Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1([C@H:9]2[CH2:13][N:12]([C@H:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH3:15])[C:11](=O)[C:10]2([F:24])[F:23])[CH2:8][CH2:7]1)=[O:5])[CH3:2].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:34])=CC=1>C1C=CC=CC=1>[CH2:1]([O:3][C:4]([C:6]1([C@H:9]2[CH2:13][N:12]([C@H:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH3:15])[C:11](=[S:34])[C:10]2([F:24])[F:23])[CH2:8][CH2:7]1)=[O:5])[CH3:2]
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: CCOC(=O)C1([C@H]2CN([C@@H](C)c3ccccc3)C(=O)C2(F)F)CC1
Solvent: c1ccccc1
Product: CCOC(=O)C1([C@H]2CN([C@@H](C)c3ccccc3)C(=S)C2(F)F)CC1
Yield: 150.7 %

Procedure:
4-(S)-(1-Ethoxycarbonylcyclopropyl)-3,3-difluoro-1-[1-(S)-phenylethyl]-2-pyrrolidone (3.621 g, 10.73 mmol) was dissolved in dry benzene (100 ml), and the solution was mixed with Lawesson's reagent (2.192 g, 5.420 mmol) and heated under reflux for 1 hour. After cooling, benzene was evaporated under reduced pressure, and the resulting residue was subjected to flash silica gel chromatography and eluted with an eluant of n-hexane:ethyl acetate=5:1, to thereby obtain 2.886 g (76.1%) of the title compound as a light yellow oil.
Reaction SMILES: [Si:1](Cl)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[OH:9][CH2:10][C@@H:11]1[CH:26]=[C:25]2[C@@H:15]([CH2:16][C:17]3[C:27]4[C:20](=[CH:21][CH:22]=[CH:23][C:24]2=4)[NH:19][CH:18]=3)[N:13]([CH3:14])[CH2:12]1.C(N(CC)CC)C.O>CN(C)C=O>[O:9]([CH2:10][C@@H:11]1[CH:26]=[C:25]2[C@@H:15]([CH2:16][C:17]3[C:27]4[C:20](=[CH:21][CH:22]=[CH:23][C:24]2=4)[NH:19][CH:18]=3)[N:13]([CH3:14])[CH2:12]1)[Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: CN1C[C@H](CO)C=C2c3cccc4[nH]cc(c34)C[C@H]21
Solvent: CCN(CC)CC
Solvent: O
Solvent: CN(C)C=O
Product: CN1C[C@H](CO[Si](C)(C)C(C)(C)C)C=C2c3cccc4[nH]cc(c34)C[C@H]21
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 96.6 %

Procedure:
Tert-butyldimethylsilyl chloride (TBS-Cl, 19.6 g) is added into a mixture of Lysergol (30 g) and triethylamine (16.7 g) in N,N-dimethylformamide (150 mL) and the mixture is stirred at room temperature for 2-3 h. The mixture is cooled and water (240 mL) is added. The resulting suspension is stirred for an additional 2 h and then filtered and washed with water. The product is dried under vacuum to give 42 g of 8β-(tert-butyldimethylsiloxymethyl)-9,10-didehydro-6-methyl-ergoline in 96.5% yield.
Reaction SMILES: [H-].[Na+].C(O)[C:4]([OH:7])=[CH:5][CH3:6].[CH2:9](Br)[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24].O.CN(C)[CH:29]=[O:30]>>[CH2:9]([O:30][CH2:29][C:5](=[CH2:6])[CH2:4][OH:7])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24]
Reactant: CN(C)C=O
Reactant: CCCCCCCCCCCCCCCCBr
Reactant: CC=C(O)CO
Agent: [H-]
Agent: [Na+]
Solvent: O
Product: C=C(CO)COCCCCCCCCCCCCCCCC
Temperature: 25 °C
Reaction time: 48 h

