Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[CH:5]=[CH:4][C:3]=1[C:12]1[CH:13]=[CH:14][C:15]2[O:19][C:18]([CH:20]3[CH2:25][CH2:24][N:23](C(OC(C)(C)C)=O)[CH2:22][CH2:21]3)=[N:17][C:16]=2[CH:33]=1.[F:34][C:35]([F:40])([F:39])[C:36]([OH:38])=[O:37]>C(Cl)Cl>[F:34][C:35]([F:40])([F:39])[C:36]([OH:38])=[O:37].[F:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:9])=[O:10])[CH:5]=[CH:4][C:3]=1[C:12]1[CH:13]=[CH:14][C:15]2[O:19][C:18]([CH:20]3[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]3)=[N:17][C:16]=2[CH:33]=1
Reactant: CC(C)(C)OC(=O)N1CCC(c2nc3cc(-c4ccc(S(C)(=O)=O)cc4F)ccc3o2)CC1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CS(=O)(=O)c1ccc(-c2ccc3oc(C4CCNCC4)nc3c2)c(F)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Tert-butyl 4-{5-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate (200 mg, 0.42 mmol) dissolved in DCM and added Trifluoroacetic acid (0.75 ml). This mixture was stirred at rt for 2 h. DCM removed from the reaction mixture to obtain 5-(2-fluoro-4-(methylsulfonyl)phenyl)-2-(piperidin-4-yl)benzo[d]oxazole 2,2,2-trifluoroacetate (190 mg). 5-(2-fluoro-4-(methylsulfonyl)phenyl)-2-(piperidin-4-yl)-benzo[d]oxazole 2,2,2-trifluoroacetate (190 mg, 0.39 mmol) was dissolved in DCM (20 ml) and added TEA (0.43 ml, 3.12 mmol). This mixture stirred at rt for 30 mins and added isopropyl chloroformate in toluene (0.095 g, 0.78 mmol). After 1 h, reaction mass diluted with water and extracted with DCM. Removal of DCM afforded crude. Crude was purified by combiflash using a mixture of EtOAc and Petether (35:65) as eluent to afford the titled compound (120 mg) as a pale-yellow solid. M.P.: 96.5-101.2° C. 1H-NMR (δ ppm, CDCl3, 400 MHz): 7.87 (s, 1H), 7.81 (dd, J 1.7, 8, 1H), 7.80-7.75 (m, 1H), 7.67 (t, J 7.5, 1H), 7.59 (d, J 8.4, 1H), 7.50 (d, J 8.5, 1H), 4.94 (septet, J 6.2, 1H), 4.19 (d, J 10.9, 2H), 3.22-3.13 (m, 1H), 3.12 (s, 3H), 3.04 (t, J 10.9, 2H), 2.22-2.14 (m, 2H), 2.00-1.88 (m, 2H), 1.26 (d, J 6.2, 6H).
Reaction SMILES: Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([Cl:9])=[CH:5][CH:4]=1.[C:10]([S:14][C:15](=[O:20])[CH2:16][C:17](=[O:19])[CH3:18])([CH3:13])([CH3:12])[CH3:11]>>[C:10]([S:14][C:15](=[O:20])[CH:16]([CH2:2][C:3]1[CH:8]=[CH:7][C:6]([Cl:9])=[CH:5][CH:4]=1)[C:17](=[O:19])[CH3:18])([CH3:13])([CH3:11])[CH3:12]
Reactant: CC(=O)CC(=O)SC(C)(C)C
Reactant: Clc1ccc(CBr)cc1
Product: CC(=O)C(Cc1ccc(Cl)cc1)C(=O)SC(C)(C)C

