Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][CH:2]([Cl:6])[C:3](Cl)=[O:4].[NH2:7][C:8]1[CH:9]=[CH:10][C:11]([O:14][CH3:15])=[N:12][CH:13]=1.N1C=CC=CC=1>C(Cl)Cl>[CH3:15][O:14][C:11]1[CH:10]=[CH:9][C:8]([NH:7][C:3](=[O:4])[CH:2]([Cl:6])[Cl:1])=[CH:13][N:12]=1
Reactant: O=C(Cl)C(Cl)Cl
Reactant: COc1ccc(N)cn1
Solvent: c1ccncc1
Solvent: ClCCl
Product: COc1ccc(NC(=O)C(Cl)Cl)cn1
Reaction time: 1 h

Procedure:
Dichloroacetyl chloride, 97% (2.0 ml, 0.03 mol) was added over a period of 30 seconds to a mixture of 5-amino-2-methoxypyridine (3.7 g, 0.03 mol), pyridine (5.0 ml) and methylene chloride (100 ml). The reaction was exothermic and allowed to stand at room temperature for one hour. The reaction was then washed with 5% sodium carbonate solution (2×100 ml), dried over anhydrous magnesium carbonate, filtered, and evaporated in vacuo to give a solid that was triturated with hexane to yield 6.4 g of the title compound, m.p. 104°-107° C. The title product was identified by infrared (IR), nuclear magnetic resonance (NMR) and mass spectrocopy (MS) analysis.
Reaction SMILES: [NH2:1][CH:2]([C:5]1[CH:20]=[CH:19][C:8]2[O:9][CH2:10][C:11]3[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=3[C:13](=[O:14])[C:7]=2[CH:6]=1)[C:3]#[N:4].Cl.[OH-:22].[NH4+]>>[NH2:1][CH:2]([C:5]1[CH:20]=[CH:19][C:8]2[O:9][CH2:10][C:11]3[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=3[C:13](=[O:14])[C:7]=2[CH:6]=1)[C:3]([NH2:4])=[O:22]
Reactant: N#CC(N)c1ccc2c(c1)C(=O)c1ccccc1CO2
Reactant: [OH-]
Agent: Cl
Agent: [NH4+]
Product: NC(=O)C(N)c1ccc2c(c1)C(=O)c1ccccc1CO2
Temperature: 25 °C

Procedure:
Stir at room temperature 5.0 gm. of the aminoacetonitrile of Step B in 30 ml. of concentrated hydrochloric acid for 30 minutes. Slowly pour the reaction mixture into cold ammonium hydroxide. Extract the mixture with ether and dry over sodium sulfate. Evaporate the extract to dryness to obtain the title product.
Reaction SMILES: Cl[CH2:2][C:3]([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([O:12]C)[CH:7]=1)=[O:4].[Al+3].[Cl-].[Cl-].[Cl-]>Cl>[OH:12][C:8]1[CH:7]=[C:6]2[C:11]([CH2:2][C:3](=[O:4])[NH:5]2)=[CH:10][CH:9]=1
Reactant: COc1cccc(NC(=O)CCl)c1
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Product: O=C1Cc2ccc(O)cc2N1
Temperature: 120 °C
Reaction time: 0.17 h
Yield: 62.9 %

