopropylethylamine are added to a solution of 500 mg (1.31 mmol) of (3S)-3-{[(benzyloxy)carbonyl]amino}-6-[(tert-butoxycarbonyl)amino]hexanoic acid in 25 ml of anhydrous DMF. After stirring at RT for 15 min, 333.5 mg (1.446 mmol) of benzyl (2-aminoethyl)carbamate hydrochloride are added. The reaction mixture is stirred at RT for 15 h. The solvent is then evaporated and the residue is taken up in dichloromethane. The organic phase is washed with water, dried over magnesium sulfate and concentrated. The crude product is purified by preparative HPLC.
Reaction SMILES: CC1C=CC(S(O[C@@H:12]2[CH2:25][C:24]3[C@@:15]([CH3:38])([C@@H:16]4[C@@H:21]([CH2:22][CH:23]=3)[C@@H:20]3[CH2:26][CH2:27][C@H:28]([C@@H:29]([CH2:31][CH2:32][CH2:33][CH:34]([CH3:36])[CH3:35])[CH3:30])[C@@:19]3([CH3:37])[CH2:18][CH2:17]4)[CH2:14][CH2:13]2)(=O)=O)=CC=1.[CH2:39]([OH:50])[CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][OH:49]>O1CCOCC1>[CH3:36][CH:34]([CH2:33][CH2:32][CH2:31][C@H:29]([C@@H:28]1[C@:19]2([CH3:37])[C@H:20]([C@H:21]3[C@H:16]([CH2:17][CH2:18]2)[C@:15]2([CH3:38])[C:24]([CH2:25][C@@H:12]([O:50][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][OH:49])[CH2:13][CH2:14]2)=[CH:23][CH2:22]3)[CH2:26][CH2:27]1)[CH3:30])[CH3:35]
Reactant: Cc1ccc(S(=O)(=O)O[C@H]2CC[C@@]3(C)C(=CC[C@H]4[C@@H]5CC[C@H]([C@H](C)CCCC(C)C)[C@@]5(C)CC[C@@H]43)C2)cc1
Reactant: OCCCCCCCCCCO
Solvent: C1COCCO1
Product: CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@H](OCCCCCCCCCCO)CC[C@]4(C)[C@H]3CC[C@]12C
Temperature: 25 °C
Yield: 78.2 %

Procedure:
In a 500 mL round-bottomed flask was cholesteryl tosylate (10.0 g, 18.5 mmol) and 1,10-Decanediol (48.3 g, 277 mmol) suspended in Dioxane (200 ml) to give a white suspension. The flask was fitted with a temperature sensor and reflux condenser. The mixture was heated to reflux and allowed to stir at reflux overnight. The reaction mixture was cooled to room temperature and the solids were filtered off. The solution was concentrated in vacuo. The mixture was re-dissolved in methanol (250 mL) and water (ca. 40 mL) was added to precipitate out the crude product. The precipitate was filtered and dried in vacuo. The residue was further purified via column chromatography on a 100 g Biotage SNAP column eluting over 2 L of a 0-25% EtOAc in Hexanes gradient. Pure fractions were combined and concentrated to give 7.85 g (82%) of a white solid. 1H NMR (300 mHz, CDCl3) δ0.69 (3H, s); 0.85-1.66 (50H, m); 1.75-2.09 (5H, m); 2.14-2.29 (1H, m); 2.32-2.43 (1H, m); 3.14 (1H, tt, J=11.2, 4.4 Hz); 3.46 (2H, dt, J=6.9, 0.4 Hz); 3.65 (2H, t, J=6.6 Hz); 5.36 (1H, d, J=5.3 Hz).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:9]([N:12]2[CH2:16][CH2:15][N:14]=[N:13]2)=[CH:8][C:4]=1[C:5]([OH:7])=O.Cl.[CH2:18]([O:20][CH2:21][CH2:22][N:23]1[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=2[N:25]=[C:24]1[NH:32][CH:33]1[CH2:38][CH2:37][N:36]([CH2:39][CH2:40][C:41]2([C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)[CH2:45][CH2:44][NH:43][CH2:42]2)[CH2:35][CH2:34]1)[CH3:19]>>[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:9]([N:12]2[CH2:16][CH2:15][N:14]=[N:13]2)=[CH:8][C:4]=1[C:5]([N:43]1[CH2:44][CH2:45][C:41]([CH2:40][CH2:39][N:36]2[CH2:37][CH2:38][CH:33]([NH:32][C:24]3[N:23]([CH2:22][CH2:21][O:20][CH2:18][CH3:19])[C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=4[N:25]=3)[CH2:34][CH2:35]2)([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[CH2:42]1)=[O:7]
Reactant: COc1ccc(N2CCN=N2)cc1C(=O)O
Reactant: CCOCCn1c(NC2CCN(CCC3(c4ccccc4)CCNC3)CC2)nc2ccccc21
Agent: Cl
Product: CCOCCn1c(NC2CCN(CCC3(c4ccccc4)CCN(C(=O)c4cc(N5CCN=N5)ccc4OC)C3)CC2)nc2ccccc21

