Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[C:5]([N+:7]([O-])=O)[CH:4]=[C:3]1[C:10]([OH:12])=[O:11].C(=O)([O-])[O-].[Na+].[Na+].[C:19]1([S:25](Cl)(=[O:27])=[O:26])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>[Pd].C1COCC1>[CH3:1][N:2]1[CH:6]=[C:5]([NH:7][S:25]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)(=[O:27])=[O:26])[CH:4]=[C:3]1[C:10]([OH:12])=[O:11]
Reactant: Cn1cc([N+](=O)[O-])cc1C(=O)O
Reactant: O=S(=O)(Cl)c1ccccc1
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Cn1cc(NS(=O)(=O)c2ccccc2)cc1C(=O)O
Temperature: 0 °C
Reaction time: 2 h
Yield: 93.7 %

Procedure:
1-Methyl-4-nitro-1H-pyrrole-2-carboxylic acid (Int. 15) (350 mg, 2.057 mmol) was dissolved in aqueous 1M sodium carbonate (15 ml, 15.00 mmol); 10% Pd/C (219 mg) was added, and the mixture was hydrogenated in a Parr apparatus at 40 psi for 2 hours. The catalyst was filtered off maintaining the mixture under nitrogen flow and the filtrate was collected in a cooled flask (ice bath). THF (20 ml) and benzenesulfonyl chloride (0.318 ml, 2.469 mmol) were added to the cooled solution and the resulting mixture was stirred at 0° C. for 0.5 hours and then at RT for 1 hour. The reaction mixture was extracted with Et2O and the organic layer was discarded. The aqueous layer was cautiously acidified by addition of solid KHSO4 to pH=3 and extracted twice with DCM. The combined organic layers were dried over Na2SO4 and the solvent was removed under vacuum to afford 1-methyl-4-(phenylsulfonamido)-1H-pyrrole-2-carboxylic acid (Int. 16) (540 mg, 1.927 mmol, MS/ESI+280.9 [MH]+), which was used without purification.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([Cl:14])[CH:9]=2)[N:5]=[C:4]([CH2:15][CH3:16])[N:3]=1.[NH2:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][C:25]([NH2:27])=[O:26])=[CH:20][CH:19]=1.Cl.C([O-])(O)=O.[Na+]>O1CCOCC1.C(O)(=O)C>[Cl:14][C:10]1[CH:9]=[C:8]([C:6]2[N:5]=[C:4]([CH2:15][CH3:16])[N:3]=[C:2]([NH:17][C:18]3[CH:19]=[CH:20][C:21]([CH2:24][C:25]([NH2:27])=[O:26])=[CH:22][CH:23]=3)[CH:7]=2)[CH:13]=[CH:12][CH:11]=1
Reactant: CCc1nc(Cl)cc(-c2cccc(Cl)c2)n1
Reactant: NC(=O)Cc1ccc(N)cc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: C1COCCO1
Product: CCc1nc(Nc2ccc(CC(N)=O)cc2)cc(-c2cccc(Cl)c2)n1
Temperature: 85 °C
Yield: 38.3 %

Procedure:
A mixture of 4-chloro-6-(3-chlorophenyl)-2-ethylpyrimidine (0.080 g, 0.32 mmol) and 2-(4-aminophenyl)acetamide (0.057 g, 0.38 mmol) and 4M HCl in dioxane (2 drops) in acetic acid (2.5 mL) was heated for 2.5 h at 85° C. After this time, the mixture was cooled to 0° C., neutralized with NaHCO3, extracted with CH2Cl2 (2×30 mL) and EtOAc, dried (Na2SO4), filtered, and concentrated. The residue was purified by silica gel chromatography eluting with methylene chloride and methanol to afford the title compound (0.045 g, 40%) as a white solid. MW=366.84. 1H NMR (DMSO-d6, 500 MHz) δ 9.60 (s, 1H), 8.05 (d, J=2.0 Hz, 1H), 7.95-7.93 (m, 1H), 7.64 (d, J=8.4 Hz, 2H), 7.58-7.54 (m, 2H), 7.42 (br s, 1H), 7.23 (d, J=8.4 Hz, 2H), 7.05 (s, 1H), 6.85 (br s, 1H), 2.81 (q, J=7.6 Hz, 2H), 1.32 (t, J=7.6 Hz, 3H); ESI MS m/z 367 [M+H]+.
Reaction SMILES: [CH3:1][N:2]1[C:7](=[N:8][N+:9]([O-:11])=[O:10])[NH:6][CH2:5][O:4][CH2:3]1.[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19]Cl)=[CH:15][N:14]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][N:6]2[CH2:5][O:4][CH2:3][N:2]([CH3:1])[C:7]2=[N:8][N+:9]([O-:11])=[O:10])=[CH:15][N:14]=1
Reactant: ClCc1ccc(Cl)nc1
Reactant: CN1COCNC1=N[N+](=O)[O-]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CN1COCN(Cc2ccc(Cl)nc2)C1=N[N+](=O)[O-]