Procedure:
2-chloro-N-(3-methoxyphenyl)acetamide (3.1 g, 16 mmol) and anhydrous AlCl3 powder (4.4 g, 32 mmol) is heated and stirred at 120° C. for 10 minutes and exhibit a melting state. The temperature is elevated gradually to 240° C. in 40 minutes and then stirred 5 minutes. The reaction is allowed to cool to obtain a brown powder. The solid powder is poured into a mixture of 100 g of crushed ice and 50 ml of concentrated hydrochloric acid. The mixture is stirred for 10 minutes and then reflux for 10 minutes, and allowed to cool to precipitate a light yellow powder, which is filtered out and recrystallized in water to obtain 1.5 g of 6-hydroxy-indoline-2-one, with a yield of 62%.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]([CH3:21])[S:11]([C:14]2[CH:18]=[C:17]([Cl:19])[S:16][C:15]=2Cl)(=[O:13])=[O:12])=[CH:4][CH:3]=1.[Cl-].[NH4+]>O1CCCC1.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]([CH3:21])[S:11]([C:14]2[CH:18]=[C:17]([Cl:19])[S:16][CH:15]=2)(=[O:13])=[O:12])=[CH:4][CH:3]=1
Reactant: CN(CCc1ccc(F)cc1)S(=O)(=O)c1cc(Cl)sc1Cl
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: O
Product: CN(CCc1ccc(F)cc1)S(=O)(=O)c1csc(Cl)c1
Reaction time: 0.5 h
Yield: 90.9 %

Procedure:
To a solution of 2,5-dichlorothiophene-3-sulfonic acid [2-(4-fluorophenyl)ethyl]-methyl-amide (1.14 g) in tetrahydrofuran (10 mL) was added dropwise a solution of 1.59M n-butyl lithium-hexane (2.3 mL) on an ice bath. After stirring for 30 minutes, an aqueous solution of saturated ammonium chloride was poured. After diluting with water, the solution was extracted with ethyl acetate. After the organic layer was washed with saturated sodium chloride water, and was dried with anhydrous sodium sulfate. The residue that was obtained upon removing the solvent by evaporation was purified by silica gel column chromatography (hexane/ethyl acetate), and the title compound (pale yellow oily substance) (939 mg) was obtained (contains impurities).
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]([O:18]S(C(F)(F)F)(=O)=O)[CH:7]=[C:8]([O:10][S:11]([C:14]([F:17])([F:16])[F:15])(=[O:13])=[O:12])[CH:9]=1)(=[O:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC>[C:1]([C:4]1[CH:9]=[C:8]([O:10][S:11]([C:14]([F:17])([F:15])[F:16])(=[O:13])=[O:12])[CH:7]=[C:6]([OH:18])[CH:5]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)c1cc(OS(=O)(=O)C(F)(F)F)cc(OS(=O)(=O)C(F)(F)F)c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: COCCOC
Product: CC(=O)c1cc(O)cc(OS(=O)(=O)C(F)(F)F)c1
Temperature: 80 °C
Reaction time: 3 h
Yield: 51.8 %

Procedure:
Trifluoro-methanesulfonic acid 3-acetyl-5-trifluoromethanesulfonyloxy-phenyl ester (9.9 g) was dissolved in 1,2-dimethoxyethane (80 mL), followed by addition of cesium carbonate (11.6 g). The resulting suspension was stirred at 80° C. for 3 h and then quenched with saturated solution of ammonium chloride. The solution was then extracted with diethyl ether and combined etherate extracts were washed with brine, dried over anhydrous sodium sulfate, and filtered through a silica pad. The filtrate was concentrated under reduced pressure and purified on a silica gel column using ethyl acetate and hexanes to afford 3.5 g of the title compound (52% yield). HRMS calcd for C19H7O5S1F3 [M+H]+ 285.0039, observed 285.0039.
Reaction SMILES: [Br:1]Br.[F:3][C:4]([F:30])([F:29])[CH2:5][N:6]=[C:7]([NH2:28])[NH:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]([S:15][CH2:16][CH2:17][CH2:18][NH:19][C:20]([NH:26][CH3:27])=[N:21][S:22]([CH3:25])(=[O:24])=[O:23])[N:10]=1.N1C=CC=CC=1>C(Cl)Cl>[Br:1][C:14]1[C:9]([NH:8][C:7]([NH2:28])=[N:6][CH2:5][C:4]([F:29])([F:3])[F:30])=[N:10][C:11]([S:15][CH2:16][CH2:17][CH2:18][NH:19][C:20]([NH:26][CH3:27])=[N:21][S:22]([CH3:25])(=[O:23])=[O:24])=[N:12][CH:13]=1
Reactant: CNC(=NS(C)(=O)=O)NCCCSc1nccc(NC(N)=NCC(F)(F)F)n1
Reactant: BrBr
Solvent: c1ccncc1
Solvent: ClCCl
Product: CNC(=NS(C)(=O)=O)NCCCSc1ncc(Br)c(NC(N)=NCC(F)(F)F)n1
Temperature: 25 °C
Reaction time: 1 h
Yield: 57.9 %

