Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([CH:8]=[CH:7][CH:6]=[C:4]([OH:5])[CH:3]=1)[OH:2].C=O.[OH-].[Na+].[OH-].[NH4+].[O-2].[Mg+2].C.C1CCN(C(SSSSC(N2CCCCC2)=S)=S)CC1.[CH3:38][O:39]C1(C2C=C(F)C=C(OCC3C=CC4NC(C=CC=4C=3)=O)C=2)CCOCC1>C(N(CCCC)C(=S)[S-])CCC.[Ni+2].C(N(CCCC)C(=S)[S-])CCC.O>[C:1]1([CH:8]=[CH:7][CH:6]=[C:4]([OH:5])[C:3]=1[CH:38]=[O:39])[OH:2]
Reactant: COC1(c2cc(F)cc(OCc3ccc4[nH]c(=O)ccc4c3)c2)CCOCC1
Reactant: Oc1cccc(O)c1
Agent: [Ni+2]
Agent: C=O
Agent: CCCCN(CCCC)C(=S)[S-]
Solvent: O
Product: O=Cc1c(O)cccc1O
Reaction time: 0.5 h

Procedure:
Resorcinol formaldehyde adhesive latexes (RFL) were prepared from the latex by mixing 40 parts of a 4.72% aqueous resorcinol solution, 2.77 parts of a 37% aqueous formaldehyde solution, and 36.5 parts of the 47% solids copolymer latex and 20 parts of 15% aqueous sodium hydroxide (catalyst); adjusted to 20.6% solids with water and brought to a pH of 9.9 by addition of a 28% aqueous ammonium hydroxide solution. Nylon 66 fabric was treated with the RFL and heat activated. The treated fabric was then passed between two slabs of chlorosulfonated polyethylene compounded with 10 phr (parts per hundred parts rubber) magnesium oxide, 20 phr litharge, 40 phr SRF carbon black, 2 phr dipentamethylenethiuram tetrasulfide, 0.25 phr bis-benzothiazonyl sulfide and 3 phr nickel dibutyldithiocarbamate. The rubber slabs were then cured for 30 minutes at 153° C. The force required to pull the rubber and fabric apart, determined according to ASTM D-2138, was 28 pli with 80% rubber tear.
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][CH2:14][C:15]([C:17]1[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][CH2:25][CH:26]2[O:30][C:29](=[O:31])[NH:28][C:27]2=[O:32])=[CH:19][CH:18]=1)=[O:16].C(O)C.[BH4-].[Na+].Cl>O1CCCC1.O>[OH:16][CH:15]([C:17]1[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][CH2:25][CH:26]2[O:30][C:29](=[O:31])[NH:28][C:27]2=[O:32])=[CH:19][CH:18]=1)[CH2:14][CH2:13][C:3]1[N:4]=[C:5]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[O:6][C:2]=1[CH3:1]
Reactant: Cc1oc(-c2ccccc2)nc1CCC(=O)c1ccc(CCCC2OC(=O)NC2=O)cc1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Solvent: CCO
Product: Cc1oc(-c2ccccc2)nc1CCC(O)c1ccc(CCCC2OC(=O)NC2=O)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 63.7 %

Procedure:
To a solution of 5-[3-[4-[3-(5-methyl-2-phenyl-4-oxazolyl)propionyl]phenyl]propyl]-2,4-oxazolidinedione (0.25 g) in tetrahydrofuran (THF) (10 ml)-ethanol (10 ml), sodium borohydride (0.05 g) was added, followed by stirring at room temperature for 2 hours. The reaction mixture was poured over water, neutralized with 2N HCl and then extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried (MgSO4) and then concentrated under reduced pressure; the residue was purified by silica gel column chromatography. From the fraction eluted with ethyl acetate-chloroform (1:1), 5-[3-[4 -[1-hydroxy-3-(5-methyl-2-phenyl-4oxazoly) propyl]phenyl]propyl]-2,4-oxazolidinedione (0.16 g, 64%) was obtained, which was then recrystallized from acetone-isopropyl ether to yield colorless needles having a melting point of 150°-151° C.
Reaction SMILES: [C:1]1(B(O)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.Cl.[CH3:18][O:19][C:20](=[O:29])[C@@H:21]([NH2:28])[CH2:22][O:23][C:24]([CH3:27])([CH3:26])[CH3:25]>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH3:18][O:19][C:20](=[O:29])[C@@H:21]([NH:28][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[CH2:22][O:23][C:24]([CH3:25])([CH3:27])[CH3:26]
Reactant: COC(=O)[C@@H](N)COC(C)(C)C
Reactant: OB(O)c1ccccc1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)[C@H](COC(C)(C)C)Nc1ccccc1
Temperature: 25 °C
Reaction time: 120 h
Yield: 33.4 %

