Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:17]=[CH:16][C:7]([CH2:8][NH:9][C:10]2[N:15]=[CH:14][CH:13]=[CH:12][N:11]=2)=[CH:6][CH:5]=1)([O-])=O.[BH4-].[Na+]>C1COCC1.CO.[Ni](Br)Br>[N:11]1[CH:12]=[CH:13][CH:14]=[N:15][C:10]=1[NH:9][CH2:8][C:7]1[CH:16]=[CH:17][C:4]([NH2:1])=[CH:5][CH:6]=1
Reactant: O=[N+]([O-])c1ccc(CNc2ncccn2)cc1
Agent: Br[Ni]Br
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: Nc1ccc(CNc2ncccn2)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 26 %

Procedure:
In THF (20 ml) and methanol (20mi) was dissolved N-(4-nitrobenzyl)-N-(2-pyrimidinyl)amine (921 mg, 4.00 mmol), and to the mixture were added at 0° C. nickel bromide (137 mg) and sodium boro hydride(955 mg). The mixture was stirred at room temperature for 30 minutes and concentrated under reduced pressure. To the residue were added ethyl acetate, THF and water, and the insoluble materials were filtered off. The aqueous layer was extracted with ethyl acetate-THF, and the organic layer was dried with anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified with column chromatography (silica gel 30 g, ethyl acetate/hexane=1/1), and the desired fraction was concentrated under reduced pressure. To the residue was added diethylether, and the insoluble materials were filtered, which were washed with diethylether and dried under reduced pressure to give 4-[N-(2-pyrimidinyl)aminomethyl]aniline (208 mg, 1.04 mmol, 26%).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[CH:16]=[N:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[N:8]=2)[CH2:3][CH2:2]1.[C:17]1([C:23]2[C:24]([C:32]3[CH:39]=[CH:38][C:35]([CH:36]=O)=[CH:34][CH:33]=3)=[N:25][C:26]3[N:27]([CH:29]=[CH:30][N:31]=3)[CH:28]=2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>CN1C(=O)CCC1.C(O)(=O)C.C(N(CC)CC)C>[C:17]1([C:23]2[C:24]([C:32]3[CH:33]=[CH:34][C:35]([CH2:36][N:1]4[CH2:2][CH2:3][CH:4]([C:7]5[CH:16]=[N:15][C:14]6[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=6)[N:8]=5)[CH2:5][CH2:6]4)=[CH:38][CH:39]=3)=[N:25][C:26]3[N:27]([CH:29]=[CH:30][N:31]=3)[CH:28]=2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: O=Cc1ccc(-c2nc3nccn3cc2-c2ccccc2)cc1
Reactant: c1ccc2nc(C3CCNCC3)cnc2c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN1CCCC1=O
Solvent: CC(=O)O
Solvent: CCN(CC)CC
Product: c1ccc(-c2cn3ccnc3nc2-c2ccc(CN3CCC(c4cnc5ccccc5n4)CC3)cc2)cc1
Reaction time: 1 h

Procedure:
195 mg (0.6 mmol) 2-Piperidine-4-ylquinoxaline are dissolved in 4.9 mL NMP. After addition of 0.19 mL triethylamine the reaction mixture is stirred for one hour. 170 mg (0.57 mmol) 4-(6-Phenyl-imidazo[1,2-a]pyrimidin-7-yl)-benzaldehyde (intermediate example 1.0) and 0.06 mL acetic acid are added. The reaction mixture is stirred overnight at room temperature. 132 mg (0.63 mmol) NaBH(OAc)3, are added in portions and the reaction mixture is stirred at room temperature for 18 hours. Additionally 75 mg NaBH(OAc)3 and 0.03 mL acetic acid are added and the stirring is continued for 23 hours. The reaction mixture is treated with saturated NaHCO3 and stirred vigorously for one hour. The precipitate is filtered off, washed with water and dried. After chromatography of the precipitate on silica gel (dichloromethane/methanol) 127.4 mg (45.2%) of the pure product are obtained. Another 66.1 mg (23.4%) of slightly contaminated product are obtained.
Reaction SMILES: Cl.[CH3:2][NH:3][O:4][CH3:5].C(N(CC)CC)C.[CH:13]1([C:16](Cl)=[O:17])[CH2:15][CH2:14]1>C(Cl)Cl>[CH3:5][O:4][N:3]([CH3:2])[C:16]([CH:13]1[CH2:15][CH2:14]1)=[O:17]
Reactant: O=C(Cl)C1CC1
Reactant: CNOC
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CON(C)C(=O)C1CC1
Reaction time: 1 h
Yield: 61.4 %

