Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([Cl:11])=[CH:8][CH:9]=2)[NH:4][C:3]=1[C:12](=[O:22])[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([NH2:21])=[O:20])[CH:14]=1.[C:23](Cl)(=[O:25])[CH3:24]>C(OCC)(=O)C.CCCCCC>[C:23]([NH:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([Cl:11])=[CH:8][CH:9]=2)[NH:4][C:3]=1[C:12](=[O:22])[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([NH2:21])=[O:20])[CH:14]=1)(=[O:25])[CH3:24]
Reactant: CC(=O)Cl
Reactant: NC(=O)c1cccc(C(=O)c2[nH]c3cc(Cl)ccc3c2N)c1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: CC(=O)Nc1c(C(=O)c2cccc(C(N)=O)c2)[nH]c2cc(Cl)ccc12

Procedure:
The title compound was prepared according to the procedure described in Example 19 employing 3-amino-2-(3-aminocarbonylbenzoyl)-6-chloroindole (Example 128) and acetyl chloride. m.p.: 243-247° C. (ethyl acetate/hexane)
Reaction SMILES: [NH:1]1[CH:5]=[N:4][CH:3]=[N:2]1.Cl[C:7]1[N:8]=[C:9]([NH:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:10]2[CH:15]=[C:14]([CH2:16][CH3:17])[S:13][C:11]=2[N:12]=1>>[N:1]1([C:7]2[N:8]=[C:9]([NH:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:10]3[CH:15]=[C:14]([CH2:16][CH3:17])[S:13][C:11]=3[N:12]=2)[CH:5]=[N:4][CH:3]=[N:2]1
Reactant: CCc1cc2c(NCc3ccccc3)nc(Cl)nc2s1
Reactant: c1nc[nH]n1
Product: CCc1cc2c(NCc3ccccc3)nc(-n3cncn3)nc2s1

Procedure:
Following the procedure of Example 97, the reaction of 1,2,4-triazole with 2-chloro-6-ethyl-4-benzylamino-thieno-[2,3-d]-pyrimidine gives 2-(1,2,4-triazol-1-yl)-6-ethyl-4-benzylamino-thieno-[2,3-d]-pyrimidine.
Reaction SMILES: [C:1]1([NH2:8])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH2:7].[CH2:9](O)[CH3:10]>C(O)C1C=CC=CC=1>[CH:6]1[C:1]2[NH:8][C:9]3[C:10](=[CH:6][C:1]4[C:2]([CH:3]=3)=[N:8][C:1]3[C:2](=[CH:3][CH:4]=[CH:5][CH:6]=3)[N:7]=4)[NH:7][C:2]=2[CH:3]=[CH:4][CH:5]=1
Reactant: Nc1ccccc1N
Reactant: CCO
Solvent: OCc1ccccc1
Product: c1ccc2c(c1)Nc1cc3nc4ccccc4nc3cc1N2
Temperature: 137.5 °C
Reaction time: 20 h
Yield: 92 %

Procedure:
2,5-Dihydroxy-1,4-dibenzoquinone (4, 30.0 g, 0.2 mol) was added to a solution of o-phenylendiamine (5, 115.79 g, 1.1 mol) in benzyl alcohol (11.6 vol). The reaction mixture was heated to 135-140° C. and stirred for 20 hours. The reaction mixture was cooled to room temperature, and ethanol (120 mL) was added. The resulting suspension was filtered through a Buchner funnel and the solid was washed with ethanol (120 mL) and dried under vacuum in an oven at 60-70° C. to furnish 5,14-Dihydro-5,7,12,14-tetraazapentacene 3. Yield: 92%; HPLC purity: 99.56%.
Reaction SMILES: [NH2:1][C:2]1[C:17]([Cl:18])=[CH:16][C:5]([C:6]([NH:8][CH2:9][CH2:10][N:11]([CH2:14]C)[CH2:12]C)=[O:7])=[C:4]([O:19]C)[CH:3]=1.NC1C(Cl)=CC(C(NCCN(C)C)=O)=C(OC)C=1>>[NH2:1][C:2]1[C:17]([Cl:18])=[CH:16][C:5]([C:6]([NH:8][CH2:9][CH2:10][N:11]([CH3:14])[CH3:12])=[O:7])=[C:4]([OH:19])[CH:3]=1
Reactant: CCN(CC)CCNC(=O)c1cc(Cl)c(N)cc1OC
Agent: COc1cc(N)c(Cl)cc1C(=O)NCCN(C)C
Product: CN(C)CCNC(=O)c1cc(Cl)c(N)cc1O
Yield: 89 %

