Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(C1N=C(N2CCC(F)(F)C2)C2N=NN(CC)C=2N=1)(C)(C)C.[C:23]([C:27]1[N:28]=[C:29]([N:36]2[CH2:42][C:38]3([CH2:41][O:40][CH2:39]3)[CH2:37]2)[C:30]2[N:35]=[N:34][NH:33][C:31]=2[N:32]=1)([CH3:26])([CH3:25])[CH3:24].Cl[CH2:44][C:45]1[O:49][N:48]=[C:47]([CH3:50])[N:46]=1>>[C:23]([C:27]1[N:28]=[C:29]([N:36]2[CH2:37][C:38]3([CH2:39][O:40][CH2:41]3)[CH2:42]2)[C:30]2[N:35]=[N:34][N:33]([CH2:44][C:45]3[O:49][N:48]=[C:47]([CH3:50])[N:46]=3)[C:31]=2[N:32]=1)([CH3:26])([CH3:24])[CH3:25]
Reactant: Cc1noc(CCl)n1
Reactant: CC(C)(C)c1nc(N2CC3(COC3)C2)c2nn[nH]c2n1
Agent: CCn1nnc2c(N3CCC(F)(F)C3)nc(C(C)(C)C)nc21
Product: Cc1noc(Cn2nnc3c(N4CC5(COC5)C4)nc(C(C)(C)C)nc32)n1

Procedure:
In analogy to the procedure described for the synthesis of 5-tert-butyl-7-(3,3-difluoropyrrolidin-1-yl)-3-ethyl-3H-[1,2,3]triazolo[4,5-d]pyrimidine (example 61), the title compound was prepared from 5-tert-Butyl-7-(2-oxa-6-aza-spiro[3.3]hept-6-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and 5-(chloromethyl)-3-methyl-1,2,4-oxadiazole and isolated as light-red solid. MS(m/e): 371.2 (MH+).
Reaction SMILES: [CH2:1]([NH:8][C:9](=[O:28])[C@@H:10]([CH2:19][O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[NH:11]C(OC(C)(C)C)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClCCl.FC(F)(F)C(O)=O.[OH-].[Na+]>O>[CH2:1]([NH:8][C:9](=[O:28])[C@@H:10]([CH2:19][O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[NH2:11])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)N[C@H](COCc1ccccc1)C(=O)NCc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: N[C@H](COCc1ccccc1)C(=O)NCc1ccccc1
Reaction time: 2 h
Yield: 93 %

Procedure:
To a solution of N-benzyl-O-benzyl-N2-Boc-D-serinamide (16 g) and dichloromethane (80 mL), trifluoroacetic acid (80 mL) was added. The solution was stirred for 2 hours and the reaction was monitored for completion of reaction. The solution was concentrated under vacuum to obtain solid which was dissolved in water. The aqueous solution was basified to pH 8-10 with 5% sodium hydroxide and was extracted with ethyl acetate. The organic layer was separated and washed with a brine solution. The organic layer was concentrated under vacuum to obtain an oily residue 11 g of N-benzyl-O-benzyl-D-serinamide.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([C:15]([OH:17])=O)[CH2:10][O:11][CH2:12][CH:13]=[CH2:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:19][O:20][C:21](=[O:24])[CH2:22][NH2:23].C(N(CC)C(C)C)(C)C.C1C=C2N=NN(O)C2=CC=1.O.CCN=C=NCCCN(C)C.Cl>CN(C=O)C>[CH3:19][O:20][C:21](=[O:24])[CH2:22][NH:23][C:15](=[O:17])[C@H:9]([CH2:10][O:11][CH2:12][CH:13]=[CH2:14])[NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7]
Reactant: C=CCOC[C@H](NC(=O)OC(C)(C)C)C(=O)O
Reactant: COC(=O)CN
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: C=CCOC[C@H](NC(=O)OC(C)(C)C)C(=O)NCC(=O)OC
Temperature: 0 °C
