Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][CH:18]4[CH2:23][CH2:22][CH2:21][C:20](=[O:24])[CH2:19]4)[C:14]([F:25])=[CH:13][N:12]=3)=[CH:9][N:8]([S:26]([C:29]3[CH:34]=[CH:33][C:32](C)=[CH:31][CH:30]=3)(=[O:28])=[O:27])[C:5]2=[N:6][CH:7]=1.Cl[C:37]1C=C2C(C3N=C(NC4CCCC(=O)C4)C(F)=CN=3)=CN(S(C3C=CC=CC=3)(=O)=O)C2=NC=1.C[Mg]Br>C1COCC1.C(OCC)(=O)C.[NH4+].[Cl-]>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][CH:18]4[CH2:23][CH2:22][CH2:21][C:20]([CH3:37])([OH:24])[CH2:19]4)[C:14]([F:25])=[CH:13][N:12]=3)=[CH:9][N:8]([S:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)(=[O:28])=[O:27])[C:5]2=[N:6][CH:7]=1
Reactant: O=C1CCCC(Nc2nc(-c3cn(S(=O)(=O)c4ccccc4)c4ncc(Cl)cc34)ncc2F)C1
Reactant: Cc1ccc(S(=O)(=O)n2cc(-c3ncc(F)c(NC4CCCC(=O)C4)n3)c3cc(Cl)cnc32)cc1
Agent: C[Mg]Br
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC1(O)CCCC(Nc2nc(-c3cn(S(=O)(=O)c4ccccc4)c4ncc(Cl)cc34)ncc2F)C1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a cold (0° C.) solution of 3-[[2-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-pyrimidin-4-yl]amino]cyclohexanone, 28a, (0.47 g, 0.92 mmol) in THF (5 mL) was added methylmagnesium bromide (3.30 ml of 1.4M solution, 4.58 mmol). The reaction mixture was stirred at 0° C. for 1 h. The reaction mixture was diluted with ethyl acetate and aqueous saturated NH4Cl solution. The organic phase was separated, dried (MgSO4), filtered and concentrated in vacuo. The products were purified by silica chromatography with DCM and methanol, two products were eluded with 95% DCM and 5% methanol no separation. The two diastereomers were taken on as a mixture without further purification.
Reaction SMILES: Br[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=1.C([Li])CCC.C[O:18][C:19]1[CH2:23][CH2:22][C:21](=O)[CH:20]=1>O1CCCC1>[CH:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH:10]=[CH:11][C:2]=1[C:21]1[CH2:22][CH2:23][C:19](=[O:18])[CH:20]=1
Reactant: COC1=CC(=O)CC1
Reactant: Brc1ccc2ccccc2c1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: O=C1C=C(c2ccc3ccccc3c2)CC1
Temperature: -20 °C
Reaction time: 0.25 h

Procedure:
A solution of 2-bromonapthalene (8.03 g, 38.8 mmol) in anhydrous tetrahydrofuran (200 mL) at −78° C. was treated with a solution of n-butyllithium (1.6 M in hexane; 26.9 mL, 43.0 mmol, 1.1 eq.) such that the reaction temperature remained at −78° C. After 15 min, a solution of 3-methoxy-2-cyclopenten-1-one (5.0 g, 44.6 mmol, 1.1 eq.) in anhydrous tetrahydrofuran (50 mL) was added such that the reaction temperature remained below −78° C. The reaction was warmed to −20° C. over 2 h, quenched with a solution of 1N HCl (100 mL) and concentrated in vacuo to remove tetrahydrofuran. A solution of 1N HCl (100 mL) was added, stirred for 30 min and extracted with ethylacetate (3×100 mL). The combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate (100 mL), brine (100 mL), dried over magnesium sulphate, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography using 3:7 ethyl acetate/petrol as the eluting solvent to afford (2.77 g, 28%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 2.63-2.66 (2H, m, CH2), 3.17-3.20 (2H, m, CH2), 6.70 (1H, t, J 1.6 Hz, CH), 7.53-7.59 (2H, m, ArH), 7.75 (1H, dd, J 1.6, 8.5 Hz, ArH), 7.85-7.93 (3H, m, ArH), 8.12 (1H, s, ArH).
Reaction SMILES: Br[CH2:2][C:3]1[C:4]([CH3:14])=[N:5][C:6]2[C:11]([CH:12]=1)=[CH:10][C:9]([Cl:13])=[CH:8][CH:7]=2.[P:15]([O:20]C)([O:18][CH3:19])[O:16][CH3:17]>C1(C)C=CC=CC=1>[Cl:13][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[C:4]([CH3:14])[C:3]([CH2:2][P:15]([O:18][CH3:19])([O:16][CH3:17])=[O:20])=[CH:12]2
Reactant: COP(OC)OC
Reactant: Cc1nc2ccc(Cl)cc2cc1CBr
Solvent: Cc1ccccc1
Product: COP(=O)(Cc1cc2cc(Cl)ccc2nc1C)OC
Yield: 100.1 %