Procedure:
The general procedure of Preparation 1A was repeated except that the 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxybenzamide utilized therein was replaced by 4-amino-5-chloro-N-[2-(dimethylamino)ethyl]-2-methoxybenzamide (prepared according to U.K. Patent Specification 1,793,771). The solvent (DMF) was removed in vacuo, and the residue treated with water and methylene chloride saturated with carbon dioxide, concentrated, and the crude product isolated in 89% yield by extraction with ethanol. A sample was chromatographed on a silica gel column using methylene chloride (97), methanol (3), ammonia (0.3) solvent system. The appropriate fractions were combined and concentrated in vacuo. The residue was crystallized from methanol to give the title compound as a colorless solid, mp. 163°-165°.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.[C:10]([O:14][CH2:15][CH3:16])(=[O:13])[CH:11]=[CH2:12].C(N(CC)CC)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:9][O:8][C:5]1[N:6]=[CH:7][C:2]([CH:12]=[CH:11][C:10]([O:14][CH2:15][CH3:16])=[O:13])=[CH:3][CH:4]=1
Reactant: C=CC(=O)OCC
Reactant: COc1ccc(Br)cn1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CCOC(=O)C=Cc1ccc(OC)nc1
Temperature: 90 °C

Procedure:
A solution of the 5-bromo-2-methoxypyridine 7-2 (74.3 g, 0.4 mol), ethyl acrylate (150 mL, 1.4 mol), triethylamine (150 mL, 1.08 mol), palladium acetate (10 g, 0.045 mol) and tri-o-tolylphosphine (20 g, 0.066 mol) in 100 mL acetonitrile was degassed with argon for 10 minutes. The mixture is heated at 90° C. for 12 hr, then the volatiles were removed m vacuo. Toluene (300 mL) was added and the mixture concentrated again. Diethyl ether (300 mL) was added and the mixture filtered through a pad of silica gel eluting with 800 mL of diethyl ether. After removal of the diethyl ether, the residue was chromatographed on silica gel eluting with EtOAc/hexane 1:19 then 1:14 then 1:9 to give 7-3 as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 1.34 (3H, t), 3.97 (3H, s), 4.26 (2H, q), 6.34 (1H, d),6.76 (1H, d), 7.63 (1H, d), 7.77 (1H, dd),8.27 (1H, d).
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]([OH:12])=O)=[CH:9][C:4]=2[N:3]=[CH:2]1.[CH3:13][O:14][C:15]1[C:28]2[CH2:27][CH2:26][C@H:25]3[C@H:20]([CH2:21][CH2:22][CH2:23][NH:24]3)[C:19]=2[CH:18]=[CH:17][CH:16]=1>>[NH:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]([N:24]3[C@@H:25]4[C@@H:20]([C:19]5[CH:18]=[CH:17][CH:16]=[C:15]([O:14][CH3:13])[C:28]=5[CH2:27][CH2:26]4)[CH2:21][CH2:22][CH2:23]3)=[O:12])=[CH:9][C:4]=2[N:3]=[CH:2]1
Reactant: COc1cccc2c1CC[C@@H]1NCCC[C@H]21
Reactant: O=C(O)c1ccc2[nH]cnc2c1
Product: COc1cccc2c1CC[C@H]1[C@@H]2CCCN1C(=O)c1ccc2[nH]cnc2c1
Yield: 85 %

