Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Mn]([O-])(=O)(=O)=O.[K+].[O:7]1[C:12]2[CH:13]=[CH:14][C:15]([CH:17]=[O:18])=[CH:16][C:11]=2[O:10][CH2:9][CH2:8]1.[OH-:19].[K+]>O>[CH2:8]1[O:7][C:12]2[CH:13]=[CH:14][C:15]([C:17]([OH:19])=[O:18])=[CH:16][C:11]=2[O:10][CH2:9]1
Reactant: [OH-]
Reactant: O=Cc1ccc2c(c1)OCCO2
Agent: O=[Mn](=O)(=O)[O-]
Agent: [K+]
Solvent: O
Product: O=C(O)c1ccc2c(c1)OCCO2
Temperature: 25 °C
Reaction time: 0.75 h

Procedure:
A solution of potassium permanganate (3.31 g) in water (100 mL) was added over 30 min to a stirred solution of 1,4-benzodioxan-6-carboxaldehyde (2.50 g) in water (40 mL) at 90° C. Stirring was continued at 90° C. for an additional 45 min and the mixture was then cooled to ambient temperature. The mixture was made basic (pH 10) with aqueous 1M KOH solution, filtered, and the filtrate was cooled in an ice-bath and acidified to pH 3 with concentrated HCl. The precipitated solid was collected by filtration, washed with water, and dried. The solid was dissolved in dichloromethane, washed with saturated sodium chloride solution, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure to furnish 2H,3H-benzo[e]1,4-dioxane-6-carboxylic acid as a white powder. A portion of this material (1.05 g) was dissolved in thionyl chloride (10 mL) and the mixture heated at 50° C. under a nitrogen atmosphere for 7 h. After cooling to room temperature, the excess thionyl chloride was removed under reduced pressure and the residue dried under high vacuum for 1 h. The solid was cooled in an ice-bath and treated with ammonium hydroxide solution (10 mL, 28-30% ammonia). The mixture was stirred at 0° C. for 5 min, and at room temperature for an additional 1 hr. The product was collected by filtration, washed with water and dried under high vacuum to provide 2H,3H-benzo[e]1,4-dioxane-6-carboxamide as a white powder. A portion of this material (0.90 g) was suspended in anhydrous dichloromethane under nitrogen and treated with oxalyl chloride (3.8 mL of a 2M solution in dichloromethane). The mixture was heated at reflux for 15 h, cooled to room temperature, and concentrated under reduced pressure. The residue was dissolved in anhydrous tetrahydrofuran (10 mL), cooled in an ice-bath, and treated with 3-iodoaniline (604 μL). The ice-bath was removed and the reaction mixture was stirred at ambient temperature for 45 min. The resulting solid was filtered, washed with dichloromethane and methanol, and dried under high vacuum to produce the title compound as a white powder.
Reaction SMILES: C([O:4][C@@H:5]1[C@@H:10]([O:11]C(=O)C)[C@H:9]([O:15]C(=O)C)[C@@H:8]([CH2:19][O:20]C(=O)C)[O:7][C@H:6]1[C:24]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:27]([F:34])=[C:26]([CH2:35][C:36]2[S:37][C:38](Br)=[CH:39][CH:40]=2)[CH:25]=1)(=O)C.[C:42]([C:44]1[CH:45]=[C:46](B(O)O)[CH:47]=[CH:48][CH:49]=1)#[N:43]>>[C@@H:6]1([C:24]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:27]([F:34])=[C:26]([CH2:35][C:36]3[S:37][C:38]([C:48]4[CH:47]=[CH:46][CH:45]=[C:44]([C:42]#[N:43])[CH:49]=4)=[CH:39][CH:40]=3)[CH:25]=2)[O:7][C@H:8]([CH2:19][OH:20])[C@@H:9]([OH:15])[C@H:10]([OH:11])[C@H:5]1[OH:4]
Reactant: CC(=O)OC[C@H]1O[C@@H](c2cc(Cc3ccc(Br)s3)c(F)c3ccccc23)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: N#Cc1cccc(B(O)O)c1
Product: N#Cc1cccc(-c2ccc(Cc3cc([C@@H]4O[C@H](CO)[C@@H](O)[C@H](O)[C@H]4O)c4ccccc4c3F)s2)c1