Procedure:
A solution of bromine (0.064 g.) in methylene chloride (2 ml.) was added dropwise over 15 minutes to a stirred solution of 4-[2-(2,2,2-trifluoroethyl)guanidino]-2-[3-(2-methylsulphonyl-3-methylguanidino)propylthio]pyrimidine (0.176 g.) and pyridine (0.2 ml.) in methylene chloride (10 ml.), and the mixture stirred at room temperature for one hour. The solution was evaporated to dryness, and the residue purified by preparation thin layer chromatography using ethyl acetate/methanol/ammonia 6:1:0.5 v/v/v as developing solvent to give 5-bromo-4-[2-(2,2,2-trifluoroethyl)guanidino]-2-[3-(2-methylsulphonyl-3-methylguanidino)propylthio]pyrimidine (0.12 g.), m.p. 166°-167° after recrystallisation from ethanol.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([OH:13])[C:6](=[CH:11][CH:12]=1)[C:7]([O:9][CH3:10])=[O:8].[C:14]([O:18][C:19]([NH:21][CH2:22][CH2:23][CH2:24]Br)=[O:20])([CH3:17])([CH3:16])[CH3:15].[I-].[K+]>CN(C)C=O.O>[C:14]([O:18][C:19]([NH:21][CH2:22][CH2:23][CH2:24][O:13][C:5]1[CH:4]=[C:3]([O:2][CH3:1])[CH:12]=[CH:11][C:6]=1[C:7]([O:9][CH3:10])=[O:8])=[O:20])([CH3:17])([CH3:16])[CH3:15]
Reactant: COC(=O)c1ccc(OC)cc1O
Reactant: CC(C)(C)OC(=O)NCCCBr
Agent: [I-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(OC)cc1OCCCNC(=O)OC(C)(C)C
Reaction time: 60 h
Yield: 93.2 %

Procedure:
To a solution of methyl 4-methoxysalicylate (11.48 g, 63 mmol) in dimethylformamide (30 mL) was added solid K2 CO3 (13.06 g, 94.5 mmol), 1-tert-butoxycarbonylamino-3-bromopropane (22.5 g, 94.5 mmol), and freshly ground potassium iodide (1.5 g). The resulting slurry was placed under a nitrogen atmosphere and stirred for 2.5 days. The slurry was diluted with water (250 mL), washed with 1 N NaOH (2×250 mL), water (250 mL), and brine (250 mL), then dried over sodium sulfate and concentrated in vacuo. The crude mixture was purified on a preparative HPLC chromatograph using two silica columns and a hexanes through 1:1 hexanes:EtOAc gradient to provide methyl 2-(3-tert-butoxycarbonylaminopropoxy)-4-methoxybenzoate (19.93 g, 93.3%) as a colorless oil.
Reaction SMILES: [C:1]([N:8]1[CH2:12][CH2:11][CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C([Li])(CC)C.[O:18]1[CH:22]=[CH:21][CH:20]=[C:19]1[CH:23]=[O:24]>C(OCC)C>[O:18]1[CH:22]=[CH:21][CH:20]=[C:19]1[CH:23]([CH:12]1[CH2:11][CH2:10][CH2:9][N:8]1[C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[OH:24]
Reactant: CC(C)(C)OC(=O)N1CCCC1
Reactant: O=Cc1ccco1
Agent: [Li]C(C)CC
Solvent: CCOCC
Product: CC(C)(C)OC(=O)N1CCCC1C(O)c1ccco1
Temperature: -78 °C
Reaction time: 2 h

