Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[CH2:2][C:3]1[O:7][N:6]=[C:5]([CH2:8][CH3:9])[N:4]=1.[Cl:10][C:11]1[C:12]([O:34][CH3:35])=[CH:13][C:14]([O:32][CH3:33])=[C:15]([CH2:17][CH2:18][C:19]2([CH:27]3[CH2:31][CH2:30][CH2:29][CH2:28]3)[O:24][C:23](=[O:25])[CH2:22][C:21](=[O:26])[CH2:20]2)[CH:16]=1>>[Cl:10][C:11]1[C:12]([O:34][CH3:35])=[CH:13][C:14]([O:32][CH3:33])=[C:15]([CH2:17][CH2:18][C:19]2([CH:27]3[CH2:31][CH2:30][CH2:29][CH2:28]3)[O:24][C:23](=[O:25])[C:22]([CH2:2][C:3]3[O:7][N:6]=[C:5]([CH2:8][CH3:9])[N:4]=3)=[C:21]([OH:26])[CH2:20]2)[CH:16]=1
Reactant: COc1cc(OC)c(CCC2(C3CCCC3)CC(=O)CC(=O)O2)cc1Cl
Reactant: CCc1noc(CCl)n1
Product: CCc1noc(CC2=C(O)CC(CCc3cc(Cl)c(OC)cc3OC)(C3CCCC3)OC2=O)n1
Yield: 7 %

Procedure:
The title compound was prepared as described in Example B(53), using 5-(chloromethyl)-3-ethyl-1,2,4-oxadiazole (Step 1, below) in place of 5-(chloromethyl)-1,3-dimethyl-1H-1,2,4-triazole, and using 6-[2-(5-chloro-2,4-dimethoxyphenyl)ethyl]-6-cyclopentyldihydro-2H-pyran-2,4(3H)-dione in place of 6-[2-(3-chloro-4-methoxyphenyl)ethyl]-6-cyclopentyldihydro-2H-pyran-2,4(3H)-dione. Yield: 7%.
Reaction SMILES: [C:1]1([CH3:45])[C:2]([C:7]([CH2:9][N:10]2[C:16]3[CH:17]=[C:18]([CH3:21])[CH:19]=[CH:20][C:15]=3[N:14]([C:22](=[O:28])[CH:23]([CH3:27])[CH2:24][CH2:25][CH3:26])[CH2:13][CH:12]([NH:29][C:30]([NH:32][C:33]3[CH:38]=[CH:37][CH:36]=[C:35]([C:39]([O:41]CC)=[O:40])[CH:34]=3)=[O:31])[C:11]2=[O:44])=[O:8])=[CH:3][CH:4]=[CH:5][CH:6]=1.O.[OH-].[Li+].O1CCCC1>CO>[C:1]1([CH3:45])[C:2]([C:7]([CH2:9][N:10]2[C:16]3[CH:17]=[C:18]([CH3:21])[CH:19]=[CH:20][C:15]=3[N:14]([C:22](=[O:28])[CH:23]([CH3:27])[CH2:24][CH2:25][CH3:26])[CH2:13][CH:12]([NH:29][C:30](=[O:31])[NH:32][C:33]3[CH:34]=[C:35]([CH:36]=[CH:37][CH:38]=3)[C:39]([OH:41])=[O:40])[C:11]2=[O:44])=[O:8])=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CCCC(C)C(=O)N1CC(NC(=O)Nc2cccc(C(=O)OCC)c2)C(=O)N(CC(=O)c2ccccc2C)c2cc(C)ccc21
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: CCCC(C)C(=O)N1CC(NC(=O)Nc2cccc(C(=O)O)c2)C(=O)N(CC(=O)c2ccccc2C)c2cc(C)ccc21
Yield: 59.7 %

Procedure:
1-[1-(2-Toluoylmethyl)-2-oxo-5-(2-methylpentanoyl)-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl]-3-(3-ethoxycarbonylphenyl)urea (560 mg) was dissolved in methanol (26 ml), aqueous lithium hydroxide monohydrate (192 mg) solution (13 ml) and tetrahydrofuran (13 ml) were added, and the mixture was refluxed for one hour. The reaction mixture was concentrated under reduced pressure, 1N hydrochloric acid was added, and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, the solvent was evaporated under reduced pressure, and diisopropyl ether was added to the residue for trituration, collected by filtration, to thereby obtain 319 mg of the titled compound.
Reaction SMILES: S(Cl)([Cl:3])=O.[F:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12]O)=[CH:8][C:7]=1[O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.O>N1C=CC=CC=1.C(OCC)C>[F:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][Cl:3])=[CH:8][C:7]=1[O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: OCc1ccc(F)c(Oc2ccccc2)c1
Reactant: O=S(Cl)Cl
Solvent: O
Solvent: CCOCC
Solvent: c1ccncc1
Product: Fc1ccc(CCl)cc1Oc1ccccc1
Temperature: 25 °C
Yield: 92 %

