Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([Br:5])(Br)(Br)[Br:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:25]([C:29]1[CH:34]=[CH:33][C:32]([C:35]2[CH:40]=[CH:39][C:38]([CH:41]=O)=[CH:37][CH:36]=2)=[CH:31][CH:30]=1)[CH2:26][CH2:27][CH3:28]>ClCCl>[CH2:25]([C:29]1[CH:34]=[CH:33][C:32]([C:35]2[CH:36]=[CH:37][C:38]([CH:41]=[C:1]([Br:5])[Br:2])=[CH:39][CH:40]=2)=[CH:31][CH:30]=1)[CH2:26][CH2:27][CH3:28]
Reactant: CCCCc1ccc(-c2ccc(C=O)cc2)cc1
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CCCCc1ccc(-c2ccc(C=C(Br)Br)cc2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 26.4 %

Procedure:
60 g of carbon tetrabromide was dissolved in 185 ml of dichloromethane, and 100 g of triphenylphosphine was added at 0° C. or less. Next, 22 g of 4'-butyl-4-biphenylaldehyde was dissolved in 93 ml of dichloromethane, which then was added dropwise to the first dichloromethane solution over a period of one hour. The combined solutions were then agitated at room temperature for one hour. After completion of the reaction, the dichloromethane was distilled off, and 500 ml hexane was added to the residue. The resulting crystals were filtrated and further washed with hexane three times. The residue was recrystallized with hexane to obtain 9.6 g of 4-(4'-butylphenyl)-β,β-dibromostyrene.
Reaction SMILES: [SH:1][C:2]1[NH:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.O[CH2:12][C:13]1[C:14]2[N:15]([CH:19]=[C:20]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[N:21]=2)[CH:16]=[CH:17][CH:18]=1.C(O)(=O)C.C(=O)([O-])[O-].[K+].[K+]>Br.O>[C:22]1([C:20]2[N:21]=[C:14]3[C:13]([CH2:12][S:1][C:2]4[NH:6][C:5]5[CH:7]=[CH:8][CH:9]=[CH:10][C:4]=5[N:3]=4)=[CH:18][CH:17]=[CH:16][N:15]3[CH:19]=2)[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: OCc1cccn2cc(-c3ccccc3)nc12
Reactant: Sc1nc2ccccc2[nH]1
Agent: Br
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC(=O)O
Product: c1ccc(-c2cn3cccc(CSc4nc5ccccc5[nH]4)c3n2)cc1
Temperature: 25 °C

Procedure:
A mixture of 1.24 g (10 mmole) of 3-hydroxymethyl-2-pyridinamine and 2.0 g (10 mmole) of α-bromoacetophenone in 25 ml of ethanol was stirred at room temperature. After 18 hours the resultant solid was collected, washed with ethano, and dissolved in water. The solution was made basic with aqueous potassium carbonate and extracted with dichloromethane. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was triturated with diethyl ether, collected by filtration, washed with diethyl ether, and air dried to yield 1.4 g of 8-hydroxymethyl-2-phenylimidazo[1,2-a]pyridine, as confirmed by the nmr and infrared spectra and by elemental analysis. [Calcd. for C14H12N2O2 : C, 74.98; H, 5.39; N, 12.49. Found: C, 74.68; H, 5.39; N, 12.40.] A mixture of 871 mg (5.8 mmole) of 2-mercaptobenzimidazole and 1.3 g (5.8 mmole) of 8-hydroxymethyl-2-phenylimidazo[1,2-a]pyridine was dissolved in 10 ml of 47% aqueous hydrobromic acid and 10 ml of acetic acid and heated to reflux. After being cooled to room temperature, the mixture was poured into water, made alkaline with potassium carbonate, and extracted with dichloromethane. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Trituration of the residue with diethyl ether yielded 1.8 g of the analytically pure title compound. Structure assignment was supported by the nmr and infrared spectra and by elemental analysis.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[C:9]([C@@H:11]([NH:14]S(C(C)(C)C)=O)[CH2:12][CH3:13])[CH:8]=[CH:7][N:6]=1)(=[O:4])=[O:3].[ClH:21].O1CCOCC1>CO>[ClH:21].[CH3:1][S:2]([C:5]1[CH:10]=[C:9]([C@@H:11]([NH2:14])[CH2:12][CH3:13])[CH:8]=[CH:7][N:6]=1)(=[O:4])=[O:3]
Reactant: CC[C@H](NS(=O)C(C)(C)C)c1ccnc(S(C)(=O)=O)c1
Agent: Cl
Solvent: CO
Solvent: C1COCCO1
Product: CC[C@H](N)c1ccnc(S(C)(=O)=O)c1
Reaction time: 1 h

