Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:12]([S:13]([C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)(=[O:15])=[O:14])[CH:11]=[C:10]([CH:22]=[O:23])[CH:9]=1.[Br:24]N1C(=O)CCC1=O.C(=O)([O-])O.[Na+]>CN(C)C=O>[Br:24][C:11]1[N:12]([S:13]([C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)(=[O:15])=[O:14])[C:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])=[CH:9][C:10]=1[CH:22]=[O:23]
Reactant: O=C1CCC(=O)N1Br
Reactant: O=Cc1cc(-c2ccccc2F)n(S(=O)(=O)c2cccnc2)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=Cc1cc(-c2ccccc2F)n(S(=O)(=O)c2cccnc2)c1Br
Temperature: 80 °C
Reaction time: 2 h
Yield: 66 %

Procedure:
5-(2-Fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carbaldehyde (330 mg) was dissolved in N,N-dimethylformamide (30 mL), N-bromosuccinimide (356 mg) was added and the mixture was stirred at 80° C. for 2 hr. The reaction mixture was allowed to cool, a saturated aqueous sodium hydrogencarbonate solution was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=7:3) and crystallized from diisopropyl ether to give the title compound as colorless crystals (yield 270 mg, 66%).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:29]=[CH:30][CH:31]=1)[C:5]([NH:7][C:8]1[CH:9]=[C:10]([CH:26]=[CH:27][CH:28]=1)[CH2:11][NH:12][C:13]1[C:22]2[C:17](=[C:18]([C:23]([NH2:25])=[O:24])[CH:19]=[CH:20][CH:21]=2)[N:16]=[CH:15][N:14]=1)=[O:6].C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:39][CH2:40][O:41][CH3:42].O>CN(C=O)C>[CH3:42][O:41][CH2:40][CH2:39][O:1][C:2]1[CH:3]=[C:4]([CH:29]=[CH:30][CH:31]=1)[C:5]([NH:7][C:8]1[CH:9]=[C:10]([CH:26]=[CH:27][CH:28]=1)[CH2:11][NH:12][C:13]1[C:22]2[C:17](=[C:18]([C:23]([NH2:25])=[O:24])[CH:19]=[CH:20][CH:21]=2)[N:16]=[CH:15][N:14]=1)=[O:6]
Reactant: NC(=O)c1cccc2c(NCc3cccc(NC(=O)c4cccc(O)c4)c3)ncnc12
Reactant: COCCBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: COCCOc1cccc(C(=O)Nc2cccc(CNc3ncnc4c(C(N)=O)cccc34)c2)c1
Temperature: 50 °C
Reaction time: 120 h

Procedure:
41 mg (0.1 mmol) 4-[3-(3-Hydroxy-benzoylamino)-benzylamino]-quinazoline-8-carboxylic acid amide were dissolved in 1 ml DMF. 97 mg (0.3 mmol) Cs2CO3 and 15 mg (0.11 mmol) 1-Bromo-2-methoxy-ethane were added. The mixture was stirred for 5 days at 50° C. Water was added to the reaction mixture, the percipitate was filtered and dried. 15.9 mg, off-white solid.
Reaction SMILES: [C:1]([C:9]1[CH:37]=[CH:36][C:12]2[N:13]([CH2:17][CH2:18][O:19][C:20]3[CH:35]=[CH:34][C:23]([CH2:24][CH:25]([C:30]([O:32][CH3:33])=[O:31])[C:26]([O:28][CH3:29])=[O:27])=[CH:22][CH:21]=3)[C:14](=[O:16])[S:15][C:11]=2[CH:10]=1)(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:38][O:39][NH2:40].N1C=CC=CC=1>CO.O>[CH3:38][O:39][N:40]=[C:1]([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:9]1[CH:37]=[CH:36][C:12]2[N:13]([CH2:17][CH2:18][O:19][C:20]3[CH:21]=[CH:22][C:23]([CH2:24][CH:25]([C:30]([O:32][CH3:33])=[O:31])[C:26]([O:28][CH3:29])=[O:27])=[CH:34][CH:35]=3)[C:14](=[O:16])[S:15][C:11]=2[CH:10]=1
Reactant: COC(=O)C(Cc1ccc(OCCn2c(=O)sc3cc(C(=O)c4ccccc4)ccc32)cc1)C(=O)OC
Reactant: CON
Solvent: CO
Solvent: c1ccncc1
Solvent: O
Product: CON=C(c1ccccc1)c1ccc2c(c1)sc(=O)n2CCOc1ccc(CC(C(=O)OC)C(=O)OC)cc1