Procedure:
In a dry flask were placed in succession 5 ml of diethyl ether, 1.21 g (0.0102 mole) of thionyl chloride, and one drop of pyridine. A solution of 1.85 g (0.0085 mole) of (4-fluoro-3-phenoxyphenyl)methyl alcohol in 5 ml of diethyl ether was added dropwise to the reaction mixture. Upon completion of addition, the reaction mixture was heated at reflux for one hour. After being cooled to room temperature, 10 ml of water was added slowly to the reaction mixture. The phases were separated. Twice the aqueous phase was extracted with 15 ml of diethyl ether, and these extracts were combined with the organic phase. The latter was washed successively twice with 10 ml of a saturated aqueous solution of sodium chloride, once with 10 ml of an aqueous solution of sodium bicarbonate, and twice with the saturated aqueous solution of sodium chloride. After being dried over anhydrous sodium sulfate and being filtered, the solvent was evaporated under reduced pressure, leaving 1.85 g of (4-fluoro-3-phenoxyphenyl)methyl chloride as a light yellow liquid. The nmr and ir spectra were consistent with the proposed structure.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].[F:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1B(O)O.C(=O)([O-])[O-].[K+].[K+].Cl>CO.CC(OC)(C)C.Cl[Pd]Cl>[ClH:1].[F:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6]
Reactant: OB(O)c1ccc(F)cc1F
Reactant: COC(=O)c1ccnc(Cl)c1
Agent: Cl[Pd]Cl
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: COC(C)(C)C
Solvent: CO
Product: COC(=O)c1ccnc(-c2ccc(F)cc2F)c1
Temperature: 100 °C
Reaction time: 0.25 h
Yield: 80.1 %

Procedure:
Methyl 2-chloroisonicotinate (3 g, 17.48 mmol), 2,4-difluorophenylboronic acid (4.14 g, 26.23 mmol), potassium carbonate (1.812 g, 13.11 mmol) and PdCl2 (dppf) (0.380 g, 0.52 mmol) were mixed in methanol (30 mL) in two separate 20 mL microwave vials. The vials were capped and heated at 100° C. for 10 min in a single node microwave reactor. Water and DCM were added and the phases were separated. The water phase (pH 9) was extracted with DCM and the combined organic phase washed with brine, passed through a phase separator and evaporated to yield a brown solid. The solid was dissolved in MTBE and stirred for 15 minutes, then filtered. The orange MTBE layer was treated with hydrogen chloride (4 M in dioxane, 4.37 mL, 17.48 mmol) and stirred for 1 h at room temperature. The formed solid was collected by filtration. Methyl 2-(2,4-difluorophenyl)isonicotinate hydrochloride (4.0 g, 80%) was isolated as a slightly orange solid. MS m/z 250 (M+H)+
Reaction SMILES: [CH2:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[NH:12][C:13]([C:15]2[N:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]3=[N:17][CH:16]=2)=[O:14])[N:5]([CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([OH:31])[N:26]=2)[N:4]=1)[CH3:2].CS(O[C@@H:37]1[CH2:41][CH2:40][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:38]1)(=O)=O.C([O-])([O-])=O.[Cs+].[Cs+]>CC(N(C)C)=O>[CH2:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[NH:12][C:13]([C:15]2[N:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]3=[N:17][CH:16]=2)=[O:14])[N:5]([CH2:24][C:25]2[N:26]=[C:27]([O:31][C@H:41]3[CH2:37][CH2:38][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:40]3)[CH:28]=[CH:29][CH:30]=2)[N:4]=1)[CH3:2]
Reactant: CCc1nn(Cc2cccc(O)n2)c2cccc(NC(=O)c3cnc4ccccn34)c12
Reactant: CC(C)(C)OC(=O)N1CC[C@@H](OS(C)(=O)=O)C1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC(=O)N(C)C
Product: CCc1nn(Cc2cccc(O[C@H]3CCN(C(=O)OC(C)(C)C)C3)n2)c2cccc(NC(=O)c3cnc4ccccn34)c12
Temperature: 90 °C
Reaction time: 6 h
Yield: 50.6 %