Procedure:
To a solution of 2-methyl-propane-2-sulfinic acid [(S)-1-(2-methanesulfonyl-pyridin-4-yl)-propyl]-amide (26 g, 82 mmol) in methanol (150 mL) is added a solution of 4 N HCl in dioxane (22.5 mL, 89.8 mmol). After 1 hour, the solution is concentrated to half the original volume and diluted with toluene (100 mL), and concentrated. The crude material is co-evaporated from toluene (3×100 mL) and dried in vacuo for 18 hours to afford the title compound as a solid.
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[N:11]1[CH:15]=[C:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)[N:13]=[N:12]1.[NH2:22][C:23]1[C:24]([O:38][CH3:39])=[C:25]([NH:33][S:34]([CH3:37])(=[O:36])=[O:35])[CH:26]=[C:27]([C:29]([CH3:32])([CH3:31])[CH3:30])[CH:28]=1>>[C:29]([C:27]1[CH:26]=[C:25]([NH:33][S:34]([CH3:37])(=[O:36])=[O:35])[C:24]([O:38][CH3:39])=[C:23]([NH:22][C:6](=[O:8])[C:5]2[CH:9]=[CH:10][C:2]([CH3:1])=[C:3]([N:11]3[CH:15]=[C:14]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=4)[N:13]=[N:12]3)[CH:4]=2)[CH:28]=1)([CH3:32])([CH3:30])[CH3:31]
Reactant: COc1c(N)cc(C(C)(C)C)cc1NS(C)(=O)=O
Reactant: Cc1ccc(C(=O)O)cc1-n1cc(-c2ccccn2)nn1
Product: COc1c(NC(=O)c2ccc(C)c(-n3cc(-c4ccccn4)nn3)c2)cc(C(C)(C)C)cc1NS(C)(=O)=O

Procedure:
Example 3 was prepared by coupling 4-methyl-3-(4-pyridin-2-yl-[1,2,3]triazol-1-yl)-benzoic acid with N-(3-amino-5-tert-butyl-2-methoxy-phenyl)-methane-sulfonamide in the same manner as Example 1. ESI MS m/z 533 [C27H30N6O4S+H]+.
Reaction SMILES: C([Li])CCC.[CH2:6]([N:13]1[CH:17]=[CH:16][N:15]=[CH:14]1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[C:18]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>C1COCC1.C(=O)([O-])[O-].[Na+].[Na+]>[CH2:6]([N:13]1[CH:17]=[CH:16][N:15]=[C:14]1[C:18]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[OH:25])[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1
Reactant: O=C(c1ccccc1)c1ccccc1
Reactant: c1ccc(Cn2ccnc2)cc1
Agent: O=C([O-])[O-]
Agent: [Li]CCCC
Agent: [Na+]
Solvent: C1CCOC1
Product: OC(c1ccccc1)(c1ccccc1)c1nccn1Cc1ccccc1
Temperature: 23 °C
Reaction time: 0.33 h

