Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[C:6]([CH3:14])[N:5]2[N:15]=[C:16]([CH3:18])[N:17]=[C:4]2[N:3]=1.[CH:19]([C:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=1)=[O:20].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.ClCCl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:18][C:16]1[N:17]=[C:4]2[N:3]=[C:2]([C:24]3[CH:25]=[CH:26][C:21]([CH:19]=[O:20])=[CH:22][CH:23]=3)[C:7]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)=[C:6]([CH3:14])[N:5]2[N:15]=1
Reactant: Cc1nc2nc(Cl)c(-c3ccccc3)c(C)n2n1
Reactant: O=Cc1ccc(B(O)O)cc1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: O
Solvent: ClCCl
Solvent: COCCOC
Product: Cc1nc2nc(-c3ccc(C=O)cc3)c(-c3ccccc3)c(C)n2n1
Temperature: 110 °C

Procedure:
To a mixture of 1.25 g 5-chloro-2,7-dimethyl-6-phenyl[1,2,4]triazolo[1,5-a]pyrimidine and 0.87 g 4-formylphenylboronic acid in 25 mL 1,2-dimethoxyethane were added 0.18 g dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct and 9.30 mL of a 10% w/w sodium carbonate solution. The resulting mixture was heated to 110° C. by microwave irradiation under an inert gas atmosphere for 45 min. The work up was performed by diluting the reaction mixture with water and dichloromethane, separating the phases and extraction of the aqueous phase with dichloromethane. The combined organic layers were dried over sodium sulphate and the solvent was evaporated. The residue was purified by chromatography on silica gel (dichloromethane/methanol). The desired product was suspended in ethyl acetate/petrolether and isolated by filtration.
Reaction SMILES: Cl.Cl.Cl.[CH3:4][C:5]1[C:9]([C:10]2[C:19]3[O:18][CH2:17][C@H:16]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=4)[N:15]4[C:26]([N:28]5[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]5)=[N:27][C:13]([C:14]=34)=[CH:12][CH:11]=2)=[C:8]([CH3:34])[O:7][N:6]=1.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:42][C:43]([N:45]([CH3:47])[CH3:46])=[O:44]>C(Cl)Cl.CO>[CH3:4][C:5]1[C:9]([C:10]2[C:19]3[O:18][CH2:17][C@H:16]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=4)[N:15]4[C:26]([N:28]5[CH2:33][CH2:32][N:31]([CH2:42][C:43]([N:45]([CH3:47])[CH3:46])=[O:44])[CH2:30][CH2:29]5)=[N:27][C:13]([C:14]=34)=[CH:12][CH:11]=2)=[C:8]([CH3:34])[O:7][N:6]=1
Reactant: CN(C)C(=O)CCl
Reactant: Cc1noc(C)c1-c1ccc2nc(N3CCNCC3)n3c2c1OC[C@@H]3c1ccccn1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: ClCCl
Product: Cc1noc(C)c1-c1ccc2nc(N3CCN(CC(=O)N(C)C)CC3)n3c2c1OC[C@@H]3c1ccccn1
Temperature: 60 °C
Reaction time: 0.08 h
Yield: 28.4 %

Procedure:
To a solution of (4S)-7-(3,5-dimethylisoxazol-4-yl)-2-piperazin-1-yl-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazine trihydrochloride (10 mg, 0.03 mmol) in methylene chloride (1.0 mL), potassium carbonate (18 mg, 0.13 mmol) was added, followed by 2-chloro-N,N-dimethylacetamide (2.7 μL, 0.026 mmol) and the mixture was stirred for 5 min. The mixture was then heated at 60° C. overnight. The mixture was diluted with methanol and purified by preparative LCMS using pH 10 buffer to give the title compound, (3.7 mg, 30%). LCMS calc. for C27H32N7O3 (M+H)+: m/z=502.2. found: 502.3.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([N+:9]([O-:11])=[O:10])[C:3]=1[O:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.O[CH2:20][C:21]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:22]>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:20][C:21]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:22])=[C:4]([N+:9]([O-:11])=[O:10])[C:3]=1[O:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: O=C(CO)c1ccccc1
Reactant: O=[N+]([O-])c1c(O)ccc(Br)c1Oc1ccccc1
Product: O=C(COc1ccc(Br)c(Oc2ccccc2)c1[N+](=O)[O-])c1ccccc1

