Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:5]1[CH:10]=[C:9]([C:11]([CH3:14])([CH3:13])[CH3:12])[CH:8]=[CH:7][C:6]=1[OH:15])([CH3:4])([CH3:3])[CH3:2].[C:16]1(=O)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1.Cl>CCCCCC>[C:1]([C:5]1[CH:10]=[C:9]([C:11]([CH3:14])([CH3:13])[CH3:12])[CH:8]=[C:7]([C:16]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH:17]=2)[C:6]=1[OH:15])([CH3:4])([CH3:3])[CH3:2]
Reactant: O=C1CCCCCC1
Reactant: CC(C)(C)c1ccc(O)c(C(C)(C)C)c1
Agent: Cl
Solvent: CCCCCC
Product: CC(C)(C)c1cc(C2=CCCCCC2)c(O)c(C(C)(C)C)c1
Reaction time: 22 h
Yield: 9 %

Procedure:
A mixture consisting of 82.5 g (0.40 mol) of 2,4-di-tert-butylphenol and 22.5 g (0.20 mol) of cycloheptanone is melted together and is then saturated, with stirring, with hydrochloric acid gas at 35-40° C. After 22 hours, the reaction mixture is again saturated with hydrochloric acid gas and then stirred for 17 hours. Subsequently, the reaction mixture is diluted with hexane and washed with water and sodium chloride solution. The organic phase is dried over magnesium sulfate and concentrated on a rotary evaporator. The residue is chromatographed over silica gel using the solvent system hexane/ethyl acetate=99:1 and the pure fractions are crystallised from ethanol, giving 5.4 g (9%) of 2,4-di-tert-butyl-6-cyclohepten-1-yl-phenol, m.p. 78-80° C. (compound (105), Table 1).
Reaction SMILES: [F:1][C:2]1([F:26])[C:8]([CH3:10])([CH3:9])[O:7][CH2:6][C:5](=S)[NH:4][C@@:3]1([C:13]1[CH:18]=[C:17]([C:19]2[CH:20]=[N:21][CH:22]=[N:23][CH:24]=2)[CH:16]=[CH:15][C:14]=1[F:25])[CH3:12].[NH3:27].C(OO)(C)(C)C>CO>[F:1][C:2]1([F:26])[C:8]([CH3:10])([CH3:9])[O:7][CH2:6][C:5]([NH2:27])=[N:4][C@@:3]1([C:13]1[CH:18]=[C:17]([C:19]2[CH:20]=[N:21][CH:22]=[N:23][CH:24]=2)[CH:16]=[CH:15][C:14]=1[F:25])[CH3:12]
Reactant: N
Reactant: CC1(C)OCC(=S)N[C@](C)(c2cc(-c3cncnc3)ccc2F)C1(F)F
Agent: CC(C)(C)OO
Solvent: CO
Product: CC1(C)OCC(N)=N[C@](C)(c2cc(-c3cncnc3)ccc2F)C1(F)F
Temperature: 25 °C
Reaction time: 16 h
Yield: 41 %

Procedure:
A solution of (R)-6,6-difluoro-5-(2-fluoro-5-(pyrimidin-5-yl)phenyl)-5,7,7-trimethyl-1,4-oxazepane-3-thione (239 mg, 627 μmol) in methanol (7.2 ml), was treated with ammonia (7 M in methanol, 5.37 ml) and tert-butyl hydroperoxide (70% in water, 517 μl). The mixture was stirred at room temperature for 16 hours. For the workup, the reaction mixture was extracted with water and dichloromethane. The organic layer was washed with water and brine, the aqueous layers were reextracted with dichloromethane. The combined organic layers were dried over sodium sulphate, filtered and evaporated to give brown oil. The residue was purified by chromatography on an amino-silica phase using dichloromethane as the eluent. The (R)-6,6-difluoro-5-(2-fluoro-5-(pyrimidin-5-yl)phenyl)-5,7,7-trimethyl-2,5,6,7-tetrahydro-1,4-oxazepin-3-amine (94 mg, 41% yield) was obtained as a white foam. MS (ISP): m/z=365.2 [M+H]+.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([OH:11])[C:5](=[CH:9][CH:10]=1)[C:6]([OH:8])=[O:7].C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:18]([CH2:36]S([O-])(=O)=O)[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]/[CH:26]=[CH:27]/[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]C>CN(C=O)C>[CH2:36]([O:7][C:6](=[O:8])[C:5]1[C:4](=[CH:3][C:2]([NH2:1])=[CH:10][CH:9]=1)[OH:11])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]/[CH:25]=[CH:26]/[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]
Reactant: CCCCCCCC/C=C/CCCCCCCCCS(=O)(=O)[O-]
Reactant: Nc1ccc(C(=O)O)c(O)c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CCCCCCCC/C=C/CCCCCCCCOC(=O)c1ccc(N)cc1O
Temperature: 35 °C
Reaction time: 48 h
Yield: 51.3 %

