Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH3:7][C:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[S:10][C:9]=1[C:17](OC)=[O:18].[Cl-].[NH4+]>C1COCC1>[CH3:7][C:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[S:10][C:9]=1[CH2:17][OH:18]
Reactant: COC(=O)c1sc2ccccc2c1C
Agent: [Al+3]
Agent: [Cl-]
Agent: [H-]
Solvent: C1CCOC1
Product: Cc1c(CO)sc2ccccc12
Temperature: 0 °C
Reaction time: 0.08 h
Yield: 99.6 %

Procedure:
To an ice-cold suspension of lithium aluminum hydride (103 mg, 2.72 mmol) in THF (4.4 mL) was added dropwise over 15 minutes under N2 atmosphere, a solution of the above-mentioned methyl 3-methylbenzothiophene-2-carboxylate (560 mg, 2.72 mmol) in THF (1 mL). The mixture was stirred under ice-cooling for 45 minutes, then at room temperature for 5 minutes, to which was added dropwise under ice-cooling saturated aqueous ammonium chloride solution. The mixture was filtered through a layer of Celite, washed with ethyl acetate. Combined organic layers were washed with saturated brine. After drying over anhydrous sodium sulfate, the solvent was removed under reduced pressure to give the titled compound as a white crystal (483 mg, yield 99%).
Reaction SMILES: [CH2:1]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[N:23]=[CH:22][C:21]([O:24][CH2:25][CH:26]([OH:31])[C:27]([F:30])([F:29])[F:28])=[CH:20][N:19]=3)=[CH:14][CH:13]=2)=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH2:4][CH3:5].[CH2:32](I)[CH2:33][CH2:34][CH2:35][CH3:36]>[Ag]=O>[CH2:1]([C:6]1[CH:7]=[CH:8][C:9]([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[N:23]=[CH:22][C:21]([O:24][CH2:25][CH:26]([O:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])[C:27]([F:30])([F:28])[F:29])=[CH:20][N:19]=3)=[CH:16][CH:17]=2)=[CH:10][CH:11]=1)[CH2:2][CH2:3][CH2:4][CH3:5]
Reactant: CCCCCc1ccc(-c2ccc(-c3ncc(OCC(O)C(F)(F)F)cn3)cc2)cc1
Reactant: CCCCCI
Agent: O=[Ag]
Product: CCCCCOC(COc1cnc(-c2ccc(-c3ccc(CCCCC)cc3)cc2)nc1)C(F)(F)F
Reaction time: 8 h
Yield: 43 %

Procedure:
A mixture of 2-(4'-pentylbiphenyl-4-yl)-5-(2-hydroxy-3,3,3-trifluoropropoxy)-pyrimidine (60 mg), pentyl iodide (30 mg) and silver oxide (40 mg) was stirred overnight, followed by filtering off insoluble substance, concentrating the mother liquid and recrystallizing from ethanol to obtain 2-(4'-pentylbiphenyl-4-yl)-5-(2-pentyloxy-3,3,3-trifluoropropoxy)-pyrimidine (30 mg).
Reaction SMILES: [CH3:1][C:2]([CH3:10])([CH:5]([OH:9])[CH:6]([CH3:8])[CH3:7])[CH2:3][OH:4].[OH-].[Na+].[CH2:13](Cl)[C:14](=[CH2:16])[CH3:15]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH3:15][C:14](=[CH2:13])[CH2:16][O:4][CH2:3][C:2]([CH3:10])([CH3:1])[CH:5]([OH:9])[CH:6]([CH3:8])[CH3:7]
Reactant: C=C(C)CCl
Reactant: CC(C)C(O)C(C)(C)CO
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Agent: [Na+]
Product: C=C(C)COCC(C)(C)C(O)C(C)C
Temperature: 100 °C
Reaction time: 3 h
Yield: 101.8 %