Procedure:
The title compound is prepared from 1H-benzoimidazole-5-carboxylic acid and cis-7-methoxy-1,2,3,4,4a,5,6,10b-octahydro-benzo[f]quinoline following a procedure analogous to that described in Example 1. Yield: 85% of theory; LC (method 1): tR=2.62 min; Mass spectrum (ESI+): m/z=362 [M+H]+.
Reaction SMILES: [NH2:1][C:2]1[CH:19]=[CH:18][C:5]([O:6][C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][N:8]=2)=[CH:4][CH:3]=1.[C:20](Cl)(Cl)=[O:21]>C1(C)C=CC=CC=1>[Cl:13][C:12]1[C:7]([O:6][C:5]2[CH:18]=[CH:19][C:2]([N:1]=[C:20]=[O:21])=[CH:3][CH:4]=2)=[N:8][CH:9]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:11]=1
Reactant: Nc1ccc(Oc2ncc(C(F)(F)F)cc2Cl)cc1
Reactant: O=C(Cl)Cl
Solvent: Cc1ccccc1
Product: O=C=Nc1ccc(Oc2ncc(C(F)(F)F)cc2Cl)cc1

Procedure:
A mixture of 2-(4-aminophenoxy)-3-chloro-5-trifluoromethylpyridine (0.45 g) and a solution of phosgene in toluene (50 ml of a 12% solution) was heated at the reflux temperature for 6 hours. Evaporation of the volatile portion under reduced pressure yielded 3-chloro-5-trifluoromethyl-2-(4-isocyanatophenoxy)pyridine as a residual pale brown oil (0.5 g) which was used without further purification.
Reaction SMILES: CON(C)C(C1SC=NC=1)=O.CON(C)[C:15](=[O:25])[C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=1.[CH3:27][N:28]1[C:32](C(C2SC=NC=2)=O)=[CH:31][N:30]=[CH:29]1>>[CH3:27][N:28]1[C:32]([C:15]([C:16]2[CH:17]=[CH:18][C:19]([N+:22]([O-:24])=[O:23])=[CH:20][CH:21]=2)=[O:25])=[CH:31][N:30]=[CH:29]1
Reactant: Cn1cncc1C(=O)c1cncs1
Reactant: CON(C)C(=O)c1ccc([N+](=O)[O-])cc1
Agent: CON(C)C(=O)c1cncs1
Product: Cn1cncc1C(=O)c1ccc([N+](=O)[O-])cc1

Procedure:
The title compound was prepared by substituting N-methoxy-N-methylthiazole-5-carboxamide (Intermediate 11: step a) with N-methoxy-N-methyl-4-nitrobenzamide (Intermediate 20: step a) then following the procedure described for the preparation of (1-methyl-1H-imidazol-5-yl)(thiazol-5-yl)methanone (Intermediate 13).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH:9]([C:11]([OH:13])=[O:12])[O:8][C:7]([CH:20]3[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]3)([CH:14]3[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]3)[C:6]=2[CH:26]=1.[C:27]1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)(O)[O-].[Na+]>CO>[CH3:27][O:12][C:11]([CH:9]1[O:8][C:7]([CH:20]2[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]2)([CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)[C:6]2[CH:26]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=2[O:10]1)=[O:13]
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Reactant: O=C(O)C1Oc2ccc(Cl)cc2C(C2CCCCC2)(C2CCCCC2)O1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Product: COC(=O)C1Oc2ccc(Cl)cc2C(C2CCCCC2)(C2CCCCC2)O1
Temperature: 25 °C