Procedure:
N,O-dimethyl-hydroxylamine HCl (40 g, 410 mmol) was suspended under nitrogen in DCM (400 mL) and cooled in ice. Triethylamine (63 mL, 451 mmol) was added slowly, then cyclopropanecarbonyl chloride (41 mL, 451 mmol) was added slowly. Stirring without cooling was continued for 1 h. Extraction: 2×DCM, 1×1 N HCl, 1×NaCl. Distillation: 75° C./20 mbar. One obtained 32.5 g (61%) of a colorless oil.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][N:3]=1.[H-].[Na+].[CH3:11][O:12][CH2:13]Cl>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:11][O:12][CH3:13])=[CH:4][N:3]=1
Reactant: Oc1ccc(Cl)nc1
Reactant: COCCl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COCOc1ccc(Cl)nc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 55.9 %

Procedure:
2-Chloro-5-hydroxy-pyridine (3 g, 30.9 mmol) in DMF (5 mL) was added to a cold (0° C.) solution of NaH (1.5 g, 37.1 mmol) in DMF (20 mL). The mixture was stirred at 0° C. for 1 h. Chloromethyl methyl ether (4.95 g, 60.8 mmol) was added. The reaction mixture was allowed to warm to rt, stirred overnight, cooled to 0° C., quenched by addition of water, and extracted with EtOAc. The organic layer was dried (Na2SO4), filtered, and concentrated. The residue was purified by silica gel column chromatography (hexane/ethyl acetate, 98:2) to afford 3 g of the title compound. tR: 0.56 min (LC-MS 2); ESI-MS: 174.0 [M+H]+ (LC-MS 2); Rf=0.67 (hexane/ethyl acetate, 1:1).
Reaction SMILES: [Cl:1][C:2]1[C:7]([N+:8]([O-])=O)=[C:6]([NH2:11])[CH:5]=[C:4]([Cl:12])[N:3]=1>CO.[Ni]>[Cl:1][C:2]1[C:7]([NH2:8])=[C:6]([NH2:11])[CH:5]=[C:4]([Cl:12])[N:3]=1
Reactant: Nc1cc(Cl)nc(Cl)c1[N+](=O)[O-]
Agent: [Ni]
Solvent: CO
Product: Nc1cc(Cl)nc(Cl)c1N
Reaction time: 2 h

Procedure:
To a solution of 2,6-dichloro-3-nitro-pyridin-4-amine (2.6 g, 14.4 mmol) from Step A in MeOH (150 mL) was added Raney Nickel catalyst (2 g) and the reaction agitated under a hydrogen atmosphere in a Parr apparatus (35 p.s.i.) for 2 h. The reaction mixture was filtered through a pad of Celite and concentrated to yield the title compound. MS: w/z=179 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[NH2:9].[C:10](Cl)(Cl)=[S:11].CN(C=O)C>ClC1C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N:9]=[C:10]=[S:11]
Reactant: S=C(Cl)Cl
Reactant: Nc1c(F)cccc1Cl
Solvent: CN(C)C=O
Solvent: Clc1ccccc1
Product: Fc1cccc(Cl)c1N=C=S
Yield: 96.4 %