Procedure:
To 18.5 g of washed sodium hydride in 500 ml of dry dimethylformamide in a water bath is added dropwise, 67.4 g of 2-butene-1,2-diol. A solution of 235 g of hexadecylbromide in 100 ml of dimethylformamide is added dropwise. This mixture is stirred at room temperature for 2 days then poured into water and extracted with ether. The ether extract is separated, dried, evaporated and purified by chromatography, to give 30 g of the desired compound.
Reaction SMILES: [C:1]1([S:7][C:8]2[CH:16]=[CH:15][CH:14]=[CH:13][C:9]=2[C:10](Cl)=[O:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1(SC2C=CC=CC=2C(O)=O)C=CC=CC=1.S(Cl)(Cl)=O.[OH-].[NH4+:38]>CC(C)=O>[C:1]1([S:7][C:8]2[CH:16]=[CH:15][CH:14]=[CH:13][C:9]=2[C:10]([NH2:38])=[O:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: [NH4+]
Reactant: O=C(Cl)c1ccccc1Sc1ccccc1
Agent: O=C(O)c1ccccc1Sc1ccccc1
Agent: [OH-]
Solvent: O=S(Cl)Cl
Solvent: CC(C)=O
Product: NC(=O)c1ccccc1Sc1ccccc1

Procedure:
Following the procedure described in Example 1, 2-(phenylthio)benzoyl chloride is prepared from 0.065 mole of 2-(phenylthio)benzoic acid and excess thionyl chloride. A solution of the oily acid chloride in 50 ml. of acetone is added dropwise with stirring to 100 ml. of concentrated ammonium hydroxide. The mixture is heated to refluxing for 3 hours. On cooling, the product separates and is collected.
Reaction SMILES: Cl[C:2]([O:4][CH:5]([Cl:7])[CH3:6])=[O:3].[CH3:8][O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][O:15][CH2:16][CH2:17][O:18][CH2:19][CH2:20][O:21][CH2:22][CH2:23][O:24][CH2:25][CH2:26][OH:27].N1C=CC=CC=1>C(Cl)Cl>[C:2](=[O:3])([O:27][CH2:26][CH2:25][O:24][CH2:23][CH2:22][O:21][CH2:20][CH2:19][O:18][CH2:17][CH2:16][O:15][CH2:14][CH2:13][O:12][CH2:11][CH2:10][O:9][CH3:8])[O:4][CH:5]([Cl:7])[CH3:6]
Reactant: CC(Cl)OC(=O)Cl
Reactant: COCCOCCOCCOCCOCCOCCO
Solvent: ClCCl
Solvent: c1ccncc1
Product: COCCOCCOCCOCCOCCOCCOC(=O)OC(C)Cl

Procedure:
In a manner similar to the method described in Example 3, 1-chloroethyl chloroformate was reacted with 2,5,8,11,14,17-hexaoxanonadecan-19-ol (TCI) and pyridine in methylene chloride at −78° C. for 3 h to give 1-chloroethyl 2,5,8,11,14,17-hexaoxanonadecan-19-yl carbonate. This was then reacted with 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoic acid in the presence of cesium carbonate in dimethylformamide overnight to give, after flash chromatography purification (hexane/ethyl acetate, 80/20 to 20/80), 21-oxo-2,5,8,11,14,17,20,22-octaoxatetracosan-23-yl-4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoate as a white solid. LCMS (ES+) m/z calcd. for C47H60Cl2F2N3O13 [(M+H)+]: 982, found: 982.
Reaction SMILES: Cl[C:2]1[C:11]([N+:12]([O-:14])=[O:13])=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].Cl.[Cl:19][CH2:20][CH2:21][NH2:22].CCN(CC)CC>CO>[Cl:19][CH2:20][CH2:21][NH:22][C:2]1[C:11]([N+:12]([O-:14])=[O:13])=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16]
Reactant: NCCCl
Reactant: COC(=O)c1cc([N+](=O)[O-])c(Cl)c([N+](=O)[O-])c1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CO
Product: COC(=O)c1cc([N+](=O)[O-])c(NCCCl)c([N+](=O)[O-])c1
Temperature: 25 °C
Yield: 154.4 %

Procedure:
To a solution of methyl 4-chloro-3,5-dinitrobenzoate (D25a) (5.0 g, 19.2 mmol, 1 equiv) in MeOH (300 ml) was added 2-chloroethylamine hydrochloride (4.64 mg, 40 mmol, 2.1 equiv) and NEt3 (5.5 ml, 40 mmol, 2.1 equiv) and the resulting mixture was refluxed for 5 min then cooled to room temperature. Most of the solvent was evaporated in vacuo and the residue filtered off to give methyl 4-[(2-chloroethyl)amino]-3,5-dinitrobenzoate (D208) (9 g, 156%) as a yellow solid which was used in the next step without further purification. [M+H]+=304.1, RT=3.06 min.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1I.[Br:11][C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[SH:19].BrC1C=C(F)C=CC=1N.NC1C=CC=C(C)C=1.CC1C=CC=C(S)C=1>>[Br:11][C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[S:19][C:3]1[CH:4]=[CH:5][C:6]([O:8][CH3:9])=[CH:7][C:2]=1[Cl:1]
Reactant: Fc1ccc(S)c(Br)c1
Reactant: COc1ccc(I)c(Cl)c1
Agent: Cc1cccc(S)c1
Agent: Nc1ccc(F)cc1Br
Solvent: Cc1cccc(N)c1
Product: COc1ccc(Sc2ccc(F)cc2Br)c(Cl)c1