Procedure:
N-Boc-pyrrolidine (5.0 g) was dissolved in diethyl ether (60 mL) and the solution was cooled to −78° C. N,N,N′,N″-Tetramethylethylenediamine (TMEDA) (4.4 mL) was added to the mixture followed by sec-butyl lithium (27.0 mL, 1.3 M in cyclohexane) maintaining the temperature below −60° C. After 2 h, 2-furaldehyde (2.9 mL) was added and the mixture was stirred at −70° C. for an additional 30 min. The reaction mixture was allowed to warm to room temperature and was then quenched with water and poured into EtOAc (200 mL). The separated organic layer was washed with saturated aq. ammonium chloride (3×50 mL) followed by brine (50 mL), dried (MgSO4), and concentrated. The crude product was purified by column chromatography (heptane/EtOAc, 8/1; 5/1) to afford 4.97 g of 2-furyl(N-Boc-pyrrolidin-2-yl)methanol as a mixture of diastereomers. The resulting 2-furyl(N-Boc-pyrrolidin-2-yl)methanol (4.43 g) was dissolved in dichloromethane (200 mL) and trifluoroacetic acid (30 mL) was added. The mixture was poured into a 1 M solution of sodium hydroxide. The organic layer was separated and washed with saturated aq. sodium bicarbonate (2×100 mL). The aqueous layers were extracted with dichloromethane (4×50 mL) and the combined organic layers were concentrated. The crude product was purified by column chromatography (CH2Cl2/methanol/NH4OH, 95/5/1; 90/10/1). The resulting oil was distilled in a Kugelrohr apparatus (175-200° C., 0.2 Torr) to afford 0.20 g of the title compound as a mixture of diastereomers. Physical characteristics. MS (ESI+) m/z 168 (M+H)−.
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH:10]=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O1C[CH2:15][CH2:14][CH2:13]1>>[C:2]1([CH2:1][O:8][CH2:9][C@@H:10]([OH:11])[CH2:15][CH:14]=[CH2:13])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C1CCOC1
Reactant: O=CCOCc1ccccc1
Product: C=CC[C@H](O)COCc1ccccc1

Procedure:
The optically active tetrahydrofuran derivatives are prepared according to Scheme V. Benzyloxyacetaldehyde is reacted with optically active 2-allyl-1,3,2-dioxaborolane-4,5-dicarboxylic acid ester, XVII, to give optically pure (S)-1-phenylmethoxy-4-penten-2-ol, XVIII. Cyclization of alcohol, XVIII, with iodine in the presence of sodium bicarbonate gives a mixture of optically pure 2,5-anhydro-1,3-dideoxy-1-iodo-D-threopentitol, XIX, ##STR112## and 2,5-anhydro-1,3-dideoxy1-iodo-D-erythro-pentitol, XX, which is separated by flash chromatography using silica gel. ##STR113##
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[C:16]([F:20])[C:17](F)=[CH:18][C:13]=2[NH:12][C:11](=[S:21])[CH2:10][N:9]=1.[CH2:22]([OH:24])[CH3:23].[H-].[Na+]>C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[C:16]([F:20])[C:17]([O:24][CH2:22][CH3:23])=[CH:18][C:13]=2[NH:12][C:11](=[S:21])[CH2:10][N:9]=1
Reactant: Fc1cc2c(cc1F)C(c1ccccc1Cl)=NCC(=S)N2
Reactant: CCO
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Product: CCOc1cc2c(cc1F)C(c1ccccc1Cl)=NCC(=S)N2