Procedure:
To N-(3-ethyl-1-((6-hydroxypyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (21 mg, 0.051 mmol) in DMA (2 mL) was added (R)-tert-butyl 3-(methylsulfonyloxy)pyrrolidine-1-carboxylate (20 mg, 0.076 mmol) and Cs2CO3 (33 mg, 0.10 mmol). The reaction vial was sealed, and the reaction was heated to 90° C. and stirred for 6 hours. DMA was removed under reduce pressure. The residue was diluted with EtOAc (20 mL), washed with saturated NaHCO3 aqueous solution (5 mL) and brine (5 mL), and concentrated. Silica gel chromatography of the crude material (DCM/MeOH 10:0.5) provided the desired product (15 mg).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[N:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:19])[N:11]=[C:10]([C:20]([F:26])([F:25])[C:21]([F:24])([F:23])[F:22])[CH2:9]2)=[CH:4][CH:3]=1.[CH3:27][S:28][C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)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>[Cl:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[N:12]1[CH:8]([C:5]2[CH:6]=[CH:7][C:2]([C:32]3[CH:33]=[CH:34][C:29]([S:28][CH3:27])=[CH:30][CH:31]=3)=[CH:3][CH:4]=2)[CH2:9][C:10]([C:20]([F:25])([F:26])[C:21]([F:22])([F:24])[F:23])=[N:11]1
Reactant: CSc1ccc(B(O)O)cc1
Reactant: FC(F)(F)C(F)(F)C1=NN(c2ccccc2Cl)C(c2ccc(Br)cc2)C1
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: [Na+]
Solvent: CN(C)C=O
Product: CSc1ccc(-c2ccc(C3CC(C(F)(F)C(F)(F)F)=NN3c3ccccc3Cl)cc2)cc1
Yield: 58.8 %

Procedure:
A solution of 5-(4-bromo-phenyl)-1-(2-chloro-phenyl)-3-pentafluoroethyl-4,5-dihydro-1H-pyrazole (100.0 mg, 0.19 mmol) prepared in Step 3 of Preparation 1, 4-(methylthio)phenylboronic acid (80.0 mg, 0.28 mmol), Pd(PPh3)4 (26 mg, cat.), and a 2N sodium carbonate solution 0.6 mL in N,N-dimethylformamide (5 mL) were stirred at 80° C. for 6 hours. The reaction mixture was concentrated under reduced pressure and then extracted with ethyl acetate. The extract was washed with distilled water, dried on anhydrous magnesium sulfate, and then concentrated under reduced pressure to give a yellow liquid residue. The resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/n-hexane=1/20) to give 55.5 mg of the titled compound as a pale yellow liquid.
Reaction SMILES: [F:1][CH:2]([F:14])[CH2:3][NH:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N+:11]([O-])=O>CO.[Pd]>[F:1][CH:2]([F:14])[CH2:3][NH:4][C:5]1[C:6]([NH2:11])=[CH:7][CH:8]=[CH:9][CH:10]=1
Reactant: O=[N+]([O-])c1ccccc1NCC(F)F
Agent: [Pd]
Solvent: CO
Product: Nc1ccccc1NCC(F)F
Temperature: 25 °C
Reaction time: 3 h
Yield: 97.8 %

