Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]([O:5][C:6]([N:8]1[CH:12]2[CH2:13][CH:14]([OH:16])[CH2:15][CH:9]1[CH2:10][CH2:11]2)=[O:7])([CH3:4])[CH3:3].C1OCCOCCOCCOCCOCCOC1.CC(C)([O-])C.[K+].Cl[CH2:42][C:43]1[C:44]([CH:51]2[CH2:53][CH:52]2[C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)=[N:45][O:46][C:47]=1[CH:48]1[CH2:50][CH2:49]1>C1COCC1.O>[CH:48]1([C:47]2[O:46][N:45]=[C:44]([CH:51]3[CH2:53][CH:52]3[C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)[C:43]=2[CH2:42][O:16][CH:14]2[CH2:15][CH:9]3[N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH:12]([CH2:11][CH2:10]3)[CH2:13]2)[CH2:50][CH2:49]1
Reactant: ClCc1c(C2CC2c2ccccc2)noc1C1CC1
Reactant: CC(C)(C)OC(=O)N1C2CCC1CC(O)C2
Agent: C1COCCOCCOCCOCCOCCO1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1C2CCC1CC(OCc1c(C3CC3c3ccccc3)noc1C1CC1)C2
Reaction time: 0.17 h

Procedure:
A solution of N-Boc-nortropine (80 mg, 0.35 mmol) and 18-crown-6 (125 mg, 0.5 mmol) in THF (2.5 mL) was cooled to 0° C., treated with potassium tert-butoxide (59 mg, 0.53 mmol) and stirred for 10 min. A solution of 4-(chloromethyl)-5-cyclopropyl-3-(2-phenylcyclopropyl)isoxazole (80 mg, 0.29 mmol) in THF (0.5 mL) was added and the resulting mixture stirred at rt for 2 h and then poured into water and extracted with EtOAc. The organic layer was collected, washed with brine, dried over Na2SO4, filtered, concentrated to yield tert-butyl 3-((5-cyclopropyl-3-(2-phenylcyclopropyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octane-8-carboxylate. MS m/z 409.1 (M−56+1).
Reaction SMILES: [NH2:1][C:2]12[CH2:9][CH2:8][C:5]([CH2:10][OH:11])([CH2:6][CH2:7]1)[CH2:4][CH2:3]2.Br[CH2:13][C:14]([N:16]1[CH2:20][C@@H:19]([F:21])[CH2:18][C@H:17]1[C:22]#[N:23])=[O:15]>>[OH:11][CH2:10][C:5]12[CH2:8][CH2:9][C:2]([NH:1][CH2:13][C:14]([N:16]3[CH2:20][C@@H:19]([F:21])[CH2:18][C@H:17]3[C:22]#[N:23])=[O:15])([CH2:3][CH2:4]1)[CH2:7][CH2:6]2
Reactant: N#C[C@@H]1C[C@H](F)CN1C(=O)CBr
Reactant: NC12CCC(CO)(CC1)CC2
Product: N#C[C@@H]1C[C@H](F)CN1C(=O)CNC12CCC(CO)(CC1)CC2
Yield: 93.3 %

Procedure:
Using 4-amino-1-hydroxymethylbicyclo[2,2,2]octane (50.0 mg) and (2S,4S)-1-(2-bromoacetyl)-4-fluoropyrrolidine-2-carbonitrile (75.7 mg), the same procedure was followed as in Example 5 to obtain (2S,4S)-1-[[N-(4-hydroxymethylbicyclo[2,2,2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (93.0 mg).
Reaction SMILES: [NH:1]1[CH2:4][CH:3]([O:5][C:6]2[C:11]3[CH:12]=[C:13]([CH3:15])[O:14][C:10]=3[CH:9]=[C:8]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:7]=2)[CH2:2]1.[CH3:21][S:22](Cl)(=[O:24])=[O:23]>C(Cl)Cl>[CH3:15][C:13]1[O:14][C:10]2[CH:9]=[C:8]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:7]=[C:6]([O:5][CH:3]3[CH2:4][N:1]([S:22]([CH3:21])(=[O:24])=[O:23])[CH2:2]3)[C:11]=2[CH:12]=1
Reactant: CCOC(=O)c1cc(OC2CNC2)c2cc(C)oc2c1
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Product: CCOC(=O)c1cc(OC2CN(S(C)(=O)=O)C2)c2cc(C)oc2c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 79.9 %

