Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:3]([F:45])=[C:4]([C@@H:8]2[C@:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10][C@H:9]2[C:28]([NH:30][C:31]2[CH:40]=[CH:39][C:34]([C:35]([O:37]C)=[O:36])=[C:33]([C:41]([F:44])([F:43])[F:42])[CH:32]=2)=[O:29])[CH:5]=[CH:6][CH:7]=1.C1COCC1.[OH-].[Na+].Cl>CO>[Cl:21][C:18]1[CH:19]=[CH:20][C:15]([C@@:12]2([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:26])([CH3:25])[CH3:27])[NH:10][C@@H:9]([C:28]([NH:30][C:31]3[CH:40]=[CH:39][C:34]([C:35]([OH:37])=[O:36])=[C:33]([C:41]([F:43])([F:44])[F:42])[CH:32]=3)=[O:29])[C@@H:8]2[C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=2[F:45])=[C:16]([F:22])[CH:17]=1
Reactant: COC(=O)c1ccc(NC(=O)[C@@H]2N[C@@H](CC(C)(C)C)[C@](C#N)(c3ccc(Cl)cc3F)[C@H]2c2cccc(Cl)c2F)cc1C(F)(F)F
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: CC(C)(C)C[C@@H]1N[C@@H](C(=O)Nc2ccc(C(=O)O)c(C(F)(F)F)c2)[C@H](c2cccc(Cl)c2F)[C@@]1(C#N)c1ccc(Cl)cc1F
Temperature: 50 °C
Reaction time: 3 h
Yield: 45.8 %

Procedure:
In a 50 mL round-bottomed flask, methyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-2-(trifluoromethyl)benzoate (290 mg, 434 μmol, Eq: 1.00) was combined with THF (8 ml) and MeOH (8.00 ml) to give a colorless solution. 1.5 M NaOH (3 ml, 4.5 mmol, Eq: 10.4) was added. The reaction mixture was heated to 50° C. and stirred for 3 h. The reaction mixture was acidified with 1N HCl and was extracted with EtOAc (3×15 mL). The organic layers were combined, washed with saturated NaCl (1×10 mL), dried over Na2SO4 and concentrated in vacuum. The crude material was dissolved in DMSO and purified by preparative HPLC (70-100% ACETONITRILE/water). Obtained was a white solid (130 mg, 46% yield). MS (ES+) m/z Calcd: [(M+H)+]: 654. found: 654.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]1[CH:9]=[C:8]([CH:15]([CH3:19])[C:16]([OH:18])=[O:17])[CH:7]=[CH:6][C:5]2=1.[OH-].[Na+].Cl[CH2:23][C:24]1[CH:33]=[CH:32][C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[N:25]=1.Cl>O.CS(C)=O>[CH3:19][CH:15]([C:8]1[CH:7]=[CH:6][C:5]2[C:4]3[C:12](=[CH:13][CH:14]=[C:2]([O:1][CH2:23][C:24]4[CH:33]=[CH:32][C:31]5[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=5)[N:25]=4)[CH:3]=3)[N:11]([CH2:23][C:24]3[CH:33]=[CH:32][C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[N:25]=3)[C:10]=2[CH:9]=1)[C:16]([OH:18])=[O:17]
Reactant: CC(C(=O)O)c1ccc2c(c1)[nH]c1ccc(O)cc12
Reactant: ClCc1ccc2ccccc2n1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CS(C)=O
Product: CC(C(=O)O)c1ccc2c3cc(OCc4ccc5ccccc5n4)ccc3n(Cc3ccc4ccccc4n3)c2c1