Procedure:
The title compound was prepared by the method of Preparation 34a using 1-bromomethyl-4-chlorobenzene and 3-oxothiobutyric acid S-tert-butyl ester.
Reaction SMILES: C(O[C:4](=O)[C:5]([CH3:15])(C)CC1C=CC(S)=CC=1)C.Br[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[S:24]([C:27]1[CH:32]=[CH:31][C:30]([C:33]([OH:39])([CH3:38])[C:34]([F:37])([F:36])[F:35])=[CH:29][CH:28]=1)(=[O:26])=[O:25]>>[CH:15]1([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[S:24]([C:27]2[CH:32]=[CH:31][C:30]([C@@:33]([OH:39])([CH3:38])[C:34]([F:37])([F:36])[F:35])=[CH:29][CH:28]=2)(=[O:26])=[O:25])[CH2:5][CH2:4]1
Reactant: CCOC(=O)C(C)(C)Cc1ccc(S)cc1
Reactant: CC(O)(c1ccc(S(=O)(=O)c2ccccc2Br)cc1)C(F)(F)F
Product: C[C@](O)(c1ccc(S(=O)(=O)c2ccccc2C2CC2)cc1)C(F)(F)F

Procedure:
Using the methods described above in Example 12, but substituting 2-Bromo-benzenethiol for 3-(4-mercaptophenyl)-2,2-dimethylpropionic acid ethyl ester in step a, 2-[4-(2-bromobenzenesulfonyl)phenyl]-1,1,1-trifluoropropan-2-ol was prepared.
Reaction SMILES: C(OC([N:6]1[CH2:27][CH2:26][N:9]2[C:10]3[CH:25]=[CH:24][CH:23]=[CH:22][C:11]=3[CH2:12][N:13]3[C:21]4[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=4[CH:15]=[C:14]3[CH:8]2[CH2:7]1)=O)C.[OH-].[K+]>C(O)C>[CH2:7]1[CH:8]2[C:14]3[N:13]([C:21]4[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=4[CH:15]=3)[CH2:12][C:11]3[CH:22]=[CH:23][CH:24]=[CH:25][C:10]=3[N:9]2[CH2:26][CH2:27][NH:6]1
Reactant: CCOC(=O)N1CCN2c3ccccc3Cn3c(cc4ccccc43)C2C1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: c1ccc2c(c1)Cn1c(cc3ccccc31)C1CNCCN21

Procedure:
To a solution of 4.4 g of 1,3,4,16b-tetrahydro-2-ethoxycarbonyl-2H,10H-indolo[2,1-c]pyrazino[1,2-a][1,4]benzodiazepine in 88 ml ethanol is added 24 ml of 50% potassium hydroxide solution. The reaction mixture is heated at reflux temperature for 6 hours. The solvent is evaporated to dryness under reduced pressure and the residue extracted with a mixture of 350 ml of diethyl ether and 250 ml of water. The ethereal extract is washed with water, separated and then dried over anhydrous magnesium sulfate. The solvent is evaporated to yield 1,3,4,16b-tetrahydro-2H,10H-indolo[2,1-c]pyrazino[1,2-a][1,4]benzodiazepine which is converted to the hydrochloride salt, mp 263° dec.
Reaction SMILES: Cl.[CH3:2][O:3][C:4]1[C:9]2[N:10]=[C:11]([C:13]3[NH:14][C:15]4[CH2:20][CH2:19][NH:18][CH2:17][C:16]=4[N:21]=3)[S:12][C:8]=2[C:7]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[CH:6][CH:5]=1.C(N(C(C)C)C(C)C)C.[C:37]1([CH3:46])[C:38]([C:43](Cl)=[O:44])=[CH:39][CH:40]=[CH:41][CH:42]=1>O1CCCC1>[CH3:2][O:3][C:4]1[C:9]2[N:10]=[C:11]([C:13]3[NH:14][C:15]4[CH2:20][CH2:19][N:18]([C:43]([C:38]5[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=5[CH3:46])=[O:44])[CH2:17][C:16]=4[N:21]=3)[S:12][C:8]=2[C:7]([N:22]2[CH2:23][CH2:24][O:25][CH2:26][CH2:27]2)=[CH:6][CH:5]=1
Reactant: Cc1ccccc1C(=O)Cl
Reactant: COc1ccc(N2CCOCC2)c2sc(-c3nc4c([nH]3)CCNC4)nc12
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: COc1ccc(N2CCOCC2)c2sc(-c3nc4c([nH]3)CCN(C(=O)c3ccccc3C)C4)nc12
Yield: 50 %