Procedure:
The compound obtained in Example 18 is dissolved in a minimum of methanol and then 4 equivalents of O-methylhydroxylamine, previously dissolved in a few milliliters of water, and 4.5 equivalents of pyridine are added in succession. The reaction mixture is heated at reflux for 24 hours and then hydrolysed in water and filtered; the resulting precipitate is recrystallised from methanol.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6](Cl)[CH:5]=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].[CH:12]1[CH:17]=[CH:16][C:15]([S-:18])=[CH:14][CH:13]=1.[Na+].[H-].[Na+].C1(S)C=CC=CC=1>CN(C)C=O>[NH2:1][C:2]1[CH:7]=[C:6]([S:18][C:15]2[CH:16]=[CH:17][CH:12]=[CH:13][CH:14]=2)[CH:5]=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10]
Reactant: [S-]c1ccccc1
Reactant: Nc1cc(Cl)ccc1[N+](=O)[O-]
Agent: Sc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Nc1cc(Sc2ccccc2)ccc1[N+](=O)[O-]
Reaction time: 3 h

Procedure:
5 G. of 2-amino-4-chloro-1-nitrobenzene is added to a solution of sodium phenyl mercaptide, prepared under nitrogen from 2.53 g. 57% sodium hydride and 6.2 ml. thiophenol in 20 ml. dimethylformamide, with a 10 ml. dimethylformamide rinse. The mixture is stirred under nitrogen for 3 hours at 20°-30° C and then diluted with water. The crude product is washed with water and hexane, then recrystallized from methanol, yielding 2-amino-4-phenylthio-1-nitrobenzene.
Reaction SMILES: [N:1]1([C:6]2[CH:11]=[CH:10][C:9]([CH:12]=[CH:13][CH:14]=O)=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1.N1(C2C=C[C:24]([CH:25]=[O:26])=CC=2)C=CC=N1>>[N:1]1([C:6]2[CH:7]=[CH:8][C:9]([CH:12]=[CH:13][CH:14]=[CH:24][CH:25]=[O:26])=[CH:10][CH:11]=2)[CH:5]=[CH:4][CH:3]=[N:2]1
Reactant: O=Cc1ccc(-n2cccn2)cc1
Reactant: O=CC=Cc1ccc(-n2cccn2)cc1
Product: O=CC=CC=Cc1ccc(-n2cccn2)cc1

Procedure:
The title compound was prepared by a procedure analogous to Reference Example 30 by substituting 3-[4-(1H-pyrazol-1-yl)phenyl]-2-propenal (prepared as described in Reference Example 30) for the 4-(1H-pyrazol-1-yl)-benzaldehyde of Reference Example 30. MS 225 (M+H)+.
Reaction SMILES: [CH3:1][S:2][C:3]1[N:8]=[C:7]([NH:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([Cl:19])[CH:12]=2)[C:6]([C:20]([OH:22])=O)=[CH:5][N:4]=1.[N:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[CH2:29][NH2:30].ON1C2C=CC=CC=2N=N1.Cl.ClCCCl>CN(C)C=O>[CH3:1][S:2][C:3]1[N:8]=[C:7]([NH:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([Cl:19])[CH:12]=2)[C:6]([C:20](=[O:22])[NH:30][CH2:29][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][N:23]=2)=[CH:5][N:4]=1
Reactant: NCc1ccccn1
Reactant: COc1ccc(CNc2nc(SC)ncc2C(=O)O)cc1Cl
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: ClCCCl
Product: COc1ccc(CNc2nc(SC)ncc2C(=O)NCc2ccccn2)cc1Cl
Temperature: 0 °C
Reaction time: 8 h