Procedure:
A mixture consisting of 6-hydroxy-α-methyl carbazole-2-acetic acid (2.6 g, 0.010 mol), dimethyl sulfoxide (200 mL), sodium hydroxide (2.0 g in 20 mL H2O, 0.05 mol) and 2-chloromethylquinoline.HCl (4.0 g, 0.018 mol) is heated to 80° C. for 3 hours. The reaction mixture is cooled, poured into water (1000 mL), and the pH is adjusted to 4 with 1N HCl. The aqueous solution is extracted with ethyl acetate (4×300 mL) and the organic layers are combined, washed with water (2×300 mL), once with brine (300 mL), dried over MgSO4, filtered and concentrated to give 3.0 g of crude product. The latter is chromatographed on silica gel using 10% methanol/methylene chloride as an eluent to give 8 g of product, m.p. 197°-199° C.
Reaction SMILES: CN(C[N:5]=[CH:6][CH:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1)C.[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22]Br)=[CH:16][CH:15]=1.C1(C)C=CC=CC=1.[ClH:31]>CCOCC.C(N(CC)CC)C>[ClH:13].[ClH:31].[NH2:5][CH2:6][CH:7]1[CH2:8][CH2:9][N:10]([CH2:22][CH2:21][O:20][C:17]2[CH:18]=[CH:19][C:14]([Cl:13])=[CH:15][CH:16]=2)[CH2:11][CH2:12]1
Reactant: CN(C)CN=CC1CCNCC1
Reactant: Clc1ccc(OCCBr)cc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCOCC
Solvent: Cc1ccccc1
Product: NCC1CCN(CCOc2ccc(Cl)cc2)CC1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A mixture of 4-(dimethylaminomethyliminomethyl)piperidine (7.2 g, prepared as in Example 1), 2-bromoethyl 4-chlorophenyl ether (10.0 g), toluene (100 ml) and triethylamine (5.9 ml) was heated on a steam bath for 6 hours. The mixture was evaporated to dryness and the residue was dissolved in a 1:1 mixture of methanol/concentrated aqueous ammonia solution (S.G. 0.880, 80 ml). The mixture was stirred at ambient temperature for 16 hours and then evaporated to dryness. Water (50 ml) was added to the residue and the mixture was extracted with dichloromethane to give an oil. The oil was dissolved in ether and acidified with ethereal hydrogen chloride to give 4-aminomethyl-1-[2-(4-chlorophenoxy)ethyl]piperidine dihydrochloride m.p. 250°-252° C.
Reaction SMILES: [Cl-].[NH4+].[F:3][C:4]1[CH:9]=[C:8]([N+:10]([O-])=O)[CH:7]=[C:6]([F:13])[C:5]=1[N:14]1[CH2:18][CH:17]=[CH:16][CH2:15]1>CCO.O.[Fe]>[N:14]1([C:5]2[C:4]([F:3])=[CH:9][C:8]([NH2:10])=[CH:7][C:6]=2[F:13])[CH2:18][CH:17]=[CH:16][CH2:15]1
Reactant: O=[N+]([O-])c1cc(F)c(N2CC=CC2)c(F)c1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCO
Solvent: O
Product: Nc1cc(F)c(N2CC=CC2)c(F)c1
Yield: 99.2 %

Procedure:
Ammonium chloride (1.18 g, 22.1 mmol) is added to a mixture of 1-(2,6-difluoro-4-nitrophenyl)-2,5-dihydro-1H-pyrrole (Step 1, 0.5 g, 2.21 mmol) dissolved in EtOH/water (2:1, 18.0 mL) and heated to reflux. Iron powder (0.37 g, 6.63 mmol) is added in portions over one hour. After refluxing for another 45 min, the reaction mixture is cooled, filtered, and extracted three times with dichloromethane. The organic layers are washed with saline, dried (MgSO4) and concentrated to provide the title compound (0.43 g, >95%), MS (m/z): [M+H]+=197; 1H NMR (300 MHz, CDCl3): δ 3.63 (bs, 2H), 4.10 (s, 4H), 5.84 (s, 2H), 6.17 (d, 2H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1OS(C(F)(F)F)(=O)=O)=[N:9][C:8]([O:20][CH3:21])=[CH:7][CH:6]=2.[CH2:22]([Sn](CCCC)(CCCC)CCCC)[CH:23]=[CH2:24]>CN(C=O)C>[CH2:24]([C:11]1[C:2]([Cl:1])=[CH:3][N:4]=[C:5]2[C:10]=1[N:9]=[C:8]([O:20][CH3:21])[CH:7]=[CH:6]2)[CH:23]=[CH2:22]
Reactant: C=CC[Sn](CCCC)(CCCC)CCCC
Reactant: COc1ccc2ncc(Cl)c(OS(=O)(=O)C(F)(F)F)c2n1
Solvent: CN(C)C=O
Product: C=CCc1c(Cl)cnc2ccc(OC)nc12
Temperature: 100 °C
Reaction time: 4 h
Yield: 77 %