Procedure:
To a suspension of para-amino-salicyclic acid (PAS) (0.47 g, 31 mmol) and Cesium carbonate (0.98 g, 3.0 mmol) in 50 ml anhydrous DMF was added elaidylmesylate (1.0 g, 2.9 mmol) and the reaction mixture was stirred at ambient temperature for 60 hours and at 35° C. for 48 hours. The reaction mixture was extracted with ether and water, and the organic phase was washed with NaHCO3(aq) and water. The solvent was evaporated off and the residue was purified on acolumn of silica gel with heptane/CH2Cl2/AcOH/MeOH (85:15:2:2) as the solvent system. Product containing fractions was repurified (70:30:2:2) and homogenous fractions were evaporated to give 0.6 g (51%) of the title compound.
Reaction SMILES: [CH3:1][C:2]1[N:3]([CH2:31][C:32]([O:34]CC)=[O:33])[C:4]2[C:9]([C:10]=1[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([NH:18][C:19](=[O:30])[C:20]3[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=3)=[CH:14][CH:13]=1)=[CH:8][CH:7]=[CH:6][CH:5]=2.O.[OH-].[Li+].O1CCCC1.CO>O>[CH3:1][C:2]1[N:3]([CH2:31][C:32]([OH:34])=[O:33])[C:4]2[C:9]([C:10]=1[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([NH:18][C:19](=[O:30])[C:20]3[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=3)=[CH:14][CH:13]=1)=[CH:8][CH:7]=[CH:6][CH:5]=2
Reactant: CCOC(=O)Cn1c(C)c(Cc2ccc(NC(=O)c3ccc(C(F)(F)F)cc3)cc2)c2ccccc21
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: O
Solvent: C1CCOC1
Product: Cc1c(Cc2ccc(NC(=O)c3ccc(C(F)(F)F)cc3)cc2)c2ccccc2n1CC(=O)O
Temperature: 25 °C
Reaction time: 1 h
Yield: 85 %

