Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:25])([F:24])[C:3]1[CH:8]=[CH:7][C:6]([NH:9][S:10]([C:13]2[CH:14]=[C:15]([CH:21]=[CH:22][CH:23]=2)[C:16]([O:18]CC)=[O:17])(=[O:12])=[O:11])=[CH:5][CH:4]=1.C(O)C.[OH-].[Na+].Cl>O>[F:25][C:2]([F:1])([F:24])[C:3]1[CH:4]=[CH:5][C:6]([NH:9][S:10]([C:13]2[CH:14]=[C:15]([CH:21]=[CH:22][CH:23]=2)[C:16]([OH:18])=[O:17])(=[O:11])=[O:12])=[CH:7][CH:8]=1
Reactant: CCOC(=O)c1cccc(S(=O)(=O)Nc2ccc(C(F)(F)F)cc2)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: O=C(O)c1cccc(S(=O)(=O)Nc2ccc(C(F)(F)F)cc2)c1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
To the product of Step A was added ethanol (25 mL) followed by a solution of NaOH (1.93 g, 48.3 mmol) in water (25 mL). The reaction was stirred at ambient temperature for 1.5 hours. To the mixture was added dropwise 1 N HCl (95 mL), and the mixture was stirred at ambient temperature overnight. The solids were collected by filtration, washed with water (2×20 mL), and dried in a vacuum oven at 45° C. overnights to give 3-({[4-(trifluoromethyl)phenyl]amino}sulfonyl)benzoic acid: 1H NMR (400 MHz, DMSO-d6) δ ppm 7.28 (d, J=8.4 Hz, 2H), 7.62 (d, J=8.5 Hz, 2H), 7.71 (t, J=7.8 Hz, 1H), 8.03 (ddd, J=7.8, 1.9, 1.1 Hz, 1H), 8.15 (dt, J=7.8, 1.4 Hz, 1H), 8.34 (t, J=1.7 Hz, 1H), 10.98 (s, 1H), 13.54 (s, 1H); MS (EST) m/z 344 (M−H)−.
Reaction SMILES: [C:1]([OH:6])(=O)[CH:2]([CH3:4])[OH:3].[CH2:7]([NH2:10])[CH2:8][NH2:9]>O>[CH2:7]([NH:10][C:1](=[O:6])[CH:2]([CH3:4])[OH:3])[CH2:8][NH:9][C:1](=[O:6])[CH:2]([CH3:4])[OH:3]
Reactant: CC(O)C(=O)O
Reactant: NCCN
Solvent: O
Product: CC(O)C(=O)NCCNC(=O)C(C)O
Temperature: 125 °C

Procedure:
Lactic acid (441 g; 4.90 moles) was placed in a reaction flask equipped with a distillation head. Under a nitrogen atmosphere, ethylene diamine (147 g; 2.45 moles) was slowly added with stirring to the reaction flask. During the course of the addition, the reaction mixture turned a deep orange and the temperature reached 140° C. The reaction mixture was then heated at 150° C. overnight with the water being removed by distillation. The reaction mixture was allowed to cool to 125° C. then it was poured into an aluminum pan and allowed to cool to ambient temperature. to provide 468 g of crude product. This material was recrystallized from methanol (1.9 L) to provide N,N'-1,2-ethanediylbislactamide, m.p. 188° C.
Reaction SMILES: CS(O[CH2:6][CH2:7][S:8][C:9]1[N:14]2[CH:15]=[CH:16][N:17]=[C:13]2[CH:12]=[CH:11][CH:10]=1)(=O)=O.[CH2:18]([N:20](CC)CC)C.CN.CO>C(Cl)(Cl)Cl>[CH3:18][NH:20][CH2:6][CH2:7][S:8][C:9]1[N:14]2[CH:15]=[CH:16][N:17]=[C:13]2[CH:12]=[CH:11][CH:10]=1
Reactant: CCN(CC)CC
Reactant: CS(=O)(=O)OCCSc1cccc2nccn12
Agent: CN
Solvent: ClC(Cl)Cl
Solvent: CO
Product: CNCCSc1cccc2nccn12
Yield: 47.1 %