Procedure:
To a suspension of phenylboronic acid (1.46 g) and 4A molecular sieves (4.5 g) in dichloromethane (40 mL) were added triethylamine (1.66 mL), methyl-(2S)-2-amino-3-tert-butoxypropanoate hydrochloride (1.26 g) and copper (II) acetate (1.19 g), then the mixture was stirred at ambient temperature for 5 days. The reaction was quenched with 7N ammonia in methanol (15 mL) and the mixture was filtered through a bed of celite. The filtrate was concentrated in vacuo and the residue was purified by silica gel column chromatography (eluent; n-hexane/ethyl acetate (2:1)) to afford methyl-(2S)-2-phenylamino-3-tert-butoxypropanoate (500 mg) as a colorless syrup.
Reaction SMILES: [NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:5]=[C:4]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:3]=1.[C:18]1([S:24](Cl)(=[O:26])=[O:25])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.Cl>CN(C)C1C=CN=CC=1.N1C=CC=CC=1>[C:7]1([N:6]2[C:2]([NH:1][S:24]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)(=[O:26])=[O:25])=[CH:3][C:4]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[N:5]2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: CCOC(=O)c1cc(N)n(-c2ccccc2)n1
Reactant: O=S(=O)(Cl)c1ccccc1
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: c1ccncc1
Product: CCOC(=O)c1cc(NS(=O)(=O)c2ccccc2)n(-c2ccccc2)n1
Temperature: 85 °C
Reaction time: 8 h
Yield: 55.6 %

Procedure:
Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate (498 mg) synthesized according to the method described in WO2004/98589 and 4-dimethylaminopyridine (21 mg) were dissolved in pyridine (10 mL), and benzenesulfonyl chloride (461 mg) was added at room temperature. After stirring at 85° C. for 8 hr, 1 mol/L hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The extract was washed with 1 mol/L hydrochloric acid, water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent:hexane-ethyl acetate=1:1→ethyl acetate), and the obtained solid was washed with a mixed solvent of diisopropyl ether and ethyl acetate to give the title compound as a brown powder (yield 445 mg, yield 69%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][CH:11]([C:14](O)=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1>O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[CH2:9][CH2:10][CH:11]([CH2:14][OH:15])[CH2:12][CH2:13]2)=[CH:6][CH:7]=1
Reactant: O=C(O)C1CCC(c2ccc(Cl)cc2)CC1
Solvent: O
Product: OCC1CCC(c2ccc(Cl)cc2)CC1
Yield: 62.3 %

Procedure:
4-(4-Chlorophenyl)cyclohexane carboxylic acid (0.35 g, 1.5 mmol) was reacted via Method E over 72 hours. The solid was poured into a water (40 mL) solution and extracted with ethyl acetate (EtOAc) (4×10 mL). The combined organic layers were washed with brine (40 mL) and dried over anhydrous Na2SO4. The organic layer was concentrated in vacuo to obtain [4-(4-chlorophenyl)cyclohexyl]methanol (0.210 g, 64% yield).
Reaction SMILES: C[O:2][C:3](=[O:17])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([N:10]2[CH2:14][CH2:13][CH2:12][C:11]2=[O:15])[C:5]=1[F:16].[Li+].[OH-]>>[F:16][C:5]1[C:6]([N:10]2[CH2:14][CH2:13][CH2:12][C:11]2=[O:15])=[CH:7][CH:8]=[CH:9][C:4]=1[C:3]([OH:17])=[O:2]
Reactant: COC(=O)c1cccc(N2CCCC2=O)c1F
Agent: [Li+]
Agent: [OH-]
Product: O=C(O)c1cccc(N2CCCC2=O)c1F