Procedure:
Into a dry reaction vessel, ethyl 2-[2-methyl-3-[4-[4-(trifluoromethyl)benzamido]benzyl]-1H-indol-1-yl]acetate (600 mg, 1.21 mmol), lithium hydroxide monohydrate (153 mg, 3.64 mmol), 10 mL tetrahydrofuran, 10 mL methanol, 10 mL water were weighed, and stirred at room temperature for 1 h. The reaction was monitored to be complete by TLC. The solvent was rotate evaporated. It was adjusted to pH=3-4 with 2 N HCl solution. It was filtered, and the filter cake was washed with 20 mL methanol to obtain the product 480 mg as a white solid, at a yield of 85.1%.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=1)[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:23](OCC)C.CO.C[Si](C=[N+]=[N-])(C)C>CCCCCC>[CH3:23][O:11][C:10](=[O:12])[CH:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=1
Reactant: CC(C)(C)OC(=O)NC(Cc1ccc([N+](=O)[O-])cc1)C(=O)O
Reactant: CCOCC
Agent: C[Si](C)(C)C=[N+]=[N-]
Solvent: CO
Solvent: CCCCCC
Product: COC(=O)C(Cc1ccc([N+](=O)[O-])cc1)NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a mixture of the compound (1.15 g) obtained in Example 63, diethyl ether (6 ml) and methanol (14 ml), a solution of trimethylsilyldiazomethane in n-hexane (2.0 M, 7.4 ml) was added and the resulting mixture was stirred at room temperature for 16 h. The reaction solution was concentrated under reduced pressure to give the titled compound quantitatively.
Reaction SMILES: [N+:1]([C:4]1[O:5][C:6]2[C:18]([C:19]([OH:21])=[O:20])=[CH:17][CH:16]=[CH:15][C:7]=2[C:8]=1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)([O-:3])=[O:2].Cl.[CH2:23]([N:25]([CH2:28][CH2:29]Cl)[CH2:26][CH3:27])[CH3:24].C(N(CC)CC)C>CN(C)C=O>[N+:1]([C:4]1[O:5][C:6]2[C:18]([C:19]([O:21][CH2:24][CH2:23][N:25]([CH2:28][CH3:29])[CH2:26][CH3:27])=[O:20])=[CH:17][CH:16]=[CH:15][C:7]=2[C:8]=1[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)([O-:3])=[O:2]
Reactant: CCN(CC)CCCl
Reactant: O=C(O)c1cccc2c(-c3ccccc3)c([N+](=O)[O-])oc12
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CCN(CC)CCOC(=O)c1cccc2c(-c3ccccc3)c([N+](=O)[O-])oc12
Reaction time: 48 h

Procedure:
A mixture of 14.2 g (0.05 mole) of 2-nitro-3-phenyl-7-benzofurancarboxylic acid, 8.6 g (0.05 mole) of N,N-diethylamino-2-chloroethane hydrochloride, 10.1 g (0.1 mole) of triethylamine and 75 ml of N,N-dimethylformamide is heated at 90° to 100° C. for 16 hours, then left standing at 23° C. for 2 days. The mixture is cooled with an ice bath, then filtered to remove the white solid by-product. The filtrate is dissolved in diethyl ether, washed thrice with water and twice with saturated sodium chloride solution and dried. The solution is evaporated to provide an oil, N,N-diethylaminoethyl 2-nitro-3-phenyl-7-benzofurancarboxylate. This oil is dissolved in diethyl ether and treated with 25 ml of 4N-hydrochloric acid in isopropanol to provide a product which gradually solidifies. The product is recrystallized twice from ethanol to provide, N,N-diethylaminoethyl 2-nitro-3-phenyl-7-benzofurancarboxylate hydrochloride, m.p. 194.5°-195° C., as a light yellow solid.
Reaction SMILES: [N:1]1([S:5]([NH2:8])(=[O:7])=[O:6])[CH2:4][CH2:3][CH2:2]1.Cl[C:10]1[N:15]=[C:14]([S:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:19]=2[F:25])[N:13]=[C:12]([O:26][C@@H:27]2[CH2:31][O:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28]2)[CH:11]=1>>[N:1]1([S:5]([NH:8][C:10]2[N:15]=[C:14]([S:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:19]=3[F:25])[N:13]=[C:12]([O:26][C@@H:27]3[CH2:31][O:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28]3)[CH:11]=2)(=[O:7])=[O:6])[CH2:4][CH2:3][CH2:2]1
Reactant: CC(C)(C)OC(=O)N1C[C@H](Oc2cc(Cl)nc(SCc3cccc(F)c3F)n2)CO1
Reactant: NS(=O)(=O)N1CCC1
Product: CC(C)(C)OC(=O)N1C[C@H](Oc2cc(NS(=O)(=O)N3CCC3)nc(SCc3cccc(F)c3F)n2)CO1

