Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: N[C:2]1[CH:15]=[CH:14][C:13]2[C:4](=[C:5]([C:24]#[C:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:6]3[C:11]([C:12]=2[C:16]#[C:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:10][CH:9]=[CH:8][CH:7]=3)[CH:3]=1.C1C2C=CC3C(=CC=CC=3)C=2C=CC=1>C1COCC1.C(N(CC)CC)C>[CH:29]1[CH:28]=[CH:27][C:26]([C:25]#[C:24][C:5]2[C:6]3[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=3)[C:12]([C:16]#[C:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[C:13]3[C:4]=2[CH:3]=[CH:2][CH:15]=[CH:14]3)=[CH:31][CH:30]=1
Reactant: Nc1ccc2c(C#Cc3ccccc3)c3ccccc3c(C#Cc3ccccc3)c2c1
Agent: c1ccc2c(c1)ccc1ccccc12
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: C(#Cc1c2ccccc2c(C#Cc2ccccc2)c2ccccc12)c1ccccc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 39.6 %

Procedure:
To 120 mg of 2-[4-(carboxybutyl)methylaminophenyl]-3-phenyl-5,6-dihydrothioxene prepared as described above (0.5 mmol) in 5.0 mL of THF was cooled in an ice bath for 30 minutes. 5.0 mL of oxalyl chloride was added to the cooled solution. The reaction mixture was stirred at 4° C. for 3 hours. Oxalyl chloride was evaporated on the rotovap under reduced pressure to give the acid chloride of 2-[4-(carboxybutyl)methylaminophenyl]-3-phenyl-5,6-dihydrothioxene. 2-Amino 9,10-bis-phenylethynyl anthracene (1.0 mmol) in 25 mL of dry THF was added to the residue followed by 2 drops of triethyl amine. The heterogeneous reaction mixture was stirred at room temperature for 24 hours. The reaction mixture was worked up as described for thioxene-phenanthrene. The product, 2-amino-9,10-bis(phenylethynyl)anthracene amide of 2-[4-(carboxybutyl)methylaminophenyl]-3-phenyl-5,6-dihydrothioxene (compound 7 in Table 1) was purified on preparative TLC (CH2Cl2: hexane 9:1) to yield 150 mg of yellow glassy solid.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][NH2:5].[CH3:6][O:7][C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][C:17]=1[O:18][CH3:19])[N:14]=[CH:13][CH:12]=[C:11]2[O:20][C:21]1[CH:22]=[CH:23][C:24]([NH:27][C:28]([C:30]2[C:31](=[O:43])[N:32]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[CH:33]=[CH:34][C:35]=2I)=[O:29])=[N:25][CH:26]=1>C(O)(C)C.ClCCl>[CH3:6][O:7][C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][C:17]=1[O:18][CH3:19])[N:14]=[CH:13][CH:12]=[C:11]2[O:20][C:21]1[CH:22]=[CH:23][C:24]([NH:27][C:28]([C:30]2[C:31](=[O:43])[N:32]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[CH:33]=[CH:34][C:35]=2[NH:5][CH2:4][CH2:3][O:2][CH3:1])=[O:29])=[N:25][CH:26]=1
Reactant: COc1cc2nccc(Oc3ccc(NC(=O)c4c(I)ccn(-c5ccccc5)c4=O)nc3)c2cc1OC
Reactant: COCCN
Solvent: ClCCl
Solvent: CC(C)O
Product: COCCNc1ccn(-c2ccccc2)c(=O)c1C(=O)Nc1ccc(Oc2ccnc3cc(OC)c(OC)cc23)cn1
Temperature: 100 °C
Yield: 75.1 %