Procedure:
To a solution of 2-chloro-6-fluorobenzenamine (5.0 g, 34 mmol) in chlorobenzene (52 mL) was added carbonothioic dichloride (thiophosgene) (5.1 g, 45 mmol) and DMF (0.27 mL). The reaction mixture was refluxed for 2 h and then concentrated to leave the title compound as a brown oil (6.15 g), which was used in Step C without further purification.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([CH:13]1[CH2:15][CH2:14]1)[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.Cl.[C:39]([CH:41]1[CH2:44][NH:43][CH2:42]1)#[N:40].C(N(CC)C(C)C)(C)C.Cl>ClCCl.O>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([CH:13]1[CH2:15][CH2:14]1)[C:10]([N:43]1[CH2:44][CH:41]([C:39]#[N:40])[CH2:42]1)=[O:12])([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C)(C)OC(=O)N[C@@H](C(=O)O)C1CC1
Reactant: N#CC1CNC1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[B-](F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Product: CC(C)(C)OC(=O)N[C@@H](C(=O)N1CC(C#N)C1)C1CC1
Temperature: 25 °C
Reaction time: 5 h
Yield: 83.5 %

Procedure:
(R)-2-(tert-butoxycarbonylamino)-2-cyclopropylacetic acid (2.25 g, 10.5 mmol) and O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (3.69 g, 11.5 mmol) were dissolved in dichloromethane (105 mL). 3-Cyanoazetidine hydrochloride (1.36 g, 11.5 mmol) and then N,N-diisopropylethylamine (4.5 mL, 26.1 mmol) were added and the mixture was stirred at room temperature for 5 h. Water, dilute HCl and more dichloromethane were added, the layers were separated and the aqueous layer was extracted once more with dichloromethane. The combined organic layers were washed with sodium chloride solution, dried over sodium sulfate and concentrated. The residue was purified by silica gel chromatography (methanol/dichloromethane) to give 2.45 g (83%) of [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-carbamic acid tert-butyl ester.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:12]([NH2:17])=[N:13][CH:14]=[CH:15][CH:16]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Cl[CH2:21][CH2:22][S:23](Cl)(=[O:25])=[O:24].O>C1COCC1.CCCCCC>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:12]3=[N:17][S:23](=[O:25])(=[O:24])[CH2:22][CH2:21][N:13]3[CH:14]=[CH:15][CH:16]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)c1ccc(-c2cccnc2N)cc1
Reactant: O=S(=O)(Cl)CCCl
Agent: [H-]
Agent: [Na+]
Solvent: CCCCCC
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)c1ccc(C2=CC=CN3CCS(=O)(=O)N=C23)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 76.8 %

Procedure:
A mixture of 3-(4-tert-butylphenyl)pyridin-2-amine (350 mg) in dehydrated THF (5 mL) was added to a mixture of sodium hydride (60%, 309 mg) and 2-chloroethanesulfonyl chloride (756 mg) in dehydrated THF (5 mL) under ice-cooling. The reaction mixture was stirred at room temperature overnight, and water and hexane were added. The resulting precipitate was collected by filtration, and washed with water and diisopropyl ether to give the title compound (376 mg) as a white solid. The obtained solid was crystallized from THF, acetonitrile and diisopropyl ether to give a white solid.
Reaction SMILES: [F:1][C:2]1[C:3]([F:15])=[C:4]([F:14])[C:5]([F:13])=[C:6]2[C:11](=[O:12])[O:10][C:8](=[O:9])[C:7]=12.[OH2:16]>Cl.S(=O)(=O)(O)O>[F:1][C:2]1[C:3]([F:15])=[C:4]([F:14])[C:5]([F:13])=[C:6]([C:11]([OH:10])=[O:12])[C:7]=1[C:8]([OH:16])=[O:9]
Reactant: O=C1OC(=O)c2c(F)c(F)c(F)c(F)c21
Reactant: O
Agent: Cl
Agent: O=S(=O)(O)O
Product: O=C(O)c1c(F)c(F)c(F)c(F)c1C(=O)O