Procedure:
The subtitle compound was prepared from azetidine-1-sulfonamide (prepared according to patent WO 2004/011443, 0.22 g) and 1,1-Dimethylethyl (S)-4-[6-chloro-2-[[(2,3-difluorophenyl)methyl]thio]pyrimidin-4-yloxy]isoxazolidine-2-carboxylate (the product of step i) (0.13 g) according to the procedure outlined in Example 1, step iv). The crude material was purified by column chromatography using EtOAc/isohexane (2:8) as eluent. Yield: 0.14 g
Reaction SMILES: [CH3:1][S:2][CH2:3][CH2:4][NH:5][CH2:6][CH2:7][S:8][CH3:9].C(N(C(C)C)CC)(C)C.[CH3:19][O:20][C:21](=[O:24])[CH2:22]Br.C(Cl)Cl>C(#N)C>[CH3:19][O:20][C:21](=[O:24])[CH2:22][N:5]([CH2:6][CH2:7][S:8][CH3:9])[CH2:4][CH2:3][S:2][CH3:1]
Reactant: CSCCNCCSC
Reactant: COC(=O)CBr
Solvent: ClCCl
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)CN(CCSC)CCSC
Temperature: 25 °C
Reaction time: 18 h

Procedure:
165 mg of bis-(2-methylthioethyl)-amine (Example 8b) is dissolved in 20 ml of acetonitrile and mixed with 174 μl of diisopropylethylamine. 92.7 μl of bromoacetic acid methyl ester, dissolved in 20 ml of acetonitrile, is added in drops under a cover-gas atmosphere, and the batch is stirred for 18 hours at room temperature. The acetonitrile is drawn off, the residue is taken up with methylene chloride and washed twice with saturated sodium bicarbonate solution. The organic phase is dried with sodium sulfate and concentrated by evaporation, and the residue is purified by chromatography with the mobile solvent system of methylene chloride/methanol: Yield 183 mg=77% of theory.
Reaction SMILES: C([O:8][C:9](=[O:46])[C@H:10]([CH2:42][CH:43]([CH3:45])[CH3:44])[NH:11][C:12](=[O:41])[C@@H:13]([CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[CH2:14][C@@H:15]([C:23]([O:25][CH2:26][O:27][C:28](=[O:33])[C:29]([CH3:32])([CH3:31])[CH3:30])=[O:24])[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)C1C=CC=CC=1>C(O)C.[Pd]>[C:28]([O:27][CH2:26][O:25][C:23]([C@@H:15]([CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[CH2:14][C@H:13]([CH2:34][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)[C:12]([NH:11][C@H:10]([C:9]([OH:46])=[O:8])[CH2:42][CH:43]([CH3:44])[CH3:45])=[O:41])=[O:24])(=[O:33])[C:29]([CH3:30])([CH3:31])[CH3:32]
Reactant: CC(C)C[C@H](NC(=O)[C@@H](Cc1ccccc1)C[C@H](Cc1ccccc1)C(=O)OCOC(=O)C(C)(C)C)C(=O)OCc1ccccc1
Agent: [Pd]
Solvent: CCO
Product: CC(C)C[C@H](NC(=O)[C@@H](Cc1ccccc1)C[C@H](Cc1ccccc1)C(=O)OCOC(=O)C(C)(C)C)C(=O)O

Procedure:
0.85 g of N-[4-pivaloyloxymethoxycarbonyl-(R*,R*)-2,4-dibenzylbutyryl]-(L)-leucine benzyl ester in 20 ml of ethanol is hydrogenated at atmospheric pressure in the presence of 0.1 g of 5% palladium on carbon. The reaction is filtered and evaporated to give N-[4-pivaloyloxymethoxycarbonyl-(R*,R*)-2,4-dibenzylbutyryl]-(L)-leucine.
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:9]=[C:8]([Cl:10])[C:7]([O:11][CH:12]([CH3:14])[CH3:13])=[CH:6][C:5]=1[N:15]1[C:19](=[O:20])[NH:18][C:17]([C:21]([F:24])([F:23])[F:22])=[N:16]1.I[CH3:26]>CN(C)C=O>[Cl:3][C:4]1[CH:9]=[C:8]([Cl:10])[C:7]([O:11][CH:12]([CH3:14])[CH3:13])=[CH:6][C:5]=1[N:15]1[C:19](=[O:20])[N:18]([CH3:26])[C:17]([C:21]([F:22])([F:23])[F:24])=[N:16]1
Reactant: CC(C)Oc1cc(-n2nc(C(F)(F)F)[nH]c2=O)c(Cl)cc1Cl
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)Oc1cc(-n2nc(C(F)(F)F)n(C)c2=O)c(Cl)cc1Cl
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 92.6 %

