Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[N:19]([CH:20]=[CH2:21])[C:18]3[CH:22]=[CH:23][CH:24]=[CH:25][C:17]=3[N:16]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.[IH:26]>CO>[IH:26].[IH:26].[N:11]1([C:15]2[N:19]([CH:20]=[CH2:21])[C:18]3[CH:22]=[CH:23][CH:24]=[CH:25][C:17]=3[N:16]=2)[CH2:12][CH2:13][CH2:14][NH:8][CH2:9][CH2:10]1
Reactant: C=Cn1c(N2CCCN(C(=O)OC(C)(C)C)CC2)nc2ccccc21
Agent: I
Solvent: CO
Product: C=Cn1c(N2CCCNCC2)nc2ccccc21
Temperature: 25 °C
Reaction time: 2 h
Yield: 95.4 %

Procedure:
Treat a stirred solution of 4-(1-vinyl-1H-benzoimidazol-2-yl)-[1,4]diazepane-1-carboxylic acid tert-butyl ester (0.97 g, 2.8 mmol) and methanol (20 mL) at 0° C. with 57% hydroiodic acid (467 microliters, 6.21 mmol) solution. Stir at room temperatue for two hours, add 57% hydroiodic acid (934 microliters) and reflux for 30 minutes. Cool to room temperature, concentrate in vacuo to approximately 5 mL final volume, and add ether (total of 200 mL) to afford a tacky solid. Stir the suspension overnight, collect the solid by filtration under nitrogen and dry in vacuo for two hours. Dry in vacuo (0.2 Torr) at room temperature overnight to afford 1.33 g of 2-[1,4]diazepan-1-yl-1-vinyl-1H-benzoimidazole dihydroiodide.
Reaction SMILES: [Cl:1][C:2]1[C:14](I)=[CH:13][C:5]2[NH:6][C:7]([C:9]([F:12])([F:11])[F:10])=[N:8][C:4]=2[CH:3]=1.[Cl:16][C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[C:21]([Cl:23])[CH:22]=1.O1CCOCC1.[Na+].C(O[O-])=O.[Na+].C(O[O-])=O>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.O>[Cl:1][C:2]1[C:14]([C:19]2[CH:18]=[C:17]([Cl:16])[CH:22]=[C:21]([Cl:23])[CH:20]=2)=[CH:13][C:5]2[NH:6][C:7]([C:9]([F:12])([F:11])[F:10])=[N:8][C:4]=2[CH:3]=1
Reactant: FC(F)(F)c1nc2cc(Cl)c(I)cc2[nH]1
Reactant: OB(O)c1cc(Cl)cc(Cl)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=CO[O-]
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: FC(F)(F)c1nc2cc(Cl)c(-c3cc(Cl)cc(Cl)c3)cc2[nH]1
Temperature: 100 °C
Reaction time: 8 h

Procedure:
Compound number 247 (i.e., 6-chloro-5-(3,5-dichlorophenyl)-2-trifluoromethylbenzimidazole) was prepared as follows. A 100-mL round-bottom flask was purged and maintained with an inert atmosphere of nitrogen. 5-chloro-6-iodo-2-(trifluoromethyl)-1H-1,3-benzodiazole (200 mg, 0.58 mmol, 1.00 equiv), (3,5-dichlorophenyl)boronic acid (110 mg, 0.58 mmol, 2.00 equiv), dioxane (15 mL), Pd(PPh3)4 (66.8 mg, 0.06 mmol, 0.10 equiv), water (5 mL) and sodium methaneperoxoate sodium (183.8 mg, 1.72 mmol, 3.00 equiv) was placed in the flask. The resulting solution was stirred overnight at 100° C. in an oil bath. The reaction was then quenched by the addition of 15 mL of water. The resulting solution was extracted with 3×20 mL of ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:10). The crude product (100 mg) was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-2): Column, C18 silica gel; mobile phase, water increasing to acetonitrile within 40 min; Detector, UV 254 nm. 47.7 mg product was obtained. This resulted in 47.7 mg (23%) of 6-chloro-5-(3,5-dichlorophenyl)-2-trifluoromethylbenzimidazole as a white solid.
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:42]=[CH:41][C:34]([C:35]([O:37][CH2:38][CH2:39][OH:40])=[O:36])=[CH:33][C:32]=2[O:43][CH3:44])=[O:29])[CH:5]=[CH:6][CH:7]=1.[C:46]([O:50][C:51]([N:53]([CH3:58])[CH2:54][C:55](O)=[O:56])=[O:52])([CH3:49])([CH3:48])[CH3:47]>>[C:46]([O:50][C:51]([N:53]([CH3:58])[CH2:54][C:55]([O:40][CH2:39][CH2:38][O:37][C:35](=[O:36])[C:34]1[CH:41]=[CH:42][C:31]([NH:30][C:28]([C@H:9]2[C@H:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=3[F:45])[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]([CH3:25])([CH3:26])[CH3:27])[NH:10]2)=[O:29])=[C:32]([O:43][CH3:44])[CH:33]=1)=[O:56])=[O:52])([CH3:49])([CH3:48])[CH3:47]
Reactant: CN(CC(=O)O)C(=O)OC(C)(C)C
Reactant: COc1cc(C(=O)OCCO)ccc1NC(=O)[C@@H]1N[C@@H](CC(C)(C)C)[C@](C#N)(c2ccc(Cl)cc2F)[C@H]1c1cccc(Cl)c1F
Product: COc1cc(C(=O)OCCOC(=O)CN(C)C(=O)OC(C)(C)C)ccc1NC(=O)[C@@H]1N[C@@H](CC(C)(C)C)[C@](C#N)(c2ccc(Cl)cc2F)[C@H]1c1cccc(Cl)c1F