Procedure:
Prepared from 2-chloro-1-iodo-4-methoxy-benzene and 2-bromo-4-fluoro-benzenethiol (prepared from 2-bromo-4-fluoro-phenylamine by diazotization according to the procedure reported for the conversion of 3-toluidine to 3-thiocresol by Tarbell and Fukushima J. Am. Chem. Soc. 1946, 68, 1456-1460).
Reaction SMILES: Cl[CH2:2][C:3]([NH:5][C:6]1[C:14]2[C:9](=[CH:10][C:11]([Cl:15])=[CH:12][CH:13]=2)[NH:8][N:7]=1)=[O:4].[CH3:16][N:17]([CH3:21])[CH2:18][CH2:19][NH2:20]>C(#N)C>[Cl:15][C:11]1[CH:10]=[C:9]2[C:14]([C:6]([NH:5][C:3](=[O:4])[CH2:2][NH:20][CH2:19][CH2:18][N:17]([CH3:21])[CH3:16])=[N:7][NH:8]2)=[CH:13][CH:12]=1
Reactant: O=C(CCl)Nc1n[nH]c2cc(Cl)ccc12
Reactant: CN(C)CCN
Solvent: CC#N
Product: CN(C)CCNCC(=O)Nc1n[nH]c2cc(Cl)ccc12

Procedure:
The process is performed as in Example 75, starting with 500 mg of 2-chloro-N-(6-chloro-1H-indazol-3-yl)acetamide, 15 cm3 of acetonitrile and 0.68 cm3 of N,N-dimethylethylenediamine. The reaction medium is refluxed for 2 hours and then concentrated to dryness under reduced pressure (2 kPa; 50° C.); the crude product is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 μm; diameter 2.5 cm), eluting with a methylene chloride/methanol/aqueous ammonia mixture (95/5/1 by volume). The fractions containing the expected product are combined, concentrated under reduced pressure and then dried (90 Pa; 45° C.) to give 113 mg of N-(6-chloro-1H-indazol-3-yl)-2-[[2-(dimethylamino)ethyl]amino]acetamide in the form of a white solid melting at 104° C.
Reaction SMILES: [Cl:1][C:2]1[N:11]=[C:10](Cl)[C:9]2[CH2:8][CH2:7][CH2:6][CH:5]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)[C:4]=2[N:3]=1.[CH3:20][NH:21][CH2:22][CH3:23]>CO>[Cl:1][C:2]1[N:11]=[C:10]([N:21]([CH2:22][CH3:23])[CH3:20])[C:9]2[CH2:8][CH2:7][CH2:6][CH:5]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)[C:4]=2[N:3]=1
Reactant: Fc1ccc(C2CCCc3c(Cl)nc(Cl)nc32)cc1
Reactant: CCNC
Solvent: CO
Product: CCN(C)c1nc(Cl)nc2c1CCCC2c1ccc(F)cc1
Yield: 100.3 %

Procedure:
A solution of 2,4-dichloro-8-(4-fluorophenyl)-5,6,7,8-tetrahydroquinazoline (115 mg, 0.387 mmol) and excess N-methylethanamine (0.332 mL, 3.87 mmol) in MeOH (2 mL) was stirred at room temperature for 30 min. The solvent was removed in vacuum to afford 2-chloro-N-ethyl-8-(4-fluorophenyl)-N-methyl-5,6,7,8-tetrahydroquinazolin-4-amine (124 mg, 0.388 mmol, 100% yield). LC-MS (M+H)+=320.2.
Reaction SMILES: [Cl:1][C:2]1[CH:16]=[CH:15][C:5]([O:6][CH2:7][C:8](=[O:14])[C:9]([CH3:13])([CH3:12])[CH2:10][F:11])=[CH:4][CH:3]=1.[Br:17]Br.O>C(Cl)Cl>[Br:17][CH:7]([O:6][C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:16][CH:15]=1)[C:8](=[O:14])[C:9]([CH3:12])([CH3:13])[CH2:10][F:11]
Reactant: CC(C)(CF)C(=O)COc1ccc(Cl)cc1
Reactant: BrBr
Solvent: O
Solvent: ClCCl
Product: CC(C)(CF)C(=O)C(Br)Oc1ccc(Cl)cc1
Yield: 78.3 %