Procedure:
A solution of 5-[2-(methylsulfonyloxy)ethylthio]imidazo[1,2-a]pyridine (2.18 g, 8 mmoles), triethylamine (2.24 ml, 16 mmoles) and a 40% methylamine-methanol solution (20 ml) in chloroform (20 ml) was heated at reflux for 3 hours. The reaction solution was washed with an aqueous 3N-sodium hydroxide solution and dried over anhydrous magnesium sulfate. After the solvent was distilled off, the residue was purified by column chromatography (eluent: methanol/chloroform=1:10) to obtain 781 mg of the desired product (47.1%, light brown oily product).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]2[N:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:11]=[C:10]([C:18]3[CH:19]=[N:20][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:22][CH:23]=3)[N:9]=2)[CH:5]=[CH:4][N:3]=1.[C:28]([NH:32][S:33]([C:36]1[CH:37]=[C:38](B(O)O)[CH:39]=[CH:40][CH:41]=1)(=[O:35])=[O:34])([CH3:31])([CH3:30])[CH3:29]>>[C:28]([NH:32][S:33]([C:36]1[CH:37]=[CH:38][CH:39]=[C:40]([C:2]2[CH:7]=[C:6]([C:8]3[N:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:11]=[C:10]([C:18]4[CH:19]=[N:20][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:22][CH:23]=4)[N:9]=3)[CH:5]=[CH:4][N:3]=2)[CH:41]=1)(=[O:35])=[O:34])([CH3:31])([CH3:29])[CH3:30]
Reactant: FC(F)(F)c1ccc(-c2cc(C(F)(F)F)nc(-c3ccnc(Cl)c3)n2)cn1
Reactant: CC(C)(C)NS(=O)(=O)c1cccc(B(O)O)c1
Product: CC(C)(C)NS(=O)(=O)c1cccc(-c2cc(-c3nc(-c4ccc(C(F)(F)F)nc4)cc(C(F)(F)F)n3)ccn2)c1

Procedure:
3-{4-[4-Trifluoromethyl-6-(6-trifluoromethyl-pyridin-3-yl)-pyrimidin-2-yl]-pyridin-2-yl}-benzenesulfonic acid tert-butylamide was prepared from 2-(2-chloro-pyridin-4-yl)-4-trifluoromethyl-6-(6-trifluoromethyl-pyridin-3-yl)-pyrimidine (example B.4) (0.81 g, 2.0 mmol) and commercially available 3-(tert.-butylsulfamoyl)-phenylboronic acid (0.62 g, 2.4 mmol) according to the general procedure III. Obtained as off-white solid (0.71 g), which was subsequently deprotected.
Reaction SMILES: I[C:2]1[CH:3]=[C:4]([C:20]([NH:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[CH:26][CH:25]=2)=[O:21])[C:5](=[O:19])[N:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)[C:7]=1[CH3:8].[CH3:34][C:35]1[CH:39]=[C:38]([Sn](CCCC)(CCCC)CCCC)[O:37][N:36]=1>COCCOC.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>[CH3:8][C:7]1[N:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:17])([F:18])[F:16])[CH:10]=2)[C:5](=[O:19])[C:4]([C:20]([NH:22][CH2:23][C:24]2[CH:25]=[CH:26][C:27]([S:30]([CH3:33])(=[O:31])=[O:32])=[CH:28][CH:29]=2)=[O:21])=[CH:3][C:2]=1[C:38]1[O:37][N:36]=[C:35]([CH3:34])[CH:39]=1
Reactant: Cc1c(I)cc(C(=O)NCc2ccc(S(C)(=O)=O)cc2)c(=O)n1-c1cccc(C(F)(F)F)c1
Reactant: CCCC[Sn](CCCC)(CCCC)c1cc(C)no1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: COCCOC
Product: Cc1cc(-c2cc(C(=O)NCc3ccc(S(C)(=O)=O)cc3)c(=O)n(-c3cccc(C(F)(F)F)c3)c2C)on1

