Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:3]=1[C:4]([N:6]=[C:7]=[O:8])=[O:5].[CH3:14][O:15][C:16]1[CH:17]=[C:18]([C:25]2[NH:26][C:27]([CH2:30][C:31]([O-:33])=[O:32])=[N:28][N:29]=2)[CH:19]=[CH:20][C:21]=1[N+:22]([O-])=O>C(#N)C>[Cl:1][C:2]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:3]=1[C:4]([NH:6][C:7](=[O:8])[NH:22][C:21]1[CH:20]=[CH:19][C:18]([C:25]2[NH:26][C:27]([CH2:30][C:31]([OH:33])=[O:32])=[N:28][N:29]=2)=[CH:17][C:16]=1[O:15][CH3:14])=[O:5]
Reactant: COc1cc(-c2nnc(CC(=O)[O-])[nH]2)ccc1[N+](=O)[O-]
Reactant: O=C=NC(=O)c1ccc(F)cc1Cl
Solvent: CC#N
Product: COc1cc(-c2nnc(CC(=O)O)[nH]2)ccc1NC(=O)NC(=O)c1ccc(F)cc1Cl
Temperature: 25 °C
Reaction time: 8 h

Procedure:
The solution of equivalent amounts of 2-chloro-4-fluorobenzoyl isocyanate in acetonitrile was added dropwise to the solution of 89 mg of [5-(3-methoxy-4-nitrophenyl)-4H-[1,2,4]triazol-3-yl]acetate in 5 ml of acetonitrile and the mixture was stirred at room temperature overnight. The solid formed was then filtered off with suction and dried under reduced pressure.
Reaction SMILES: C(N(CC)CC)C.[C:8](Cl)(=[O:12])[C:9]([CH3:11])=[CH2:10].[CH3:14][C:15]1([OH:24])[CH2:23][C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:16]1>C1(C)C=CC=CC=1>[C:8]([O:24][C:15]1([CH3:14])[CH2:23][C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:16]1)(=[O:12])[C:9]([CH3:11])=[CH2:10]
Reactant: CC1(O)Cc2ccccc2C1
Reactant: C=C(C)C(=O)Cl
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: C=C(C)C(=O)OC1(C)Cc2ccccc2C1

Procedure:
With stirring and ice cooling, 111 g of triethylamine was added to a mixture of 120 g of methacrylic acid chloride, 200 g of 2-methyl-2-hydroxyindane, and 1500 g of toluene. The mixture was stirred at room temperature for 16 hours. By standard aqueous work-up and solvent distillation, a crude product was obtained. It was purified by column chromatography, yielding the target compound, 2-methylindan-2-yl methacrylate, designated Monomer 1.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C@H:9]([C:11]2[N:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:15](=[O:23])[C:14]3=[C:24]([CH3:27])[CH:25]=[CH:26][N:13]3[N:12]=2)[CH3:10])[C:3]=1Br.[CH3:29][O:30][C:31]1[CH:36]=[CH:35][C:34]([S:37]([NH:40][C:41]2[CH:46]=[CH:45][CH:44]=[C:43](B3OC(C)(C)C(C)(C)O3)[CH:42]=2)(=[O:39])=[O:38])=[CH:33][CH:32]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(P([Pd-4](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)C=CC=CC=1>[NH2:1][C:2]1[C:3]([C:43]2[CH:42]=[C:41]([NH:40][S:37]([C:34]3[CH:35]=[CH:36][C:31]([O:30][CH3:29])=[CH:32][CH:33]=3)(=[O:39])=[O:38])[CH:46]=[CH:45][CH:44]=2)=[C:4]([NH:8][C@H:9]([C:11]2[N:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:15](=[O:23])[C:14]3=[C:24]([CH3:27])[CH:25]=[CH:26][N:13]3[N:12]=2)[CH3:10])[N:5]=[CH:6][N:7]=1
Reactant: COc1ccc(S(=O)(=O)Nc2cccc(B3OC(C)(C)C(C)(C)O3)c2)cc1
Reactant: Cc1ccn2nc([C@H](C)Nc3ncnc(N)c3Br)n(-c3ccccc3)c(=O)c12
Agent: c1ccc([PH](c2ccccc2)(c2ccccc2)[Pd-4]([PH](c2ccccc2)(c2ccccc2)c2ccccc2)([PH](c2ccccc2)(c2ccccc2)c2ccccc2)[PH](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Product: COc1ccc(S(=O)(=O)Nc2cccc(-c3c(N)ncnc3N[C@@H](C)c3nn4ccc(C)c4c(=O)n3-c3ccccc3)c2)cc1
Yield: 47.5 %