Procedure:
To a 1 L flask equipped with a reflux condenser and a thermometer, was added 292.5 g (2.0 mol) of 2,2,4-trimethylpentan-1,3-diol, 352.0 g (4.4 mol) of 50% aqueous NaOH, and 6.45 g (20 mmol) of tetrabutyl ammonium bromide. This mixture was heated in an oil bath and when the reaction mixture reached 50° C., 199.2 g (2.2 mol) of methallyl chloride was added drop-wise over 50 minutes. During the addition, the oil bath temperature was gradually raised to 100° C. and the reaction was continued for an additional 3 hours at 100° C. The reaction mixture was cooled, quenched with 400 ml of water, and extracted twice with 100 ml of toluene. The combined organic layers were washed with 50 ml of saturated ammonium chloride and 50 ml of saturated sodium chloride and evaporated to give 408 g of crude 1-(2-methyl-2-propenyloxy)-2,2,4-trimethylpentan-3-ol. After reduced pressure distillation (71–80° C., 3 mmHg), 377.1 g (yield 94.1%) of 1-(2-methyl-2-propenyloxy)-2,2,4-trimethylpentan-3-ol was obtained.
Reaction SMILES: C([C@H]1COC(=O)N1[C:14](=[O:49])[CH2:15][C@@H:16]([C:22]1[CH:48]=[CH:47][C:25]([O:26][CH2:27][C:28]2[CH:29]=[C:30]([NH:34][C:35](=[O:46])[C:36]3[CH:41]=[CH:40][C:39]([C:42]([F:45])([F:44])[F:43])=[CH:38][CH:37]=3)[CH:31]=[CH:32][CH:33]=2)=[CH:24][CH:23]=1)[C:17]1[CH:21]=[CH:20][O:19][N:18]=1)C1C=CC=CC=1.[OH:50]O.[Li+].[OH-].Cl>C1COCC1.O>[F:44][C:42]([F:43])([F:45])[C:39]1[CH:40]=[CH:41][C:36]([C:35]([NH:34][C:30]2[CH:29]=[C:28]([CH:33]=[CH:32][CH:31]=2)[CH2:27][O:26][C:25]2[CH:24]=[CH:23][C:22]([C@@H:16]([C:17]3[CH:21]=[CH:20][O:19][N:18]=3)[CH2:15][C:14]([OH:49])=[O:50])=[CH:48][CH:47]=2)=[O:46])=[CH:37][CH:38]=1
Reactant: O=C(Nc1cccc(COc2ccc([C@H](CC(=O)N3C(=O)OC[C@@H]3Cc3ccccc3)c3ccon3)cc2)c1)c1ccc(C(F)(F)F)cc1
Reactant: OO
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)C[C@@H](c1ccc(OCc2cccc(NC(=O)c3ccc(C(F)(F)F)cc3)c2)cc1)c1ccon1
Reaction time: 2 h
Yield: 46.1 %

