Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[CH3:11][O:12][C:13]1[CH:23]=[CH:22][C:16]([C:17]([N:19]=[C:20]=[S:21])=[O:18])=[CH:15][CH:14]=1>CCOCC>[NH2:6][C:4]([C:3]1[CH:7]=[CH:8][CH:9]=[CH:10][C:2]=1[NH:1][C:20](=[S:21])[NH:19][C:17](=[O:18])[C:16]1[CH:22]=[CH:23][C:13]([O:12][CH3:11])=[CH:14][CH:15]=1)=[O:5]
Reactant: NC(=O)c1ccccc1N
Reactant: COc1ccc(C(=O)N=C=S)cc1
Solvent: CCOCC
Product: COc1ccc(C(=O)NC(=S)Nc2ccccc2C(N)=O)cc1
Reaction time: 8 h
Yield: 833 %

Procedure:
To a stirred mixture of 7.5 g of 2-aminobenzamide and 150 ml of ether was added dropwise, a mixture of 1.0 g of 4-methoxybenzoyl isothiocyanate in ether over 15 minutes. After stirring overnight, the solid was collected, giving 14.2 g of the desired product as grey crystals, mp 193°-196° C.
Reaction SMILES: [Cl:1][C:2]1[N:10]([CH2:11][CH:12]=[CH2:13])[C:9]2[C:8](=[O:14])[NH:7][C:6](=[O:15])[N:5]([CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[C:4]=2[N:3]=1.[C:21](=O)([O-])[O-].[Cs+].[Cs+].IC>CN(C=O)C>[Cl:1][C:2]1[N:10]([CH2:11][CH:12]=[CH2:13])[C:9]2[C:8](=[O:14])[N:7]([CH3:21])[C:6](=[O:15])[N:5]([CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[C:4]=2[N:3]=1
Reactant: O=C([O-])[O-]
Reactant: C=CCn1c(Cl)nc2c1c(=O)[nH]c(=O)n2CCCCC
Agent: [Cs+]
Solvent: CI
Solvent: CN(C)C=O
Product: C=CCn1c(Cl)nc2c1c(=O)n(C)c(=O)n2CCCCC
Reaction time: 18 h

Procedure:
To a solution of 8-chloro-3-pentyl-7-(2-propen-1-yl)-3,7-dihydro-1H-purine-2,6-dione (3.9 g, 13.3 mmol) in DMF (35 ml) was added cesium carbonate and the mixture stirred for 10 min whereupon iodomethane (0.91 ml, 14.6 mmol) was added and the mixture stirred for 18 h. The reaction was partitioned between ethyl acetate and 2N HCl solution and the organics isolated, dried (MgSO4) and concentrated. Chromatography on silica SPE eluting with cyclohexane/ethyl acetate (5%-20%) provided the product as an oil, 2.78 g, 68%. m/z 311[MH+].
Reaction SMILES: [NH2:1][N:2]1[C:7](=[O:8])[C:6]([C:9]2[NH:14][C:13]3[CH:15]=[CH:16][CH:17]=[CH:18][C:12]=3[S:11](=[O:20])(=[O:19])[N:10]=2)=[C:5]([OH:21])[C:4]2[S:22][CH:23]=[CH:24][C:3]1=2.[CH3:25][C:26]([CH3:30])=[CH:27][CH:28]=O>CN(C)C(=O)C>[O:19]=[S:11]1(=[O:20])[C:12]2[CH:18]=[CH:17][CH:16]=[CH:15][C:13]=2[NH:14][C:9]([C:6]2[C:7](=[O:8])[N:2]([N:1]=[CH:28][CH:27]=[C:26]([CH3:30])[CH3:25])[C:3]3[CH:24]=[CH:23][S:22][C:4]=3[C:5]=2[OH:21])=[N:10]1
Reactant: CC(C)=CC=O
Reactant: Nn1c(=O)c(C2=NS(=O)(=O)c3ccccc3N2)c(O)c2sccc21
Solvent: CC(=O)N(C)C
Product: CC(C)=CC=Nn1c(=O)c(C2=NS(=O)(=O)c3ccccc3N2)c(O)c2sccc21
Temperature: 25 °C
Yield: 80.4 %