Procedure:
A mixture of 3-bromomethyl-6-chloro-2-methylquinoline (0.85 g, 3.0 mmol) and trimethyl phosphite (1.2 ml, 9.6 mmol) was refluxed in toluene (20 ml) for 16 hours. The reaction mixture was then concentrated in vacuo and the residue was flash chromatographed on silica gel. Elution with ethyl acetate afforded 0.90 g of 6-chloro-3-(dimethylphosphonomethyl)-2-methylquinoline.
Reaction SMILES: [OH-:1].[K+].C(P(C(C)(C)C)C1C=CC=CC=1[C:14]1[C:19](C(C)C)=[CH:18][C:17](C(C)C)=[CH:16][C:15]=1[CH:26](C)C)(C)(C)C>C1(C)C=CC=CC=1.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:26]([O:1][CH2:26][C:15]1[CH:14]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:14]=1
Reactant: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C(C)(C)C)C(C)(C)C)c(C(C)C)c1
Reactant: [OH-]
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Product: c1ccc(COCc2ccccc2)cc1
Temperature: 60 °C
Reaction time: 1.25 h

Procedure:
Method C) Compound 10 was dissolved in toluene (8 mml/mmol) and to the solution was added potassium hydroxide (2 eq, 11.7N) and the solution was degassed. To the solution was added properly substituted benzyl bromide (1.1 eq), 2-di-t-butylphosphino-2′,4′,6′-triisopropylbiphenyl (0.06 eq) and tris-(dibenzylideneaceton)-dipalladium(0) (0.03 eq). The mixture was stirred at 60° C. for 1.25 hrs. The mixture was cooled to room temperature, diluted with EtOAc and washed with 5% NaHCO3 solution (10 ml/mmol). The organic layers were dried on MgSO4, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography to give compound 12 in yields varying from 30-80%.
Reaction SMILES: Cl[C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[O:8][C:4]=2[N:5]=[CH:6][N:7]=1.CCN(C(C)C)C(C)C.Cl.[CH3:27][O:28][C:29](=[O:36])[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][NH2:35]>CN(C=O)C>[CH3:27][O:28][C:29](=[O:36])[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][NH:35][C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[O:8][C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: Clc1ncnc2oc(-c3ccccc3)cc12
Reactant: COC(=O)CCCCCN
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)CCCCCNc1ncnc2oc(-c3ccccc3)cc12
Temperature: 160 °C
Reaction time: 4 h

Procedure:
Heat 2.0 g (8.67 mmol) 4-chloro-6-phenylfuro[2,3-d]pyrimidine and 6.04 ml (34.7 mmol) DIEA in 5 ml DMF to 160° C. Add 3.15 g (17.34 mmol) 6-aminohexanoic acid methyl ester hydrochloride and stir for 4 h at 160° C. After cooling, add the mixture to ice water and extract three times with ethyl acetate. Combine the organic phases and wash with saturated ammonium chloride solution, dry over magnesium sulphate and concentrate under vacuum. Add methanol to the oil residue. Filter off the precipitated solid with suction, wash with methanol again and dry the solid at high vacuum. 1.85 g (57.2% of theor.) of the target compound is obtained.
Reaction SMILES: [H-].[Na+].C(OP([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])(OCC)=O)C.[C:17]1(=O)[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1.Cl>O1CCCC1.O>[C:17]1(=[CH:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1
Reactant: O=C1CCCCCCC1
Reactant: CCOC(=O)CP(=O)(OCC)OCC
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CCOC(=O)C=C1CCCCCCC1
Reaction time: 0.5 h