Procedure:
In a manner similar to the method described in Example 3, 2-hydroxyethyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoate was reacted with 2-(tert-butoxycarbonyl(methyl)amino)-acetic acid to give 4-{[(2R,3S,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid 2-[2-(tert-butoxycarbonyl-methyl-amino)-acetoxy]-ethyl ester. MS (ES+) m/z calcd. for C41H47Cl2F2N4O8: [(M+H)+]: 831. found: 831.
Reaction SMILES: [I-].C[S+](C)C.[CH2:6]([O:8][CH:9]([CH2:23][CH3:24])[CH2:10][CH2:11][CH2:12][CH2:13][CH:14]1[CH2:22][CH2:21][CH:20]2[CH:15]1[CH2:16][C:17]12[CH2:19][O:18]1)[CH3:7].[I-].[Li+]>>[CH2:6]([O:8][CH:9]([CH2:23][CH3:24])[CH2:10][CH2:11][CH2:12][CH2:13][CH:14]1[CH2:22][CH2:21][CH:20]2[CH:15]1[CH2:16][C:19](=[O:18])[CH2:17]2)[CH3:7]
Reactant: CCOC(CC)CCCCC1CCC2C1CC21CO1
Agent: C[S+](C)C
Agent: [I-]
Agent: [Li+]
Product: CCOC(CC)CCCCC1CCC2CC(=O)CC12

Procedure:
Disclosed is a method of synthesizing a compound, such as 6-(5-ethoxyhept-1-yl)bicyclo[3.3.0]octan-3-one or methoxyheptyl bicyclooctanone, from 3-(5-ethoxyhept-1-yl)cyclopentene or other starting material. Such a method comprises reacting 3-(5-ethoxyhept-1-yl)cyclopentene with dichloroketene to form a first mixture comprising 7,7-dichloro-4-(5-ethoxyhept-1-yl)bicyclo[3.2.0]heptan-6-one and 6,6-dichloro-4-(5-ethoxyhept-1-yl)bicyclo[3.2.0]-heptan-7-one. The first mixture is reacted with acetic acid and zinc to form a second mixture comprising 4-(5-ethoxyhept-1-yl)bicyclo[3.2.0]heptan-6-one and 4-(5-ethoxyhept-1-yl)bicyclo-[3.2.0]heptan-7-one. The second mixture is reacted with trimethylsulfonium iodide to form a third mixture comprising 2-(5-ethoxyhept-1-yl)spiro[bicyclo[3.2.0]heptane-6,2′-oxirane]. The third mixture is reacted with lithium iodide to form 6-(5-ethoxyhept-1-yl)bicyclo[3.3.0]octan-3-one.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]2[C:17](=[O:42])[N:18]([C:28]3[CH:41]=[CH:40][C:31]([O:32][CH2:33][C:34](N(OC)C)=[O:35])=[CH:30][CH:29]=3)[C:19]3[N:20]([N:25]=[CH:26][CH:27]=3)[C:21]=2[CH2:22][CH2:23][CH3:24])=[CH:11][CH:10]=1)#[N:2].[CH3:43][Mg]Br.C(OCC)(=O)C.[Cl-].[NH4+]>O1CCCC1>[OH:35][CH:34]([CH3:43])[CH2:33][O:32][C:31]1[CH:30]=[CH:29][C:28]([N:18]2[C:17](=[O:42])[C:16]([CH2:15][C:12]3[CH:13]=[CH:14][C:9]([C:4]4[C:3]([C:1]#[N:2])=[CH:8][CH:7]=[CH:6][CH:5]=4)=[CH:10][CH:11]=3)=[C:21]([CH2:22][CH2:23][CH3:24])[N:20]3[N:25]=[CH:26][CH:27]=[C:19]23)=[CH:41][CH:40]=1
Reactant: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n(-c2ccc(OCC(=O)N(C)OC)cc2)c2ccnn12
Reactant: C[Mg]Br
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n(-c2ccc(OCC(C)O)cc2)c2ccnn12
Reaction time: 1 h
Yield: 73 %