Procedure:
The product of Example 268D (0.10 g, 0.27 mmol) was reacted with 3-methylbut-2-enal (0.5 g, 5.9 mmol) in N,N-dimethylacetamide (3 mL) in a sealed tube at 130° C. for 40 minutes in a microwave reactor. The reaction was cooled to 25° C. and concentrated under vacuum. The resulting residue was triturated with diethyl ether and filtered to give the title compound (0.093 g, 80%).
Reaction SMILES: [C:1]([CH2:3][C:4]([NH:6][CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)=[O:5])#[N:2].[CH:13](OCC)(OCC)[O:14][CH2:15][CH3:16]>C(OC(=O)C)(=O)C>[C:1]([C:3](=[CH:13][O:14][CH2:15][CH3:16])[C:4]([NH:6][CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)=[O:5])#[N:2]
Reactant: N#CCC(=O)NC1CCCCC1
Reactant: CCOC(OCC)OCC
Solvent: CC(=O)OC(C)=O
Product: CCOC=C(C#N)C(=O)NC1CCCCC1
Yield: 35.4 %

Procedure:
2-cyano-N-cyclohexyl-acetamide (Intermediate #18) (1.35 g, 8.09 mmol) was suspended in acetic anhydride (20 mL). Triethyl orthoformate (3.91 g, 21 mmol) was added and the mixture heated to reflux for 5 h. The reaction mixture was cooled to ambient and to volatiles removed by evaporation in vacuo to leave a brown oil which was which was purified by chromatography on silica gel eluting with an EtOAc/DCM gradient (0-10%) to give the title compound as a solid (637 mg, 35%)
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]([CH3:23])[S:19]([CH3:22])(=[O:21])=[O:20])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:30][C:31]1[NH:32][C:33]2[C:38]([C:39]=1[CH3:40])=[CH:37][C:36]([OH:41])=[CH:35][CH:34]=2>CN(C=O)C>[CH3:30][C:31]1[NH:32][C:33]2[C:38]([C:39]=1[CH3:40])=[CH:37][C:36]([O:41][C:2]1[C:11]3[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]([CH3:23])[S:19]([CH3:22])(=[O:21])=[O:20])=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][N:3]=1)=[CH:35][CH:34]=2
Reactant: COc1cc2c(Cl)ncnc2cc1OCCCN(C)S(C)(=O)=O
Reactant: Cc1[nH]c2ccc(O)cc2c1C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCCCN(C)S(C)(=O)=O
Temperature: 100 °C
Reaction time: 5 h
Yield: 41.5 %