Procedure:
A mixture of 1.44 g of 3-methyl-4-nitroiminoperhydro-1,3,5-oxadiazine, 2.2 g of 2-chloro-5-chloromethylpyridine, 3.7 g of potassium carbonate and 20 ml of N,N-dime-thylformamide is heated for 4 hours at 50° and filtered, the filtrate is evaporated in vacuo on a rotary evaporator, and the residue is purified by chromatography [silica gel; dichloromethane/methanol (95:5)]. This gives the title compound which melts at 116 to 118°.
Reaction SMILES: S(=O)(=O)(O)O.[CH3:6][C:7]1[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[CH:12][C:8]=1[C:9]([OH:11])=[O:10].[C:19](=O)(O)[O-].[Na+]>CO.C(OCC)(=O)C>[CH3:19][O:10][C:9](=[O:11])[C:8]1[CH:12]=[C:13]([N+:16]([O-:18])=[O:17])[CH:14]=[CH:15][C:7]=1[CH3:6]
Reactant: O=C([O-])O
Reactant: Cc1ccc([N+](=O)[O-])cc1C(=O)O
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CO
Product: COC(=O)c1cc([N+](=O)[O-])ccc1C

Procedure:
300 μl of concentrated sulfuric acid is added to a suspension of 2 g of 2-methyl-5-nitrobenzoic acid in 7 ml of methanol. It is refluxed for 6 hours. Then, the reaction mixture is diluted with ethyl acetate and poured into saturated sodium bicarbonate solution. The phases are separated, and the aqueous phase is extracted with ethyl acetate. The combined organic phases are then washed with saturated sodium chloride solution, dried on sodium sulfate, and concentrated by evaporation in a vacuum. The crude product that is obtained is incorporated without purification into the next step.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8](F)(=[O:10])=[O:9].C[Si]([C:16]([F:19])([F:18])[F:17])(C)C>>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([C:16]([F:19])([F:18])[F:17])(=[O:10])=[O:9]
Reactant: C[Si](C)(C)C(F)(F)F
Reactant: O=S(=O)(F)c1ccccc1F
Product: O=S(=O)(c1ccccc1F)C(F)(F)F

Procedure:
reacting the 2-fluorobenzenesulfonyl fluoride, Ruppert's reagent (CH3SiCF3), and tris(dimethylamino)sulfonium difluorotrimethylsilicate at about room temperature to provide 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene and isolating or not isolating the 1-fluoro-2-((trifluoromethyl)sulfonyl)benzene;
Reaction SMILES: [CH3:1][O:2][C:3](=[O:20])[C:4](=[N:12][NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:5](=[O:11])[CH2:6][C:7](OC)=[O:8]>ClC1C=CC=CC=1Cl>[CH3:1][O:2][C:3]([C:4]1[C:5]([OH:11])=[CH:6][C:7](=[O:8])[N:13]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:12]=1)=[O:20]
Reactant: COC(=O)CC(=O)C(=NNc1ccccc1)C(=O)OC
Solvent: Clc1ccccc1Cl
Product: COC(=O)c1nn(-c2ccccc2)c(=O)cc1O
Reaction time: 20 h
Yield: 99.1 %