Procedure:
The title compound was synthesized in the same way as Example 29 but starting from 5-iodo-6-methyl-N-[4-(methylsulfonyl)benzyl]-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxamide (50 mg, 0.085 mmol), tetrakis(triphenylphosphine)palladium (5 mg, 0.0043 mmol) and 3-methyl-5-(tributylstannyl)isoxazole [synthesized as described in Tetrahedron, 47, 28, 5111, 1991] (63 mg, 0.169 mmol) in DME (0.85 ml). Yield: 15 mg, 0.033 mmol (39%).
Reaction SMILES: Cl[C:2]1[N:24]=[C:5]2[C:6]([NH:10][CH2:11][C:12]3[C:13]([N:18]([CH3:23])[S:19]([CH3:22])(=[O:21])=[O:20])=[N:14][CH:15]=[CH:16][CH:17]=3)=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.[N:25]1([CH2:30][CH2:31][O:32][C:33]2[CH:38]=[CH:37][C:36]([NH2:39])=[CH:35][CH:34]=2)[CH2:29][CH2:28][CH2:27][CH2:26]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)CCCCC1>>[CH3:23][N:18]([C:13]1[C:12]([CH2:11][NH:10][C:6]2[C:5]3[N:4]([N:3]=[C:2]([NH:39][C:36]4[CH:37]=[CH:38][C:33]([O:32][CH2:31][CH2:30][N:25]5[CH2:29][CH2:28][CH2:27][CH2:26]5)=[CH:34][CH:35]=4)[N:24]=3)[CH:9]=[CH:8][CH:7]=2)=[CH:17][CH:16]=[CH:15][N:14]=1)[S:19]([CH3:22])(=[O:21])=[O:20]
Reactant: CN(c1ncccc1CNc1cccn2nc(Cl)nc12)S(C)(=O)=O
Reactant: Nc1ccc(OCCN2CCCC2)cc1
Agent: c1ccc(P(C2CCCCC2)C2CCCCC2)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c1
Product: CN(c1ncccc1CNc1cccn2nc(Nc3ccc(OCCN4CCCC4)cc3)nc12)S(C)(=O)=O

Procedure:
N-Methyl-N-[3-({2-[4-(2-pyrrolidin-1-yl-ethoxy)-phenylamino]-[1,2,4]triazolo[1,5-a]pyridin-8-ylamino}-methyl)-pyridin-2-yl]-methanesulfonamide was prepared from N-{3-[(2-chloro-[1,2,4]triazolo[1,5-a]pyridin-8-ylamino)-methyl]-pyridin-2-yl}-N-methyl-methanesulfonamide and 4-(2-pyrrolidin-1-yl-ethoxy)-phenylamine (51.0 mg, 0.247 mmol) (prepared as described in J. Med. Chem., 2006, 49, 4451-4454) with 2,2′-bis-dicyclohexylphosphanyl-biphenyl (25.0 mg, 0.0457 mmol) as the ligand in a manner analogous to Example 2d. Product isolated as a tan foam (0.021 g, 19%). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.42-8.39 (m, 1H), 7.85 (d, J=7.6 z, 1H), 7.80 (d, J=6.6 Hz, 1H), 7.48 (d, J=8.9 Hz, 2H), 7.30-7.25 (m, 1H), 6.92 (d, J=9.0 Hz, 2H), 6.64 (t, J=7.4 Hz, 1H), 6.52 (s, 1H), 6.29 (d, J=7.8 Hz, 1H), 5.27 (t, J=6.2, 1H), 4.77 (d, J=6.4 Hz, 2H), 4.10 (t, J=6.0 Hz, 2H), 3.32 (s, 3H), 3.09 (s, 3H), 2.90 (t, J=6.0 Hz, 2H), 2.68-2.58 (m, 4H), 1.86-1.76 (m, 4H). MS=537 (MH)+.
Reaction SMILES: [OH:1][CH2:2][CH:3]([C@@H:5]1[CH2:10][CH2:9][C@@H:8]([CH3:11])[CH2:7][C@H:6]1[OH:12])[CH3:4].[H-].[Na+].[CH:15](I)([CH3:17])[CH3:16].O>C(COC)OC>[CH:15]([O:1][CH2:2][CH:3]([C@@H:5]1[CH2:10][CH2:9][C@@H:8]([CH3:11])[CH2:7][C@H:6]1[OH:12])[CH3:4])([CH3:17])[CH3:16]
Reactant: CC(CO)[C@@H]1CC[C@@H](C)C[C@H]1O
Reactant: CC(C)I
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: COCCOC
Product: CC(C)OCC(C)[C@@H]1CC[C@@H](C)C[C@H]1O
Reaction time: 0.5 h
Yield: 71.1 %