Procedure:
A mixture of 4-chloro-6-methoxy-7-(3-(N-methyl-N-methylsulphonylamino)propoxy)quinazoline (360 mg, 1.00 mmol), (prepared as described for the starting material in Example 152), potassium carbonate (215 mg, 1.56 mmol) and 2,3-dimethyl-5-hydroxyindole (177 mg, 1.10 mmol), (Arch. Pharm. 1972, 305, 159), in DMF (8.0 ml) was stirred at 100° C. for 5 hours and allowed to cool to ambient temperature. The solvent was removed by evaporation and the residue purified by silica column chromatography eluting with methanol (2.5%) in dichloromethane. The resulting solid was recrystallised from tertbutyl methyl ether/acetonitrile, filtered and washed with diethyl ether to give 4-(2,3-dimethylindol-5-yloxy)-6-methoxy-7-(3-(N-methyl-N-methylsulphonylamino)propoxy)quinazoline (201 mg, 42%).
Reaction SMILES: [OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([C:23]3[CH:28]=[C:27]([O:29][CH3:30])[C:26]([O:31][CH3:32])=[C:25]([O:33][CH3:34])[CH:24]=3)=[C:7]([C:19]([O:21][CH3:22])=[O:20])[N:8]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[C:9]2=[O:12])=[CH:4][C:3]=1[O:35][CH3:36].Cl.[N:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1[CH2:44][Cl:45].C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CN(C)C=O.O>[ClH:45].[CH3:36][O:35][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:2]=1[O:1][CH2:44][C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][N:38]=1)[C:9](=[O:12])[N:8]([N:13]1[CH2:14][CH2:15][O:16][CH2:17][CH2:18]1)[C:7]([C:19]([O:21][CH3:22])=[O:20])=[C:6]2[C:23]1[CH:28]=[C:27]([O:29][CH3:30])[C:26]([O:31][CH3:32])=[C:25]([O:33][CH3:34])[CH:24]=1
Reactant: ClCc1ccccn1
Reactant: COC(=O)c1c(-c2cc(OC)c(OC)c(OC)c2)c2cc(OC)c(O)cc2c(=O)n1N1CCOCC1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: O
Product: COC(=O)c1c(-c2cc(OC)c(OC)c(OC)c2)c2cc(OC)c(OCc3ccccn3)cc2c(=O)n1N1CCOCC1
Temperature: 50 °C
Reaction time: 8 h
Yield: 74.1 %

Procedure:
To a solution of the compound obtained in Example 2 (300 mg) in dimethylformamide (3 ml) are added 2-picolyl chloride hydrochloride (118 mg) and potassium carbonate (182 mg), and the mixture is stirred at 50° C. overnight. To the mixture are added ethyl acetate and water. The ethyl acetate layer is separated, washed, dried, and concentrated under reduced pressure. The residue (chemical name; 6-methoxy-3-methoxycarbonyl-2-morpholino-7-(2-pyridylmethyloxy)-4-(3,4,5-trimethoxyphenyl-1(2H)-isoquinolinone) is dissolved in ethyl acetate, and thereto is added a 4M solution of hydrogen chloride in ethyl acetate (150 μl). The mixture is stirred at room temperature for 30 minutes. The precipitated crystals are collected by filtration, and washed with ethyl acetate to give 6-methoxy-3-methoxycarbonyl-2-morpholino-7-(2-pyridylmethyloxy)-4-(3,4,5-trimethoxyphenyl)-1(2H)-isoquinolinone hydrochloride (279 mg) as listed in Table 1.
Reaction SMILES: [CH:1](=O)[CH2:2][CH2:3]C.N1CCOCC1.[CH3:12][O:13][C:14]([C:16]1[C:20](=O)O[C:18]2=[CH:22][CH:23]=[C:24]([CH:27]([CH3:29])[CH3:28])[CH:25]=[CH:26][C:17]=12)=[O:15]>C(O)C>[CH3:12][O:13][C:14]([C:16]1[C:17]2[C:18]([CH:22]=[CH:23][C:24]([CH:27]([CH3:29])[CH3:28])=[CH:25][CH:26]=2)=[C:1]([CH2:2][CH3:3])[CH:20]=1)=[O:15]
Reactant: COC(=O)c1c2ccc(C(C)C)ccc-2oc1=O
Reactant: CCCC=O
Solvent: C1COCCN1
Solvent: CCO
Product: CCc1cc(C(=O)OC)c2ccc(C(C)C)ccc1-2