Procedure:
To a solution of oxazolidinone 27.4 (71.8 mg, 0.107 mmol) dissolved in THF (10 mL), was added a 30% hydrogen peroxide solution (0.121 mL, 1.07 mmol) followed by a 2M LiOH solution (0.268 mL, 0.535 mmol). The resulting slurry was stirred for two hours. The reaction mixture was diluted with water and acidified with hydrochloric acid to a pH ˜3. The mixture was then extracted with EtOAc (1×50 mL), and the organic layer was washed with acidic sodium sulfite solution (2×30 mL), brine (1×30 mL), and dried over magnesium sulfate. The filtrate was concentrated under reduced pressure, and the residue was purified by reverse phase HPLC to give 27 (25.2 mg). MS ESI (pos.) m/e 511.1 (M+H). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.21 (1H, br. s.), 10.51 (1H, s), 8.75 (1H, d, J=1.6 Hz), 8.15 (2H, d, J=8.2 Hz), 7.91 (2H, d, J=8.2 Hz), 7.87 (1H, s), 7.74 (1H, d, J=8.2 Hz), 7.38 (1H, t, J=7.8 Hz), 7.23 (2H, d, J=8.6 Hz), 7.19 (1H, d, J=7.8 Hz), 6.96 (2H, d, J=9.0 Hz), 6.50 (1H, d, J=1.6 Hz), 5.08 (2H, s), 4.48 (1H, t, J=7.8 Hz), 3.07 (1H, dd, J=16.4, 8.2 Hz), 2.88 (1H, dd, J=16.2, 7.2 Hz).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([CH3:34])=[C:5]([C:25]([O:32][CH3:33])=[C:26]([O:30][CH3:31])[C:27]=1[O:28][CH3:29])[CH2:6][C:7]1[C:8](OS(C(F)(F)F)(=O)=O)=[C:9]([CH:14]=[CH:15][CH:16]=1)[C:10]([O:12][CH3:13])=[O:11].C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[Li+].B1([C:49]2[CH:54]=[CH:53][CH:52]=[N:51][CH:50]=2)OCCCO1>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[C:4]([CH3:34])=[C:5]([C:25]([O:32][CH3:33])=[C:26]([O:30][CH3:31])[C:27]=1[O:28][CH3:29])[CH2:6][C:7]1[C:8]([C:49]2[CH:50]=[N:51][CH:52]=[CH:53][CH:54]=2)=[C:9]([CH:14]=[CH:15][CH:16]=1)[C:10]([O:12][CH3:13])=[O:11]
Reactant: COC(=O)c1cccc(Cc2c(C)c(OC)c(OC)c(OC)c2OC)c1OS(=O)(=O)C(F)(F)F
Reactant: c1cncc(B2OCCCO2)c1
Agent: O=C([O-])[O-]
Agent: [Cl-]
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: COC(=O)c1cccc(Cc2c(C)c(OC)c(OC)c(OC)c2OC)c1-c1cccnc1
Temperature: 95 °C
Reaction time: 16 h
Yield: 85 %

Procedure:
To a solution of methyl 3-(3,4,5,6-tetramethoxy-2-methylbenzyl)-2-(trifluoromethanesulfonyl)oxybenzoate (316 mg, 0.6220 mmol) in toluene (7.1 ml) were added tetrakistriphenylphosphine palladium (22 mg, 0.0190 mmol), aqueous solution of sodium carbonate (2M aqueous solution, 0.81 ml), lithium chloride (53 mg, 1.2502 mmol) and ethanolic solution (1.3 ml) of pyridine-3-boronic acid 1,3-propanediol cyclic ester (151 mg, 0.9320 mmol) and the mixture was heated with stirring at 95° C. for 16 hours. The reaction solution was diluted with ethyl acetate (100 ml), washed with water and dried and the solvent was evaporated therefrom. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1) to give the title compound (231 mg, 0.5286 mmol, 85%).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][S:8]([C:11]1[CH:16]=[CH:15][C:14]([NH:17]C(=O)C)=[CH:13][CH:12]=1)(=[O:10])=[O:9].[OH-].[Na+]>C(O)C.COCC(O)C>[NH2:17][C:14]1[CH:15]=[CH:16][C:11]([S:8]([NH:7][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)(=[O:10])=[O:9])=[CH:12][CH:13]=1
Reactant: CC(=O)Nc1ccc(S(=O)(=O)Nc2ccccn2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: COCC(C)O
Solvent: CCO
Product: Nc1ccc(S(=O)(=O)Nc2ccccn2)cc1
Temperature: 25 °C
Yield: 70.7 %