Procedure:
To a solution of 2-(4-{6-[(2′-cyanobiphenyl-4-yl)methyl]-5-oxo-7-propylpyrazolo[1,5-a]pyrimidin-4(5H)-yl}phenoxy)-N-methoxy-N-methylacetamide (0.44 g) in tetrahydrofuran (4 mL) was added dropwise methylmagnesium bromide (1 M tetrahydrofuran solution, 1.6 mL) at 0° C., and the mixture was stirred for 1 hr. Ethyl acetate and then saturated aqueous ammonium chloride solution were added. The mixture was extracted with ethyl acetate, and the organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was dissolved in ethanol (4 mL), and sodium borohydride (0.030 g) was added at 0° C. After stirring at 0° C. for 30 min, ethyl acetate and then saturated aqueous ammonium chloride solution were added. The mixture was extracted with ethyl acetate, and the organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography to give the title compound as a pale-yellow amorphous solid (0.30 g, 73%).
Reaction SMILES: [C:1](N1C=CN=C1)([N:3]1[CH:7]=[CH:6][N:5]=[CH:4]1)=[O:2].[OH:13][CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][N:19]([C:22](=[O:24])[CH3:23])[CH2:18][CH2:17]1.O>C(Cl)Cl>[N:3]1([C:1]([O:13][CH2:14][CH2:15][N:16]2[CH2:21][CH2:20][N:19]([C:22](=[O:24])[CH3:23])[CH2:18][CH2:17]2)=[O:2])[CH:7]=[CH:6][N:5]=[CH:4]1
Reactant: CC(=O)N1CCN(CCO)CC1
Reactant: O=C(n1ccnc1)n1ccnc1
Solvent: ClCCl
Solvent: O
Product: CC(=O)N1CCN(CCOC(=O)n2ccnc2)CC1
Yield: 95.8 %

Procedure:
A solution of 1,1′-carbonyldiimidazole (5 g, 31 mmol) in DCM (200 mL) was treated with a solution of 1-[4-(2-hydroxyethyl)-1-piperazinyl]-1-ethanone (see step (i) above; 5 g, 29 mmol) in DCM (50 mL). The reaction mixture was stirred at rt overnight before water was added. The layers were separated, and the organic layer was washed with water, dried and concentrated in vacuo to yield 7.4 g (96%) of the title compound.
Reaction SMILES: [H-].[Na+].[F:3][C:4]([F:14])([F:13])[C:5]([C:9]([F:12])([F:11])[F:10])([CH3:8])[CH2:6][OH:7].[Cl:15][C:16]1[CH:21]=[C:20](Cl)[N:19]=[CH:18][N:17]=1.[Cl-].[NH4+]>O1CCCC1>[Cl:15][C:16]1[CH:21]=[C:20]([O:7][CH2:6][C:5]([C:9]([F:11])([F:10])[F:12])([C:4]([F:13])([F:14])[F:3])[CH3:8])[N:19]=[CH:18][N:17]=1
Reactant: Clc1cc(Cl)ncn1
Reactant: CC(CO)(C(F)(F)F)C(F)(F)F
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CC(COc1cc(Cl)ncn1)(C(F)(F)F)C(F)(F)F
Reaction time: 0.17 h