Procedure:
n-Butyraldehyde (61.5 g, 0.853 mole) and morpholine (61.9 g, 0.71 mole) are added to cooled ethanol (400 ml), and then the compound (5) (68 g, 0.276 mole) is added thereto. The obtained mixture is stirred and warmed to dissolve the solid substance homogeneously. It is heated under reflux for 8 hours, and then the solvent is distilled off under reduced pressure to precipitate an oily material. The obtained oily material is dissolved in benzene (450 ml), washed twice with the same volume of water, three times with 1N HCl (400 ml), and further twice with water (400 ml). The obtained benzene solution is passed through alumina (500 g), and the eluted solution is concentrated to obtain the compound (1) at a yield of 57.4 g, 81.2%. It is recrystallized in n-hexane to give the purified product (55 g) in the purple crystalline form.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][C:17]=1[Cl:18])[NH:5][C@@H:6]1[CH2:10][CH2:9][CH2:8][C@H:7]1[NH:11][CH2:12][CH:13]=[CH2:14].C(N(CC)CC)C.Cl[C:27]([O:29][CH2:30][C:31]([Cl:34])([Cl:33])[Cl:32])=[O:28].C(=O)(O)[O-].[Na+]>C(OCC)C>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][C:17]=1[Cl:18])[NH:5][C@@H:6]1[CH2:10][CH2:9][CH2:8][C@H:7]1[N:11]([CH2:12][CH:13]=[CH2:14])[C:27]([O:29][CH2:30][C:31]([Cl:34])([Cl:33])[Cl:32])=[O:28]
Reactant: C=CCN[C@@H]1CCC[C@H]1Nc1ccc(Cl)c(Cl)c1
Reactant: O=C(Cl)OCC(Cl)(Cl)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: CCOCC
Product: C=CCN(C(=O)OCC(Cl)(Cl)Cl)[C@@H]1CCC[C@H]1Nc1ccc(Cl)c(Cl)c1
Product: Cl
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a mixture of 17.9 g (0.05 mole) of the above trans-3,4-dichloro-N-[2-(N-allylamino)cyclopentyl]-aniline, released from its hydrochloride salt and 5.5 g (0.05 mole) of triethylamine in 400 ml of ethyl ether there was added dropwise 10.6 g (0.05 mole) of 2,2,2-trichloroethyl chloroformate in 50 ml of ethyl ether while cooling the reaction vessel in ice in 30 minutes. The mixture was then stirred overnight at room temperature. The next day 250 ml of saturated sodium bicarbonate solution was added. The organic layer was then separated and washed with saturated sodium chloride solution, dried over magnesium sulfate and evaporated to a yellow oil, weighing 23.0 g. This was the crude sub-titled amine. A 1.0 g portion of this amine oil was converted to its hydrochloride salt with excess ethereal hydrogen chloride and the salt was recrystallized from a mixture of 15 ml of methanol and 80 ml of ethyl ether to obtain the trans-3,4-dichloro-N-[2-(N-allyl-N-trichloroethoxycarbonylamino)cyclopentyl]aniline hydrochloride, m.p. 160°-162° C., softens, then melts.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[F:11].[C-:12]#[N:13].[Na+]>C(O)C.O>[F:11][C:4]1[C:5]([O:9][CH3:10])=[CH:6][CH:7]=[CH:8][C:3]=1[CH2:2][C:12]#[N:13]
Reactant: [C-]#N
Reactant: COc1cccc(CCl)c1F
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: COc1cccc(CC#N)c1F
Temperature: 70 °C
Yield: 82.3 %

Procedure:
To a solution of 1-(chloromethyl)-2-fluoro-3-methoxybenzene (8.6 g, 49.3 mmol) in ethanol (60 mL) and water (10 mL), sodium cyanide (4.8 g, 98.5 mmol) was added. The resulting solution was heated at 70° C. for 16 h. After cooling to room temperature, the solution was poured into water (200 mL) and extracted with ethyl acetate (2×200 mL). The combined organic layers were washed (brine), dried (Na2SO4), and concentrated in vacuo to give the title compound (6.7 g). 1H NMR (CDCl3): δ 7.13-7.07 (m, 1H), 7.02-6.92 (m, 2H), 3.89 (s, 3H), 3.81 (s, 2H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([O:8]C)[N:5]=[C:4]([CH2:10][C:11]([N:13]2[C:21]3[C:16](=[C:17]([F:22])[CH:18]=[CH:19][CH:20]=3)[CH2:15][CH2:14]2)=[O:12])[N:3]=1.[I-].[K+].C(#N)C.C[Si](C)(C)Cl>CCOC(C)=O>[Cl:1][C:2]1[N:3]=[C:4]([CH2:10][C:11]([N:13]2[C:21]3[C:16](=[C:17]([F:22])[CH:18]=[CH:19][CH:20]=3)[CH2:15][CH2:14]2)=[O:12])[NH:5][C:6](=[O:8])[CH:7]=1
Reactant: COc1cc(Cl)nc(CC(=O)N2CCc3c(F)cccc32)n1
Agent: C[Si](C)(C)Cl
Agent: [I-]
Agent: [K+]
Solvent: CC#N
Solvent: CCOC(C)=O
Product: O=C(Cc1nc(Cl)cc(=O)[nH]1)N1CCc2c(F)cccc21
Reaction time: 8 h
Yield: 59 %