Procedure:
Prepare by the method of Example 59.1 using 2-methoxy-5-(4H-triazol-1-yl)benzoic acid and 3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-phenylpyrrolidine hydrochloric acid salt (prepared from (−)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine (R,R)-di-p-anisoyltartaric acid salt) to give the title compound.
Reaction SMILES: [ClH:1].[NH:2]1[CH2:7][CH2:6][CH:5]([CH:8]2[CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]2=[O:17])[CH2:4][CH2:3]1.[CH:18]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=1)=[CH2:19].O.O.O.C([O-])(=O)C.[Na+].O>CO>[ClH:1].[ClH:1].[N:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[CH2:18][CH2:19][N:2]1[CH2:3][CH2:4][CH:5]([CH:8]2[CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]2=[O:17])[CH2:6][CH2:7]1
Reactant: C=Cc1ccccn1
Reactant: O=C1c2ccccc2CC1C1CCNCC1
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: CO
Product: O=C1c2ccccc2CC1C1CCN(CCc2ccccn2)CC1

Procedure:
A mixture of 0.251 g (0.001 mol) of 2-(4-piperidyl)-1-indanone hydrochloride, 0.21 g (0.002 mol) of 2-vinylpyridine, 0.272 g (0.002 mol) sodium acetate trihydrate, 2 mL of water, and 2 mL of methanol was stirred and refluxed for 20 hours. The solvent was evaporated in vacuo and the residue was dissolved in ethyl acetate and dried over magnesium sulfate. The product was isolated in pure form by chromatography on silica gel using 5% methanol in chloroform. A hydrochloride salt was prepared and was recrystallized from ethanol to give 2-[1-(2-pyridylethyl)-4-piperidyl]-1-indanone dihydrochloride, mp 195°-196° C.
Reaction SMILES: [CH3:1][O:2][C:3]([C@H:5]1[CH2:10][CH2:9][C@H:8]2[C@H:11]3[C@H:21]([C:22](=[O:24])[CH2:23][C@:6]12[CH3:7])[C@:19]1([CH3:20])[C@H:14]([CH2:15][CH:16]=[CH:17][CH2:18]1)[CH2:13][CH2:12]3)=[O:4].ClC1C=CC=C(C(OO)=[O:33])C=1>C(Cl)(Cl)Cl>[O:33]1[C@H:16]2[CH2:15][C@H:14]3[C@:19]([CH3:20])([CH2:18][C@@H:17]12)[C@@H:21]1[C@H:11]([C@H:8]2[C@@:6]([CH2:23][C:22]1=[O:24])([CH3:7])[C@@H:5]([C:3]([O:2][CH3:1])=[O:4])[CH2:10][CH2:9]2)[CH2:12][CH2:13]3
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: COC(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4CC=CC[C@]4(C)[C@H]3C(=O)C[C@]12C
Solvent: ClC(Cl)Cl
Product: COC(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@@H]5O[C@@H]5C[C@]4(C)[C@H]3C(=O)C[C@]12C