Procedure:
In 4 ml of tetrahydrofuran was suspended 0.11 g of sodium hydride (60% in oil), to which 0.5 ml of a solution containing 0.44 g of 2,2-bis(trifluoromethyl)propanol in tetrahydrofuran was added dropwise at room temperature, followed by stirring for 10 minutes. To this was added dropwise 0.5 ml of a solution containing 0.3 g of 4,6-dichloropyrimidine in tetrahydrofuran at 0° C., followed by stirring at the same temperature for 1.5 hours. The reaction mixture was then poured into a saturated aqueous ammonium chloride solution, which was extracted three times with t-butyl methyl ether. The combined organic layers were washed with a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate to give a crude product of 4-chloro-6-[2,2-bis(trifluoromethyl)propoxy]pyrimidine.
Reaction SMILES: NO.[CH:3](=[O:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[C:11]1(C)C=CC=CC=1.C[Zn]C>CCCCCCC.CCOCC>[CH3:11][C@@H:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: O=Cc1ccccc1
Reactant: Cc1ccccc1
Agent: C[Zn]C
Agent: NO
Solvent: CCCCCCC
Solvent: CCOCC
Product: C[C@@H](O)c1ccccc1
Reaction time: 72 h
Yield: 73 %

Procedure:
To a vial containing aminoalcohol 1 (0.05 g, 0.17 mmol) prepared as in Example 1 was added a solution containing benzaldehyde (0.32 g, 3.0 mmol), toluene (3.0 mL), and 1 M dimethylzinc in heptane (6.0 mL). After 3 days at room temperature, the mixture was diluted in ether (50 mL) and the reaction was quenched by dropwise addition of half-saturated aqueous ammonium chloride (50 mL). The ether layer was separated and the aqueous layer was further extracted with ether (2×50 mL). The combined ether layers were dried over magnesium sulfate whereupon the solvent was removed at reduced pressure. The residue was purified by flash chromatography on 220-400 mesh silica with 70% hexane and 30% ethyl acetate as eluant. The solvent was distilled to afford (R)-(+)-sec-phenethyl alcohol (0.27 grams, 73%) with spectroscopic properties identical to a commercial sample. [α]D25=+55.3, c=1.96 g/100 mL chloroform indicating enantiomeric excess was 99%.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH2:10][O:11][CH3:12])=[CH:5][N:4]=1.C[Li].CN([CH:18]=[O:19])C>C1COCC1.C(NC(C)C)(C)C>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:6]([O:9][CH2:10][O:11][CH3:12])=[CH:5][N:4]=1)[CH:18]=[O:19]
Reactant: CN(C)C=O
Reactant: COCOc1ccc(OC)nc1
Agent: [Li]C
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Product: COCOc1cnc(OC)cc1C=O
Temperature: 0 °C
Reaction time: 3 h
Yield: 95.4 %

Procedure:
To a mixture of 2-methoxy-5-(methoxymethoxy)pyridine (30 g, 0.178 mol) and diisopropylamine (507 uL, 3.6 mmol) in THF (500 mL) was added methyl lithium (1.6 M/THF, 200 mL, 0.32 mol) at −40° C. Upon the completion of addition, the mixture was warmed to 0° C. and continued to stir at 0° C. for 3 h. The reaction mixture was then cooled back down to −40° C. followed by addition of DMF (24.7 mL, 0.32 mol) slowly. The mixture was then stirred at −40° C. for 1 h and quenched with a mixture of HCl (12 N, 120 mL) and THF (280 mL). Water (200 mL) was added and the pH of the mixture was adjusted to pH 8-9 with solid K2CO3. The mixture was extracted with EtOAc (300 mL) twice. The organic layer was combined, dried over Na2SO4, and concentrated to give 2-methoxy-5-(methoxymethoxy)isonicotinaldehyde (33.5 g, 95.7%) as a brown solid, which was used for next step without further purification. 1H NMR (400 MHz; CD3OD) 7.90 (s, 1H), 6.92 (s, 1H), 5.64 (s, 1H), 5.20 (s, 2H), 3.84 (s, 3H), 3.48 (s, 3H); MS (ESI) m/z 198.1 [M+H]+.
Reaction SMILES: [BH4-].[Na+].[C:3]([CH:6]1[CH2:10][CH2:9][CH:8]([CH3:11])[C:7]1([CH3:14])[CH:12]=[O:13])([CH3:5])=[CH2:4]>C(O)(C)C>[C:3]([CH:6]1[CH2:10][CH2:9][CH:8]([CH3:11])[C:7]1([CH3:14])[CH2:12][OH:13])([CH3:5])=[CH2:4]
Reactant: C=C(C)C1CCC(C)C1(C)C=O
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(C)O
Product: C=C(C)C1CCC(C)C1(C)CO