Procedure:
A solution of 2 g 6-chloro-4,4-dicyclohexyl-4H-benzo[1,3]dioxine-2-carboxylic acid and 73 mg para-toluenesulfonic acid in 4 ml methanol was refluxed for 4 hours. After cooling to room temperature, 50 mg sodium bicarbonate was added and the solvent was removed in vacuo. The residue was dissolved in 10 ml EtOAc, washed with water and dried over Na2SO4. The solvent was removed in vacuo. Yield 1.3 g.
Reaction SMILES: [Mg].Br[C:3]1[S:4][CH:5]=[CH:6][CH:7]=1.Br[C:9]1[CH:10]=[CH:11][C:12]([N:15]([CH3:17])[CH3:16])=[N:13][CH:14]=1.O>C1COCC1>[S:4]1[CH:5]=[CH:6][CH:7]=[C:3]1[C:9]1[CH:10]=[CH:11][C:12]([N:15]([CH3:17])[CH3:16])=[N:13][CH:14]=1
Reactant: Brc1cccs1
Reactant: CN(C)c1ccc(Br)cn1
Agent: [Mg]
Solvent: C1CCOC1
Solvent: O
Product: CN(C)c1ccc(-c2cccs2)cn1
Temperature: 25 °C
Reaction time: 3 h
Yield: 29.5 %

Procedure:
To a suspension of magnesium (0.119 g, 4.97 mmol) in THF (3 mL) was added 2-bromothiophene (0.811 g, 4.97 mmol) and the reaction mixture was stirred for 3 h. Another equivalent of 2-bromothiophene (0.811 g, 4.97 mmol) was added and the reaction mixture was heated at the reflux temperature for 2 h, then allowed to cool to room temperature. The resulting mixture was added to a solution of 5-bromo-2-dimethylaminopyridine (1.0 g, 4.97 mmol) in THF (12 mL) and the reaction was heated at the reflux temperature for 11 h, then was allowed to cool to room temperature. The resulting mixture was treated with water (10 mL), extracted with EtOAc (3×30 mL), dried (MgSO4) and concentrated under reduced pressure. The crude product was purified by flash chromatography (10% EtOAc/hex) to give 5-(2-thienyl)-2-dimethylaminopyridine (0.3 g, 29%): TLC (10% EtOAc/hex) Rf 0.24; HPLC ES-MS m/z (relative abundance) 205 (MH+, 100%).
Reaction SMILES: [C:1]1([NH:12][C:13](=[O:15])[CH3:14])[C:6]2[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:5]=2[CH:4]=[CH:3][CH:2]=1.[O-:16]S([O-])(=O)=O.[Mg+2].[O-][Mn](=O)(=O)=O.[K+]>CC(C)=O>[O:16]=[C:7]1[C:6]2[C:1]([NH:12][C:13](=[O:15])[CH3:14])=[CH:2][CH:3]=[CH:4][C:5]=2[CH2:11][CH2:10][CH2:9][CH2:8]1
Reactant: O=S(=O)([O-])[O-]
Reactant: CC(=O)Nc1cccc2c1CCCCC2
Agent: O=[Mn](=O)(=O)[O-]
Agent: [K+]
Agent: [Mg+2]
Solvent: CC(C)=O
Product: CC(=O)Nc1cccc2c1C(=O)CCCC2
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of the product from Example 132B (1 g, 4.92 mmol) in acetone (150 ml) was added 15% MgSO4 (15 mL). To the solution was added KMnO4 (1.944 g, 12.30 mmol) and stirred at ambient temperature for 2 hours. Then heated at slightly reflux for 40 hours. The mixture was filtered through diatomaceous earth, and washed with CH2Cl2. The organic was separated, diluted with CH2Cl2, washed with saturated Na2S2O3, dried and concentrated. The residue was purified by chromatography on silica gel column eluting with 20% EtOAc/hexanes to provide the title product. 1H NMR (DMSO-d6) δ 1.68-1.74 (m, 4H), 1.94 (s, 3H), 2.55-2.59 (m, 2H), 2.70 (t, J=6.04 Hz, 2H), 6.98 (d, J=7.34 Hz, 1H), 7.22 (d, J=7.34 Hz, 1H), 7.32 (t, J=7.70 Hz, 1H), 9.90 (s, 1H). MS (M+H)+ m/z 218.
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:22]2[CH:31]=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[C:24]([F:32])[CH:23]=2)=[N:4][C:5]([CH:8]2[CH2:13][CH2:12][CH:11]([NH:14]CC3C=CC=CC=3)[CH2:10][CH2:9]2)=[CH:6][N:7]=1.[H][H]>[Pd].CO>[NH2:1][C:2]1[C:3]([C:22]2[CH:31]=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[C:24]([F:32])[CH:23]=2)=[N:4][C:5]([CH:8]2[CH2:13][CH2:12][CH:11]([NH2:14])[CH2:10][CH2:9]2)=[CH:6][N:7]=1
Reactant: COC(=O)c1ccc(-c2nc(C3CCC(NCc4ccccc4)CC3)cnc2N)cc1F
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: COC(=O)c1ccc(-c2nc(C3CCC(N)CC3)cnc2N)cc1F
Temperature: 25 °C
Reaction time: 14 h
Yield: 82.9 %