Procedure:
(S)-2-(1-((6-Amino-5-bromopyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (215 mg, 0.49 mmol) was treated with 4-methoxy-N-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)benzenesulfonamide (291 mg, 0.75 mmol), sodium carbonate (159 mg, 3.08 mmol) and tetrakis(triphenylphosphino)palladium(0) (29 mg, 0.03 mmol) according to the method described in Example 3 to give 145 mg (48% yield) of the title compound as a solid. Purity 100%.
Reaction SMILES: [NH2:1][CH:2]1[CH2:8][CH2:7][CH2:6][CH2:5][N:4]2[C:9](=[O:19])[CH:10]=[C:11]([C:13]3[CH:18]=[CH:17][N:16]=[CH:15][N:14]=3)[N:12]=[C:3]12.C(N(CC)CC)C.Cl[C:28]([O:30][CH2:31][CH3:32])=[O:29]>O1CCCC1>[CH2:31]([O:30][C:28](=[O:29])[NH:1][CH:2]1[CH2:8][CH2:7][CH2:6][CH2:5][N:4]2[C:9](=[O:19])[CH:10]=[C:11]([C:13]3[CH:18]=[CH:17][N:16]=[CH:15][N:14]=3)[N:12]=[C:3]12)[CH3:32]
Reactant: NC1CCCCn2c1nc(-c1ccncn1)cc2=O
Reactant: CCOC(=O)Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CCOC(=O)NC1CCCCn2c1nc(-c1ccncn1)cc2=O
Reaction time: 0.17 h
Yield: 72.7 %

Procedure:
0.3 g (1.17 mmol) of (+/−)10-amino-2-pyrimidin-4-yl-7,8,9,10-tetrahydropyrimido[1,2-a]azepin-4(6H)-one (compound 3.4 of example 3) was diluted in 8 mL of tetrahydrofuran. 0.18 mL (1.28 mmol) of triethylamine was added at 0° C. and the mixture was stirred for 10 min and 0.12 mL (1.28 mmol) of ethyl chloroformate was added. The resulting mixture was stirred at room temperature for 1 h and quenched by adding a saturated solution of ammonium chloride. The product was extracted with dichloromethane, dried over sodium sulfate and the solvent was evaporated. The residue was triturated with diethyl ether and filtered to afford 0.28 g (72%) of (4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydro-pyrimido[1,2-a]azepin-10-yl)-carbamic acid ethyl ester as a yellow solid (Mp.: 168-170° C.). The compound was used as such in the next step.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:18][CH2:19][O:20][CH3:21])=[C:6]([CH:17]=1)[C:7]([C:9]1[C:14]([CH:15]=O)=[CH:13][CH:12]=[CH:11][N:10]=1)=[O:8].Cl.NO.C([N:27](CC)CC)C.C(OC(=O)C)(=O)C>C(#N)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:18][CH2:19][O:20][CH3:21])=[C:6]([CH:17]=1)[C:7]([C:9]1[C:14]([C:15]#[N:27])=[CH:13][CH:12]=[CH:11][N:10]=1)=[O:8]
Reactant: CCN(CC)CC
Reactant: COCOc1ccc(Cl)cc1C(=O)c1ncccc1C=O
Agent: Cl
Agent: NO
Solvent: CC(=O)OC(C)=O
Solvent: CC#N
Product: COCOc1ccc(Cl)cc1C(=O)c1ncccc1C#N
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 65.2 %