Procedure:
2-methoxyethylamine (137 μl, 1573 μmol) was added to a suspension of N-(5-(6,7-dimethoxyquinolin-4-yloxy)pyridin-2-yl)-4-iodo-2-oxo-1-phenyl-1,2-dihydropyridine-3-carboxamide (122 mg, 197 μmol) in iso-propanol (1 mL). The reaction mixture was heated at 100° C. for 80 min. An aliquot was taken and analyzed by LCMS: The reaction was done. The reaction mixture was diluted with dichloromethane. The crude was adsorbed on silica and purified by MPLC (CH2Cl2/MeOH: 100/0 to 95/5) to afford the title compound N-(5-(6,7-dimethoxyquinolin-4-yloxy)pyridin-2-yl)-4-(2-methoxyethylamino)-2-oxo-1-phenyl-1,2-dihydropyridine-3-carboxamide (84 mg, 148 μmol, 75% yield). MS (ESI pos. ion) m/z: 568 (MH+). Calc'd exact mass for C31H29N5O6: 567. 1H NMR (400 MHz, DMSO-d6) 13.28 (s, 1H), 10.80-10.71 (m, 1H), 8.49 (d, J=5.2 Hz, 1H), 8.34 (d, J=9.1 Hz, 1H), 8.30 (d, J=2.8 Hz, 1H), 7.79 (dd, J=9.2, 3.1 Hz, 1H), 7.73 (d, J=7.8 Hz, 1H), 7.58-7.37 (m, 7H), 6.53 (d, J=5.2 Hz, 1H), 6.32 (d, J=8.1 Hz, 1H), 3.95 (s, 3H), 3.94 (s, 3H), 3.64-3.54 (m, 4H), 3.34 (s, 3H).
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[N:11]1[CH2:14][CH:13]([OH:15])[CH2:12]1.C([O-])([O-])=O.[Cs+].[Cs+].[Br:22][C:23]1[CH:24]=[N:25][CH:26]=[CH:27][C:28]=1Cl>CN(C=O)C.O>[Br:22][C:23]1[CH:24]=[N:25][CH:26]=[CH:27][C:28]=1[O:15][CH:13]1[CH2:12][N:11]([C:2]2[CH:3]=[CH:4][C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[N:1]=2)[CH2:14]1
Reactant: Clc1ccncc1Br
Reactant: OC1CN(c2ccc3ccccc3n2)C1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: Brc1cnccc1OC1CN(c2ccc3ccccc3n2)C1
Temperature: 90 °C
Reaction time: 8 h
Yield: 61.2 %

Procedure:
To a solution of 1-(quinolin-2-yl)azetidin-3-ol (see PREPARATION P1.2, step 1; 320 mg, 1.60 mmol) in DMF (10 mL) was added Cs2CO3 (1.04 g, 3.2 mmol) and 3-bromo-4-chloropyridine (307 mg, 1.60 mmol). The mixture was stirred at 90° C. overnight and then diluted with water (20 mL) and extracted with EtOAc (2×30 mL). The combined organic extracts were washed with water (30 mL) and brine (30 mL), dried over Na2SO4, and filtered. The filtrate was evaporated in vacuo and the residue was purified by flash column chromatography on silica gel (5% to 30% EtOAc in petroleum ether) to give the title product (350 mg, 0.98 mmol, 61% yield) as white solid. ESI-MS (M+1): 356 calc. for C17H14BrN3O 355.
Reaction SMILES: C1C=CC=CC=1.[NH2:7][C:8]1[CH:13]=[N:12][N:11]([C:14]([CH3:17])([CH3:16])[CH3:15])[C:10](=[O:18])[C:9]=1[OH:19].C(=O)[C:21]1[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=1>C1(C)C=CC(S(O)(=O)=O)=CC=1.C(OCC)(=O)C>[C:14]([N:11]1[C:10](=[O:18])[CH:9]([OH:19])[C:8](=[N:7][C:21]2[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=2)[CH:13]=[N:12]1)([CH3:16])([CH3:15])[CH3:17]
Reactant: CC(C)(C)n1ncc(N)c(O)c1=O
Reactant: O=Cc1ccncc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCOC(C)=O
Solvent: c1ccccc1
Product: CC(C)(C)N1N=CC(=Nc2ccncc2)C(O)C1=O
Yield: 74.9 %