Reaction time: 1 h
Yield: 83.7 %

Procedure:
Purified N-tert-butoxycarbonyl O-allyl L-serine 3 (6.94 g, 28.3 mmol) was dissolved in 30 mL DMF and the solution cooled to 0° C. (icebath). Glycine methyl ester hydrochloride (3.55 g, 28.3 mmol) was suspended in 10 mL DMF and N,N-diisopropylethyl amine (3.66 g, 28.3 mmol) added. The suspension was then added in one portion to the solution of 3 together with an additional 5 mL DMF. HOBt hydrate (4.33 g, 28.3 mmol) was added. Finally, EDC hydrochloride (5.97 g, 31.1 mmol) was added together with an additional 10 mL DMF. The reaction mixture was stirred at 0° C. for 1 hour. In total the reaction mixture was stirred for 24 hours before the solvent was evaporated. The residue was taken up in 150 mL EtOAc and washed with 1 M aqueous H2SO4 (3×100 mL), 7.5% (w/w) aqueous K2CO3 (3×100 mL) and finally saturated brine (100 mL). The solution was dried with anhydrous MgSO4 and the solvent evaporated affording a clear and slightly greenish/yellowish liquid (7.49 g, 84%); δH (200 MHz; d6-DMSO) 8.31 (1H, t, J 6, NH(Gly)), 6.85 (1H, d, J 8, NH(Ser(All))), 5.86 (1H, ddt, J 5, 11 and 17, CH═CH2), 5.29-5.11 (2H, m, CH═CH2), 4.22 (1H, ddd, J 8 and 12, CαH(Ser(All))), 3.94 (2H, dt, J 1 and 5, CH2CH═CH2), 3.86 (1H, d, J 6, CαHH(Gly)), 3.83 (1H, d, J 6, CαHH(Gly)), 3.62 (3H, s, OCH3), 3.56-3.44 (2H, m, CH2), 1.38 (9H, s, (CH3)3); δC (50 MHz; d6-DMSO) 170.3, 170.0, 155.1, 134.9, 116.3, 78.2, 70.9, 69.6, 54.1, 51.6, 40.5, 28.1; m/z (ESI) 339.1541 ([M+Na]+; C14H24N2O6Na requires 339.1532)
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([C:13]([NH2:15])=[O:14])[C:8](=[O:16])[CH2:7]2)([O-])=O.[H][H]>[Pd].CN(C)C=O>[NH2:1][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([C:13]([NH2:15])=[O:14])[C:8](=[O:16])[CH2:7]2
Reactant: NC(=O)N1C(=O)Cc2cc([N+](=O)[O-])ccc21
Reactant: [H][H]
Agent: [Pd]
Solvent: CN(C)C=O
Product: NC(=O)N1C(=O)Cc2cc(N)ccc21

Procedure:
To a solution of 5.0 g. of 5-nitro-2-oxindole-1-carboxamide in 110 ml. of N,N-dimethylformamide was added 0.5 g. of 10% palladium-on-carbon, and the resulting mixture was shaken under an atmosphere of hydrogen at an initial pressure of 5 kg/cm2 until hydrogen uptake ceased. The catalyst was removed by filtration, and the filtrate was diluted with brine and extracted with ethyl acetate. The extracts were dried (MgSO4) and evaporated in vacuo to give a dark-colored oil which solidified after trituration under water. This afforded 3.0 g. of the title compound as a yellow solid, mp 189°-191° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH:11]([C:22]2[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=2[F:29])[C:12]2[C:13]([CH3:21])=[CH:14][C:15]([C:18](O)=[O:19])=[N:16][CH:17]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.Cl.CN.O[N:34]1[C:38]2C=CC=CC=2N=N1.CN1CCOCC1.Cl.C(N=C=NCCCN(C)C)C>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([CH:11]([C:22]2[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=2[F:29])[C:12]2[C:13]([CH3:21])=[CH:14][C:15]([C:18]([NH:34][CH3:38])=[O:19])=[N:16][CH:17]=2)(=[O:10])=[O:9])=[CH:6][CH:7]=1