Procedure:
2 g of 2-(4-chloro-6-methoxypyrimidin-2-yl)-1-(4-fluoro-2,3-dihydroindol-1-yl)ethanone (example 17b, step 1b), potassium iodide (3.1 g), 30 ml of acetonitrile and 2.03 g of trimethylchlorosilane are placed in a reactor suitable for microwave-heating. The reactor is closed and irradiated for 30 minutes at 100° C. and then left overnight at A.T. The reaction medium is diluted with EtOAc and then washed twice with water and then with brine. The organic phases are combined, dried over magnesium sulfate, filtered and evaporated. The product obtained is chromatographed on silica. Elution is then carried out with dichloromethane/methanol (from 100/0 to 95/5). The fractions containing the expected product are evaporated under reduced pressure. The compound obtained is triturated from methanol, filtered and dried. 2-(4-Chloro-6-oxopyrimidin-2-yl)-1-(4-fluoro-2,3-dihydroindol-1-yl) ethanone is isolated (1.13 g); yield=59% (LCMS ES+ retention time Tr (min)=1.04; [M+H]+: m/z 308).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([S:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([N+:19]([O-])=O)[CH:12]=2)[CH:6]=[C:5]([O:22][CH3:23])[C:4]=1[O:24][CH3:25]>C(O)(=O)C.ClCCl.C(OCC)(=O)C.[Zn]>[CH3:18][O:17][C:14]1[CH:15]=[CH:16][C:11]([CH2:10][S:9][C:7]2[CH:6]=[C:5]([O:22][CH3:23])[C:4]([O:24][CH3:25])=[C:3]([O:2][CH3:1])[CH:8]=2)=[CH:12][C:13]=1[NH2:19]
Reactant: COc1ccc(CSc2cc(OC)c(OC)c(OC)c2)cc1[N+](=O)[O-]
Agent: [Zn]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: COc1ccc(CSc2cc(OC)c(OC)c(OC)c2)cc1N
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A room temperature suspension of zinc dust (2.35 g) in acetic acid (20 mL) was treated dropwise with a solution of Example 89A (100 mg, 0.27 mmol) and acetic acid (0.40 mL) in dichloromethane (1 mL), stirred at room temperature for 30 minutes, diluted with ethyl acetate (100 mL), filtered, and concentrated. The concentrate was dissolved in ethyl acetate, washed with saturated NaHCO3 and brine, dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 5% ethyl acetate/dichloromethane to provide the desired product.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([CH3:11])[CH:3]=1.S(=O)(=O)(O)O.O.[CH:18]1[CH:23]=CC=C[CH:19]=1>C(O)(C)C>[CH:18]([O:7][C:6](=[O:8])[C:5]1[CH:9]=[CH:10][C:2]([Br:1])=[CH:3][C:4]=1[CH3:11])([CH3:23])[CH3:19]
Reactant: c1ccccc1
Reactant: Cc1cc(Br)ccc1C(=O)O
Agent: O=S(=O)(O)O
Solvent: CC(C)O
Solvent: O
Product: Cc1cc(Br)ccc1C(=O)OC(C)C

