Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:31]=[CH:30][C:6]([C:7]([NH:9][C:10]2[CH:15]=[C:14]([C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)[CH:13]=[CH:12][C:11]=2[NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:8])=[CH:5][CH:4]=1.[OH:32]O>C(Cl)Cl>[C:25]([O:24][C:23]([NH:22][C:11]1[CH:12]=[CH:13][C:14]([C:16]2[CH:17]=[CH:18][N+:19]([O-:32])=[CH:20][CH:21]=2)=[CH:15][C:10]=1[NH:9][C:7](=[O:8])[C:6]1[CH:30]=[CH:31][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)=[O:29])([CH3:28])([CH3:26])[CH3:27]
Reactant: OO
Reactant: COc1ccc(C(=O)Nc2cc(-c3ccncc3)ccc2NC(=O)OC(C)(C)C)cc1
Solvent: ClCCl
Product: COc1ccc(C(=O)Nc2cc(-c3cc[n+]([O-])cc3)ccc2NC(=O)OC(C)(C)C)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 61.4 %

Procedure:
A solution of compound 461 (0.55 g, 1.31 mmol) and ReO3Me (33 mg, 0.13 mmol) in DCM (10 mL) was stirred 5 min, 35% H2O2 (0.14 mL, 1.53 mmol) was added and the reaction was stirred at room temperature for 2 h. The reaction mixture was quenched with water, and AcOEt was added. The white precipitate was filtered and washed with AcOEt and MeOH (5 mL) to afford the title compound 462 (350 mg, 61%) as a white solid.
Reaction SMILES: CC(C)([O-])C.[K+].[CH:7]1([C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[CH2:18][O:19][Si:20]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21])=[O:11])[CH2:9][CH2:8]1>C(O)(C)C>[CH:7]1([C@@H:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[CH2:18][O:19][Si:20]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:21])[CH3:22])[OH:11])[CH2:8][CH2:9]1
Reactant: CC(C)(C)[Si](C)(C)OCc1ccccc1C(=O)C1CC1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CC(C)O
Product: CC(C)(C)[Si](C)(C)OCc1ccccc1[C@@H](O)C1CC1
Reaction time: 36 h
Yield: 94 %

Procedure:
To a suspension of dichloro[(R)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl][(R)-1,1′-bis(p-methoxyphenyl)-2-isopropylethane-1,2-diamine]ruthenium (II) (111 mg) and potassium-tert-butoxide (44.9 mg) in isopropanol (100 ml) was added (cyclopropyl)[2-(tert-butyldimethylsilyloxymethyl)phenyl]methanone (5.81 g) obtained in Step 2 of Example 58, and the mixture was subjected to medium pressure hydrogenation (5.0 kgf/cm2) at room temperature for 36 hr. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:5) to give the title compound (5.50 g).
Reaction SMILES: [Br:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5]([NH:18][S:19]([C:22]2[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=2)(=[O:21])=[O:20])=[CH:4][CH:3]=1.[OH-].[K+].[CH3:31]I>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.ClC1C=CC=CC=1>[Br:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5]([N:18]([CH3:31])[S:19]([C:22]2[CH:23]=[CH:24][C:25]([CH3:28])=[CH:26][CH:27]=2)(=[O:21])=[O:20])=[CH:4][CH:3]=1
Reactant: CI
Reactant: Cc1ccc(S(=O)(=O)Nc2ccc(Br)c3c2C(=O)c2ccccc2C3=O)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Agent: [K+]
Solvent: Clc1ccccc1
Product: Cc1ccc(S(=O)(=O)N(C)c2ccc(Br)c3c2C(=O)c2ccccc2C3=O)cc1
Temperature: 30 °C
Reaction time: 1 h
Yield: 97.9 %