Procedure:
17β-Methoxycarbonyl-5α-androst-2-en-11-one (6.63 g.) and m-chloroperbenzoic acid (4.84 g.) were stirred with chloroform (115 ml.) for 16 hours. The solution was diluted with chloroform, washed with 2% aqueous potassium hydrogen carbonate, dried (MgSO4) and evaporated to a gum. Crystallisation from ethyl acetate/light petroleum afforded pure title compound. (1.64 g.) as colourless rods; m.p. 140°-145°; [α]D + 74.2°.
Reaction SMILES: C[O:2][C:3]([C:5]1([NH:9][S:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[N+:19]([O-:21])=[O:20])(=[O:12])=[O:11])[CH2:8][CH2:7][CH2:6]1)=[O:4].[CH2:22]1COCC1.CO.O[Li].O>O>[CH3:22][CH:6]1[CH2:7][CH2:8][C:5]1([NH:9][S:10]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[N+:19]([O-:21])=[O:20])(=[O:12])=[O:11])[C:3]([OH:2])=[O:4]
Reactant: C1CCOC1
Reactant: COC(=O)C1(NS(=O)(=O)c2ccccc2[N+](=O)[O-])CCC1
Agent: [Li]O
Solvent: O
Solvent: CO
Product: CC1CCC1(NS(=O)(=O)c1ccccc1[N+](=O)[O-])C(=O)O
Temperature: 25 °C
Reaction time: 12 h
Yield: 98 %

Procedure:
methyl-1-(2-nitrophenylsulfonamido)cyclobutanecarboxylate (500 mg, 1.59 mmol) was charged and dissolved through addition of THF (5 ml), and methanol (5 ml). LiOH.H2O dissolved in H2O (5 ml) was added thereto, followed by stirring for 12 hours at room temperature. After the stirring for 12 hours, the resultant solution was vacuum-evaporated, acidified with 2N—HCl to pH 2-3, and extracted with EA (×2). The organic layer was dried with MgSO4, and filtered. Then, through vacuum distillation, the solvent was removed so as to obtain methyl-1-(2-nitrophenylsulfonamido)cyclobutanecarboxylic acid (468 mg, 1.56 mmol, 98%).
Reaction SMILES: [OH-].[Na+].[CH3:3][C:4]1[CH:9]=[C:8]([CH3:10])[CH:7]=[CH:6][C:5]=1[OH:11].C=O.[C:14]([O-])(=[O:16])C>O.C(O)(=O)C>[CH3:3][C:4]1[CH:9]=[C:8]([CH3:10])[CH:7]=[C:6]([CH2:14][OH:16])[C:5]=1[OH:11]
Reactant: CC(=O)[O-]
Reactant: Cc1ccc(O)c(C)c1
Agent: C=O
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: O
Product: Cc1cc(C)c(O)c(CO)c1
Reaction time: 8 h
Yield: 97.4 %

Procedure:
75 g of NaOH were dissolved in 300 ml of deionized (DI) water. 183.3 g 2,4-dimethylphenol were added, and the mixture was cooled to 15°-20° C. 188 g of aqueous formaldehyde (made from 152g 37% formalin diluted with 36 g water) were added over half an hour, while the temperature was maintained below 20° C. After stirring overnight, Thin Layer Chromotography (TLC) in 2:1 hexane/ethyl. acetate showed a single spot, and no remaining 2,4-dimethylphenol. The pH was then adjusted to 6-7 with about 200 ml of 50% aqueous acetic acid. The mixture was transferred to a 2 liter beaker, and extracted with ethyl acetate (400 ml). Removal of the ethyl acetate in a vacuum gave 221.0 g (97.4%) of the desired product as a clear oil or a low-melting solid.