Procedure:
To a suspension of 60% sodium hydride/mineral oil (969 mg) in tetrahydrofuran (50 mL) was added ethyl diethylphosphonoacetate (5.48 mL) dropwise under ice cooling. After stirring the solution under ice cooling for 30 minutes, a solution of cyclooctanone (2.52 g) in tetrahydrofuran (70 mL) was added dropwise to the solution under ice cooling. The resulting solution was stirred under ice cooling for 2 hours and at room temperature for 40 hours. Water and 3N hydrochloric acid were then added to the solution, and the mixture was extracted with diethyl ether. The organic layer was washed with water and saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and then, concentrated under reduced pressure. The resulting residue was purified by chromatography (silica gel, hexane:ethyl acetate=9:1) to give the title compound (1.96 g)
Reaction SMILES: [CH2:1]1[O:3][CH:2]1[CH2:4][OH:5].[C:6]([OH:25])(=[O:24])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23]>>[CH3:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][C:6]([O:25][CH2:1][CH:2]([OH:3])[CH2:4][OH:5])=[O:24]
Reactant: CCCCCCCCCCCCCCCCCC(=O)O
Reactant: OCC1CO1
Product: CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO
Yield: 80.9 %

Procedure:
The experiment was carried out under the same conditions as in Example 3 but using a molar ratio of glycidol:stearic acid of 1.3:1. After 3 hours the amount of glycidol equivalent to the stearic acid had reacted and the mixture was cooled and worked up in a manner analogous to Example 1. There were obtained 116 grams of monostearin (80.9% yield) with the following properties:
Reaction SMILES: C([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][C:7]([C:13]#[N:14])=[C:6]2[O:15][CH:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1)=O.COC1C=CC(/[CH:36]=[C:37]2/[C:38]([NH:40][C:41]([S:43]/2)=[NH:42])=[O:39])=CC=1OC1CCCC1.C([O-])(=O)C.[Na+]>C(O)(=O)C>[NH2:42][C:41]1[S:43]/[C:37](=[CH:36]\[C:3]2[CH:4]=[C:5]3[C:10](=[CH:11][CH:12]=2)[N:9]=[CH:8][C:7]([C:13]#[N:14])=[C:6]3[O:15][CH:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)/[C:38](=[O:39])[N:40]=1
Reactant: COc1ccc(/C=C2\SC(=N)NC2=O)cc1OC1CCCC1
Reactant: N#Cc1cnc2ccc(C=O)cc2c1OC1CCOCC1
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CC(=O)O
Product: N#Cc1cnc2ccc(/C=C3\SC(N)=NC3=O)cc2c1OC1CCOCC1

Procedure:
Similar procedure as described in example 28c was used, starting from 6-formyl-4-(tetrahydro-pyran-4-yloxy)-quinoline-3-carbonitrile (example 76b), pseudothiohydantoin, sodium acetate and acetic acid to give 6-[2-amino-4-oxo-4H-thiazol-(5Z)-ylidenemethyl]-4-(tetrahydro-pyran-4-yloxy)-quinoline-3-carbonitrile. LC-MS m/e 381 (MH+).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N+:8]([O-:10])=[O:9].[CH3:11][C@H:12]1[CH2:17][NH:16][CH2:15][CH2:14][NH:13]1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1>[CH3:11][C@@H:12]1[NH:13][CH2:14][CH2:15][N:16]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[N+:8]([O-:10])=[O:9])[CH2:17]1
Reactant: O=[N+]([O-])c1ccccc1Br
Reactant: C[C@H]1CNCCN1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Product: C[C@H]1CN(c2ccccc2[N+](=O)[O-])CCN1
Yield: 479.1 %