Procedure:
The above 1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-3-(5-bromo-2-thienylmethyl)-4-fluoronaphthalene and 3-cyanophenylboronic acid were treated in a manner similar to Example 168 to give 1-(β-D-glucopyranosyl)-3-(5-(3-cyanophenyl)-2-thienylmethyl)-4-fluoronaphthalene. APCI-Mass m/Z 523 (M+NH4).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([F:12])[CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[C:7]2[CH3:11].[NH3:13]>O>[CH3:11][C:7]1[C:6]2[C:10](=[C:2]([NH2:13])[CH:3]=[C:4]([F:12])[CH:5]=2)[NH:9][CH:8]=1
Reactant: N
Reactant: Cc1c[nH]c2c(Br)cc(F)cc12
Solvent: O
Product: Cc1c[nH]c2c(N)cc(F)cc12
Temperature: 170 °C

Procedure:
A mixture of 7-bromo-5-fluoro-3-methyl-indole (2.5 g), Cu (0.77 g), CuBr (1.57 g) and NH3 (30 ml of a 33% aqueous solution) was heated in an autoclave for 2 h at 170° C. The mixture was diluted with water and extracted with EtOAc. The organic phase was dried and the solvent removed to give 3-methyl-5-fluoro-7-amino-indole as an oil which was used without further purification. UPLC/MS found for C9H9FN2 as (M+H)+165.2
Reaction SMILES: [O:1]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:25]([C:26]([NH2:28])=[O:27])=[C:17]3[NH:18][C:19]4[CH2:24][CH2:23][NH:22][CH2:21][C:20]=4[N:16]3[N:15]=2)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:29]([CH2:31][C:32](O)=[O:33])#[N:30]>>[C:29]([CH2:31][C:32]([N:22]1[CH2:23][CH2:24][C:19]2[NH:18][C:17]3[N:16]([N:15]=[C:14]([C:11]4[CH:10]=[CH:9][C:8]([O:1][C:2]5[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=5)=[CH:13][CH:12]=4)[C:25]=3[C:26]([NH2:28])=[O:27])[C:20]=2[CH2:21]1)=[O:33])#[N:30]
Reactant: N#CCC(=O)O
Reactant: NC(=O)c1c(-c2ccc(Oc3ccccc3)cc2)nn2c3c([nH]c12)CCNC3
Product: N#CCC(=O)N1CCc2[nH]c3c(C(N)=O)c(-c4ccc(Oc5ccccc5)cc4)nn3c2C1

Procedure:
The desired compound was prepared from 2-(4-phenoxyphenyl)-5,6,7,8-tetrahydro-4H-pyrazolo[5′,1′:2,3]imidazo[4,5-c]pyridine-3-carboxamide and 2-cyanoacetic acid according to the procedure similar to that for compound 54. 1H NMR (400 MHz, DMSO-d6 at 80° C.) δ 11.55 (s, 1H), 7.68 (d, J=8.6 Hz, 2H), 7.41 (d, J=7.6 Hz, 1H), 7.39 (d, J=7.6 Hz, 1H), 7.16 (t, J=7.6 Hz, 1H), 7.11-6.93 (m, 4H), 6.22 (br s, 2H), 4.68 (s, 2H), 4.14 (s, 2H), 3.86-3.79 (m, 2H), 2.84-2.73 (m, 2H). MS (ESI) m/e [M+1]+ 440.9.
Reaction SMILES: [H-].[Na+].[NH2:3][C:4]1[N:9]=[CH:8][N:7]=[C:6]([NH:10][C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[NH:16][CH:15]=[CH:14]3)[CH:5]=1.[CH2:20]([NH:22][C:23](=[O:31])OC1C=CC=CC=1)[CH3:21]>CN(C)C=O>[CH2:20]([NH:22][C:23]([N:16]1[C:17]2[C:13](=[CH:12][C:11]([NH:10][C:6]3[CH:5]=[C:4]([NH:3][C:23]([NH:22][CH2:20][CH3:21])=[O:31])[N:9]=[CH:8][N:7]=3)=[CH:19][CH:18]=2)[CH:14]=[CH:15]1)=[O:31])[CH3:21]
Reactant: CCNC(=O)Oc1ccccc1
Reactant: Nc1cc(Nc2ccc3[nH]ccc3c2)ncn1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCNC(=O)Nc1cc(Nc2ccc3c(ccn3C(=O)NCC)c2)ncn1
Reaction time: 0.5 h
Yield: 4.5 %