Procedure:
20.0 g (0.12 mol) of (1R, 2S, 5R)-2-(2-hydroxy-1-methylethyl)-5-methylcyclohexanol was dissolved in 100 ml of dimethoxyethane, and 3.3 g (0.14 mol) of sodium hydride was added to the solution. The mixture was agitated for 30 min, and 23.7 g (0.14 mol) of isopropyl iodide was dropped thereinto and continued to agitate at room temperature for 24 hr. After the completion of the reaction, 300 ml of water was added to the reaction fluid and agitated. The reaction product was extracted with ether. The resultant ether phase was dried over anhydrous magnesium sulfate, and the solvent was distilled off, thereby obtaining 18.3 g (yield: 73.6%) of (1R, 2S, 5R)-2-(2-isopropoxy-1-methylethyl)-5-methylcyclohexanol in the form of a colorless liquid. The mass spectrometry and NMR data of the obtained compound are as follows:
Reaction SMILES: [C:1](N1C=CN=C1)([N:3]1[CH:7]=[CH:6][N:5]=[CH:4]1)=O.[CH2:13]([C:15]1([CH2:44][CH3:45])[C:18](=[O:19])[N:17]([C:20]([NH:22][CH:23]([C:27]2[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=2)[CH2:24][CH2:25][CH3:26])=[O:21])[CH:16]1[O:34][C:35]1[CH:43]=[CH:42][C:38]([C:39]([OH:41])=O)=[CH:37][CH:36]=1)[CH3:14].CN(C)CCN.C1C=CC=CC=1>C(Cl)Cl>[CH3:1][N:3]([CH3:4])[CH2:7][CH2:6][NH:5][C:39]([C:38]1[CH:42]=[CH:43][C:35]([O:34][CH:16]2[C:15]([CH2:44][CH3:45])([CH2:13][CH3:14])[C:18](=[O:19])[N:17]2[C:20]([NH:22][CH:23]([C:27]2[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=2)[CH2:24][CH2:25][CH3:26])=[O:21])=[CH:36][CH:37]=1)=[O:41]
Reactant: CCCC(NC(=O)N1C(=O)C(CC)(CC)C1Oc1ccc(C(=O)O)cc1)c1ccc(C)cc1
Reactant: O=C(n1ccnc1)n1ccnc1
Agent: CN(C)CCN
Solvent: c1ccccc1
Solvent: ClCCl
Product: CCCC(NC(=O)N1C(=O)C(CC)(CC)C1Oc1ccc(C(=O)NCCN(C)C)cc1)c1ccc(C)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 0.104 g carbonyldiimidazole in 2 ml methylene chloride is added a solution of 0.227 g of [S-(R*,S*)]-4-((3,3-diethyl-1-((-1-(4-methylphenyl)butylamino)carbonyl)-4-oxo-2-azetidinyl)-oxy)benzoic acid in 3 ml methylene chloride. The mixture is stirred at ambient temperature for 30 minutes at which time 0.100 g of N,N-dimethylethylenediamine is added. After stirring overnight at room temperature the reaction mixture is poured into benzene (50 ml) and washed with water. The organic layer is separated, dried through sodium sulfate and concentrated in vacuo. Silica gel chromatography using 5% methanol in methylene chloride yields 0.160 g of 2-[4-[[[2-(dimethylamino)-ethyl]amino]carbonyl]phenoxy]-3,3-diethyl-N-[1-(4-methylphenyl)butyl]-4-oxo-1-azetidinecarboxamide. (Compound 73).
Reaction SMILES: [C:1](Cl)(=O)[C:2]([Cl:4])=[O:3].[N+:7]([C:10]1[CH:15]=[CH:14][C:13](CC(O)=O)=[CH:12][CH:11]=1)([O-:9])=[O:8].CN(C=O)C>ClCCl>[N+:7]([C:10]1[CH:15]=[CH:14][C:13]([CH2:1][C:2]([Cl:4])=[O:3])=[CH:12][CH:11]=1)([O-:9])=[O:8]
Reactant: O=C(O)Cc1ccc([N+](=O)[O-])cc1
Reactant: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Product: O=C(Cl)Cc1ccc([N+](=O)[O-])cc1
Reaction time: 0.5 h