Procedure:
To a suspension of 0.01 g 2-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine hydrochloride in 0.8 ml tetrahydrofurane were added at 0–4° C. 0.02 ml N-ethyldiisopropylamine and 0.004 ml o-toluoyl chloride. The mixture was refluxed over night, silicagel was added and the solvent was distilled off. The residue was transferred to a column prefilled with silicagel and was chromatographed with ethylacetate/methanol 98:2 to yield 0.006 g (50%)[2-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-1,4,6,7-tetrahydro-imidazo[4,5-c]pyridin-5-yl]-o-tolyl-methanone as yellow solid; MS (ISP): m/e=490 (M+H+).
Reaction SMILES: [CH2:1]([O:3][C:4]([N:6]1[CH2:21][CH2:20][C:10]2[C:11]3[C:12](=[O:19])[CH:13]([F:18])[CH2:14][C:15]=3[CH:16]=[CH:17][C:9]=2[CH2:8][CH2:7]1)=[O:5])[CH3:2].[Si](OS(C(F)(F)[F:34])(=O)=O)(C(C)(C)C)(C)C.[B-](F)(F)(F)F.[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+](F)(CC2)C1>C(Cl)Cl.C(#N)C>[CH2:1]([O:3][C:4]([N:6]1[CH2:21][CH2:20][C:10]2[C:11]3[C:12](=[O:19])[C:13]([F:34])([F:18])[CH2:14][C:15]=3[CH:16]=[CH:17][C:9]=2[CH2:8][CH2:7]1)=[O:5])[CH3:2]
Reactant: CCOC(=O)N1CCc2ccc3c(c2CC1)C(=O)C(F)C3
Reactant: CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F
Agent: F[B-](F)(F)F
Agent: F[N+]12CC[N+](CCl)(CC1)CC2
Solvent: CC#N
Solvent: ClCCl
Product: CCOC(=O)N1CCc2ccc3c(c2CC1)C(=O)C(F)(F)C3
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
Into a 500 ml flask, the product from step (a) (6.01 g, 20.65 mmol) dissolved in DCM (100 ml) was added. The solution was cooled to 0° C. and TEA (17.27 ml, 123.91 mmol) was added, followed by TBDMS-triflate (14.222 ml, 61.95 mmol). After 10 minutes, the ice bath was removed and the mixture was stirred at room temperature for 16 hours. The contents were washed with saturated aqueous NaHCO3, 1M citric acid, saturated aqueous NaHCO3, brine, and dried over Na2SO4. Evaporation of solvent yielded a brown liquid which was immediately dissolved in acetonitrile (100 ml). The solution was cooled to 0° C. and Selectfluor (14.6 g, 41.3 mmol) was added portion-wise at 0° C. over 30 minutes. The flask was then warmed to room temperature and stirred for 1 hour. The contents were partitioned between DCM and water and the aqueous layer was extracted with DCM (3×). The combined DCM extracts were washed with brine, dried over Na2SO4, and solvent evaporated in vacuo to give the crude product. Purification by silica-gel chromatography (gradient elution: 0 to 40% EtOAc) gave the sub-title product an off-white solid (5.1 g). 1H NMR (300 MHz, CDCl3) δ7.45 (d, J=7.8 Hz, 1H); 7.23 (d, J=7.5 Hz, 1H); 4.16 (t, J=6.9 Hz, 2H); 3.63-3.57 (m, 6H); 3.46 (t, J=12.9 Hz, 2H); 3.01-2.98 (m, 2H); 1.27 (t, J=7.2 Hz, 3H); MS: ESI (positive): 310 (M+1).
Reaction SMILES: [C:1]([C:5]1[CH:11]=[CH:10][CH:9]=[C:8]([CH3:12])[C:6]=1[NH2:7])([CH3:4])([CH3:3])[CH3:2].[CH3:13][N:14]([CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH:19]1[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:15](Cl)=[O:16]>N1C=CC=CC=1.ClCCl>[C:1]([C:5]1[CH:11]=[CH:10][CH:9]=[C:8]([CH3:12])[C:6]=1[NH:7][C:15]([N:14]([CH3:13])[CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH:19]1[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)=[O:16])([CH3:4])([CH3:3])[CH3:2]
Reactant: CN(C(=O)Cl)C1CCCCC1c1ccccc1
Reactant: Cc1cccc(C(C)(C)C)c1N
Solvent: ClCCl
Solvent: c1ccncc1
Product: Cc1cccc(C(C)(C)C)c1NC(=O)N(C)C1CCCCC1c1ccccc1
Temperature: 25 °C