Procedure:
175 g (0.71 mol) of 1-(4-chlorophenoxy)-3,3-dimethyl-4-fluoro-2-butanone were dissolved in 500 ml of methylene chloride, and 114 g (0.71 mol) of bromine were added dropwise at 20° to 30° C., while stirring and cooling. The mixture was subsequently stirred at 20° C. for 2 hours, 200 ml of water were added carefully and the methylene chloride phase was washed several times with ice-water and dried over sodium sulphate. After distilling off the solvent in vacuo, the residue was recrystallized from cyclohexane. 180 g (78% of theory) of 1-bromo-1-(4-chlorophenoxy)-3,3-dimethyl-4-fluoro-2-butanone of melting point 73° to 75° C. were obtained. ##STR16##
Reaction SMILES: [NH2:1][CH:2]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[F:15])[C:6]2[CH:16]=[CH:17][CH:18]=[CH:19][C:5]=2[NH:4][C:3]1=[O:20].[NH:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=[C:22]1[C:30](Cl)=[O:31].C(N(CC)CC)C>C(Cl)Cl>[F:15][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[C:7]1[C:6]2[CH:16]=[CH:17][CH:18]=[CH:19][C:5]=2[NH:4][C:3](=[O:20])[CH:2]([NH:1][C:30]([C:22]2[NH:21][C:29]3[C:24]([CH:23]=2)=[CH:25][CH:26]=[CH:27][CH:28]=3)=[O:31])[N:8]=1
Reactant: O=C(Cl)c1cc2ccccc2[nH]1
Reactant: NC1N=C(c2ccccc2F)c2ccccc2NC1=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(NC1N=C(c2ccccc2F)c2ccccc2NC1=O)c1cc2ccccc2[nH]1
Reaction time: 0.17 h

Procedure:
3-(RS)-Amino-1,3-dihydro-5-(2-fluorophenyl)-2H-1,4-benzodiazepin-2-one (1.5 gm, 5.57 mmol), indole-2-carbonyl chloride (1.05 gm, 5.85 mmol) and triethylamine (0.814 ml, 5.85 mmol) were combined in CH2Cl2 (15 ml) and stirred 10 min. The reaction was concentrated and chromatographed on silica gel (5% MeOH in CH2Cl2) to give the title compound as a white solid from CH2Cl2 : (m.p. 290°-291°).
Reaction SMILES: [C:1]1(=[O:11])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3](=[O:10])[CH2:2]1.[Cl:12][C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][C:20]=1[Cl:21])[CH:16]=O>CCO.N1CCCCC1>[Cl:12][C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][C:20]=1[Cl:21])[CH:16]=[C:2]1[C:1](=[O:11])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=[O:10]
Reactant: O=Cc1ccc(Cl)c(Cl)c1
Reactant: O=C1CC(=O)c2ccccc21
Solvent: CCO
Solvent: C1CCNCC1
Product: O=C1C(=Cc2ccc(Cl)c(Cl)c2)C(=O)c2ccccc21
Yield: 85 %