Procedure:
This compound was synthesized according to the procedure of Example 76, Step 5, using 4-bromo-2-nitro-3-phenoxyphenol and 2-hydroxy-1-phenylethanone as the starting materials. LCMS calculated for C20H15BrNO5 (M+H)+: m/z=428.0, 430.0. found: 427.9, 429.9.
Reaction SMILES: C([O:5][C:6]([CH2:8][N:9]([C@@H:21]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[CH2:22][N:23]1[CH2:27][CH2:26][C@H:25]([OH:28])[CH2:24]1)[C:10](=[O:20])[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([Cl:19])[CH:13]=1)=[O:7])(C)(C)C.Cl>CO>[C:6]([CH2:8][N:9]([C@@H:21]([C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)[CH2:22][N:23]1[CH2:27][CH2:26][C@H:25]([OH:28])[CH2:24]1)[C:10](=[O:20])[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([Cl:19])[CH:13]=1)([OH:7])=[O:5]
Reactant: CC(C)(C)OC(=O)CN(C(=O)Cc1ccc(Cl)c(Cl)c1)[C@H](CN1CC[C@H](O)C1)c1ccccc1
Agent: Cl
Solvent: CO
Product: O=C(O)CN(C(=O)Cc1ccc(Cl)c(Cl)c1)[C@H](CN1CC[C@H](O)C1)c1ccccc1
Reaction time: 2 h
Yield: 56.5 %

Procedure:
A mixture of N-(t-butoxycarbonyl)methyl-2-(3,4-dichlorophenyl)-N-[2-(3-(S)-hydroxypyrrolidin-1-yl)-1-(S)-phenylethyl]acetamide (306 mg, 0.6 mmol), HCl gas saturated methanol solution (8 ml), and methanol (2 ml) was refluxed with stirring for 2 h. After evaporation of the solvent, the resulting oil was crystallized from CH2Cl2 /MeOH to give 153 mg (52.3%) of desired compound as HCl salt of white powder.
Reaction SMILES: [NH4+:1].[OH-].[CH:3](=O)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1>CC(O)C>[CH:7]1[CH:8]=[CH:9][C:4](/[CH:3]=[N:1]/[CH:3]([C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)/[N:1]=[CH:3]/[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)=[CH:5][CH:6]=1
Reactant: [NH4+]
Reactant: O=Cc1ccccc1
Agent: [OH-]
Solvent: CC(C)O
Product: C(=N/C(/N=C/c1ccccc1)c1ccccc1)\c1ccccc1
Reaction time: 43 h
Yield: 97.5 %

Procedure:
To a 3 L 3-necked flask equipped with a mechanical stirrer and a thermometer was added 1 L of concentrated NH4OH (ca 30%) (14.8 moles). A solution of benzaldehyde (265 g, 2.50 mol) in 500 mL of 2-propanol was added in one portion. The mixture was stirred vigorously at ca 22° C. for 43 hr. The resulting slurry was filtered and the filter cake was washed with water (1 L). After drying in vacuo, 242.4 g of hydrobenzamide was obtained as a white solid (mp 100°-102° C.) for a 97.4% yield.
Reaction SMILES: C=O.[BH3-][C:4]#[N:5].[Na+].[Cl:7][C:8]1[CH:9]=[C:10]([CH2:15][C:16]([N:18]2[CH:27]3[CH:22]([CH2:23][CH2:24][CH2:25][CH:26]3[N:28]3[CH2:32][CH2:31][CH2:30][CH2:29]3)N[CH2:20][CH2:19]2)=[O:17])[CH:11]=[CH:12][C:13]=1[Cl:14].C([O-])([O-])=O.[Na+].[Na+]>CO.C(O)(=O)C>[Cl:7][C:8]1[CH:9]=[C:10]([CH2:15][C:16]([N:18]2[CH:27]3[CH:22]([CH2:23][CH2:24][CH2:25][CH:26]3[N:28]3[CH2:32][CH2:31][CH2:30][CH2:29]3)[N:5]([CH3:4])[CH2:20][CH2:19]2)=[O:17])[CH:11]=[CH:12][C:13]=1[Cl:14]
Reactant: O=C(Cc1ccc(Cl)c(Cl)c1)N1CCNC2CCCC(N3CCCC3)C21
Reactant: [BH3-]C#N
Agent: C=O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: CN1CCN(C(=O)Cc2ccc(Cl)c(Cl)c2)C2C1CCCC2N1CCCC1
Reaction time: 1.5 h