Procedure:
Under a dry nitrogen atmosphere 0.1 g (0.0038 mole) of dry sodium hydride was added to a stirred solution of 1.3 g (0.0035 mole) of 1-[2,4-dichloro-5-(1-methylethoxy)phenyl]-3-trifluoromethyl-4,5-dihydro-1,2,4-triazol-5(1H)-one in 30 mL of N,N-dimethylformamide. The mixture was stirred at room temperature for 20 minutes and 0.6 g (0.0038 mole) of iodomethane was added. After complete addition the mixture was warmed to 65° C. and stirred at that temperature for one hour. The mixture was allowed to cool to room temperature and stir for approximately 18 hours. Most of the solvent was removed by distillation under reduced pressure to leave a liquid residue. This residue was partitioned between water and diethyl ether. The organic phase was washed first with a 2N sodium hydroxide solution followed by water. The organic solution was dried over an anhydrous magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure to yield 1.2 g of 1-[2,4-dichloro-5-(1-methylethoxy)phenyl]-3-trifluoromethyl-4,5-dihydro-4-methyl-1,2,4-triazol-5(1H)-one as a solid (mp 96°-98° C.), Compound 35.
Reaction SMILES: Cl.[CH2:2]([C:6]1[CH:7]=[CH:8][C:9]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[C:10]([CH:12]=1)[NH2:11])[CH:3]([CH3:5])[CH3:4].[CH3:19][N:20]([CH3:23])[C:21]#[N:22].C1C(O)=CC=CC=1C>>[CH3:19][N:20]([CH3:23])[C:21]([NH2:22])=[N:11][C:10]1[CH:12]=[C:6]([CH2:2][CH:3]([CH3:5])[CH3:4])[CH:7]=[CH:8][C:9]=1[N:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1
Reactant: CC(C)Cc1ccc(N2CCOCC2)c(N)c1
Reactant: CN(C)C#N
Agent: Cl
Solvent: Cc1cccc(O)c1
Product: CC(C)Cc1ccc(N2CCOCC2)c(N=C(N)N(C)C)c1

Procedure:
A mixture of 5-isobutyl-2-morpholinoaniline hydrochloride (4.1 g), N,N-dimethylcyanamide (1.77 g) and m-cresol (15 ml) was heated at 90°-95° C. for 6 hours to yield a residue which was extracted with hot hexane, decolourised with charcoal and purified by chromatography on an alumina column eluted with a 2:98 mixture of methanol and dichloromethane. The resulting product was crystallised from a 1:3 mixture of ethylacetate and hexane. The initial precipitate was removed by filtration and the filtrate evaporated to dryness to give a residue which was recrystallised from a 1:3 mixture of ethylacetate and hexane to give 1,1-dimethyl-2-(5-isobutyl-2-morpholinophenyl)guanidine.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[N:9]1[CH2:18][C:17]2[C:12](=[N:13][C:14]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][N:29]([CH2:32][CH3:33])[CH2:30][CH3:31])=[CH:22][CH:21]=3)=[N:15][CH:16]=2)[N:11]([C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([CH2:40][CH2:41][N:42]3C(=O)C4=CC=CC=C4C3=O)[CH:35]=2)[C:10]1=[O:53].O.NN>C(O)C>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[N:9]1[CH2:18][C:17]2[C:12](=[N:13][C:14]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][N:29]([CH2:30][CH3:31])[CH2:32][CH3:33])=[CH:22][CH:21]=3)=[N:15][CH:16]=2)[N:11]([C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([CH2:40][CH2:41][NH2:42])[CH:35]=2)[C:10]1=[O:53]
Reactant: CCN(CC)CCOc1ccc(Nc2ncc3c(n2)N(c2cccc(CCN4C(=O)c5ccccc5C4=O)c2)C(=O)N(c2ccc(Cl)cc2Cl)C3)cc1
Agent: NN
Solvent: O
Solvent: CCO
Product: CCN(CC)CCOc1ccc(Nc2ncc3c(n2)N(c2cccc(CCN)c2)C(=O)N(c2ccc(Cl)cc2Cl)C3)cc1
Yield: 23 %