Procedure:
To a solution of 2-bromo-nitrobenzene (0.6 g, 3.0 mmol) in 1,4-dioxane (15 mL) was added (S)-(+)-2-methylpiperazine (0.5 g, 0.5 mmol) and powdered K2CO3 (15.0 mmol, 1.5 g) and the resulting suspension was heated at reflux for 10 h. After the suspension was cooled, it was filtered through a sintered glass funnel and the solvent was evaporated in vacuo. The resulting residue was purified by column chromatography on silica gel (1:1 hexane/EtOAc followed by 4:1 EtOAc/MeOH) to yield (S)-(+)-3-methyl-1-(2-nitrophenyl)-piperazine as an orange oil (0.53 g, 80%). It was converted into (S)-(+)-3-methyl-1-(2-nitrophenyl)-4-(3-aminopropyl)-piperazine by the usual procedure.
Reaction SMILES: Cl.[NH:2]1[CH2:5][CH:4]([C:6](=[O:8])[CH3:7])[CH2:3]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.Cl.[CH3:40][N:41]1[CH2:46][CH2:45][C:44]2([CH2:55][C:54]3[C:49](=[N:50][CH:51]=[C:52](/[CH:56]=[CH:57]/[C:58](O)=[O:59])[CH:53]=3)[NH:48][C:47]2=[O:61])[CH2:43][CH2:42]1>CN(C)C=O>[C:6]([CH:4]1[CH2:5][N:2]([C:58](=[O:59])/[CH:57]=[CH:56]/[C:52]2[CH:53]=[C:54]3[C:49](=[N:50][CH:51]=2)[NH:48][C:47](=[O:61])[C:44]2([CH2:45][CH2:46][N:41]([CH3:40])[CH2:42][CH2:43]2)[CH2:55]3)[CH2:3]1)(=[O:8])[CH3:7]
Reactant: CN1CCC2(CC1)Cc1cc(/C=C/C(=O)O)cnc1NC2=O
Reactant: CC(=O)C1CNC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(=O)C1CN(C(=O)/C=C/c2cnc3c(c2)CC2(CCN(C)CC2)C(=O)N3)C1
Reaction time: 8 h

Procedure:
1-(Azetidin-3-yl)ethanone hydrochloride (110 mg, 0.8 mmol), EDCI (153 mg, 0.8 mmol), HOBt (108 mg, 0.8 mmol) and diisopropylethylamine (700 μL, 4.0 mmol) were successively added to a solution of (E)-3-(1′-methyl-2-oxo-2,4-dihydro-1H-spiro[[1,8]naphthyridine-3,4′-piperidine]-6-yl)acrylic acid hydrochloride (136 mg, 0.4 mmol) in dimethylformamide (15 mL) at room temperature. The reaction mixture was stirred overnight. After concentration to dryness, the residue was purified by chromatography on silica gel using dichloromethane/methanol/ammoniac (9:1:0.1) as eluent. Precipitation in a mixture DCM/pentane allowed isolation of the title product as a yellow solid (44.6 mg, 29%).
Reaction SMILES: O[N:2]=[C:3]([C:11](=O)[C:12]1[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=1)[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5].[C:19]1([CH2:29][NH2:30])[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21][CH:20]=1>C1(C)C=CC=CC=1>[C:19]1([C:29]2[NH:30][C:11]([C:12]3[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=3)=[C:3]([C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5])[N:2]=2)[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21][CH:20]=1
Reactant: NCc1cccc2ccccc12
Reactant: CC(C)(C)OC(=O)C(=NO)C(=O)c1ccncc1
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)c1nc(-c2cccc3ccccc23)[nH]c1-c1ccncc1
Yield: 17.5 %