Procedure:
50 ml of a dry benzene solution of 3.1 g of 5-amino-2-tert-butyl-4-hydroxypyridazin-3-(2H)-one, 1.9 g of isonicotinaldehyde and 0.17 g of p-toluene sulfonic acid, was reacted for 1.5 hours under heating and refluxing by means of a Dean Stark trap. After cooling, 100 ml of ethyl acetate was added to the reaction mixture, and the mixture was washed with water and then with a saturated sodium chloride aqueous solution, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 3.3 g of 2-tert-butyl-4-hydroxy-5-(4-pyridylimino)pyridazin-3-(2H)-one as a powder.
Reaction SMILES: [CH:1]([CH:3]([NH:8][C:9](=[O:26])[C@H:10]([CH2:22][CH:23]([CH3:25])[CH3:24])[NH:11][C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13])[CH2:4][CH2:5][CH2:6][CH3:7])=O.[CH2:27]([SH:31])[CH2:28][CH2:29][SH:30].B(F)(F)F.CCOCC>C(Cl)Cl>[S:30]1[CH2:29][CH2:28][CH2:27][S:31][CH:1]1[CH:3]([NH:8][C:9](=[O:26])[C@H:10]([CH2:22][CH:23]([CH3:25])[CH3:24])[NH:11][C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13])[CH2:4][CH2:5][CH2:6][CH3:7]
Reactant: CCCCC(C=O)NC(=O)[C@H](CC(C)C)NC(=O)OCc1ccccc1
Reactant: SCCCS
Agent: FB(F)F
Solvent: ClCCl
Solvent: CCOCC
Product: CCCCC(NC(=O)[C@H](CC(C)C)NC(=O)OCc1ccccc1)C1SCCCS1
Yield: 72.1 %

Procedure:
In 20 ml of anhydrous methylene chloride was dissolved 1.0 g of N-benzyloxycarbonyl-L-leucine-(1-formyl)pentylamide obtained in the same manner as in Example 4-(b), and 300 mg of 1,3-propanedithiol and 0.8 ml of boron trifluoride ethyl etherate were added thereto. The mixture was allowed to react at room temperature for 12 hours. After completion of the reaction, the solvent was removed by distillation under reduced pressure, and the residue was purified by medium-pressure column chromatography on silica gel to obtain 900 mg of the titled compound as a colorless crystal.
Reaction SMILES: [SH:1][C:2]1[NH:6][C:5]2[CH:7]=[CH:8][C:9]([O:11][C:12]([F:17])([F:16])[CH:13]([F:15])[F:14])=[CH:10][C:4]=2[N:3]=1.[Cl-].Cl[CH2:20][C:21]1[CH:26]=[C:25]([O:27][CH3:28])[C:24]([O:29][CH3:30])=[CH:23][NH+:22]=1.[OH-].[Na+]>C(O)C>[CH3:28][O:27][C:25]1[C:24]([O:29][CH3:30])=[CH:23][N:22]=[C:21]([CH2:20][S:1][C:2]2[NH:6][C:5]3[CH:7]=[CH:8][C:9]([O:11][C:12]([F:17])([F:16])[CH:13]([F:15])[F:14])=[CH:10][C:4]=3[N:3]=2)[CH:26]=1
Reactant: COc1c[nH+]c(CCl)cc1OC
Reactant: FC(F)C(F)(F)Oc1ccc2[nH]c(S)nc2c1
Agent: [Cl-]
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: COc1cnc(CSc2nc3cc(OC(F)(F)C(F)F)ccc3[nH]2)cc1OC