Procedure:
To a mixture of 2-(5-chloro-2-methoxymethoxybenzoyl)-3-formylpyridine (2.34 g), hydroxylamine hydrochloride (532 mg) and triethylamine (775 mg) was added acetonitrile (30 ml), which was stirred for 1.5 hour at room temperature. The reaction mixture was concentrated, which was partitioned with ethyl acetate/water. The organic layer was washed with a saturated aqueous saline solution, dried (anhydrous sodium sulfate), and concentrated to give 2-(5-chloro-2-methoxymethoxybenzoyl)-3-hydroxylminomethylpyridine (2.39 g). A mixture of this compound and acetic anhydride (15 ml) was heated for one hour under reflux, followed by distilling off acetic anhydride under reduced pressure. The residue was purified by means of 10 a silica gel column chromatography (eluent: ethyl acetate/hexane) to give 2-(5-chloro-2-methoxymethoxybenzoyl)-3-cyanopyridine (1.51 g) (Compound E-12).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([CH3:12])[C:3]=1[C:13]([O:15]CC)=O.[C:18]1([NH:24][NH2:25])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C1(C)C(C)=CC=CC=1>C(OCC)C>[CH3:12][C:4]1[NH:5][C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:11]=2[C:2]2[C:3]=1[C:13](=[O:15])[N:24]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[N:25]=2
Reactant: NNc1ccccc1
Reactant: CCOC(=O)c1c(C)nc2ccccc2c1Cl
Solvent: Cc1ccccc1C
Solvent: CCOCC
Product: Cc1[nH]c2ccccc2c2nn(-c3ccccc3)c(=O)c1-2
Temperature: 25 °C

Procedure:
The mixture of 3.6 g of ethyl 4-chloro-2-methylquinolin-3-carboxylate, 1.8 g of phenylhydrazine and 40 ml of xylene is refluxed for 4 hours, cooled to room temperature, diluted with diethyl ether and filtered. The residue is dissolved in 50 ml of 2 N aqueous sodium hydroxide, the solution washed with diethyl ether and its pH adjusted to 8.5 with ammonium chloride. The precipitate formed is collected, washed successively with hot water, methanol and diethyl ether, to yield the 4-methyl-2-phenylpyrazolo[4,3-c]quinolin-3(5H)-one, showing in the IR-spectrum peaks at 874, 867, 858, 850, 822, 780, 765, 756, 750, 740 and 722 cm-1. Analogously the 4-methyl-2-(p-chlorophenyl)-pyrazolo[4-3,-c]quinolin-3(5H)-one is prepared, melting at 349°-350°.
Reaction SMILES: [N:1]#[C:2][CH:3]=[CH:4][C:5]1[C:10]2[O:11][C@@H:12]([CH2:15][O:16][S:17]([C:20]3[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=3)(=[O:19])=[O:18])[CH2:13][O:14][C:9]=2[CH:8]=[CH:7][C:6]=1[N+:27]([O-])=O.O.O.[Sn](Cl)Cl>C(OCC)(=O)C>[CH3:26][C:23]1[CH:24]=[CH:25][C:20]([S:17]([O:16][CH2:15][CH:12]2[O:11][C:10]3=[C:5]4[C:6](=[CH:7][CH:8]=[C:9]3[O:14][CH2:13]2)[N:27]=[C:2]([NH2:1])[CH:3]=[CH:4]4)(=[O:19])=[O:18])=[CH:21][CH:22]=1
Reactant: Cc1ccc(S(=O)(=O)OC[C@H]2COc3ccc([N+](=O)[O-])c(C=CC#N)c3O2)cc1
Agent: Cl[Sn]Cl
Solvent: CCOC(C)=O
Solvent: O
Product: Cc1ccc(S(=O)(=O)OCC2COc3ccc4nc(N)ccc4c3O2)cc1

Procedure:
To a solution of 2.5 g (6.0 mmole) of toluene-4-sulfonic acid (2R)-8-(3-nitrilo-propenyl)-7-nitro-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl ester in 200 mL of ethyl acetate was added 6.8 g (30 mmole) of tin (II) chloride dihydrate and the mixture was refluxed under nitrogen for 5 hours. The solvent was then removed in vacuum and replaced with 250 mL of methanol. Concentrated HCl (5 mL) was added and the mixture was refluxed under a nitrogen atmosphere for 15 hours. The solvent was again removed in vacuum and 500 mL of saturated aqueous sodium bicarbonate added. This was extracted twice with 250 mL portions of ethyl acetate and the combined organics washed with 400 mL portions of water and saturated brine, dried over sodium sulfate, filtered and concentrated in vacuum. The residue was column chromatographed on silica gel with 5% methanol in chloroform as eluant to give 0.80 g of the (R)-enantiomer of the title compound as a yellow solid. 1H-NMR (CDCl3): doublet 8.0 δ (1 H); doublet 7.8 δ (2 H); doublet 7.3 δ (2 H); doublet 7.2 δ (1 H); doublet 7.1 δ (1 H); doublet 6.7 δ (1 H); multiplet 4.5 δ (1 H); multiplet 4.3 δ (3 H); doublet of doublets 4.1 δ (1 H); singlet 2.4 δ (3 H).
Reaction SMILES: [BH4-].[Na+].[CH3:3][C:4]1[C:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:8][NH:7][C:6](=[S:16])[N:5]=1.Cl>O>[CH3:3][CH:4]1[C:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:8][NH:7][C:6](=[S:16])[NH:5]1
Reactant: Cc1nc(=S)[nH]nc1-c1ccccc1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Product: CC1NC(=S)NN=C1c1ccccc1