Reactant: Cc1cc(C(=O)O)ncc1C(c1cc(F)ccc1F)S(=O)(=O)c1ccc(Cl)cc1
Reactant: On1nnc2ccccc21
Agent: CCN=C=NCCCN(C)C
Agent: CN
Agent: Cl
Solvent: ClCCl
Solvent: CN1CCOCC1
Product: CNC(=O)c1cc(C)c(C(c2cc(F)ccc2F)S(=O)(=O)c2ccc(Cl)cc2)cn1
Temperature: 25 °C
Reaction time: 5 h
Yield: 80 %

Procedure:
To a solution of 5-[[(4-chlorophenyl)sulfonyl](2,5-difluorophenyl)methyl]-4-methylpyridine-2-carboxylic acid (88 mg, 0.20 mmol) in methylene chloride (2 ml), methylamine hydrochloride (15 mg, 0.22 mmol), 1-hydroxybenzotriazole (30 mg, 0.22 mmol), 4-methylmorpholine (0.048 ml, 0.44 mmol), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (42 mg, 0.22 mmol) were added at room temperature. After stirring for 5 hours at room temperature, the reaction mixture was washed with saturated aqueous sodium hydrogencarbonate. The organic layer was dried over anhydrous sodium sulfate and filtered, then the filtrate was concentrated under reduced pressure, and the resulting residue was subjected to flash silica gel chromatography. The fraction obtained from an elution with hexane:ethyl acetate=3:1 was concentrated under reduced pressure, and the resulting residue was washed with a mixed solvent of diethyl ether and hexane and then collected by filtration to obtain the title compound (73 mg, 0.16 mmol, 81%) as a white solid.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[CH:8][C:7]([S:10](=[O:20])(=[O:19])[NH:11][C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1.Br[CH2:23][CH:24]([CH3:26])[CH3:25].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CCOC(C)=O>[CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[CH:8][C:7]([S:10](=[O:20])(=[O:19])[N:11]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[CH2:23][CH:24]([CH3:26])[CH3:25])=[CH:6][CH:5]=1
Reactant: COC(=O)c1ccc(S(=O)(=O)Nc2ccc(F)cc2)cc1
Reactant: CC(C)CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COC(=O)c1ccc(S(=O)(=O)N(CC(C)C)c2ccc(F)cc2)cc1
Temperature: 90 °C
Yield: 143.2 %

Procedure:
A mixture of 4-(4-fluoro-phenylsulfamoyl)-benzoic acid methyl ester (1.00 g, 3.23 mmol), 1-bromo-2-methyl propane (527 μL, 4.85 mmol), and K2CO3 (891 mg, 6.46 mmol) in DMF (10 mL) was heated at 90° C. for 18 hours. The cooled mixture was diluted with EtOAc, washed with water and brine, dried over Na2SO4 and concentrated under vacuum. Purification by silica gel column chromatography (0-50% EtOAc in cyclohexane) gave 4-[(4-fluoro-phenyl)-isobutyl-sulfamoyl]-benzoic acid methyl ester (1.69 g, 77%). 1H NMR (300 MHz, CDCl3) δ 8.12 (d, J=8.3 Hz, 2H), 7.63 (d, J=8.3 Hz, 2H), 6.99 (d, J=6.5 Hz, 4H), 3.96 (s, 3H), 3.31 (d, J=7.3 Hz, 2H), 1.58-1.56 (m, 1H), 0.92 (d, J=6.7 Hz, 6H). LCMS (m/z, Method A) ES+ 366.1 [M+1]+.