Procedure:
A solution of n-butyllithium in hexanes (1.6 M, 45.0 mL, 72.0 mmol, 1.14 equiv) was added to a solution of 1-benzylimidazole (1-1, 10.0 g, 63.2 mmol, 1 equiv) in THF (200 mL) at −78° C. and the resulting mixture was stirred for 20 min. A solution of benzophenone (15.5 mL, 95.0 mmol, 1.50 equiv) in THF (30 mL) was added and the reaction mixture was stirred at −78° C. for 1 h, then warmed to 23° C. The mixture was partitioned between saturated ammonium chloride solution (200 mL) and ethyl acetate (400 mL), and the organic layer was separated, dried over magnesium sulfate and concentrated to give a yellow oil. The oil was suspended in saturated aqueous sodium carbonate solution and the resulting precipitate was filtered, washed with water (200 mL) then ethyl ether (2×100 mL) and air dried to afford (1-benzyl-1H-imidazol-2-yl)(diphenyl)methanol (1-2) as a white solid. 1H NMR (300 MHz, DMSO) δ 7.25 (m, 12H), 7.04 (m, 2H), 6.93 (s, 2H), 6.78 (s, 1H), 5.02 (s, 2H). LRMS m/z (M-OH) 323.1 found, 323.2 required.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH3:37])[C:12]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)([CH3:13])[N:11]([C:21](Cl)=[O:22])[C:10]([C:24]3[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][C:25]=3[O:34][CH2:35][CH3:36])=[N:9]2)=[CH:4][CH:3]=1.[CH3:38][N:39]1[CH2:44][CH2:43][N:42]([CH:45]2[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]2)[CH2:41][CH2:40]1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@:8]2([CH3:37])[C@:12]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)([CH3:13])[N:11]([C:21]([N:48]3[CH2:47][CH2:46][CH:45]([N:42]4[CH2:41][CH2:40][N:39]([CH3:38])[CH2:44][CH2:43]4)[CH2:50][CH2:49]3)=[O:22])[C:10]([C:24]3[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:31])[F:32])=[CH:26][C:25]=3[O:34][CH2:35][CH3:36])=[N:9]2)=[CH:6][CH:7]=1
Reactant: CN1CCN(C2CCNCC2)CC1
Reactant: CCOc1cc(C(F)(F)F)ccc1C1=NC(C)(c2ccc(Cl)cc2)C(C)(c2ccc(Cl)cc2)N1C(=O)Cl
Product: CCOc1cc(C(F)(F)F)ccc1C1=N[C@@](C)(c2ccc(Cl)cc2)[C@@](C)(c2ccc(Cl)cc2)N1C(=O)N1CCC(N2CCN(C)CC2)CC1

Procedure:
In a manner analogous to the method described in example 5, rac-(4S*,5R*)-4,5-bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl chloride was reacted with 1-methyl-4-piperidin-4-yl-piperazine (Oakwood Products) to give the title compound. HR-MS (ES, m/z) calculated for C37H43N5O2F3Cl2 [(M+H)+] 716.2741, observed 716.2746.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][N:9]=[CH:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H][H]>O1CCCC1.[Pd]>[C:1]([O:5][C:6]([NH:8][NH:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)NN=Cc1ccccc1
Reactant: [H][H]
Agent: [Pd]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)NNCc1ccccc1
Yield: 96.2 %

Procedure:
To a solution of N'-benzylidenehydrazinecarboxylic acid tert-butyl ester (2.7 g, 12.3 mmol) in tetrahydrofuran (100 ml) was added 10% palladium on carbon (0.3 g) and the mixture was hydrogenated with 280 ml of hydrogen for 40 min at atmospheric pressure. The mixture was filtered through a plug of celite and the filtrate was concentrated in vacuo to give 2.63 g of N'-benzylhydrazinecarboxylic acid tert-butyl ester.
Reaction SMILES: [CH3:1][C:2]1[C:7]([OH:8])=[C:6]([C:9](=[O:11])[CH3:10])[C:5]([CH:12]=[CH2:13])=[CH:4][N:3]=1.[CH2:14]([Mg]Br)[CH3:15]>O1CCCC1>[CH3:1][C:2]1[C:7]([OH:8])=[C:6]([C:9]([OH:11])([CH2:14][CH3:15])[CH3:10])[C:5]([CH:12]=[CH2:13])=[CH:4][N:3]=1
Reactant: CC[Mg]Br
Reactant: C=Cc1cnc(C)c(O)c1C(C)=O
Solvent: C1CCOC1
Product: C=Cc1cnc(C)c(O)c1C(C)(O)CC
Reaction time: 48 h