Procedure:
A mixture of 3-oxo-2-(phenyl-hydrazono)-pentanedioic acid dimethyl ester (4.38 g, 15.7 mmol) in 1,2-dichlorobenzene (15 mL) was refluxed. After 20 hours, the reaction mixture was concentrated under reduced pressure to give 3.83 g (99%) of the desired product.
Reaction SMILES: [Na+:1].C([S:5][CH2:6][CH:7]([CH2:20][C:21]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=1)[C:8]([NH:10][C:11]1[CH:12]=[C:13]([CH:17]=[CH:18][CH:19]=1)[C:14]([O-:16])=[O:15])=[O:9])(=O)C.[OH-].[Na+].Cl>O>[Na+:1].[SH:5][CH2:6][CH:7]([CH2:20][C:21]1[CH:22]=[CH:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=1)[C:8]([NH:10][C:11]1[CH:12]=[C:13]([CH:17]=[CH:18][CH:19]=1)[C:14]([O-:16])=[O:15])=[O:9]
Reactant: COc1ccc(CC(CSC(C)=O)C(=O)Nc2cccc(C(=O)[O-])c2)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: COc1ccc(CC(CS)C(=O)Nc2cccc(C(=O)[O-])c2)cc1
Reaction time: 1 h
Yield: 39 %

Procedure:
3-[[2-Acetylthiomethyl-3-(4-methoxyphenyl)-propionyl]amino]benzoic acid sodium salt (compound of Example 36) (2.0 g) is dissolved in water (20 ml), and the mixture is adjusted to pH 12.0 with 1 N aqueous sodium hydroxide solution under nitrogen. After reacting at room temperature for one hour, the reaction mixture is adjusted to pH 8.0 with 10% hydrochloric acid and is purified by a medium pressure column chromatography with CHP-20P (eluant, water-acetonitrile). The fractions containing the desired compound are collected, and acetonitrile is distilled off under reduced pressure and then lyophilized to give the title compound (0.7 g).
Reaction SMILES: [CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]=1[C:13]1[N:14]=[C:15]2[CH:20]=[C:19]([C:21]([OH:23])=O)[CH:18]=[CH:17][N:16]2[CH:24]=1.[CH2:25]([NH2:31])[C:26]1[O:30][CH:29]=[CH:28][CH:27]=1>>[O:30]1[CH:29]=[CH:28][CH:27]=[C:26]1[CH2:25][NH:31][C:21]([C:19]1[CH:18]=[CH:17][N:16]2[CH:24]=[C:13]([C:3]3[C:4]([C:7]4[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=4)=[N:5][O:6][C:2]=3[CH3:1])[N:14]=[C:15]2[CH:20]=1)=[O:23]
Reactant: NCc1ccco1
Reactant: Cc1onc(-c2ccccc2)c1-c1cn2ccc(C(=O)O)cc2n1
Product: Cc1onc(-c2ccccc2)c1-c1cn2ccc(C(=O)NCc3ccco3)cc2n1
Yield: 72 %

Procedure:
As described for Example 11b, 2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid (64 mg, 0.2 mmol) was converted, using furfurylamine instead of aminomethylcyclopropane, to the title compound (57 mg, 72%) which was obtained as a yellow foam. MS: m/e=399.1 [M+H]+.
Reaction SMILES: [CH3:1][NH:2][CH2:3][C:4]1[O:8][C:7]([CH2:9][OH:10])=[CH:6][CH:5]=1.[Cl:11][C:12]1[C:17]([Cl:18])=[CH:16][CH:15]=[CH:14][C:13]=1[S:19]([NH:22][C:23]1[C:28](Cl)=[N:27][CH:26]=[CH:25][N:24]=1)(=[O:21])=[O:20]>>[Cl:11][C:12]1[C:17]([Cl:18])=[CH:16][CH:15]=[CH:14][C:13]=1[S:19]([NH:22][C:23]1[C:28]([O:10][CH2:9][C:7]2[O:8][C:4]([CH2:3][NH:2][CH3:1])=[CH:5][CH:6]=2)=[N:27][CH:26]=[CH:25][N:24]=1)(=[O:20])=[O:21]
Reactant: O=S(=O)(Nc1nccnc1Cl)c1cccc(Cl)c1Cl
Reactant: CNCc1ccc(CO)o1
Product: CNCc1ccc(COc2nccnc2NS(=O)(=O)c2cccc(Cl)c2Cl)o1