Procedure:
In the second step, high-purity tetrafluorophthalic acid can be obtained by first isolating tetrafluorophthalic anhydride formed as a reaction intermediate, or separating the product in solution from the reaction system, and hydrolyzing the product under acidic or neutral conditions, and this embodiment is particularly preferred. For example, by hydrolyzing the N-substituted tetrafluorophthalimide under acid conditions (e.g., H2SO4 concentration: from about 50 to 98%) and, after cooling, extracting the product with an aprotic solvent (e.g., toluene, benzene, chlorobenzene, xylene, etc.), a solution of tetrafluorophthalic anhydride can be obtained. Furthermore, by removing the solvent from the extract thus obtained, tetrafluorophthalic anhydride can be isolated. In this case, the tetrafluorophthalic anhydride may be purified by distillation, if desired, under a reduced pressure. Then, by hydrolyzing the tetrafluorophthalic anhydride thus obtained under acid or neutral conditions, tetrafluorophthalic acid can be obtained. In the hydration reaction, water is generally used in an amount of from 1 to 5000 mols per mol of the tetrafluorophthalic anhydride and the reaction temperature is usually from about 0° to 100° C. The reaction can be conducted by adding an acid (e.g., hydrochloric acid and sulfuric acid) as a catalyst. This technique of isolating tetrafluorophthalic anhydride or separating it as a solution is preferred, since the purification of tetrafluorophthalic acid, which is the desired product, can be easily performed and high-purity tetrafluorophthalic acid can be obtained.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([CH2:28][CH2:29]CS([O-])(=O)=O)[CH2:13][CH2:12][N:11]([C:14](=[O:27])[C:15]3[CH:20]=[C:19]([O:21][CH3:22])[C:18]([O:23][CH3:24])=[C:17]([O:25][CH3:26])[CH:16]=3)[CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].Cl.[C:36]1([C:42]2([C:48]([NH2:50])=[O:49])[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]2)[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([CH2:28][CH2:29][N:45]3[CH2:44][CH2:43][C:42]([C:36]4[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=4)([C:48]([NH2:50])=[O:49])[CH2:47][CH2:46]3)[CH2:13][CH2:12][N:11]([C:14](=[O:27])[C:15]3[CH:16]=[C:17]([O:25][CH3:26])[C:18]([O:23][CH3:24])=[C:19]([O:21][CH3:22])[CH:20]=3)[CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: COc1cc(C(=O)N2CCC(CCCS(=O)(=O)[O-])(c3ccc(Cl)c(Cl)c3)C2)cc(OC)c1OC
Reactant: NC(=O)C1(c2ccccc2)CCNCC1
Agent: Cl
Product: COc1cc(C(=O)N2CCC(CCN3CCC(C(N)=O)(c4ccccc4)CC3)(c3ccc(Cl)c(Cl)c3)C2)cc(OC)c1OC

Procedure:
Prepare by the method of example 3.3 using (+)-2-[3-(3,4-dichloro-phenyl)-1-(3,4,5-trimethoxy-benzoyl)-pyrrolidin-3-yl]-ethyl-methanesulfonate (1.351 mmol) and 4-phenyl-piperidine-4-carboxylic acid amide hydrochloride (480 mg, 1.99 mmol, 1.5 eq.) to obtain a residue. The residue was chromatographed on silica gel (70 g) packed with ethyl acetate, loaded with ethyl acetate, and eluted with ethyl acetate, 6% methanol in dichloromethane, and then 10% methanol in dichloromethane to give the title compound:
Reaction SMILES: [CH3:1][CH:2]([CH3:10])[CH2:3][CH2:4][CH2:5][C:6]([O:8]C)=O.[CH3:11][P:12](=[O:17])([O:15][CH3:16])[O:13][CH3:14]>>[CH3:10][CH:2]([CH3:1])[CH2:3][CH2:4][CH2:5][C:6](=[O:8])[CH2:11][P:12](=[O:17])([O:15][CH3:16])[O:13][CH3:14]
Reactant: COP(C)(=O)OC
Reactant: COC(=O)CCCC(C)C
Product: COP(=O)(CC(=O)CCCC(C)C)OC

Procedure:
Dimethyl (6-methyl-2-oxoheptyl)phosphonate was prepared from methyl 5-methylcaproate and dimethyl methylphosphonate according to the known method.
Reaction SMILES: [Mg].II.Br[C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:6]=1[CH3:12].C[O:14][B:15](OC)[O:16]C>C1COCC1.BrCCBr.O>[CH3:12][C:6]1[CH:7]=[C:8]([F:11])[CH:9]=[CH:10][C:5]=1[B:15]([OH:16])[OH:14]
Reactant: COB(OC)OC
Reactant: Cc1cc(F)ccc1Br
Agent: II
Agent: [Mg]
Solvent: BrCCBr
Solvent: O
Solvent: C1CCOC1
Product: Cc1cc(F)ccc1B(O)O
Temperature: 25 °C
Reaction time: 48 h