Procedure:
A solution of 3.93 g. of the product from Step A in 200 ml. of tetrahydrofuran was treated dropwise with 110% excess of ethyl magnesium bromide in tetrahydrofuran. After aging 2 days at ambient temperature the reaction was quenched on ice-water (100 ml.) containing 10 g. of ammonium chloride. The aqueous layer was separated and extracted with ether. The combined organic layers were dried over magnesium sulfate and evaporated to dryness to give 2-methyl-3-hydroxy-4-(2-hydroxybut-2-yl)-5-vinylpyridine, which was used directly in the next step.
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:19]=[CH:18][C:9]([O:10][CH2:11][CH2:12][N:13]2[CH:17]=[CH:16][N:15]=[CH:14]2)=[C:8]([Cl:20])[CH:7]=1)=[O:5])C.[OH-].[K+].C(O)(=O)C>O>[C:4]([C:6]1[CH:19]=[CH:18][C:9]([O:10][CH2:11][CH2:12][N:13]2[CH:17]=[CH:16][N:15]=[CH:14]2)=[C:8]([Cl:20])[CH:7]=1)([OH:5])=[O:3]
Reactant: CCOC(=O)c1ccc(OCCn2ccnc2)c(Cl)c1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CC(=O)O
Product: O=C(O)c1ccc(OCCn2ccnc2)c(Cl)c1
Yield: 62.5 %

Procedure:
A mixture of 1-[2-(4-ethoxycarbonyl-2-chlorophenoxy)ethyl]imidazole (115 mg) and potassium hydroxide (50 mg) in water (6.25 ml) was heated on a steam bath for 18 hours. The resulting solution was just acidified with acetic acid and evaporated to a small volume. The resulting solid was filtered off, washed with water and crystallised from water to give 1-[2-(4-carboxy-2-chlorophenoxy)ethyl]imidazole (65 mg), m.p. 204° C. Found: C, 53.44; H, 4.15; N, 10.52. C12H11ClN2O3 requires: C, 54.04; H, 4.16; N, 10.51%.
Reaction SMILES: Cl.[Br:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][NH:9][CH2:10]2)=[CH:5][CH:4]=1.[C:13]([O-:16])([O-])=[O:14].[Na+].[Na+]>C(Cl)Cl.O>[C:6]([O:16][C:13]([N:9]1[CH2:8][CH2:7][C:6]2[C:11](=[CH:12][C:3]([Br:2])=[CH:4][CH:5]=2)[CH2:10]1)=[O:14])([CH3:11])([CH3:7])[CH3:5]
Reactant: O=C([O-])[O-]
Reactant: Brc1ccc2c(c1)CNCC2
Agent: Cl
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: CC(C)(C)OC(=O)N1CCc2ccc(Br)cc2C1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of 7-bromo-1,2,3,4-tetrahydro-isoquinoline hydrochloride (1.0 g, 4.0 mmol) in DCM (18 mL) and 2M aqueous Na2CO3 solution (5.0 mL, 10.0 mmol) was added a solution of BOC-anhydride (1.0 g, 4.6 mmol) in DCM (7 mL). The reaction mixture was stirred at RT for 3 h and then diluted with water and DCM (1:1, 100 mL). The organic phase was then separated and washed with brine, dried (MgSO4) and filtered. The solvent was evaporated and then carried to next step without purification.
Reaction SMILES: [CH3:1][N+:2]([CH2:5][C@H:6]([NH2:11])[CH2:7][C:8]([O-:10])=[O:9])([CH3:4])[CH3:3].C(N(C(C)C)CC)(C)C.[N:21]([C:24]1[S:28][C:27]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[N:26][C:25]=1[CH3:35])=[C:22]=[O:23]>CO>[CH3:35][C:25]1[N:26]=[C:27]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[S:28][C:24]=1[NH:21][C:22](=[O:23])[NH:11][C@@H:6]([CH2:5][N+:2]([CH3:3])([CH3:4])[CH3:1])[CH2:7][C:8]([O-:10])=[O:9]
Reactant: Cc1nc(-c2ccccc2)sc1N=C=O
Reactant: C[N+](C)(C)C[C@H](N)CC(=O)[O-]
Solvent: CO
Solvent: CCN(C(C)C)C(C)C
Product: Cc1nc(-c2ccccc2)sc1NC(=O)N[C@H](CC(=O)[O-])C[N+](C)(C)C
Reaction time: 18 h