Procedure:
Formalin (37%, 223 mg, 2.7 mmol) was dissolved in 5 ml of MeOH and NaBH3CN (17.2 mg, 0.27 mmol) was added. The pH was adjusted to 5 with concentrated acetic acid. 2-(3,4-Dichlorophenyl)-1-[(4aRS,8SR,8aRS)-8-(pyrrolidin-1-yl)-perhydroquinoxalin-1-yl]-ethan-1-one (109 mg, 0.27 mmol), dissolved in MeOH (15 ml), was then added to the mixture and the mixture was stirred for 1.5 hours. After addition of saturated Na2CO3 solution (12 ml), the mixture was stirred at room temperature for 15 minutes. The precipitate formed was filtered off and MeOH was evaporated off from the filtrate under 100 mbar. The aqueous phase was extracted by shaking five times with CH2Cl2 and the combined organic phases were dried over Na2SO4 and evaporated in vacuo. The residue was purified by flash chromatography (Ø 2 cm, CH2Cl2/MeOH/NH3 9.5:0.5:0.05, l=16 cm, V=5 ml). A yellowish resin was isolated.
Reaction SMILES: [H-].[Na+].O1CCCC1.[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([S:15]([CH:18]([C:29]2[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=2[F:36])[CH2:19][CH2:20][CH2:21][NH:22][C:23](=[O:28])[O:24][CH2:25][CH2:26]I)(=[O:17])=[O:16])=[CH:11][CH:10]=1.O>C(OCC)(=O)C.CCCCCC.CCCCCC>[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([S:15]([CH:18]([C:29]2[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=2[F:36])[CH2:19][CH2:20][CH2:21][N:22]2[CH2:26][CH2:25][O:24][C:23]2=[O:28])(=[O:17])=[O:16])=[CH:11][CH:10]=1
Reactant: O=C(NCCCC(c1cc(F)ccc1F)S(=O)(=O)c1ccc(Cl)cc1)OCCI
Agent: [H-]
Agent: [Na+]
Solvent: CCCCCC
Solvent: O
Solvent: CCOC(C)=O
Product: O=C1OCCN1CCCC(c1cc(F)ccc1F)S(=O)(=O)c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 42.8 %

Procedure:
Under a nitrogen atmosphere and at 0° C., sodium hydride (60% dispersion in mineral oil, 13.6 mg, 0.340 mmol) was added to a tetrahydrofuran solution (5 ml) of 2-iodoethyl N-[4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)butyl]carbamate (158 mg, 0.283 mmol). The resulting mixture was stirred at room temperature for 18 hours. Water was added to the reaction mixture, followed by extraction wth ethyl acetate. The extract was washed with brine, dried over magnesium sulfate and then concentrated. The residue thus obtained was subjected to flash chromatography on a silica gel column, and the fraction obtained from the hexane:ethyl acetate=1:2 eluate was concentrated. The solid thus obtained was recrystallized from ethyl acetate-hexane, whereby the title compound (52.1 mg, 0.121 mmol, 43%) was obtained as colorless needle crystals.
Reaction SMILES: C(OC([N:8]1[CH2:13][C@@H:12]([N:14]([C:19]([C:21]2[N:22]=[N:23][N:24]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[C:25]=2[CH2:26][CH2:27][CH2:28][CH2:29][O:30][CH3:31])=[O:20])[CH2:15][CH:16]([CH3:18])[CH3:17])[CH2:11][C@@H:10]([C:38]([OH:40])=O)[CH2:9]1)=O)(C)(C)C.[CH3:41][C:42]1NN=[N:44][N:43]=1.C1(N=C=NC2CCCCC2)CCCCC1.O>C1(C)C=CC=CC=1>[CH3:31][O:30][CH2:29][CH2:28][CH2:27][CH2:26][C:25]1[N:24]([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[N:23]=[N:22][C:21]=1[C:19]([N:14]([C@H:12]1[CH2:11][C@@H:10]([C:38]2[O:40][C:42]([CH3:41])=[N:43][N:44]=2)[CH2:9][NH:8][CH2:13]1)[CH2:15][CH:16]([CH3:17])[CH3:18])=[O:20]
Reactant: COCCCCc1c(C(=O)N(CC(C)C)[C@H]2C[C@@H](C(=O)O)CN(C(=O)OC(C)(C)C)C2)nnn1-c1ccccc1
Reactant: Cc1nnn[nH]1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: O
Solvent: Cc1ccccc1
Product: COCCCCc1c(C(=O)N(CC(C)C)[C@@H]2CNC[C@H](c3nnc(C)o3)C2)nnn1-c1ccccc1
Temperature: 80 °C
Reaction time: 15 h
Yield: 47.8 %