Procedure:
To a solution of 0.82 g of 2-tert-butyl-6-methylaniline in pyridine is added a solution of 1.2 g of N-methyl-N-(2-phenylcyclohexyl)carbamoylchloride in dichloromethane dropwise. The mixture is stirred at room temperature until starting compounds disappear on TLC. The mixture is concentrated and the residue is dissolved in ethyl ether. The solution is washed with diluted hydrochloric acid, aqueous sodium hydrogencarbonate solution and brine. The organic layer is dried over sodium sulfate and filtered off. The filtrate is distilled away and the resuling residue is crystallized to give N-(2-tert-butyl-6-methylphenyl)-N'-methyl-N'-(2-phenylcyclohexyl)urea.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][OH:5].CC(C)([O-])C.[K+].Cl[C:13]1[C:22]2[C:17](=[C:18]([NH:23][C:24](=[O:33])[C:25]3[C:30]([Cl:31])=[CH:29][CH:28]=[CH:27][C:26]=3[Cl:32])[CH:19]=[CH:20][CH:21]=2)[N:16]=[CH:15][CH:14]=1>CN1CCCC1=O.C(OCC)(=O)C>[Cl:32][C:26]1[CH:27]=[CH:28][CH:29]=[C:30]([Cl:31])[C:25]=1[C:24]([NH:23][C:18]1[CH:19]=[CH:20][CH:21]=[C:22]2[C:17]=1[N:16]=[CH:15][CH:14]=[C:13]2[O:5][CH2:4][CH2:3][O:2][CH3:1])=[O:33]
Reactant: COCCO
Reactant: O=C(Nc1cccc2c(Cl)ccnc12)c1c(Cl)cccc1Cl
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN1CCCC1=O
Product: COCCOc1ccnc2c(NC(=O)c3c(Cl)cccc3Cl)cccc12
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 78.6 %

Procedure:
To a stirred solution of 2-methoxyethanol (130 mg) in N-methylpyrrolidone (2 ml) was added potassium tert-butoxide (172 mg) under ice-cooling, and the mixture was stirred for 30 minutes at ambient temperature. To the mixture was added 4-chloro-8-(2,6-dichlorobenzoylamino)quinoline (200 mg), and the mixture was stirred for 5 hours at 80° C. The mixture was diluted with ethyl acetate, washed with water and brine, dried over magnesium sulfate and evaporated in vacuo. The residue was recrystallized from ethanol to give 8-(2,6-dichlorobenzoylamino)-4-(2-methoxyethoxy)quinoline (175 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([O:13]CC)=[O:12])=[N:7][NH:8]2)=[CH:4][C:3]=1[C:16]1[CH:21]=[CH:20][C:19]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[CH:18][CH:17]=1.[OH-].[Na+]>C(O)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:13])=[O:12])=[N:7][NH:8]2)=[CH:4][C:3]=1[C:16]1[CH:21]=[CH:20][C:19]([N:22]2[CH2:23][CH2:24][O:25][CH2:26][CH2:27]2)=[CH:18][CH:17]=1
Reactant: CCOC(=O)c1n[nH]c2cc(Cl)c(-c3ccc(N4CCOCC4)cc3)cc12
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)c1n[nH]c2cc(Cl)c(-c3ccc(N4CCOCC4)cc3)cc12
Temperature: 70 °C
Reaction time: 3 h
Yield: 30.9 %