Procedure:
To a solution of (R)-aminocarnitine (21 mg, 0.13 mmol) and diisopropylethylamine (68 uL, 0.39 mmol) in MeOH (2 mL) was added 5-isocyanato-4-methyl-2-phenylthiazole (57 mg, 0.26 mmol) and the reaction stirred for 18 hrs. The MeOH was removed in vacuo and the residue stirred with 1:1 ether/EtOAc. Impurities dissolved into the ether/EtOAc which were discarded and the remaining material taken up into 90:10 CH2Cl2/MeOH and then loaded onto a short SiOH plug. The title compound was eluted by increasing MeOH content in 10% steps to 60%. The compound was then taken up into 90:10 CH2Cl2/MeOH and filtered through a plug of celite which gave after drying the title compound as a yellow powder (6 mg, 12%). 1H NMR (400 MHz, CD3OD) δ 7.85-7.82 (m, 2H), 7.47-7.41 (m, 3H), 4.73-4.71 (m, 1H), 3.82-3.57 (m, 2H), 3.26 (s, 9H), 2.79-2.75 (m, 2H), 2.37 (s, 3H); MS ESI 377.1 [M+H]+, calcd for [C18H24N4O3S+H]+ 377.47.
Reaction SMILES: [O:1]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[NH:3][C:2]1=[O:10].C1C(=O)N([Br:18])C(=O)C1.O>CN(C=O)C>[Br:18][C:7]1[CH:8]=[C:9]2[O:1][C:2](=[O:10])[NH:3][C:4]2=[N:5][CH:6]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: O=c1[nH]c2ncccc2o1
Solvent: CN(C)C=O
Solvent: O
Product: O=c1[nH]c2ncc(Br)cc2o1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 5.07 g oxazolo[4,5-b]pyridin-2(3H)-one dissolved in 85 ml of DMF under nitrogen is added 7.46 g NBS in 50 ml of DMF. This is allowed to stir at room temperature overnight. To this is added 35 ml of water and chilled. The solid material which separates is filtered and washed with 3×100 ml H2O. This is then dried in a vac oven at 70° C. and then used directly in the next step.
Reaction SMILES: [C:1]([O:5][C:6]([CH2:8][O:9][C:10]1[CH:11]=[C:12]([C:16](=[O:18])[CH3:17])[CH:13]=[CH:14][CH:15]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:19](=O)[C:20]1[CH:25]=[CH:24][CH:23]=[N:22][CH:21]=1.N1CCCCC1>CCO>[N:22]1[CH:23]=[CH:24][CH:25]=[C:20]([CH:19]=[CH:17][C:16]([C:12]2[CH:13]=[CH:14][CH:15]=[C:10]([O:9][CH2:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH:11]=2)=[O:18])[CH:21]=1
Reactant: CC(=O)c1cccc(OCC(=O)OC(C)(C)C)c1
Reactant: O=Cc1cccnc1
Solvent: CCO
Solvent: C1CCNCC1
Product: CC(C)(C)OC(=O)COc1cccc(C(=O)C=Cc2cccnc2)c1