Procedure:
2-Fluoro-3-(2-oxopyrrolidin-1-yl)benzoic acid methyl ester (D26) (137 mg, 0.58 mmol) was treated with 1M LiOH as described in D25 to afford D27 (85 mg, 66%).
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]([C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=2[O:17][CH3:18])=[O:9])=[CH:6][N:5]=[C:4]([NH:19][CH:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)[N:3]=1.[Cl:26][CH2:27][CH2:28][CH2:29][S:30](Cl)(=[O:32])=[O:31]>>[NH2:1][C:2]1[C:7]([C:8]([C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=2[O:17][CH3:18])=[O:9])=[CH:6][N:5]=[C:4]([NH:19][CH:20]2[CH2:21][CH2:22][N:23]([S:30]([CH2:29][CH2:28][CH2:27][Cl:26])(=[O:32])=[O:31])[CH2:24][CH2:25]2)[N:3]=1
Reactant: COc1ccc(F)cc1C(=O)c1cnc(NC2CCNCC2)nc1N
Reactant: O=S(=O)(Cl)CCCCl
Product: COc1ccc(F)cc1C(=O)c1cnc(NC2CCN(S(=O)(=O)CCCCl)CC2)nc1N

Procedure:
The compound was prepared from [4-amino-2-(piperidin-4-ylamino)-pyrimidin-5-yl]-(5-fluoro-2-methoxy-phenyl)-methanone (Example 59) and chloropropanesulfonyl chloride (Aldrich) in an analogous manner as described in Example 177. HR-MS (ES, m/z) calculated for C20H26N5O4SFCI [(M+H)+] 486.1373, observed 486.1375.
Reaction SMILES: ClC1C=NC=C(Cl)C=1CO.[Cl:11][C:12]1[C:13]([CH2:21][O:22][C:23]2[CH:24]=[CH:25][CH:26]=[C:27]3[C:32]=2[N:31]=[C:30]([CH3:33])[CH:29]=[C:28]3[C:34]2[N:35]([CH3:39])[N:36]=[CH:37][CH:38]=2)=[C:14]([C:18](=[O:20])[CH3:19])[CH:15]=[N:16][CH:17]=1>>[Cl:11][C:12]1[C:13]([CH2:21][O:22][C:23]2[CH:24]=[CH:25][CH:26]=[C:27]3[C:32]=2[N:31]=[C:30]([CH3:33])[CH:29]=[C:28]3[C:34]2[N:35]([CH3:39])[N:36]=[CH:37][CH:38]=2)=[C:14]([CH:18]([OH:20])[CH3:19])[CH:15]=[N:16][CH:17]=1
Reactant: CC(=O)c1cncc(Cl)c1COc1cccc2c(-c3ccnn3C)cc(C)nc12
Agent: OCc1c(Cl)cncc1Cl
Product: Cc1cc(-c2ccnn2C)c2cccc(OCc3c(Cl)cncc3C(C)O)c2n1

Procedure:
Reduction of the ketone in 1-{5-chloro-4-[2-methyl-4-(2-methyl-2H-pyrazol-3-yl)-quinolin-8-yloxymethyl]-pyridin-3-yl}-ethanone according to the synthesis of (3,5-dichloro-pyridin-4-yl)-methanol yielded the title compound. MS (m/z): 409.0 [M+H+].
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:13]3[C:14]([CH3:28])=[C:15]([NH:20][C:21](=[O:27])[CH2:22][C:23]([CH3:26])([CH3:25])[CH3:24])[C:16]([CH3:19])=[C:17]([CH3:18])[C:12]=3[O:11][CH2:10]2)=[CH:5][CH:4]=1)=[O:2].[CH3:29][Mg]Br>>[OH:2][CH:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:13]3[C:14]([CH3:28])=[C:15]([NH:20][C:21](=[O:27])[CH2:22][C:23]([CH3:24])([CH3:25])[CH3:26])[C:16]([CH3:19])=[C:17]([CH3:18])[C:12]=3[O:11][CH2:10]2)=[CH:5][CH:4]=1)[CH3:29]
Reactant: C[Mg]Br
Reactant: Cc1c(C)c2c(c(C)c1NC(=O)CC(C)(C)C)C(c1ccc(C=O)cc1)CO2
Product: Cc1c(C)c2c(c(C)c1NC(=O)CC(C)(C)C)C(c1ccc(C(C)O)cc1)CO2
Yield: 93 %