Procedure:
Sodium borohydride (0.71 g) and 5-methyl-6-phenyl-1,2,4-triazine-3(2H)-thione which have methanol of crystallization (4.03 g) were reacted in tetrahydrofuran according to a similar manner to that of EXAMPLE 2:(2). The reaction mixture was treated with a mixture of 1N-hydrochloric acid and water, and then extracted with ethyl acetate. The extract was washed successively with 1N hydrochloric acid, brine, an aqueous solution of sodium carbonate and brine, dried over magnesium sulfate and concentrated to dryness. The resultant solid was washed with diisopropyl ether and recrystallized from ethanol to give 5-methyl-6-phenyl-4,5-dihydro-1,2,4-triazine-3(2H)-thione (1.48 g), mp 213°~214.5° C.
Reaction SMILES: O=C1C2C(=CC=CC=2)C(=O)[N:3]1[CH2:12][CH2:13][N:14]1[C:23]2[C:18](=[N:19][CH:20]=[C:21]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[CH:22]=2)[C:17]([OH:32])=[C:16]([C:33](OCC)=[O:34])[C:15]1=[O:38].[N:39]1([CH2:45][CH2:46][NH2:47])[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1.NN>CCO.O>[NH2:3][CH2:12][CH2:13][N:14]1[C:23]2[C:18](=[N:19][CH:20]=[C:21]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[CH:22]=2)[C:17]([OH:32])=[C:16]([C:33]([NH:47][CH2:46][CH2:45][N:39]2[CH2:44][CH2:43][O:42][CH2:41][CH2:40]2)=[O:34])[C:15]1=[O:38]
Reactant: CCOC(=O)c1c(O)c2ncc(Cc3ccc(F)cc3)cc2n(CCN2C(=O)c3ccccc3C2=O)c1=O
Reactant: NCCN1CCOCC1
Agent: NN
Solvent: CCO
Solvent: O
Product: NCCn1c(=O)c(C(=O)NCCN2CCOCC2)c(O)c2ncc(Cc3ccc(F)cc3)cc21
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of ethyl 1-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-7-[(4-fluorophenyl)methyl]-4-hydroxy-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylate (0.252 g, 0.49 mmol) in EtOH (15 mL) under nitrogen was treated with 2-(4-morpholinyl)ethanamine (0.321 mL, 2.44 mmol) for 30 min. (150° C. in a microwave vessel. The reaction was further microwaved for an additional 30 min.@150° C. after the addition of another equivalent (0.064 mL) of the amine. The reaction was transferred to a test tube, diluted with EtOH (30 mL), and treated with hydrazine (0.4 mL, 13 mmol)@50° C. overnight. After the reaction was cooled to ambient temperature the resulting suspension was diluted with water (120 mL) and refrigerated overnight. The resulting suspension was filtered, washed with 2:1 water:EtOH and thoroughly dried under high vacuum to provide the title compound as a pale yellow solid: 1H NMR (300 MHz, DMSO-d6) δ ppm 2.27 (s, 1 H), 2.39-2.46 (m, 5 H), 2.70-2.81 (m, 2 H), 3.40-3.53 (m, 1 H), 3.57-3.61 (m, 6 H), 4.16 (s, 2 H), 4.18-4.26 (m, 2 H), 7.10-7.17 (m, 2 H), 7.35-7.41 (m, 2 H), 8.13-8.15 (m, 1 H), 8.50-8.51 (m, 1 H), 10.36-10.43 (m, 1 H); ES+ MS: 470 (M+H+).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][N:10]2[C:14]([CH2:15][CH2:16][CH:17]=O)=[CH:13][N:12]=[CH:11]2)=[CH:5][CH:4]=1)#[N:2].CC(C)([O-])C>C(O)C>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]3[CH:11]=[N:12][CH:13]=[C:14]3[CH2:15][CH2:16][CH:17]=2)=[CH:5][CH:4]=1)#[N:2]
Reactant: N#Cc1ccc(Cn2cncc2CCC=O)cc1
Agent: CC(C)(C)[O-]
Solvent: CCO
Product: N#Cc1ccc(C2=CCCc3cncn32)cc1