Procedure:
A mixture of 16 (4.0 g, 16 mmol), nicotinaldehyde (1.89 mL, 20 mmol), and piperidine (4.0 mL, 40 mmol) in absolute EtOH (65 mL) was heated at reflux for 16 h. The mixture was cooled and concentrated in vacuo. Chromatography on silica gel (30-60% EtOAc/hexanes) gave a mixture of unreacted nicotinaldehyde and 17 (both have the same Rf on TLC). Washing of the mixture with hexane in a filter funnel provide 1.73 g (32%) of pure 17 as a yellow crystal. 1H NMR (CDCl3, 300 MHz) 8.87 (d, J=2.1 Hz, 1H), 8.66 (dd, J=4.8, 1.5 Hz, 1 H), 7.97 (d, J=7.9 Hz, 1H), 7.80 (d, J=16.7 Hz, 1H), 7.66 (d, J=7.6 Hz, 1H), 7.60 (d, J=15.9 Hz, 1H), 7.55 (s, 1H), 7.46 (t, J=7.8 Hz, 1H), 7.38 (dd, J=7.9, 4.8 Hz, 1H), 7.20 (dd, J=8.2, 2.6 Hz, 1H), 4.62 (s, 2H), 1.52 (s, 9H); 13C NMR (CDCl3, 75MHz) 189.7, 175.0, 168.0, 158.7, 151.6, 150.5, 141.4, 139.5, 134.9, 131.0, 130.2, 124.2, 122.3, 120.6, 114.1, 83.1, 66.2, 28.4.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]([CH3:12])([CH3:11])[N:10]=1.[CH3:13][N:14]([CH3:23])[C:15]1[CH:22]=[CH:21][C:18]([CH:19]=[O:20])=[CH:17][CH:16]=1>>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:19]([C:18]2[CH:21]=[CH:22][C:15]([N:14]([CH3:23])[CH3:13])=[CH:16][CH:17]=2)[O:20][C:9]([CH3:11])([CH3:12])[N:10]=1
Reactant: CC1(C)N=C1c1ccccc1Cl
Reactant: CN(C)c1ccc(C=O)cc1
Product: CN(C)c1ccc(C2OC(C)(C)N=C2c2ccccc2Cl)cc1

Procedure:
According to the procedure described in Example 1, from 30 g of 3-(o-chlorophenyl)-2,2-dimethyl-2H-azirine and 24 g of p-(dimethylamino)benzaldehyde there was obtained 4-(o-chlorophenyl)-5-[p-(dimethylamino)phenyl]-2,2-dimethyl-3-oxazoline which melted at 72.5°-73.5° C. after drying for 4 hours at 35° C. and 13 Torr.
Reaction SMILES: [NH2:1][C:2]1([C:17]2[CH:18]=[C:19]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH3:30])[CH:24]=3)[CH:20]=[CH:21][CH:22]=2)[CH2:6][CH:5]([O:7][Si:8]([C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:10])[CH3:9])[CH2:4][CH:3]1[CH2:15][OH:16].[C:31]([N:39]=[C:40]=[S:41])(=[O:38])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>C1COCC1>[Si:8]([O:7][CH:5]1[CH2:6][C:2]([NH:1][C:40]([NH:39][C:31](=[O:38])[C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)=[S:41])([C:17]2[CH:18]=[C:19]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH3:30])[CH:24]=3)[CH:20]=[CH:21][CH:22]=2)[CH:3]([CH2:15][OH:16])[CH2:4]1)([C:11]([CH3:13])([CH3:12])[CH3:14])([CH3:9])[CH3:10]
Reactant: COc1cccc(-c2cccc(C3(N)CC(O[Si](C)(C)C(C)(C)C)CC3CO)c2)c1
Reactant: O=C(N=C=S)c1ccccc1
Solvent: C1CCOC1
Product: COc1cccc(-c2cccc(C3(NC(=S)NC(=O)c4ccccc4)CC(O[Si](C)(C)C(C)(C)C)CC3CO)c2)c1
Yield: 77.5 %