Procedure:
Prepared by the method of Example 28 using (5-methylaminomethyl-2-furanyl)methanol (0.2 g) and 2,3-dichloro-N-(3-chloro-2-pyrazinyl)benzenesulphonamide (Example 28) (0.4 g). Purified by silica gel chromatography eluting with methanol/dichloromethane mixtures. Yield 0.12 g.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)[CH:6]=[CH:5]2.[CH3:22][O:23][C:24](=[O:35])[C:25]1[CH:30]=[CH:29][C:28]([CH3:31])=[C:27](B(O)O)[CH:26]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C(OCC)(=O)C.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>[CH3:21][O:20][C:17]1[CH:18]=[CH:19][C:14]([CH2:13][N:7]2[CH:6]=[CH:5][C:4]3[C:9](=[CH:10][CH:11]=[C:2]([C:27]4[CH:26]=[C:25]([CH:30]=[CH:29][C:28]=4[CH3:31])[C:24]([O:23][CH3:22])=[O:35])[CH:3]=3)[C:8]2=[O:12])=[CH:15][CH:16]=1
Reactant: COc1ccc(Cn2ccc3cc(Br)ccc3c2=O)cc1
Reactant: COC(=O)c1ccc(C)c(B(O)O)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COC(=O)c1ccc(C)c(-c2ccc3c(=O)n(Cc4ccc(OC)cc4)ccc3c2)c1
Temperature: 95 °C

Procedure:
A mixture of 6-bromo-2-(4-methoxy-benzyl)-2H-isoquinolin-1-one (product of step iv)) (1.2 g), intermediate 2 (0.7 g), potassium carbonate (1.0 g) and tetrakis(triphenylphosphine)palladium(0) (0.4 g) in N,N-dimethylformamide (20 mL) was heated to 95° C. for 17 hours. The reaction mixture was diluted with ethyl acetate and washed with water and brine. The organic phase was dried, filtered and evaporated. The residue was purified (SiO2, 1:2 ethyl acetate:iso-hexane as eluent) to yield the sub-titled compound (1.03 g).
Reaction SMILES: [C:1]([O:5][C:6](=[O:36])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:19]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[CH:20][C:21]4[NH:27][C:26](=[O:28])[CH2:25][CH2:24][NH:23][C:22]=4[N:29]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:39]I.O>CN(C=O)C>[C:1]([O:5][C:6](=[O:36])[NH:7][C:8]1([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[C:19]([C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=4)=[CH:20][C:21]4[N:27]([CH3:39])[C:26](=[O:28])[CH2:25][CH2:24][NH:23][C:22]=4[N:29]=3)=[CH:16][CH:17]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CI
Reactant: CC(C)(C)OC(=O)NC1(c2ccc(-c3nc4c(cc3-c3ccccc3)NC(=O)CCN4)cc2)CCC1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CN1C(=O)CCNc2nc(-c3ccc(C4(NC(=O)OC(C)(C)C)CCC4)cc3)c(-c3ccccc3)cc21
Temperature: 25 °C
Reaction time: 1 h
Yield: 38.3 %