Procedure:
Sodium hydride (69 mg, 1.73 mmol) was suspended in N,N-dimethylformamide (3 ml); 6-amino-4-(1H-5-indolylamino)pyrimidine (311 mg, 1.38 mmol) was added thereto at room temperature under nitrogen stream; the reaction mixture was stirred for 30 minutes; phenyl N-ethylcarbamate (286 mg, 1.73 mmol) was added thereto; and the reaction mixture was stirred overnight. The reaction mixture was partitioned between a solvent mixture of ethyl acetate-tetrahydrofuran (1:1) and a saturated aqueous solution of sodium hydrogencarbonate; the organic layer was washed with water and brine, and dried over anhydrous sodium sulfate; the solvent was distilled off; the residue was purified by silica gel column chromatography (eluent; ethyl acetate:tetrahydrofuran=1:1); eluted fractions were concentrated; ethyl acetate was added to the residue to crystallize; and the crystals were filtered off, and dried under aeration to yield the title compound (14.3 mg, 0.039 mmol, 2.8%) as white crystals.
Reaction SMILES: Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[NH:6]2.O.[CH3:17][N:18](C=O)C>>[C:17]([C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[NH:6]2)#[N:18]
Reactant: CCOC(=O)c1cc2c(Br)cccc2[nH]1
Reactant: CN(C)C=O
Solvent: O
Product: CCOC(=O)c1cc2c(C#N)cccc2[nH]1
Temperature: 150 °C
Yield: 82 %

Procedure:
To a stirred solution of ethyl 4-bromo-1H-indole-2-carboxylate (500 mg, 1.86 mmol) in DMF (10 mL) was added Cu(I)CN (501 mg, 5.59 mmol) and heated to 150° C. for 24 h. The reaction mixture was cooled to room temperature, the water (25 mL) was added and the reaction mixture extracted with ethyl acetate (4×50 mL). The organic layer was washed with water (25 mL), brine (25 mL), dried over anhydrous Na2SO4 and evaporated under reduced pressure to get the crude product. The crude product was purified by column chromatography over silica gel (100-200 mesh) using a solvent gradient of 10% ethyl acetate in petroleum ether to afford 330 mg (82%) of ethyl 4-cyano-1H-indole-2-carboxylate (I-3a) as an off-white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:26])([CH3:25])[CH2:9][CH:10](I)[Sn:11]([CH2:20][CH2:21][CH2:22][CH3:23])([CH2:16][CH2:17][CH2:18][CH3:19])[CH2:12][CH2:13][CH2:14][CH3:15])=[CH:4][CH:3]=1.O1CCCC1>O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:26])([CH3:25])[CH:9]=[CH:10][Sn:11]([CH2:16][CH2:17][CH2:18][CH3:19])([CH2:12][CH2:13][CH2:14][CH3:15])[CH2:20][CH2:21][CH2:22][CH3:23])=[CH:4][CH:3]=1
Reactant: CCCC[Sn](CCCC)(CCCC)C(I)CC(C)(C)c1ccc(Cl)cc1
Solvent: O
Solvent: C1CCOC1
Product: CCCC[Sn](C=CC(C)(C)c1ccc(Cl)cc1)(CCCC)CCCC
Yield: 75.2 %