Procedure:
2-Methylthio-4-(3-chloro-4-methoxybenzylamino)-5-carboxypyrimidine (prepared in Example 79) 0.500 g, 2-pyridylmethylamine 0.1749 g, 1-hydroxybenzotriazole 0.1987 g, 1,2-dichloroethane hydrochloride 0.3102 g and anhydrous dimethylformamide 5 ml are mixed together and stirred at 0° C. overnight and triturated with ethyl acetate-isopropyl ether to give 2-methylthio-4-(3-chloro-4-methoxybenzylamino)-5-[N-(2-pyridylmethyl)carbamoyl]pyrimidine as a colorless powder, 0.5966 g. mp 143-144.5° C.
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([F:19])[CH:18]=[C:13]3[CH:12]=[C:11]2[C:20]([C:27]2[CH:32]=[CH:31][C:30]([S:33]([CH3:35])=[O:34])=[CH:29][CH:28]=2)([OH:26])[CH2:21][CH:22]2[CH2:25][CH2:24][CH2:23]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Mn]([O-])(=O)(=O)=[O:37].[K+]>CO.O.C(OCC)(=O)C>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([F:19])[CH:18]=[C:13]3[CH:12]=[C:11]2[C:20]([C:27]2[CH:28]=[CH:29][C:30]([S:33]([CH3:35])(=[O:37])=[O:34])=[CH:31][CH:32]=2)([OH:26])[CH2:21][CH:22]2[CH2:25][CH2:24][CH2:23]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CS(=O)c1ccc(C(O)(CC2CCC2)c2cc3cc(F)cnc3n2S(=O)(=O)c2ccccc2)cc1
Reactant: O=[Mn](=O)(=O)[O-]
Agent: [K+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CO
Product: CS(=O)(=O)c1ccc(C(O)(CC2CCC2)c2cc3cc(F)cnc3n2S(=O)(=O)c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 123 %

Procedure:
To a stirred solution of 1-(1-benzenesulfonyl-5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-cyclobutyl-1-(4-methylsulfinyl-phenyl)-ethanol (512 mg, 1 mmol) in methanol (50 mL) and water (10 mL) was added potassium permanganate (126 mg, 0.8 mmol) at room temperature. The mixture was stirred at room temperature for 2 h, diluted with ethyl acetate (150 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to afford 1-(1-benzenesulfonyl-5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-cyclobutyl-1-(4-methylsulfonyl-phenyl)-ethanol (520 mg, quant.) as a light yellow solid: LC/MS m/e calcd for C26H25FN2O5S2 [M+H]+ 529.63, observed 529.0.
Reaction SMILES: [C:1]([O:5][C:6](=[O:13])[NH:7][N:8]1[CH:12]=[CH:11][CH:10]=[CH:9]1)([CH3:4])([CH3:3])[CH3:2].[F:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19]Br)=[CH:17][CH:16]=1.[H-].[Na+]>>[C:1]([O:5][C:6](=[O:13])[N:7]([CH2:19][C:18]1[CH:21]=[CH:22][C:15]([F:14])=[CH:16][CH:17]=1)[N:8]1[CH:12]=[CH:11][CH:10]=[CH:9]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)Nn1cccc1
Reactant: Fc1ccc(CBr)cc1
Agent: [H-]
Agent: [Na+]
Product: CC(C)(C)OC(=O)N(Cc1ccc(F)cc1)n1cccc1