Procedure:
A mixture of 4-bromo-1-p-toluenesulfonylaminoanthraquinone (purity 98%, 46.5 g), monochlorobenzene (550 g), tetra-n-butyl ammonium bromide (0.3 g) and 96% potassium hydroxide (12.0 g) was stirred for 1 hour at 30° C. and methyl iodide (28.4 g) was added thereto at 30° C. over 2 hours. A mixture was stirred at 30° C. for 30 minutes and 40° C. for 3 hours, successively. Then, the same aftertreatment as in Example 3 was effected to obtain 4-bromo-N-p-toluenesulfonyl-1-methylaminoanthraquinone (46.9 g, purity 92.5%, yield 92.3%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:14]([F:17])([F:16])[F:15])[CH2:13][CH2:12][NH:11][CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.[Br:18][C:19]1[CH:24]=[C:23](F)[CH:22]=[CH:21][C:20]=1[N+:26]([O-:28])=[O:27].C(=O)([O-])[O-].[K+].[K+].O>CN1CCCC1=O>[Br:18][C:19]1[CH:24]=[C:23]([N:11]2[CH2:12][CH2:13][C:9]([C:4]3[CH:3]=[C:2]([Cl:1])[CH:7]=[C:6]([Cl:8])[CH:5]=3)([C:14]([F:17])([F:16])[F:15])[CH2:10]2)[CH:22]=[CH:21][C:20]=1[N+:26]([O-:28])=[O:27]
Reactant: O=[N+]([O-])c1ccc(F)cc1Br
Reactant: FC(F)(F)C1(c2cc(Cl)cc(Cl)c2)CCNC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN1CCCC1=O
Solvent: O
Product: O=[N+]([O-])c1ccc(N2CCC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)cc1Br
Temperature: 100 °C
Reaction time: 3 h
Yield: 70.9 %

Procedure:
To the solution of 3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidine (1.3 g) and 2-bromo-4-fluoro-1-nitrobenzene (1.0 g) in 1-methyl-2-pyrrolidinone was added potassium carbonate (1.3 g), and the mixture was heated with stirring at 100° C. for 3 hours. The mixture was cooled to room temperature and then poured into water, which was extracted twice with ethyl acetate. The organic layer was combined, which was then washed with water and dried over anhydrous magnesium sulfate. After the drying agent was filtered off, the solvent was distilled away under the reduced pressure, and the residue was then purified by silica gel chromatography to yield 1-(3-bromo-4-nitrophenyl)-3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidine (1.56 g). 1H-NMR (CDCl3) δ: 2.53-2.66 (1H, m), 2.89-2.97 (1H, m), 3.51-3.71 (2H, m), 3.83 (1H, d), 4.16 (1H, d), 6.53 (1H, dd), 6.84 (1H, d), 7.27 (2H, br s), 7.42 (1H, t), 8.07 (1H, d).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.[NH:9]1[CH:13]=[N:12][N:11]=[N:10]1.C(=O)([O-])[O-].[K+].[K+].O>CN1CCCC1=O>[N:9]1([C:2]2[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=2)[CH:13]=[N:12][N:11]=[N:10]1
Reactant: Brc1ccc(Br)nc1
Reactant: c1nnn[nH]1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN1CCCC1=O
Solvent: O
Product: Brc1ccc(-n2cnnn2)nc1

Procedure:
In 10 ml of 1-methyl-2-pyrrolidone was dissolved 1.0 g of 2,5-dibromopyridine and the solution was added with 0.5 g of 1,2,3,4-tetrazole, along with 1.75 g of potassium carbonate. The reaction mixture was reacted at 100° C. for 3 hours with stirring. After completion of the reaction, the reaction mixture was added with water and extracted with ethyl acetate. The organic layer thus obtained was dehydrated, filtered and concentrated and the concentrate was subjected to column chromatography to give the title compound. 0.8 g.
Reaction SMILES: [NH:1]([C:3](=[O:20])[C@@H:4]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[NH2:2].[C:21](OCC)(OCC)(OCC)[CH3:22].CC(O)=O>C1(C)C=CC=CC=1>[CH3:21][C:22]1[O:20][C:3]([C@@H:4]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:17])([CH3:16])[CH3:18])[CH2:5][C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)=[N:1][N:2]=1
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)C(=O)NN
Reactant: CCOC(C)(OCC)OCC
Solvent: Cc1ccccc1
Solvent: CC(=O)O
Product: Cc1nnc([C@H](Cc2ccccc2)NC(=O)OC(C)(C)C)o1
Temperature: 80 °C
Reaction time: 2 h