Procedure:
To methyl 4-(3-amino-6-(4-(benzylamino)cyclohexyl)pyrazin-2-yl)-2-fluorobenzoate (350 mg, 0.806 mmol) in a round bottom flask that was flushed with argon was added Pd—C 10% degaussa, wet (171 mg, 0.161 mmol). Then under argon with syringe, was added MeOH (5 mL) and last a hydrogen balloon. The flask was evacuated and refilled with hydrogen six times. The reaction was stirred at room temperature for 14 h. The reaction was purged with argon, then Pd—C 10% degaussa, wet (171 mg, 0.161 mmol) was carefully added. Then a hydrogen balloon was added, and the flask was evacuated and refilled with hydrogen six times. The reaction was stirred for additional 10 h to give a total of 24 h, followed by LCMS. The reaction was flushed with argon and 35 mL of DCM was added. The crude mixture was filtered through a Celite plug, and concentrated to constant mass to give 230 mg of desired product (which is 2:1 trans to cis ratio), used as is (83%). LCMS (m/z): 345.2 (MH+), 0.48 min and 0.51 min.
Reaction SMILES: [NH2:1][CH2:2][C:3]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH2:4][OH:5].[Cl:18][C:19]1[CH:26]=[CH:25][C:22]([CH:23]=O)=[CH:21][CH:20]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[Cl:18][C:19]1[CH:26]=[CH:25][C:22]([CH:23]2[NH:1][CH2:2][C:3]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)([C:6]3[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=3)[CH2:4][O:5]2)=[CH:21][CH:20]=1
Reactant: NCC(CO)(c1ccccc1)c1ccccc1
Reactant: O=Cc1ccc(Cl)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: Clc1ccc(C2NCC(c3ccccc3)(c3ccccc3)CO2)cc1

Procedure:
This product is obtained by reacting 3-amino-2,2-diphenyl-1-propanol with 4-chlorobenzaldehyde in refluxing toluene in the presence of p-toluenesulphonic acid for 5 hours.
Reaction SMILES: Br[C:2]1[C:3]([O:9][CH3:10])=[CH:4][C:5]([Cl:8])=[N:6][CH:7]=1.[CH3:11][N:12](C=O)C>[C-]#N.[C-]#N.[Zn+2].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>[Cl:8][C:5]1[N:6]=[CH:7][C:2]([C:11]#[N:12])=[C:3]([O:9][CH3:10])[CH:4]=1
Reactant: COc1cc(Cl)ncc1Br
Reactant: CN(C)C=O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [C-]#N
Agent: [Zn+2]
Product: COc1cc(Cl)ncc1C#N
Temperature: 95 °C
Reaction time: 12 h