Procedure:
To a solution of ethyl 6-chloro-5-[4-(morpholin-4-yl)phenyl]-1H-indazole-3-carboxylate (72 mg, 0.19 mmol) in ethanol (2 mL) was added 6N aqueous sodium hydroxide (0.5 mL, 3.0 mmol). The mixture was stirred for three hours at 70° C. The cooled reaction mixture was neutralized with Dowex acid resin concentrated in vacuo. The crude product was purified by reverse phase column (water/acetonitrile, 0-40%, 20CV) to give the title compound (21 mg).
Reaction SMILES: [C:1]1([CH:7]2[CH2:11][CH2:10][CH2:9][NH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:12]1([CH3:22])[CH:17]=[CH:16][C:15]([S:18](Cl)(=[O:20])=[O:19])=[CH:14][CH:13]=1>>[C:1]1([CH:7]2[CH2:11][CH2:10][CH2:9][N:8]2[S:18]([C:15]2[CH:16]=[CH:17][C:12]([CH3:22])=[CH:13][CH:14]=2)(=[O:20])=[O:19])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: c1ccc(C2CCCN2)cc1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Product: Cc1ccc(S(=O)(=O)N2CCCC2c2ccccc2)cc1

Procedure:
The title compound, white solid, m.p. 109° C. and MS: m/e=301 (M+) was prepared in accordance with the general method of example 1e from (RS)-2-phenyl-pyrrolidine and toluene-4-sulfonyl chloride.
Reaction SMILES: [C:1]([NH2:5])(=[NH:4])[CH2:2][CH3:3].CO[CH:8]=[C:9]([CH2:12][NH:13][CH:14]=[O:15])[C:10]#[N:11]>C(O)C>[CH2:2]([C:1]1[N:5]=[C:10]([NH2:11])[C:9]([CH2:12][NH:13][CH:14]=[O:15])=[CH:8][N:4]=1)[CH3:3]
Reactant: CCC(=N)N
Reactant: COC=C(C#N)CNC=O
Solvent: CCO
Product: CCc1ncc(CNC=O)c(N)n1
Temperature: 25 °C
Yield: 100 %

Procedure:
In 50 parts by volume of ethanol is dissolved 14 parts of α-methoxymethylene-β-formylaminopropionitrile. To the solution is added 100 parts by volume of an ethanol solution containing 17 parts of propioamidine. The mixture is reacted at 30°C for 0.5 hour. After the reaction, ethanol is distilled off and the residue is cooled at 25°C, whereby 18 parts of 2-ethyl-4-amino-5-formylaminomethylpyrimidine is obtained as crystals. (Yield: 100 %). Recrystallization of the crystals from benzene-ethanol mixture gives colorless crystals melting at 185°C.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:9][C:10]1[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[CH:13]=[CH:12][C:11]=1F)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:27]1[CH2:31][CH2:30][CH2:29][CH2:28]1>>[C:1]([O:5][C:6]([N:8]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:9][C:10]1[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[CH:13]=[CH:12][C:11]=1[N:27]1[CH2:31][CH2:30][CH2:29][CH2:28]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: C1CCNC1
Reactant: CC(C)(C)OC(=O)N(Cc1cc([N+](=O)[O-])ccc1F)C(=O)OC(C)(C)C
Product: CC(C)(C)OC(=O)N(Cc1cc([N+](=O)[O-])ccc1N1CCCC1)C(=O)OC(C)(C)C
Yield: 80 %

Procedure:
Using the compound obtained in Example 263 as a starting material and also using pyrrolidine as a reagent, the same procedure of Example 264 gave the titled compound (yield, 80%).
Reaction SMILES: [CH3:1][O:2][CH2:3][O:4][CH2:5][CH2:6][N:7]([CH2:14][CH2:15][O:16][CH2:17][O:18][CH3:19])[CH2:8][CH2:9][O:10][CH2:11][O:12][CH3:13].ClC1C=CC=C(C(OO)=[O:28])C=1>ClCCl>[CH3:19][O:18][CH2:17][O:16][CH2:15][CH2:14][N+:7]([O-:28])([CH2:6][CH2:5][O:4][CH2:3][O:2][CH3:1])[CH2:8][CH2:9][O:10][CH2:11][O:12][CH3:13]
Reactant: COCOCCN(CCOCOC)CCOCOC
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: COCOCC[N+]([O-])(CCOCOC)CCOCOC
Reaction time: 1 h