Procedure:
Into a 250 ml flask equipped with stirrer, thermometer reflux condensor, heating mantle and nitrogen blanket apparatus are placed 15 grams of sodium borohydride, 100 ml anhydrous isopropyl alcohol and 65 grams of 2-isopropenyl-1,5-dimethylcyclopentane carboxaldehyde having the structure: ##STR26## prepared according to U.S. Pat. No. 4,474,992 issued on Oct. 2, 1984.
Reaction SMILES: C([O:3][C:4](=O)[CH:5]([O:20][CH2:21][CH2:22][CH2:23][CH3:24])[C:6]1[CH:15]=[CH:14][C:13]2[C:12]([CH3:17])([CH3:16])[CH2:11][CH2:10][C:9]([CH3:19])([CH3:18])[C:8]=2[CH:7]=1)C.CC(C[AlH]CC(C)C)C.[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>CCOCC.CCCCCC.O>[CH2:21]([O:20][CH:5]([C:6]1[CH:15]=[CH:14][C:13]2[C:12]([CH3:17])([CH3:16])[CH2:11][CH2:10][C:9]([CH3:18])([CH3:19])[C:8]=2[CH:7]=1)[CH2:4][OH:3])[CH2:22][CH2:23][CH3:24]
Reactant: CCCCOC(C(=O)OCC)c1ccc2c(c1)C(C)(C)CCC2(C)C
Agent: CC(C)C[AlH]CC(C)C
Agent: O=C([O-])[C@H](O)[C@@H](O)C(=O)[O-]
Agent: [K+]
Solvent: CCOCC
Solvent: O
Solvent: CCCCCC
Product: CCCCOC(CO)c1ccc2c(c1)C(C)(C)CCC2(C)C
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 102.1 %

Procedure:
3.4 g of (RS)-butoxy-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-acetic acid ethyl ester were dissolved in 40 ml of ether. After the dropwise addition of 30 ml of a 1M solution of DIBAH in hexane at −78° C., the reaction mixture was warmed to 0° C. and stirred at this temperature for 1.5 hours. For work up, the solution was cooled to −10° C., carefully treated with 1 ml of a 2 molar solution of Rochelle salt in water followed by addition of further 7 ml of this reagent. The resulting white suspension was stirred at room temperature for 1.5 hours, filtered, the residue washed well with ether and the combined organic solution dried (MgSO4) and the solvent evaporated to give 3.05 g of (RS)-2-butoxy-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-ethanol as colorless oil. It was used in the next step without further purification.
Reaction SMILES: Br[CH2:2][C:3]1[C:4]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[N:5][C:6]2[C:11]([C:12]=1[C:13]([OH:15])=[O:14])=[CH:10][CH:9]=[CH:8][CH:7]=2.[CH3:22][S-:23].[Na+]>O1CCCC1>[CH3:22][S:23][CH2:2][C:3]1[C:4]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[N:5][C:6]2[C:11]([C:12]=1[C:13]([OH:15])=[O:14])=[CH:10][CH:9]=[CH:8][CH:7]=2
Reactant: O=C(O)c1c(CBr)c(-c2ccccc2)nc2ccccc12
Reactant: C[S-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CSCc1c(-c2ccccc2)nc2ccccc2c1C(=O)O
Reaction time: 8 h

Procedure:
To a solution of 3-(Bromomethyl)-2-phenylquinoline-4-carboxylic acid (650 mg, 1.9 mmol) in tetrahydrofuran (40 mL) was added sodium methanethiolate (400 mg, 5.7 mmol). The mixture was stirred overnight, concentrated, diluted with pH 4 buffer (40 mL) and ethyl acetate (40 mL), and extracted. The organic phase was dried (MgSO4), and concentrated to afford the desired product as a brown oil which was used without purification.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[NH:9][C:10]([C:12]1[CH:26]=[CH:25][C:15]([CH2:16][P:17](=[O:24])([O:21][CH2:22][CH3:23])[O:18][CH2:19][CH3:20])=[CH:14][CH:13]=1)=O)#[N:2].[CH3:27][NH2:28]>C1COCC1>[CH3:27][NH:28][C:1]1[C:3]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:9]=[C:10]([C:12]2[CH:26]=[CH:25][C:15]([CH2:16][P:17](=[O:24])([O:21][CH2:22][CH3:23])[O:18][CH2:19][CH3:20])=[CH:14][CH:13]=2)[N:2]=1
Reactant: CCOP(=O)(Cc1ccc(C(=O)Nc2ccccc2C#N)cc1)OCC
Reactant: CN
Solvent: C1CCOC1
Product: CCOP(=O)(Cc1ccc(-c2nc(NC)c3ccccc3n2)cc1)OCC
Temperature: 70 °C