Procedure:
1.40 g of the title compound are obtained as a yellow oil by the procedure described in Example 1, by reacting 1.07 g of 2-mercapto-5-(1,1,2,2-tetrafluoroethoxy)-1H-benzimidazole with 0.90 g of 2-chloromethyl-4,5-dimethoxypyridinium chloride in 15 ml of ethanol with the addition of 17 ml of 0.5N sodium hydroxide solution. Recrystallization from petroleum ether yields 1.20 g (72% of theoretical) of the desired compound as colorless crystals of m.p. 125°-127° C.
Reaction SMILES: [Li+].CC([N-]C(C)C)C.[CH2:9]1[CH2:13][O:12][CH2:11][CH2:10]1.[Se:14]1[CH:18]=[CH:17][CH:16]=[C:15]1[C:19]1[Se:20][C:21]([C:24]2[Se:25]C=CC=2)=[CH:22][CH:23]=1.CN(C=O)C>C(OCC)(=O)C>[CH:11]([C:10]1[Se:25][C:24]([C:21]2[Se:20][C:19]([C:15]3[Se:14][CH:18]=[CH:17][CH:16]=3)=[CH:23][CH:22]=2)=[CH:13][CH:9]=1)=[O:12]
Reactant: c1c[se]c(-c2ccc(-c3ccc[se]3)[se]2)c1
Reactant: C1CCOC1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: O=Cc1ccc(-c2ccc(-c3ccc[se]3)[se]2)[se]1
Temperature: -78 °C
Reaction time: 3 h
Yield: 75 %

Procedure:
LDA (1.0 M solution in THF, 310 mL) was added to an anhydrous THF solution (4 mL) containing 2,2′:5′,2″-terselenophene (100 mg) under N2 at −78° C. The solution was stirred at −78° C. for 3 h, anhydrous DMF (1 mL) was added, stirred at −78° C. for 1 h, and slowly warmed to room temperature. The reaction solution was diluted with ethyl acetate (100 mL) and washed with H2O (4×100 mL). The organic layer was separated, dried over MgSO4, filtered, and the solvent was removed under vacuum. The residue was chromatographed over silica gel using CH2Cl2 to afford 2-formyl-5,2′:5′,2″-terselenophene in 75% yield.
Reaction SMILES: [O-][C:2]#[N:3].[Na+].S(C1C=CC(C)=CC=1)(O[CH2:9][CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[F:18])(=O)=O.O>CS(C)=O>[F:18][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[CH2:11][CH2:10][CH2:9][C:2]#[N:3]
Reactant: N#C[O-]
Reactant: Cc1ccc(S(=O)(=O)OCCCc2ccccc2F)cc1
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: N#CCCCc1ccccc1F
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a solution of 9.89 gm of sodium cyanate in 35 ml of dimethylsulfoxide (hereinafter abbreviated as DMSO) was added dropwise a solution of 31.2 gm of the compound prepared in (4) above in 70 ml of DMSO. The mixture was stirred for 12 hours at room temperature. After the addition of 500 ml of water, the mixture was extracted twice with 200 ml of ether. The extract was washed with water and saturated brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to obtain 15.4 gm of the title compound.
Reaction SMILES: [F:1][C:2]([F:23])([F:22])[C:3]1[C:16]2[C:7](=[CH:8][C:9]3[CH2:10][CH2:11][CH:12]([CH3:20])[N:13]([CH2:17][CH2:18][CH3:19])[C:14]=3[CH:15]=2)[NH:6][C:5](=[O:21])[CH:4]=1.[CH:24]1(C=O)CC1>>[F:23][C:2]([F:1])([F:22])[C:3]1[C:16]2[C:7](=[CH:8][C:9]3[CH2:10][CH2:11][CH:12]([CH3:20])[N:13]([CH2:17][CH:18]4[CH2:24][CH2:19]4)[C:14]=3[CH:15]=2)[NH:6][C:5](=[O:21])[CH:4]=1
Reactant: O=CC1CC1
Reactant: CCCN1c2cc3c(C(F)(F)F)cc(=O)[nH]c3cc2CCC1C
Product: CC1CCc2cc3[nH]c(=O)cc(C(F)(F)F)c3cc2N1CC1CC1