Procedure:
(3R,5S)-1-(tert-Butoxycarbonyl)-5-[{[5-(4-methoxybutyl)-1-phenyl-1H-1,2,3-triazol-4-yl]carbonyl}(2-methylpropyl)amino]piperidine-3-carboxylic acid (200 mg) was dissolved in toluene (5 ml), 5-methyl-1H-tetrazole (36 mg) and N,N′-dicyclohexylcarbodiimide (96 mg) were added and the mixture was stirred at 80° C. for 15 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (1:3-1:1) was concentrated under reduced pressure. The residue was dissolved in toluene (1 ml), trifluoroacetic acid (1 ml) was added and the mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure, basified with saturated aqueous sodium hydrogen carbonate, and the mixture was extracted twice with ethyl acetate. The extract was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The residue was dissolved in methanol (1 ml), fumaric acid (12 mg) was added and the mixture was concentrated under reduced pressure to give the object product (85 mg).
Reaction SMILES: [C:1]1([CH:7]2[CH2:16][CH2:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH:8]2[C:17]2[CH:22]=[CH:21][C:20]([CH:23]=[CH:24][C:25]([OH:27])=O)=[CH:19][CH:18]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:28][S:29]([NH2:32])(=[O:31])=[O:30]>>[C:1]1([CH:7]2[CH2:16][CH2:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH:8]2[C:17]2[CH:22]=[CH:21][C:20]([CH:23]=[CH:24][C:25]([NH:32][S:29]([CH3:28])(=[O:31])=[O:30])=[O:27])=[CH:19][CH:18]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CS(N)(=O)=O
Reactant: O=C(O)C=Cc1ccc(C2c3ccccc3CCC2c2ccccc2)cc1
Product: CS(=O)(=O)NC(=O)C=Cc1ccc(C2c3ccccc3CCC2c2ccccc2)cc1

Procedure:
Prepared by coupling 7d and methylsulfonamide in accordance with Procedure 1, Method A described hereinabove. Yield (56%); 1H NMR (CDCl3) δ 7.63 (d, J=15.4 Hz, 1H), 7.14 (m, 8H), 6.83 (m, 3H), 6.46 (d, J=8.1 Hz, 2H), 6.26 (d, J=15.4 Hz, 1H), 4.37 (d, J=5.1 Hz, 1H), 3.46 (m, 1H), 3.34 (s, 3H), 3.13 (m, 2H), 2.16 (m, 1H), 1.88 (m, 1H); ESI m/z: 430 (M−H−, 100%).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]#[N:26])[CH:20]=2)[CH:5]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][N:10]=2)[CH:7]=1.[N-:27]=[N+:28]=[N-:29].[Na+]>O.C(OCC)(=O)C.Cl.[Br-].[Zn+2].[Br-]>[CH3:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][N:10]=2)[CH:5]=[C:4]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]3[NH:29][N:28]=[N:27][N:26]=3)[CH:20]=2)[CH:3]=1
Reactant: Cc1cc(Nc2nccc(C(F)(F)F)n2)cc(-c2cccc(C#N)c2)c1
Reactant: [N-]=[N+]=[N-]
Agent: Cl
Agent: [Br-]
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Product: Cc1cc(Nc2nccc(C(F)(F)F)n2)cc(-c2cccc(-c3nnn[nH]3)c2)c1
Temperature: 115 °C