Procedure:
tert-Butyl 2-hydroxyimino-3-oxo-3-(4-pyridyl)propionate (5.0 g) and 1-naphthylmethylamine (3.5 g) were dissolved in toluene (60 ml). The mixture was refluxed under heating for 3 hr while dehydrating with Dean-stark trap. After cooling, the precipitated crystals were collected by filtration and dried to give tert-butyl 2-(1-naphthyl)-5-(4-pyridyl)imidazole-4-carboxylate (1.3 g), melting point 184-190° C.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([CH:17]=O)[CH:12]=2)[CH:3]=1.[CH3:19][N:20]([CH3:24])[CH2:21][CH2:22][NH2:23].C([BH3-])#N.[Na+].[C:29]([OH:36])(=[O:35])/[CH:30]=[CH:31]/[C:32]([OH:34])=[O:33]>C(O)(=O)C.CO>[C:29]([OH:36])(=[O:35])/[CH:30]=[CH:31]/[C:32]([OH:34])=[O:33].[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([CH2:17][NH:23][CH2:22][CH2:21][N:20]([CH3:24])[CH3:19])[CH:12]=2)[CH:3]=1
Reactant: N#Cc1ccc(Cl)cc1Oc1cccc(C=O)c1
Reactant: CN(C)CCN
Agent: O=C(O)/C=C/C(=O)O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: CN(C)CCNCc1cccc(Oc2cc(Cl)ccc2C#N)c1
Yield: 90.6 %

Procedure:
4-Chloro-2-(3-formylphenoxy)benzonitrile (0.20 g, 0.78 mmol), N,N-dimethylethylenediamine (90 μL, 72 mg, 0.82 mmol) and sodium cyanoborohydride (60 mg, 0.96 mmol) were stirred at ambient temperature in a 1% acetic acid/methanol solution (20 mL) for 5 days. The solvent was removed in vacuo. The residue was treated with 10% sodium carbonate solution and extracted with ethyl acetate. The ethyl acetate layer was separated and fumaric acid (0.10 g, 0.86 mmol) was added. After the solvent was removed in vacuo, the residue was triturated with ethyl acetate overnight, collected by filtration, and dried to give 4-chloro-2-{3-[(2-dimethylaminoethylamino)methyl]-phenoxy}benzonitrile fumarate (315 mg, 90%) as a white solid.
Reaction SMILES: Cl[C:2]1[C:11]([O:12][CH:13]([C:18]2[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=2)[C:14]([F:17])([F:16])[F:15])=[N:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.CS(C)=O.[C:28]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[S:36]([NH2:39])(=[O:38])=[O:37])#[N:29].C(=O)([O-])[O-].[K+].[K+]>C(O)(=O)C>[C:28]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[S:36]([NH:39][C:2]1[C:11]([O:12][CH:13]([C:18]2[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=2)[C:14]([F:17])([F:16])[F:15])=[N:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1)(=[O:38])=[O:37])#[N:29]
Reactant: FC(F)(F)C(Oc1nc2ccccc2nc1Cl)c1cccnc1
Reactant: N#Cc1ccccc1S(N)(=O)=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: CC(=O)O
Product: N#Cc1ccccc1S(=O)(=O)Nc1nc2ccccc2nc1OC(c1cccnc1)C(F)(F)F
Temperature: 25 °C
Yield: 68.7 %

Procedure:
According to Example 132, by use of 2-chloro-3-[2,2,2-trifluoro-1-(pyridin-3-yl)ethoxy]-quinoxaline (Compound BJ) (70 mg, 0.21 mmol), dimethyl sulfoxide (2 mL), 2-cyanobenzenesulfonamide (38 mg, 0.21 mmol) and potassium carbonate (28 mg, 0.21 mmol), the mixture was stirred and reacted at 150° C. for 1.5 hours. The reaction mixture was allowed to cool down to room temperature, a 1% aqueous acetic acid solution was added thereto, and extraction with ethyl acetate was performed. The organic layer was washed with a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate, and then the solvent was evaporated off under reduced pressure. The residue was subjected to slurry purification using methanol, to give 2-cyano-N-{3-[2,2,2-trifluoro-1-(pyridin-3-yl)ethoxy]-quinoxalin-2-yl}benzenesulfonamide (Compound 145) (70 mg, 70%).
Reaction SMILES: [N+:1]([CH2:4][C:5]1[CH2:6][CH2:7][N:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:9][CH:10]=1)([O-])=O.N.[H][H]>[Ni].CO>[NH2:1][CH2:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:7][CH2:6]1
Reactant: [H][H]
Reactant: CCOC(=O)N1CC=C(C[N+](=O)[O-])CC1
Agent: [Ni]
Agent: N
Solvent: CO
Product: CCOC(=O)N1CCC(CN)CC1
Yield: 98.9 %