Procedure:
A 3.7 g portion of diethyl 4-[N-(2-cyanophenyl)carbamoyl]benzylphosphonate and 10 ml of a 40% aqueous methylamine solution were dissolved in 50 ml of THF and refluxed with heating at 70° C. for 30 hours. After completion of the reaction, the solvent was distilled off under reduced pressure. The residue was subjected to silica gel column chromatography (eluent: chloroform: methanol=100:1) and the crude crystals obtained were recrystallized from chloroform-n-hexane to provide 1.0 g of the objective compound as colorless crystals. Table 1 also shows the structure and physical property (melting point) of the compound thus obtained.
Reaction SMILES: [N:1]1([CH2:6][C:7]2[CH:17]=[CH:16][C:10]3[N:11]([CH3:15])[C:12]([OH:14])=[N:13][C:9]=3[CH:8]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.[H-].[Na+].Cl[CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>CN(C)C=O>[N:1]1([CH2:6][C:7]2[CH:17]=[CH:16][C:10]3[N:11]([CH3:15])[C:12](=[O:14])[N:13]([CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:9]=3[CH:8]=2)[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: Cn1c(O)nc2cc(Cn3ccnc3)ccc21
Reactant: ClCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cn1c(=O)n(Cc2ccccc2)c2cc(Cn3ccnc3)ccc21
Temperature: 50 °C
Reaction time: 0.5 h
Yield: 78.5 %

Procedure:
A mixture of 4.5 parts of 5-(1H-imidazol-1-ylmethyl)-1-methyl-1H-benzimidazol-2-ol, 0.46 parts of a sodium hydride dispersion 50% and 56 parts of N,N-dimethylformamide was stirred for 30 minutes at 50° C. After the addition of 2.53 parts of (chloromethyl)benzene, the solution was stirred for 2 hours at 50° C. The N,N-dimethylformamide layer was evaporated in vacuo. The residue was diluted with water and the product was extracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was crystallized from a mixture of 27 parts of ethyl acetate and 44 parts of 2,2'-oxybispropane. The product was filtered off and dried, yielding 5 parts (78.5%) of 1,3-dihydro-5-(1H-imidazol-1-ylmethyl)-1-methyl-3-(phenylmethyl)-2H-benzimidazol-2-one; mp. 129.4° C. (compound 226).
Reaction SMILES: [OH:1][CH:2]([CH3:39])[CH2:3][CH:4]([CH:11]1[CH:15]([OH:16])[CH2:14][CH:13]([CH:17]=[CH:18][CH:19]([O:25][CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][O:27]2)[CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH:12]1[O:32][CH:33]1[CH2:38][CH2:37][CH2:36][CH2:35][O:34]1)[CH:5]1[O:10][CH2:9][CH2:8][CH2:7][O:6]1.CC(C)=O.OS(O)(=O)=O.O=[Cr](=O)=O.C(O)(C)C>CC(C)=O>[O:1]=[C:2]([CH3:39])[CH2:3][CH:4]([CH:11]1[C:15](=[O:16])[CH2:14][CH:13]([CH:17]=[CH:18][CH:19]([O:25][CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][O:27]2)[CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH:12]1[O:32][CH:33]1[CH2:38][CH2:37][CH2:36][CH2:35][O:34]1)[CH:5]1[O:10][CH2:9][CH2:8][CH2:7][O:6]1
Reactant: CCCCCC(C=CC1CC(O)C(C(CC(C)O)C2OCCCO2)C1OC1CCCCO1)OC1CCCCO1
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Solvent: CC(C)=O
Solvent: CC(C)O
Product: CCCCCC(C=CC1CC(=O)C(C(CC(C)=O)C2OCCCO2)C1OC1CCCCO1)OC1CCCCO1
Reaction time: 0.5 h