Procedure:
To a solution of ethyl 4-(azetidin-3-yloxy)-2-methyl-1-benzofuran-6-carboxylate (324b) (200 mg, 0.73 mmol) in DCM containing TEA (0.4 mL, 2.9 mmol) was added methanesulfonyl chloride (0.07 mL, 0.87 mmol). The mixture was stirred at room temperature for 2 hrs. The reaction was diluted with DCM, washed with NaHCO3, brine, dried over Na2SO4 and concentrated under reduced pressure. The product was purified via gradient silica gel chromatography using EtOAc/Hexanes (10/90 to 30/70) to provide the product (206 mg, 80%) as a white solid after evaporation of the solvents. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.34-1.51 (m, 3 H) 2.49 (s, 3 H) 2.89-3.07 (m, 3 H) 4.06-4.22 (m, J=9.23, 4.33 Hz, 2 H) 4.33-4.54 (m, 4 H) 5.07-5.23 (m, 1 H) 6.52 (s, 1 H) 7.02 (s, 1 H) 7.82 (s, 1 H); MS (ESI, pos): 354.
Reaction SMILES: [CH3:1][N:2]1[C@H:11]2[C@@:6]([CH3:17])([C:7]3[CH:15]=[CH:14][C:13]([SH:16])=[CH:12][C:8]=3[CH2:9][CH2:10]2)[CH2:5][CH2:4][C:3]1=[O:18].C(=O)([O-])[O-].[K+].[K+].Cl[C:26]1[S:27][C:28]2[C:34]([CH3:35])=[CH:33][CH:32]=[C:31]([CH3:36])[C:29]=2[N:30]=1.CN(C)C=O>C(OCC)(=O)C>[CH3:1][N:2]1[C@H:11]2[C@@:6]([CH3:17])([C:7]3[CH:15]=[CH:14][C:13]([S:16][C:26]4[S:27][C:28]5[C:34]([CH3:35])=[CH:33][CH:32]=[C:31]([CH3:36])[C:29]=5[N:30]=4)=[CH:12][C:8]=3[CH2:9][CH2:10]2)[CH2:5][CH2:4][C:3]1=[O:18]
Reactant: CN1C(=O)CC[C@]2(C)c3ccc(S)cc3CC[C@@H]12
Reactant: Cc1ccc(C)c2sc(Cl)nc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Cc1ccc(C)c2sc(Sc3ccc4c(c3)CC[C@H]3N(C)C(=O)CC[C@]43C)nc12
Yield: 69.1 %

Procedure:
A 15 mL round bottom flask was charged with (+)-(4aR)-(10bR)-4-methyl-8-mercapto-10b-methyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolin-3-one (100 mg, 0.38 mmol), potassium carbonate (158 mg, 1.14 mmol), 2-chloro-4,7-dimethylbenzothiazole (91 mg, 0.46 mmol) and 1 mL of anhydrous dimethylformamide, fitted with a reflux condenser, and the stirred mixture was heated at 60°, under nitrogen, for 18 h. The mixture was cooled, diluted with ethyl acetate (75 mL) and washed with brine (2×25 mL). The combined organic extracts were dried over sodium sulfate, concentrated, and purified by silica gel chromatography (80% ethyl acetate/hexanes eluent) to give 111 mg (69%) of the title compound as an amorphous foam. FDMS: m/e=422. α[D]589 =+63.27 (c=0.95, chloroform).
Reaction SMILES: [CH3:1][C@@H:2]([NH2:14])[CH2:3][CH2:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[NH:7][CH:6]=1.[N:15]1[N:16]=[N:17][N:18]2[CH:23]=[C:22]([C@@H:24]3[CH2:26][O:25]3)[CH:21]=[CH:20][C:19]=12>C(O)C>[CH3:1][C@@H:2]([NH:14][CH2:26][C@@H:24]([C:22]1[CH:21]=[CH:20][C:19]2[N:18]([N:17]=[N:16][N:15]=2)[CH:23]=1)[OH:25])[CH2:3][CH2:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[NH:7][CH:6]=1
Reactant: c1cc2nnnn2cc1[C@@H]1CO1
Reactant: C[C@@H](N)CCc1c[nH]c2ccccc12
Solvent: CCO
Product: C[C@H](CCc1c[nH]c2ccccc12)NC[C@H](O)c1ccc2nnnn2c1