Procedure:
This compound was prepared in a similar fashion as that described in Example 84 from Compound 187 (Structure 33 of Scheme VI, where R1=methyl, n=1) and cyclopropanecarboxaldehyde. 1H NMR (400 MHz, CDCl3) 10.91 (br. s, 1H), 7.14 (s, 1H), 7.01 (s, 1H), 6.94 (s, 1H), 3.65 (m, 1H), 3.35 (dd, 1H, J=15.0, 5.5), 3.09 (dd, 1H, J=15.0, 6.2), 2.97-2.82 (m, 2H), 2.00-1.94 (m, 1H), 1.84-1.79 (m, 1H), 1.17 (d, 3H, J=6.5), 0.88-0.85 (m, 1H), 0.58 (m, 2H), 0.28 (dd, 2H, J=10.3, 5.0).
Reaction SMILES: CN[C:3]([C:5]1[S:6][C:7]([CH3:19])=[C:8]([CH3:18])[C:9]=1[C:10](=[O:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:4].[OH-:20].[K+]>CO.O>[C:10]([C:9]1[C:8]([CH3:18])=[C:7]([CH3:19])[S:6][C:5]=1[C:3]([OH:20])=[O:4])(=[O:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: [OH-]
Reactant: CNC(=O)c1sc(C)c(C)c1C(=O)c1ccccc1
Agent: [K+]
Solvent: CO
Solvent: O
Product: Cc1sc(C(=O)O)c(C(=O)c2ccccc2)c1C

Procedure:
A solution of 16a (0.281 g, 1.03 mmole) in methanol-water 1:1 containing 10% KOH was heated at reflux for 12 hours, neutralized and extracted with ethyl acetate. The solid after evaporation was crystallized from ethanol. Yield 0.19 g, 71%.
Reaction SMILES: C1(N=C=NC2CCCCC2)CCCCC1.[C:16]([NH:26][C@H:27]([C:30]([OH:32])=O)[CH2:28][OH:29])([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17].[C:33]1([CH2:39][CH2:40][CH2:41][N:42]2[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]2)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.OS1C2C=CC=CC=2N=C1>CN(C)C=O.C(OCC)(=O)C>[CH2:19]([O:18][C:16]([NH:26][CH:27]([CH2:28][OH:29])[C:30]([N:45]1[CH2:46][CH2:47][N:42]([CH2:41][CH2:40][CH2:39][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH2:43][CH2:44]1)=[O:32])=[O:17])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: O=C(N[C@@H](CO)C(=O)O)OCc1ccccc1
Reactant: c1ccc(CCCN2CCNCC2)cc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: O[SH]1C=Nc2ccccc21
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: O=C(NC(CO)C(=O)N1CCN(CCCc2ccccc2)CC1)OCc1ccccc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 73.1 %

Procedure:
Dicyclohexylcarbodiimide (1.58 g) was added to an ice-cooled solution of 2.0 g of N-carbobenzyloxyserine, 1.57 g of 1-(3-phenylpropyl)piperazine and 1.04 g of 1-hydroxybenzotiazole in 30 ml of N,N-dimethylformamide. The mixture was stirred at room temperature for 24 hours, then diluted with ethyl acetate, washed in sequence with two portions of 4% aqueous sodium hydrogen carbonate, one portion of water and one portion of saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give 2.39 g of 1-[2-(benzyloxycarbonylamino)-3-hydroxypropionyl]-4-(3-phenylpropyl}piperazine. Melting point 95°-97° C.
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9](=[O:11])[CH3:10].[Br:14]Br>ClCCl>[Br:14][CH2:10][C:9]([C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=1[C:2]([F:12])([F:13])[F:1])=[O:11]
Reactant: BrBr
Reactant: CC(=O)c1ccccc1C(F)(F)F
Solvent: ClCCl
Product: O=C(CBr)c1ccccc1C(F)(F)F
Yield: 92.8 %