Reaction SMILES: [NH2:1][C:2]1[C:3](=[O:35])[N:4]([CH2:14][C:15]([NH:17][CH:18]([CH:32]([CH3:34])[CH3:33])[CH:19]([O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])[C:20]([F:23])([F:22])[F:21])=[O:16])[C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[CH:6][CH:7]=1.[CH2:36]([N:43]=[C:44]=[O:45])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.C(N(CC)CC)C>O1CCCC1.C(OCC)(=O)C.Cl>[Si:25]([O:24][CH:19]([C:20]([F:23])([F:21])[F:22])[CH:18]([NH:17][C:15](=[O:16])[CH2:14][N:4]1[C:5]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)=[CH:6][CH:7]=[C:2]([NH:1][C:44]([NH:43][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[O:45])[C:3]1=[O:35])[CH:32]([CH3:33])[CH3:34])([C:28]([CH3:29])([CH3:30])[CH3:31])([CH3:27])[CH3:26]
Reactant: CC(C)C(NC(=O)Cn1c(-c2ccccc2)ccc(N)c1=O)C(O[Si](C)(C)C(C)(C)C)C(F)(F)F
Reactant: O=C=NCc1ccccc1
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CC(C)C(NC(=O)Cn1c(-c2ccccc2)ccc(NC(=O)NCc2ccccc2)c1=O)C(O[Si](C)(C)C(C)(C)C)C(F)(F)F
Reaction time: 18 h
Yield: 78 %

Procedure:
R=benzylaminocarbonyl: To a solution of 2-(3-amino-2-oxo-6-phenyl-1,2-dihydro-1-pyridyl)-N-(2-tert-butyldimethylsilyloxy-3,3,3-trifluoro-1-isopropylpropyl)acetamide (300 mg) in dry tetrahydrofuran (10 mL) was added benzyl isocyanate (86 mg). After 20 h triethyl amine (65 mg) and benzyl isocyanate (43 mg) were added. After another 18 h the reaction mixture was diluted with ethyl acetate and 10% hydrochloric acid. The organic portion was separated, washed with 10% hydrochloric acid and brine, and evaporated to give a crude oil. The reaction was found to be incomplete. To a solution of the recovered oil in dry tetrahydrofuran (6 mL) was added triethyl amine (80 mg) and benzyl isocyanate (86 mg). The solution was heated under reflux for 6 h and stirred 18 h. The reaction mixture was diluted with ethyl acetate; washed with saturated aqueous sodium bicarbonate, 10% hydrochloric acid and brine; dried; evaporated; and dried under vacuum to give a crude solid. Purification by chromatography, eluting with ethanol:ethyl acetate:dichloromethane (0.25:3:96.75 ), gave N-(2-tert-butyldimethylsilyloxy-3,3,3-trifluoro-1-isopropylpropyl)-2-[2-oxo-6-phenyl-3-(3-benzylureido)-1,2-dihydro-1-pyridyl]acetamide (295 mg); TLC: Rf =0.20, ethanol:ethyl acetate:dichloromethane (0.5:4:95.5); MS: m/z=645(M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:16]=[CH:15][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([NH:13][CH3:14])=[CH:9][N:8]=2)=[C:4]([CH3:17])[CH:3]=1.C(N(CC)CC)C.[Cl:25][C:26]1[CH:34]=[CH:33][CH:32]=[C:31]([Cl:35])[C:27]=1[C:28](Cl)=[O:29]>C(Cl)Cl>[Cl:25][C:26]1[CH:34]=[CH:33][CH:32]=[C:31]([Cl:35])[C:27]=1[C:28]([N:13]([C:10]1[CH:9]=[N:8][C:7]([O:6][C:5]2[CH:15]=[CH:16][C:2]([Cl:1])=[CH:3][C:4]=2[CH3:17])=[CH:12][CH:11]=1)[CH3:14])=[O:29]
Reactant: CNc1ccc(Oc2ccc(Cl)cc2C)nc1
Reactant: O=C(Cl)c1c(Cl)cccc1Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1cc(Cl)ccc1Oc1ccc(N(C)C(=O)c2c(Cl)cccc2Cl)cn1
Temperature: 22 °C
Reaction time: 18 h

Procedure:
2-(4-Chloro-2-methyl-phenoxy)-5-(N-methylamino)pyridine (32 mg, 0.13 mmol) dissolved in methylene chloride (0.25 mL) was treated with triethylamine (0.026 mL, 0.18 mmol) followed by a solution of 2,6-dichlorobenzoyl chloride (31 mg, 0.15 mmol) dissolved in methylene chloride (0.15 mL). The reaction mixture was shaken at 22° C. for 18 hours followed by quenching with saturated aqueous NH4Cl and stirring for an additional 5 hours. The organic layer was separated and dried over Na2SO4 then concentrated in vacuo. The crude product was purified by chromatography on SiO2 using 1:1 ethyl acetate/hexane as eluent. MS (m/z): 422/424 (M+H)+; C20H15N2O2Cl3 requires 422.