Procedure:
28.1 g (0.1 mole) of tris(2-(methoxymethoxy)ethyl)-amine was dissolved in 85 g of dichloromethane, which was ice cooled. To the solution, 26.5 g (0.1 mole) of 65% pure m-chloroperbenzoic acid in 250 g of dichloromethane was added dropwise at such a rate that the mixture might not exceed 5° C. The mixture was allowed to mature for one hour at room temperature. The reaction solution was concentrated below 30° C. and the residue was purified by column chromatography (basic alumina, elute; dichloromethane/methanol). The eluate was concentrated whereupon the desired compound solidified. The amount was 27.3 g and the yield was 92*.
Reaction SMILES: [OH:1][C:2]12[CH2:11][CH:6]3[CH2:7][CH:8]([CH2:10][CH:4]([CH:5]3[NH:12][C:13]3[C:18]([C:19]#N)=[CH:17][N:16]=[C:15]4[NH:21][CH:22]=[CH:23][C:14]=34)[CH2:3]1)[CH2:9]2.[H-].C([Al+]CC(C)C)C(C)C.C1(C)C=CC=CC=1.Cl.[O:42]1CCCC1>>[OH:1][C:2]12[CH2:11][CH:6]3[CH2:7][CH:8]([CH2:10][CH:4]([CH:5]3[NH:12][C:13]3[C:18]([CH:19]=[O:42])=[CH:17][N:16]=[C:15]4[NH:21][CH:22]=[CH:23][C:14]=34)[CH2:3]1)[CH2:9]2
Reactant: C1CCOC1
Reactant: N#Cc1cnc2[nH]ccc2c1NC1C2CC3CC1CC(O)(C3)C2
Agent: CC(C)C[Al+]CC(C)C
Agent: Cl
Agent: [H-]
Solvent: Cc1ccccc1
Product: O=Cc1cnc2[nH]ccc2c1NC1C2CC3CC1CC(O)(C3)C2
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a solution of 4-[(5-hydroxyadamantan-2-yl)amino]-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile (150 mg) in tetrahydrofuran (3 ml) was added 1.01M diisobutylaluminum hydride/toluene solution (1.93 ml) at 778° C. The reaction solution was stirred for 18 hours under ambient temperature. To the reaction solution was added 1M hydrochloric acid under ice cooling, and the mixture was stirred for 30 minutes. The mixture was extracted with chloroform and washed with water. The organic layer was dried over magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to obtain 4-[(5-hydroxyadamantan-2-yl)amino]-1H-pyrrolo[2,3-b]pyridine-5-carbaldehyde (100 mg) as a pale yellow amorphous substance.
Reaction SMILES: [CH3:1][C:2]1[O:3][C:4]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)=[CH:5][C:6]=1[C:7](OC)=[O:8].[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+]>O1CCCC1.CCOCC.O>[CH3:1][C:2]1[O:3][C:4]([C:11]2[CH:12]=[CH:13][C:14]([C:17]([F:19])([F:18])[F:20])=[CH:15][CH:16]=2)=[CH:5][C:6]=1[CH2:7][OH:8]
Reactant: COC(=O)c1cc(-c2ccc(C(F)(F)F)cc2)oc1C
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCOCC
Solvent: O
Product: Cc1oc(-c2ccc(C(F)(F)F)cc2)cc1CO
Reaction time: 4 h

Procedure:
A solution of methyl 2-methyl-5-[4-(trifluoromethyl)phenyl]-3-furoate (intermediate 23, 0.27 g) in tetrahydrofuran (10 ml) stirred at 0° C. under a nitrogen atmosphere was treated with 1M lithium aluminium hydride in ether (1.0 ml). The reaction mixture was stirred at this temperature for 4 hours and then water (2 ml) and 2M aqueous sodium hydroxide (2 ml) added. The reaction mixture was further diluted with water; extracted with ethyl acetate and the organic solution extracted with water and dried with brine and over sodium sulfate and concentrated. The product isolated after evaporation of the solvent was further purified by Biotage™ chromatography using a mixture of petroleum ether:ethyl acetate (1:1) as eluent to give the title compound as a white solid.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([O:10]N)=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH3:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([C:20](=[O:28])[CH2:21][C:22](=O)[CH2:23][CH2:24][CH2:25][CH3:26])=[CH:16][CH:15]=1>C(O)(=O)C>[CH2:23]([C:22]1[O:10][C:7]2[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][C:6]=2[C:21]=1[C:20](=[O:28])[C:17]1[CH:18]=[CH:19][C:14]([O:13][CH3:12])=[CH:15][CH:16]=1)[CH2:24][CH2:25][CH3:26]
Reactant: NOc1ccc([N+](=O)[O-])cc1
Reactant: CCCCC(=O)CC(=O)c1ccc(OC)cc1
Solvent: CC(=O)O
Product: CCCCc1oc2ccc([N+](=O)[O-])cc2c1C(=O)c1ccc(OC)cc1
Temperature: 70 °C
Reaction time: 3 h
Yield: 70 %