Procedure:
The isolated N-[4-[(2-pyridinylamino)sulfonyl]phenyl]-acetamide was dissolved in 2.5 l of a mixture of ethanol and 1-methoxy-2-propanol (1/1). 105 g (2.66 mol) NaOH was added and the mixture was refluxed for an hour. The reaction mixture was allowed to cool down to room temperature and the solvent was removed under reduced pressure. The residue was dissolved in 1300 ml water and the mixture was acidified to pH 1 using HCl (conc.). The precipitated impurities were removed by filtration and the aqueous fraction was extracted three times with 450 ml methylene chloride. The aqueous fraction was neutralized to pH 7, using a 10 N NaOH solution. 4-amino-N-2-pyridinyl-benzenesulfonamide precipitated from the medium, was isolated by filtration and dried. 93.4 g (70.7%) of 4-amino-N-2-pyridinyl-benzenesulfonamide was isolated.
Reaction SMILES: [CH2:1]([N:3]1[C:7]2[CH:8]=[CH:9][C:10]([C:12]3[CH2:17][S:16][C:15](=[O:18])[N:14]([CH2:19][CH2:20][O:21]C4CCCCO4)[N:13]=3)=[CH:11][C:6]=2[N:5]=[C:4]1[C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([O:34][CH3:35])[CH:29]=1)[CH3:2].Cl>CO.C(=O)([O-])O.[Na+]>[CH2:1]([N:3]1[C:7]2[CH:8]=[CH:9][C:10]([C:12]3[CH2:17][S:16][C:15](=[O:18])[N:14]([CH2:19][CH2:20][OH:21])[N:13]=3)=[CH:11][C:6]=2[N:5]=[C:4]1[C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([O:34][CH3:35])[CH:29]=1)[CH3:2]
Reactant: CCn1c(-c2cccc(OC)c2)nc2cc(C3=NN(CCOC4CCCCO4)C(=O)SC3)ccc21
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Product: CCn1c(-c2cccc(OC)c2)nc2cc(C3=NN(CCO)C(=O)SC3)ccc21
Yield: 71.7 %

Procedure:
200 mg (0.40 mM) of 5-[1-ethyl-2-(3-methoxyphenyl)-1H-benzimidazol-5-yl]-3-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]-3,6-dihydro-2H-1,3,4-thiadiazin-2-one and 50 μl (0.6 mM) of 37% hydrochloric acid in 2 ml of methanol are stirred for 16 hours at room temperature. The solvent is evaporated off under vacuum and the residue obtained is taken up in aqueous sodium hydrogen carbonate solution. The resulting mixture is extracted with ethyl acetate and the organic phase is washed with demineralised water and then dried over anhydrous sodium sulfate. The solvent is evaporated off under vacuum to give an oil, which is purified by chromatography on silica, using a dichloromethane/acetone mixture (90/10) as eluent, to give 119 mg of 5-[1-ethyl-2-(3-methoxyphenyl)-1H-benzimidazol-5-yl]-3-(2-hydroxyethyl)-3,6-dihydro-2H-1,3,4-thiadiazin-2-one in the form of an oil that crystallises.
Reaction SMILES: [CH:1]1([CH2:6][C@H:7]([CH2:44][N:45]([CH:54]=[O:55])[O:46]CC2C=CC=CC=2)[C:8]([N:10]2[C@H:14]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([C:24]([O:26]CC4C=CC=CC=4)=[O:25])=[CH:20][CH:19]=3)=[O:16])[CH2:13][CH2:12][N:11]2C(OCC2C=CC=CC=2)=O)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1>CO.[OH-].[OH-].[Pd+2]>[CH:1]1([CH2:6][C@H:7]([CH2:44][N:45]([CH:54]=[O:55])[OH:46])[C:8]([N:10]2[C@H:14]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([C:24]([OH:26])=[O:25])=[CH:20][CH:19]=3)=[O:16])[CH2:13][CH2:12][NH:11]2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: O=CN(C[C@@H](CC1CCCC1)C(=O)N1[C@H](C(=O)Nc2ccc(C(=O)OCc3ccccc3)cc2)CCN1C(=O)OCc1ccccc1)OCc1ccccc1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CO
Product: O=CN(O)C[C@@H](CC1CCCC1)C(=O)N1NCC[C@H]1C(=O)Nc1ccc(C(=O)O)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 52.3 %