Procedure:
Using N-(3-(4-formylphenyl)-4,6,7-trimethyl-2,3-dihydro-1-benzofuran-5-yl)-3,3-dimethylbutanamide obtained in Example 174 and methylmagnesium bromide, the title compound was synthesized in the same manner as Example 22.
Reaction SMILES: [C:1]([N:4]1[CH2:9][CH2:8][CH:7]([N:10]2[C:23](=[O:24])[C@H:22]([NH:25]C(=O)OCC3C=CC=CC=3)[CH2:21][C:20]3[CH:19]=[CH:18][C:17]4[NH:16][N:15]=[CH:14][C:13]=4[C:12]=3[CH2:11]2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].C1(OC)C=CC=CC=1.[CH3:44][S:45]([OH:48])(=[O:47])=[O:46]>ClCCl.C(OCC)C>[CH3:44][S:45]([OH:48])(=[O:47])=[O:46].[C:1]([N:4]1[CH2:9][CH2:8][CH:7]([N:10]2[C:23](=[O:24])[C@H:22]([NH2:25])[CH2:21][C:20]3[CH:19]=[CH:18][C:17]4[NH:16][N:15]=[CH:14][C:13]=4[C:12]=3[CH2:11]2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]
Reactant: CC(=O)N1CCC(N2Cc3c(ccc4[nH]ncc34)C[C@@H](NC(=O)OCc3ccccc3)C2=O)CC1
Agent: CS(=O)(=O)O
Solvent: COc1ccccc1
Solvent: ClCCl
Solvent: CCOCC
Product: CC(=O)N1CCC(N2Cc3c(ccc4[nH]ncc34)C[C@@H](N)C2=O)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
(R)-benzyl 9-(1-acetylpiperidin-4-yl)-8-oxo-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-ylcarbamate (38 mg, 0.08 mmol) was dissolved in dichloromethane (1 mL). Anisole (30 μL, 0.27 mmol) was added to the mixture followed by methanesulfonic acid (250 μL). Reaction stirred at room temperature for 2 hours. Mixture was diluted with diethyl ether. Mixture sat at room temperature for 30 minutes. Solvents were decanted off. Remaining residue was dried in vacuo. Title compound was obtained as dark oil in quantitative yield. MS m/e (M+H)+=342.
Reaction SMILES: [OH-].[Na+].Cl[C:4]1[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][C:5]=1[CH:6]=[O:7].[F:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[SH:20]>O>[F:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[S:20][C:4]1[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][C:5]=1[CH:6]=[O:7]
Reactant: Fc1ccccc1S
Reactant: O=Cc1cc(Cl)ccc1Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=Cc1cc(Cl)ccc1Sc1ccccc1F

Procedure:
solution of 3.4 g sodium hydroxide in 6 ml of water and then 14 g of 2,5-dichlorobenzaldehyde (H. Erdmann, Justus Liebigs Ann. Chem. 272, 155, 1893) are added to a solution of 10.8 g 2-fluorothiophenol (reference above) in 20 ml of hexamethylphosphortriamide. Then, the mixture is heated for 5.5 hours to 100° C. After cooling it is diluted with 150 ml of water and extracted with benzene. The extract is washed with a 5% sodium hydroxide solution and with water, dried with magnesium sulfate and evaporated. Crude 2-(2-fluorophenylthio) 5-chlorobenzaldehyde is obtained which is then recrystallized from 20 ml ethanol; 16.0 g, m.p. 85.5°-88° C. A further crystallization affords an analytically pure product, m.p. 87°-88° C.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:12]=[CH:13][CH:14]=1)[C:5]([O:7][CH2:8][CH2:9][CH2:10][Cl:11])=[O:6].[Si:15](Cl)([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16].N1C=CN=C1>CN(C=O)C.O>[Si:15]([O:1][C:2]1[CH:3]=[C:4]([CH:12]=[CH:13][CH:14]=1)[C:5]([O:7][CH2:8][CH2:9][CH2:10][Cl:11])=[O:6])([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16]
Reactant: O=C(OCCCCl)c1cccc(O)c1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)Oc1cccc(C(=O)OCCCCl)c1
Reaction time: 1 h
Yield: 92 %