Procedure:
A solution of 4-bromo-2-methyl-benzoic acid (Aldrich, 5.4 g, 25 mmol) in benzene (75 mL) and isopropanol (75 mL) was treated with concentrated sulfuric acid (1.5 mL) and heated to reflux over 4 days using a Dean-Stark water trap. The volatiles were evaporated in vacuo, the residue was diluted with water and extracted with diethyl ether. The organic phase was washed with water and saturated, aqueous sodium bicarbonate solution, dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to afford the title product as a clear oil that was used as such for the next step (6.12 g, 95%).
Reaction SMILES: C([C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][C:13]=1[O:14][CH3:15])[C:6]([O:8][CH2:9][CH3:10])=[O:7])=O.[CH:16]([O:21][CH3:22])([O:19][CH3:20])OC.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)(O)[O-].[Na+]>CO>[CH3:22][O:21][CH:16]([O:19][CH3:20])[C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][C:13]=1[O:14][CH3:15])[C:6]([O:8][CH2:9][CH3:10])=[O:7]
Reactant: COC(OC)OC
Reactant: CCOC(=O)c1ccc(OC)c(C=O)c1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: O
Product: CCOC(=O)c1ccc(OC)c(C(OC)OC)c1
Yield: 97 %

Procedure:
Ethyl 3-formyl-4-methoxybenzoate (500 mg) obtained in step C of Example 1-2-1 was dissolved in 10 mL of methanol. Trimethyl orthoformate (263 μL) and 41 mg of p-toluenesulfonic acid monohydrate were added to the solution, and then the mixture was heated for 2 hours under reflux. After the reaction solution was cooled, 5 mL of a saturated aqueous solution of sodium bicarbonate was added, and the resulting mixture was concentrated under reduced *pressure. The residue was diluted with ethyl acetate, washed with purified water and then with a saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate. The anhydrous sodium sulfate was separated by filtration, whereafter the filtrate was concentrated under reduced pressure. The residue was dried under reduced pressure to obtain 596 mg (97%) of ethyl 3-dimethoxymethyl-4-methoxybenzoate.
Reaction SMILES: FC(F)(F)S(O[C:7]1[C:8]2[CH2:28][N:27]([C:29](=[O:31])[CH3:30])[CH2:26][CH2:25][C:9]=2[N:10]=[C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[O:24][CH:23]=[N:22][CH:21]=3)=[CH:16][CH:15]=2)[N:12]=1)(=O)=O.[CH:34]1([NH:37][CH2:38][CH2:39][C:40]#[N:41])[CH2:36][CH2:35]1>CS(C)=O>[C:29]([N:27]1[CH2:26][CH2:25][C:9]2[N:10]=[C:11]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([C:20]4[O:24][CH:23]=[N:22][CH:21]=4)=[CH:16][CH:15]=3)[N:12]=[C:7]([N:37]([CH:34]3[CH2:36][CH2:35]3)[CH2:38][CH2:39][C:40]#[N:41])[C:8]=2[CH2:28]1)(=[O:31])[CH3:30]
Reactant: CC(=O)N1CCc2nc(Nc3ccc(-c4cnco4)cc3)nc(OS(=O)(=O)C(F)(F)F)c2C1
Reactant: N#CCCNC1CC1
Solvent: CS(C)=O
Product: CC(=O)N1CCc2nc(Nc3ccc(-c4cnco4)cc3)nc(N(CCC#N)C3CC3)c2C1
Reaction time: 8 h
Yield: 49.9 %