Reaction SMILES: [N:1]([CH3:4])=[C:2]=[O:3].[NH2:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][CH2:13][N:14]2[CH2:19][CH2:18][CH:17]([NH:20][C:21]3[N:25]([CH2:26][C:27]4[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=4)[C:24]4[CH:34]=[CH:35][CH:36]=[CH:37][C:23]=4[N:22]=3)[CH2:16][CH2:15]2)=[CH:8][CH:7]=1>O1CCCC1>[F:33][C:30]1[CH:29]=[CH:28][C:27]([CH2:26][N:25]2[C:24]3[CH:34]=[CH:35][CH:36]=[CH:37][C:23]=3[N:22]=[C:21]2[NH:20][CH:17]2[CH2:16][CH2:15][N:14]([CH2:13][CH2:12][C:9]3[CH:10]=[CH:11][C:6]([NH:5][C:2]([NH:1][CH3:4])=[O:3])=[CH:7][CH:8]=3)[CH2:19][CH2:18]2)=[CH:32][CH:31]=1
Reactant: CN=C=O
Reactant: Nc1ccc(CCN2CCC(Nc3nc4ccccc4n3Cc3ccc(F)cc3)CC2)cc1
Solvent: C1CCOC1
Product: CNC(=O)Nc1ccc(CCN2CCC(Nc3nc4ccccc4n3Cc3ccc(F)cc3)CC2)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 39.9 %

Procedure:
A mixture of 0.6 parts of isocyanatomethane, 4.43 parts of N-[1-[2-(4-aminophenyl)ethyl]-4-piperidinyl]-1-(4-fluorophenylmethyl)-1H-benzimidazol-2-amine and 135 parts of tetrahydrofuran was stirred for 3 hours at room temperature. The precipitated product was filtered off and crystallized from acetonitrile, yielding 2 parts (39.9%) of N-[4-[2-[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]-1-piperidinyl]ethyl]phenyl]-N'methylurea; mp. +300° C. (compound 57).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=2)[CH:5]=[CH:6][C:7]=1[CH:8]=O.Cl.[NH2:18][OH:19]>>[F:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=2)[CH:5]=[CH:6][C:7]=1[CH:8]=[N:18][OH:19]
Reactant: O=Cc1ccc(-c2ccc(O)cc2)cc1F
Reactant: NO
Agent: Cl
Product: ON=Cc1ccc(-c2ccc(O)cc2)cc1F

Procedure:
The title compound was prepared by reacting 3-fluoro-4′-hydroxy-1,1′-biphenyl-4-carbaldehyde (154 mg, 0.713 mmol) with hydroxylamine hydrochloride (99 mg, 1.43 mmol) according to Method C to yield 156 mg (95%) of yellowish solid: mp 181-183° C.; 1H NMR (DMSO-d6): δ 6.84-6.87 (2H, m), 7.48-7.53 (2H, m), 7.57-7.60 (2H, m), 7.76 (1H, t, J=8.14 Hz), 8.22 (1H, s), 9.74 (1H, s), 11.56 (1H, s); MS (ESI) m/z 230 (M−H)−, 232 