Procedure:
##STR39## To a solution of 3-chloropropyl 3-hydroxybenzoate (12.0 g, 0.055 mol) and tert-butyldimethylsilyl chloride (TBDMS-Cl, 10.00 g, 0.067 mol) in anhydrous DMF (10 mL) was added imidazole (7.61 g, 0.11 mol). The reaction mixture was stirred for 1 hour after which it was diluted with water (50 mL) and extracted with hexane (4×20 mL). The hexane layer was washed with water (2×10 mL) and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give the desired compound (16.64 g, 0.0506 mol, 90%): 1H NMR (CDCl3) δ 0.216 (s, 6H), 0.994 (s, 9H), 2.19-2.27 (m, 2H), 3.69 (t, 2H, J=6.3 Hz), 4.46 (t, 2H, J=6.3 Hz), 7.01-7.64 (m, 4H); MS exact mass; calcd. 328.1264, found 328.1257.
Reaction SMILES: [N-:1]=[N+:2]=[N-:3].[Na+].[Br:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:12]Br)[N:7]=1>CS(C)=O.O>[N:1]([CH2:12][C:8]1[CH:9]=[CH:10][CH:11]=[C:6]([Br:5])[N:7]=1)=[N+:2]=[N-:3]
Reactant: [N-]=[N+]=[N-]
Reactant: BrCc1cccc(Br)n1
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: [N-]=[N+]=NCc1cccc(Br)n1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
Sodium azide (3.11 g, 47.8 mmol) and 2-bromo-6-(bromomethyl)pyridine (4.00 g, 15.94 mmol) were combined in DMSO (30 mL) and stirred at room temperature for 4 h. The mixture was subsequently diluted with water and extracted with diethyl ether (2×). The combined organic extracts were washed with brine, dried (MgSO4), and evaporated. The residue was purified by flash chromatography (0-10% EtOAc/hexanes) to yield the title compound as a colorless oil. LRMS (APCI) calc'd for C6H6BrN4 [M+H]+: 213, Found: 213.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:29])[C@@H:5]([NH:13][C:14](=[O:28])[C:15]1[CH:20]=[CH:19][C:18]([N:21]2[CH2:26][CH2:25][C:24](=O)[CH2:23][CH2:22]2)=[CH:17][CH:16]=1)[CH2:6][CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH3:2].[NH2:30][CH2:31][C@@H:32]([C:34]1[CH:35]=[CH:36][C:37]([OH:45])=[C:38]([NH:40][S:41]([CH3:44])(=[O:43])=[O:42])[CH:39]=1)[OH:33]>>[OH:33][C@H:32]([C:34]1[CH:35]=[CH:36][C:37]([OH:45])=[C:38]([NH:40][S:41]([CH3:44])(=[O:43])=[O:42])[CH:39]=1)[CH2:31][NH:30][CH:24]1[CH2:25][CH2:26][N:21]([C:18]2[CH:19]=[CH:20][C:15]([C:14]([NH:13][C@@H:5]([CH2:6][CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[C:4]([O:3][CH2:1][CH3:2])=[O:29])=[O:28])=[CH:16][CH:17]=2)[CH2:22][CH2:23]1
Reactant: CS(=O)(=O)Nc1cc([C@@H](O)CN)ccc1O
Reactant: CCOC(=O)CC[C@H](NC(=O)c1ccc(N2CCC(=O)CC2)cc1)C(=O)OCC
Product: CCOC(=O)CC[C@H](NC(=O)c1ccc(N2CCC(NC[C@H](O)c3ccc(O)c(NS(C)(=O)=O)c3)CC2)cc1)C(=O)OCC