Procedure:
To a solution of tert-butyl(1-(4-(2-oxo-8-phenyl-2,3,4,5-tetrahydro-1H-pyrido[2,3-b][1,4]diazepin-7-yl)phenyl)cyclobutyl)carbamate (53 mg, 0.11 mmol) in dry DMF (1 ml) was added sodium hydride (4.4 mg, 0.11 mmol) and methyliodide (6.9 μl, 0.11 mmol) under nitrogen. The resulting mixture was stirred for 1 hour at room temperature. Water was added and the mixture was extracted with EtOAc (3×15 ml). The combined organic phases were dried over Na2SO4 and concentrated to dryness under reduced pressure. The resulting residue was purified by Biotage silica gel chromatography (gradient 0 to 57% EtOAc in cyclohexane) to give the title compound (21 mg, 38%). 1H NMR (500 MHz, CDCl3): 7.39 (1H, s), 7.27-7.23 (7H, m), 7.16-7.14 (2H, m), 5.04 (1H, s), 4.91 (1H, br s), 3.88 (2H, br s), 3.39 (3H, s), 2.74 (2H, t), 2.55-2.25 (4H, m), 2.10-2.03 (1H, m), 1.86-1.78 (1H, m), 1.44-1.15 (9H, br).
Reaction SMILES: [CH2:1]([NH:3][CH2:4][CH3:5])[CH3:2].CS(O[CH2:11][CH2:12][CH2:13][N:14]([C:16]([O:18][CH:19]([CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45]/[CH:46]=[CH:47]\[CH2:48]/[CH:49]=[CH:50]\[CH2:51][CH2:52][CH2:53][CH2:54][CH3:55])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]/[CH:28]=[CH:29]\[CH2:30]/[CH:31]=[CH:32]\[CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])=[O:17])[CH3:15])(=O)=O>CCO.C(Cl)Cl>[CH2:1]([N:3]([CH2:4][CH3:5])[CH2:11][CH2:12][CH2:13][N:14]([CH3:15])[C:16](=[O:17])[O:18][CH:19]([CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45]/[CH:46]=[CH:47]\[CH2:48]/[CH:49]=[CH:50]\[CH2:51][CH2:52][CH2:53][CH2:54][CH3:55])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]/[CH:28]=[CH:29]\[CH2:30]/[CH:31]=[CH:32]\[CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])[CH3:2]
Reactant: CCCCC/C=C\C/C=C\CCCCCCCCC(CCCCCCCC/C=C\C/C=C\CCCCC)OC(=O)N(C)CCCOS(C)(=O)=O
Reactant: CCNCC
Solvent: ClCCl
Solvent: CCO
Product: CCCCC/C=C\C/C=C\CCCCCCCCC(CCCCCCCC/C=C\C/C=C\CCCCC)OC(=O)N(C)CCCN(CC)CC
Reaction time: 50 h
Yield: 42 %

Procedure:
A solution of diethylamine (2 mL) in EtOH (10 mL) was treated with 3-((((6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-yloxy)carbonyl)(methyl)amino)propyl methanesulfonate (500 mg, 0.7 mmol) in CH2Cl2 (2.5 mL). The solution was stirred (50 h), concentrated and subjected to chromatography (EtOAc) to yield (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-yl (3-(diethylamino)propyl)(methyl)carbamate (207 mg, 42%) as a pale yellow oil. Rf 0.43 (10% CH3OH—CH2Cl2), 1H NMR (400 MHz, CDCl3, δH) 5.41-5.28 (m, 8H, C═CH×8), 4.79-4.70 (m, 1H, CHO2CNR2), 3.28 (br. s, 2H, CH2NCH3), 2.94-2.83 (br. s, 3H, CO2NCH3), 2.79 (app. t, 4H, bis-allylic CH2×2), 2.52 (q, 4H, N(CH2CH3)2), 2.09-2.01 (m, 8H, CH2HC═C×4), 1.75-1.65 (m 4H, CH2×2), 1.59-1.45 (m, 4H, CH2×2), 1.42-1.22 (m, 36H, CH2×18), 1.15 (t, 6H, N(CH2CH3)2), 0.90 (t, 6H, CH3×2). FW 699.19, C46H86N2O2.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][N:4]=1.N1C=CC=CC=1.[CH2:15]([O:29][C:30]1[CH:38]=[CH:37][C:33]([C:34](Cl)=[O:35])=[CH:32][CH:31]=1)[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28]>C(Cl)Cl>[N:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=1[CH2:2][NH:1][C:34](=[O:35])[C:33]1[CH:32]=[CH:31][C:30]([O:29][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])=[CH:38][CH:37]=1
Reactant: CCCCCCCCCCCCCCOc1ccc(C(=O)Cl)cc1
Reactant: NCc1ccccn1
Solvent: ClCCl
Solvent: c1ccncc1
Product: CCCCCCCCCCCCCCOc1ccc(C(=O)NCc2ccccn2)cc1
Temperature: 0 °C
Reaction time: 2 h
Yield: 62.8 %