Procedure:
A solution of (2-amino-4-(tert-butyldimethylsilyloxy)-2-(3′-methoxybiphenyl-3-yl)cyclopentyl)methanol (9.44 g, 22.1 mmol) and benzoyl isothiocyanate (3.49 g, 21.0 mmol) in THF (88 mL) is stirred for 1.5 hours at room temperature and concentrated under reduced pressure. The crude product is purified by silica gel chromatography eluting with a linear gradient of 0% to 5% methanol in dichloromethane over 27 minutes to give the title compound (9.61 g, 70%). ES/MS m/e: 589 (M−1).
Reaction SMILES: [Na:1].[NH2:2][C:3]1[N:11]=[C:10]2[C:6]([N:7]=[CH:8][N:9]2[CH2:12][O:13][CH2:14][CH2:15][O:16]C(=O)C2C=CC=CC=2)=[C:5](Cl)[N:4]=1.O.[CH2:27]([OH:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>>[Na:1].[NH2:2][C:3]1[N:11]=[C:10]2[C:6]([N:7]=[CH:8][N:9]2[CH2:12][O:13][CH2:14][CH2:15][OH:16])=[C:5]([O:34][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[N:4]=1
Reactant: OCc1ccccc1
Reactant: Nc1nc(Cl)c2ncn(COCCOC(=O)c3ccccc3)c2n1
Agent: [Na]
Solvent: O
Product: Nc1nc(OCc2ccccc2)c2ncn(COCCO)c2n1
Temperature: 120 °C

Procedure:
A solution of sodium benzylate in benzyl alcohol was prepared from sodium (2.58 g) and benzyl alcohol (28 ml). The solution was heated to 120° C. and 2-amino-6-chloro-9-(2-benzoyloxyethoxymethyl)purine (3.47 g) was added over a 10 minute period. The reaction mixture was heated overnight with stirring at 120°-130° C. and then poured into a mixture of ice and water. The resulting mixture was extracted thoroughly with chloroform. The aqueous phase was neutralized with acetic acid, giving a white precipitate which was recrystallized from methanol and then from water to give analytically pure 2-amino-6-benzyloxy-9-(2-hydroxyethoxymethyl)purine, m.p. 291°-292° C. (dec.) in 50% yield.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][CH2:7][CH2:8][OH:9].[Br:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]Br.[OH-].[Na+]>O>[Br:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][O:9][CH2:8][CH2:7][CH2:6][C:2]1[S:1][CH:5]=[CH:4][CH:3]=1
Reactant: OCCCc1cccs1
Reactant: BrCCCCCCBr
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: BrCCCCCCOCCCc1cccs1
Temperature: 25 °C
Reaction time: 8 h
Yield: 61.5 %

Procedure:
A mixture of 2-thiphenepropanol (5 g), 1,6-dibromohexane (25 g), 50% aqueous sodium hydroxide (25 ml) and TAB (500 mg) was stirred at room temperature overnight. Water (100 ml) was added over and the mixture was extracted with ether (2×100 ml). The organic layer was dried and concentrated to an oil which was purified by FCC eluting with hexane to give the title compound as a colourless oil (6.6 g). T.l.c. (hexane-diethyl ester 9:1) Rf 0.50.
Reaction SMILES: [CH2:1]([CH:8]1[CH2:13][CH2:12][N:11]([C:14]2[NH:15][C:16]3[C:21]([CH:22]=2)=[CH:20][C:19]([C:23]([NH2:25])=[O:24])=[CH:18][CH:17]=3)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[K+].[C:28](Cl)(=[O:31])[CH:29]=[CH2:30]>CC(C)=O>[C:28]([N:15]1[C:16]2[C:21](=[CH:20][C:19]([C:23]([NH2:25])=[O:24])=[CH:18][CH:17]=2)[CH:22]=[C:14]1[N:11]1[CH2:10][CH2:9][CH:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:13][CH2:12]1)(=[O:31])[CH:29]=[CH2:30]
Reactant: NC(=O)c1ccc2[nH]c(N3CCC(Cc4ccccc4)CC3)cc2c1
Reactant: C=CC(=O)Cl
Agent: [K+]
Agent: [OH-]
Solvent: CC(C)=O
Product: C=CC(=O)n1c(N2CCC(Cc3ccccc3)CC2)cc2cc(C(N)=O)ccc21