Procedure:
0.45 g of 1[4(3-hydroxy-1(1,3-dioxa-2-cyclohexyl)butyl]-2(3-tetrahydropyranyloxy-1-octenyl)-3(tetrahydropyranyloxy)-5-hydroxy-cyclopentane (IV) (Example 3) were dissolved in 30 ml of acetone. At -20° to -25° C., 2 ml of Jones reagent (2.1 g of chromic acid, 6 ml of water, 1.7 ml of concentrated sulfuric acid) were added under argon. The mixture was stirred for 30 minutes, 3 ml of isopropanol were added and stirring was continued for a further 10 minutes to destroy the oxidation reagent in excess. Next, 100 ml of methylene chloride and 100 ml of water were added, the mixture was shaken and the phases were separated. The organic phase was dried with MgSO4 and the solvent was removed under reduced pressure at a temperature of at most +5° C. 0.32 g of compound VIII in the form of an almost colorless clear oil was obtained.
Reaction SMILES: [C:1]1(=[O:10])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][NH:2]1.Br[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=1.C([O-])([O-])=O.[Cs+].[Cs+].C1OCCOCCOCCOCCOCCOC1>CC(C)=O.CCCCCC.C(OCC)(=O)C>[CH3:20][O:19][C:16]1[CH:17]=[CH:18][C:13]([CH2:12][N:2]2[CH2:3][C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[C:1]2=[O:10])=[CH:14][CH:15]=1
Reactant: COc1ccc(CBr)cc1
Reactant: O=C1NCc2ccccc21
Agent: C1COCCOCCOCCOCCOCCO1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC(C)=O
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: COc1ccc(CN2Cc3ccccc3C2=O)cc1
Temperature: 70 °C
Reaction time: 16 h
Yield: 31.6 %

Procedure:
A mixture of 2,3-dihydro-isoindol-1-one (0.133 g, 1 mmol), 1-bromomethyl-4-methoxy-benzene (0.222 g, 1.2 mmol,), Cs2CO3 (0.816 g, 2.5 mmol), and 18-crown-6 (0.026 g, 0.1 mmol) in acetone (5 mL) was stirred at 70° C. for 16 h. Workup and silica gel column chromatography using 30% ethyl acetate in hexane afforded 2-(4-methoxy-benzyl)-2,3-dihydro-isoindol-1-one (0.080 g, 63%). 1H NMR (300 MHz, CDCl3): δ (ppm) 3.80 (s, 3H), 4.24 (s, 2H), 4.76 (s, 2H), 6.88 (d, 2H), 7.25 (d, 2H), 7.36-7.52 (m, 3H), 7.90 (d, 1H).
Reaction SMILES: [CH2:1]([N:8]1[CH:15](O)[C@H:14]2[N:10]([C@H:11]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[S:12][CH2:13]2)[C:9]1=[O:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:24]([Si](C)(C)C)[CH:25]=[CH2:26].B(F)(F)F.CCOCC>ClCCl.CCOCC>[CH2:26]([C@H:15]1[C@H:14]2[N:10]([C@H:11]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[S:12][CH2:13]2)[C:9](=[O:23])[N:8]1[CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH:25]=[CH2:24]
Reactant: C=CC[Si](C)(C)C
Reactant: O=C1N(Cc2ccccc2)C(O)[C@@H]2CS[C@@H](c3ccccc3)N12
Agent: FB(F)F
Solvent: CCOCC
Solvent: ClCCl
Product: C=CC[C@H]1[C@@H]2CS[C@@H](c3ccccc3)N2C(=O)N1Cc1ccccc1
Yield: 98 %

Procedure:
To a solution of compound 6-benzyl-7-hydroxy-3-phenyl-(3S, 7aR)-perhydroimidazo[1,5-C][1,3]thiazol-5-one of formula (6) (0.326 parts, 1 mmol) in dichloromethane (10 parts) was added allyltrimethylsilane (0.228 parts, 2 mmol). Then Lewis acid for example BF3.Et2O (0.142 parts, 1 mmol) was added drop wise to reaction mixture at 30° C. was stirred for 30 mints. and the reaction mixture was quenched with saturated ammonium chloride (10 parts). Then the organic layer was separated, concentrated and column purification with ethylacetate:pet.ether (15:85) as eluent provided compound 7-allyl-6-benzyl-3-phenyl-(3S, 7S, 7aR)-perhydroimidazo[1,5-C][1,3]thiazol-5-one of formula (7f) (viscous liquid, 0.343 parts, 0.98 mmol) in 98% yield.