Procedure:
The title compound was prepared from (2S)-2-[4-(4-oxo-piperidine-1-yl)-benzoylamino]-pentanedioic acid diethyl ester (which was obtained in Example 157) and N-[5-((1R)-2-amino-1-hydroxy-ethyl)-2-hydroxy-phenyl]-methanesulfonamide (which was obtained in Example 10) according to the procedure of Example 180 as a white solid; mp >75° C. (decomposed); 1H NMR (300 MHz, DMSO-d6) δ 1.18 (t, J=7.1 Hz, 3H), 1.19 (t, J=7.1 Hz, 3H), 1.20-1.45 (m, 2H), 1.80-2.10 (m, 4H), 2.41 (t, J=7.4 Hz, 2H), 2.50-2.95 (m, 5H), 2.93 (s, 3H), 3.75-3.85 (m, 2H), 4.05 (q, J=7.1 Hz, 2H), 4.10 (q, J=7.1 Hz, 2H), 4.35-4.45 (m, 1H), 4.45-4.55 (m, 1H), 6.82 (d, J=8.3 Hz, 1H), 6.94 (d, J=8.9 Hz, 2H), 7.01 (dd, J=8.3, 2.0 Hz, 1H), 7.18 (d, J=2.0 Hz, 1H), 7.74 (d, J=8.9 Hz, 2H), 8.38 (d, J=7.5 Hz, 1H); MS (ES) m/z: 635.1 (MH+); HRMS Calcd. for C30H43N4O9S(MH+): 635.2745. Found: 635.2735.
Reaction SMILES: Cl.Cl.[NH2:3][CH2:4][C:5]([C:7]1[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=1)=[O:6].[F:13][C:14]1[CH:22]=[CH:21][C:17]([C:18](Cl)=[O:19])=[CH:16][CH:15]=1.C(=O)([O-])O.[Na+].O1CCCC1>C(OCC)(=O)C.O>[F:13][C:14]1[CH:22]=[CH:21][C:17]([C:18]([NH:3][CH2:4][C:5]([C:7]2[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=2)=[O:6])=[O:19])=[CH:16][CH:15]=1
Reactant: O=C(Cl)c1ccc(F)cc1
Reactant: NCC(=O)c1cccnc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Solvent: CCOC(C)=O
Product: O=C(CNC(=O)c1ccc(F)cc1)c1cccnc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 66.2 %

Procedure:
A mixture of 3-(2-aminoacetyl)pyridine dihydrochloride (50.00 g), 4-fluorobenzoylchloride (41.71 g) and sodium hydrogen carbonate (100.44 g) in ethyl acetate (1 liter) and water (0.6 liter) was stirred at room temperature for 2 hours. To the reaction mixture were added tetrahydrofuran (0.5 liter) and water (1 liter), and the organic layer was collected. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The resulting residue was triturated with ethyl acetate to obtain 3-[2-(4-fluorobenzoyl)aminoacetyl]pyridine (40.87 g) as pale yellowish powder.
Reaction SMILES: [CH3:1][C:2]1([CH3:22])[CH:6]([C:7]2[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][CH:8]=2)[C:5]2[C:14]([CH3:21])=[C:15]([NH2:20])[C:16]([CH3:19])=[C:17]([CH3:18])[C:4]=2[O:3]1.[CH3:23][O:24][C:25]1[CH:26]=[C:27]2[C:32](=O)[O:31][C:29](=[O:30])[C:28]2=[CH:34][C:35]=1[O:36][CH3:37].C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.[OH-].[Na+]>O1CCCC1.O>[CH3:37][O:36][C:35]1[CH:34]=[C:28]2[C:27](=[CH:26][C:25]=1[O:24][CH3:23])[C:32](=[O:31])[N:20]([C:15]1[C:16]([CH3:19])=[C:17]([CH3:18])[C:4]3[O:3][C:2]([CH3:22])([CH3:1])[CH:6]([C:7]4[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][CH:12]=4)[C:5]=3[C:14]=1[CH3:21])[C:29]2=[O:30]
Reactant: COc1cc2c(cc1OC)C(=O)OC2=O
Reactant: Cc1ccc(C2c3c(C)c(N)c(C)c(C)c3OC2(C)C)cc1
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: COc1cc2c(cc1OC)C(=O)N(c1c(C)c(C)c3c(c1C)C(c1ccc(C)cc1)C(C)(C)O3)C2=O
Temperature: 25 °C
Yield: 85.2 %