Procedure:
A flask charged with trifluoromethanesulfonic acid 3-chloro-6-methoxy-[1,5]naphthyridin-4-yl ester (1.50 g; prepared according to WO 2004/058144), allyltributylstannane (1.68 g) and DMF was degassed with N2. The reaction mixture was treated with LiCl (695 mg) and Pd(PPh3)4 (126 mg) and further stirred at 100° C. for 4 h. After cooling, the mixture was poured into 10% aq. NH4OH and EA, the aq. layer was extracted with EA and the combined org. layers were washed with water (2×) and brine, dried over MgSO4 and concentrated. The residue was purified by CC (Hept/EA 4:1), affording a yellow oil (795 mg; 77% yield).
Reaction SMILES: [OH:1][C:2]1[C:3]2[O:16][N:15]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=3)[C:4]=2[C:5](I)=[N:6][C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9].[CH3:25]B(O)O.C(=O)([O-])[O-].[Cs+].[Cs+]>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>[OH:1][C:2]1[C:3]2[O:16][N:15]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=3)[C:4]=2[C:5]([CH3:25])=[N:6][C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9]
Reactant: CB(O)O
Reactant: CCOC(=O)c1nc(I)c2c(-c3ccc(OC)cc3)noc2c1O
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: [Cs+]
Product: CCOC(=O)c1nc(C)c2c(-c3ccc(OC)cc3)noc2c1O
Yield: 16.7 %

Procedure:
Ethyl 7-hydroxy-4-iodo-3-(4-methoxyphenyl)isoxazolo[4,5-c]pyridine-6-carboxylate (280 mg, 0.64 mmol), methylboronic acid (155 mg, 127 mmol), Pd(PPh3)4 (147 mg, 0.13 mmol) and cesium carbonate (622 mg, 1.91 mmol) were added to a flask and the flask evacuated. After refilling with nitrogen, 6.5 mL of 1,2-dimethoxyethane was added and the resulting suspension was refluxed for 16 h. The reaction mixture diluted with EtOAc (40 mL) and the solid was filtered. The solid was added to a mixture of 10% hydrochloric acid and extracted several times with EtOAc. The combined organic layer was dried over MgSO4 and concentrated, and the residue was purified flash chromatography (0-40% EtOAc/hexanes) to afford 35 mg of the title compound. MS: (+) m/z 329.41 (M+1).
Reaction SMILES: C1(O[C:8](=[O:21])[NH:9][C:10]2[C:11]([O:19][CH3:20])=[N:12][C:13]([CH3:18])=[C:14]([CH2:16][CH3:17])[CH:15]=2)C=CC=CC=1.[N+:22]([C:25]1[CH:30]=[CH:29][C:28]([N:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)=[CH:27][CH:26]=1)([O-:24])=[O:23]>>[CH2:16]([C:14]1[CH:15]=[C:10]([NH:9][C:8]([N:34]2[CH2:35][CH2:36][N:31]([C:28]3[CH:27]=[CH:26][C:25]([N+:22]([O-:24])=[O:23])=[CH:30][CH:29]=3)[CH2:32][CH2:33]2)=[O:21])[C:11]([O:19][CH3:20])=[N:12][C:13]=1[CH3:18])[CH3:17]
Reactant: O=[N+]([O-])c1ccc(N2CCNCC2)cc1
Reactant: CCc1cc(NC(=O)Oc2ccccc2)c(OC)nc1C
Product: CCc1cc(NC(=O)N2CCN(c3ccc([N+](=O)[O-])cc3)CC2)c(OC)nc1C
Yield: 70 %