Procedure:
A solution of 50 mg (0.07 mmol) of 3-(2,4-dichlorophenyl)-7-[4-[2-(diethylamino)ethoxy]anilino]-3,4-dihydro-1-[3-(2-phthalimidoethyl)phenyl]pyrimido[4,5-d]pyrimidin-2(1H)-one in 5 ml of ethanol was treated with 0.5 ml of hydrazine hydrate. After 18 hours the mixture was evaporated and the product purified by column chromatography on silica gel using dichloromethane/methanol/acetic acid/water (60:18:2:3) for the elution. Product-containing fractions were combined, evaporated and the residue evaporated with toluene. The residue was then dissolved in 40 ml of dichloromethane, washed with 40 ml of saturated aqueous sodium bicarbonate solution, dried over magnesium sulfate, filtered and evaporated. The residue was triturated with pentane and filtered to give 10 mg (23%) of 3-(2,4-dichlorophenyl)-7-[4-[2-(diethylamino)ethoxy]anilino]-3,4-dihydro-1-[3-(2-aminoethyl)phenyl]pyrimido[4,5-d]pyrimidin-2(1H)-one as a white solid of melting point 108° C.
Reaction SMILES: [CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:19])[CH2:15][O:16][CH2:17][CH3:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:20]([O:27][C:28]1[CH:35]=[CH:34][C:31]([CH:32]=[O:33])=[C:30]([C:36]([F:39])([F:38])[F:37])[CH:29]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[O-]S(C(F)(F)F)(=O)=O.C([B+]CCCC)CCC>C(N(CC)CC)C>[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:19])[C@@H:15]([O:16][CH2:17][CH3:18])[C@@H:32]([C:31]1[CH:34]=[CH:35][C:28]([O:27][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:29][C:30]=1[C:36]([F:37])([F:38])[F:39])[OH:33])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=Cc1ccc(OCc2ccccc2)cc1C(F)(F)F
Reactant: CCOCC(=O)N1C(=O)OC[C@@H]1Cc1ccccc1
Agent: CCCC[B+]CCCC
Agent: O=S(=O)([O-])C(F)(F)F
Solvent: CCN(CC)CC
Product: CCO[C@H](C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1)[C@H](O)c1ccc(OCc2ccccc2)cc1C(F)(F)F