Procedure:
To dry magnesium (113 g, 46.4 mmol) in 25 mL THF was added a small amount of 1,2-dibromoethane (2 drops) and iodine (2crystals). 1-Bromo-4-fluoro-2-methylbenzene (4.95 mL, 39.15 mmol) was added the resulting solution was refluxed for 4 h. The solution was cooled to RT and transferred by syringe to a solution of trimethylborate (4.5 mL, 40 mmol) in 20 mL THF at −78° C. The solution was warmed to RT and stirred for 2 days. Water (200 mL) was added and the mixture was concentrated (to remove most of the organics). The mixture was then treated with 2N HCl (200 mL) and stirred 2 hrs. The suspension was extracted with ethyl ether, dried over MgSO4, filtered and concentrated to give 2-methyl-4-fluoro-phenylboronic acid. LC1: 1.72 min.
Reaction SMILES: [CH3:1][C:2]1[S:6][C:5]2[NH:7][C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:13]=3[N:14]=[C:15]([N:16]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)[C:4]=2[CH:3]=1.[C:23]([OH:31])(=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C(OCC)(=O)C>[CH3:1][C:2]1[S:6][C:5]2[C:4](=[C:15]([N:16]3[CH2:17][CH2:18][N:19]([CH3:22])[CH2:20][CH2:21]3)[NH:14][C:13]3[C:8]([N:7]=2)=[CH:9][CH:10]=[CH:11][CH:12]=3)[CH:3]=1.[CH:27]1[CH:28]=[CH:29][C:24]([C:23]([OH:31])=[O:30])=[CH:25][CH:26]=1
Reactant: Cc1cc2c(s1)Nc1ccccc1N=C2N1CCN(C)CC1
Agent: O=C(O)c1ccccc1
Solvent: CCOC(C)=O
Product: Cc1cc2c(s1)=Nc1ccccc1NC=2N1CCN(C)CC1
Temperature: 25 °C

Procedure:
To a clear solution (50° C.) of 100 g olanzapine free base in 2000 ml ethyl acetate, was added slowly a clear solution of 39.2 g benzoic acid in 250 ml ethyl acetate while stirring mechanically. When almost all benzoic acid was added, the crystallization process started (T=50-55° C.). The mixture was allowed to cool to room temperature while stirring. The pale yellow crystals were isolated by filtration and dried overnight at 40° C. in vacuum. Isolated yield: 130.1 gram (94%). 1H-NMR confirms the molar ratio of olanzapine:acid=1:1. DSC: peak at 222.99° C.
Reaction SMILES: C1O[C@H](CO)[C@@H](O)[C@H]1O.[C:10]1([NH2:17])[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[NH2:16].C(OC(=O)C)(=O)C.[Br:25]Br.S([O-])([O-])=O.[Na+].[Na+]>C(O)(=O)C>[Br:25][C:14]1[CH:13]=[CH:12][C:11]([NH2:16])=[C:10]([NH2:17])[CH:15]=1
Reactant: Nc1ccccc1N
Reactant: BrBr
Agent: O=S([O-])[O-]
Agent: OC[C@H]1OC[C@H](O)[C@@H]1O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CC(=O)OC(C)=O
Product: Nc1ccc(Br)cc1N
Temperature: 0 °C