Procedure:
To (S)-tert-butyl (1-hydrazinyl-1-oxo-3-phenylpropan-2-yl)carbamate (120 mg, 0.43 mmol) in PhMe (4.3 mL) was added triethyl orthoacetate (396 μL, 2.15 mmol) and AcOH (443 μL, 7.73 mmol). The resulting solution was stirred at 80° C. for 2 h, then concentrated in vacuo and used in the subsequent step without purification. MS (ESI+) m/z 304.3 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:37]=[CH:36][C:5]2[NH:6][C:7]([C@@H:9]([NH:19][C:20](=[O:35])[C:21]3[CH:26]=[CH:25][C:24]([C:27]([N:29]4[CH2:33][CH2:32][CH2:31][CH2:30]4)=[O:28])=[C:23]([CH3:34])[CH:22]=3)[CH2:10][CH2:11][NH:12][C:13]([NH:15][CH2:16][CH2:17]Cl)=[O:14])=[N:8][C:4]=2[CH:3]=1.CC(C)([O-])C.[K+]>CN(C)C=O>[Cl:1][C:2]1[CH:37]=[CH:36][C:5]2[NH:6][C:7]([C@@H:9]([NH:19][C:20](=[O:35])[C:21]3[CH:26]=[CH:25][C:24]([C:27]([N:29]4[CH2:30][CH2:31][CH2:32][CH2:33]4)=[O:28])=[C:23]([CH3:34])[CH:22]=3)[CH2:10][CH2:11][N:12]3[CH2:17][CH2:16][NH:15][C:13]3=[O:14])=[N:8][C:4]=2[CH:3]=1
Reactant: Cc1cc(C(=O)N[C@@H](CCNC(=O)NCCCl)c2nc3cc(Cl)ccc3[nH]2)ccc1C(=O)N1CCCC1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1cc(C(=O)N[C@@H](CCN2CCNC2=O)c2nc3cc(Cl)ccc3[nH]2)ccc1C(=O)N1CCCC1
Temperature: 40 °C
Reaction time: 5 h
Yield: 61 %

Procedure:
0.1 g (0.257 mmol) of N-{(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-[3-(2-chloroethyl)ureido]propyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide is dissolved in 5 mL of dimethylformamide and, after the addition of 50 mg (0.45 mmol) of potassium tert-butoxide, stirred for 5 hours at 40° C. Then the mixture is poured onto ice water and extracted with dichloromethane. The combined organic extracts are dried over sodium sulfate and concentrated by evaporation. The crude product is triturated with diethyl ether and suction filtered. Yield: 61%; Rf value: 0.70 (silica gel; dichloromethane/ethanol=4:1); C26H29ClN6O3 (509.01); mass spectrum: (M+H)+=509/511 (chlorine isotope) and (M−H)−=507/509 (chlorine isotope).
Reaction SMILES: [F:1][C:2]([F:8])([CH:5]([F:7])[F:6])[CH2:3][OH:4].N1C=CC=CC=1.C(=O)=O.[CH2:18]([O:20][C:21](Cl)=[O:22])[CH3:19]>COC(C)(C)C>[C:21](=[O:22])([O:4][CH2:3][C:2]([F:8])([F:1])[CH:5]([F:7])[F:6])[O:20][CH2:18][CH3:19]
Reactant: OCC(F)(F)C(F)F
Reactant: CCOC(=O)Cl
Agent: O=C=O
Solvent: COC(C)(C)C
Solvent: c1ccncc1
Product: CCOC(=O)OCC(F)(F)C(F)F
Temperature: 25 °C