Procedure:
In analogy to the procedure described in example 1 a], (S)-4-benzyl-3-ethoxyacetyl-oxazolidin-2-one (for the preparation of (S)-4-benzyl-3-ethoxyacetyl-oxazolidin-2-one see: D. Haigh, H. C. Birrell, B. C. C. Cantello, D. S. Eggleston, R. C. Haltiwanger, R. M. Hindley, A. Ramaswamy, N. C. Stevens, Tetrahedron: Asymmetry 1999, 10, 1353-1367) was reacted with 4-benzyloxy-2-trifluoromethyl-benzaldehyde in the presence of triethylamine and di-n-butylboron triflate to give (S)-4-benzyl-3-[(2S,3R)-3-(4-benzyloxy-2-trifluoromethyl-phenyl)-2-ethoxy-3-hydroxy-propionyl]-oxazolidin-2-one as colorless liquid. According to 1H-NMR spectroscopy, one of the four isomers is strongly predominating. The configuration was tentatively assigned as 2S,3R according to D. Haigh et al., Tetrahedron: Asymmetry 1999, 10, 1353-1367.
Reaction SMILES: [OH:1][C:2]1[CH:28]=[CH:27][C:5]2[C:6]([CH2:9][CH2:10][C:11]3[N:12]=[C:13]([C:19]4[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:20]=4[Cl:26])[O:14][C:15]=3[CH:16]([CH3:18])[CH3:17])=[N:7][O:8][C:4]=2[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:35](Br)[CH:36]=[CH2:37]>CC(C)=O>[CH2:37]([O:1][C:2]1[CH:28]=[CH:27][C:5]2[C:6]([CH2:9][CH2:10][C:11]3[N:12]=[C:13]([C:19]4[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:20]=4[Cl:26])[O:14][C:15]=3[CH:16]([CH3:18])[CH3:17])=[N:7][O:8][C:4]=2[CH:3]=1)[CH:36]=[CH2:35]
Reactant: CC(C)c1oc(-c2ccc(Cl)cc2Cl)nc1CCc1noc2cc(O)ccc12
Reactant: C=CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: C=CCOc1ccc2c(CCc3nc(-c4ccc(Cl)cc4Cl)oc3C(C)C)noc2c1
Reaction time: 20 h
Yield: 76.5 %

Procedure:
The obtained 6-hydroxy-3-[2-[2-(2,4-dichlorophenyl)-5-isopropyl-4-oxazolyl]ethyl]-1,2-benzisoxazole (500 mg, 1.20 mmol) and potassium carbonate (249 mg, 1.80 mmol) were suspended in acetone (30 mL). Allyl bromide (217 mg, 1.80 mmol) was dropwise added to the suspension for 1 minute while cooling with ice. The mixture was allowed to room temperature, and stirred for 20 hours. After insoluble was filtered off, the filter cake was washed with acetone. The filtrate and washings were combined, and concentrated. The residue was purified by column chromatography on silica gel with hexane/ethyl acetate (4/1) to give the desired compound (420 mg) as colorless oil (yield 77%).
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]=[C:7]2[C:9]([C:13]3[N:23]([S:24]([C:27]4[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=4)(=[O:26])=[O:25])[C:16]4[N:17]=[CH:18][CH:19]=[C:20]([CH:21]=[O:22])[C:15]=4[CH:14]=3)=[CH:10][N:11]([CH3:12])[C:6]2=[CH:5][C:4]=1[O:34][CH3:35].[BH4-].[Na+]>CO.O.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[N:8]=[C:7]2[C:9]([C:13]3[N:23]([S:24]([C:27]4[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=4)(=[O:26])=[O:25])[C:16]4=[N:17][CH:18]=[CH:19][C:20]([CH2:21][OH:22])=[C:15]4[CH:14]=3)=[CH:10][N:11]([CH3:12])[C:6]2=[CH:5][C:4]=1[O:34][CH3:35]
Reactant: COc1cc2c(nc1OC)c(-c1cc3c(C=O)ccnc3n1S(=O)(=O)c1ccc(C)cc1)cn2C
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: CCOC(C)=O
Solvent: O
Product: COc1cc2c(nc1OC)c(-c1cc3c(CO)ccnc3n1S(=O)(=O)c1ccc(C)cc1)cn2C
Temperature: 25 °C
Reaction time: 3 h
Yield: 100 %