Procedure:
Prepared according to the benzylation condition used in Example 1 step b) from pyrrol-1-yl-carbamic acid tert-butyl ester (1.0 eq.), 4-fluorobenzyl bromide (1.2 eq.) and sodium hydride (1.5 eq.). ESI (m/z): 291 (M+H)+.
Reaction SMILES: [C:1]([C:5]1[N:6]=[C:7]([N:22]2[CH2:27][CH2:26]O[CH2:24][CH2:23]2)[C:8]2[N:13]=[N:12][N:11]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[Cl:21])[C:9]=2[N:10]=1)([CH3:4])([CH3:3])[CH3:2].[C:28](C1N=C(Cl)C2N=NN(CC3C=CC=CC=3Cl)C=2N=1)(C)(C)C.N1CCCCC1>>[C:1]([C:5]1[N:6]=[C:7]([N:22]2[CH2:27][CH2:26][CH2:28][CH2:24][CH2:23]2)[C:8]2[N:13]=[N:12][N:11]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[Cl:21])[C:9]=2[N:10]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)c1nc(N2CCOCC2)c2nnn(Cc3ccccc3Cl)c2n1
Reactant: CC(C)(C)c1nc(Cl)c2nnn(Cc3ccccc3Cl)c2n1
Solvent: C1CCNCC1
Product: CC(C)(C)c1nc(N2CCCCC2)c2nnn(Cc3ccccc3Cl)c2n1

Procedure:
In analogy to the procedure described for the synthesis of 5-tert-butyl-3-(2-chloro-benzyl)-7-morpholin-4-yl-3H-[1,2,3]triazolo[4,5-d]pyrimidine (example 1, step c), the title compound was prepared from 5-tert-butyl-7-chloro-3-(2-chlorobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and piperidine and isolated as light-yellow solid (10.0 mg, 55%). MS (m/e): 385.4 (MH+).
Reaction SMILES: Cl.Br[C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1.[CH2:9]([NH2:12])[CH2:10][NH2:11]>>[NH2:11][CH2:10][CH2:9][NH:12][C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1
Reactant: Brc1ccncc1
Reactant: NCCN
Agent: Cl
Product: NCCNc1ccncc1
Reaction time: 13 h

Procedure:
A mixture of 38.9 g of 4-bromo-pyridine-hydrochloride and 480 g of ethylenediamine is refluxed with stirring for 13 hours. The reaction mixture is thereafter concentrated under reduced pressure and the residue is treated with toluene and concentrated once more. The residue is made alkaline with a concentrated aqueous solution of sodium hydroxide and extracted with five 75 ml portions of methylene chloride. The combined extracts are dried over sodium sulphate and concentrated under reduced pressure. Recrystallisation of the residue from methylene chloride yields 4-(2-aminoethylamino)-pyridine as a light yellow crystalline substance with a melting point of 120°-121° C.
Reaction SMILES: [Br:1][C:2]1[C:10]2[N:9]=[N:8][N:7]([CH2:11][C:12]([CH3:15])([CH3:14])[CH3:13])[C:6]=2[CH:5]=[CH:4][C:3]=1[OH:16].[C:17]([C:20]1[C:21](F)=[N:22][CH:23]=[CH:24][CH:25]=1)(=[O:19])[CH3:18].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[Br:1][C:2]1[C:10]2[N:9]=[N:8][N:7]([CH2:11][C:12]([CH3:13])([CH3:15])[CH3:14])[C:6]=2[CH:5]=[CH:4][C:3]=1[O:16][C:21]1[C:20]([C:17](=[O:19])[CH3:18])=[CH:25][CH:24]=[CH:23][N:22]=1
Reactant: CC(C)(C)Cn1nnc2c(Br)c(O)ccc21
Reactant: CC(=O)c1cccnc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CC(=O)c1cccnc1Oc1ccc2c(nnn2CC(C)(C)C)c1Br