Procedure:
3.75 ml (7.5 mmoles) of a 2 M solution of oxalyl chloride in dichloromethane is added at 20° C. to a solution of 0.9 g (5 mmoles) of 4-nitrophenylacetic acid in a mixture composed of 10 ml of dichloromethane and 0.5 ml of DMF. After agitation for 30 minutes, the solution is concentrated under vacuum. The yellow oil obtained is used without additional purification in the following stage.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[O:25][N:24]=[C:23]([CH3:26])[C:22]=4[CH2:27]Br)=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].[CH3:29][C@H:30]1[C@@H:34]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[O:33][C:32](=[O:41])[NH:31]1>>[CH2:1]([O:3][C:4]([C:6]1([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[O:25][N:24]=[C:23]([CH3:26])[C:22]=4[CH2:27][N:31]4[C@@H:30]([CH3:29])[C@@H:34]([C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)[O:33][C:32]4=[O:41])=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]
Reactant: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4CBr)cc3)cc2)CC1
Reactant: C[C@@H]1NC(=O)O[C@@H]1c1ccccc1
Product: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4CN4C(=O)O[C@H](c5ccccc5)[C@@H]4C)cc3)cc2)CC1

Procedure:
Prepared according to the procedure described in Example 5, Step 3, using 1-[4′-(4-bromomethyl-3-methyl-isoxazol-5-yl)-biphenyl-4-yl]-cyclopropanecarboxylic acid ethyl ester and (4S,5R)-4-methyl-5-phenyl-oxazolidin-2-one.
Reaction SMILES: [CH:1](=O)/[CH:2]=[CH:3]/[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH3:11][C:12]([C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)=[O:13].[OH-].[Na+]>C(O)C>[CH3:21][O:20][C:17]1[CH:18]=[CH:19][C:14]([C:12](=[O:13])[CH:11]=[CH:1][CH:2]=[CH:3][C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)=[CH:15][CH:16]=1
Reactant: COc1ccc(C(C)=O)cc1
Reactant: O=C/C=C/c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: COc1ccc(C(=O)C=CC=Cc2ccccc2)cc1
Reaction time: 12 h
Yield: 72 %

Procedure:
2 ml of trans-cinnamaldehyde and 2.5 g of 4-methoxy acetophenone were dissolved in 50 ml of ethanol at room temperature. 10 ml of sodium hydroxide solution was then added and stirred for 12 h to form yellow solid precipitation. Filtering the precipitation to obtain the compound 1, with yield of 72% and purity of 96.3%. FIG. 1 and FIG. 2 respectively show the NMR and UV spectrum of compound 1; wherein the maximum adsorptive wavelength of compound 1 is 345 nm, and the adsorptive coefficient ε is 4.5×104, both listed on Table 1.
Reaction SMILES: FC(F)(F)C(OC1C(F)=C(F)C(F)=C(F)C=1F)=O.[Cl:19][CH2:20][CH2:21][CH2:22][O:23][C:24]1[CH:33]=[C:32]2[C:27]([C:28]([NH:34][C:35]3[CH:36]=[N:37][N:38]([CH2:40][C:41](O)=[O:42])[CH:39]=3)=[N:29][CH:30]=[N:31]2)=[CH:26][CH:25]=1.N1C=CC=CC=1.[NH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1.Cl>CN(C)C=O>[Cl:19][CH2:20][CH2:21][CH2:22][O:23][C:24]1[CH:33]=[C:32]2[C:27]([C:28]([NH:34][C:35]3[CH:36]=[N:37][N:38]([CH2:40][C:41]([NH:50][C:51]4[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=4)=[O:42])[CH:39]=3)=[N:29][CH:30]=[N:31]2)=[CH:26][CH:25]=1
Reactant: Nc1ccccc1
Reactant: O=C(O)Cn1cc(Nc2ncnc3cc(OCCCCl)ccc23)cn1
Agent: Cl
Agent: O=C(Oc1c(F)c(F)c(F)c(F)c1F)C(F)(F)F
Solvent: c1ccncc1
Solvent: CN(C)C=O
Product: O=C(Cn1cc(Nc2ncnc3cc(OCCCCl)ccc23)cn1)Nc1ccccc1
Reaction time: 0.08 h
Yield: 53.9 %