Procedure:
A mixture of 41 parts of ethyl 3,6-dihydro-4-(nitromethyl)-1(2H)pyridinecarboxylate and 400 parts of methanol, saturated with ammonia, was hydrogenated at normal pressure and at room temperature with 6 parts of Raney-nickel catalyst. After the calculated amount of hydrogen was taken up, the catalyst was filtered off and the filtrate was evaporated, yielding 35 parts (98.9%) of ethyl 4-(aminomethyl)-1-piperidinecarboxylate (intermediate 4).
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6](Cl)=[O:7].[CH:9]1([NH2:15])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1.C(N(CC)CC)C.CN(C1C=CC=CN=1)C>ClCCl>[CH:9]1([NH:15][C:6](=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2][Cl:1])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1
Reactant: NC1CCCCC1
Reactant: O=C(Cl)CCCCCl
Agent: CN(C)c1ccccn1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(CCCCCl)NC1CCCCC1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
A stirred solution of 5-chlorovaleryl chloride (50.0 g, 0.322 mol) in dichloromethane (300 ml) at 0° C. was treated dropwise with a solution containing cyclohexylamine (31.68 g, 0.320 mol), triethylamine (32.32 g, 0.320 mol) and dimethylaminopyridine (0.02 g) in dichloromethane (300 ml). The resulting solution was stirred for 2 hours at 0° C. and then for an additional 16 hours at room temperature. The solution was diluted with dichloromethane (400 ml), washed with water (3×200 ml), saturated aqueous sodium hydrogen carbonate (3×100 ml), saturated aqueous ammonium chloride (3×100 ml), and brine (2×100 ml) and then dried over anhydrous sodium sulfate. The solvent was evaporated off under reduced pressure to yield a crude product. The crude product was recrystallized from ethyl acetate-hexane to yield N-cyclohexyl-5-chloropentanamide as a colorless crystalline solid, having a melting point of 70°-71° C. and the following physical characteristics:
Reaction SMILES: [CH2:1]([N:4]1[C:13](=[O:14])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]=[C:5]1[NH:15][NH:16][C:17](=O)[CH2:18][CH2:19][Cl:20])[CH:2]=[CH2:3].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(O)C>[CH2:1]([N:4]1[C:13](=[O:14])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]2[C:17]([CH2:18][CH2:19][Cl:20])=[N:16][N:15]=[C:5]12)[CH:2]=[CH2:3]
Reactant: C=CCn1c(NNC(=O)CCCl)nc2ccccc2c1=O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: CCO
Product: C=CCn1c(=O)c2ccccc2n2c(CCCl)nnc12
Yield: 52.6 %

Procedure:
A mixture of 5.30 g of 3-allyl-2-[2-(3-chloropropionyl)hydrazino]quinazolin-4(3H)-one (0.0173 mol) and 10 mg of p-toluenesulfonic acid hydrate in 300 ml of ethanol was refluxed for 17 hours until TLC indicated that no starting material remained. The mixture was evaporated to dryness and the remaining yellow oil was dissolved in dichloromethane. The solution was washed twice with water, dried over MgSO4, filtered and evaporated. The resulting solid was purified by column chromatography using Kieselgel 60 with CH2Cl2 +1% MeOH as eluant and then was finally crystallized from ethanol to obtain 2.625 g (53% yield) of 4-allyl-1-(2-chloroethyl)[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-one melting at 142.5°-144° C.
Reaction SMILES: [CH3:1][N:2]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[O:19]=O>>[CH2:11]([N:2]([CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10])[CH:1]=[O:19])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: O=O
Reactant: CCCCCCCCN(C)CCCCCCCC
Product: CCCCCCCCN(C=O)CCCCCCCC
Yield: 4.5 %