Procedure:
To a solution of 3,6 g (18 mM) of N-(2,2-difluoroethyl)-2-nitroaniline in 25 ml of methanol, were added 470 mg of palladium on carbon at 5%. The reaction mixture was stirred for 3 h at room temperature under hydrogen atmosphere, at room pressure and room temperature. The catalyst was filtrated on Celite and the filtrate was evaporated under vacuum to give 3 g of N-(2,2-difluoro ethyl)benzene-1,2-diamine as an oil. Yield: 97,5%.
Reaction SMILES: [CH3:1][N:2]([CH3:6])[CH2:3][CH2:4][NH2:5].CC(O)=O.[Br:11][C:12]1[CH:31]=[CH:30][C:15]2[O:16][CH2:17][C:18](=O)[CH2:19][N:20]3[C:28]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[CH:22]=[C:21]3[C:14]=2[CH:13]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl>[Br:11][C:12]1[CH:31]=[CH:30][C:15]2[O:16][CH2:17][CH:18]([NH:5][CH2:4][CH2:3][N:2]([CH3:6])[CH3:1])[CH2:19][N:20]3[C:28]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[CH:22]=[C:21]3[C:14]=2[CH:13]=1
Reactant: O=C1COc2ccc(Br)cc2-c2cc3ccccc3n2C1
Reactant: CN(C)CCN
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCCl
Product: CN(C)CCNC1COc2ccc(Br)cc2-c2cc3ccccc3n2C1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
N′,N′-dimethylethane-1,2-diamine (39 mg, 0.440 mmol) and CH3COOH (26 mg, 0.440 mmol) were added to the mixture of 2-bromo-6H-benzo[2,3][1,5]oxazocino[5,4-a]indol-7(8H)-one (100 mg, 0.293 mmol) in 1,2-dichloroethane (2 mL). The mixture was stirred at room temperature for 20 minutes. Then NaBH(OAc)3 (93 mg, 0.440 mmol) was added to the mixture. The mixture was stirred at room temperature for 2 hours. The mixture was then quenched with saturated NaHCO3 (30 mL) and extracted with ethyl acetate (15 mL×3). The organic layer was washed with brine (20 mL), dried over Na2SO4 and concentrated in vacuo. The resulting residue was purified using p-TLC (dichloromethane:MeOH=1:1) to provide N1-(2-bromo-7,8-dihydro-6H-benzo[2,3][1,5]oxazocino[5,4-a]indol-7-yl)-N2,N2-dimethylethane-1,2-diamine. 1H-NMR (CDCl3, 400 MHz) δ 7.51˜7.56 (m, 2H), 7.42 (s, 1H), 7.29˜7.32 (m, 1H), 7.16˜7.18 (m, 1H), 7.06 (t, J=7.2 Hz, 1H), 6.85 (d, J=8.8 Hz, 1H), 6.56 (s, 1H), 3.86˜4.32 (m, 4H), 2.81˜3.03 (m, 5H), 2.59 (s, 6H). MS (M+H)+: 414/416.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][C:9]([NH:11][C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][C:20]=2[N+:21]([O-])=O)[N:17]([CH3:24])[C:16](=[O:25])[C:15]3([CH3:27])[CH3:26])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>C(O)(=O)C.[Fe]>[CH3:24][N:17]1[C:18]2[CH:19]=[C:20]3[NH:21][C:9]([CH2:8][CH2:7][C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)=[N:11][C:12]3=[CH:13][C:14]=2[C:15]([CH3:27])([CH3:26])[C:16]1=[O:25]
Reactant: CN1C(=O)C(C)(C)c2cc(NC(=O)CCc3ccccc3)c([N+](=O)[O-])cc21
Agent: [Fe]
Solvent: CC(=O)O
Product: CN1C(=O)C(C)(C)c2cc3nc(CCc4ccccc4)[nH]c3cc21
Yield: 69.4 %

Procedure:
To a solution of 3-phenyl-N-(1,3,3-trimethyl-6-nitro-2-oxo-2,3-dihydro-1H-indol-5-yl)-propionamide (125 mg; 248 μmol) in acetic acid (3 ml) is added iron powder (403 mg; 7 mmol). The mixture is heated and irradiated in a microwave apparatus (150° C.; 900 s). After re-cooling the mixture is filtered and evaporated. The residue is taken-up in water (40 ml) and saturated K2CO3 solution (10 ml) and extracted with CH2Cl2 (4×50 ml). The combined organic layer is dried over MgSO4 and concentrated in vacuo. The desired compound (55.0 mg) is obtained by preparative RP-HPLC eluting with a water/MeCN gradient.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.[CH2:12]([O:19][C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(N(CC)CC)C>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Br:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][N:6]2[C:23]1[CH:24]=[CH:25][C:20]([O:19][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:21][CH:22]=1
Reactant: OB(O)c1ccc(OCc2ccccc2)cc1
Reactant: Fc1cc(Br)c2cc[nH]c2c1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Fc1cc(Br)c2ccn(-c3ccc(OCc4ccccc4)cc3)c2c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 55.3 %