Procedure:
A solution of 16 g of 1-(1H-indol-3-yl)-3-butanone, 10.3 g of R(+)-1-phenylethylamine and 0.2 g of TsOH.H2O in 80 ml of benzene is heated at reflux with water removal (Dean-Stark trap) for 24 hours. The reaction mixture is concentrated under reduced pressure and the residue redissolved in 80 ml of methanol. To this solution 8 g of Ra(Ni) catalyst is added and the mixture hydrogenated under positive hydrogen pressure for 32 hours. The reaction mixture is filtered through celite and the filtrate concentrated. The residue is chromatographed on silica gel to afford the (R,R,)-diastereomer. This material (6.2 g) is converted into its hydrochloride salt and dissolved in 50 ml of ethanol and hydrogenated over 1.6 g of 5% Pd(C) for 18 hours. The reaction mixture is then filtered and the filtrate concentrated under reduced pressure to dryness. The residue is chromatographed on silica gel to give 1(R)-methyl-3-(1H-indol-3-yl)propyl amine. This amine (650 mg) is condensed with 650 mg of (R)-2-(tetrazolo-[1,5-a]pyrid-6-yl)oxirane in 15 ml of absolute ethanol at reflux for 3 hours. The reaction mixture is concentrated under reduced pressure and the residue purified by chromatography on silica gel to give (R)-α-[[(1(R)-methyl-3-(1H-indol-3-yl)propyl)amino]methyl]tetrazolo[1,5-a]pyridine-6-methanol. This tetrazole (0.6 g) in 15 ml of methanol is treated with 0.6 g of SnCl2.2H2O and the reaction mixture heated at reflux for 18 hours. The reaction solution is partially concentrated under reduced pressure. This concentrated solution is added to a mixture of CH2Cl2 (20 ml) and 12 ml of 2N NaOH solution. The mixture is stirred for twenty minutes and then the layers are separated. The aqueous layer is further extracted with CH2Cl2. The combined organic extracts are backwashed with saturated sodium chloride solution and dried with anhydrous magnesium sulfate. The solution is concentrated and the residue chromatographed on silica gel to give the titled compound after conversion to its hydrochloride salt with ethanolic HCl.
Reaction SMILES: [C:1]1([OH:11])[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.C([O-])([O-])=O.[Na+].[Na+].F[C:19]1[CH:20]=[N+:21]([O-:28])[CH:22]=[CH:23][C:24]=1[N+:25]([O-:27])=[O:26].O>CN(C=O)C>[N+:25]([C:24]1[CH:23]=[CH:22][N+:21]([O-:28])=[CH:20][C:19]=1[O:11][C:1]1[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1)([O-:27])=[O:26]
Reactant: O=[N+]([O-])c1cc[n+]([O-])cc1F
Reactant: Oc1cccc2c1CCCC2
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1cc[n+]([O-])cc1Oc1cccc2c1CCCC2
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To 5,6,7,8-tetrahydro-1-naphthol (6.0 g) in DMF (100 ml) was added Na2CO3 (10 g) portionwise at room temperature. Then a solution of 3-fluoro-4-nitropyridine-N-oxide (6.0 g) in 20 ml of DMF was added dropwise and the mixture was stirred at room temperature for four hours. The mixture was then poured into water and extracted with ethyl acetate. The organic layer was washed with water and dried (sat NaCl, anhy. MgSO4).
Reaction SMILES: [CH:1]([NH:4][C:5]([N:7]1[C:15]2[C:10](=[CH:11][C:12]([C:16]([F:19])([F:18])[F:17])=[CH:13][CH:14]=2)[C:9]([NH:20][CH2:21][C:22](=[O:28])[NH:23][CH:24]2[CH2:27][NH:26][CH2:25]2)=[N:8]1)=[O:6])([CH3:3])[CH3:2].[CH:29]1([CH:36]2[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]2)[CH2:34][CH2:33][C:32](=O)[CH2:31][CH2:30]1>>[CH:1]([NH:4][C:5]([N:7]1[C:15]2[C:10](=[CH:11][C:12]([C:16]([F:18])([F:19])[F:17])=[CH:13][CH:14]=2)[C:9]([NH:20][CH2:21][C:22](=[O:28])[NH:23][CH:24]2[CH2:25][N:26]([CH:39]3[CH2:40][CH2:41][CH:36]([CH:29]4[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]4)[CH2:37][CH2:38]3)[CH2:27]2)=[N:8]1)=[O:6])([CH3:3])[CH3:2]
Reactant: CC(C)NC(=O)n1nc(NCC(=O)NC2CNC2)c2cc(C(F)(F)F)ccc21
Reactant: O=C1CCC(C2CCCCC2)CC1
Product: CC(C)NC(=O)n1nc(NCC(=O)NC2CN(C3CCC(C4CCCCC4)CC3)C2)c2cc(C(F)(F)F)ccc21