Procedure:
A suspension of 3′-methyl-5′-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}biphenyl-3-carbonitrile (354 mg, 1.00 mmol), zinc bromide (225 mg, 1.00 mmol), and sodium azide (68.3 mg, 1.05 mmol) in water (2 mL) was heated to 115° C. for 24 hours. The reaction mixture was then diluted with ethyl acetate (15 mL) and aqueous 2 M hydrochloric acid (2.25 mL) to give two layers. The layers were separated and the aqueous layer was extracted with ethyl acetate (15 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified via reverse phase HPLC to yield N-[5-methyl-3′-(1H-tetrazol-5-yl)biphenyl-3-yl]-4-(trifluoromethyl)pyrimidin-2-amine MS ESI calc'd. for C19H15F3N7 [M+H]+ 398, found 398. 1H NMR (500 MHz, DMSO-d6) δ 10.28 (s, 1H), 8.83 (d, J=4.9 Hz, 1H), 8.30 (s, 1H), 8.02 (d, J=7.8 Hz, 1H), 7.99 (s, 1H), 7.82 (d, J=7.9 Hz, 1H), 7.70 (t, J=7.8 Hz, 1H), 7.59 (s, 1H), 7.27 (d, J=4.9 Hz, 1H), 7.24 (s, 1H), 2.38 (s, 3H).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]([CH2:18][CH3:19])[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])=[CH:4][CH:3]=1.[CH3:20][S:21](Cl)(=[O:23])=[O:22]>N1C=CC=CC=1>[CH2:18]([N:10]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[CH2:9][CH2:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][S:21]([CH3:20])(=[O:23])=[O:22])=[CH:3][CH:4]=1)[CH3:19]
Reactant: CS(=O)(=O)Cl
Reactant: CCCCCCCN(CC)CCc1ccc(N)cc1
Solvent: c1ccncc1
Product: CCCCCCCN(CC)CCc1ccc(NS(C)(=O)=O)cc1
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
A solution of 5.45 g (0.0207 mol) of N-[2-(4-aminophenyl)ethyl]-N-ethyl-N-heptylamine from Preparation 20 in 22 ml of dry pyridine, under nitrogen, is cooled in an ice bath and treated dropwise with 1.90 ml (2.81 g, 0.0245 mol) of methanesulfonyl chloride over 10 min. The mixture is stirred for 30 min in the cold, for 2.5 hrs at room temperature and set overnight at room temperature. The solvent is azeotroped in vacuo with toluene and the residue treated with ice water. Aqueous NaHCO3 is added to give a mixture of pH 9 which is extracted with EtOAc (4×250 ml). The pooled extract is washed with brine, dried (NaHCO3) and concentrated in vacuo. The residue is chromatographed over 2100 ml of silica gel with 0.5% NH4OH/5% MeOH/CHCl3 (2000 ml), then 0.75% NH4OH/7.5% MeOH/CHCl3 (2000 ml) and finally 1.0% NH4OH/10% MeOH/CHCl3 ; 42 ml fractions are taken. Fractions at approximately 110-136 give the title compound which is identical as that prepared in Example 3 above.
Reaction SMILES: [Cl:1][C:2]1[CH:25]=[CH:24][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([CH2:17][C:18]3[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=3)=[N:9][N:8]=2)=[CH:4][CH:3]=1.ClC1C=CC=C(C(OO)=[O:34])C=1.C(=O)([O-])O.[Na+]>C([O-])(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([CH2:17][C:18]3[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=3)=[N+:9]([O-:34])[N:8]=2)=[CH:24][CH:25]=1
Reactant: Clc1ccc(Nc2nnc(Cc3ccncc3)c3ccccc23)cc1
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: CC(=O)[O-]
Agent: O=C([O-])O
Agent: [Na+]
Product: [O-][n+]1nc(Nc2ccc(Cl)cc2)c2ccccc2c1Cc1ccncc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A mixture of 1.53 g (4.41 mmol) 1-(4-chloroanilino)-4-(4-pyridylmethyl)phthalazine (see Example 4), 1.74 g (about 5.75 mmol) 3-chloroperbenzoic acid (about 57%), and 80 ml acetate is stirred for 1 h at RT. Then 25 ml 1 N aqueous sodium hydrogencarbonate solution is added to the reaction mixture, which is stirred for 10 min, filtered, washed with water, then acetate, and the filter residue purified by means of flash chromatography on silica gel with particle size 0.04-0.06 mm, using an acetate/methanol mixture (19:1). Title compound is obtained after evaporation of the product-containing fractions under vacuum and recrystallization of the filter residue from methanol; m.p. 226-228° C.; ESI-MS: (M+H)+=363.
Reaction SMILES: C([N:3]1[CH2:8][CH2:7][N:6](C=O)[CH2:5][CH:4]1[CH2:11][O:12][CH2:13][CH:14]([C:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[CH:18][CH:17]=1)[OH:15])=O.[ClH:26].C(O)C>CO>[ClH:26].[ClH:26].[C:16]1([CH:14]([OH:15])[CH2:13][O:12][CH2:11][CH:4]2[CH2:5][NH:6][CH2:7][CH2:8][NH:3]2)[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[CH:18][CH:17]=1
Reactant: O=CN1CCN(C=O)C(COCC(O)c2cccc3ccccc23)C1
Agent: Cl
Solvent: CO
Solvent: CCO
Product: OC(COCC1CNCCN1)c1cccc2ccccc12
Reaction time: 8 h