Procedure:
6-Acetyl-2-(4-(oxazol-5-yl)phenylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl trifluoromethanesulfonate (35 mg, 0.07 mmol, Example 26a) in DMSO (1 mL) was dispensed in a library plate. 3-(cyclopropylamino)propanenitrile (7.71 mg, 0.07 mmol) was added and it was left to shake overnight at 80° C. before filtered and purified by preparative HPLC to yield 3-((6-Acetyl-2-(4-(oxazol-5-yl)phenylamino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)(cyclopropyl)amino)propanenitrile (15.5 mg, 48%).
Reaction SMILES: [CH:1]([O:4][S:5]([C:8]1[C:17]([N:18]=[N:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)=[C:16]([OH:28])[C:15]2[C:10](=[CH:11][C:12]([NH2:29])=[CH:13][CH:14]=2)[CH:9]=1)(=[O:7])=[O:6])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.[C:39](Cl)(=[O:46])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>ClCCl>[CH:1]([O:4][S:5]([C:8]1[C:17]([N:18]=[N:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)=[C:16]([OH:28])[C:15]2[C:10](=[CH:11][C:12]([NH:29][C:39](=[O:46])[C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)=[CH:13][CH:14]=2)[CH:9]=1)(=[O:6])=[O:7])([CH3:3])[CH3:2]
Reactant: COc1ccc(N=Nc2c(S(=O)(=O)OC(C)C)cc3cc(N)ccc3c2O)cc1
Reactant: O=C(Cl)c1ccccc1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccc(N=Nc2c(S(=O)(=O)OC(C)C)cc3cc(NC(=O)c4ccccc4)ccc3c2O)cc1
Reaction time: 16 h
Yield: 47.9 %

Procedure:
7-Amino-4-hydroxy-3-(4-methoxy-phenylazo)-napthalene-2-sulfonic acid isopropyl ester (Example 6, 200 mg, 0.48 mmol ) was dissolved in dichloromethane (3 mL) and diisopropylethylamine (160 μL, 114 mg, 0.96 mmol) was added. Benzoyl chloride (85 mg, 0.60 mmol ) was then added under nitrogen. The reaction mixture was allowed to stir for 16 h. The suspension was filtered to provide the title compound (120 mg, 0.23 mmol, 48%) as a red solid: NMR (DMSO-d6): δ 16.25 (s, 1H), 10.81 (s, 1H), 8.52 (m, 1H), 8.37 (d, J=9 Hz, 1H), 8.08 (d, J=9 Hz, 1H), 8.02 (d, J=9 Hz, 2H), 7.81 (d, J=9 Hz, 2H), 7.64 (m, 3H), 7.18 (d, J=9 Hz, 2H), 4.82 (m, 1H), 3.83 (s, 3H), 1.25 (d, J=6 Hz, 6H); Analytical HPLC: 95% pure; MS (ES-NEG): [M−H] 518; Anal. Calc. for C27H24N3O6SNa: C, 62.42, H, 4.85, N, 8.09. Found: C, 60.61, H, 4.77, N, 7.70.
Reaction SMILES: C([O:3][C:4]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][N:16]1[C:20]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[C:19]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[N:18]=[C:17]1[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:5])C.[OH-].[Na+]>>[C:4]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][N:16]1[C:20]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)=[C:19]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[N:18]=[C:17]1[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)([OH:5])=[O:3]
Reactant: CCOC(=O)CCCCCCCCCCn1c(-c2ccccc2)nc(-c2ccccc2)c1-c1ccccc1
Agent: [Na+]
Agent: [OH-]
Product: O=C(O)CCCCCCCCCCn1c(-c2ccccc2)nc(-c2ccccc2)c1-c1ccccc1