Procedure:
To a solution of phenylmethyl (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-3-{[(4-{[(phenylmethyl)oxy]carbonyl}phenyl)amino]carbonyl}-1-pyrazolidinecarboxylate (330 mg, 0.442 mmol) in methanol (20 mL) was added Pd(OH)2/C (330 mg). The mixture was stirred at rt under H2 atmosphere for 2 h. The catalyst was filtered off, the filtrate was concentrated under vacuum, and the residue was purified by preparative HPLC to provide the title compound (100 mg). LCMS: (M+H)+: 482.2.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].Br[CH:8]([CH3:10])[CH3:9].[Br:11][C:12]1[CH:13]=[C:14]([CH:17]=[CH:18][C:19]=1[OH:20])[CH:15]=[O:16]>CN(C)C=O>[Br:11][C:12]1[CH:13]=[C:14]([CH:17]=[CH:18][C:19]=1[O:20][CH:8]([CH3:10])[CH3:9])[CH:15]=[O:16]
Reactant: CC(C)Br
Reactant: O=Cc1ccc(O)c(Br)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)Oc1ccc(C=O)cc1Br
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Potassium carbonate (10.28 g, 7.4 mmol) and 2-bromopropane (8.7 ml) were added to 3-bromo-4-hydroxybenzaldehyde (7.46 g, 3.7 mmol) in N,N-dimethylformamide (20 ml). The mixture was stirred at room temperature for 3 hours, then partitioned between ethyl acetate and water. The organic phase was washed with brine and dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with hexane/EtOAc (90:10 increasing to 80:20) to give the title compound (5.34 g). 1H NMR (250 MHz, CDCl3) δ 9.82 (1H, s), 8.03 (1H, d, J=2.0 Hz), 7.82-7.78 (1H, dd, J=6.0, 2.0 Hz), 7.00 (1H, d, J=6.0 Hz), 4.72 (1H, septet, J=6.0 Hz), and 1.40 (6H, d, J=6.0 Hz).
Reaction SMILES: [F:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][CH:7]2[CH2:10][N:9]([C:11](Cl)=[O:12])[CH2:8]2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:22]([NH2:25])[C:23]#[CH:24]>O1CCCC1.O>[F:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][CH:7]2[CH2:10][N:9]([C:11]([NH:25][CH2:22][C:23]#[CH:24])=[O:12])[CH2:8]2)=[CH:4][CH:3]=1
Reactant: O=C(Cl)N1CC(Oc2ccc(F)cc2)C1
Reactant: C#CCN
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: C#CCNC(=O)N1CC(Oc2ccc(F)cc2)C1
Yield: 174.6 %

Procedure:
A mixture of 5.52 g (0.022 mole) of crude 3-(4-fluorophenoxy)-1-azetidine carbonyl chloride and 3 g (0.02 mole) of potassium carbonate in 30 ml of tetrahydrofuran was cooled in an ice bath and while stirring treated with 1.1 g (0.02 mole) of propargylamine added dropwise. After stirring for 5 hr, the reaction mixture was diluted with 250 ml of water and the resulting solid collected by filtration to yield 8.67 g of wet product. Recrystallization from acetone after filtration to remove some amorphous material, gave a tacky solid. A second recrystallization from benzene after treating with charcoal yielded 2.7 g (50%) of beige crystals, m.p. 106°-108° C.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[O:8])[S:5][CH:6]=1.S(O)(C1C=CC(C)=CC=1)(=O)=O.O.[CH3:21][C:22]([CH3:27])([CH2:25]O)[CH2:23][OH:24].C(=O)([O-])O.[Na+]>C1C=CC=CC=1.C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([CH:7]2[O:24][CH2:23][C:22]([CH3:27])([CH3:25])[CH2:21][O:8]2)[S:5][CH:6]=1
Reactant: O=Cc1cc(Br)cs1
Reactant: CC(C)(CO)CO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Solvent: c1ccccc1
Product: CC1(C)COC(c2cc(Br)cs2)OC1
Temperature: 0 °C