Procedure:
To a 0° C. solution of 0.674 g 2-(aminomethyl)-pyridine, 20 ml methylene chloride and 1.83 ml pyridine is added, dropwise over 20 minutes, 2.0 g of product from Example 3 dissolved in 25 ml of methylene chloride. The reaction is stirred at 0° C. for 2 hours followed by stirring at room temperature for 17 hours. The reaction mixture is partitioned between chloroform and saturated sodium bicarbonate, washed with water and saturated sodium chloride, dried and concentrated in vacuo. The residue is purified by column chromatography (silica g81:75% ethyl acetate/hexane) to give 1.51 g of the desired product.
Reaction SMILES: [CH3:1][N:2]([CH3:23])[C:3]1[CH:4]=[CH:5][C:6]([C:12](=O)[C:13]2[CH:18]=[CH:17][C:16]([N:19]([CH3:21])[CH3:20])=[CH:15][CH:14]=2)=[C:7]([CH:11]=1)[C:8]([OH:10])=[O:9].[CH3:24][N:25]([CH3:39])[C:26]1[CH:38]=[CH:37][C:29]([NH:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[CH:28][CH:27]=1>>[CH3:23][N:2]([CH3:1])[C:3]1[CH:11]=[C:7]2[C:6]([C:12]([C:13]3[CH:18]=[CH:17][C:16]([N:19]([CH3:21])[CH3:20])=[CH:15][CH:14]=3)([N:30]([C:29]3[CH:28]=[CH:27][C:26]([N:25]([CH3:39])[CH3:24])=[CH:38][CH:37]=3)[C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)[O:10][C:8]2=[O:9])=[CH:5][CH:4]=1
Reactant: CN(C)c1ccc(C(=O)c2ccc(N(C)C)cc2C(=O)O)cc1
Reactant: CN(C)c1ccc(Nc2ccccc2)cc1
Product: CN(C)c1ccc(N(c2ccccc2)C2(c3ccc(N(C)C)cc3)OC(=O)c3cc(N(C)C)ccc32)cc1
Yield: 75.6 %

Procedure:
Following a procedure similar to that described in Example 1 but employing 3.1 g of 5-(dimethylamino)-2-[4-(dimethylamino)benzoyl]benzoic acid and 3.0 g of 4-(dimethylamino)-N-phenylaniline there was obtained 3.8 g of 6-(dimethylamino)-3-[4-(dimethylamino)phenyl]-3-{[4-(dimethylamino)phenyl]phenylamino}phthalide, m.p. 163°-164° C. A toluene solution of the product contacted with acidic clay or phenolic resin developed a brown-colored image which changed to green on clay after fluorescent light exposure.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.[Br:10][CH:11]=[CH:12][CH2:13]Br>>[Br:10]/[CH:11]=[CH:12]\[CH2:13][O:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1
Reactant: BrC=CCBr
Reactant: O=Cc1ccc(O)cc1
Product: O=Cc1ccc(OC/C=C\Br)cc1

Procedure:
4-Hydroxybenzaldehyde and 1,3-dibromo-1-propene were processed as described in Example 33B to provide the title compound.
Reaction SMILES: Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][C:6]2=[O:11].B([O-])O[CH2:14][CH3:15].C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.[Ag]=O>[CH2:14]([C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][C:6]2=[O:11])[CH3:15]
Reactant: O=C1CCc2c(Br)cccc21
Reactant: CCOB[O-]
Agent: O=[Ag]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Product: CCc1cccc2c1CCC2=O
Temperature: 100 °C
Reaction time: 4 h
Yield: 92 %

Procedure:
4-Bromoindan-1-one (600 mg, 2.84 mmol) was dissolved in toluene (10 mL), and ethyl boronate (105 mg, 8.52 mmol), silver oxide (I) (274 mg, 7.10 mmol), potassium carbonate (196 mg, 8.52 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloride dichloromethane complex (46 mg, 0.0568 mmol) were added thereto, and then, the resulting mixture was stirred under a nitrogen atmosphere at 100° C. for 4 hours. After cooling to room temperature, the reaction solution was filtered, and the solvent was distilled off under reduced pressure, whereby a crude product was obtained. This crude product was purified by silica gel column chromatography (hexane:ethyl acetate=100:0 to 80:20 (v/v)), whereby the objective title compound was obtained as a colorless oily substance (421 mg, yield: 92%).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[N:6]([CH2:12][CH2:13][CH2:14][CH3:15])[CH2:5]2.C([O-])([O-])=O.[K+].[K+].CS(O[CH2:27][C:28]1[C:29]([CH3:41])=[N:30][C:31]([CH3:40])=[CH:32][C:33]=1[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)(=O)=O.O>CN(C=O)C>[CH2:12]([N:6]1[CH2:5][C:4]2[C:8](=[CH:9][CH:10]=[C:2]([NH:1][CH2:27][C:28]3[C:29]([CH3:41])=[N:30][C:31]([CH3:40])=[CH:32][C:33]=3[C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)[CH:3]=2)[C:7]1=[O:11])[CH2:13][CH2:14][CH3:15]
Reactant: CCCCN1Cc2cc(N)ccc2C1=O
Reactant: Cc1cc(-c2ccccc2)c(COS(C)(=O)=O)c(C)n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCCCN1Cc2cc(NCc3c(-c4ccccc4)cc(C)nc3C)ccc2C1=O
Reaction time: 8 h
Yield: 41.3 %