Procedure:
Under a nitrogen atmosphere, a stirred solution of 8.7 grams (0.015 mole) of 3-(4-chlorophenyl)-3-methyl-1-iodo-1-tributylstannylbutane and 6.5 mL (0.045 mole) of 1,8-diazabicyclo 5.4.0!undec-7-ene (DBU)in 50 mL of tetrahydrofuran was heated at reflux for about 18 hours. The reaction mixture was cooled and poured into about 225 mL of water. The mixture was then made acidic with aqueous 2N hydrochloric acid and extracted with two 150 mL portions of diethyl ether. The combined extracts were dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue. The residue was subjected to column chromatography on silica gel, using 5% methylene chloride in petroleum ether as the eluant. The product-containing fractions were combined and concentrated under reduced pressure, yielding 5.3 grams of 3-(4-chlorophenyl)-3-methyl-1-tributylstannyl-1-butene. The NMR spectrum was consistent with the proposed structure.
Reaction SMILES: [C:1]([N:8]1[CH2:12][CH2:11][CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CN(C)CCN(C)C.C([Li])(CC)C.[CH:26](=[O:33])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C(OCC)C>[C:1]([N:8]1[CH2:9][CH2:10][CH2:11][CH:12]1[CH:26]([OH:33])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]
Reactant: CC(C)(C)OC(=O)N1CCCC1
Reactant: O=Cc1ccccc1
Agent: CN(C)CCN(C)C
Agent: [Li]C(C)CC
Solvent: CCOCC
Product: CC(C)(C)OC(=O)N1CCCC1C(O)c1ccccc1
Temperature: -78 °C
Reaction time: 2 h

Procedure:
N-Boc-pyrrolidine (5.0 g) is dissolved in diethyl ether (60 mL) and the solution is cooled to −78° C. N,N,N′,N′-Tetramethylethylenediamine (TMEDA) (4.4 mL) is added to the mixture followed by sec-butyl lithium (27.0 mL, 1.3 M in cyclohexane) maintaining the temperature below 60° C. After 2 h, benzaldehyde (3.6 mL) is added and the mixture is stirred at −70° C. for an additional 30 mL The reaction mixture is allowed to warm to room temperature and is then quenched with water and poured into EtOAc (200 mL). The separated organic layer is washed with saturated aq. ammonium chloride (3×50 mL) followed by brine (50 mL), dried (MgSO4), and concentrated. The crude product is purified by column chromatography (heptane/EtOAc, 8/1; 6/1) to afford 6.3 g of N-Boc-2-(hydroxy(phenyl)methyl)-pyrrolidine as a mixture of diasteromers. The resulting N-Boc-2-(hydroxy(phenyl)-methyl)pyrrolidine (5.6 g) is dissolved in dichloromethane (500 mL) and trifluoroacetic acid (60 mL) is added. The mixture is concentrated, dissolved in dichloromethane (200 mL), and washed with saturated aq. sodium bicarbonate (3×100 DL). The aqueous layers are extracted with dichloromethane (4×50 mL) and the combined organic layers are concentrated. The crude product is distilled in a Kugelrohr apparatus (150-175° C., 0.2 Torr) to afford 2.47 g of the title compound as a mixture of diasteromers. Physical characteristics. MS (ESI+) m/z 178 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:31]=[CH:30][CH:29]=[C:28]([Cl:32])[C:3]=1[CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[N:11]([CH2:15][CH2:16][CH2:17][C:18]#[N:19])[C:10]([C:20]([N:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1)=[O:21])=[CH:9]2.[N:33]([Si](C)(C)C)=[N+:34]=[N-:35].C([Sn](=O)CCCC)CCC>C1(C)C=CC=CC=1>[Cl:32][C:28]1[CH:29]=[CH:30][CH:31]=[C:2]([Cl:1])[C:3]=1[CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[N:11]([CH2:15][CH2:16][CH2:17][C:18]1[NH:35][N:34]=[N:33][N:19]=1)[C:10]([C:20]([N:22]1[CH2:23][CH2:24][O:25][CH2:26][CH2:27]1)=[O:21])=[CH:9]2
Reactant: N#CCCCn1c(C(=O)N2CCOCC2)cc2cc(OCc3c(Cl)cccc3Cl)ccc21
Reactant: C[Si](C)(C)N=[N+]=[N-]
Agent: CCCC[Sn](=O)CCCC
Solvent: Cc1ccccc1
Product: O=C(c1cc2cc(OCc3c(Cl)cccc3Cl)ccc2n1CCCc1nnn[nH]1)N1CCOCC1
Yield: 79.8 %