Procedure:
0.318 g (1 mmol) of (4-benzylpiperidinyl)-indole-5-carboxamide was taken in 15 mL dry acetone and was reacted with 0.2 g (5 mmol) of powdered KOH for 15 Min. The mixture was cooled in ice and 0.225 mg (2.5 mmol) of acryloyl chloride was added in one lot. Stirring continued at 0° C. for 20 Min., after which the reaction was further stirred at room temp. for 1 h. the solvent was removed in vacuo and the residue was extracted with ethyl acetate from water. The extract was dried and evaporated. TLC (ethyl acetate-hexane) and mass spectrum (M+ at 372) confirmed the desired product. This product was used without further purification for the next step.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[CH:14]=[C:13]2[C:9]([C:10]([CH:24]=[O:25])=[C:11]([CH:21]([CH3:23])[CH3:22])[N:12]2[CH2:15][C:16]2[O:17][CH:18]=[CH:19][N:20]=2)=[CH:8][CH:7]=1)=[O:5])[CH3:2].[O-:26]Cl=O.[Na+]>CC(O)(C)C.CC(=CC)C.O>[CH2:1]([O:3][C:4]([C:6]1[CH:14]=[C:13]2[C:9]([C:10]([C:24]([OH:26])=[O:25])=[C:11]([CH:21]([CH3:22])[CH3:23])[N:12]2[CH2:15][C:16]2[O:17][CH:18]=[CH:19][N:20]=2)=[CH:8][CH:7]=1)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1ccc2c(C=O)c(C(C)C)n(Cc3ncco3)c2c1
Reactant: [O-][Cl+][O-]
Agent: CC=C(C)C
Agent: [Na+]
Solvent: O
Solvent: CC(C)(C)O
Product: CCOC(=O)c1ccc2c(C(=O)O)c(C(C)C)n(Cc3ncco3)c2c1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
Following General Procedure D, ethyl3-formyl-2-isopropyl-1-(oxazol-2-ylmethyl)-1H-indole-6-carboxylate (Compound 38, 240 mg, 0.70 mmol) in t-BuOH (20 ml), 2-methyl-2-butene (2.0 ml) was added a solution of NaH2PO4 (1.69 g, 14.0 mmol) and NaClO2 (80%, 1.27 g, 14.0 mmol) in H2O (4 ml). The mixture was stirred at room temperature for 12 h. The reaction mixture was extracted with EtOAc (×3) and the combined organic layer was washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by chromatography on silica gel (0→55% EtOAc-hexanes) to yield the title compound as a light tan solid.
Reaction SMILES: Cl[CH2:2][CH2:3][CH:4]1[CH2:9][S:8][CH2:7][CH2:6][N:5]1[S:10]([C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][CH:14]=1)(=[O:12])=[O:11].[CH3:23][CH:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1>>[CH3:23][CH:24]1[CH2:29][CH2:28][N:27]([CH2:2][CH2:3][CH:4]2[CH2:9][S:8][CH2:7][CH2:6][N:5]2[S:10]([C:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[CH:16]=[CH:15][CH:14]=2)(=[O:12])=[O:11])[CH2:26][CH2:25]1
Reactant: O=S(=O)(c1cccc2ccccc12)N1CCSCC1CCCl
Reactant: CC1CCNCC1
Product: CC1CCN(CCC2CSCCN2S(=O)(=O)c2cccc3ccccc23)CC1
Yield: 63 %

Procedure:
The title compound (250 mg, 63%) was prepared according to the procedure outlined in Examples 5-44 using 3-(2-chloroethyl)-4-(naphthalene-1-sulfonyl)thiomorpholine and 4-methylpiperidine. MH+ 419.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]([OH:12])=O)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[CH3:13][NH2:14]>>[CH3:13][NH:14][C:10]([C:6]1[CH:5]=[C:4]2[C:9](=[CH:8][CH:7]=1)[NH:1][CH:2]=[CH:3]2)=[O:12]
Reactant: CN
Reactant: O=C(O)c1ccc2[nH]ccc2c1
Product: CNC(=O)c1ccc2[nH]ccc2c1

Procedure:
The title compound was prepared by following the similar procedure as described in Intermediate-10, using 1H-indole-5-carboxylic acid and methylamine (0.320 g, 59%); MS: 175(M+1).