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[C:3]2[N:4]([C:8](=[S:28])[NH:9][C:10]=2[C:11]2[C:20]([F:21])=[C:19]3[C:14]([CH:15]=[CH:16][C:17]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[N:18]3)=[CH:13][CH:12]=2)[CH:5]=[CH:6][N:7]=1.Cl[C:30]1[N:35]=[CH:34][CH:33]=[CH:32][N:31]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[F:21][C:20]1[C:11]([C:10]2[N:9]=[C:8]([S:28][C:30]3[N:35]=[CH:34][CH:33]=[CH:32][N:31]=3)[N:4]3[CH:5]=[CH:6][N:7]=[C:2]([NH2:1])[C:3]=23)=[CH:12][CH:13]=[C:14]2[C:19]=1[N:18]=[C:17]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH:16]=[CH:15]2
Reactant: Nc1nccn2c(=S)[nH]c(-c3ccc4ccc(-c5ccccc5)nc4c3F)c12
Reactant: Clc1ncccn1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Nc1nccn2c(Sc3ncccn3)nc(-c3ccc4ccc(-c5ccccc5)nc4c3F)c12
Temperature: 100 °C
Reaction time: 0.17 h

Procedure:
A 10 mL microwave vessel was charged with a solution of 8-amino-1-(8-fluoro-2-phenyl-quinolin-7-yl)-2H-imidazo[1,5-a]pyrazine-3-thione (10 mg, 0.00002 mol), 2-chloropyrimidine (0.0059 g, 0.000052 mol) and potassium carbonate (0.011 g, 0.000077 mol) in DMF. The reaction mixture was heated in the microwave at 100° C. for 10 min followed by 120° C. for 10 min to get full consumption of SM. The reaction mixture was concentrated in vacuo. Purification by Gilson HPLC eluting with 10→60% acetonitrile: H2O afforded the title compound as a light yellow solid. 1H NMR (400 MHz, CDCl3): δ=7.07 (t, J=4.93 Hz, 1H), 7.21 (d, J=5.05 Hz, 1H), 7.48-7.59 (m, 4H), 7.74-7.85 (m, 2H), 8.04 (d, J=8.59 Hz, 1H), 8.25 (dd, J=8.21, 1.39 Hz, 2H), 8.31 (dd, J=8.72, 1.39 Hz, 1H), 8.50 (d, J=4.80 Hz, 2H). MS(ES+): m/z 465.98 (100)[MH+]. HPLC: tR=2.75 min (Open Lynx polar—5 min).
Reaction SMILES: Br[C:2]1[N:3]=[C:4]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[C:29]([F:32])([F:31])[F:30])[N:5]([C:7]2[CH:12]=[CH:11][C:10]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([S:19]([CH3:22])(=[O:21])=[O:20])[CH:14]=3)=[CH:9][CH:8]=2)[CH:6]=1.[NH:33]1[CH2:36][CH2:35][CH2:34]1.N1CCC[C@H]1C(O)=O.[C:45]([O-:48])([O-])=[O:46].[Cs+].[Cs+]>[Cu]I.CN(C=O)C>[C:45]([OH:48])([C:29]([F:32])([F:31])[F:30])=[O:46].[N:33]1([C:2]2[N:3]=[C:4]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[C:29]([F:31])([F:30])[F:32])[N:5]([C:7]3[CH:8]=[CH:9][C:10]([C:13]4[CH:18]=[CH:17][CH:16]=[C:15]([S:19]([CH3:22])(=[O:21])=[O:20])[CH:14]=4)=[CH:11][CH:12]=3)[CH:6]=2)[CH2:36][CH2:35][CH2:34]1
Reactant: C1CNC1
Reactant: CS(=O)(=O)c1cccc(-c2ccc(-n3cc(Br)nc3-c3ccccc3C(F)(F)F)cc2)c1