Procedure:
A solution of 5-bromo-2-chloro-4-methoxypyridine (5.0 g, 22.48 mmol) in DMF (80 mL) was purged with nitrogen for 15 minutes. At this point, Zn(CN)2 (3.96 g, 33.7 mmol) and Pd(Ph3P)4 (2.60 g, 2.25 mmol) were added, successively. The resulting suspension was stirred at 95° C. for 12 hours under nitrogen atmosphere. The reaction mixture was cooled to ambient temperature, and filtered to remove inorganic solid. The solvent (DMF) was evaporated to provide the crude residue as an oil, which was purified on silica gel and eluted with 0-30% ethyl acetate/hexanes to afford the product.
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[NH:10][N:9]=2)[CH2:4][CH2:3]1.CCOCC.[F:22][C:23]1[CH:31]=[CH:30][C:26]([C:27](Cl)=[O:28])=[CH:25][CH:24]=1>>[F:22][C:23]1[CH:31]=[CH:30][C:26]([C:27]([N:10]2[C:11]3[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=3)[C:8]([CH:5]3[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]3)=[N:9]2)=[O:28])=[CH:25][CH:24]=1
Reactant: CN1CCC(c2n[nH]c3ccccc23)CC1
Reactant: O=C(Cl)c1ccc(F)cc1
Solvent: CCOCC
Product: CN1CCC(c2nn(C(=O)c3ccc(F)cc3)c3ccccc23)CC1
Yield: 53 %

Procedure:
A solution of 3.0 g of 3-(1-methyl-4-piperidinyl)-1H-indazole in 15 ml of 4-fluorobenzoyl chloride was heated at 100° for 2 hrs. The reaction mixture was poured into ether and the precipitate was collected. The precipitate was treated with dilute aqueous sodium hydroxide solution and extracted with chloroform. The chloroform extract was dried over anhydrous magnesium sulfate and the solvent removed in vacuo to yield 2.5 g (53%) of product, mp 132°-133° C.
Reaction SMILES: N1C2C(=CC=CC=2)C=C1.C([N:17]1[C:29]2[C:28]([OH:30])=[C:27]3[N:31](C(OC(C)(C)C)=O)[C:32]4[CH:33]=[CH:34][C:35]([Br:38])=[CH:36][C:37]=4[C:26]3=[CH:25][C:24]=2[C:23]2[C:18]1=[CH:19][CH:20]=[C:21]([Br:46])[CH:22]=2)(OC(C)(C)C)=O.[CH3:47][O:48][CH2:49][CH2:50][O:51][CH2:52][CH2:53]O>>[Br:38][C:35]1[CH:36]=[C:37]2[C:32](=[CH:33][CH:34]=1)[NH:31][C:27]1[C:28]([O:30][CH2:53][CH2:52][O:51][CH2:50][CH2:49][O:48][CH3:47])=[C:29]3[NH:17][C:18]4[CH:19]=[CH:20][C:21]([Br:46])=[CH:22][C:23]=4[C:24]3=[CH:25][C:26]2=1
Reactant: CC(C)(C)OC(=O)n1c2ccc(Br)cc2c2cc3c4cc(Br)ccc4n(C(=O)OC(C)(C)C)c3c(O)c21
Reactant: COCCOCCO
Agent: c1ccc2[nH]ccc2c1
Product: COCCOCCOc1c2[nH]c3ccc(Br)cc3c2cc2c1[nH]c1ccc(Br)cc12