Procedure:
The title compound was prepared as a white solid from reaction of 3-[(azetidin-3-ylcarbamoylmethyl)-amino]-5-trifluoromethyl-indazole-1-carboxylic acid isopropylamide (as prepared in Example 90, Step A) and bicyclohexyl-4-one using the procedure described in Step E of Example 1.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:15])[CH2:4][CH:5]([C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH3:14])[CH:8]=1)[OH:6].[CH3:16]I.[H-].[Na+]>>[CH3:1][O:2][C:3](=[O:15])[CH2:4][CH:5]([C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH3:14])[CH:8]=1)[O:6][CH3:16]
Reactant: CI
Reactant: COC(=O)CC(O)c1cccc(OC)c1
Agent: [H-]
Agent: [Na+]
Product: COC(=O)CC(OC)c1cccc(OC)c1

Procedure:
Methylβ-(m-methoxyphenyl)-β-hydroxy-propionate was reacted with methyl iodide/sodium hydride to give methyl-β-(m-methoxyphenyl)-β-methoxy-propionate, which was then reduced with LiAlH4 in dry ether to give 3-(m-methoxyphenyl)-3-methoxy-propanol. This latter product was converted into 3-(m-methoxyphenyl)-3-methoxy-propanal by oxidation with pyridinium chlorochromate in dry dichloromethane.
Reaction SMILES: [CH:1]1([CH:6]([C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=2)[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:5][CH2:4][CH2:3][CH2:2]1.N(C(C)(C)C#N)=NC(C)(C)C#N.[Br:33]N1C(=O)CCC1=O>ClC(Cl)(Cl)Cl>[Br:33][CH2:20][C:17]1[CH:18]=[CH:19][C:14]([CH:6]([CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)[C:7]([O:9][C:10]([CH3:12])([CH3:11])[CH3:13])=[O:8])=[CH:15][CH:16]=1
Reactant: Cc1ccc(C(C(=O)OC(C)(C)C)C2CCCC2)cc1
Reactant: O=C1CCC(=O)N1Br
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: ClC(Cl)(Cl)Cl
Product: CC(C)(C)OC(=O)C(c1ccc(CBr)cc1)C1CCCC1
Temperature: 0 °C