Procedure:
O-4-nitrophenylhydroxylamine (100 mg), was suspended in 0.5 ml acetic acid and 1-(4-methoxyphenyl)-heptane-1,3-dione was added. The mixture was stirred at 70° C. for 3 h and then at 100° C. for an additional 14 h. The mixture was cooled to room temperature and the solvent evaporated under vacuum. Yield 70% of 2-butyl-3-(4-methoxybenzoyl)-5-nitrobenzofuran.
Reaction SMILES: [NH2:1][C@H:2]([C:8]([OH:10])=[O:9])[CH2:3][CH2:4][C:5](=[O:7])[NH2:6].CO.O.C(#N)C>O1CCCC1>[NH2:1][C@@H:2]([C:8]([OH:10])=[O:9])[CH2:3][CH2:4][C:5](=[O:7])[NH2:6]
Reactant: NC(=O)CC[C@H](N)C(=O)O
Solvent: C1CCOC1
Solvent: CC#N
Solvent: CO
Product: NC(=O)CC[C@@H](N)C(=O)O

Procedure:
Example 1 was repeated with the difference that the sample to be tested was a glutamine of unknown enantiomer composition, the comparison samples were (RS)-, (R)-, and (S)-glutamine, and the mobile phase was a mixture of methanol, water, acetonitrile, and tetrahydrofuran in a 1:1:2:2 ratio by volume. In this case, the (R)-glutamine gave a spot with an Rf -value of 0.70 and the (S)-glutamine gave a spot with an Rf -value of 0.62.
Reaction SMILES: [Br:1][C:2]1[C:15]2[C:16]3=[C:17]4[C:12](=[CH:13][CH:14]=2)[CH:11]=[CH:10][CH:9]=[C:8]4[CH:7]=[CH:6][C:5]3=[CH:4][CH:3]=1.[C:18](O)(=[O:20])C>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:16]3=[C:17]4[C:8]([CH:9]=[CH:10][CH:11]=[C:12]4[CH:13]=[CH:14][C:15]=13)=[CH:7][CH:6]=2.[CH2:18]=[O:20]
Reactant: CC(=O)O
Agent: Brc1ccc2ccc3cccc4ccc1c2c34
Product: C=O

Procedure:
Another photoconductor material used was bromopyrene resin. This product is obtained by condensation of 3-bromopyrene, melting point 94° to 95° C. (Organic Synthesis, Vol. 48 (1968), page 30) with formaldehyde in glacial acetic acid.
Reaction SMILES: [N:1]1([C:6]2[CH:15]=[CH:14][C:9]([O:10][CH2:11][CH2:12][OH:13])=[CH:8][CH:7]=2)[CH:5]=[N:4][CH:3]=[N:2]1.[S:16](Cl)(=[O:19])(=[O:18])[NH2:17].C(N(C(C)C)CC)(C)C>C(#N)C>[N:2]1[N:1]([C:6]2[CH:7]=[CH:8][C:9]([O:10][CH2:11][CH2:12][O:13][S:16](=[O:19])(=[O:18])[NH2:17])=[CH:14][CH:15]=2)[CH:5]=[N:4][CH:3]=1
Reactant: NS(=O)(=O)Cl
Reactant: OCCOc1ccc(-n2cncn2)cc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: NS(=O)(=O)OCCOc1ccc(-n2cncn2)cc1
Reaction time: 2 h
Yield: 55 %