Procedure:
4-Bromo-1-(2,2-dimethylpropyl)-1H-1,2,3-benzotriazol-5-ol (1-6) (1 g, 3.52 mmol, 1.0 equiv.), 3-acetyl-2-fluoropyridine (0.979 g, 7.04 mmol, 2.0 equiv.) and potassium carbonate (0.973 g, 7.04 mmol, 2.0 equiv.) were dissolved in acetonitrile (10 ml). The mixture was irradiated at 200° C. in microwave reactor until LCMS showed mostly desired product. The solvent was evaporated in vacuo, the mixture was neutralized with saturated aqueous NH4Cl, and then extracted with EtOAc. The organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (EtOAc/Hexane gradient from 0 to 100%) to obtain 2. 1H NMR (CDCl3) δ 8.30-8.24 (1H, m), 8.24 (1H, s), 7.83 (1H, d, J=2.06 Hz), 7.56 (1H, d, J=8.91 Hz), 7.29 (1H, dd, J=2.1, 8.9 Hz), 7.16-7.10 (1H, m), 4.42 (2H, s), 2.80 (3H, s), 1.09 (9H, s) ppm. LRMS m/z (M+H) 403.0 and 405.0 (intensity ratio ˜1:1) found, 403.1 and 405.1 required.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:9]([N+:14]([O-])=O)([CH2:12][OH:13])[CH2:10][OH:11])[C:5]([Cl:8])=[N:6][CH:7]=1.N1C=CC=CC=1.[Cl:23][CH2:24][C:25](Cl)=[O:26].Cl.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.CC(OC)(C)C>[Br:1][C:2]1[CH:3]=[C:4]([C:9]([NH:14][C:25](=[O:26])[CH2:24][Cl:23])([CH2:12][OH:13])[CH2:10][OH:11])[C:5]([Cl:8])=[N:6][CH:7]=1
Reactant: O=C(Cl)CCl
Reactant: O=[N+]([O-])C(CO)(CO)c1cc(Br)cnc1Cl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: COC(C)(C)C
Solvent: c1ccncc1
Product: O=C(CCl)NC(CO)(CO)c1cc(Br)cnc1Cl
Temperature: -30 °C
Reaction time: 1.5 h

Procedure:
To a suspension of 2-(5-bromo-2-chloro-pyridin-3-yl)-2-nitropropane-1,3-diol (904 mg, 3.21 mmol) in DCM (64 ml) was added pyridine (2.6 ml, 32.1 mmol), after cooling to −30° C. a solution of chloro-acetylchloride (1.022 ml, 12.84 mmol) in DCM (32 ml) was added within 10 min., the reaction mixture was stirred at −30° C. for 1.5 h. At −30° C. 1M HCl and DCM was added, the layers were separated, the aq. phase extracted with DCM and the combined organic layers washed with halfsaturated aq. NaHCO3 and halfsaturated aq. NaCl, dried with Na2SO4 and evaporated. The obtained per-acetylated product was dissolved in methanol (19.3 ml) and K2CO3 powder (222 mg, 1.6 mmol) added, the mixture was stirred at room temperature for 30 min. After addition of 1M HCl and TBME the layers were separated, the aq. layer was extracted with TBME, the combined organic layers were washed with halfsaturated aq. NaCl, dried with Na2SO4 and evaporated. The residue was purified by chromatography on silica gel (cyclohexane/EtOAc 1:0 to cyclohexane/EtOAc 0:1) to provide the title compound as colorless solid.
Reaction SMILES: Cl[C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][S:18]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)(=[O:20])=[O:19])=[CH:13][CH:12]=3)=[CH:9][N:8]([CH:27]([CH3:29])[CH3:28])[C:4]=2[N:5]=[CH:6][N:7]=1.[NH3:30]>O1CCOCC1>[NH2:30][C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][S:18]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)(=[O:20])=[O:19])=[CH:13][CH:12]=3)=[CH:9][N:8]([CH:27]([CH3:29])[CH3:28])[C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: N
Reactant: CC(C)n1cc(-c2ccc(NS(=O)(=O)c3ccccc3)cc2)c2c(Cl)ncnc21
Solvent: C1COCCO1
Product: CC(C)n1cc(-c2ccc(NS(=O)(=O)c3ccccc3)cc2)c2c(N)ncnc21
Temperature: 120 °C
Reaction time: 16 h