Procedure:
To a solution of 4.9 g of 2-(5,6-dimethoxy-1-methyl-1H-pyrrolo[3,2-b]pyridin-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-4-carbaldehyde in 100 cm3 of methanol, at a temperature in the region of 20° C., is added 0.57 g of sodium borohydride. The reaction medium is stirred at room temperature for 3 hours. The reaction medium is concentrated under reduced pressure. The residue obtained is taken up in 100 cm3 of water and 100 cm3 of ethyl acetate. After separation of the phases by settling, the organic phase is dried over magnesium sulfate, filtered and then concentrated under reduced pressure. 4.92 g of [2-(5,6-dimethoxy-1-methyl-1H-pyrrolo[3,2-b]pyridin-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]methanol are obtained with the following characteristics:
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[C:4]([N+:9]([O-])=O)[C:3]=1[CH3:12]>C(O)(=O)C.C(OCC)C.[Fe]>[Br:1][C:2]1[C:3]([CH3:12])=[C:4]([NH2:9])[C:5]([CH3:8])=[CH:6][CH:7]=1
Reactant: Cc1ccc(Br)c(C)c1[N+](=O)[O-]
Agent: [Fe]
Solvent: CCOCC
Solvent: CC(=O)O
Product: Cc1ccc(Br)c(C)c1N
Temperature: 80 °C
Reaction time: 2 h

Procedure:
To a solution of crude 1-bromo-2,4-dimethyl-3-nitrobenzene (0.58 g, 2.9 mmol) in glacial acetic acid (12 mL) was added iron powder (0.65 g, 11.6 mmol). The mixture was stirred rapidly at 80° C. under nitrogen for 2 hours. Upon completion, the mixture was cooled, diluted with diethyl ether and extracted with aqueous sodium hydroxide solution (2N). The organic layer was dried over sodium sulfate, decanted and concentrated under reduced pressure to give 3-bromo-2,6-dimethylphenylamine as a yellow oil which was used without further purification.
Reaction SMILES: [C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7](Cl)=[O:8])=[CH:5][CH:4]=1)#[N:2].[C:12]([N:16]1[C:20](=[O:21])[C:19]([NH:22][CH:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)=[C:18]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[S:17]1(=[O:36])=[O:35])([CH3:15])([CH3:14])[CH3:13]>CN(C=O)C>[C:12]([N:16]1[C:20](=[O:21])[C:19]([NH:22][CH:23]2[CH2:28][CH2:27][N:26]([C:7]([C:6]3[CH:10]=[CH:11][C:3]([C:1]#[N:2])=[CH:4][CH:5]=3)=[O:8])[CH2:25][CH2:24]2)=[C:18]([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[S:17]1(=[O:36])=[O:35])([CH3:15])([CH3:13])[CH3:14]
Reactant: CC(C)(C)N1C(=O)C(NC2CCNCC2)=C(c2ccccc2)S1(=O)=O
Reactant: N#Cc1ccc(C(=O)Cl)cc1
Solvent: CN(C)C=O
Product: CC(C)(C)N1C(=O)C(NC2CCN(C(=O)c3ccc(C#N)cc3)CC2)=C(c2ccccc2)S1(=O)=O
Yield: 11 %

Procedure:
The title compound was prepared as described for Example 105 from 4-cyanobenzoyl chloride and 2-tert-butyl-5-phenyl-4-(piperidin-4-ylamino)isothiazol-3(2H)-one 1,1-dioxide (Example 75) using DMF as solvent. The reaction mixture was evaporated and the residue was purified by silica gel column chromatography (Horizons Biotage) using 50% EtOAc in petroleum ether 40-60° C. as eluent. The product containing fractions were evaporated, dissolved in DCM, washed through a cation exchange column and evaporated to give the title compound (0.015 g, 11%). 1H NMR (500 MHz CDCl3): δ 7.70 (d, 1H), 7.55-7.50 (m, 2H), 7.49-7.40 (m, 5H), 5.21 (d, 1H), 4.52-4.40 (m, 1H), 3.50-3.36 (m, 1H), 3.24-3.14 (m, 2H), 2.62-2.44 (m, 2H), 1.92-1.78 (m, 1H), 1.74 (s, 9H), 1.67-1.54 (m, 2H), 1.48-1.16 (m, 2H); 13C NMR (125 MHz CDCl3): δ 168.5, 159.7, 140.1, 133.9, 132.7, 131.8, 130.3, 129.0, 127.7, 125.2, 118.2, 113.9, 107.9, 61.9, 50.1, 46.0, 40.9, 32.9, 32.1, 27.8; M+H+ 493.