Procedure:
2,2,3,3-tetrafluoropropan-1-ol (121 g 0.92 mol), pyridine (76 g 0.96 mol) and 350 mL of methyl-t-butyl ether were combined in a 1 L 3-neck round bottom flask. The flask was equipped with an overhead stirring mechanism, thermocouple, addition funnel, cold water condenser, and a dry nitrogen bubbler. The reaction flask was kept cool using solid CO2 in a water bath. Ethylchloroformate (100 g, 0.92 mol) was added via an addition funnel dropwise at a rate such that the temperature of the reaction mix did not exceed 0° C. Once the addition was complete the mix was allowed to warm to room temperature on its own. The reaction mix was then quenched with 100 mL of water. The water portion was extracted with 2×100 mL portions of methyl t-butyl ether. The combined organic extracts were washed with 100 mL of 1N HCl and 100 mL of water. The solvent was removed by rotary evaporation and the carbonate was purified by fractional distillation using a concentric tube column. The structure of the product was confirmed by GC/MS and the purity by GC-FID was 99.05% of the desired compound.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH2:9][CH2:10][CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][CH:16]([C:19]3[CH:20]=[C:21]([NH:25][C:26](=[O:30])[CH:27]([CH3:29])[CH3:28])[CH:22]=[CH:23][CH:24]=3)[CH2:15][CH2:14]2)=[CH:4][CH:3]=1.Cl.[CH3:33][O:34][C:35]1[CH:40]=[CH:39][C:38]([NH:41]N)=[CH:37][CH:36]=1>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[NH:41][C:38]3[C:39]([C:9]=2[CH2:10][CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][CH:16]([C:19]4[CH:20]=[C:21]([NH:25][C:26](=[O:30])[CH:27]([CH3:28])[CH3:29])[CH:22]=[CH:23][CH:24]=4)[CH2:15][CH2:14]2)=[CH:40][C:35]([O:34][CH3:33])=[CH:36][CH:37]=3)=[CH:6][CH:7]=1
Reactant: CC(C)C(=O)Nc1cccc(C2CCN(CCCCC(=O)c3ccc(Br)cc3)CC2)c1
Reactant: COc1ccc(NN)cc1
Agent: Cl
Product: COc1ccc2[nH]c(-c3ccc(Br)cc3)c(CCCN3CCC(c4cccc(NC(=O)C(C)C)c4)CC3)c2c1

Procedure:
Prepared by Procedure E and Scheme M using N-(3-{1-[5-(4-bromophenyl)-5-oxopentyl]-4-piperidinyl}phenyl)-2-methylpropanamide and 4-methoxyphenylhydrazine hydrochloride: ESMS m/e: 588.1 (M+H)+.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6](=[S:8])[NH2:7].Br[CH2:10][C:11](=O)[C:12]([O:14][CH2:15][CH3:16])=[O:13]>C(O)C>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[S:8][CH:10]=[C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[N:7]=1
Reactant: CCOC(=O)C(=O)CBr
Reactant: NC(=S)c1ccco1
Solvent: CCO
Product: CCOC(=O)c1csc(-c2ccco2)n1

Procedure:
To a solution of 2-furan-thiocarboxamide (1.63 g) dissolved in dry ethanol (65 ml) with heating was added ethyl bromopyruvate (1.97 ml) and the mixture was refluxed for 30 minutes. Then the solvent was removed from the reaction mixture, and the residue was treated with water, neutralized with 4% aqueous sodium carbonate and extracted three times with ethyl acetate. The organic layer was washed with saturated aqueous NaCl, dried (anhydrous Na2SO4) and concentrated to give yellowish crystals of ethyl 2-(2-furyl)-4-thiazolecarboxylate (3.12 g).
Reaction SMILES: [CH:1]1[C:6](/[CH:7]=[CH:8]/[C:9]([OH:11])=[O:10])=[CH:5][CH:4]=[N:3][CH:2]=1.N>O.[Rh]>[NH:3]1[CH2:4][CH2:5][CH:6]([CH2:7][CH2:8][C:9]([OH:11])=[O:10])[CH2:1][CH2:2]1
Reactant: O=C(O)/C=C/c1ccncc1
Agent: [Rh]
Agent: N
Solvent: O
Product: O=C(O)CCC1CCNCC1
Temperature: 30 °C
Reaction time: 8 h
Yield: 100.7 %