Procedure:
To a solution of 20.00 g (0.11 mole) of 2′-(trifluoromethyl)acetophenone in 200 mL of dichloromethane was added 5.5 mL (0.11 mole) of bromine over 90 minutes. A stream of nitrogen was bubbled through the reaction mixture for 15 minutes. The mixture solvent was removed under reduced pressure. The residue was dissolved with ethanol, and then concentrated under reduced pressure to give 27.25 g of 2-bromo-1-(2-trifluoromethyl-phenyl)-ethanone as a yellow oil, which was used in the next step without further purification.
Reaction SMILES: [C:1]([O:5][C:6](=[O:16])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][OH:15])=[CH:10][CH:9]=1)([CH3:4])([CH3:3])[CH3:2].O>N1C=CC=CC=1.[O-2].[O-2].[O-2].[Cr+6]>[C:1]([O:5][C:6](=[O:16])[NH:7][C:8]1[CH:9]=[CH:10][C:11]([CH:14]=[O:15])=[CH:12][CH:13]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)Nc1ccc(CO)cc1
Agent: [Cr+6]
Agent: [O-2]
Solvent: O
Solvent: c1ccncc1
Product: CC(C)(C)OC(=O)Nc1ccc(C=O)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 61.1 %

Procedure:
Chromium trioxide (2.4 g) is added in portions to pyridine (29 mL) to maintain the temperature between 0°–10° C. A yellow suspension is formed. A solution of (4-hydroxymethylphenyl)carbamic acid tert-butyl ester (1.8 g) in pyridine (29 mL) is added dropwise to the yellow suspension. The reaction mixture is warmed to room temperature and stirred for 30 minutes. The reaction mixture is poured into water and extracted twice with ethyl acetate. The combined organics are washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, concentrated under reduced pressure and chromatographed on silica gel (4:1 ethyl acetate/hexane used as eluant) to give 1.09 g product as a white solid. MS: m/z 222 (M+H)+.
Reaction SMILES: [C:1]([O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][N:15]1[C:23]2[C:22](Cl)=[N:21][CH:20]=[N:19][C:18]=2[CH:17]=[CH:16]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:25][C:26]1[CH:45]=[CH:44][C:29]([O:30][CH:31]2[CH2:36][CH2:35][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:33][CH2:32]2)=[C:28]([Cl:46])[CH:27]=1>C(O)(C)C>[C:1]([O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][N:15]1[C:23]2[C:22]([NH:25][C:26]3[CH:45]=[CH:44][C:29]([O:30][CH:31]4[CH2:32][CH2:33][N:34]([C:37]([O:39][C:40]([CH3:42])([CH3:43])[CH3:41])=[O:38])[CH2:35][CH2:36]4)=[C:28]([Cl:46])[CH:27]=3)=[N:21][CH:20]=[N:19][C:18]=2[CH:17]=[CH:16]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)N1CCC(Oc2ccc(N)cc2Cl)CC1
Reactant: O=C(OCCOCCn1ccc2ncnc(Cl)c21)c1ccccc1
Solvent: CC(C)O
Product: CC(C)(C)OC(=O)N1CCC(Oc2ccc(Nc3ncnc4ccn(CCOCCOC(=O)c5ccccc5)c34)cc2Cl)CC1
Temperature: 80 °C
Reaction time: 8 h
Yield: 73.8 %