Procedure:
To a solution of 4-[5-(2,6-dichlorobenzyloxy)-2-(1-morpholin-4-yl-methanoyl)indol-1-yl]butyronitrile (0.085 g, 0.18 mmol) in toluene (10 mL) was added azidotrimethylsilane (0.071 mL, 0.54 mmol) and dibutyltin oxide (0.014 g, 0.054 mmol). The reaction mixture was heated to reflux and stirred under argon at reflux temperature for 40 h. The solution was then cooled and the toluene removed under reduced pressure. Methanol was then added and removed under reduced pressure. Ethyl acetate was added and the reaction mixture was washed with water and brine. The organic layer was dried over MgSO4, filtered, and the solvent removed under reduced pressure. Purification by flash chromatography (silica gel, 10% methanol/dichloromethane) yielded a white solid (0.074 g, 79%). MS(ES) m/e 515.2 [M+H]+.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:17](=[O:19])[CH3:18])[C:5]2[N:9]=[CH:8][N:7](C3CCCCO3)[C:6]=2[CH:16]=1.CC1C=CC(S(O)(=O)=O)=CC=1>O.CO>[F:1][C:2]1[CH:3]=[C:4]([C:17](=[O:19])[CH3:18])[C:5]2[N:9]=[CH:8][NH:7][C:6]=2[CH:16]=1
Reactant: CC(=O)c1cc(F)cc2c1ncn2C1CCCCO1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: CO
Product: CC(=O)c1cc(F)cc2[nH]cnc12
Temperature: 80 °C
Yield: 99.6 %

Procedure:
A mixture of 1-(6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-4-yl)ethanone (1.0 g, 3.82 mmol) and TsOH (1.97 g, 11.45 mmol) in water (10 mL) and MeOH (50 mL) was heated at 80° C. for 3 h. The reaction mixture was quenched with EtOAc (50 mL) and water (50 mL). The aqueous phase was extracted with EtOAc (50 mL×2). The combined organic layers were washed with water and brine, dried (Na2SO4), filtered, and concentrated in vacuo to afford 1-(6-fluoro-1H-benzo[d]imidazol-4-yl)ethanone as a yellow solid (678 mg, 99.8%). MS (ESI): m/z=179.3 [M+1].
Reaction SMILES: [Si]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH:15]=[C:14]([CH2:19][N:20]1[CH2:23][CH:22]([C:24]([O:26][CH3:27])=[O:25])[CH2:21]1)[CH:13]=[CH:12]2)(C(C)(C)C)(C)C.Cl.C([O-])(O)=O.[Na+]>CO>[OH:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH:15]=[C:14]([CH2:19][N:20]1[CH2:23][CH:22]([C:24]([O:26][CH3:27])=[O:25])[CH2:21]1)[CH:13]=[CH:12]2
Reactant: COC(=O)C1CN(Cc2ccc3cc(O[Si](C)(C)C(C)(C)C)ccc3c2)C1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Product: COC(=O)C1CN(Cc2ccc3cc(O)ccc3c2)C1
Reaction time: 1 h
Yield: 47.3 %