Procedure:
A solution of 0.24 g of 1-(p-cyanophenylmethyl)-5-(2-formylethyl)-1H-imidazole in 10 ml of anhydrous ethanol is refluxed under nitrogen for 2 h with 20 mg of potasssium tert-butoxide, cooled and evaporated to yield the title compound.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH:19]4[CH2:21][O:20]4)=[CH:13][CH:12]=3)[NH:8][C:5]2=[N:6][CH:7]=1.[NH:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1>>[Br:1][C:2]1[CH:3]=[C:4]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH:19]([OH:20])[CH2:21][N:22]4[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]4)=[CH:13][CH:12]=3)[NH:8][C:5]2=[N:6][CH:7]=1
Reactant: C1CCNCC1
Reactant: Brc1cnc2[nH]c(-c3ccc(OCC4CO4)cc3)nc2c1
Product: OC(COc1ccc(-c2nc3cc(Br)cnc3[nH]2)cc1)CN1CCCCC1

Procedure:
The title compound was prepared from 6-bromo-2-[4-(oxiran-2-ylmethoxy)phenyl]-3H-imidazo[4,5-b]pyridine and piperidine.
Reaction SMILES: [CH3:1][N:2]([CH3:20])[C:3]1[CH:19]=[CH:18][C:6]([C:7]([C:9]2[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=2[C:11]([OH:13])=[O:12])=O)=[CH:5][CH:4]=1.[C:21]([NH:24][C:25]1[CH:37]=[CH:36][C:28]([NH:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[CH:27][CH:26]=1)(=[O:23])[CH3:22]>>[CH3:20][N:2]([CH3:1])[C:3]1[CH:4]=[CH:5][C:6]([C:7]2([N:29]([C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)[C:28]3[CH:27]=[CH:26][C:25]([NH:24][C:21](=[O:23])[CH3:22])=[CH:37][CH:36]=3)[C:9]3[C:10](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:11](=[O:12])[O:13]2)=[CH:18][CH:19]=1
Reactant: CC(=O)Nc1ccc(Nc2ccccc2)cc1
Reactant: CN(C)c1ccc(C(=O)c2ccccc2C(=O)O)cc1
Product: CC(=O)Nc1ccc(N(c2ccccc2)C2(c3ccc(N(C)C)cc3)OC(=O)c3ccccc32)cc1
Yield: 83.2 %

Procedure:
Following a procedure similar to that described in Example 1 but employing 4.0 g of 2-[4-(dimethylamino)benzoyl]benzoic acid and 3.4 g of 4-acetamido-N-phenylaniline there was obtained 5.9 g of 3-[4-(dimethylamino)phenyl]-3-[N-(4-acetamidophenyl)phenylamino]phthalide, m.p. 182°-184.5° C. An acetone solution of the product contacted with acidic clay or phenolic resin developed an orange-colored image.
Reaction SMILES: [Mg].II.Br[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[N:11]1[C:18](Cl)=[N:17][C:15](Cl)=[N:14][C:12]=1[Cl:13]>CCOCC.C1C=CC=CC=1>[Cl:13][C:12]1[N:14]=[C:15]([C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=2)[N:17]=[C:18]([C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=2)[N:11]=1
Reactant: Brc1ccccc1
Reactant: Clc1nc(Cl)nc(Cl)n1
Agent: II
Agent: [Mg]
Solvent: c1ccccc1
Solvent: CCOCC
Product: Clc1nc(-c2ccccc2)nc(-c2ccccc2)n1
Reaction time: 8 h
Yield: 134.2 %