Procedure:
A mixture of 2-[2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidin-5-yl)ethoxy]ethyl benzoate (3.46 g), tert-butyl 4-(4-amino-2-chlorophenoxy)piperidine-1-carboxylate (3.27 g) and isopropyl alcohol (50 mL) was stirred at 80° C. overnight. The reaction mixture was concentrated under reduced pressure, water and saturated aqueous sodium hydrogen carbonate solution were added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, methanol:ethyl acetate=0:100→10:90). The object fraction was concentrated under reduced pressure. The residue was crystallized from ethyl acetate-diisopropyl ether to give the title compound (4.70 g) as a white powder.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]2[N:13]3[C:14]([CH3:17])=[N:15][N:16]=[C:12]3[CH2:11][N:10]=[C:9]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=3)[C:8]=2[CH:24]=1)([O-:3])=[O:2].[C:25](Cl)(=O)[CH3:26]>CN(C)C=O>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]2[N:13]3[C:14]([CH2:17][CH2:12][N:13]([CH2:14][CH2:25][CH3:26])[CH2:7][CH2:6][CH3:5])=[N:15][N:16]=[C:12]3[CH2:11][N:10]=[C:9]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=3)[C:8]=2[CH:24]=1)([O-:3])=[O:2]
Reactant: CC(=O)Cl
Reactant: Cc1nnc2n1-c1ccc([N+](=O)[O-])cc1C(c1ccccn1)=NC2
Solvent: CN(C)C=O
Product: CCCN(CCC)CCc1nnc2n1-c1ccc([N+](=O)[O-])cc1C(c1ccccn1)=NC2

Procedure:
In the manner given in Example 1, a solution of 8-nitro-1-methyl-6-(2-pyridyl)-4H-s-triazolo[4,3-a][1,4]benzodiazepine in dimethylformamide, N,N,N',N'-tetrapropyldiaminomethane and acetyl chloride (in 0.1 molar excess compared to the N,N,N'N'-tetrapropyldiaminomethane) are reacted together to give 8-nitro-1-[2-(dipropylamino)ethyl]-6-(2-pyridyl)-4H-s-triazolo[4,3-a][1,4]benzodiazepine.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][C:5]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)=[N:9][NH:10][C:4]=2[CH:3]=1.[H-].[Na+].[C:20](Cl)([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>CN(C=O)C.O>[Cl:1][C:2]1[N:7]=[CH:6][C:5]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)=[N:9][N:10]([C:20]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)([C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=3)[C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:4]=2[CH:3]=1
Reactant: Fc1ccc(-c2n[nH]c3cc(Cl)ncc23)cc1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: Fc1ccc(-c2nn(C(c3ccccc3)(c3ccccc3)c3ccccc3)c3cc(Cl)ncc23)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 82.4 %

Procedure:
6-Chloro-3-(4-fluorophenyl)-1H-pyrazolo[4,3-c]pyridine (1 g, 4.04 mmol) was dissolved in DMF (20 mL) and cooled to 0° C. Sodium hydride (0.242 g, 6.06 mmol) was then added and the reaction mixture stirred for one hour. Trityl chloride (1.351 g, 4.85 mmol) was then added and the reaction mixture warmed to room temperature and stirred for 1.5 hours. The reaction mixture was diluted with water and stirred at 0° C. for one hour to promote perception. The solid was filtered and rinsed with water. The solid was diluted with DCM and concentrated in vacuo while loading onto silica gel. The residue was purified by flash chromatography (2-30% EtOAc/isohexane) to give 6-chloro-3-(4-fluorophenyl)-1-trityl-1H-pyrazolo[4,3-c]pyridine (1.63 g, 3.33 mmol, 82%). MS ESI calc'd. For C31H21ClFN3 [M+1]+ 490, found 490.
Reaction SMILES: [N:1]1([C:7]2[N:8]=[C:9]([CH2:14][C:15]([O-:17])=O)[NH:10][C:11](=[O:13])[CH:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[Na+].[CH3:19][C:20]1[C:26]([CH3:27])=[CH:25][CH:24]=[CH:23][C:21]=1[NH2:22]>>[CH3:19][C:20]1[C:26]([CH3:27])=[CH:25][CH:24]=[CH:23][C:21]=1[NH:22][C:15](=[O:17])[CH2:14][C:9]1[NH:10][C:11](=[O:13])[CH:12]=[C:7]([N:1]2[CH2:2][CH2:3][O:4][CH2:5][CH2:6]2)[N:8]=1
Reactant: O=C([O-])Cc1nc(N2CCOCC2)cc(=O)[nH]1
Reactant: Cc1cccc(N)c1C
Agent: [Na+]
Product: Cc1cccc(NC(=O)Cc2nc(N3CCOCC3)cc(=O)[nH]2)c1C
Yield: 55.8 %