Procedure:
To a solution of indan-1,3-dione (1a) (960 mg, 6.6 mmol) in EtOH (8.2 mL) was added 3,4-dichlorobenzaldehyde (1b) (1.3 g, 7.2 mmol) followed by piperidine (3 drops). The reaction mixture was heated to reflux for 30 min. After cooling, the reaction was diluted with EtOH (8 mL) and the precipitate was filtered. The resulting solid was triturated twice with EtOH and dried under high vacuum to give 2-(3,4-dichloro-benzylidene)-indane-1,3-dione (1c) (1.7 g, 82% yield).
Reaction SMILES: [Cl:1][C:2]([Cl:7])([Cl:6])[C:3](Cl)=[O:4].[CH3:8][N:9]1[CH:13]=[CH:12]N=[CH:10]1.[CH2:14](Cl)Cl>>[CH3:8][N:9]1[CH:13]=[CH:12][CH:14]=[C:10]1[C:3](=[O:4])[C:2]([Cl:7])([Cl:6])[Cl:1]
Reactant: O=C(Cl)C(Cl)(Cl)Cl
Reactant: ClCCl
Reactant: Cn1ccnc1
Product: Cn1cccc1C(=O)C(Cl)(Cl)Cl
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Under argon, 1.09 ml (12.3 mmol) of trichloroacetyl chloride are initially charged in 5 ml of DCM, and a solution of N-methylimidazole and 3 ml of DCM is added dropwise at RT over a period of 30 min. The reaction solution is allowed to stir at RT overnight and then concentrated, and the residue is purified over a flash frit (cyclohexane, cyclohexane/ethyl acetate 40:1). This gives the product as a liquid.
Reaction SMILES: I.[CH3:2][N:3]1[CH:7]=[CH:6][N:5]=[C:4]1[NH:8][C:9](SC)=[N:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.CCOCC>CC(O)(C)C>[CH3:2][N:3]1[CH:7]=[CH:6][N:5]=[C:4]1[NH:8][C:9]([N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)=[N:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: CSC(=Nc1ccccc1)Nc1nccn1C
Reactant: C1COCCN1
Agent: I
Solvent: CC(C)(C)O
Solvent: CCOCC
Product: Cn1ccnc1NC(=Nc1ccccc1)N1CCOCC1

Procedure:
A solution of 1.5 g (0.004 mole) of methyl N-(1-methylimidazol-2-yl)-N'-phenylcarbamimidothioate hydroiodide and 0.73 g (0.0084 mole) of morpholine in 30 ml of t-BuOH is refluxed overnight. Upon cooling, ether is added and morpholine hydroiodide is removed by filtration. The filtrate is taken to dryness and the residue is taken up in CH2Cl2 and converted to the free base with 3 N NaOH. The organic layer is separated, dried over K2CO3, filtered and the solvent is removed in vacuo to give a residue of N-(1-methylimidazol-2-yl)-N'-phenyl-4-morpholine carboximidamide, which is taken up in acetone and converted to the hydrochloride salt with ethereal HCl.
Reaction SMILES: CO[C:3]([C:5]1[NH:6][N:7]=[C:8]([O:10][CH2:11][C:12]2[C:13]([CH2:18][CH2:19][CH2:20][CH3:21])=[N:14][O:15][C:16]=2[CH3:17])[CH:9]=1)=[O:4].C[O:23][C:24]([C:26]1[NH:27]N=C(OCC2C(C3C=CC=CC=3)=NOC=2C)[CH:30]=1)=O.N[C@H](CO)C>>[OH:23][CH2:24][C@@H:26]([NH:27][C:3]([C:5]1[NH:6][N:7]=[C:8]([O:10][CH2:11][C:12]2[C:13]([CH2:18][CH2:19][CH2:20][CH3:21])=[N:14][O:15][C:16]=2[CH3:17])[CH:9]=1)=[O:4])[CH3:30]
Reactant: CCCCc1noc(C)c1COc1cc(C(=O)OC)[nH]n1
Reactant: COC(=O)c1cc(OCc2c(-c3ccccc3)noc2C)n[nH]1
Agent: C[C@H](N)CO
Product: CCCCc1noc(C)c1COc1cc(C(=O)N[C@@H](C)CO)[nH]n1
Yield: 6 %