Procedure:
The title compound was prepared in a manner analogous to Example 28 except the starting indole is 5,7-diBOC-2,10-dibromo-6-hydroxyindolo[2,3-b]carbazole and the reagent is diethylene glycol monomethyl ether. 1H-NMR (400 MHz, CDCl3) δ ppm 8.74 (s, 1 H), 8.21 (d, J=2.0 Hz, 2 H), 7.50-7.26 (m, 4 H), 4.50-4.38 (m, 2 H), 3.88-3.73 (m, 6 H), 3.55 (s, 3 H); MS (ESI) m/z 531.0 (M−H)−
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[CH2:7][C:8]1[S:9][C:10]2[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=2[N:12]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[F:50][C:51]1[CH:56]=[CH:55][C:54]([C:57]2[S:61][C:60]([CH3:62])=[N:59][C:58]=2[C:63](O)=[O:64])=[CH:53][CH:52]=1>CN(C=O)C>[S:9]1[C:10]2[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=2[N:12]=[C:8]1[CH2:7][CH:2]1[CH2:3][CH2:4][CH2:5][CH2:6][N:1]1[C:63]([C:58]1[N:59]=[C:60]([CH3:62])[S:61][C:57]=1[C:54]1[CH:55]=[CH:56][C:51]([F:50])=[CH:52][CH:53]=1)=[O:64]
Reactant: Cc1nc(C(=O)O)c(-c2ccc(F)cc2)s1
Reactant: c1ccc2sc(CC3CCCCN3)nc2c1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1nc(C(=O)N2CCCCC2Cc2nc3ccccc3s2)c(-c2ccc(F)cc2)s1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
2-Piperidin-2-ylmethylbenzothiazole, D30 (0.135 g), HATU (0.228 g), diisopropylethylamine (0.300 ml) and 5-(4-fluorophenyl)-2-methylthiazol-4-carboxylic acid (0.144 g) were dissolved in dry DMF and shaken at room temperature for 16 hours. The solvent was then evaporated and the residue partitioned between dichloromethane and brine. The organic layer was dried (MgSO4), evaporated and the residue chromatographed over silica gel. Elution with diethyl ether provided the title compound as a foam (220 mg).
Reaction SMILES: [NH2:1][C:2]1[N:3]([CH3:24])[C:4](=[O:23])[C:5]2([C:15]3[C:10](=[CH:11][CH:12]=[C:13](Br)[CH:14]=3)[O:9][CH:8]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:7]2)[N:6]=1.[N:25]1[CH:30]=[CH:29][CH:28]=[C:27](B(O)O)[CH:26]=1>O1CCOCC1.C([O-])([O-])=O.[Cs+].[Cs+].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>[NH2:1][C:2]1[N:3]([CH3:24])[C:4](=[O:23])[C:5]2([C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:27]4[CH:26]=[N:25][CH:30]=[CH:29][CH:28]=4)[CH:14]=3)[O:9][CH:8]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:7]2)[N:6]=1
Reactant: CN1C(=O)C2(CC(c3ccccc3)Oc3ccc(Br)cc32)N=C1N
Reactant: OB(O)c1cccnc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: C1COCCO1
Product: CN1C(=O)C2(CC(c3ccccc3)Oc3ccc(-c4cccnc4)cc32)N=C1N
Temperature: 120 °C
Yield: 90 %