Procedure:
A mixture of 4-bromo-6-fluoro-1H-indole (D16), (200 mg, 0.935 mmol), 4-benzyloxyphenylboronic acid (426 mg, 1.87 mmol), copper (II) acetate (332 mg, 1.87 mmol) and triethylamine (0.26 mL, 188 mg, 1.87 mmol) in dichloromethane (5 mL) was stirred in air at room temperature for 16 hours. The mixture was filtered through celite, concentrated and purified by chromatography on silica gel (elution with 0-20% ethyl acetate in hexanes) to give the title compound as a pink solid (D19), (205 mg).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([OH:8])[N:5]2[N:9]=[C:10]([C:21]([F:24])([F:23])[F:22])[C:11]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[C:14]=3[Cl:20])=[C:4]2[N:3]=1.[CH3:25][CH:26]1[O:31][CH2:30][CH2:29][NH:28][CH2:27]1>C(O)C.C(OCC)(=O)C>[Cl:20][C:14]1[C:15]([Cl:19])=[CH:16][CH:17]=[CH:18][C:13]=1[CH2:12][C:11]1[C:10]([C:21]([F:24])([F:23])[F:22])=[N:9][N:5]2[C:6]([OH:8])=[CH:7][C:2]([N:28]3[CH2:29][CH2:30][O:31][CH:26]([CH3:25])[CH2:27]3)=[N:3][C:4]=12
Reactant: CC1CNCCO1
Reactant: Oc1cc(Cl)nc2c(Cc3cccc(Cl)c3Cl)c(C(F)(F)F)nn12
Solvent: CCOC(C)=O
Solvent: CCO
Product: CC1CN(c2cc(O)n3nc(C(F)(F)F)c(Cc4cccc(Cl)c4Cl)c3n2)CCO1

Procedure:
To a solution of 5-chloro-3-[(2,3-dichlorophenyl)methyl]-2-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-7-ol (79 mg, 0.2 mmol), prepared as described in Example 7 step b, in ethanol (2 mL) was added 2-methylmorpholine (101 mg, 1.0 mmol) in a microwave reaction vessel. It was sealed and irradiated (microwave) at 150° C. for seven hours. The reaction mixture was diluted with ethyl acetate (20 mL), washed with 5% HCl solution (5 mL). Organic layer was dried, filtered, and concentrated. The crude product was purified by reverse-phase HPLC to provide the titled compound. (17 mg, 18%); LC/MS: MS (ES+) m/e 461 (MH+); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.13 (d, J=6.32 Hz, 3H) 2.68 (m, 1H) 2.96 (m, 1H) 3.56 (m, 2H) 3.71 (m, 2H) 3.88 (m, 1H) 4.20 (s, 2H) 5.23 (s, 1H) 6.85 (s, 1H) 7.25 (t, J=7.96 Hz, 1H) 7.53 (d, J=7.58 Hz, 1H) 11.24 (s, 1H).
Reaction SMILES: [Br:1][CH:2]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])[C:3](Cl)=[O:4].[CH3:16][NH:17][C@@H:18]1[C@@H:24]([OH:25])[C@H:23]([O:26][C@@H:27]2[O:35][C@H:34]([CH2:36][OH:37])[C@H:32]([OH:33])[C@H:30]([OH:31])[C@H:28]2[OH:29])[C@@H:22]([CH2:38][OH:39])[O:21][CH:19]1[OH:20].C(=O)([O-])[O-].[Na+].[Na+]>C(O)CCC>[Br:1][CH:2]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])[C:3]([C:19]1([O:21][C@H:22]([CH2:38][OH:39])[C@@H:23]([O:26][C@@H:27]2[O:35][C@H:34]([CH2:36][OH:37])[C@H:32]([OH:33])[C@H:30]([OH:31])[C@H:28]2[OH:29])[C@H:24]([OH:25])[C@H:18]1[NH:17][CH3:16])[OH:20])=[O:4]
Reactant: CN[C@H]1C(O)O[C@H](CO)[C@@H](O[C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2O)[C@@H]1O
Reactant: CCCCCCCCCCC(Br)C(=O)Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCCCO
Product: CCCCCCCCCCC(Br)C(=O)C1(O)O[C@H](CO)[C@@H](O[C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2O)[C@H](O)[C@H]1NC
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Alpha-bromolauroyl chloride (2.4 g) was added drop-wise to a 30% aqueous solution of N-methyl-lactosamine (3.5 g) at zero degrees centigrade. The pH of the solution was maintained above 9 by the addition of a saturated aqueous sodium carbonate solution. The reaction was stirred overnight at room temperature. It was then heated up to 36° C. for an additional hour. The final product was obtained by extraction two times with n-butanol. The organic layer was dried with sodium sulfate and then rotevaporated under vacuum. The final product was taken for NMR analysis. The result confirmed that the solid material is the expected product. The yield of reaction was 80%.
Reaction SMILES: [O:1]=[C:2]1[CH2:7][NH:6][CH2:5][CH2:4][N:3]1[C:8]1[S:9][C:10]2[CH:16]=[CH:15][C:14]([C:17]#[N:18])=[CH:13][C:11]=2[N:12]=1.[CH3:19][C:20]1[C:28]2[CH2:27][O:26][C:25](=[O:29])[C:24]=2[CH:23]=[CH:22][C:21]=1[C@@H:30]1[CH2:32][O:31]1>CCO>[OH:31][C@H:30]([C:21]1[CH:22]=[CH:23][C:24]2[C:25](=[O:29])[O:26][CH2:27][C:28]=2[C:20]=1[CH3:19])[CH2:32][N:6]1[CH2:5][CH2:4][N:3]([C:8]2[S:9][C:10]3[CH:16]=[CH:15][C:14]([C:17]#[N:18])=[CH:13][C:11]=3[N:12]=2)[C:2](=[O:1])[CH2:7]1
Reactant: N#Cc1ccc2sc(N3CCNCC3=O)nc2c1
Reactant: Cc1c([C@@H]2CO2)ccc2c1COC2=O
Solvent: CCO
Product: Cc1c([C@@H](O)CN2CCN(c3nc4cc(C#N)ccc4s3)C(=O)C2)ccc2c1COC2=O
Temperature: 145 °C