Procedure:
To a solution of methyl 1-((6-(tert-butyldimethylsilyloxy)naphthalen-2-yl)methyl)azetidine-3-carboxylate (4.5 g, 11.7 mmol) in methanol (50 mL) at 0° C. was added con. HCl (5 mL) dropwise. The reaction mixture was stirred at r.t for 1 h. The mixture was neutralized by sat. NaHCO3 and evaporated off most of solvent, extracted with DCM and washed with brine, dried over Na2SO4 and concentrated to obtain crude product. The crude product was purified by silica gel chromatography (DCM:MeOH=40:1), extracted with DCM and washed with brine, dried over Na2SO4 and concentrated to obtain crude product. The crude product was purified by silica gel chromatography (DCM:MeOH=40;1) to give the title compound (1.5 g, 47%) as a gray solid. ESI-MS (M+1)+: 272.0. 1H NMR (400 MHz, CDCl3) δ: 8.14 (s, 1H), 7.59-7.52 (m, 2H), 7.39-7.28 (m, 2H), 7.09-7.04 (m, 2H), 3.92 (s, 2H), 3.86-3.82 (m, 2H), 3.70 (s, 3H), 3.63-3.59 (m, 2H), 3.252-3.46 (m, 1H).
Reaction SMILES: [CH2:1]([N:4]([CH2:15][CH:16]=[CH2:17])[S:5]([C:8]1[CH:9]=[N:10][CH:11]=[CH:12][C:13]=1Cl)(=[O:7])=[O:6])[CH:2]=[CH2:3].[I-].[Li+].[NH3:20]>>[CH2:1]([N:4]([CH2:15][CH:16]=[CH2:17])[S:5]([C:8]1[CH:9]=[N:10][CH:11]=[CH:12][C:13]=1[NH2:20])(=[O:7])=[O:6])[CH:2]=[CH2:3]
Reactant: C=CCN(CC=C)S(=O)(=O)c1cnccc1Cl
Reactant: N
Agent: [I-]
Agent: [Li+]
Product: C=CCN(CC=C)S(=O)(=O)c1cnccc1N
Temperature: 120 °C
Yield: 59 %

Procedure:
A mixture of N,N-diallyl-4-chloropyridine-3-sulfonamide (1.5 g, 5.5 mmol), lithium iodide (0.74 g, 5.5 mmol) and ammonia (7 M in methanol, 14 mL, 5.5 mmol) under an atmosphere of argon was heated at 120° C. for 2 h in a microwave reactor. Silica was added and the solvent was evaporated. Purification by column chromatography, using chloroform/methanol (95:5) as the eluent, gave the title compound in 59% yield.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9](/[CH:12]=[CH:13]/[C:14]2[O:15][C:16]3[CH:22]=[CH:21][CH:20]=[CH:19][C:17]=3[N:18]=2)=[CH:8][CH:7]=1.[NH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1.Cl>>[N:23]1([CH2:2][CH2:3][CH2:4][O:5][C:6]2[CH:11]=[CH:10][C:9](/[CH:12]=[CH:13]/[C:14]3[O:15][C:16]4[CH:22]=[CH:21][CH:20]=[CH:19][C:17]=4[N:18]=3)=[CH:8][CH:7]=2)[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1
Reactant: C1CCNCC1
Reactant: ClCCCOc1ccc(/C=C/c2nc3ccccc3o2)cc1
Agent: Cl
Product: C(=C/c1nc2ccccc2o1)\c1ccc(OCCCN2CCCCC2)cc1
Yield: 41 %