Procedure:
A mixture of 0.5 g (0.00155 mole) of 5-(2-chlorophenyl)-1,3-dihydro-7,8-difluoro-2H-1,4-benzodiazepin-2-thione (IImm), 10 mL of ethanol and 0.62 g of 60% sodium hydride was heated at reflux for 24 hours. The mixture was cooled, diluted with ethyl acetate and washed successively with water and then brine. The ethyl acetate extract was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 0.52 g of 5-(2-chlorophenyl)-1,3-dihydro-8-ethoxy-7-fluoro-2H-1,4-benzodiazepin-2-thione (IIg) as a yellow solid. MH+/Z=349.
Reaction SMILES: [CH3:1][N:2]1[CH2:15][CH2:14][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.[OH-].[K+].[CH3:18][C:19]1[CH:24]=[N:23][C:22]([CH:25]=[CH2:26])=[CH:21][N:20]=1>CN1CCCC1=O.O>[CH3:1][N:2]1[CH2:15][CH2:14][C:5]2[N:6]([CH2:26][CH2:25][C:22]3[CH:21]=[N:20][C:19]([CH3:18])=[CH:24][N:23]=3)[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1
Reactant: Cc1ccc2[nH]c3c(c2c1)CN(C)CC3
Reactant: C=Cc1cnc(C)cn1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CN1CCCC1=O
Product: Cc1ccc2c(c1)c1c(n2CCc2cnc(C)cn2)CCN(C)C1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 31.2 %

Procedure:
To a solution of 2,8-Dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (0.1 g, 0.5 mmol) in N-methyl 2-pyrolidone (0.75 mL) was added powdered potassium hydroxide (0.281 g, 5.0 mmol) and allowed to stir for 10 min at RT. 2-methyl-5-vinyl pyrazine (0.151 g, 1.2 mmol) was added and stirred for further 2 h. at 60 deg C. After completion (TLC), reaction mixture was diluted with water (25 mL) and extracted with ethyl acetate (3×100 mL). The organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure. The crude was purified through column chromatography (6% MeOH:DCM in silica 100-200 mesh, Diameter of column−2.5 cm, Height of silica—approx. 5 inch) to provide the desired compound as yellow oil (0.05 g, 31% yield). 2,8-Dimethyl-5-[2-(5-methyl-pyrazin-2-yl)-ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (0.05 g, 0.156 mmol) was dissolved in THF (2.0 mL). A solution of oxalic acid dihydrate (0.015 g, 0.000119 mol) in THF (1.0 mL) was added and stirred for 30 min at RT. Precipitate obtained was filtered and dried to give oxalate salt as white solid (0.03 g, 47% yield).
Reaction SMILES: [NH2:1][C:2]1[CH:18]=[CH:17][C:5]([O:6][C:7]2[N:11]([CH3:12])[C:10]3[CH:13]=[CH:14][CH:15]=[CH:16][C:9]=3[N:8]=2)=[CH:4][CH:3]=1.Cl[C:20](Cl)(Cl)[S:21]([SH-]C(=S)[S-])(=O)=O>O>[N:1]([C:2]1[CH:3]=[CH:4][C:5]([O:6][C:7]2[N:11]([CH3:12])[C:10]3[CH:13]=[CH:14][CH:15]=[CH:16][C:9]=3[N:8]=2)=[CH:17][CH:18]=1)=[C:20]=[S:21]
Reactant: O=S(=O)([SH-]C(=S)[S-])C(Cl)(Cl)Cl
Reactant: Cn1c(Oc2ccc(N)cc2)nc2ccccc21
Solvent: O
Product: Cn1c(Oc2ccc(N=C=S)cc2)nc2ccccc21