Procedure:
4-bromothiophene-2-carbaldehyde (884 mg, 4.62 mmol), TsOH hydrate (44 mg, 0.231 mmol) and 2,2-dimethylpropane-1,3-diol (578 mg, 5.55 mmol) were dissolved in 9.2 mL benzene and refluxed in a Dean Stark apparatus for 5 hours. The mixture was cooled to 0° C. and aqueous sodium hydrogen carbonate was added. DCM was added and the phases separated with a phase extractor. The solvent was removed under reduced pressure to give the title compound.
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[OH:10].[N:11]1[CH:16]=[CH:15][CH:14]=[C:13](B(O)O)[CH:12]=1.C(=O)([O-])[O-].[Na+].[Na+].O>C(COC)OC.O.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]>[CH3:9][C:4]1[CH:5]=[C:6]([CH3:8])[CH:7]=[C:2]([C:13]2[CH:12]=[N:11][CH:16]=[CH:15][CH:14]=2)[C:3]=1[OH:10]
Reactant: Cc1cc(C)c(O)c(Br)c1
Reactant: OB(O)c1cccnc1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: O
Solvent: COCCOC
Product: Cc1cc(C)c(O)c(-c2cccnc2)c1
Reaction time: 1 h
Yield: 70.3 %

Procedure:
2-bromo-4,6-dimethylphenol (1 g, 5 mmol) was dissolved in dimethoxyethane/water (2:1). Pyridin-3-ylboronic acid (0.62 g, 5 mmol) and Pd(dppf)Cl2 (0.20 g, 0.25 mmol), sodium carbonate (2.1 g, 25 mmol) were added thereto, followed by stirring for 1 hour under reflux. After the completion of the reaction, the reaction mixture was added with water, and extracted with ethyl acetate. The obtained organic layer was dried over magnesium sulfate, concentrated under reduced pressure, and purified by column chromatography to obtain 2,4-dimethyl-6-(pyridin-3-yl)phenol (0.7 g, 70%).
Reaction SMILES: O=[CH:2][C@@H:3]([C@H:5]([C@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])[OH:4].[CH2:13]([NH2:31])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30]>>[CH:2]1([CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][NH2:31])[O:10][C@H:9]([CH2:11][OH:12])[C@H:7]([OH:8])[C@H:5]([OH:6])[C@H:3]1[OH:4]
Reactant: CCCCCCCCCCCCCCCCCCN
Reactant: O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CO
Product: NCCCCCCCCCCCCCCCCCCC1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O

Procedure:
The preparation is analogous to Example 1, starting from 11 g of galactose and 20 g of octadecylamine.
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[C:7]([Cl:9])[CH:6]=[CH:5][C:3]=1[NH2:4].[Br:10][CH2:11][C:12](Br)=[O:13].C(N(CC)CC)C>C(Cl)Cl>[Br:10][CH2:11][C:12]([NH:4][C:3]1[CH:5]=[CH:6][C:7]([Cl:9])=[CH:8][C:2]=1[Cl:1])=[O:13]
Reactant: Nc1ccc(Cl)cc1Cl
Reactant: O=C(Br)CBr
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(CBr)Nc1ccc(Cl)cc1Cl
Yield: 80.4 %