Procedure:
27.4 g (0.1 mol) of the compound from Example XXI are dissolved in 200 ml of tetrachloromethane and the solution is heated to boiling. After addition of 0.82 g of azobisisobutyronitrile, 18.7 g (0.105 mol) of N-bromosuccinimide are added in portions and the mixture is then refluxed for 1 h, cooled to 0° C. and succinimide is filtered off. After concentrating the filtrate the product precipitates. It is washed with petroleum ether (40/60) and dried.
Reaction SMILES: C(=O)([O-])[O-].[Na+].[Na+].Br[C:8]1[CH:9]=[CH:10][C:11]([NH2:14])=[N:12][CH:13]=1.[OH:15][CH2:16][C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[CH:21][CH:22]=1.C(O)C>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:14][C:11]1[N:12]=[CH:13][C:8]([C:21]2[CH:22]=[C:17]([CH2:16][OH:15])[CH:18]=[CH:19][CH:20]=2)=[CH:9][CH:10]=1
Reactant: OCc1cccc(B(O)O)c1
Reactant: Nc1ccc(Br)cn1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCO
Product: Nc1ccc(-c2cccc(CO)c2)cn1
Temperature: 80 °C
Yield: 86.2 %

Procedure:
2.0 g of tetrakis(triphenylphosphine)palladium and 75 ml of a 2M solution of sodium carbonate are added to a round-bottomed flask containing a solution of 5.0 g of 5-bromopyridin-2-ylamine in 140 ml of toluene, 5.7 g of 3-(hydroxymethyl)phenylboronic acid and 70 ml of ethanol degassed beforehand. The mixture is heated at 80° C. for 16 h. After cooling, the reaction mixture is concentrated under reduced pressure. The residue is taken up between water and ethyl acetate. The organic phase is separated, dried and concentrated under reduced pressure. The residue is purified by silica gel chromatography, elution being carried out with a dichloromethane/methanol mixture. 4.99 g of compound are obtained.
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:15](=[O:17])[NH:14][C:13](=[O:18])[N:12]([CH3:19])[C:11]=2[N:10]=[C:9]1[Br:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:22][C:23]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:24]>>[CH2:1]([N:8]1[C:16]2[C:15](=[O:17])[N:14]([CH2:22][C:23](=[O:24])[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:13](=[O:18])[N:12]([CH3:19])[C:11]=2[N:10]=[C:9]1[Br:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Cn1c(=O)[nH]c(=O)c2c1nc(Br)n2Cc1ccccc1
Reactant: O=C(CBr)c1ccccc1
Product: Cn1c(=O)n(CC(=O)c2ccccc2)c(=O)c2c1nc(Br)n2Cc1ccccc1

Procedure:
7-Benzyl-8-bromo-3-methyl-3,7-dihydropurine-2,6-dione (77A) and 2-bromoacetophenone were reacted and purified as described in the General procedure G, Step B, to afford 77B.
Reaction SMILES: [F:1][C:2]1[C:7](F)=[CH:6][CH:5]=[C:4]([N+:9]([O-:11])=[O:10])[C:3]=1[CH2:12][C:13](=[O:15])[CH3:14].[C:16](=O)([O-])[O-:17].[K+].[K+]>CO>[F:1][C:2]1[C:7]([O:17][CH3:16])=[CH:6][CH:5]=[C:4]([N+:9]([O-:11])=[O:10])[C:3]=1[CH2:12][C:13](=[O:15])[CH3:14]
Reactant: O=C([O-])[O-]
Reactant: CC(=O)Cc1c([N+](=O)[O-])ccc(F)c1F
Agent: [K+]
Solvent: CO
Product: COc1ccc([N+](=O)[O-])c(CC(C)=O)c1F
Yield: 73.6 %