Procedure:
Pentafluorophenyl trifluoroacetate (0.867 g, 3.10 mmol) was added dropwise, at room temperature, to a stirred suspension of (4-{[7-(3-chloropropoxy)quinazolin-4-yl]amino}-1H-pyrazol-1-yl)acetic acid (0.800 g, 2.21 mmol) and pyridine (0.245 g, 3.10 mmol) in dimethylformamide (8 ml). After stirring for 5 minutes, aniline (0.412 g, 4.43 mmol) was added and the reaction mixture was stirred for 2 hours. The mixture was poured into dilute hydrochloric acid (0.2N, 25 ml) and the resultant solid filtered and then washed with water. The residue was stirred in dilute aqueous sodium hydroxide solution and filtered and the residue washed successively with water, methanol and diethylether to give 2-(4-{[7-(3-chloropropoxy)quinazolin-4-yl]amino}-1H-pyrazol-1-yl)-N-phenylacetamide (0.520 g, 54% yield): MS (+ve ESI): 437 (M+H)+.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([C:8]2[C:16]3[O:15][CH:14]([CH2:17]OS(C4C=CC(C)=CC=4)(=O)=O)[CH2:13][C:12]=3[CH:11]=[C:10]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[CH3:35][NH2:36]>>[CH3:1][C:2]1[CH:3]=[C:4]([C:8]2[C:16]3[O:15][CH:14]([CH2:17][NH:36][CH3:35])[CH2:13][C:12]=3[CH:11]=[C:10]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH:9]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: CN
Reactant: Cc1ccc(S(=O)(=O)OCC2Cc3cc(-c4ccccc4)cc(-c4cccc(C)c4)c3O2)cc1
Product: CNCC1Cc2cc(-c3ccccc3)cc(-c3cccc(C)c3)c2O1

Procedure:
The title compound was prepared (0.055 g, 70%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7-(3-methylphenyl)-5-phenyl-2,3-dihydro-1-benzofuran-2-yl]methyl}4-methylbenzenesulfonate (0.10 g, 0.21 mmol) and methylamine (0.30 g, 9.8 mmol). mp 230-234° C.
Reaction SMILES: [C:1]([O-:4])(=[O:3])[CH3:2].[C:5]([O-:8])(=[O:7])[CH3:6].[C:9]([O-:12])(=[O:11])[CH3:10].C([O-])(=O)C.[Pb+4:17].[Cl:18][C:19]1[CH:35]=[CH:34][C:22]([C:23]2[CH:24]=[CH:25][C:26]([CH2:32][CH3:33])=[C:27](B(O)O)[CH:28]=2)=[CH:21][CH:20]=1>>[C:1]([O-:4])(=[O:3])[CH3:2].[C:5]([O-:8])(=[O:7])[CH3:6].[C:9]([O-:12])(=[O:11])[CH3:10].[Cl:18][C:19]1[CH:35]=[CH:34][C:22]([C:23]2[CH:24]=[CH:25][C:26]([CH2:32][CH3:33])=[C:27]([Pb+3:17])[CH:28]=2)=[CH:21][CH:20]=1
Reactant: CCc1ccc(-c2ccc(Cl)cc2)cc1B(O)O
Reactant: [Pb+4]
Agent: CC(=O)[O-]
Product: CCc1ccc(-c2ccc(Cl)cc2)cc1[Pb+3]
Temperature: 40 °C
Yield: 100 %

Procedure:
To a mixture of lead tetraacetate (2.15 g, 4.85 mmol) and mercuric diacetate (0.15 g, 0.47 mmol), thoroughly flushed with nitrogen, is added anhydrous chloroform (6 ml). This mixture is warmed to 40° C., and 4′-chloro-4-ethylbiphen-3-ylboronic acid (1.17 g, 4.50 mmol) is added in one portion and the suspension is heated at this temperature for 5 hours. The mixture is than cooled to room temperature, concentrated to a small volume and triturated with hexanes and filtered to yield crude 4′-chloro-4-ethylbiphen-3-yllead triacetate (2.70 g).
Reaction SMILES: [NH:1]([CH2:5][C:6]([O-:8])=O)[C:2]([NH2:4])=[O:3].[NH2:9][OH:10]>O1CCOCC1>[OH:10][NH:9][C:6](=[O:8])[CH2:5][NH:1][C:2]([NH2:4])=[O:3]
Reactant: NC(=O)NCC(=O)[O-]
Reactant: NO
Solvent: C1COCCO1
Product: NC(=O)NCC(=O)NO