Procedure:
This compound was prepared similarly to Example II-11 from 4.2 g of 2,4-dichloroaniline and 5.76 g of bromoacetyl bromide and 2.89 g of triethylamine in methylene chloride. This gave 5.9 g (80.4%) of the title compound.
Reaction SMILES: [CH:1]1[CH:2]=[CH:3][C:4]2[C:5](=[C:7]3[N:39]=[C:38]4[N:40]=[C:31]([C:32]5[CH:33]=[CH:34][CH:35]=[CH:36][C:37]=54)[N:30]=[C:28]4[NH:29][C:21]([C:22]5[CH:23]=[CH:24][CH:25]=[CH:26][C:27]=54)=[N:20][C:18]4=[N:19][C:11]([C:12]5[CH:13]=[CH:14][CH:15]=[CH:16][C:17]=54)=[N:10][C:9]=2[NH:8]3)[CH:6]=1.C1C=C2C3[N-]C(C2=CC=1)=NC1=NC(C2C1=CC=CC=2)=NC1=NC(C2C1=CC=CC=2)=NC1[N-]C(=C2C=1C=CC=C2)N=3.[O-2].[Ti+4:82].S(=O)(=O)(O)O>O>[Ti:82].[CH:2]1[CH:1]=[CH:6][C:5]2[C:4](=[C:9]3[N:10]=[C:11]4[N:19]=[C:18]([C:17]5[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=54)[N:20]=[C:21]4[NH:29][C:28]([C:27]5[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=54)=[N:30][C:31]4=[N:40][C:38]([C:37]5[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=54)=[N:39][C:7]=2[NH:8]3)[CH:3]=1
Reactant: [Ti+4]
Agent: O=S(=O)(O)O
Agent: [O-2]
Agent: c1ccc2c(c1)-c1nc-2nc2[nH]c(nc3nc(nc4[nH]c(n1)c1ccccc41)-c1ccccc1-3)c1ccccc21
Solvent: O
Product: [Ti]
Reaction time: 1 h

Procedure:
The aforesaid 3-a phthalocyanine derivative (0.5 parts) was added to 10 parts of the TiOPc crude prepared in Example 1 and mixed together. The mixture was added to 80 parts of 78% sulfuric acid at 10° C. and the resulting solution was stirred for 1 hour with maintaining its temperature at not higher than 10°. The solution was poured into 400 parts of water, and precipitated crystals were filtrated. The crystals were washed with distilled water until the acid did not remain, and dried to give titanium phthalocyanine compound.
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([F:8])[C:5]([Br:9])=[CH:4][C:3]=1[F:10].C([Li])CCC.[CH3:16][N:17]1[CH2:22][CH2:21][C:20](=[O:23])[CH2:19][CH2:18]1.[Cl-].[NH4+]>C(OCC)C.O>[Br:9][C:5]1[C:6]([F:8])=[CH:7][C:2]([C:20]2([OH:23])[CH2:21][CH2:22][N:17]([CH3:16])[CH2:18][CH2:19]2)=[C:3]([F:10])[CH:4]=1
Reactant: CN1CCC(=O)CC1
Reactant: Fc1cc(Br)c(F)cc1Br
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: O
Solvent: CCOCC
Product: CN1CCC(O)(c2cc(F)c(Br)cc2F)CC1
Temperature: -75 °C
Reaction time: 0.75 h
Yield: 42.5 %