Procedure:
A mixture of 2-(2-Oxopiperazin-1-yl)-1,3-benzothiazole-5-carbonitrile [I-8] (25 mg, 0.10 mmol) and 4-methyl-5-[(2R)-oxiran-2-yl]-2-benzofuran-1(3H)-one (37 mg, 0.19 mmol) in EtOH (2 mL) in a 5 mL microwave tube was heated to 145° C. for 1.5 hours. LC showed formation of the title product, which was purified by silica gel flash chromatography. LC-MS (IE, m/z): 449 [M+1]+.
Reaction SMILES: [F:1][CH:2]([F:22])[O:3][C:4]1[CH:9]=[CH:8][N:7]=[C:6]([CH2:10][S:11][C:12]2[NH:13][C:14]3[CH:20]=[CH:19][CH:18]=[CH:17][C:15]=3[N:16]=2)[C:5]=1[CH3:21].ClC1C=CC=C(C(OO)=[O:31])C=1>C(Cl)(Cl)Cl.CO>[F:22][CH:2]([F:1])[O:3][C:4]1[CH:9]=[CH:8][N:7]=[C:6]([CH2:10][S:11]([C:12]2[NH:16][C:15]3[CH:17]=[CH:18][CH:19]=[CH:20][C:14]=3[N:13]=2)=[O:31])[C:5]=1[CH3:21]
Reactant: Cc1c(OC(F)F)ccnc1CSc1nc2ccccc2[nH]1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: CO
Solvent: ClC(Cl)Cl
Product: Cc1c(OC(F)F)ccnc1CS(=O)c1nc2ccccc2[nH]1
Yield: 71 %

Procedure:
In chloroform (20 ml) - methanol (10 ml) was dissolved 2-[(4-difluoromethoxy-3-methyl-2-pyridyl)methylthio]benzimidazole (2.0 g). To the solution was added dropwise, under ice-cooling, a solution of m-chloroperbenzoic acid (MCPBA) (80%, 1.5 g in chloroform (20 ml). The reaction mixture was washed with a saturated aqueous solution of sodium hydrogencarbonate and water, in that order, then dried (MgSO4). The solvent was distilled off. The residual solid was subjected to a silica gel column chromatography. From the portion eluted with ethyl acetate - methanol (100:3, v/v), was obtained 2-[(4-difluoromethoxy-3-methyl-2-pyridyl)methylsulfinyl]benzimidazole (1.5 g, 71%). Recrystallization from ethyl acetate--ether gave colorless needles, m.p. 157°-158° C. (decomp.).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][CH:9]=[O:10].C[O-].[Na+].[Br:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[O:21][CH2:22]Cl>C(O)C>[Br:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[O:21][CH2:22][O:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][CH:9]=[O:10]
Reactant: ClCOc1ccccc1Br
Reactant: O=CNc1ccccc1O
Agent: C[O-]
Agent: [Na+]
Solvent: CCO
Product: O=CNc1ccccc1OCOc1ccccc1Br
Reaction time: 0.5 h
Yield: 37.1 %