Reactant: O=C([O-])[O-]
Agent: [Cu]I
Agent: O=C(O)[C@@H]1CCCN1
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CS(=O)(=O)c1cccc(-c2ccc(-n3cc(N4CCC4)nc3-c3ccccc3C(F)(F)F)cc2)c1
Product: O=C(O)C(F)(F)F
Temperature: 120 °C
Yield: 52.3 %

Procedure:
4-bromo-1-(3′-(methylsulfonyl)biphenyl-4-yl)-2-(2-(trifluoromethyl)phenyl)-1H-imidazole (188 mgs, 0.361 mmol), azetidine (0.4 mL 5.94 mmol), L-proline (50 mg, 0.434 mmol), Cs2CO3 (517 mg, 1.44 mmol), 2.5 mL anhydrous DMF, and CuI (69 mg, 362 mmol) were added to a 5 mL microwave tube and sealed. The tube was purged with an argon balloon for five minutes. The reaction was heated at 120° C. for 24 h and then cooled to room temperature. The crude reaction mixture was purified directly by HPLC using water: TFA: acetonitrile as eluents to afford 4-(azetidin-1-yl)-1-(3′-(methylsulfonyl)biphenyl-4-yl)-2-(2-(trifluoromethyl)phenyl)-1H-imidazole (47 mgs, 26%) as a light yellow solid. 1H-NMR (DMSO, 400 MHz) δ 8.12-8.11 (m, 1H), 8.02-7.99 (m, 1H), 7.91-7.88 (m, 1H), 7.82-7.80 (m, 1H), 7.76 (d, J=8.60 Hz, 2H), 7.73-7.69 (m, 1H), 7.65-7.62 (m, 2H), 7.46-7.44 (m, 1H), 7.23 (d, J=8.60 Hz, 2H), 6.77 (s, 1H), 3.74 (t, J=7.34 Hz, 4H), 3.28 (s, 3H), 2.33-2.25 (m, 2H); MS (ES): 498.3 [M+H]+.
Reaction SMILES: C(OC([C:6]1[CH:38]=[CH:37][CH:36]=C[C:7]=1[O:8][C:9]1[C:23]([O:24][C:25]2[CH:30]=[CH:29][C:28]([S:31]([CH3:34])(=[O:33])=[O:32])=[CH:27][CH:26]=2)=[CH:22][C:12]2[NH:13][C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=3)=[N:15][C:11]=2[CH:10]=1)=O)C.OC1C=CC=C[N:41]=1>>[N:41]1[CH:36]=[CH:37][CH:38]=[CH:6][C:7]=1[O:8][C:9]1[C:23]([O:24][C:25]2[CH:26]=[CH:27][C:28]([S:31]([CH3:34])(=[O:32])=[O:33])=[CH:29][CH:30]=2)=[CH:22][C:12]2[NH:13][C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=3)=[N:15][C:11]=2[CH:10]=1
Reactant: Oc1ccccn1
Reactant: CCOC(=O)c1ccccc1Oc1cc2nc(-c3ccccn3)[nH]c2cc1Oc1ccc(S(C)(=O)=O)cc1
Product: CS(=O)(=O)c1ccc(Oc2cc3[nH]c(-c4ccccn4)nc3cc2Oc2ccccn2)cc1

Procedure:
The entitled compound was obtained as a brown solid in the same method as in Example 14 or in accordance with the method or by combining it with an ordinary method but using 5-fluoro-4-(4-methanesulfonyl-phenoxy)-2-nitro-phenylamine obtained in Example 14 and 2-hydroxypyridine.