Procedure:
Phenyl-N-(5-ethyl-2-methoxy-6-methylpyridin-3-yl)carbamate and 1-(4-nitrophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound.
Reaction SMILES: Cl[CH2:2][CH2:3][O:4][C:5]1[C:13]2[C:8](=[N:9][CH:10]=[N:11][C:12]=2[NH:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=3)=[C:17]([CH3:29])[CH:16]=2)[NH:7][N:6]=1.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1>>[CH3:29][C:17]1[CH:16]=[C:15]([NH:14][C:12]2[N:11]=[CH:10][N:9]=[C:8]3[NH:7][N:6]=[C:5]([O:4][CH2:3][CH2:2][N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)[C:13]=23)[CH:20]=[CH:19][C:18]=1[O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1
Reactant: Cc1cc(Nc2ncnc3[nH]nc(OCCCl)c23)ccc1OCc1ccccn1
Reactant: C1COCCN1
Product: Cc1cc(Nc2ncnc3[nH]nc(OCCN4CCOCC4)c23)ccc1OCc1ccccn1
Yield: 41 %

Procedure:
The procedure described in Example 23 was repeated using 3-(2-chloroethoxy)-N-[3-methyl-4-(pyridin-2-ylmethoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine and morpholine to give the title compound in 41% yield; NMR Spectrum: 2.26 (s, 3H), 2.51 (hidden by DMSO, 4H), 2.79 (t, 2H), 3.55 (t, 4H), 4.43 (t, 2H), 5.21 (s, 2H), 7.00 (d, 1H), 7.35 (t, 1H), 7.44 (m, 2H), 7.55 (d, 1H), 7.86 (t, 1H), 8.24 (s, 1H), 8.28 (s, 1H), 8.59 (d, 1H); Mass Spectrum: 462 (MH+).
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N+:14]2=[N:17]O[C:19]([O-])=[C:13]2[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OC(N1CCNC(C(O)=O)C1)=O)C1C=CC=CC=1.[F:40][C:41]([F:45])([F:44])[C:42]#C>CC1C=CC=CC=1C>[F:40][C:41]([F:45])([F:44])[C:42]1[CH:19]=[C:13]2[CH2:12][N:11]([C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[O:10])[CH2:16][CH2:15][N:14]2[N:17]=1
Reactant: O=C(OCc1ccccc1)N1CC[n+]2noc([O-])c2C1
Reactant: C#CC(F)(F)F
Agent: O=C(O)C1CN(C(=O)OCc2ccccc2)CCN1
Solvent: Cc1ccccc1C
Product: O=C(OCc1ccccc1)N1CCn2nc(C(F)(F)F)cc2C1
Temperature: -78 °C
Yield: 61 %

Procedure:
5-[(Benzyloxy)carbonyl]-4,5,6,7-tetrahydro[1,2,3]oxadiazolo[3,4-a]pyrazin-8-ium-3-olate (C58, prepared from 4-[(benzyloxy)carbonyl]piperazine-2-carboxylic acid using the general procedure described by T. S. Mansour et al., 2006, PCT Intl. Appl. WO 2006/130588) (65 g, 0.24 mol) was dissolved in o-xylene (250 mL) and cooled to −78° C. in a bomb reactor. 3,3,3-Trifluoroprop-1-yne (25 g, 0.27 mol) was injected into the reaction mixture, and the bomb was heated to 270° C. for 24 hours. After cooling to room temperature, the reaction was concentrated in vacuo, and the residue was purified by silica gel chromatography to provide C60 as white crystals. Yield: 7.5 g, 23 mmol, 10%. [The major regioisomer, benzyl 2-(trifluoromethyl)-6,7-dihydropyrazolo[1,5-a]pyrazine-5(4H)-carboxylate (C59), was also isolated, in 61% yield.]
Reaction SMILES: [CH3:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][C:7]2[C:8](=[O:14])[NH:9][C:10](=S)[NH:11][CH:12]=2)=[CH:4][CH:3]=1.CC1C=CC(CC2C(=O)NC(SC)=NC=2)=CC=1.N1C=CC=NC1=O.[CH3:41][C:42]1[NH:46][CH:45]=[N:44][C:43]=1[CH2:47][S:48][CH2:49][CH2:50][NH2:51].[ClH:52]>>[ClH:52].[ClH:52].[CH3:41][C:42]1[NH:46][CH:45]=[N:44][C:43]=1[CH2:47][S:48][CH2:49][CH2:50][NH:51][C:10]1[NH:9][C:8](=[O:14])[C:7]([CH2:6][C:5]2[CH:15]=[CH:16][C:2]([CH3:1])=[CH:3][CH:4]=2)=[CH:12][N:11]=1
Reactant: Cc1[nH]cnc1CSCCN
Reactant: Cc1ccc(Cc2c[nH]c(=S)[nH]c2=O)cc1
Agent: CSc1ncc(Cc2ccc(C)cc2)c(=O)[nH]1
Agent: Cl
Agent: O=c1nccc[nH]1
Product: Cc1ccc(Cc2cnc(NCCSCc3nc[nH]c3C)[nH]c2=O)cc1