Procedure:
A mixture of 1-(2,3-difluoro-6-nitrophenyl)-propan-2-one (183 g) and potassium carbonate (100 g) in methanol (1 L) was heated at reflux for 3 h. The reaction mixture was then cooled and concentrated in vacuo to remove most of the methanol. The residue was diluted with ethyl acetate (1 L), filtered and washed with water. The separated aqueous layer was neutralized with 2N HCl and extracted with ethyl acetate (2×500 mL). The combined organic layer was washed with brine, dried (Na2SO4) and concentrated in vacuo to give a brown solid. The solid was triturated with diethyl ether and filtered to provide 1-(2-fluoro-3-methoxy-6-nitrophenyl)-propan-2-one (121 g, 71%) as a yellow solid. LC/MS; (M+H)+=228.2. C. A mixture of 1-(2-fluoro-3-methoxy-6-nitrophenyl)-propan-2-one from previous step (454 mg, 21 mmol) and pyridinium chloride (0.9 g, 7.8 mmol) was stirred at 180° C. for 75 min. The reaction was cooled to room temperature, diluted with 1N HCl (3 mL) and ethyl acetate (10 mL) and filtered. The filtrate was washed with brine (2×), dried and concentrated in vacuo to give 1-(2-fluoro-3-hydroxy-6nitrophenyl)-propan-2-one (410 mg, 96%) as a grey solid, which was used without further purification for the next step. LC/MS; (M+H)+=214. 1HNMR (CDCl3): δ 2.37 (s, 3H), 4.22 (s, 2H), 6.95 (dd, 1H), 7.95 (d, 1H, J=9.35 Hz). D. 1-(2-fluoro-3-hydroxy-6-nitrophenyl)-propan-2-one from previous step (50 g, 0.234 mol) was added to 2 liter round bottom flask. Water (1 L) was added, and the yellow suspension was stirred at RT. Sodium dithionite (225 g, 5.5 eq) was added in one portion and the reaction mixture was stirred and kept <30° C. until HPLC analysis indicated no starting material remained (typically less than 1 hour). Upon completion, the reaction mixture was cooled to 0° C. and the tan solid product was collected by vacuum filtration. The wet product was dried at <50° C. under house vacuum to afford 4-fluoro-2-methyl-1H-indol-5-ol (31.4 g, 81% yield) which was isolated as a tan crystalline powder. The material had an HPLC purity of >99.8. 1H NMR (CDCl3, 400 MHz) δ 7.8 (s, 1H), 6.9-6.7 (m, 2H), 6.2 (s,1H), 4.7 (s, 1H), 2.4 (s, 3H).
Reaction SMILES: C(N(CC)CC)C.Cl[C:9]1[N:14]=[C:13]([CH:15]=[CH:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:12]=[C:11]([CH3:23])[CH:10]=1.[H][H]>[Pd].CC([O-])=O.CC([O-])=O.[Pb+2].C(O)C>[CH3:23][C:11]1[CH:10]=[CH:9][N:14]=[C:13]([CH:15]=[CH:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:12]=1
Reactant: Cc1cc(Cl)nc(C=Cc2ccccc2)n1
Reactant: [H][H]
Agent: [Pd]
Agent: CC(=O)[O-]
Agent: [Pb+2]
Solvent: CCO
Solvent: CCN(CC)CC
Product: Cc1ccnc(C=Cc2ccccc2)n1