Procedure:
To a solution of (+)-2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-amine (6.00 g, 20.3 mmol) in tetrahydrofuran (50 ml) was added under an argon atmosphere 4,5-dimethoxyphthalic anhydride (4.43 g, 21.3 mmol) and the mixture was refluxed with heating for 3 hours. The reaction mixture was cooled down to room temperature and then 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (WSC) hydrochloride (4.67 g, 24.4 mmol) and 1-hydroxy-1H-benzotriazole (HOBT) monohydrate (3.74 g, 24.4 mmol) were added to the mixture. The resulting mixture was refluxed with heating for 14 hours and then cooled down to room temperature. Water and an 8 N aqueous solution of sodium hydroxide were added into the reaction mixture and the product was extracted twice with ethyl acetate. The combined extracts were washed with an aqueous saturated solution of sodium hydrogen carbonate, dried on magnesium sulfate, filtered, and then concentrated under reduced pressure to obtain 8.40 g of (+)-5,6-dimethoxy-2-[2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-yl]-1H-isoindole-1,3(2H)-dione as a crude product. To a solution of aluminum chloride (13.6 g, 102 mmol) in tetrahydrofuran (60 ml) was added lithium aluminum hydride (3.87 g, 102 mmol) and the resulting mixture was stirred for 10 minutes. To this mixture was added a solution of the above-described crude product in tetrahydrofuran (30 ml) and the resulting mixture was refluxed with heating for 3 hours. The reaction mixture was cooled down to room temperature and water was added into the mixture. The product was extracted twice with ethyl acetate. The combined extracts were washed with a 1 N aqueous solution of sodium hydroxide, dried on magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography (hexane-ethyl acetate 8:1) on silica gel to obtain 6.23 g (68% yield) of the title compound. Melting point: 157-159° C. [α]D=+62.3° (c=0.488, methanol).
Reaction SMILES: [OH:1][C:2]1[C:10]([CH3:11])=[C:9]([CH3:12])[CH:8]=[C:7]([CH3:13])[C:3]=1[C:4]([OH:6])=[O:5].[C:14]1(O)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.P(Cl)(Cl)(Cl)=O.Cl>O.C1(C)C=CC=CC=1>[C:14]1([O:5][C:4](=[O:6])[C:3]2[C:7]([CH3:13])=[CH:8][C:9]([CH3:12])=[C:10]([CH3:11])[C:2]=2[OH:1])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: Cc1cc(C)c(C(=O)O)c(O)c1C
Reactant: Oc1ccccc1
Agent: Cl
Solvent: O
Solvent: O=P(Cl)(Cl)Cl
Solvent: Cc1ccccc1
Product: Cc1cc(C)c(C(=O)Oc2ccccc2)c(O)c1C
Temperature: 100 °C
Yield: 49.4 %