Procedure:
An amount of 4.8 g of 2-(4'-aminophenoxy)-1-methylbenzimidazole is stirred with 2.3 g of bis-(trichloromethane-sulphonyl-trithiocarbonate in 25 ml of water for 24 hours at room temperature. The precipitate is separated, washed with sodium bicarbonate solution, and taken up in chloroform. After drying and distillation of the chloroform solution, the residue is boiled out with cyclohexane, filtered hot, and the filtrate diluted with petroleum ether. The 2-(4'-isothiocyanophenoxy)-1-methylbenzimidazole crystallising out melts at 59° to 61°C.
Reaction SMILES: O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH3:13][O:14][C:15](=[O:31])[C:16]1[C:21]([CH2:22][O:23]C2CCCCO2)=[C:20]([Cl:30])[CH:19]=[N:18][CH:17]=1>CO>[CH3:13][O:14][C:15](=[O:31])[C:16]1[C:21]([CH2:22][OH:23])=[C:20]([Cl:30])[CH:19]=[N:18][CH:17]=1
Reactant: COC(=O)c1cncc(Cl)c1COC1CCCCO1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: CO
Product: COC(=O)c1cncc(Cl)c1CO
Temperature: 25 °C
Reaction time: 1 h

Procedure:
p-Toluenesulfonic acid monohydrate (26.7 mg, 0.140 mmol) was added to a stirred solution of 5-chloro-4-(tetrahydro-pyran-2-yloxymethyl)-nicotinic acid methyl ester (20 mg, 0.070 mmol) in MeOH (4 mL). After stirring for 60 min at room temperature, the reaction mixture was concentrated in vacuo and the residue was partitioned between EA (10 mL) and saturated NaHCO3 solution (10 mL). After extraction of the aqueous layer with DCM (2×10 mL) the combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The resulting title compound was used for the next reaction without purification. MS (m/z): 202.0 [M+H+].
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](=O)[NH:8][N:7]=[CH:6]2.N#N.P(Cl)(Cl)([Cl:18])=O>C(#N)C>[Cl:18][C:9]1[C:10]2[C:5](=[CH:4][C:3]([O:2][CH3:1])=[CH:12][CH:11]=2)[CH:6]=[N:7][N:8]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: COc1ccc2c(=O)[nH]ncc2c1
Agent: N#N
Solvent: CC#N
Product: COc1ccc2c(Cl)nncc2c1
Yield: 98.2 %

Procedure:
A suspension of 6-methoxy-2H-phthalazin-1-one (6.4 g, 36.3 mmoles), prepared as described in example 3, in acetonitrile (65 ml) under stirring and dry N2 at room temperature, was dropwise added with phosphorous oxychloride (6.8 ml, 73 mmoles), then the mixture was refluxed. After 3 hours the mixture was concentrated, taken up in water, neutralised with NaHCO3 and extracted more times with CH2Cl2. The organic phases were washed with water, anhydrified and concentrated to give 6.94 g of the title compound (yield: 98.3%). m.p.: 181-183° C.
Reaction SMILES: [F:1][C:2]([F:27])([F:26])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:13]3[CH:14]=[CH:15][C:16](OS(C(F)(F)F)(=O)=O)=[CH:17][C:12]=3[S:11][N:10]=2)=[CH:5][CH:4]=1.[CH2:28]([N:30]([CH2:35][CH2:36][O:37][CH3:38])[CH:31]([CH3:34])[C:32]#[CH:33])[CH3:29]>>[CH2:28]([N:30]([CH2:35][CH2:36][O:37][CH3:38])[CH:31]([CH3:34])[C:32]#[C:33][C:16]1[CH:15]=[CH:14][C:13]2[C:9]([C:6]3[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:26])[F:27])=[CH:8][CH:7]=3)=[N:10][S:11][C:12]=2[CH:17]=1)[CH3:29]
Reactant: O=S(=O)(Oc1ccc2c(-c3ccc(C(F)(F)F)cc3)nsc2c1)C(F)(F)F
Reactant: C#CC(C)N(CC)CCOC
Product: CCN(CCOC)C(C)C#Cc1ccc2c(-c3ccc(C(F)(F)F)cc3)nsc2c1