Procedure:
By essentially the procedure of Example 1, a tube was charged with 40 g of methyldioctylamine and 1.0 g of CuCl2. 2H2O. The reaction was run at 109°-120° C. for 25 min while oxygen (0.2 mole) was injected incrementally at 160-275 psi. GC/MS analysis showed a 72.0% conversion of methyldioctylamine and a 4.5% yield of dioctylformamide.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][N+:5]([O-])=[CH:4][CH:3]=1.C[Si]([C:13]#[N:14])(C)C>>[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:13]#[N:14])[CH:3]=1
Reactant: [O-][n+]1ccc(Br)cc1
Reactant: C[Si](C)(C)C#N
Product: N#Cc1cc(Br)ccn1

Procedure:
The title compound was prepared from 4-bromopyridine-1-oxide (Rec. Trav. chim., 1951, 70, 581) and trimethylsilyl cyanide, using the procedure described in Chem. Pharm. Bull., 1985, 33, 565, and obtained as a solid (49% yield), m.p. 88°-93° C. Rf 0.53 (SS 11). Found: C,39.15; H,1.50; N,15.07. C6H3BrN2 requires C,39.37; E,1.65; N,15.30%.
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[N:13]=[CH:12][C:11]([NH2:14])=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.CN1CCN(C2C=CC(N[C:29]([C:31]3[C:32]4[N:33]=[CH:34][CH:35]=[N:36][C:37]=4[C:38]([C:41]4[C:50]5[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=5)[CH:44]=[CH:43][CH:42]=4)=[CH:39][CH:40]=3)=[O:30])=CC=2)CC1>>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[N:13]=[CH:12][C:11]([NH:14][C:29]([C:31]3[C:32]4[N:33]=[CH:34][CH:35]=[N:36][C:37]=4[C:38]([C:41]4[C:50]5[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=5)[CH:44]=[CH:43][CH:42]=4)=[CH:39][CH:40]=3)=[O:30])=[CH:10][CH:9]=2)[CH2:4][CH2:3]1
Reactant: CN1CCN(c2ccc(N)cn2)CC1
Reactant: CN1CCN(c2ccc(NC(=O)c3ccc(-c4cccc5ccccc45)c4nccnc34)cc2)CC1
Product: CN1CCN(c2ccc(NC(=O)c3ccc(-c4cccc5ccccc45)c4nccnc34)cn2)CC1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
The title compound was prepared in analogy to the procedure described in Step 14.1 but stirring the reaction mixture for 20 h at rt and using 6-(4-methylpiperazin-1-yl)-pyridin-3-ylamine (prepared as described in Example 33 but using N-methyl-piperazine in Step 33.2) and 8-naphthalen-1-yl-quinoxaline-5-carboxylic acid (Example 46). Title compound: ESI-MS: 475.0 [M+H]+; tR=3.76 min (System 1).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]#[N:10])=[CH:4][CH:3]=1.Br[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[N:13]=1.CC1C=CC(S([O-])=O)=CC=1.[Na+].[H-].[Na+]>C1COCC1.O>[C:9]([CH:8]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[N:13]=1)[C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)#[N:10]
Reactant: Cc1cccc(Br)n1
Reactant: N#CCc1ccc(F)cc1
Agent: Cc1ccc(S(=O)[O-])cc1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: Cc1cccc(C(C#N)c2ccc(F)cc2)n1
Yield: 83.8 %

Procedure:
To a mixture of 4-fluorophenylacetonitrile (3.97 g), 2-bromo-6-methylpyridine (5.00 g) and sodium 4-methylphenylsulfinate (10.48 g) in THF (125 ml) was added sodium hydride (2.35 g, 60%) at 0° C. under argon atmosphere, and the mixture was heated to reflux for 3 hours. The reaction mixture was added to water and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate and concentrated under reduced pressure, and the obtained residue was separated and purified by column chromatography (ethyl acetate:hexane 1:4), to give 2-(α-cyano-4-fluorobenzyl)-6-methylpyridine (5.51 g) as yellow oil.