Procedure:
A mixture of N-[4-(4-chloro-7-isopropylpyrrolo[2,3-d]pyrimidin-5-yl)phenyl]-benzenesulphonamide (0.34 g), concentrated ammonia (30 ml, SG 0.880) and 1,4-dioxane (30 ml) was heated with stirring at 120° C. in a pressure vessel for 16 hours. The mixture was allowed to cool to ambient temperature and the solvent was removed under reduced pressure to give a residue which was partitioned between water (40 ml) and ethyl acetate (40 ml). The organic layer was separated and the aqueous layer was further extracted with ethyl acetate (2×40 ml). The combined ethyl acetate extracts were washed, dried, filtered and evaporated to give a solid which was purified by flash column chromatography on silica using ethyl acetate/cyclohexane (8:2) as the mobile phase. Appropriate fractions were collected, combined and concentrated to give N-[4-(4-amino-7-isopropyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)phenyl]benzenesulphonamide, m.p. 238-240° C.
Reaction SMILES: [CH:1]1([N:4]2[C:11](=[O:12])[CH2:10][CH2:9][N:8]([CH2:13][C:14]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)=[O:15])[C:7]3[CH:23]=[CH:24][C:25]([O:27][CH3:28])=[CH:26][C:6]=3[CH2:5]2)[CH2:3][CH2:2]1.[BH4-].[Na+].CC(C)=O.ClCCl>C(O)C>[CH:1]1([N:4]2[C:11](=[O:12])[CH2:10][CH2:9][N:8]([CH2:13][CH:14]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[OH:15])[C:7]3[CH:23]=[CH:24][C:25]([O:27][CH3:28])=[CH:26][C:6]=3[CH2:5]2)[CH2:2][CH2:3]1
Reactant: COc1ccc2c(c1)CN(C1CC1)C(=O)CCN2CC(=O)c1ccc(F)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CC(C)=O
Solvent: CCO
Product: COc1ccc2c(c1)CN(C1CC1)C(=O)CCN2CC(O)c1ccc(F)cc1
Temperature: 25 °C
Yield: 45.9 %

Procedure:
To a solution of 5-cyclopropyl-1-(2-(4-fluorophenyl)-2-oxoethyl)-8-methoxy-2,3,5,6-tetrahydrobenzo[b][1,5]diazocin-4(1H)-one (65.0 mg, 0.170 mmol) from Example 5 in ethanol (1 ml) was added sodium borohydride (6.4 mg, 0.170 mmol) and the reaction mixture was stirred at room temperature over weekend. Then was added acetone (0.062 ml) followed by dilution with dichloromethane. The resulting solution was washed with water and the organic phase was dried over sodium sulfate and filtered. Evaporation gave the desired product (30 mg, 46%).
Reaction SMILES: [CH3:1][C@H]1OC(=O)C2C(O)=CC(O)=C(Cl)C=2CC(=O)C=CC=C[C@H]2O[C@H]2C1.OCCCCCCCCCCCC(O)=O.[CH:41]1([N:47]=[C:48]=[N:49][CH:50]2[CH2:55][CH2:54][CH2:53]CC2)CCCCC1>O1CCCC1>[CH3:1][N:47]([C:48]1[CH:53]=[CH:54][CH:55]=[CH:50][N:49]=1)[CH3:41]
Reactant: C[C@@H]1C[C@@H]2O[C@@H]2C=CC=CC(=O)Cc2c(Cl)c(O)cc(O)c2C(=O)O1
Reactant: C(=NC1CCCCC1)=NC1CCCCC1
Agent: C[C@@H]1C[C@@H]2O[C@@H]2/C=C\C=C\C(=O)Cc2c(Cl)c(O)cc(O)c2C(=O)O1
Agent: O=C(O)CCCCCCCCCCCO
Solvent: C1CCOC1
Product: CN(C)c1ccccn1