Procedure:
3-(4-pyridine)acrylic acid (18 kg) was added to 75 kg of water. The resulting suspension was stirred and neutralized (pH 7.5) with 6.8 kg of aqueous ammonia (25%). A slurry of Rh/Al2O3 (0.9 kg) in 5 kg of water was added to the reaction mixture, which was then made inert under nitrogen. The mixture was hydrogenated under a pressure of 3-3.5 bar at 85-95° C. After eight hours, when no further change in pressure was observed, the mixture was cooled to 25-35° C. The catalyst was filtered and washed with 4.0 kg of water. Ammonia and most of the water in the reaction mixture were removed under vacuum at 80-90° C., and the product began to precipitate. Acetonitrile (116 kg) was added and then the mixture was concentrated (ca. 50%) under vacuum. Additional acetonitrile (57.1 kg) was added to aid in crystallization and the reaction mixture was stirred for 1-4 hours at 15-25° C. until precipitation of the product was complete. The product was centrifuged and oven dried under vacuum at 45-55° C. to afford 19.1 kg (100%) of the title compound.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([C:8]([CH3:13])([CH3:12])[C:9](=[O:11])[CH3:10])[CH:5]=[CH:6][CH:7]=1.[CH:14](NC(C)C)(C)[CH3:15].C(I)C.C(=O)([O-])[O-].[K+].[K+]>C(O)C>[CH2:14]([O:1][C:2]1[CH:3]=[C:4]([C:8]([CH3:13])([CH3:12])[C:9](=[O:11])[CH3:10])[CH:5]=[CH:6][CH:7]=1)[CH3:15]
Reactant: CC(C)NC(C)C
Reactant: CC(=O)C(C)(C)c1cccc(O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCI
Solvent: CCO
Product: CCOc1cccc(C(C)(C)C(C)=O)c1

Procedure:
The mixture of 3-(3-hydroxy-phenyl)-3-methyl-butan-2-one (3.4 g, 19.08 mmol), diisopropylamine (16.7 mL, 95.4 mmoL) and ethyl iodide (6.2 mL, 76.32 mmol) in 60 mL of ethanol was heated at refluxed overnight. Thin layer chromatography still showed starting material. Potassium carbonate (9 g) was added, and the mixture was heated at reflux for 12 h. It was concentrated in vacuo, and the residue was taken in ethyl acetate. After being washed with water and brine, the organic layer was dried over anhydrous sodium sulfate. The solids were filtered off, and the filtrate was concentrated to give 3.727 g of 3-(3-ethoxy-phenyl)-3-methyl-butan-2-one as light brown oil. It was used without further purification.
Reaction SMILES: [CH:1]1([CH2:4][NH:5][C:6]2[N:14]=[CH:13][N:12]=[C:11]3[C:7]=2[N:8]=[CH:9][N:10]3[C@H:15]2[CH2:19][CH2:18][C@@H:17]([CH2:20][OH:21])[O:16]2)[CH2:3][CH2:2]1.C(N(CC)CC)C.[CH3:29][C:30]1[CH:38]=[CH:37][C:33]([C:34](Cl)=[O:35])=[CH:32][CH:31]=1>CN(C)C1C=CN=CC=1.C(#N)C>[CH:1]1([CH2:4][NH:5][C:6]2[N:14]=[CH:13][N:12]=[C:11]3[C:7]=2[N:8]=[CH:9][N:10]3[C@H:15]2[CH2:19][CH2:18][C@@H:17]([CH2:20][O:21][C:34](=[O:35])[C:33]3[CH:37]=[CH:38][C:30]([CH3:29])=[CH:31][CH:32]=3)[O:16]2)[CH2:2][CH2:3]1
Reactant: OC[C@@H]1CC[C@H](n2cnc3c(NCC4CC4)ncnc32)O1
Reactant: Cc1ccc(C(=O)Cl)cc1
Agent: CN(C)c1ccncc1
Solvent: CC#N
Solvent: CCN(CC)CC
Product: Cc1ccc(C(=O)OC[C@@H]2CC[C@H](n3cnc4c(NCC5CC5)ncnc43)O2)cc1
Temperature: 25 °C
Reaction time: 6 h
Yield: 81 %