Procedure:
5-(4-Methylbenzyl)-2-thiouracil (4.65 g) was converted into 5-(4-methylbenzyl)-2-methylthio-4-pyrimidone (m.p. 208.5°-211° ex methanol/ethanol) by the method described in Example 1(i). Reaction of this pyrimidone (1.6 g) with 2-(5-methyl-4-imidazolylmethylthio)ethylamine (1.2 g) by the method described in Example 1(ii) and acidification with dilute ethanolic hydrogen chloride followed by evaporation to dryness and recrystallisation from ethanol gave 2-[2-(5-methyl-4-imidazolylmethylthio)ethylamino]-5-(4-methylbenzyl)-4-pyrimidone dihydrochloride, m.p. 197°-198.5°.
Reaction SMILES: [C:1]1([C:7]2[N:8]=[C:9]([CH2:18][NH:19][CH:20]3[C:28]4[C:23](=[C:24]([O:29][CH3:30])[CH:25]=[CH:26][CH:27]=4)[CH2:22][CH2:21]3)[O:10][C:11]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CI.[C:33]([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH3:33][N:19]([CH:20]1[C:28]2[C:23](=[C:24]([O:29][CH3:30])[CH:25]=[CH:26][CH:27]=2)[CH2:22][CH2:21]1)[CH2:18][C:9]1[O:10][C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[N:8]=1
Reactant: COc1cccc2c1CCC2NCc1nc(-c2ccccc2)c(-c2ccccc2)o1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CN(C)C=O
Product: COc1cccc2c1CCC2N(C)Cc1nc(-c2ccccc2)c(-c2ccccc2)o1
Reaction time: 16 h
Yield: 69.8 %

Procedure:
To a solution of 1-(4,5-diphenyloxazol-2-yl)methylamino-2,3-dihydro-4-methoxy-1H-indene (0.18 g) and methyl iodide (85 mg) in DMF (3 ml) was added K2CO3 (0.12 g). After being stirred for 16 hours, the solution was extracted with ethyl acetate. The mixture was washed with brine, dried over MgSO4 and evaporated in vacuo. The residue was purified by chromatography on silica gel to afford 1-[N-methyl-N-[(4,5-diphenyloxazol-2-yl)methyl]amino]-2,3-dihydro-4-methoxy-1H-indene (0.13 g). MS (m/z): (M+ +1) NMR (CDCl3, δ): 2.02-2.28 (1H, m), 2.44 (3H, s), 2.64-3.17 (3H, m), 3.82 (5H, s), 4.60 (1H, br), 6.73 (1H, d, J=7.9 Hz), 7.08-7.32 (2H, m), 7.32-7.48 (6H, m), 7.58-7.72 (4H, m)
Reaction SMILES: [OH-:1].[K+].[CH2:3]([O:10][C:11]1[CH:12]=[C:13]([C:17]2[N:22]=[CH:21][C:20](Br)=[CH:19][N:18]=2)[CH:14]=[CH:15][CH:16]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.O.Cl>C(O)CO.[S]>[CH2:3]([O:10][C:11]1[CH:12]=[C:13]([C:17]2[N:22]=[CH:21][C:20]([OH:1])=[CH:19][N:18]=2)[CH:14]=[CH:15][CH:16]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: [OH-]
Reactant: Brc1cnc(-c2cccc(OCc3ccccc3)c2)nc1
Agent: Cl
Agent: [K+]
Agent: [S]
Solvent: O
Solvent: OCCO
Product: Oc1cnc(-c2cccc(OCc3ccccc3)c2)nc1
Reaction time: 3 h
Yield: 80.5 %