Procedure:
In 1.5 ml of methanol was dissolved 250 mg of 2-[(1,4-diformylpiperazin-2-yl)methoxy]-1-(1-naphthyl)ethanol. To the solution was added 1.5 ml of a 5N dry hydrogen chloride-ethanol solution. The mixture was allowed to stand at room temperature overnight. The resulting crystals were collected by filtration, washed with ethanol, and dried to obtain 180 mg of 1-(1-naphthyl)-2-[(piperazin-2-yl)methoxy]ethanol dihydrochloride (compound No. 274 ).
Reaction SMILES: [OH-].[K+].Cl.[CH:4]1([CH2:7][NH2:8])[CH2:6][CH2:5]1.[CH2:9]([S:11][C:12]1[C:17]2[C:18]([C:28]3[CH:33]=[CH:32][CH:31]=[C:30]([Cl:34])[CH:29]=3)=[N:19][CH2:20][C:21]3[N:22]([C:23]([CH2:26]Cl)=[N:24][N:25]=3)[C:16]=2[CH:15]=[CH:14][CH:13]=1)[CH3:10]>O1CCCC1>[CH2:9]([S:11][C:12]1[C:17]2[C:18]([C:28]3[CH:33]=[CH:32][CH:31]=[C:30]([Cl:34])[CH:29]=3)=[N:19][CH2:20][C:21]3[N:22]([C:23]([CH2:26][NH:8][CH2:7][CH:4]4[CH2:6][CH2:5]4)=[N:24][N:25]=3)[C:16]=2[CH:15]=[CH:14][CH:13]=1)[CH3:10]
Reactant: NCC1CC1
Reactant: CCSc1cccc2c1C(c1cccc(Cl)c1)=NCc1nnc(CCl)n1-2
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: C1CCOC1
Product: CCSc1cccc2c1C(c1cccc(Cl)c1)=NCc1nnc(CNCC3CC3)n1-2

Procedure:
In the manner given in Example 3, a solution of potassium hydroxide and (cyclopropylmethyl)amine hydrochloride is treated with a solution of 7-(ethylthio)-1-(chloromethyl)-6-(m-chlorophenyl)-4H-s-triazolo[4,3-a][1,4]benzodiazepine in tetrahydrofuran to give 7-(ethylthio)-1-[[(cyclopropylmethyl)amino]methyl]-6-(m-chlorophenyl)-4H-s-triazolo-[4,3-a][1,4]benzodiazepine.
Reaction SMILES: [CH2:1]([N:8]1[CH2:19][CH2:18][C:11]2[N:12]=[C:13]([NH2:17])[N:14]=[C:15](Cl)[C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.O.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>[CH2:1]([N:8]1[CH2:19][CH2:18][C:11]2[N:12]=[C:13]([NH2:17])[N:14]=[C:15]([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=3[Cl:20])[C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Nc1nc(Cl)c2c(n1)CCN(Cc1ccccc1)C2
Reactant: OB(O)c1ccccc1Cl
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: O
Product: Nc1nc2c(c(-c3ccccc3Cl)n1)CN(Cc1ccccc1)CC2
Temperature: 95 °C
Yield: 61.2 %