Procedure:
6-(Cyclopropylmethylamino)-9-[(2R,5S)-tetrahydro-5-(hydroxymethyl)-2-furyl]-9H-purine (0.295 g, 1.0 mmoles), 4-dimethylaminopyridine (20 mg, 0.2 mmoles, Aldrich Chemical Co., Madison, Wis.), and triethylamine (2.0 mL, 14 mmoles, Aldrich Chemical Co., Madison, Wis.) were dissolved in 50 mL acetonitrile. p-Methylbenzoyl chloride (1.08 mL, 7.0 mmoles, Aldrich Chemical Co., Madison, Wis.) was added and the reaction was stirred at room temperature for 6 hours. The reaction was quenched with methanol and solvents were evaporated in vacuo. The residue was suspended in ethyl acetate and undissolved salts were removed by filtration. The filtrate was concentrated and applied to preparative silica gel plates (20×20×0.2 cm). The plates were developed in a mixture of chloroform:acetone (95:5). The product was scraped from the preparative plate and eluted from the silica gel with ethanol. The product was further purified by flash chromatography on a silica gel column (2.5×40 cm) with a mixture of chloroform:methanol (98:2). Lyophilization afforded 0.330 g of 6-(cyclopropylmethylamino)-9-[(2R,5S)-5-[(p-methylbenzoyloxy)-methyl]-tetrahydro-2-furyl]-9H-purine as an oil (78% yield).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:10])=[C:6]([CH:9]=1)[CH:7]=[O:8].CN(C=O)C.Cl[CH2:17][CH:18]([CH2:21][CH3:22])[CH2:19][CH3:20].C([O-])([O-])=O.[K+].[K+]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:10][CH2:17][CH:18]([CH2:21][CH3:22])[CH2:19][CH3:20])=[C:6]([CH:9]=1)[CH:7]=[O:8]
Reactant: CCC(CC)CCl
Reactant: O=Cc1cc(Cl)ccc1O
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])[O-]
Agent: [I-]
Solvent: CN(C)C=O
Product: CCC(CC)COc1ccc(Cl)cc1C=O
Temperature: 120 °C
Reaction time: 5 h

Procedure:
To a solution of 5-chloro-2-hydroxybenzaldehyde, 2.1 g (13.4 mmol) DMF (50 mL) under N2 atmosphere at RT was added 3-(chloromethyl)pentane (1.92 g 15.6 mmol), K2CO3 (4.5 g, 32.6 mmol) and tetrabutylammonium iodide (0.35 g, 0.9 mmol). The resulting mixture was stirred at 120° C. for 5 hours. The mixture was partitioned between water (80 ml) and EtOAc (80 ml). The organic layer was washed with water (80 ml) followed by brine (80 ml), dried over (Na2SO4), filtered and the volatiles were removed in vacuo. The crude product was purified on silica to yield to yield 2.83 g of 5-Chloro-2-(2-ethyl-butoxy)-benzaldehyde, 1.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].O1CCCC1.[CH3:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][C:22]([NH2:24])=O)=[CH:16][CH:15]=1>O>[CH3:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][CH2:22][NH2:24])=[CH:16][CH:15]=1
Reactant: COc1ccc(CCC(N)=O)cc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: COc1ccc(CCCN)cc1
Yield: 47.6 %

Procedure:
Lithium aluminium hydride (0.01 mol) and tetrahydrofuran (500 ml) were placed in a 1 liter flask fitted with a soxhlet extractor, with 3-(4-methoxyphenyl)propanamide (0.056 mol) in the extraction thimble. The reaction was refluxed 3 hours, was cooled and water (3.5 ml) was carefully added. After the mixture was sequentially extracted with 10% aqueous sodium hydroxide (3.5 ml) and water (10.5 ml), the mixture was filtered and concentrated. The crude product was distilled (Kugelrohr) to yield 4.4 g (48%) of a colorless oil which was stored under N2.
Reaction SMILES: N([O-])=O.[Na+].N[C:6]1[CH:7]=[CH:8][C:9]([Cl:15])=[C:10]([CH:14]=1)[C:11]([OH:13])=[O:12].Cl.[K].[C-:18]#[N:19].[K+]>O.[O-]S([O-])(=O)=O.[Cu+2]>[Cl:15][C:9]1[CH:8]=[CH:7][C:6]([C:18]#[N:19])=[CH:14][C:10]=1[C:11]([OH:13])=[O:12]
Reactant: Nc1ccc(Cl)c(C(=O)O)c1
Reactant: [C-]#N
Agent: [Cu+2]
Agent: Cl
Agent: O=N[O-]
Solvent: O
Product: N#Cc1ccc(Cl)c(C(=O)O)c1
Temperature: -5 °C
Reaction time: 1 h
Yield: 64.5 %