Procedure:
A method for synthesizing a deoxyribofuranose compound having a structure represented by the above-mentioned formula (12) will be explained. The compound can be synthesized according to the scheme shown in FIG. 2. First, 4-bromo-phenylene diamine (compound 13) is synthesized. The synthesis can be conducted by a method disclosed in Japanese Laid-Open Patent Application Nos. 63-22091 and 63-179870. Specifically, o-phenylene diamine is added to acetic acid, and further mixed with acetic anhydride under cooling, and the resultant reaction mixture is heated. After cooling, a bromine solution in acetic acid is slowly added to the reaction mixture. Then, an acidic sodium sulfite solution dissolved in ice water is added into the reaction mixture. The resultant white precipitate is collected to obtain compound 13, 4-bromo-o-phenylene diamine. By reacting compound 13 and 1,2-bis(chlorodimethylsilyl)ethane, compound 14 of which two amino groups attached to the benzene ring are protected, can be obtained. By lithiating compound 14 by reacting with butyl lithium (n-BuLi), compound 15 can be obtained. Then, 2,3,5-tri-o-benzyl ribonolactone (compound 16) dissolved in THF (20 ml) is reacted with compound 15. The protecting groups of the amino groups on the benzene ring are removed by using trifluoroborane and triethylsilane to obtain compound 17. Compound 18 can be obtained by treating compound 17 with benzoyl chloride. Treatment of compound 18 with boron tribromide in dichloroethane to convert all benzyloxy groups at 2', 3' and 5' positions of compound 18 to hydroxyl groups gives ribofuranose compound 11. Then compound 11 is reacted with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane so as to obtain compound 19 where 3' and 5' hydroxyl groups of the ribofuranose compound 11 are protected. The hydroxyl group at the 2' position of compound 19 is reacted with p-trichlorothinoformate so as to obtain compound 20. Compound 20 is reacted with tributyltin hydride in the presence of a catalytic amount of azoisobutylonitrile (AIBN) to obtain compound 21. By reacting compound 21 with tetrabutyl ammonium fluoride in THF at room temperature to remove the protection group, a deoxyribonucleoside having a deoxyribofuranose ring represented by the above-mentioned formula 12, which does not have a hydroxyl group at the 2' position, can be obtained.
Reaction SMILES: [N+:1]([C:4]1[CH:24]=[CH:23][CH:22]=[CH:21][C:5]=1[NH:6][C:7]1[S:11][C:10]2[CH:12]=[CH:13][C:14]([CH3:16])=[CH:15][C:9]=2[C:8]=1[C:17]([O:19][CH3:20])=[O:18])([O-])=O.[H][H]>[C].[Pd].C(OCC)(=O)C>[NH2:1][C:4]1[CH:24]=[CH:23][CH:22]=[CH:21][C:5]=1[NH:6][C:7]1[S:11][C:10]2[CH:12]=[CH:13][C:14]([CH3:16])=[CH:15][C:9]=2[C:8]=1[C:17]([O:19][CH3:20])=[O:18]
Reactant: COC(=O)c1c(Nc2ccccc2[N+](=O)[O-])sc2ccc(C)cc12
Reactant: [H][H]
Agent: [Pd]
Solvent: CCOC(C)=O
Product: COC(=O)c1c(Nc2ccccc2N)sc2ccc(C)cc12

Procedure:
In the same manner as in Starting Material Synthesis Example 19 and using methyl 2-(2-nitroanilino)-5-methylbenzo[b]thiophene-3-carboxylate, ethyl acetate, 10% palladium-carbon and hydrogen (60 atm kg/cm2), methyl 2-(2-aminoanilino)-5-methylbenzo[b]thiophene-3-carboxylate is obtained.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].[CH3:12][N:13]([CH3:17])[CH2:14][CH2:15][NH2:16].C(=O)([O-])[O-].[Na+].[Na+]>>[N+:9]([C:3]1[CH:4]=[C:5]([CH3:8])[CH:6]=[CH:7][C:2]=1[NH:16][CH2:15][CH2:14][N:13]([CH3:17])[CH3:12])([O-:11])=[O:10]
Reactant: CN(C)CCN
Reactant: Cc1ccc(Cl)c([N+](=O)[O-])c1
Agent: O=C([O-])[O-]
Agent: [Na+]
Product: Cc1ccc(NCCN(C)C)c([N+](=O)[O-])c1