Procedure:
Following a procedure similar to that described in Example 12, but using 365 mg of radicicol, 1.8 g of 12-hydroxydodecanoic acid, 20 ml of dry tetrahydrofuran, 1 g of dicyclohexylcarbodiimide and a catalytic amount of dimethylaminopyridine, 485 mg of the title compound were obtained.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([CH3:11])=O)=[CH:4][C:3]=1[CH3:12].[C:13](=O)([O:15]CC)[NH2:14].O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.[OH-].[Na+]>C1(C)C(C)=CC=CC=1>[CH3:11][C:9]1[NH:14][C:13](=[O:15])[C:6]2[C:5](=[CH:4][C:3]([CH3:12])=[C:2]([CH3:1])[CH:7]=2)[N:8]=1.[CH3:11][C:9]1[NH:14][C:13](=[O:15])[C:4]2[C:5](=[CH:6][CH:7]=[C:2]([CH3:1])[C:3]=2[CH3:12])[N:8]=1
Reactant: CC(=O)Nc1ccc(C)c(C)c1
Reactant: CCOC(N)=O
Agent: O=P12OP3(=O)OP(=O)(O1)OP(=O)(O2)O3
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1C
Product: Cc1nc2cc(C)c(C)cc2c(=O)[nH]1
Product: Cc1nc2ccc(C)c(C)c2c(=O)[nH]1
Temperature: 60 °C

Procedure:
A mixture of 3,4-dimethylacetanilide (16.3 g), ethyl carbamate (14 g), phosphorus pentoxide (30 g) and xylene (55 ml) was stirred vigorously using a mechanical stirrer under an atmosphere of argon. The mixture was slowly heated to approximately 60° C. whereupon a visible reaction ensued with the evolution of heat and with an increase in the viscosity of the mixture. The temperature of the mixture was raised over a period of 90 minutes to 150° C. and the mixture was stirred at this temperature for 2 hours during which time more phosphorus pentoxide (12 g in total) was added portionwise. The mixture was cooled and the xylene was decanted. A mixture of ice and water (250 ml) was added to the residue and the mixture was stirred for 30 minutes and filtered. The solid was analysed by thin layer chromatography using ethyl acetate as solvent and if it contained any product it was purified by chromatography as described for the residue obtained below. The filtrate was cooled in an ice bath to a temperature of less than 5° C. and the acidity of the solution was reduced to pH 5 by the addition of a concentrated aqueous sodium hydroxide solution. The mixture was extracted with ethyl acetate (2×50 ml) and the combined extracts were dried over magnesium sulphate, filtered and evaporated. The residue was purified by chromatography on a silica gel column using a 1:1 v/v mixture of methylene chloride and ethyl acetate as eluent. There were thus obtained, in order of elution, 3,4-dihydro-2,6,7-trimethylquinazolin-4-one (2 g) and 3,4-dihydro-2,5,6-trimethylquinazolin-4-one (2 g).
Reaction SMILES: [CH3:1][CH:2]1[CH2:11][C:10]2[C:9](=[O:12])[CH2:8][CH2:7][CH2:6][C:5]=2[NH:4][C:3]1=[O:13].[CH3:14]I>CC(C)=O>[CH3:14][N:4]1[C:5]2[CH2:6][CH2:7][CH2:8][C:9](=[O:12])[C:10]=2[CH2:11][CH:2]([CH3:1])[C:3]1=[O:13]
Reactant: CC1CC2=C(CCCC2=O)NC1=O
Reactant: CI
Solvent: CC(C)=O
Product: CC1CC2=C(CCCC2=O)N(C)C1=O

Procedure:
Prepared analogously to Example 29 from 3-methyl- 3,4,7,8-tetrahydro-2,5(1H,6H)-quinolinedione and methyl iodide in boiling acetone.
Reaction SMILES: Cl.[NH2:2][CH2:3][C:4]([C:6]1[CH:11]=[CH:10][C:9]([CH3:12])=[CH:8][CH:7]=1)=O.N1C=CC=CC=1.[N:19]#[C:20][C:21]#[N:22]>C1(C)C=CC=CC=1>[C:20]([C:21]1[NH:2][CH:3]=[C:4]([C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[CH:8][CH:7]=2)[N:22]=1)#[N:19]
Reactant: Cc1ccc(C(=O)CN)cc1
Reactant: N#CC#N
Agent: Cl
Solvent: Cc1ccccc1
Solvent: c1ccncc1
Product: Cc1ccc(-c2c[nH]c(C#N)n2)cc1
Temperature: -78 °C
Yield: 52.4 %