Procedure:
A solution of NaNO2 (2.21 g, 32 mmol) in water (10 mL) was added to a solution of 5-amino-2-chlorobenzoic acid (5.0 g, 29.14 mmol) in water (40 mL) at 0° C., followed addition of by conc. HCl (10 mL) at −5° C. The reaction mixture was stirred at −5° C. for an additional 1 h and then the diazonium solution was added dropwise into a solution of potassium cuprotetracyanide [prepared by dropwise addition of a solution of KCN (10 g, 15.38 mmol) in water (18 mL) to a solution of CuSO4 (7 g, 43.8 mmol) in water (12 mL) at 70° C.] at 50° C. for 1 h. The reaction mixture was acidified with 1.5 N HCl solution and the product was extracted with EtOAc. The combined extracts were washed with water and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica 60-120 mesh, eluant 1-2% MeOH in CHCl3) to get 2-chloro-5-cyanobenzoic acid (1.8 g, yield 34%). 1H NMR (400 MHz, DMSO-d6) δ 13.92 (br s, 1H), 8.24 (d, J=2.1 Hz, 1H), 8.02-7.99 (d, J=8.4 Hz, 2.1 Hz, 1H), 7.80-7.78 (d, J=8.2 Hz, 1H). MS (ESI) m/z: Calculated for C8H4ClNO2: 180.99. found: 179.6 (M−H)−.
Reaction SMILES: [CH3:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:5]([CH3:9])[C:3]=1[NH2:4].[CH2:10]1[C:23]2[C:14](=[N:15][C:16]3[C:17](=O)[CH2:18][CH2:19][CH2:20][C:21]=3[CH:22]=2)[C:13](=O)[CH2:12][CH2:11]1>>[CH3:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:5]([CH3:9])[C:3]=1[N:4]=[C:13]1[C:14]2[C:23](=[CH:22][C:21]3[CH2:20][CH2:19][CH2:18][C:17](=[N:4][C:3]4[C:5]([CH3:9])=[CH:6][CH:7]=[CH:8][C:2]=4[CH3:1])[C:16]=3[N:15]=2)[CH2:10][CH2:11][CH2:12]1
Reactant: O=C1CCCc2cc3c(nc21)C(=O)CCC3
Reactant: Cc1cccc(C)c1N
Product: Cc1cccc(C)c1N=C1CCCc2cc3c(nc21)C(=Nc1c(C)cccc1C)CCC3

Procedure:
was synthesized by methods similar to those in Examples 3 and 4: 2,6-dimethylaniline was condensed with 2,3,7,8-tetrahydro-1H,6H-acridine-4,5-dione to yield 4,5-bis[2,6-dimethylphenylimino]-1,2,3,4,5,6,7,8-octahydroacridine (3). The complexation of (3) with FeCl2.4H2O was carried out with azeotropic removal of methanol in benzene. The structure of final complex was proved by X-ray analysis.
Reaction SMILES: [Cl:1][C:2]1[C:6]([Cl:7])=[C:5]([CH3:8])[NH:4][C:3]=1[C:9]([NH:11][CH:12]1[CH2:17][CH2:16][N:15]([C:18]2[N:23]=[C:22]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[N:21]=[C:20]([C:30](O)=[O:31])[CH:19]=2)[CH2:14][CH2:13]1)=[O:10].Cl.[O:34]([NH2:36])[CH3:35]>>[Cl:1][C:2]1[C:6]([Cl:7])=[C:5]([CH3:8])[NH:4][C:3]=1[C:9]([NH:11][CH:12]1[CH2:13][CH2:14][N:15]([C:18]2[N:23]=[C:22]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[N:21]=[C:20]([C:30]([NH:36][O:34][CH3:35])=[O:31])[CH:19]=2)[CH2:16][CH2:17]1)=[O:10]
Reactant: CON
Reactant: Cc1[nH]c(C(=O)NC2CCN(c3cc(C(=O)O)nc(N4CCOCC4)n3)CC2)c(Cl)c1Cl
Agent: Cl
Product: CONC(=O)c1cc(N2CCC(NC(=O)c3[nH]c(C)c(Cl)c3Cl)CC2)nc(N2CCOCC2)n1