Procedure:
A solution of 4.76 g (85.3 mmol) of potassium hydroxide in 20 ml of ethylene glycol is added dropwise over the course of 2 hours at 180° C. to 7.26 g (21.3 mmol) of 2-(3-benzyloxyphenyl)-5-bromopyrimidine and 0.035 g (1.08 mmol) of sulfur in 60 ml of ethylene glycol. The mixture is kept at 180° C. for a further 3 hours, poured into water and acidified by means of 37% strength hydrochloric acid, and the solid which precipitates is isolated by filtration. Purification by chromatography (silica gel/hexane: ethyl acetate=32) gives 4.77 g of 2-(3-benzyloxyphenyl)-5-hydroxypyrimidine. ##STR28##
Reaction SMILES: [CH3:1][C:2]([CH3:5])([O-:4])[CH3:3].[K+].[CH2:7]([C:22]([CH2:40][O:41][CH2:42][CH2:43][O:44][CH2:45][CH2:46][O:47][CH2:48][CH2:49][O:50][CH2:51][CH2:52][O:53][CH3:54])([CH2:38][OH:39])[CH2:23][O:24][CH2:25][CH2:26][O:27][CH2:28][CH2:29][O:30][CH2:31][CH2:32][O:33][CH2:34][CH2:35][O:36][CH3:37])[O:8][CH2:9][CH2:10][O:11][CH2:12][CH2:13][O:14][CH2:15][CH2:16][O:17][CH2:18][CH2:19][O:20][CH3:21].[CH2:55]([O:57]CC)[CH3:56]>C1COCC1.[Cl-].[Na+].O>[CH2:23]([C:22]([CH2:40][O:41][CH2:42][CH2:43][O:44][CH2:45][CH2:46][O:47][CH2:48][CH2:49][O:50][CH2:51][CH2:52][O:53][CH3:54])([CH2:38][O:39][CH2:56][C:55]([O:4][C:2]([CH3:5])([CH3:3])[CH3:1])=[O:57])[CH2:7][O:8][CH2:9][CH2:10][O:11][CH2:12][CH2:13][O:14][CH2:15][CH2:16][O:17][CH2:18][CH2:19][O:20][CH3:21])[O:24][CH2:25][CH2:26][O:27][CH2:28][CH2:29][O:30][CH2:31][CH2:32][O:33][CH2:34][CH2:35][O:36][CH3:37]
Reactant: CC(C)(C)[O-]
Reactant: COCCOCCOCCOCCOCC(CO)(COCCOCCOCCOCCOC)COCCOCCOCCOCCOC
Reactant: CCOCC
Agent: [Cl-]
Agent: [K+]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: COCCOCCOCCOCCOCC(COCCOCCOCCOCCOC)(COCCOCCOCCOCCOC)COCC(=O)OC(C)(C)C
Reaction time: 0.5 h
Yield: 52 %