Reaction SMILES: [BH4-].[Na+].C[O:4][C:5](=O)[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:12][N:13]([CH2:22][CH2:23][CH2:24][O:25][C:26]2[CH:27]=[C:28]3[C:33](=[CH:34][CH:35]=2)[N:32]([CH3:36])[C:31](=[O:37])[CH:30]=[CH:29]3)[CH2:14][CH2:15][C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)[CH:7]=1.CO.[ClH:41]>C(OCC)(=O)C.O>[ClH:41].[ClH:41].[OH:4][CH2:5][C:6]1[CH:7]=[C:8]([CH:9]=[CH:10][CH:11]=1)[CH2:12][N:13]([CH2:22][CH2:23][CH2:24][O:25][C:26]1[CH:27]=[C:28]2[C:33](=[CH:34][CH:35]=1)[N:32]([CH3:36])[C:31](=[O:37])[CH:30]=[CH:29]2)[CH2:14][CH2:15][C:16]1[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=1
Reactant: COC(=O)c1cccc(CN(CCCOc2ccc3c(ccc(=O)n3C)c2)CCc2cccnc2)c1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CO
Product: Cn1c(=O)ccc2cc(OCCCN(CCc3cccnc3)Cc3cccc(CO)c3)ccc21
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
Sodium borohydride (16.5 mg) was added to a THE solution (4 ml) of 3-{[N-[3-(1-methyl-2-oxo-1,2-dihydroquinolin-6-yloxy)propyl]-N-(2-pyridin-3-ylethyl)amino]methyl}benzoic acid methyl ester (192 mg). Methanol (1 ml) was added to the mixture and stirred for 1.5 hour while heated under reflux. The reaction liquid was cooled to room temperature. Water was added to the reaction mixture, followed by extraction with dichloromethane. The organic layer was dried over anhydrous sodium sulfate. The filtrate was condensed under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:methanol=10:1→4:1). The purified product was condensed under reduced pressure. A 4N-hydrogen chloride in ethyl acetate solution (0.082 ml) was added to a ethyl acetate solution (1 ml) of the residue, and the liquid was stirred at room temperature. The precipitated insoluble matter was separated, washed with ether, and dried to give the title compound (53.4 mg) as a white powder.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([O:8][CH2:9][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][CH2:24][CH2:25][CH3:26])[N:5]=[C:4]([O:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH3:45])[N:3]=1.ClC1N=C(OCCCCCCCCCCCC)N=C(OCCCCCCCCCCCC)N=1.[C:79]1([C:85]2[CH:91]=[C:90]([OH:92])[CH:89]=[C:88]([C:93]3[CH:98]=[CH:97][CH:96]=[CH:95][CH:94]=3)[C:86]=2[OH:87])[CH:84]=[CH:83][CH:82]=[CH:81][CH:80]=1>>[OH:87][C:86]1[C:85]([C:79]2[CH:84]=[CH:83][CH:82]=[CH:81][CH:80]=2)=[CH:91][C:90]([O:92][C:2]2[N:7]=[C:6]([O:8][CH2:9][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][CH2:24][CH2:25][CH3:26])[N:5]=[C:4]([O:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH3:45])[N:3]=2)=[CH:89][C:88]=1[C:93]1[CH:94]=[CH:95][CH:96]=[CH:97][CH:98]=1
Reactant: CCCCCCCCCCCCCCCCCCOc1nc(Cl)nc(OCCCCCCCCCCCCCCCCCC)n1
Reactant: Oc1cc(-c2ccccc2)c(O)c(-c2ccccc2)c1
Agent: CCCCCCCCCCCCOc1nc(Cl)nc(OCCCCCCCCCCCC)n1
Product: CCCCCCCCCCCCCCCCCCOc1nc(OCCCCCCCCCCCCCCCCCC)nc(Oc2cc(-c3ccccc3)c(O)c(-c3ccccc3)c2)n1

Procedure:
The preparation of the 2-chloro-4,6-distearoxy-s-triazine was carried out in the manner indicated for the 2-chlor-4,6-dilauroxy-s-triazine in Example I. Also the addition reaction with 2,6-diphenyl hydroquinone was also performed in the same manner as Examples I and II. The resulting reaction product had a melting point of 33° C.