Procedure:
A stock solution of triphosgene was prepared from solid triphosgene (1.48 g, 5 mmol) and DCM (20 mL). The solution was cooled to −78° C. and triethylamine (2 mL, 15 mmol) was slowly added. To ArgoGel-Wang or ArgoGel-OH resin bound 2-aminoacetate 4 (0.5 g) was added the triphosgene solution (3.5 mL) and the resin was shaken at rt for 1 h. The resin was drained, washed with DCM (3×) and then suspended in a solution of secondary amine 7 (e.g., pyrrolidine, 2 mmol) and TEA (3 mmol) in DCM (2 mL). After 16 h, the resin was washed with DCM and MeOH (3× each) to yield ArgoGel-Wang or ArgoGel-OH resin bound 2-ureidoacetate 6 which was then treated with a solution of aqueous 50% hydroxylamine (2 mL) and dioxane (1 mL) for 2 days. The resin was filtered, washed with acetonitrile and the filtrates combined and purified by preparative reverse-phase (C18) HPLC to yield product N-hydroxy-2-ureidoacetamide (I).
Reaction SMILES: [CH3:1][C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:6]([C:12]2[CH:17]=[C:16]([N+:18]([O-:20])=[O:19])[CH:15]=[CH:14][C:13]=2[O:21][CH2:22][CH2:23][CH2:24][CH2:25]Br)[C:5]([C:27]([O:29][CH3:30])=[O:28])=[C:4]([CH3:31])[N:3]=1.[O:32]([CH2:39][CH2:40][CH2:41][NH2:42])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>C(#N)C>[CH3:1][C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:6]([C:12]2[CH:17]=[C:16]([N+:18]([O-:20])=[O:19])[CH:15]=[CH:14][C:13]=2[O:21][CH2:22][CH2:23][CH2:24][CH2:25][NH:42][CH2:41][CH2:40][CH2:39][O:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:5]([C:27]([O:29][CH3:30])=[O:28])=[C:4]([CH3:31])[N:3]=1
Reactant: NCCCOc1ccccc1
Reactant: COC(=O)c1c(C)nc(C)c(C(=O)OC)c1-c1cc([N+](=O)[O-])ccc1OCCCCBr
Solvent: CC#N
Product: COC(=O)c1c(C)nc(C)c(C(=O)OC)c1-c1cc([N+](=O)[O-])ccc1OCCCCNCCCOc1ccccc1

Procedure:
2.22 g of dimethyl 2,6-dimethyl-4-[(4-bromobutoxy)-5-nitro-phenyl]pyridine-3,5-dicarboxylate and 1.4 g of 3-phenoxypropylamine were dissolved in 30 ml of acetonitrile and refluxed with heating for two hours. After evaporating the solvent, the residue was subjected to silica gel column chromatography and eluted with chloroform - methanol (95:5) to give 1.8 g of caramel-like dimethyl 2,6-dimethyl-4-[5-nitro-2-[4-[(3-phenoxypropyl)amino]butoxy]phenyl]pyridine3,5-dicarboxylate. The compound thus obtained in 29 ml of ethanol was dissolved and to the solution was added a solution of 0.2 g of anhydrous oxalic acid in 5 ml of ethanol. The resultant solution was allowed to stand overnight at 4° C. The precipitated crystals were collected by filtration and recrystallized from ethanol to give 1.5 g of dimethyl 2,6-dimethyl-4-[5-nitro-2-[4-[(3-phenoxypropyl)amino]butoxy]phenyl]pyridine-3,5-dicarboxylate oxalate. This compound has the following physico-chemical properties:
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([C:10]2[CH:11]=[C:12]([CH:17]=[CH:18][N:19]=2)[C:13]([O:15][CH3:16])=[O:14])[CH:6]=[CH:7][C:8]=1F)#[N:2].[NH2:20][CH2:21][CH:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1>CS(C)=O.C(OCC)(=O)C>[C:1]([C:3]1[CH:4]=[C:5]([C:10]2[CH:11]=[C:12]([CH:17]=[CH:18][N:19]=2)[C:13]([O:15][CH3:16])=[O:14])[CH:6]=[CH:7][C:8]=1[NH:20][CH2:21][CH:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1)#[N:2]
Reactant: NCC1CCCCC1
Reactant: COC(=O)c1ccnc(-c2ccc(F)c(C#N)c2)c1
Solvent: CCOC(C)=O
Solvent: CS(C)=O
Product: COC(=O)c1ccnc(-c2ccc(NCC3CCCCC3)c(C#N)c2)c1
Temperature: 40 °C
Reaction time: 17 h