Procedure:
N-(2-Hydroxyphenyl)formamide (16.0 g, 130 mmol) was dissolved in 99.9% ethanol (65 ml). Sodium methoxide (7.0 g, 130 mmol) was suspended in 99.9% ethanol (70 ml) and added dropwise over 30 minutes. The resulting mixture was stirred for 30 minutes. 1-Bromo-2-chloromethoxybenzene (26.1 g, 118 mmol, synthesis described in J. Heterocycl. Chem., 11, 1974, 331-337) was added dropwise over 15 minutes. The reaction mixture was stirred for 2.5 h at room temperature, heated at reflux temperature for 2 h, and stirred at room temperature overnight. The mixture was filtered and the filtrate evaporated. The residue was dissolved in toluene (500 ml) and washed with a saturated sodium carbonate solution (2×200 ml). The organic phase was dried (MgSO4) and evaporated. The residue was suspended in ethanol (40 ml), filtered and washed with ethanol (3×10 ml). After drying, N-(2-(2-bromophenoxymethoxy)phenyl)formamide (14.1 g, 37%) was obtained.
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:9](=[N:11][O:12][C:13](=O)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[NH2:10])=[N:4][C:5]([Br:8])=[CH:6][N:7]=1.C([O-])(O)=O.[Na+]>O>[Br:8][C:5]1[N:4]=[C:3]([C:9]2[N:10]=[C:13]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[O:12][N:11]=2)[C:2]([NH2:1])=[N:7][CH:6]=1
Reactant: NC(=NOC(=O)c1ccccc1)c1nc(Br)cnc1N
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Product: Nc1ncc(Br)nc1-c1noc(-c2ccccc2)n1
Temperature: 70 °C
Reaction time: 3 h
Yield: 76 %

Procedure:
3-amino-N′-(benzoyloxy)-6-bromopyrazine-2-carboximidamide (890 mg, 2.648 mmol) and polyphosphonic acid (3.560 mL) were mixed and the reaction heated to 70° C. Further polyphosphonic acid (8.900 mL) was added and the reaction allowed to stir for a further 3 hours at 70° C. The mixture was then allowed to cool to RT, diluted with water and neutralised by the portionwise addition of solid NaHCO3. The resulting precipitate was isolated by filtration and dried (643 mg, 76% Yield). 1H NMR (400.0 MHz, DMSO) d 7.49 (2H, br s), 7.69 (2H, m), 7.77 (1H, m), 8.28 (2H, m), 8.43 (1H, s); MS (ES+) 319.89
Reaction SMILES: [Cl:1][C:2]([Cl:18])([Cl:17])[CH:3](O)[CH:4]([N:11]1[CH:15]=[N:14][CH:13]=[N:12]1)[C:5](=[O:10])[C:6]([CH3:9])([CH3:8])[CH3:7].S(Cl)([Cl:21])=O>>[Cl:1][C:2]([Cl:18])([Cl:17])[CH:3]([Cl:21])[CH:4]([N:11]1[CH:15]=[N:14][CH:13]=[N:12]1)[C:5](=[O:10])[C:6]([CH3:9])([CH3:8])[CH3:7]
Reactant: O=S(Cl)Cl
Reactant: CC(C)(C)C(=O)C(C(O)C(Cl)(Cl)Cl)n1cncn1
Product: CC(C)(C)C(=O)C(C(Cl)C(Cl)(Cl)Cl)n1cncn1
Temperature: 60 °C
Yield: 98 %

Procedure:
393.3 g (1.25 mol) of 1,1,1-trichloro-2-hydroxy-3-(1,2,4-triazol-1-yl)-5,5-dimethyl-hexan-4-one were introduced into 750 ml of thionyl chloride, while stirring, and the mixture was heated to 60° C. for 36 hours. Thereafter, the excess thionyl chloride was distilled off in vacuo. The residue was taken up in 1.5 liters of methylene chloride and the methylene chloride mixture was washed with 10% strength sodium bicarbonate solution until neutral, dried over sodium sulphate and concentrated by distilling off the solvent in vacuo. 408.9 g (98% of theory) of 1,1,1,2-tetrachloro-3-(1,2,4-triazol-1-yl)-5,5-dimethyl-hexan-4-one of melting point 111°-113° C. were obtained.