Procedure:
A solution of 8.2 g (0.04 mole) of 2-[4-(1H-1,2,4-triazol-1-yl)phenoxy]ethanol in 100 ml of acetonitrile was treated with a solution of 1.3 equivalents of sulfamoyl chloride in 19 ml of acetonitrile. One equivalent, 5.2 g (0.04 mole), of diisopropylethylamine was also added in one portion. The mixture was stirred for 2 hr. The precipitate was collected and partitioned between ethyl acetate and a dilute potassium carbonate solution. The organic layer was separated and concentrated to a white powder. The powder was triturated with ethyl ether, collected and dried to give 6.3 g (55%) of white powder, mp 134°-136° C.
Reaction SMILES: [Cl:1][S:2]([OH:5])(=O)=[O:3].[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([N+:13]([O-:15])=[O:14])=[CH:9][CH:8]=1>O>[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([N+:13]([O-:15])=[O:14])=[CH:9][C:8]=1[S:2]([Cl:1])(=[O:5])=[O:3]
Reactant: O=[N+]([O-])c1ccc(Cl)cc1
Reactant: O=S(=O)(O)Cl
Solvent: O
Product: O=[N+]([O-])c1ccc(Cl)c(S(=O)(=O)Cl)c1

Procedure:
321 ml. (4.7 moles) of chlorosulfonic acid and 79 g. (0.5 moles) of 4-chloro-nitrobenzene are stirred at 130° C. for 6 hours. The reaction mixture is then cooled to a temperature below 10° C. and is poured onto 750 ml. of icy water. The mixture is filtered at room temperature and the substance collected on the filter is washed solid-free with about 2 litres of water. The crude 2-chloro-5-nitrobenzene sulfonyl chloride obtained is subjected to the subsequent reaction steps without purification. 118 g. (0.935 moles) of anhydrous sodium sulfite and 20 g. of sodium bicarbonate are dissolved in 250 ml. of water, and to the solution obtained a mixture of the crude 2-chloro-5-nitrobenzene sulfonyl chloride and 20 g. of sodium bicarbonate is added at a temperature of 23° to 25° C., in one hour. The reaction mixture is stirred for two hours at a temperature of 23° to 25° C., and, after the addition of 200 ml. of toluene, for further 15 minutes. The mixture is stirred at 25° C. and the substance filtered off is washed with 100 ml. of toluene. The sodium 2-chloro-5-nitrobenzene sulfinate obtained is dissolved in 400 ml. of water at 40° C., and the solution is admixed with 200 ml. of toluene. The insoluble part is filtered off and the toluene phase is separated from the filtrate. The aqueous phase is cooled to 10° C., acidified with 100 ml. of concentrated aqueous hydrochloric acid solution and the precipitated crystals are stirred, filtered off at 10° C. and dried. 61 g. of 2-chloro-5-nitrobenzene sulfinic acid are obtained. Yield: 55% of theoretical related to 4-chloro-nitrobenzene.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][N:3]=1.[CH3:11][O:12][C:13]1[CH:19]=[C:18]([O:20][CH3:21])[CH:17]=[CH:16][C:14]=1[NH2:15]>>[Cl:1][C:2]1[N:3]=[CH:4][C:5]([C:6]([NH:15][C:14]2[CH:16]=[CH:17][C:18]([O:20][CH3:21])=[CH:19][C:13]=2[O:12][CH3:11])=[O:7])=[CH:9][CH:10]=1
Reactant: COc1ccc(N)c(OC)c1
Reactant: O=C(Cl)c1ccc(Cl)nc1
Product: COc1ccc(NC(=O)c2ccc(Cl)nc2)c(OC)c1
Yield: 59 %

Procedure:
The title compound was prepared from 6-chloronicotinoyl chloride and 2,4-dimethoxyaniline as described in Example 1. The reaction mixture was filtered to remove the precipitate and the filtrate was evaporated. The resulting solid was purified by CH2Cl2/hexane recrystallization to give a light purple solid in a yield of 59%. 1H NMR (DMSO-d6): 9.77 (s, 1H), 8.93 (s, 1H), 8.35-8.31 (m, 1H), 7.68 (d, J=7.8, 1H), 7.46 (d, J=9.0, 1H), 6.67 (d, J=2.4, 1H), 6.57-6.53 (m, 1H), 3.80 (s, 3H), 3.78 (s, 3H).