Procedure:
The procedure used was based on the method of Jones et al, AD 229453, September 1959. A stirred mixture of magnesium turnings (24.3 g, 0.935 mol) and a crystal of iodine in ether (150 ml), was added a solution of bromobenzene (155.3 g, 0.985 mol) in ether (100 ml) under a nitrogen atmosphere over a period of 3.75 hr at such a rate as to maintain a gentle reflux. Thereafter, the mixture was refluxed for 2.5 hr. The Grignard reagent thus prepared was then cooled and transferred to an addition funnel and added with stirring to a solution of cyanuric chloride (70 g, 0.38 mol) in benzene (500 ml) at 4°-15° C. (ice bath cooling) over a period of 1.25 hr. After stirring overnight the mixture was refluxed for 4 hr, cooled, and filtered. The filtrate was evaporated to dryness using a Rinco evaporator yielding 136.5 g of crude product mixture. This mixture was distilled in vacuo at 0.007 mm. The desired product, bp 140°-152° C., 63.5 g(62% yield), was crystallized three times from heptane yielding pure 2-chloro-4,6-diphenyl-s-triazine, 46.1 g (45% yield), mp 136°-138° C.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([N:12]([CH3:14])[CH3:13])=[N:7][N:6]=[CH:5]2.[CH2:15]([Sn](CCCC)(CCCC)C=C)[CH2:16]CC>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.C1(C)C=CC=CC=1>[CH3:13][N:12]([CH3:14])[C:8]1[C:9]2[C:4](=[CH:3][C:2]([CH:15]=[CH2:16])=[CH:11][CH:10]=2)[CH:5]=[N:6][N:7]=1
Reactant: CN(C)c1nncc2cc(Br)ccc12
Reactant: C=C[Sn](CCCC)(CCCC)CCCC
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: C=Cc1ccc2c(N(C)C)nncc2c1
Temperature: 85 °C
Yield: 59.3 %

Procedure:
A mixture of (6-bromo-phthalazin-1-yl)-dimethyl-amine (0.32 g, 1.27 mmol) and toluene (8 mL) was purged with N2. Pd(PPh3)4 (0.4 g, 0.346 mmol) and tributyl vinyl stannane (1.11 mL, 3.80 mmol) were added and the reaction heated to 85° C. for 4 h. The reaction was cooled, filtered through celite and rinsed with CH2Cl2. The organic layers were washed with water, brine, dried (Na2SO4) and concentrated. Column chromatography (Hexanes/EtOAc) afforded the desired product (0.15 g, 59.3%) as a white solid.
Reaction SMILES: [C:1]1([CH:7]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].C1C(=O)N([Br:27])C(=O)C1>C1COCC1>[CH2:16]([O:15][C:13](=[O:14])[C:7]([Br:27])([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH3:17]
Reactant: O=C1CCC(=O)N1Br
Reactant: CCOC(=O)C(C(=O)OCC)c1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOC(=O)C(Br)(C(=O)OCC)c1ccccc1
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 85.4 %

Procedure:
To an ice-cooled solution of diethyl phenylmalonate (3.0 g, 12.7 mmol) in THF (90 mL) was added portionwise sodium hydride (1.015 g, 60% in oil, 25.4 mmol). The mixture was stirred in the ice bath for 30 min and NBS (2.486 g, 14 mmol) was added. The mixture was stirred in the ice bath for 10 min, and then at RT for 20 min. The reaction mixture was filtered through Celite® and the filtrate concentrated in vacuo. The residue was dissolved in DCM, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, gradient 2-8% EtOAc in cyclohexane) affording the title compound as a colourless oil (3.418 g, 85%). 1H NMR (CDCl3, 300 MHz): δ 7.60-7.56 (2H, m), 7.39-7.32 (3H, m), 4.33 (2H, q, J=7.1 Hz), 4.32 (2H, q, J=7.1 Hz), 1.30 (6H, d, J=7.1 Hz).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.C1C(=O)N([Br:19])C(=O)C1>C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.C(Cl)(Cl)(Cl)Cl>[Br:19][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1cccc2cccnc12
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: BrCc1cccc2cccnc12
Temperature: 25 °C
Yield: 83.7 %