Procedure:
Potassium tert-butoxide (32 mg, 0.28 mmol) was added to 4 (100 mg, 0.14 mmol) and tert-butyl-2-bromo acetate (105 mg, 0.54 mmol) in dry THF (3 ml). The reaction mixture was shaken for 30 min. Diethyl ether (10 ml and brine (5 ml) were added and the aqueous phase was extracted with ethyl acetate (3×20 ml). The combined organic phases were washed with brine and then dried with sodium sulfate. The volatile material was removed at reduced pressure and the crude product was purified by column chromatography (ethyl acetate/methanol 9:1), which gave 60 mg (52%) of 5. 1H-NMR (CDCl3); 3.91 (s, 2H), 3.66-3.52 (m, 48H), 3.51 (s, 2H), 3.45 (s, 6H), 3.37 (s, 9H), 1.46 (s, 9H).
Reaction SMILES: C([O:4][C@H:5]1[C@@H:38]([O:39][CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C@@H:37]([CH2:47][O:48]CC=C)[O:36][C@@H:7]([O:8][CH2:9][CH:10]([CH2:12][CH2:13][CH2:14][C@H:15]([C@@H:17]2[C@:34]3([CH3:35])[C@H:20]([C@H:21]4[C@H:31]([CH2:32][CH2:33]3)[C@:29]3([CH3:30])[CH:24]([CH2:25][CH2:26][CH2:27][CH2:28]3)[CH2:23][CH2:22]4)[CH2:19][CH2:18]2)[CH3:16])[CH3:11])[C@@H:6]1[O:52][CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)C=C.II.O>O1CCCC1.C(Cl)(Cl)Cl.[Ir]>[CH2:53]([O:52][C@@H:6]1[C@@H:5]([OH:4])[C@@H:38]([O:39][CH2:40][C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=2)[C@@H:37]([CH2:47][OH:48])[O:36][C@H:7]1[O:8][CH2:9][CH:10]([CH2:12][CH2:13][CH2:14][C@H:15]([C@@H:17]1[C@:34]2([CH3:35])[C@H:20]([C@H:21]3[C@H:31]([CH2:32][CH2:33]2)[C@:29]2([CH3:30])[CH:24]([CH2:25][CH2:26][CH2:27][CH2:28]2)[CH2:23][CH2:22]3)[CH2:19][CH2:18]1)[CH3:16])[CH3:11])[C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1
Reactant: C=CCOC[C@H]1O[C@@H](OCC(C)CCC[C@@H](C)[C@H]2CC[C@H]3[C@@H]4CCC5CCCC[C@]5(C)[C@H]4CC[C@]23C)[C@H](OCc2ccccc2)[C@@H](OCC=C)[C@H]1OCc1ccccc1
Agent: [Ir]
Agent: II
Solvent: O
Solvent: ClC(Cl)Cl
Solvent: C1CCOC1
Product: CC(CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CCC4CCCC[C@]4(C)[C@H]3CC[C@]12C)CO[C@@H]1O[C@H](CO)[C@H](OCc2ccccc2)[C@H](O)[C@H]1OCc1ccccc1
Yield: 88.2 %

Procedure:
Iridium complex (1,5-cyclooctadiene bis(methyldiphenylphosphine)iridium hexafluorophosphate, 136 mg, 0.12 mmol) was suspended in tetrahydrofuran (5 mL), and activated by stirring under H2 flow. To this solution Compound 25 (940 mg, 1.16 mmol) dissolved in tetrahydrofuran (5 mL) was added, and the mixture was stirred at room temperature for 1 hour under argon gas flow. Iodine (588 mg), water (30 mL) and tetrahydrofuran (15 mL) were added thereto, and the mixture was further stirred at room temperature for 1.5 hours. The reaction mixture was diluted with chloroform, and washed successively with saturated sodium thiosulfate solution, saturated aqueous sodium hydrogencarbonate, and saturated brine. The chloroform layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (toluene:acetone=6:1) to obtain Compound 26 (748 mg, 88.2%).
Reaction SMILES: [CH3:1][C:2]1[C:3]([CH2:14][S:15][C:16]2[NH:20][C:19]3[CH:21]=[CH:22][CH:23]=[CH:24][C:18]=3[N:17]=2)=[N:4][CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]([F:13])([F:12])[F:11].C(O[O-])(=O)C1C(=CC=CC=1)C([O-])=[O:29].[Mg+2].O>C(O)C>[CH3:1][C:2]1[C:7]([O:8][CH2:9][C:10]([F:12])([F:11])[F:13])=[CH:6][CH:5]=[N:4][C:3]=1[CH2:14][S+:15]([O-:29])[C:16]1[NH:20][C:19]2[CH:21]=[CH:22][CH:23]=[CH:24][C:18]=2[N:17]=1
Reactant: Cc1c(OCC(F)(F)F)ccnc1CSc1nc2ccccc2[nH]1
Reactant: O=C([O-])c1ccccc1C(=O)O[O-]
Agent: [Mg+2]
Solvent: CCO
Solvent: O
Product: Cc1c(OCC(F)(F)F)ccnc1C[S+]([O-])c1nc2ccccc2[nH]1
Reaction time: 4 h
Yield: 165.8 %