Procedure:
1-(10-Ethoxycarbonyldecyl)-2,4,5-triphenylimidazole (1.3 g) was reacted with 2N sodium hydroxide in a method similar to Example 10 to give, after colnmn chromatography on silica gel eluted with a dichloro-methane:methanol gradient and recrystallisation from ethyl acetate/hexane, 1-(10-carboxydecyl)-2,4,5-triphenylimidazole (0.25 g, 19.2%) as a cream solid, m.p. 76°-78°; Found: C, 79.68%; H, 7.56%; N, 5.78%; C32H36N2O2 requires: C, 79.96%; H, 7.55; N, 5.83%.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C@H:8]([OH:10])[CH3:9])[CH:5]=[CH:6][CH:7]=1.[CH2:11]([Sn](CCCC)(CCCC)C=C)[CH2:12]CC>C1(C)C=CC=CC=1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH:11]([C:2]1[CH:3]=[C:4]([C@H:8]([OH:10])[CH3:9])[CH:5]=[CH:6][CH:7]=1)=[CH2:12]
Reactant: C[C@@H](O)c1cccc(Br)c1
Reactant: C=C[Sn](CCCC)(CCCC)CCCC
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: Cc1ccccc1
Product: C=Cc1cccc([C@@H](C)O)c1
Temperature: 45 °C
Reaction time: 18 h
Yield: 88.9 %

Procedure:
Bis(triphenylphosphine)palladium(II) dichloride (360 mg, 0.512 mmol) was added to a degassed solution of (R)-1-(3-bromo-phenyl)-ethanol (1.03 g, 5.123 mmol) and tributyl(vinyl)tin (1.8 ml, 6.15 mmol) in toluene (10 ml) under N2 and the reaction was stirred at 45° C. for 18 h. Tributyl(vinyl)tin (2.56 mmol, 750 uL) and bis(triphenylphosphine)palladium(II) dichloride (0.256 mmol, 180 mg) were added and stirring was continued for 18 h. The reaction was cooled and the solvent evaporated to afford a residue which was absorbed onto SiO2. Purification by SiO2 (3:11-hexane/ethyl acetate) afforded 13a as a yellow oil (675 mg, 89%). 1H NMR (300 MHz, CDCl3) δ7.49 (1H, s), 7.33 (3H, m), 6.75 (1H, dd, J=17.6, 10.9 Hz), 5.80 (1H, d, J=17.6 Hz), 5.28 (1H, d, J=10.7 Hz), 4.93 (1H, m), 1.81 (1H, d, J=3.1 Hz), 1.52 (3H, d, J=6.5 Hz).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][NH:5][C:6]1[CH:7]=[C:8]([CH:14]=[CH:15][CH:16]=1)[C:9]([N:11]([CH3:13])[CH3:12])=[O:10].[C:17]([N:19]=[C:20]([N:23]([CH3:32])[N:24]=CC1C=CC=CC=1)SC)#[N:18].Cl.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[NH2:18][C:17]1[N:19]=[C:20]([NH:1][CH2:2][CH2:3][CH2:4][NH:5][C:6]2[CH:7]=[C:8]([CH:14]=[CH:15][CH:16]=2)[C:9]([N:11]([CH3:12])[CH3:13])=[O:10])[N:23]([CH3:32])[N:24]=1
Reactant: CSC(=NC#N)N(C)N=Cc1ccccc1
Reactant: CN(C)C(=O)c1cccc(NCCCN)c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CN(C)C(=O)c1cccc(NCCCNc2nc(N)nn2C)c1
Yield: 42.7 %

Procedure:
3-[(3-Aminopropyl)amino]-N,N-dimethylbenzamide (0.8 g) and N-cyano-1-methyl-2-(phenylmethylene)hydrazine carboximidothioic acid, methyl ester (0.84 g) were heated together under reduced pressure of 14 mm Hg during 4 hr at 100°. The cooled reaction mixture was dissolved in acetone, treated with 1N hydrochloric acid (2 ml) and heated at 60° for 0.5 hr. The mixture was cooled, basified with potassium carbonate and extracted with ethyl acetate. Evaporation of the organic extracts gave a viscous oil which was triturated with ether to give the title compound (0.49 g). TLC silica; methanol:ammonia (80:1) Rf 0.63. NMR (CDCl3) 2.9 m (1H); 3.2-3.7 m (3H); 5.28 t (1H); 6.12 s (2H); 6.7 s (3H); 7.0 s (6H); 6.4-7.4 m (5H); 8.23 t (2H).