Procedure:
9.02 ml of triethylamine and 1.365 g of Lindlar catalyst are added to 13.65 g (59.17 mmol) of 6-chloro-4-methyl-2-(2-phenylethenyl)-pyrimidine in 220 ml of absolute ethanol and hydrogenation is carried out at room temperature under normal pressure. When 1 equivalent of hydrogen has been absorbed, hydrogenation is terminated (after about 7.5 hours), and the reaction mixture is filtered with suction over Hyflo Super Cel® and concentrated in a rotary evaporator. Chromatography twice on silica gel with chloroform and then n-hexane/ethyl acetate 5-20% as eluants yields the pure title compound; m.p. 65°-67°.
Reaction SMILES: [Br:1][C:2]1[C:3]([CH3:9])=[N:4][C:5]([Cl:8])=[CH:6][CH:7]=1.[Br:10]C1C(CBr)=NC=C(Br)C=1>>[Br:1][C:2]1[C:3]([CH2:9][Br:10])=[N:4][C:5]([Cl:8])=[CH:6][CH:7]=1
Reactant: Cc1nc(Cl)ccc1Br
Reactant: BrCc1ncc(Br)cc1Br
Product: Clc1ccc(Br)c(CBr)n1
Yield: 45 %

Procedure:
Compound 55B (0.33 g, 45%) was prepared from 55A (0.53 g, 2.57 mmol) using a procedure similar to the synthesis of 52B. HPLC Rt=2.47 min.
Reaction SMILES: [O:1]1[CH2:3][C@H:2]1[CH2:4][O:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[CH:8]=[CH:9][NH:10]2.[CH3:15][C:16]1[CH:17]=[CH:18][CH:19]=[C:20]2[C:24]=1[NH:23][CH:22]=[C:21]2[C:25]1[CH2:26][CH2:27][NH:28][CH2:29][CH:30]=1.C(O)C>CS(C)=O>[CH3:15][C:16]1[CH:17]=[CH:18][CH:19]=[C:20]2[C:24]=1[NH:23][CH:22]=[C:21]2[C:25]1[CH2:26][CH2:27][N:28]([CH2:3][C@H:2]([OH:1])[CH2:4][O:5][C:6]2[CH:14]=[CH:13][CH:12]=[C:11]3[C:7]=2[CH:8]=[CH:9][NH:10]3)[CH2:29][CH:30]=1
Reactant: Cc1cccc2c(C3=CCNCC3)c[nH]c12
Reactant: c1cc(OC[C@@H]2CO2)c2cc[nH]c2c1
Solvent: CS(C)=O
Solvent: CCO
Product: Cc1cccc2c(C3=CCN(C[C@H](O)COc4cccc5[nH]ccc45)CC3)c[nH]c12