Procedure:
The procedure of Example 1 was followed starting with (C) of Example 1 (2.0 g, 6.4 mmol) and using piperidine in place of dibutylamine to produce 1.1 g, (41% yield) of the named compound as the HCl salt, mp 127°-128° C. IR(KBr): 3400,1600 cm−1. MS: 363(MH+). 1H NMR (CD3 OD): δ 7.89-6.81 (m, 10H), 4.24 (t, J=5.5 Hz, 2H), 2.65 (m, 6H), 1.75 (m, 8H).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][NH2:6].[C:7](#[N:10])[CH:8]=[CH2:9]>CO>[C:7]([CH2:8][CH2:9][NH:1][CH2:2][CH2:3][CH2:4][CH2:5][NH2:6])#[N:10]
Reactant: NCCCCN
Reactant: C=CC#N
Solvent: CO
Product: N#CCCNCCCCN
Reaction time: 12 h
Yield: 79.8 %

Procedure:
To a solution of 1,4-diaminobutane (8.6 g, 97.6 mmol) in methanol (3.0 ml) was added a solution of acrylonitrile (6.2 g, 116.8 mmol) in methanol (3.0 ml) at 0° C., and the mixture was stirred for 12 hours. Evaporation of the solvent in vacuo afforded N-(2'-cyanoethyl)-1,4-diaminobutane as a colorless oil (11.0 g, 80%). 1H NMR (400 MHz, CDCl3) δ: 1.45 (4H, br, --CH2 CH2 --), 2.46 (2H, t), 2.58 (2H, t), 2.62 (2H, t) and 2.84 (2H, t).
Reaction SMILES: CO[C:3](=[O:15])[C:4]([CH3:14])([CH3:13])[CH2:5][O:6][CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][O:8]1.[C:16](#[N:18])[CH3:17].[H-].[Na+]>C1(C)C=CC=CC=1>[CH3:14][C:4]([CH3:13])([CH2:5][O:6][CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][O:8]1)[C:3](=[O:15])[CH2:17][C:16]#[N:18]
Reactant: COC(=O)C(C)(C)COC1CCCCO1
Reactant: CC#N
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CC(C)(COC1CCCCO1)C(=O)CC#N
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 101.4 %

Procedure:
A solution of 129 g (0.60 mol) of 2,2-dimethyl-3-(tetrahydro-pyran-2-yloxy)-propionic acid methyl ester and 44 mL (0.84 mol) of acetonitrile in toluene (250 mL) is added dropwise to the refluxing suspension of 33 g (0.84 mol) of sodium hydride (60% in mineral oil) in toluene (600 mL) over a period of 2 h. After the addition, the reaction mixture is stirred at reflux for 3 h. Additional 16.7 g (0.42 mol) of sodium hydride (60% dispersion in mineral oil) and 22 mL (0.42 mol) of acetonitrile are added to the reaction mixture and the refluxing is continued for another 1.5 h. After this time, the reaction mixture is cooled to room temperature and ice water (˜0.8 L) is added. The layers are separated and the aqueous layer is neutralized to pH ˜6-7 by adding 1M aqueous HCl solution. The aqueous layer is extracted with ethyl acetate (3×0.8 L). The organic layers are combined, washed with brine (1.5 L), dried over Na2SO4 and filtered. The filtrate is concentrated under reduced pressure to yield 137 g of 4,4-dimethyl-3-oxo-5-(tetrahydro-pyran-2-yloxy)-pentanenitrile as a brown oil, which is used in the next step without further purification. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.09 (6H, s), 1.10 (6H, s), 1.4-1.7 (6H, m), 3.3 (1H, m), 3.35 (1H, d), 3.4 (1H, m), 3.6 (1H, d), 3.7 (1H, m), 4.2 (1H, s); 4.55 (1H, t).
Reaction SMILES: [CH3:1][Mg]Cl.[Cl:4][C:5]1[C:13]2[CH:12]=[C:11]([C:14](N(OC)C)=[O:15])[S:10][C:9]=2[CH:8]=[CH:7][CH:6]=1.O.Cl>O1CCCC1>[Cl:4][C:5]1[C:13]2[CH:12]=[C:11]([C:14](=[O:15])[CH3:1])[S:10][C:9]=2[CH:8]=[CH:7][CH:6]=1
Reactant: CON(C)C(=O)c1cc2c(Cl)cccc2s1
Reactant: C[Mg]Cl
Agent: Cl
Solvent: C1CCOC1
Solvent: O
Product: CC(=O)c1cc2c(Cl)cccc2s1
Reaction time: 0.5 h