Procedure:
In 3 ml of DMSO was dissolved 247 mg of methyl 2-(3-cyano-4-fluorophenyl)isonicotinate, and 0.31 ml of aminomethylcyclohexane was added thereto. After being stirred at 40° C. for 17 hours, the reaction solution was diluted with ethyl acetate and washed with water and brine, successively. The organic layer was dried and concentrated under reduced pressure and then recrystallization was performed from a mixed solvent of diisopropyl ether and hexane to obtain 266 mg of methyl 2-{3-cyano-4-[(cyclohexylmethyl)amino]phenyl}isonicotinate. (2) Then, 266 mg of the compound was dissolved in a mixed solvent of 5 ml of methanol and 10 ml of THF, and 1.14 ml of a 1M aqueous sodium hydroxide solution was added thereto, followed by heating at 80° C. for 1 hour. After cooling, the reaction solution was diluted with water and washed with diethyl ether. The resulting aqueous layer was neutralized with 1M hydrochloric acid and extracted with ethyl acetate and the organic layer was dried and concentrated under reduced pressure. The resulting residue was recrystallized from a mixed solvent of ethanol and water to obtain 199 mg of 2-{3-cyano-4-[(cyclohexylmethyl)amino]phenyl}isonicotinic acid. Then, 199 mg of the compound was dissolved in 10 ml of ethanol and 0.59 ml of a 1M aqueous sodium hydroxide solution was added thereto. After stirring at room temperature for 15 minutes, the reaction solution was concentrated. The resulting residue was washed with 2-propanol to obtain 181 mg of sodium 2-{3-cyano-4-[(cyclohexylmethyl)amino]phenyl}isonicotinate.
Reaction SMILES: [Cl:1][C:2]1[C:7]2[C:8](=[O:22])[N:9]([CH3:21])[CH2:10][C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16](OCC)=[O:17])[C:6]=2[CH:5]=[CH:4][CH:3]=1.C([NH2:25])=O.C[O-].[Na+].O>O1CCOCC1>[Cl:1][C:2]1[C:7]2[C:8](=[O:22])[N:9]([CH3:21])[CH2:10][C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]([NH2:25])=[O:17])[C:6]=2[CH:5]=[CH:4][CH:3]=1
Reactant: CCOC(=O)c1ncn2c1CN(C)C(=O)c1c(Cl)cccc1-2
Reactant: NC=O
Agent: C[O-]
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: CN1Cc2c(C(N)=O)ncn2-c2cccc(Cl)c2C1=O
Reaction time: 0.17 h

Procedure:
22.8 g Ethyl 7-chloro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]-benzodiazepine-3-carboxylate (V)were suspended under stirring and argon atmosphere in 91.2 ml 1,4-dioxane. 14.1 ml Formamide and 13.9 ml sodium methanolate were successively added to yield a clear light-orange solution, which turned to a white suspension after 10 minutes. This suspension was stirred two hours at 30° C. 200 ml deionized water were added in one portion and 1,4-dioxane was distilled off at 40° C. under reduced pressure. The remaining white suspension was stirred two hours at 0° C. and filtered. The precipitate (7-chloro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxamide (VI)) was washed with 50 ml deionized water three times and dried under reduced pressure for 18 hours at 80° C. Crude product: 19.43 g as a white powder. m.p.>250° C.