Procedure:
17.2 g. of 4-chloro-3-nitrotoluene, 9 g. of 2-dimethylaminoethylamine, and 21.5 g. of anhydrous sodium carbonate are agitated for 7 hours at 135° C. Excess starting material is removed by steam distillation. The distillation residue is extracted with chloroform, the chloroform solutions are dried, filtered, and concentrated under a vacuum. By distilling the residue at 0.05 mm Hg and 133°-137° C., 10.5 g. of 3-nitro-4-(2-dimethylaminoethylamino)-toluene is obtained, m.p. 59° C. 3.5 g. of this compound is reduced as described in Example 27, and 3 g. of crude 3-amino-4-(2-dimethylaminoethylamino)-toluene is thus obtained. 400 mg. of this compound is reacted with 400 mg. of the ethyl ester of 5-nitro-1-methyl-2-imidazolyliminocarboxylic acid, as described in Example 1, thus producing 172 mg. of 1-(2-dimethylaminoethyl)-5-methyl-2-(5-nitro-1-methyl-2-imidazolyl)-benzimidazole hydrochloride, m.p. 249°-251° C.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH:8]=2)[CH:3]=[C:2]1[C:15]([O:17][CH2:18][CH3:19])=[O:16].C([O-])([O-])=O.[K+].[K+].Br[CH2:27][C:28]#[N:29]>CN(C=O)C.CCOC(C)=O>[C:28]([CH2:27][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH:8]=2)[CH:3]=[C:2]1[C:15]([O:17][CH2:18][CH3:19])=[O:16])#[N:29]
Reactant: CCOC(=O)c1ccc2cc(C(=O)OCC)[nH]c2c1
Reactant: N#CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCOC(=O)c1ccc2cc(C(=O)OCC)n(CC#N)c2c1
Temperature: 80 °C
Reaction time: 0.5 h
Yield: 84.9 %

Procedure:
To a solution of diethyl 1H-indole-2,6-dicarboxylate (Intermediate A, 4.0 g, 15.3 mmol) in dry DMF (50 mL) is added K2CO3 (6.3 g, 45.9 mmol). The reaction mixture is stirred under N2 for 30 min. Bromoacetonitrile (2.1 mL, 30.6 mmol) is added and the reaction mixture is heated to 80° C. for 4 h. After cooling, the reaction mixture is taken up in EtOAc (300 mL) and washed with water, then brine, dried (Na2SO4) and concentrated. The residue is recrystallized from ethanol to afford the title compound (3.9 g, 84%) as fine off-white needles.
Reaction SMILES: CCCCCCCCCCC.[CH2:12]([C:15]1([CH3:25])[CH:21]2[CH2:22][C:18]([CH3:23])([CH2:19][CH2:20]2)[CH2:17][C:16]1=[O:24])[CH:13]=[CH2:14].COCCO[AlH2-]OCCOC.[Na+]>C1(C)C=CC=CC=1>[CH2:12]([C:15]1([CH3:25])[CH:21]2[CH2:22][C:18]([CH3:23])([CH2:19][CH2:20]2)[CH2:17][CH:16]1[OH:24])[CH:13]=[CH2:14]
Reactant: C=CCC1(C)C(=O)CC2(C)CCC1C2
Agent: COCCO[AlH2-]OCCOC
Agent: [Na+]
Solvent: CCCCCCCCCCC
Solvent: Cc1ccccc1
Product: C=CCC1(C)C(O)CC2(C)CCC1C2
Temperature: 75 °C
Reaction time: 3 h
Yield: 100 %

Procedure:
Preparation of 2,4,8-Trimethyl-5-oxa-tricyclo[6.2.1.0*2,6]undecane (Structure 4): 4-Allyl-1,4-dimethyl-bicyclo[3.2.1]octan-3-one (288 g, 1.5 mol, obtained as above in EXAMPLE IV) was added to a solution of Red-Al (65%, 506 g, 1.5 mol) in toluene at 75° C. The reaction mixture was aged for 3 hours while the temperature was maintained at 75° C., then cooled to room temperature, and subsequently quenched with a solution of sodium bicarbonate (NaHCO3). Distillation of the organic layer provided 4-allyl-1,4-dimethyl-bicyclo[3.2.1]octan-3-ol (288 g, 1.5 mol), which was then added to a MSA solution (30 g) in toluene (500 mL) and heated to reflux for 3 hours. The reaction mixture was subsequently washed with a Na2CO3 solution. Fractional distillation of the organic layer provided 2,4,8-trimethyl-5-oxa-tricyclo[6.2.1.0*2,6*]undecane (170 g) having a boiling point of 62° C. at a pressure of 0.3 mmHg.