Procedure:
Methylmagnesium chloride (3M solution in tetrahydrofuran; 5.7 ml) was added under nitrogen to a stirred solution of 4-chloro-N-methoxy-N-methylbenzo[b]thiophene-2-carboxamide (4 g; prepared in a manner similar to that described in Example 18) in tetrahydrofuran (120 ml) then the mixture was allowed to stand at ambient temperature for 30 minutes, heated under reflux for 30 minutes and allowed to stand at ambient temperature for 30 minutes. Further methylmagnesium chloride (3M solution in tetrahydrofuran; 2.0 ml) was added and the mixture was allowed to stand at ambient temperature for 2 hours. Further methylmagnesium chloride (3M solution in tetrahydrofuran; 2.0 ml) was added and the mixture was allowed to stand at ambient temperature for 30 minutes. Water (200 ml) and 5M hydrochloric acid (15 ml) were added and the product was extracted into dichloromethane (3×80 ml). The combined extracts were dried (MgSO4) and the solvents were removed in vacuo. The residue was purified by column chromatography over silica using dichloromethane as eluant. Appropriate fractions were combined and the solvents removed in vacuo to leave 1-(4-chloro-benzo[b]thiophen-2-yl]ethan-1-one (1.8 g) as an off-white solid, m.p. 113-115° C.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:20]=[CH:19][C:18]3[O:17][C:16]4[CH:15]=[CH:14][NH:13][C:12](=[O:21])[C:11]=4[C:10](=O)[C:9]=3[CH:8]=2)[CH:2]=1.[CH3:23][Mg]Br.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>C1COCC1.ClCCCl>[CH2:23]=[C:10]1[C:11]2[C:12](=[O:21])[NH:13][CH:14]=[CH:15][C:16]=2[O:17][C:18]2[CH:19]=[CH:20][C:7]([C:3]3[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=3)=[CH:8][C:9]1=2
Reactant: O=c1[nH]ccc2oc3ccc(-c4cccnc4)cc3c(=O)c12
Reactant: C[Mg]Br
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: c1cc[nH+]cc1
Solvent: C1CCOC1
Solvent: ClCCCl
Product: C=C1c2cc(-c3cccnc3)ccc2Oc2cc[nH]c(=O)c21
Temperature: 0 °C
Reaction time: 1 h

Procedure:
A solution of 8-(pyridin-3-yl)-1H-chromeno[3,2-c]pyridine-1,10(2H)-dione (0.100 g, 0.345 mmol) in THF (3.00 mL) was cooled to 0° C. and methylmagnesium bromide (3.0 M in diethyl ether) (0.345 mL, 1.034 mmol) was added dropwise. The mixture stirred at 0° C. for 1 h. The mixture was quenched at 0° C. with saturated aqueous ammonium chloride solution and diluted with ethyl acetate. The aqueous phase was separated and extracted with ethyl acetate. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated to afford a tan solid. The material was dissolved in 1,2-dichloroethane (3.00 mL), pyridinium p-toluenesulfonate (8.66 mg, 0.034 mmol) was added, and the mixture was heated at reflux for 2 h to afford a tan suspension. This mixture was filtered, and the solids were washed with 1,2 dichloroethane and dried to afford 10-methylene-8-(pyridin-3-yl)-2,10-dihydro-1H-chromeno[3,2-c]pyridin-1-one as a tan solid. MS m/z=289.0 [M+H]+. Calcd for C18H12N2O2: 288.1.