Procedure:
As described for example 6, 5-(3-butyl-5-methyl-isoxazol-4-ylmethoxy)-2H-pyrazole-3-carboxylic acid methyl ester (100 mg, 0.34 mmol), instead of 5-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-2H-pyrazole-3-carboxylic acid methyl ester, was converted, using L-alaninol instead of ethanolamine, to the title compound (7 mg, 6%) which was obtained as a colorless oil. MS: m/e=337.4 [M+H]+.
Reaction SMILES: CI.[ClH:3].[CH3:4][NH:5][CH2:6][CH2:7][S:8][C:9]1[C:18]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[N:10]=1.[C:25](=O)([O-])[O-].[K+].[K+]>C(O)C>[ClH:3].[CH3:4][N:5]([CH3:25])[CH2:6][CH2:7][S:8][C:9]1[C:18]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[N:10]=1
Reactant: CNCCSc1nc2ccccc2cc1-c1ccccc1
Reactant: O=C([O-])[O-]
Agent: Cl
Agent: [K+]
Solvent: CCO
Solvent: CI
Product: CN(C)CCSc1nc2ccccc2cc1-c1ccccc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Methyl iodide (0.85 g.) was added to a mixture of 2-(2-methylaminoethylthio)-3-phenylquinoline hydrochloride (1.65 g.) and potassium carbonate (1.65 g.) in dry ethanol (50 ml.) at ambient temperature. The mixture was stirred at ambient temperature for 3 hr. and the solvent was then evaporated. The residue was dissolved in water (50 ml.) and extracted with diethyl ether (3×25 ml.). The diethyl ether extract was washed with brine (25 ml.), dried (MgSO4), and the solvent evaporated. The residual oil was chromatographed on basic alumina (75 g., Brockmann Grade III), eluted with increasing concentrations of methylene dichloride in petroleum ether. The eluate with 50% v/v methylene dichloride in petroleum ether was evaporated. The residue was dissolved in diethyl ether (25 ml.) and ethereal hydrogen chloride added until precipitation was complete. The mixture was filtered and the solid residue was crystallised from methanol-ethyl acetate to give 2-(2-dimethylaminoethylthio)-3-phenylquinoline hydrochloride, m.p. 196°-8°.
Reaction SMILES: [F:1][C:2]([F:40])([F:39])[C:3]1[CH:38]=[CH:37][C:6]2=[N:7][N:8]([C:10]3[CH:11]=[C:12]([CH:19]=[C:20]([C:23]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH3:24])[C:21]=3[OH:22])[CH2:13][CH2:14][C:15]([O:17]C)=[O:16])[N:9]=[C:5]2[CH:4]=1.Cl>[OH-].[Na+]>[F:39][C:2]([F:1])([F:40])[C:3]1[CH:38]=[CH:37][C:6]2=[N:7][N:8]([C:10]3[CH:11]=[C:12]([CH:19]=[C:20]([C:23]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[CH3:24])[C:21]=3[OH:22])[CH2:13][CH2:14][C:15]([OH:17])=[O:16])[N:9]=[C:5]2[CH:4]=1
Reactant: COC(=O)CCc1cc(-n2nc3ccc(C(F)(F)F)cc3n2)c(O)c(C(C)(c2ccccc2)c2ccccc2)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: CC(c1ccccc1)(c1ccccc1)c1cc(CCC(=O)O)cc(-n2nc3ccc(C(F)(F)F)cc3n2)c1O

Procedure:
The title compound is prepared by refluxing the compound prepared in Example 29 in aqueous sodium hydroxide solution followed by neutralization with aqueous hydrochloric acid.
Reaction SMILES: [CH3:1][S:2][C:3]1[N:8]=[CH:7][N:6]=[C:5]([O:9][C:10]2[CH:15]=[CH:14][C:13]([NH2:16])=[CH:12][CH:11]=2)[CH:4]=1.[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([N:24]=[C:25]=[O:26])=[CH:20][C:19]=1[C:27]([F:30])([F:29])[F:28]>C1COCC1>[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([NH:24][C:25]([NH:16][C:13]2[CH:14]=[CH:15][C:10]([O:9][C:5]3[CH:4]=[C:3]([S:2][CH3:1])[N:8]=[CH:7][N:6]=3)=[CH:11][CH:12]=2)=[O:26])=[CH:20][C:19]=1[C:27]([F:28])([F:29])[F:30]
Reactant: CSc1cc(Oc2ccc(N)cc2)ncn1
Reactant: O=C=Nc1ccc(Cl)c(C(F)(F)F)c1
Solvent: C1CCOC1
Product: CSc1cc(Oc2ccc(NC(=O)Nc3ccc(Cl)c(C(F)(F)F)c3)cc2)ncn1
Reaction time: 8 h
Yield: 71.2 %