Procedure:
In a 500 ml three-necked flask fitted with a mechanical stirrer, a reflux condenser connected to a water pump to absorb the gaseous hydrochloric acid formed during the reaction, and a dropping funnel, were placed 200 ml of dry toluene and 54 g (0.3 mole) of 2-hydroxy-3,4,6-trimethylbenzoic acid prepared in step (1), and 56.4 g (0.6 mole) of phenol were added. The mixture was heated at 100° C. until the reagents were completely dissolved. 27 ml of phosphorus oxychloride were then added dropwise over 30 minutes, and the mixture was refluxed (110° C.) for 8 hours. A substantial evolution of gaseous hydrochloric acid took place. The mixture was cooled to 80° C. and 150 ml of water were added. The aqueous layer was decanted, and the organic layer was washed a second time with an aqueous solution of sodium bicarbonate. The aqueous layer was decanted and the toluene solution was dried with anhydrous magnesium sulfate. The solution was filtered, and the toluene solvent was distilled off. The residue was dissolved in 90 ml of boiling isopropanol and the desired product crystallized upon cooling. 38 g of a white product were obtained (M.P.=74° C.).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]2[CH:11]=[N:12][CH:13]=[N:14][CH:15]=2)=[CH:5][CH:4]=1)#[N:2].CS(O[CH:21]([C:23]1[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[CH:25][CH:24]=1)[CH3:22])(=O)=O>>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]([C:10]2[CH:15]=[N:14][CH:13]=[N:12][CH:11]=2)[C:21]([C:23]2[CH:24]=[CH:25][C:26]([N+:29]([O-:31])=[O:30])=[CH:27][CH:28]=2)=[CH2:22])=[CH:5][CH:4]=1)#[N:2]
Reactant: N#Cc1ccc(Nc2cncnc2)cc1
Reactant: CC(OS(C)(=O)=O)c1ccc([N+](=O)[O-])cc1
Product: C=C(c1ccc([N+](=O)[O-])cc1)N(c1ccc(C#N)cc1)c1cncnc1

Procedure:
Starting compounds: 5-[N-(4-cyanophenyl)amino]pyrimidine and 1-(4-nitrophenyl)ethyl methanesulfonate
Reaction SMILES: Cl.Cl.[N:3]12[CH2:10][CH2:9][CH:6]([CH2:7][CH2:8]1)[C@@H:5]([NH2:11])[CH2:4]2.[CH3:12]/[C:13](/[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[CH:14]\[C:15](O)=[O:16]>>[N:3]12[CH2:10][CH2:9][CH:6]([CH2:7][CH2:8]1)[C@@H:5]([NH:11][C:15](=[O:16])/[CH:14]=[C:13](\[CH3:12])/[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH2:4]2
Reactant: C/C(=C\C(=O)O)c1ccccc1
Reactant: N[C@H]1CN2CCC1CC2
Agent: Cl
Product: C/C(=C\C(=O)N[C@H]1CN2CCC1CC2)c1ccccc1

Procedure:
Prepared as a free base by a method analogous to that described in Example 1 from (R)-1-azabicyclo[2.2.2]oct-3-ylamine dihydrochloride and E-3-methyl-3-phenylpropenoic acid, giving a light tan solid; MS (ES+) 271 (MH+).
Reaction SMILES: CCO[C:4]([S-])=[S:5].[K+:7].[NH2:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][C:17]2[N:18]=[C:19]3[CH:24]=[C:23]([CH3:25])[CH:22]=[CH:21][N:20]3[C:26]=2[CH3:27])=[CH:11][C:10]=1[OH:28]>C(O)C>[CH3:27][C:26]1[N:20]2[CH:21]=[CH:22][C:23]([CH3:25])=[CH:24][C:19]2=[N:18][C:17]=1[CH2:16][CH2:15][C:12]1[CH:13]=[CH:14][C:9]2[N:8]=[C:4]([S-:5])[O:28][C:10]=2[CH:11]=1.[K+:7]
Reactant: Cc1ccn2c(C)c(CCc3ccc(N)c(O)c3)nc2c1
Reactant: CCOC(=S)[S-]
Agent: [K+]
Solvent: CCO
Product: Cc1ccn2c(C)c(CCc3ccc4nc([S-])oc4c3)nc2c1
Yield: 64.4 %

Procedure:
A mixture of potassium ethylxanthogenate (6.25 g) and 2-[2-(4-amino-3-hydroxyphenyl)ethyl]-3,7-dimethylimidazo[1,2-a]pyridine (10.0 g) in ethanol (80 ml) was refluxed for 3 hours with stirring. The resulting precipitate was collected by filtration to give potassium 6-[2-(3,7-dimethylimidazo[1,2-a]pyridin-2-yl)ethyl]-2-benzoxazolethiolate (8.28 g).