Procedure:
A solution of 2.72 g (10 mmoles) of 1,4-dibromo-2,5-difluorobenzene in 50 ml of ethyl ether, under an argon atmosphere stirred at -75° C., was treated dropwise with 4.2 ml of 2.5 M n-butyl lithium (hexane solution). The mixture was treated dropwise with a solution of 1.20 g (10.6 mmoles) of N-methyl-4-piperidone in 10 ml of ethyl ether, stirred a further 0.75 hours at -75° C., let warm to -30° C., and poured into a solution of 0.56 g (10.5 mmoles) ammonium chloride in 15 ml of water. The ether layer was washed with two 10 ml portions of water, dried (MgSO4), and evaporated to give 2.85 g of crude product which was purified by chromatography on a column of silica gel and crystallized to give 1.30 g of the title compound; mp 133°-135° C.
Reaction SMILES: FC(F)(F)S(O[C:7]1[CH:12]=[C:11]([CH:13]2[CH2:15][CH2:14]2)[N:10]=[C:9]([C:16]2[S:17][C:18]([S:21](=[O:28])(=[O:27])[NH:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[CH:19][CH:20]=2)[N:8]=1)(=O)=O.[NH2:31][C:32]1[N:36](C(OC(C)(C)C)=O)[N:35]=[C:34]([CH:44]2[CH2:46][CH2:45]2)[CH:33]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1>[C:23]([NH:22][S:21]([C:18]1[S:17][C:16]([C:9]2[N:10]=[C:11]([CH:13]3[CH2:15][CH2:14]3)[CH:12]=[C:7]([NH:31][C:32]3[NH:36][N:35]=[C:34]([CH:44]4[CH2:46][CH2:45]4)[CH:33]=3)[N:8]=2)=[CH:20][CH:19]=1)(=[O:27])=[O:28])([CH3:26])([CH3:25])[CH3:24]
Reactant: CC(C)(C)NS(=O)(=O)c1ccc(-c2nc(OS(=O)(=O)C(F)(F)F)cc(C3CC3)n2)s1
Reactant: CC(C)(C)OC(=O)n1nc(C2CC2)cc1N
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1COCCO1
Product: CC(C)(C)NS(=O)(=O)c1ccc(-c2nc(Nc3cc(C4CC4)n[nH]3)cc(C3CC3)n2)s1
Temperature: 100 °C
Reaction time: 3 h
Yield: 26.6 %

Procedure:
A mixture of crude 2-(5-(N-tert-butylsulfamoyl)thiophen-2-yl)-6 cyclopropylpyrimidin-4-yl trifluoromethanesulfonate 220 mg, 0.41 mmol, 1.0 equiv.), tert-butyl 5-amino-3-cyclopropyl-1H-pyrazole-1-carboxylate (138 mg, 0.62 mmol, 1.2 equiv.), Ph3P (33 mg, 0.12 mmol, 0.3 equiv.), Ph(Ph3P)4 (47 mg, 0.041 mmol, 0.1 equiv.) and K2CO3 (170 mg, 1.23 mmol, 3 equiv.) in dioxane (5 mL) was stirred at 100° C. for 3 h. The mixture was extracted with EtOAc. The combined organic phase was washed (brine), dried (Na2SO4), filtered and concentrated to give a residue, which was purified by silica gel column chromatography (PE/EtOAc/MeOH=1:1:0.1) to provide N-tert-butyl-5-(4-cyclopropyl-6-(3-cyclopropyl-1H-pyrazol-5-ylamino)pyrimidin-2-yl)thiophene-2-sulfonamide (50 mg, 27%) as a white solid. LC-MS (m/z)=459.1 [M+H]+
Reaction SMILES: [C:1]([N:5]1[C:10](=[O:11])[C:9]([Cl:12])=[C:8](Cl)[CH:7]=[N:6]1)([CH3:4])([CH3:3])[CH3:2].[SH-:14].[Na+]>O>[C:1]([N:5]1[C:10](=[O:11])[C:9]([Cl:12])=[C:8]([SH:14])[CH:7]=[N:6]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)n1ncc(Cl)c(Cl)c1=O
Reactant: [SH-]
Agent: [Na+]
Solvent: O
Product: CC(C)(C)n1ncc(S)c(Cl)c1=O
Temperature: 60 °C
Reaction time: 4 h
Yield: 81.5 %

Procedure:
To 560 ml of water were added 66.3 g of 2-tert.-butyl-4,5-dichloro-3(2H)-pyridazinone and 48.0 g of 70% sodium hydrosulfide. After stirring at 60° C. for 4 hours activated carbon was added thereto. The resulting mixture was allowed to cool and then filtered. Concentrated hydrochloric acid was added to the resuling filtrate until the pH thereof was lowered to 2 or less. The resulting solid was filtered off, washed with water, dried and then recrystallized from a mixed solvent of benene and n-hexane to give the intended product as white needle-like crystals of m.p. 112°-113° C. (yield: 81.5%).