Procedure:
The product is prepared according to the procedure described in Example 5, using 260 mg of sodium [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate and 242 mg of 2,3-dimethylaniline in place of the 2,4-difluoroaniline. 190 mg of N-(2,3-dimethylphenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide are obtained in the form of a white solid, the characteristics of which are the following:
Reaction SMILES: Br[CH2:2][C:3]1[NH:7][C:6](=[O:8])[NH:5][C:4]=1[C:9](=[O:18])[C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=1.[CH3:19][NH:20][CH3:21]>C(O)C>[CH3:19][N:20]([CH2:2][C:3]1[NH:7][C:6](=[O:8])[NH:5][C:4]=1[C:9](=[O:18])[C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=1)[CH3:21]
Reactant: COc1ccc(C(=O)c2[nH]c(=O)[nH]c2CBr)cc1
Reactant: CNC
Solvent: CCO
Product: COc1ccc(C(=O)c2[nH]c(=O)[nH]c2CN(C)C)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A mixture of 3.1 g of 5-(bromomethyl)-1,3-dihydro-4-(4-methoxybenzoyl)-2H-imidazol-2-one, 12 ml of 30% aqueous dimethylamine and 24 ml of ethanol is stirred at 25° C. for 2 hours. The solvent is then evaporated from the mixture under reduced pressure and the resultant residue is recrystallized twice from ethanol to give 4-[(dimethylamino)methyl]-1,3-dihydro-5-(4-methoxybenzoyl)-2H-imidazol-2-one melting at about 165°-167° C. with decomposition.
Reaction SMILES: [Cl:1][C:2]1([C:5]([OH:21])([CH2:14][N:15]2[C:19]([SH:20])=[N:18][CH:17]=[N:16]2)[CH2:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[Cl:13])[CH2:4][CH2:3]1.[H-].[Na+].[C:24](Cl)(=[O:26])[CH3:25].C(O)C>O1CCCC1>[Cl:1][C:2]1([C:5]([OH:21])([CH2:14][N:15]2[C:19]([S:20][C:24](=[O:26])[CH3:25])=[N:18][CH:17]=[N:16]2)[CH2:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[Cl:13])[CH2:4][CH2:3]1
Reactant: OC(Cc1ccccc1Cl)(Cn1ncnc1S)C1(Cl)CC1
Reactant: CC(=O)Cl
Agent: [H-]
Agent: [Na+]
Solvent: CCO
Solvent: C1CCOC1
Product: CC(=O)Sc1ncnn1CC(O)(Cc1ccccc1Cl)C1(Cl)CC1
Reaction time: 0.5 h
Yield: 93.2 %

Procedure:
At room temperature, a mixture of 1.72 g (5 mmol) of 2-(1-chloro-cyclopropyl)-1(2-chlorophenyl)-3-(5-mercapto-1,2,4-triazol-1-yl)-propan-2-ol in 20 ml of absolute tetrahydrofuran is admixed with stirring with 0.24 g (6 mmol) of sodium hydride (60% strength in paraffin oil) and stirred for 30 minutes. 0.72 ml (10 mmol) of acetyl chloride are then added and the reaction mixture is stirred at room temperature for a further 4 hours. The reaction mixture is then admixed with 1 ml of ethanol and concentrated under reduced pressure. The residue that remains is extracted repeatedly with dichloromethane. The combined organic phases are concentrated under reduced pressure. In this manner, 1.8 g (94% of theory) of 2-(1-chloro-cyclopropyl)-1-(2-chlorophenyl)-3-(5-acetylmercapto-1,2,4-triazol-1-yl)-propan-2-ol are obtained in the form of an oil.