Procedure:
In analogy to example 14.1, Trifluoro-methanesulfonic acid 3-(4-trifluoromethyl-phenyl)-benzo[d]isothiazol-6-yl ester and Ethyl-(2-methoxy-ethyl)-(1-methyl-prop-2-ynyl)-amine were converted to yield Ethyl-(2-methoxy-ethyl)-{1-methyl-3-[3-(4-trifluoromethyl-phenyl)-benzo[d]isothiazol-6-yl]-prop-2-ynyl}-amine as brown oil, MS: 433 (MH+).
Reaction SMILES: [Cl:1][C:2]1[C:6]([Cl:7])=[C:5]([CH3:8])[NH:4][C:3]=1[C:9]([NH:11][C@@H:12]1[CH2:17][CH2:16][N:15]([C:18]2[S:19][C:20]([C:35]([O:37]C)=[O:36])=[C:21]([C:23]3[N:28]=[C:27]([N:29]4[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]4)[CH:26]=[CH:25][N:24]=3)[N:22]=2)[CH2:14][C@@H:13]1[O:39][CH3:40])=[O:10].[OH-].[Li+]>O1CCCC1.O>[Cl:1][C:2]1[C:6]([Cl:7])=[C:5]([CH3:8])[NH:4][C:3]=1[C:9]([NH:11][C@@H:12]1[CH2:17][CH2:16][N:15]([C:18]2[S:19][C:20]([C:35]([OH:37])=[O:36])=[C:21]([C:23]3[N:28]=[C:27]([N:29]4[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]4)[CH:26]=[CH:25][N:24]=3)[N:22]=2)[CH2:14][C@@H:13]1[O:39][CH3:40])=[O:10]
Reactant: COC(=O)c1sc(N2CC[C@@H](NC(=O)c3[nH]c(C)c(Cl)c3Cl)[C@@H](OC)C2)nc1-c1nccc(N2CCCCC2)n1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: CO[C@H]1CN(c2nc(-c3nccc(N4CCCCC4)n3)c(C(=O)O)s2)CC[C@H]1NC(=O)c1[nH]c(C)c(Cl)c1Cl
Temperature: 25 °C
Reaction time: 18 h
Yield: 75.7 %

Procedure:
To a stirred solution of methyl 2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl]-4-[4-(piperidin-1-yl)pyrimidin-2-yl]-1,3-thiazole-5-carboxylate (Example 184, 35 mg. 0.06 mmol) in tetrahydrofuran (5 mL) was added a solution of lithium hydroxide (9.6 mg, 0.23 mmol) in water (1 mL). The reaction mixture was stirred at room temperature for 18 h. The reaction mixture was concentrated to dryness. The resulting residue was diluted with water (2 mL) and the aqueous layer was extracted with diethyl ether (2×10 mL). The aqueous layer was acidified to pH 4-5 with 2N HCl solution, solid obtained was filtered and dried to yield 2-[(3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl]-4-[4-(piperidin-1-yl)pyrimidin-2-yl]-1,3-thiazole-5-carboxylic acid 27 mg (79%).
Reaction SMILES: [Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=4[CH3:22])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH2:23][OH:24])=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>CS(C)=O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:23]=[O:24])=[C:6]2[C:10]=1[N:9]=[C:8]1[N:11]([C:15]3[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=3[CH3:22])[CH2:12][CH2:13][CH2:14][N:7]21
Reactant: Cc1cc(Br)ccc1N1CCCn2c1nc1c(Cl)ccc(CO)c12
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: CCOC(C)=O
Solvent: CS(C)=O
Product: Cc1cc(Br)ccc1N1CCCn2c1nc1c(Cl)ccc(C=O)c12
Temperature: 25 °C
Reaction time: 1 h
Yield: 97.4 %