Procedure:
6-benzyl-4-chloro-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-ylamine (1.92 g., 7 mmoles) and 2-chlorophenylboronic acid (1.09 g., 7 mmoles) were mixed and stirred in a mixture of acetonitrile and water (50:50, 32 mls); anhydrous potassium carbonate (1.93 g., 14 mmoles) was then added to the stirred reaction mixture under nitrogen. Pd(PPh3)4 (0.2 g.) was then added to the reaction mixture which was stirred and heated at 95° C. for 3 hours also under nitrogen. The reaction mixture was then allowed to cool to room temperature and a beige solid formed. This suspension was quenched with water (150 mls) and the solid filtered and washed with water (100 mls) dried in a vacuum desiccator. The product was then eluted through a ‘silica plug’ in ethyl acetate, after evaporation the solid was slurried in ether to give, after filtering and drying a white solid (1.5 g., 61.2% yield). LC-MS (retention 2.65 mins, mass 351 M+H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.C(N(CC)CC)C.Cl.[CH2:17]([NH:33][C:34]1[CH:42]=[CH:41][C:37]([C:38](Cl)=[O:39])=[CH:36][CH:35]=1)[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32]>C(Cl)Cl>[CH2:17]([NH:33][C:34]1[CH:35]=[CH:36][C:37]([C:38]([O:8][C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)=[O:39])=[CH:41][CH:42]=1)[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32]
Reactant: CCCCCCCCCCCCCCCCNc1ccc(C(=O)Cl)cc1
Reactant: Oc1ccc(Cl)cc1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCCCCCCCCCCCCCCNc1ccc(C(=O)Oc2ccc(Cl)cc2)cc1

Procedure:
To a solution of 6.4 g. (50 m moles) 4-chlorophenol and 7.6 g. (75 m moles) triethylamine in 500 ml. methylene chloride is added 10.4 g. (25 m moles) 4-(hexadecylamino)benzoyl chloride hydrochloride in 250 ml. methylene chloride. After four hours at reflux, the solution is cooled, washed with water and dilute phosphoric acid, and dried. After passing the solution through a column of alumina, the solvent is evaporated and the residue is crystallized from diisopropyl ether.
Reaction SMILES: [N:1]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][C:17]([OH:19])=O)=[CH:12][CH:11]=2)[CH:2]=1.[C:20]([C:24]1[CH:25]=[C:26]([NH2:37])[N:27]([C:29]2[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=2[F:36])[N:28]=1)([CH3:23])([CH3:22])[CH3:21]>>[C:20]([C:24]1[CH:25]=[C:26]([NH:37][C:17](=[O:19])[CH2:16][C:13]2[CH:12]=[CH:11][C:10]([N:3]3[C:4]4=[N:5][CH:6]=[CH:7][CH:8]=[C:9]4[N:1]=[CH:2]3)=[CH:15][CH:14]=2)[N:27]([C:29]2[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=2[F:36])[N:28]=1)([CH3:23])([CH3:21])[CH3:22]
Reactant: CC(C)(C)c1cc(N)n(-c2cc(F)ccc2F)n1
Reactant: O=C(O)Cc1ccc(-n2cnc3cccnc32)cc1
Product: CC(C)(C)c1cc(NC(=O)Cc2ccc(-n3cnc4cccnc43)cc2)n(-c2cc(F)ccc2F)n1

Procedure:
The title compound is prepared as described in Example 28 but using 2-(4-imidazo[4,5-b]pyridine-3-yl-phenyl)-acetic acid and 5-tert-butyl-2-(2,5-difluoro-phenyl)-2H-pyrazol-3-ylamine. Title compound: ES-MS: 487.01 [M+H]+; tR=3.10 min (System 3).