Procedure:
The title compound was synthesised by an analogous method to Example 8 starting from 6-(4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidin-1-yl)-2-morpholin-4-ylpyrimidine-4-carboxylic acid (Example 310) and methoxylamine hydrochloride.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([N+:9]([O-])=O)[CH:6]=[CH:5][C:4]=1[C:12]1[S:13][C:14]2[CH:20]=[CH:19][CH:18]=[CH:17][C:15]=2[N:16]=1.O.O.[Sn](Cl)Cl.CCCCCC.C1COCC1>CCO>[NH2:9][C:7]1[CH:6]=[CH:5][C:4]([C:12]2[S:13][C:14]3[CH:20]=[CH:19][CH:18]=[CH:17][C:15]=3[N:16]=2)=[C:3]([O:2][CH3:1])[CH:8]=1
Reactant: COc1cc([N+](=O)[O-])ccc1-c1nc2ccccc2s1
Agent: Cl[Sn]Cl
Solvent: C1CCOC1
Solvent: O
Solvent: CCCCCC
Product: COc1cc(N)ccc1-c1nc2ccccc2s1
Yield: 95.9 %

Procedure:
Prepared as described in the Nitro Reduction section using 2-(2-methoxy-4-nitrophenyl)benzothiazole (0.1 g, 0.35 mmol) and tin (II) dichloride dihydrate (0.63 g, 2.8 mmol) in EtOH (12 ml) to give the title compound (0.086 g, 96%) as a pale orange solid after work-up and flash chromatography (2:1 Hexane/THF).
Reaction SMILES: [H-].[Na+].Cl[CH2:4][CH2:5][S:6](Cl)(=[O:8])=[O:7].[F:10][C:11]1[CH:16]=[C:15]([C:17]2[C:18]([NH2:23])=[N:19][CH:20]=[CH:21][CH:22]=2)[CH:14]=[CH:13][C:12]=1[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.O>C1COCC1.CCCCCC>[F:10][C:11]1[CH:16]=[C:15]([C:17]2[C:18]3=[N:23][S:6](=[O:8])(=[O:7])[CH2:5][CH2:4][N:19]3[CH:20]=[CH:21][CH:22]=2)[CH:14]=[CH:13][C:12]=1[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1
Reactant: O=S(=O)(Cl)CCCl
Reactant: Nc1ncccc1-c1ccc(-c2ccccc2)c(F)c1
Agent: [H-]
Agent: [Na+]
Solvent: CCCCCC
Solvent: C1CCOC1
Solvent: O
Product: O=S1(=O)CCN2C=CC=C(c3ccc(-c4ccccc4)c(F)c3)C2=N1
Yield: 54 %

Procedure:
To a suspension of 60% sodium hydride (0.76 g) in THF (20 mL) was added 2-chloroethanesulfonyl chloride (1.85 g) under ice-cooling. The reaction mixture was stirred under ice-cooling for 5 min, and a solution of 3-(2-fluorobiphenyl-4-yl)pyridin-2-amine (1.0 g) in THF (20 mL) was added. The reaction mixture was stirred at room temperature overnight, and water and hexane were added under ice-cooling. The resulting solid was collected by filtration, washed with ethyl acetate, and dried under reduced pressure to give the title compound (0.724 g).