Procedure:
5-Amino-2-butylisoindolin-1-one (63.1 mg, 0.309 mmol), K2CO3 (85 mg, 0.618 mmol) and KI (51.3 mg, 0.309 mmol) were added to a solution of (2,6-dimethyl-4-phenylpyridin-3-yl)methyl methanesulfonate (90 mg, 0.309 mmol) in DMF (6 mL). After stirring overnight, water was added, the mixture was extracted with EtOAc, the combined organic layers were washed with water and dried (MgSO4). Purification by flash chromatography (DCM/MeOH, gradient 2-8% MeOH) provided 2-butyl-5-((2,6-dimethyl-4-phenylpyridin-3-yl)methylamino)isoindolin-1-one (51 mg, 40%).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][CH:9]([OH:21])[C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([O:18][CH2:19]C)=[O:17])[CH:11]=2)[N:3]=1.[C:22]1([CH3:28])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[Pd](Cl)Cl>[OH:21][CH:9]([C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([O:18][CH3:19])=[O:17])[CH:11]=1)[CH2:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2](/[CH:4]=[CH:8]/[CH:9]([OH:21])[CH2:10][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:22][CH3:28])[N:3]=1
Reactant: CCOC(=O)c1cccc(C(O)Cc2cccc(Br)n2)c1
Reactant: Cc1ccccc1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: c1ccc(P(c2ccccc2)[c-]2cccc2)cc1
Product: CCCCCCCCC(O)/C=C/c1cccc(CC(O)c2cccc(C(=O)OC)c2)n1
Temperature: 100 °C
Reaction time: 2 h

Procedure:
A solution of 120 mg of 2-bromo-6-[(2RS)-2-hydroxy-2-(3-ethoxycarbonylphenyl)-ethyl]-pyridine in 0.7 ml of toluene is mixed with 180 mg of (1E)-1-(tri-n-butylstannyl)-1-undecen-(3RS)-3-ol and 22 mg of 1,1'-bis-(diphenylphosphino)-ferrocene-palladium(II) chloride and stirred under argon atmosphere for 2 hours at 100° C. The reaction mixture is evaporated to dryness and the residue is chromatographed on silica gel with hexane/0-15% ethyl acetate. 56 mg of the title compound is obtained as oil.
Reaction SMILES: Cl[C:2]1[C:3]2[N:11]=[CH:10][CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[CH2:12]([NH2:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.Cl>CC(O)C>[CH2:12]([NH:19][C:2]1[C:3]2[N:11]=[CH:10][CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: NCc1ccccc1
Reactant: Clc1ncnc2cccnc12
Agent: Cl
Solvent: CC(C)O
Product: c1ccc(CNc2ncnc3cccnc23)cc1
Temperature: 50 °C

Procedure:
A solution of freshly prepared 4-chloropyrido[3,2-d]pyrimidine (0.10 g, 0.60 mmol) (prepared as described in the previous experimental) and benzylamine (0.13 mL, 1.20 mmol) in propan-2-ol (15 mL) containing a trace of conc. HCl is warmed at 50° C. for 30 min, and then concentrated to dryness. The residue is partitioned between water and EtOAc, and the organic layer worked up and chromatographed on silica gel. EtOAc elutes foreruns, while MeOH/EtOAc (1:9) elutes 4-(benzylamino)pyrido[3,2-d]pyrimidine (0.11 g, 77%). 1H NMR (CDCl3) δ 8.67 (1H, s), 6.50 (1H, dd, J=4.3, 1.5 Hz), 8.10 (1H, dd, J=8.5, 1.5 Hz), 7.63 (1H, dd, J=8.8, 4.3 Hz), 7.55 (1H, brs), 7.41-7.29 (SH, m), 4.86 (2H, d, J=5.9 Hz).