Procedure:
A solution of 4-(6-methylsulfanyl-pyrimidin-4-yloxy)-phenylamine (1.3 g, 5.5 mmol) in THF (24 ml) is cooled to 0° C. A solution of 4-chloro-3-(trifluoromethyl)phenyl isocyanate (1.22 g, 5.5 mmol) in THF (24 ml) is added dropwise and stirring is continued overnight at r.t. The solvent is evaporated and the crude product is purified by silica gel chromatography using an ethyl acetate/heptane eluent (1:1) to give 1.78 g (70%) of a white solid.
Reaction SMILES: [C:1]([NH:5][S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1B(O)O)(=[O:8])=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:19]1[CH:24]=[CH:23][C:22]([C:25](=[O:27])[CH3:26])=[C:21]([F:28])[CH:20]=1>>[C:25]([C:22]1[CH:23]=[CH:24][C:19]([C:10]2[C:9]([S:6]([NH:5][C:1]([CH3:4])([CH3:3])[CH3:2])(=[O:8])=[O:7])=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:20][C:21]=1[F:28])(=[O:27])[CH3:26]
Reactant: CC(C)(C)NS(=O)(=O)c1ccccc1B(O)O
Reactant: CC(=O)c1ccc(Br)cc1F
Product: CC(=O)c1ccc(-c2ccccc2S(=O)(=O)NC(C)(C)C)cc1F

Procedure:
The title compound was prepared using conditions analogous to those described in Example 1 using (2-(N-(tert-butyl)sulfamoyl)phenyl)boronic acid and 1-(4-bromo-2-fluorophenyl)ethanone. 1H NMR (500 MHz, CDCl3) δ 8.19 (dd, J=7.9, 1.3, 1H), 7.95 (m, 1H), 7.63-7.57 (m, 1H), 7.57-7.52 (m, 1H), 7.38-7.30 (m, 2H), 7.28 (dd, J=7.5, 1.3, 1H), 2.70 (d, J=4.9, 3H), 1.05 (m, 9H).
Reaction SMILES: I[CH2:2][CH2:3][N:4]1[CH:8]=[CH:7][N:6]=[C:5]1[N+:9]([O-:11])=[O:10].C[O-].[Na+]>CO>[N+:9]([C:5]1[N:4]([CH:3]=[CH2:2])[CH:8]=[CH:7][N:6]=1)([O-:11])=[O:10]
Reactant: O=[N+]([O-])c1nccn1CCI
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: C=Cn1ccnc1[N+](=O)[O-]
Yield: 91.5 %

Procedure:
206 g of 1-(2-iodoethyl)-2-nitroimidazole were boiled under reflux for 1 hour in a solution of 41 g of sodium methylate in 2 liters of methanol. The solution was evaporated under reduced pressure and the residue was taken up with 2 liters of ethyl acetate and 1 liter of water. The organic phase was washed twice with 0.5 liters of 10% sodium chloride solution each time and evaporated to dryness. After recrystallization from diisopropyl ether, the residue yielded 98.2 g of 2-nitro-1-vinyl-imidazole, m.p. 64°-66° C.
Reaction SMILES: [NH:1]1[CH:5]=[C:4]([CH2:6][CH2:7][CH2:8][C:9]([OH:11])=O)[N:3]=[N:2]1.Cl.[NH2:13][CH2:14][CH:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][CH2:24][C:25]2[CH:30]=[C:29]([Cl:31])[CH:28]=[C:27]([Cl:32])[CH:26]=2)=[O:22])[CH2:17][CH2:16]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[NH:3]1[C:4]([CH2:6][CH2:7][CH2:8][C:9]([NH:13][CH2:14][CH:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][CH2:24][C:25]3[CH:26]=[C:27]([Cl:32])[CH:28]=[C:29]([Cl:31])[CH:30]=3)=[O:22])[CH2:17][CH2:16]2)=[O:11])=[CH:5][N:1]=[N:2]1
Reactant: O=C(O)CCCc1c[nH]nn1
Reactant: NCC1CCN(C(=O)OCc2cc(Cl)cc(Cl)c2)CC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Product: O=C(CCCc1cnn[nH]1)NCC1CCN(C(=O)OCc2cc(Cl)cc(Cl)c2)CC1

Procedure:
A mixture comprising of 4-(1H-1,2,3-triazol-4-yl)butanoic acid (Example 17, step 4) (65.8 mg, 0.424 mmol), 3,5-dichlorobenzyl 4-(aminomethyl)piperidine-1-carboxylate hydrochloride (step 2) (100 mg, 0.283 mmol), HATU (215 mg, 0.565 mmol) and TEA (197 μl, 1.414 mmol) in DMF (942 μl) was stirred at room temperature for 3 hours. Purification was carried out using preparative LC-MS under low pH conditions. The resulting product fractions were concentrated under reduced pressure to give aqueous solutions which were extracted with ethyl acetate. The organic extracts were dried over MgSO4, filtered and concentrated under reduced pressure to afford the title compound;