Procedure:
Pd(PPh3)2Cl2 (10 mg) in a 10 mL tube under Ar was treated sequentially with 2′-amino-6-bromo-1′-methyl-2-phenylspiro[chroman-4,4′-imidazol]-5′(1′H)-one (20 mg, 0.052 mmol) in 1,4-dioxane (1 mL), Cs2CO3 (2 N, 0.3 mL) and pyridin-3-ylboronic acid (13 mg, 0.1 mmol). The mixture was heated under microwave at 120° C. for 30 min. The reaction mixture was concentrated in vacuo to give the residue, which was purified by preparative TLC to give pure 2′-amino-1′-methyl-2-phenyl-6-(pyridin-3-yl)spiro[chroman-4,4′-imidazol]-5′(1′H)-one (18 mg, 80%). 1H-NMR (MeOD): 2.39 (t, 1H), 2.52 (dd, 1H), 3.28 (s, 3H), 5.80 (d, 1H), 7.10 (d, 1H), 7.31 (m, 2H), 7.35 (m, 2H), 7.39 (m, 3H), 7.51 (s, 1H), 7.61 (m, 2H), 8.19 (d, 1H).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:12]=[CH:11][C:10]([NH:13][C:14]([C:16]2[CH2:17][CH2:18][O:19][C:20]3[CH:26]=[CH:25][C:24]([C:27]4[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=4)=[CH:23][C:21]=3[CH:22]=2)=[O:15])=[CH:9][CH:8]=1.ClC1C=CC=C(C(OO)=[O:42])C=1.S([O-])([O-])(=O)=S.[Na+].[Na+]>ClCCl.C(Cl)(Cl)Cl>[O-:42][N+:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:12]=[CH:11][C:10]([NH:13][C:14]([C:16]2[CH2:17][CH2:18][O:19][C:20]3[CH:26]=[CH:25][C:24]([C:27]4[CH:28]=[CH:29][C:30]([CH3:33])=[CH:31][CH:32]=4)=[CH:23][C:21]=3[CH:22]=2)=[O:15])=[CH:9][CH:8]=1
Reactant: Cc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(-c4ccccn4)cc2)CCO3)cc1
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Product: Cc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(-c4cccc[n+]4[O-])cc2)CCO3)cc1
Temperature: 25 °C
Reaction time: 70 h
Yield: 14.5 %

Procedure:
To a suspension of N-[4-(2-pyridyl)phenyl]-7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (400 mg) in dichloromethane (10 ml) was added 3-chloro-perbenzoic acid (70%, 0.25 g) at 0° C. and the mixture was stirred at room temperature for 70 hours. To the mixture was added sodium thiosulfate solution, and the mixture was stirred for minutes. The mixture was extracted with dichloromethane. The organic layer was washed with saturated sodium bicarbonate solution and saturated sodium chloride solution, and dried with magnesium sulfate. The mixture was concentrated, purified with column chromatography (ethanol/ethyl acetate=1:1) to give crystals, which were dissolved in chloroform. The mixture was concentrated, and to the residue was added ethanol. Precipitated crystal was collected by filtration to give crystals, which were washed with ethanol to give N-[4-(1-oxidopyridin-2-yl)phenyl]-7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (Compound 160) (60 mg) as colorless crystals.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[CH:19]3[CH2:20][CH2:21][CH2:22][CH:12]2[C:13]2[CH:14]=[N:15][NH:16][C:17]=2[C:18]3=[O:23])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[BH4-].[Na+]>CO.C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[CH:19]3[CH2:20][CH2:21][CH2:22][CH:12]2[C:13]2[CH:14]=[N:15][NH:16][C:17]=2[CH:18]3[OH:23])(=[O:10])=[O:9])=[CH:4][CH:3]=1
Reactant: O=C1c2[nH]ncc2C2CCCC1N2S(=O)(=O)c1ccc(Cl)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Product: O=S(=O)(c1ccc(Cl)cc1)N1C2CCCC1C(O)c1[nH]ncc12
Yield: 77.7 %

Procedure:
To a solution of 12-(4-chloro-benzenesulfonyl)-4,5,12-triaza-tricyclo[6.3.1.02,6]dodeca-2(6),3-dien-7-one (58 mg, 0.16 mmol) in 2:1 MeOH/THF (3 mL) was added NaBH4 (12 mg, 0.33 mmol) in portions. After sixteen hours the reaction was quenched with half saturated KHSO4 and then diluted with EtOAc and water. The separated organic phase was washed with water (10 mL), brine (10 mL), dried over MgSO4 filtered and concentrated to yield 12-(4-chloro-benzenesulfonyl)-4,5,12-triaza-tricyclo[6.3.1.02,6]dodeca-2(6),3-dien-7-ol (44 mg, 76%) as a white fluffy solid. MS (ES) m/e 354.0. (M+H)