Procedure:
To a solution of [9-chloro-1-(4-bromo-2-methylphenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]methanol (4.68 g, 11.5 mmol) in dimethylsulfoxide (80 mL) was added Dess-Martin reagent (5.37 g, 12.7 mmol), and the mixture was stirred at room temperature for 1 h. To the reaction mixture was added Dess-Martin reagent (0.49 g, 1.15 mmol), and the mixture was stirred at room temperature for 1 h. To the reaction mixture was added Dess-Martin reagent (1.46 g, 3.45 mmol), and the mixture was stirred at room temperature for 1 h. The reaction mixture diluted with ethyl acetate, and the mixture was quenched by saturated aqueous sodium hydrogen carbonate. The solid was removed by filtration. The filtrate was extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give the title compound as a pale yellow powder (4.54 g, 11.2 mmol, 97%).
Reaction SMILES: Br[CH2:2][CH2:3][CH:4]([CH3:13])[CH2:5][CH2:6][CH2:7][C:8]([O:11][CH3:12])([CH3:10])[CH3:9].[CH3:14][S:15]([C:18]1[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=1)(=[O:17])=[O:16]>>[CH3:12][O:11][C:8]([CH3:10])([CH3:9])[CH2:7][CH2:6][CH2:5][CH:4]([CH3:13])[CH2:3][CH2:2][O:24][C:21]1[CH:20]=[CH:19][C:18]([S:15]([CH3:14])(=[O:17])=[O:16])=[CH:23][CH:22]=1
Reactant: COC(C)(C)CCCC(C)CCBr
Reactant: CS(=O)(=O)c1ccc(O)cc1
Product: COC(C)(C)CCCC(C)CCOc1ccc(S(C)(=O)=O)cc1

Procedure:
By use of the process of either Example 1(B) or 10(D), 1-bromo-7-methoxy-3,7-dimethyloctane is reacted with 4-(methylsulfonyl)phenol to yield 1-(7'-methoxy-3',7'-dimethyloctyloxy)-4-(methylsulfonyl)benzene. ##STR16##
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]([CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])=[N:8][CH:9]=1)([O-])=O.[H][H]>C(OCC)(=O)C.[Pd]>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])=[N:8][CH:9]=1
Reactant: CCOC(=O)Cc1ccc([N+](=O)[O-])cn1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CCOC(=O)Cc1ccc(N)cn1

Procedure:
Ethyl 2-(5-nitropyridin-2-yl)acetate (1.75 g, 8.33 mmol) was dissolved in ethyl acetate (20 ml) the added Pd/C (1.0 g, 9.4 mmol) and stirred under a balloon of hydrogen for 3 hrs. Filtered off the catalysts and concentrated to yield ethyl 2-(5-aminopyridin-2-yl)acetate: LC-MS: M+1=181
Reaction SMILES: [Cl-].Cl[C:3](=[N+:10]([CH3:12])[CH3:11])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH:13]1([NH2:19])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1>C(Cl)Cl>[CH:13]1([N:19]=[C:3]([C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)[N:10]([CH3:12])[CH3:11])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1
Reactant: C[N+](C)=C(Cl)c1ccccc1
Reactant: NC1CCCCC1
Agent: [Cl-]
Solvent: ClCCl
Product: CN(C)C(=NC1CCCCC1)c1ccccc1
Reaction time: 8 h
Yield: 49 %

Procedure:
To the solution of (α-chlorobenzylidene)dimethylammonium chloride in methylenechloride described in Example 1, there was added dropwise, a solution of 49.6 g (0.5 mole) of cyclohexylamine in 100 ml of methylenechloride. The temperature of the ensuing exothermal reaction rose from 24.5° to 42.5° C. thus keeping the solvent in reflux. After the reaction subsided, the reaction mixture, consisting of a slurry of white solids in a pale yellow solution, was heated to reflux with stirring. After standing overnight, the slurry was filtered, and the solution was stripped of the solvent and the oily residue distilled. The novel amidine (also called N'-cyclohexyl-N,N-dimethylbenzenecarboximidamide) was obtained as a colorless oil, boiling between 78° and 79° C. at 0.04 mm of mercury pressure and having a refractive index of nD 21.6, 1.5400, in 56.0 g corresponding to a 49% yield. Proton nmr infrared and elemental analysis confirmed its proposed structure.