Procedure:
The title compound was prepared in a fashion similar to that described in Example 1 using (S)-(+)-4-(oxiranylmethoxy)-1H-indole (0.389 g, 2.05 mmol) and 7-methyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole (0.400 g, 1.87 mmol) using ethanol as reaction solvent. Yield 0.292 g (39%) as an orange foam. mp 155°-158° C. FDMS m/e=401 (M+ of free base). α[D]589 =+5.9 (c=1.05, dimethylsulfoxide).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][C:10]=2[Cl:18])[CH:5]=[CH:4][N:3]=1.C(N(CC)CC)C.Cl[C:27]([O:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:28]>O1CCCC1>[Cl:18][C:10]1[CH:11]=[C:12]([N+:15]([O-:17])=[O:16])[CH:13]=[CH:14][C:9]=1[O:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:1][C:27]([O:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[O:28])[CH:7]=1
Reactant: O=C(Cl)Oc1ccccc1
Reactant: Nc1cc(Oc2ccc([N+](=O)[O-])cc2Cl)ccn1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: O=C(Nc1cc(Oc2ccc([N+](=O)[O-])cc2Cl)ccn1)Oc1ccccc1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
2-Amino-4-(2-chloro-4-nitrophenoxy)pyridine (574 mg) was dissolved in tetrahydrofuran (10 ml) under a nitrogen atmosphere, and then triethylamine (0.602 ml) and phenyl chloroformate (0.542 ml) were added dropwise thereto while cooling in an ice bath, followed by stirring at room temperature for 10 min. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated under a reduced pressure to provide a crude product of 4-(2-chloro-4-nitrophenoxy)-2-(phenoxycarbonylamino)pyridine (1.272 g). The crude product (637.3 mg) was dissolved in tetrahydrofuran (6.5 ml), and then pyrrolidine (1.06 ml) was added at room temperature, followed by stirring for 1 hr and evaporating the solvents under a reduced pressure. The resultant residue was dissolved in ethanol (20 ml)-water (5 ml), and then electrolytic iron powder (500 mg) and ammonium chloride (1 g) were added thereto, followed by heating under reflux for 1 hr. The reaction mixture was cooled down to room temperature, and filtered through celite to remove an insoluble portion, which was washed with ethyl acetate-tetrahydrofuran (1:1) and water. The organic layer of the filtrate was separated, washed with water and brine in this order, dried over anhydrous sodium sulfate. The solvent was evaporated under a reduced pressure to give a residue, which was purified by silica gel column chromatography (eluent; ethyl acetate) to provide the titled compound (227 mg) as pale yellow powder.
Reaction SMILES: [CH3:1][C:2]1([CH3:39])[CH2:11][CH2:10][C:9]([CH3:13])([CH3:12])[C:8]2[CH:7]=[C:6]([Se:14][C:15]#[C:16][C:17]3[CH:26]=[CH:25][C:20]([C:21]([O:23]C)=[O:22])=[CH:19][CH:18]=3)[CH:5]=[C:4]([O:27][CH2:28][C:29]3[CH:34]=[CH:33][C:32]([C:35]([CH3:38])([CH3:37])[CH3:36])=[CH:31][CH:30]=3)[C:3]1=2.[OH-].[Na+]>>[C:35]([C:32]1[CH:31]=[CH:30][C:29]([CH2:28][O:27][C:4]2[C:3]3[C:2]([CH3:1])([CH3:39])[CH2:11][CH2:10][C:9]([CH3:13])([CH3:12])[C:8]=3[CH:7]=[C:6]([Se:14][C:15]#[C:16][C:17]3[CH:26]=[CH:25][C:20]([C:21]([OH:23])=[O:22])=[CH:19][CH:18]=3)[CH:5]=2)=[CH:34][CH:33]=1)([CH3:36])([CH3:37])[CH3:38]
Reactant: COC(=O)c1ccc(C#C[Se]c2cc(OCc3ccc(C(C)(C)C)cc3)c3c(c2)C(C)(C)CCC3(C)C)cc1
Agent: [Na+]
Agent: [OH-]
Product: CC(C)(C)c1ccc(COc2cc([Se]C#Cc3ccc(C(=O)O)cc3)cc3c2C(C)(C)CCC3(C)C)cc1

Procedure:
In a manner similar to that of Example 1g, by reacting 640 mg (1.2 mmol) of methyl 4-[5,5,8,8-tetramethyl-4-(4-tert-butylbenzyloxy)-5,6,7,8-tetrahydro-2-napthylselanylethynyl]benzoate with 240 mg of sodium hydroxide. A yellow crystallized solid is obtained (m=530 mg; yield=92%; m.p.=285° C.).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][N:3]=1.[C:9]1([SH:15])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C[O-].[Na+]>[Cu].CO>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:15][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:4][N:3]=1
Reactant: Sc1ccccc1
Reactant: Nc1ccc(I)cn1
Agent: [Cu]
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: Nc1ccc(Sc2ccccc2)cn1
Yield: 64.3 %

Procedure:
11 G. (0.05 moles) of 2-amino 5-iodo pyridine, 7.2 ml. (0.07 moles) of thiophenol, 3.8 g. (0.07 moles) of sodium methoxide, 1.0 g of copper powder and 100 ml. of methanol are heated 150° C. for 12 hours in a glass lined bomb. The reaction mixture is concentrated to dryness, extracted with chloroform and the chloroform extracts concentrated to dryness in vacuo affording 15 g. of a crude product which is chromatographed on 600 g. of silica gel, eluting with methylene chloride and ethyl acetate-methylene chloride 50% mixture affording 6.5 g of 2-amino 5-phenylthio pyridine, m.p. 127° to 129° C.