Procedure:
1.0 g (2.8 mmol) of 2-([3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]-methyl)thio-1H-benzimidazole was dissolved in 20 Ml of 95% ethanol, and cooled to −20˜−10° C. 1.0 g (1.6 mmol) of 80% MMPP (magnesium monoperoxyphthalate) was added thereto, and the resulting mixture was stirred for 4 hours at the same temperature. Completion of the reaction was confirmed by TLC and HPLC, and 10 Ml of water was added to the reaction mixture, which was then stirred for 1 hour under ice-cooling. The reaction mixture was filtered to separate crystal, and thus separated crystal was washed with ice-cooled isopropanol-water mixture (1:1), and dried under reduced pressure, to give 0.98 g (Yield 95%) of Lansoprazole as white solid.
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][C:8]([NH2:10])=[CH:9][C:4]=2[N:3]=[CH:2]1.[N:11]1[S:15][N:14]=[C:13]2[CH:16]=[C:17]([CH:20]=O)[CH:18]=[CH:19][C:12]=12.C([O:24][C:25](=O)[C:26](=[O:31])[CH2:27][C:28](=[O:30])[CH3:29])C>C(O)C>[C:28]([C:27]1[CH:20]([C:17]2[CH:18]=[CH:19][C:12]3=[N:11][S:15][N:14]=[C:13]3[CH:16]=2)[N:10]([C:8]2[CH:7]=[CH:6][C:5]3[NH:1][CH:2]=[N:3][C:4]=3[CH:9]=2)[C:25](=[O:24])[C:26]=1[OH:31])(=[O:30])[CH3:29]
Reactant: CCOC(=O)C(=O)CC(C)=O
Reactant: O=Cc1ccc2nsnc2c1
Reactant: Nc1ccc2[nH]cnc2c1
Solvent: CCO
Product: CC(=O)C1=C(O)C(=O)N(c2ccc3[nH]cnc3c2)C1c1ccc2nsnc2c1
Temperature: 50 °C
Reaction time: 24 h

Procedure:
1H-Benzoimidazol-5-ylamine (1 mmol) and Benzo[1,2,5]thiadiazole-5-carbaldehyde (1 mmol) were added to ethanol (5 ml). After 30 min 2,4-Dioxo-pentanoic acid ethyl ester (1 mmol) was added. The reaction was heated to 50° C. and stirred for 24 h. After evaporation of the solvent the residue was purified with chromatographic methods.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]([O:12][CH3:13])=[O:11])=[CH:2]1.[N:14]1[CH:19]=[C:18](B(O)O)[CH:17]=[N:16][CH:15]=1.N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.C(N(CC)CC)C>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.C(Cl)Cl>[N:14]1[CH:19]=[C:18]([N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:3]([C:10]([O:12][CH3:13])=[O:11])=[CH:2]2)[CH:17]=[N:16][CH:15]=1
Reactant: OB(O)c1cncnc1
Reactant: COC(=O)c1c[nH]c2ccccc12
Agent: [Cu+2]
Agent: CC(=O)[O-]
Agent: c1cnc2c(c1)ccc1cccnc12
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)c1cn(-c2cncnc2)c2ccccc12
Temperature: 25 °C
Reaction time: 168 h

Procedure:
To a vial containing methyl 1H-indole-3-carboxylate (471 mg, 2.69 mmol), pyrimidin-5-ylboronic acid (1.0 g, 8.07 mmol), copper (II) acetate (635 mg, 3.5 mmol), 4 {acute over (Å)} molecular sieves (4 g) and 1,10-phenanthroline (970 mg, 5.38 mmol) were added DCM (10.7 ml) and triethylamine (0.375 ml, 2.69 mmol). The mixture was stirred at RT for 7 days then filtered through a pad of Celite (washed with MeOH). Evaporation and purification by HPLC (after dilution with DMF and filtration) afforded the title compound as a tan solid.