Procedure:
Combine 8-methyl-quinoline (1.0 g, 6.99 mmol), NBS (1.3 g, 7.13 mmol), benzoyl peroxide (6.0 mg, 0.03 mmol), carbon tetrachloride (30 mL) and reflux for 17 h. Cool the reaction mixture to ambient temperature and evaporate the solvent. Dissolve the residue in chloroform (30 mL), wash the organic solution with saturated aqueous NaHCO3 (2×10 mL), brine (10 mL) and dry over anhydrous Na2SO4. Evaporate the solvent and purify by chromatography on silica gel eluting with DCM to obtain the title compound as a white solid (1.3 g, 83%). MS (ES+) m/z: 223 (M+H)+.
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]#[N:10])=[N:7][CH:8]=1.[C:11]([Si:15]([CH3:18])([CH3:17])Cl)([CH3:14])([CH3:13])[CH3:12].N1C=CN=C1.O>CN(C)C=O>[Si:15]([O:1][CH2:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]#[N:10])=[N:7][CH:8]=1)([C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:18])[CH3:17]
Reactant: N#Cc1ccc(CO)cn1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)[Si](C)(C)OCc1ccc(C#N)nc1
Temperature: 25 °C
Yield: 84.8 %

Procedure:
5-(Hydroxymethyl)pyridine-2-carbonitrile (258 mg) was dissolved in dimethylformamide (8 ml), tert-butyl dimethylchlorosilane (347 mg) and imidazole (326 mg) were added, and the mixture was stirred at room temperature for 1% hr. Water (20 ml) was added and the mixture was stirred, extracted with ethyl acetate (once with 50 ml and once with 20 ml), washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated and the obtained residue was purified by column chromatography (Yamazen HI-FLASH™ COLUMN size 2 L, elution solvent: hexane/ethyl acetate) to give the title compound (405 mg).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4]O.Cl[C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[N:10]=[C:9]([CH3:17])[CH:8]=1.[I-].[K+]>C(N(CC)CC)C>[CH3:17][C:9]1[CH:8]=[C:7]([NH:1][CH2:2][CH2:3][CH2:4][N:10]2[CH2:11][CH2:16][CH2:7][CH2:8][CH2:9]2)[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[N:10]=1
Reactant: NCCCO
Reactant: Cc1cc(Cl)c2ccccc2n1
Agent: [I-]
Agent: [K+]
Solvent: CCN(CC)CC
Product: Cc1cc(NCCCN2CCCCC2)c2ccccc2n1

Procedure:
Synthesis and purification were performed according to the procedure stated in example 152 using reagents 3-aminopropanol (15 mmol), 4-chloro-2-methylquinoline (15 mmol), 5 ml of triethylamine, and catalytic amounts of potassium iodide in the first step. The final product was purified by flash chromatography (eluent: ethyl acetate/triethylamine (95/5)). The solvent was removed under reduced pressure. The residue was crystallized with oxalic acid from diethyl ether/ethanol.
Reaction SMILES: [C:1]1([C:7]2[O:11][C:10]([C:12]3[C:13]([NH2:24])=[N:14][CH:15]=[C:16]([C:18]4[CH2:19][CH2:20][NH:21][CH2:22][CH:23]=4)[N:17]=3)=[N:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCN(CC)CC.[CH2:32]([S:34](Cl)(=[O:36])=[O:35])[CH3:33]>C(Cl)Cl>[CH2:32]([S:34]([N:21]1[CH2:20][CH:19]=[C:18]([C:16]2[N:17]=[C:12]([C:10]3[O:11][C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)=[N:8][N:9]=3)[C:13]([NH2:24])=[N:14][CH:15]=2)[CH2:23][CH2:22]1)(=[O:36])=[O:35])[CH3:33]
Reactant: CCS(=O)(=O)Cl
Reactant: Nc1ncc(C2=CCNCC2)nc1-c1nnc(-c2ccccc2)o1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCS(=O)(=O)N1CC=C(c2cnc(N)c(-c3nnc(-c4ccccc4)o3)n2)CC1
Reaction time: 0.5 h
Yield: 100 %

Procedure:
3-(5-phenyl-1,3,4-oxadiazol-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)pyrazin-2-amine (50 mg, 0.1151 mmol) was dissolved in DCM (3 mL) and Et3N (34.94 mg, 48.13 μL, 0.3453 mmol) followed by ethanesulfonyl chloride (16.28 mg, 12.00 μL, 0.1266 mmol) were added. The reaction was allowed to stir for 30 mins and then diluted with dichloromethane and washed with water. The aqueous layer was extracted further with dichloromethane and the organics washed with saturated aqueous NaHCO3, dried over MgSO4 and concentrated in vacuo. The resultant residue was purified on silica gel by flash column chromatography (0-5% MeOH/DCM) to afford the title compound (47.47 mg, 60% Yield).