Procedure:
0.93 g (5 mmol) of 2-amino-4'-methylacetophenone hydrochloride was suspended in 30 ml of toluene in a 50-ml stainless steel autoclave. To the suspension was then added 0.79 g (10 mmol) of pyridine. The suspension was then cooled to a temperature of -78° C. To the suspension was then added about 0.5 g (9.6 mmol) of cyanogen which had been cooled and solidified at a temperature of -78° C. The autoclave was then sealed. The suspension was heated at a temperature of 100° C. for 2.5 hours, and then allowed to cool. The content was then taken out of the autoclave. The reaction mixture was then extracted with ethyl acetate and water. The resulting organic phase was dried over anhydrous sodium sulfate, and then subjected to silica gel column chromatography to obtain 0.48 g (yield: 52 %) of 2-cyano-4-(p-tolyl)imidazole.
Reaction SMILES: [F:1]C1C=C(N2C[C@H](CNC(=O)C)OC2=O)C=CC=1N1C[C@@H]2[C@@H](CN(CCO)C2)C1.[F:30][C:31]1[CH:32]=[C:33]([N:49]2[CH2:53][C@H:52]([CH2:54][NH:55][C:56](=[O:58])[CH3:57])[O:51][C:50]2=[O:59])[CH:34]=[CH:35][C:36]=1[N:37]1[CH2:44][C@@H:43]2[C@@H:39]([CH2:40][N:41]([CH2:45][CH2:46]OC)[CH2:42]2)[CH2:38]1.FC1C=C(N2C[C@H](CNC(=O)C)OC2=O)C=CC=1N1C[C@@H]2[C@@H](CN(CC#N)C2)C1.FC1C=C(N2C[C@H](CNC(=O)C)OC2=O)C=CC=1N1C[C@@H]2[C@@H](CN(C(OC)=O)C2)C1>>[F:30][C:31]1[CH:32]=[C:33]([N:49]2[CH2:53][C@H:52]([CH2:54][NH:55][C:56](=[O:58])[CH3:57])[O:51][C:50]2=[O:59])[CH:34]=[CH:35][C:36]=1[N:37]1[CH2:44][C@@H:43]2[C@@H:39]([CH2:40][N:41]([CH2:45][CH2:46][F:1])[CH2:42]2)[CH2:38]1
Reactant: COCCN1C[C@@H]2CN(c3ccc(N4C[C@H](CNC(C)=O)OC4=O)cc3F)C[C@@H]2C1
Reactant: CC(=O)NC[C@H]1CN(c2ccc(N3C[C@H]4CN(CCO)C[C@H]4C3)c(F)c2)C(=O)O1
Agent: CC(=O)NC[C@H]1CN(c2ccc(N3C[C@H]4CN(CC#N)C[C@H]4C3)c(F)c2)C(=O)O1
Agent: COC(=O)N1C[C@@H]2CN(c3ccc(N4C[C@H](CNC(C)=O)OC4=O)cc3F)C[C@@H]2C1
Product: CC(=O)NC[C@H]1CN(c2ccc(N3C[C@H]4CN(CCF)C[C@H]4C3)c(F)c2)C(=O)O1

Procedure:
(S)-N-[[3-[3-fluoro-4-[cis-3-(2-hydroxyethyl)-3,7-diazabicyclo[3.3.0]octan-7-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide; (S)-N-[[3-[3-fluoro-4-[cis-3-(2-methoxyethyl)-3,7-diazabicyclo[3.3.0]octan-7-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide; (S)-N-[[3-[3-fluoro4-[cis-3-(cyanomethyl)-3,7-diazabicyclo[3.3.0]octan-7-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide; (S)-N-[[3-[3-fluoro4-[cis-3-(carbomethoxy)-3,7-diazabicyclo[3.3.0]octan-7-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide;