Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][C:3](=[O:32])[C@@H:4]([O:29][CH2:30][CH3:31])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[N:15]=[C:16]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[O:26][CH3:27])[O:17][C:18]=2[CH3:19])=[CH:8][C:7]=1[Cl:28].[Li+].[OH-]>>[Cl:28][C:7]1[CH:8]=[C:9]([O:12][CH2:13][C:14]2[N:15]=[C:16]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[O:26][CH3:27])[O:17][C:18]=2[CH3:19])[CH:10]=[CH:11][C:6]=1[CH2:5][C@H:4]([O:29][CH2:30][CH3:31])[C:3]([OH:32])=[O:2]
Reactant: CCO[C@@H](Cc1ccc(OCc2nc(-c3ccccc3OC)oc2C)cc1Cl)C(=O)OC
Agent: [Li+]
Agent: [OH-]
Product: CCO[C@@H](Cc1ccc(OCc2nc(-c3ccccc3OC)oc2C)cc1Cl)C(=O)O

Procedure:
In analogy to the procedure described in example 1 g], (S)-3-{2-chloro-4-[2-(2-methoxy-phenyl)-5-methyl-oxazol-4-ylmethoxy]-phenyl}-2-ethoxy-propionic acid methyl ester was treated with LiOH to obtain (S)-3-{2-chloro-4-[2-(2-methoxy-phenyl)-5-methyl-oxazol-4-ylmethoxy]-phenyl}-2-ethoxy-propionic acid as colorless foam.
Reaction SMILES: [Cl-].[Ca+2].[Cl-].O1CCCC1CCO.[BH4-].[Na+].[Cl:14][C:15]1[CH:20]=[CH:19][N:18]=[C:17]([NH:21][C:22]2[CH:23]=[N:24][N:25]([C:27]([CH3:34])([CH3:33])[C:28](OCC)=[O:29])[CH:26]=2)[N:16]=1.Cl.[OH-].[Na+]>>[Cl:14][C:15]1[CH:20]=[CH:19][N:18]=[C:17]([NH:21][C:22]2[CH:23]=[N:24][N:25]([C:27]([CH3:34])([CH3:33])[CH2:28][OH:29])[CH:26]=2)[N:16]=1
Reactant: CCOC(=O)C(C)(C)n1cc(Nc2nccc(Cl)n2)cn1
Agent: Cl
Agent: OCCC1CCCO1
Agent: [BH4-]
Product: CC(C)(CO)n1cc(Nc2nccc(Cl)n2)cn1
Temperature: 25 °C
Reaction time: 1 h
Yield: 81 %

Procedure:
To a solution of calcium chloride (540 mg) in a mixed solvent of tetrahydrofuran-ethanol (v/v=1/1, 5.0 mL) was added sodium borohydride (240 mg), and the mixture was stirred at room temperature for 1 hr. To the reaction mixture was added a solution of ethyl 2-(4-((4-chloropyrimidin-2-yl)amino)-1H-pyrazol-1-yl)-2-methylpropanoate (1.0 g) obtained in Step D of Example 347 in a mixed solvent of tetrahydrofuran-ethanol (v/v=1/1, 5.0 mL) in an ice bath, and the mixture was stirred overnight while it was allowed to be gradually warmed to room temperature. To the reaction mixture was added 1 M hydrochloric acid in an ice bath, and the mixture was stirred at the same temperature for 10 min. 1 M Aqueous sodium hydroxide solution was added thereto, and the solvent was evaporated under reduced pressure. To the residue was added water, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (700 mg).
Reaction SMILES: [Cl-:1].[Cl-].[C:3]1([Zr:9]([C:41]2C=CC=CC=2)(=[SiH2:40])([CH:25]2[C:33]3[C:28](=[CH:29][CH:30]=[C:31]4[CH:37]=[CH:36][CH:35]=[CH:34][C:32]4=3)[CH:27]=[C:26]2[CH2:38]C)[CH:10]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]4[CH:22]=[CH:21][CH:20]=[CH:19][C:17]4=3)[CH:12]=[C:11]2[CH2:23]C)C=CC=CC=1.C[Zr]C>>[Cl-:1].[Cl-:1].[CH3:41][Zr:9]([CH3:3])(=[SiH2:40])([CH:25]1[C:33]2[C:28](=[CH:29][CH:30]=[C:31]3[CH:37]=[CH:36][CH:35]=[CH:34][C:32]3=2)[CH:27]=[C:26]1[CH3:38])[CH:10]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]3[CH:22]=[CH:21][CH:20]=[CH:19][C:17]3=2)[CH:12]=[C:11]1[CH3:23]
Reactant: CCC1=Cc2ccc3ccccc3c2C1[Zr](=[SiH2])(c1ccccc1)(c1ccccc1)C1C(CC)=Cc2ccc3ccccc3c21
Agent: C[Zr]C
Agent: [Cl-]
Product: CC1=Cc2ccc3ccccc3c2C1[Zr](C)(C)(=[SiH2])C1C(C)=Cc2ccc3ccccc3c21

Procedure:
diphenylsilanediylbis(2-ethylbenzindenyl)zirconium dichloride, and dmethylsilanediylbis(2-methylindenyl)hafnium dichloride and also the corresponding dimethylzirconium compounds.
Reaction SMILES: [C-:1]#[N:2].[K+].C(O)CO.O.C(=O)=O.[S:12]1[C:16]2[CH:17]=[C:18]([CH2:21]O)[CH:19]=[CH:20][C:15]=2[N:14]=[CH:13]1>O.CN(C=O)C>[S:12]1[C:16]2[CH:17]=[C:18]([CH2:21][C:1]#[N:2])[CH:19]=[CH:20][C:15]=2[N:14]=[CH:13]1
Reactant: [C-]#N
Reactant: OCc1ccc2ncsc2c1
Agent: O=C=O
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Solvent: OCCO
Product: N#CCc1ccc2ncsc2c1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
A solution of potassium cyanide (0.68 g, 0.010 mol) in water (3.0 mL) was added under nitrogen to a cooled (with an ethylene glycol/water (4/1)/dry ice bath) solution of 1,3-benzothiazol-6-ylmethanol in DMF (30 mL). The reaction mixture was warmed to 0° C., and stirred for 30 min. Water was added and the reaction mixture was extracted with DCM. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was flash chromatographed on a silica gel column with ethyl acetate in hexane from 10-30% to afford the desired product (1.07 g). Analytical LCMS: (M+H)+=175.2.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.C([Li])CCC.Br[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>O1CCCC1.[Cl-].[Zn+2].[Cl-]>[C:12]1([C:2]2[S:1][CH:5]=[CH:4][CH:3]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: c1ccsc1
Reactant: Brc1ccccc1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [Zn+2]
Solvent: C1CCOC1
Product: c1ccc(-c2cccs2)cc1
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 58.5 %

Procedure:
To a solution of thiophene (9.5 mL, 0.12 mole) in 100 mL tetrahydrofuran at 0° C. was added 2M n-butyllithium (48 mL, 0.12 mole) dropwise. The solution was stirred 2.5 h and was then added via cannula to a stirred solution of anhydrous zinc chloride (26 g, 0.19 mole) in 100 mL of THF at room temperature. After 1 h this solution was transferred via cannula into a solution of bromobenzene (8.4 mL, 0.08 mole) and tetrakis-triphenylphosphine palladium (0.2 g) in 100 mL of THF. The solution was warmed to reflux overnight. The solution was cooled to room temperature and quenched with saturated ammonium chloride solution. The mixture was extracted with ether (3×50 mL). The ether extracts were washed with brine, dried (MgSO4), filtered and concentrated. The material was distilled (20 mm Hg) to yield 7.5 g (60%) of desired product, b.p.=150° C.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:12])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1.[N+:13]([O-])([OH:15])=[O:14]>C(O)(=O)C>[CH3:1][O:2][C:3](=[O:12])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[C:7]([N+:13]([O-:15])=[O:14])[CH:6]=1
Reactant: O=[N+]([O-])O
Reactant: COC(=O)Cc1ccc(O)cc1
Solvent: CC(=O)O
Product: COC(=O)Cc1ccc(O)c([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Methyl-2-(4-hydroxyphenyl)acetate (2.0 g, 12.0 mmol) was dissolved in acetic acid (15 ml) and nitric acid (60-62%, 1.27 g, 12.1 mmol) was added at RT. The reaction mixture was stirred for 30 minutes at RT, poured into ice water (100 ml) and extracted with EA. The organic phase was dried over MgSO4, the solvent removed under a vacuum and the residue purified by means of column chromatography (n-hexane/EA=4:1).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[C:7]([NH2:9])[C:6]([CH3:10])=[C:5]([NH2:11])[CH:4]=1)#[N:2].CO[CH:14](OC)[CH2:15][CH2:16]OC.O.[OH-].[NH4+]>C(O)C.[Cl-].[Zn+2].[Cl-]>[NH2:11][C:5]1[C:6]([CH3:10])=[C:7]2[C:8]([CH:14]=[CH:15][CH:16]=[N:9]2)=[C:3]([C:1]#[N:2])[CH:4]=1
Reactant: Cc1c(N)cc(C#N)cc1N
Reactant: COCCC(OC)OC
Agent: [Cl-]
Agent: [NH4+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: Cc1c(N)cc(C#N)c2cccnc12
Temperature: 65 °C

Procedure:
A mixture of 4-cyano-2,6-diaminotoluene (3.56 g), ferric chloride hexahydrate (11.63 g), and zinc chloride (0.499 g) in ethanol (600 mL) is warmed to 65° C. A solution of 1,1,3-trimethoxypropane (5.23 g) in ethanol (90 mL) is added dropwise via syringe pump over a period of 90 minutes. The reaction is then heated to reflux for 2.5 hours. The reaction is cooled to room temperature and the solvent rotary evaporated. The residue is mixed with 300 mL of water and basified to pH=11 with concentrated ammonium hydroxide. The products are extracted with ethyl acetate (4×300 mL), and the combined extracts dried over sodium sulfate and rotary evaporated. The residue is purified by flash chromatography on silica gel, eluting with 50% ethyl acetate/hexane to afford 7-amino-5-cyano-8-methylquinoline as a yellow solid.
Reaction SMILES: [H-].[Na+].[C:3]1([NH:9][C:10]([C:12]2[NH:13][CH:14]=[CH:15][N:16]=2)=[O:11])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C1(P(C2C=CC=CC=2)(=O)[NH2:24])C=CC=CC=1.S([O-])([O-])(=O)=S.[Na+].[Na+]>CN(C=O)C>[NH2:24][N:16]1[CH:15]=[CH:14][N:13]=[C:12]1[C:10]([NH:9][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1)=[O:11]
Reactant: NP(=O)(c1ccccc1)c1ccccc1
Reactant: O=C(Nc1ccccc1)c1ncc[nH]1
Agent: O=S([O-])([O-])=S
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Nn1ccnc1C(=O)Nc1ccccc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 76 %

Procedure:
0.430 g (10.75 mmol) of sodium hydride (60% dispersion in mineral oil) was added to a 0° C. cooled solution of N-phenyl-1H-imidazole-2-carboxamide (1.55 g, 8.27 mmol) in DMF (50 mL). The mixture was stirred at 0° C. for 30 minutes and 2.70 g (11.57 mmol) of DPPONH2 (P,P-diphenylphosphinic amide, available from Sigma Aldrich®, cat. no. 5994-87-6) were added portionwise. A thick suspension formed and additional 100 mL of DMF were added. The mixture was stirred at room temperature for 3 hours and then it was poured into 150 mL of a saturated aqueous solution of sodium thiosulphate and extracted with ethyl acetate. The combined organic layer was dried over sodium sulphate, filtered and concentrated. The crude product was purified by flash chromatography (20% to 40% AcOEt/Hexanes) to yield 1.27 g (76% yield) of the title compound as a pale yellow solid.
Reaction SMILES: [C:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:13][CH:14]=3)[N:9](C(OC(C)(C)C)=O)[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:27]([OH:33])([C:29]([F:32])([F:31])[F:30])=[O:28]>C(Cl)Cl>[OH:33][C:27]([C:29]([F:32])([F:31])[F:30])=[O:28].[C:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:13][CH:14]=3)[NH:9][CH:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: COC(=O)c1ccc2c(-c3ccccc3)cn(C(=O)OC(C)(C)C)c2c1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COC(=O)c1ccc2c(-c3ccccc3)c[nH]c2c1
Reaction time: 3 h

Procedure:
To a solution of 1-tert-butyl 6-methyl 3-phenyl-1H-indole-1,6-dicarboxylate 62b (4.04 mmol, 1.42 g) in CH2Cl2 (8 mL) was added 6 mL of TFA. The resulting solution was stirred for 3 h. The mixture was then concentrated and washed with hexanes to afford 62c.
Reaction SMILES: C([O-])(=O)C.[NH4+].C([BH3-])#[N:7].[Na+].[Cl:10][C:11]1[CH:21]=[CH:20][C:14]([O:15][CH2:16][C:17](=O)[CH3:18])=[C:13]([CH3:22])[CH:12]=1>CO>[Cl:10][C:11]1[CH:21]=[CH:20][C:14]([O:15][CH2:16][CH:17]([NH2:7])[CH3:18])=[C:13]([CH3:22])[CH:12]=1
Reactant: [BH3-]C#N
Reactant: CC(=O)COc1ccc(Cl)cc1C
Agent: CC(=O)[O-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CO
Product: Cc1cc(Cl)ccc1OCC(C)N
Reaction time: 1 h
Yield: 80.3 %

Procedure:
120 g of ammonium acetate and 9.8 g of sodium cyanoborohydride were added to a solution containing 31 g of (4-chloro-2-methylphenoxy)acetone dissolved in 700 mL of methanol, and the resultant mixture was stirred for 20 hours at room temperature. After the reaction mixture was concentrated under reduced pressure. 180 mL of concentrated hydrochloric acid and 100 mL of water were added to the residue. The whole mixture was stirred for 1 hour, and then extracted with 300 mL of diethyl ether. The water layer was alkalified using a 5% aqueous solution of sodium hydroxide, and then extracted with 500 mL of ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. A fraction possessing a low boiling point was removed from the obtained oily products to afford 25 g (yield 81%) of the desired product. Refractive index: 1.5360.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH3:31])[S:9]([C:12]2[CH:13]=[C:14]([CH:28]=[CH:29][CH:30]=2)[C:15]([NH:17][C:18]2[CH:27]=[CH:26][C:21]([C:22]([O:24]C)=[O:23])=[CH:20][N:19]=2)=[O:16])(=[O:11])=[O:10])=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+]>CCO.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]([CH3:31])[S:9]([C:12]2[CH:13]=[C:14]([CH:28]=[CH:29][CH:30]=2)[C:15]([NH:17][C:18]2[CH:27]=[CH:26][C:21]([C:22]([OH:24])=[O:23])=[CH:20][N:19]=2)=[O:16])(=[O:10])=[O:11])=[CH:6][CH:7]=1
Reactant: COC(=O)c1ccc(NC(=O)c2cccc(S(=O)(=O)N(C)c3ccc(Cl)cc3)c2)nc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCO
Product: CN(c1ccc(Cl)cc1)S(=O)(=O)c1cccc(C(=O)Nc2ccc(C(=O)O)cn2)c1

Procedure:
Compound 65-b was prepared by stirring 65 (20 mg, 0.043 mmol) in EtOH/H2O (1:1, 4 mL) and K2CO3 (11.9 mg, 0.086 mmol) overnight at room temperature. Reaction mixture was then neutralized to PH 3.0, extracted with EtOAc and then dried over MgSO3 to generate 17 mg of 65-b (90%). 1H NMR (500 MHz, CDCl3) δ 3.20 (s, 3H), 7.05 (d, J=8.8 Hz, 2H), 7.30 (d, J=8.8 Hz, 2H), 7.64 (t, J=7.8 Hz, 1H), 7.70 (d, J=7.9 Hz, 1H), 8.13 (s, 1H), 8.18 (d, J=7.7 Hz, 1H), 8.38 (dd, J=2.2, 8.8 Hz, 1H), 8.43 (d, J=8.7 Hz, 1H), 8.84 (s, 1H), 8.91 (d, J=1.6 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 38.27, 52.35, 113.18, 122.67, 126.22, 127.84, 129.34, 129.78, 131.40, 131.81, 133.62, 134.77, 137.37, 139.49, 140.02, 150.09, 153.94, 163.93, 165.23. LCQ (M−H+) calcd C20H16ClN3O5S 444. found 444.
Reaction SMILES: [F:1][C:2]1[C:10]([F:11])=[C:9]([F:12])[C:8]([F:13])=[C:4]([C:5](F)=[O:6])[C:3]=1[C:14](F)=[O:15].FC1(F)C2C(=C(F)C(F)=C(F)C=2F)C(=O)[O:19]1>C(O)(=O)C>[F:1][C:2]1[C:10]([F:11])=[C:9]([F:12])[C:8]([F:13])=[C:4]2[C:5](=[O:19])[O:6][C:14](=[O:15])[C:3]=12
Reactant: O=C(F)c1c(F)c(F)c(F)c(F)c1C(=O)F
Reactant: O=C1OC(F)(F)c2c(F)c(F)c(F)c(F)c21
Solvent: CC(=O)O
Product: O=C1OC(=O)c2c(F)c(F)c(F)c(F)c21
Yield: 64.3 %

Procedure:
Into a 200 ml glass reactor equipped with a reflux condenser and a stirrer, 50 g (0.207 mol) of the mixture (1:1) of the 3,4,5,6-tetrafluorophthaloyldifluoride and the 3,3,4,5,6,7-hexafluoro-1-[3H]-isobenzofuranone of Example 2, and 50 ml of acetic acid were charged, and the mixture was refluxed for 16 hours with vigorous stirring. Then, the reaction mixture was separated by distillation to obtain 29.3 g of tetrafluorophthalic anhydride. The yield was 64.3%.
Reaction SMILES: [CH3:1][O:2][CH2:3][C:4]1[C:9]([CH2:10][O:11][CH3:12])=[CH:8][CH:7]=[C:6]([N+:13]([O-])=O)[C:5]=1[OH:16].[C:17](=S)(OCC)[S-:18].[K+]>C(O)C>[CH3:12][O:11][CH2:10][C:9]1[CH:8]=[CH:7][C:6]2[N:13]=[C:17]([SH:18])[O:16][C:5]=2[C:4]=1[CH2:3][O:2][CH3:1]
Reactant: CCOC(=S)[S-]
Reactant: COCc1ccc([N+](=O)[O-])c(O)c1COC
Agent: [K+]
Solvent: CCO
Product: COCc1ccc2nc(S)oc2c1COC
Yield: 59 %

Procedure:
Thus, the aminophenol (276 mg, 1.29 mmol) was dissolved in ethanol (10 ml) and potassium O-ethyl dithiocarbonate (228 mg, 1.42 mmol) was added thereto followed by heating to reflux for 16 hours. After cooling, the solvent was evaporated therefrom in vacuo. The residue was acidified by adding 2N hydrochloric acid thereto and extracted with ethyl acetate. The organic layer was washed with water and a saturated sodium chloride solution successively and dried over anhydrous magnesium sulfate and the solvent was evaporated therefrom. The residue was purified by a preparative thin layer chromatography (developing solvent, hexane:acetone=5:3) to provide 182 mg (yield 59%) of 6,7-bis(methoxymethyl)-2-mercaptobenzooxazole as pale brown solid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:28]([F:31])([F:30])[F:29])=[C:6]([CH:27]=1)[CH2:7][N:8]1[CH2:13][CH2:12][NH:11][C:10]2[N:14]=[CH:15][C:16]([C:18]3[CH:19]=[C:20]([CH:24]=[CH:25][CH:26]=3)[C:21]([OH:23])=O)=[CH:17][C:9]1=2.[C:32]1([N:38]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:28]([F:29])([F:31])[F:30])=[C:6]([CH:27]=1)[CH2:7][N:8]1[CH2:13][CH2:12][NH:11][C:10]2[N:14]=[CH:15][C:16]([C:18]3[CH:19]=[C:20]([C:21]([N:41]4[CH2:42][CH2:43][N:38]([C:32]5[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=5)[CH2:39][CH2:40]4)=[O:23])[CH:24]=[CH:25][CH:26]=3)=[CH:17][C:9]1=2
Reactant: O=C(O)c1cccc(-c2cnc3c(c2)N(Cc2cc(Cl)ccc2C(F)(F)F)CCN3)c1
Reactant: c1ccc(N2CCNCC2)cc1
Product: O=C(c1cccc(-c2cnc3c(c2)N(Cc2cc(Cl)ccc2C(F)(F)F)CCN3)c1)N1CCN(c2ccccc2)CC1

Procedure:
(3-{1-[5-chloro-2-(trifluoromethyl)benzyl]-1,2,3,4-tetrahydropyrido[2,3-b]pyrazin-7-yl}benzoic acid was reacted with 1-phenylpiperazine as in General Procedure 10 to give the title compound. LCMS: m/z=591.97 (M+H+); retention time=0.97 minutes.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:9]=[C:10]=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8].[C:12]1([C:18]2[O:19][CH2:20][CH:21]([OH:30])[CH:22]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[N:23]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>ClCCCl>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([O:30][CH:21]2[CH2:20][O:19][C:18]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[N:23][CH:22]2[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: O=C=Nc1ccc(Cl)c(Cl)c1
Reactant: OC1COC(c2ccccc2)=NC1c1ccccc1
Solvent: ClCCCl
Product: O=C(Nc1ccc(Cl)c(Cl)c1)OC1COC(c2ccccc2)=NC1c1ccccc1
Yield: 75.5 %

Procedure:
3,4-Dichlorophenyl isocyanate (1.15 g) is added at a temperature in the region of 20° C. to a solution, maintained under an argon atmosphere, of (4RS, 5RS)-2,4-diphenyl-5,6-dihydro-4H-1,3-oxazin-5-ol (1.52 g) in 1,2-dichloroethane (20 cc). The solution obtained is heated to reflux for 6 hours and then concentrated to dryness under reduced pressure (2.7 kPa). After recrystallization in acetonitrile, (4RS, 5RS)-5-(3,4-dichlorophenylcarbamoyloxy)-2,4-diphenyl-5,6-dihydro-4H-1,3-oxazine (2 g), m.p. 184° C., is obtained.
Reaction SMILES: [OH:1][C:2]1[C:32]([O:33][CH3:34])=[C:31]([O:35][CH3:36])[CH:30]=[C:29]([CH3:37])[C:3]=1[C:4]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]([OH:28])=[O:27])=[O:5].[C:38]1(C)C=CC(S(O)(=O)=O)=CC=1.O>CO>[OH:1][C:2]1[C:32]([O:33][CH3:34])=[C:31]([O:35][CH3:36])[CH:30]=[C:29]([CH3:37])[C:3]=1[C:4]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]([O:28][CH3:38])=[O:27])=[O:5]
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Reactant: COc1cc(C)c(C(=O)CCCCCCCCCCCCCCCCCCCCC(=O)O)c(O)c1OC
Solvent: O
Solvent: CO
Product: COC(=O)CCCCCCCCCCCCCCCCCCCCC(=O)c1c(C)cc(OC)c(OC)c1O
Temperature: 25 °C

Procedure:
To a solution of 3 g of the above 21-(2-hydroxy-3,4-dimethoxy-6-methylbenzoyl)heneicosanoic acid in 10 ml of methanol is added p-toluenesulfonic acid (30 mg), followed by heating under reflux for 2 hours. After cooling to room temperature, water is added and the mixture is stirred at 0° C. to give colorless crystals of methyl 21-(2-hydroxy-3,4-dimethoxy-6-methylbenzoyl)heneicosanoate. m.p. 72°-72.5° C.
Reaction SMILES: [CH:1]([O:4][C:5]([O:7][C:8]1[CH:15]=[CH:14][C:11]([CH:12]=[CH2:13])=[CH:10][CH:9]=1)=[O:6])([CH3:3])[CH3:2].[OH:16][C:17]1[CH:24]=[CH:23][C:20]([CH:21]=[CH2:22])=[CH:19][CH:18]=1.[CH2:25]([O:27][CH:28]=C)[CH3:26]>>[CH2:25]([O:27][CH2:28][CH2:5][O:7][C:8]1[CH:9]=[CH:10][C:11]([CH:12]=[CH2:13])=[CH:14][CH:15]=1)[CH3:26].[OH:16][C:17]1[CH:24]=[CH:23][C:20]([CH:21]=[CH2:22])=[CH:19][CH:18]=1.[CH:1]([O:4][C:5]([O:7][C:8]1[CH:9]=[CH:10][C:11]([CH:12]=[CH2:13])=[CH:14][CH:15]=1)=[O:6])([CH3:3])[CH3:2]
Reactant: C=COCC
Agent: C=Cc1ccc(O)cc1
Agent: C=Cc1ccc(OC(=O)OC(C)C)cc1
Product: C=Cc1ccc(OCCOCC)cc1

Procedure:
Using 10.0 g of poly(p-isopropoxycarbonyloxystyrene/p-hydroxystyrene) according to (3) above and 0.8 g of ethylvinyl ether, reaction and after-treatments were carried out according to (3) of Preparation Example 1 to obtain 8.9 g of poly(p-1-ethoxyethoxystyrene/p-hydroxystyrene/p-isopropoxycarbonyloxystyrene) as white powdery crystal. P-1-ethoxyethoxystyrene unit/p-hydroxystyrene unit/p-isopropoxycarbonyloxystyrene unit molar ratio in the polymer≈10:70:20 (1H NMR). Mw≈8,300; Mw/Mn=1.60 (GPC with polystyrene calibration).
Reaction SMILES: O.O.[Sn](Cl)(Cl)(Cl)Cl.[CH2:8]([N:15]([CH3:40])[CH2:16][CH2:17][CH2:18][NH:19][C:20]1[CH:36]=[CH:35][C:23]([C:24]([N:26]([CH2:31][CH:32]([CH3:34])[CH3:33])[CH2:27][CH:28]([CH3:30])[CH3:29])=[O:25])=[CH:22][C:21]=1[N+:37]([O-])=O)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C([O-])(O)=O.[Na+]>C(OCC)(=O)C>[NH2:37][C:21]1[CH:22]=[C:23]([CH:35]=[CH:36][C:20]=1[NH:19][CH2:18][CH2:17][CH2:16][N:15]([CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH3:40])[C:24]([N:26]([CH2:27][CH:28]([CH3:29])[CH3:30])[CH2:31][CH:32]([CH3:33])[CH3:34])=[O:25]
Reactant: CC(C)CN(CC(C)C)C(=O)c1ccc(NCCCN(C)Cc2ccccc2)c([N+](=O)[O-])c1
Agent: Cl[Sn](Cl)(Cl)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Product: CC(C)CN(CC(C)C)C(=O)c1ccc(NCCCN(C)Cc2ccccc2)c(N)c1
Temperature: 20 °C
Yield: 78 %

Procedure:
Tin chloride dihydrate (3.58 g, 5 eq) is added to a solution of 4-({3-[benzyl(methyl)amino]propyl}amino)-N,N-diisobutyl-3-nitrobenzamide (1.44 g, prepared according to the procedure described for Example A1), in ethyl acetate (40 ml). The mixture is heated under reflux for 7 hours then cooled down to a temperature of approximately 20° C. and poured into a saturated solution of NaHCO3. After decanting and extracting with ethyl acetate, the organic phases are combined, washed with salt water, dried over sodium sulphate and concentrated under reduced pressure at 40° C. Purification by flash chromatography on silica gel (eluent dichloromethane/methanol 95:5) produces the compound in the form of a foam (1.06 g, 78% yield).
Reaction SMILES: CON(C)[C:4]([C:6]1[N:7]=[N:8][CH:9]=[CH:10][CH:11]=1)=[O:5].[CH3:13]OC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=S)=CC=1>O1CCOCC1>[N:8]1[CH:9]=[CH:10][CH:11]=[C:6]([CH:4]([OH:5])[CH3:13])[N:7]=1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: CON(C)C(=O)c1cccnn1
Solvent: C1COCCO1
Product: CC(O)c1cccnn1
Temperature: 150 °C
Reaction time: 0.58 h
Yield: 328.8 %

Procedure:
A suspension of compound 2 (20 mg, 0.049 mmol) and Lawesson's Reagent (20 mg, 0.049 mmol) in anhydrous dioxane (1 mL) was stirred at 150° C. for 35 min in a CEM microwave reactor. The mixture was concentrated in vacuo, and the residue was purified by prep-TLC to give compound 3 (20 mg, 96%) as a yellow solid.
Reaction SMILES: [C:1]1([C:7]2[CH:13]=[C:12]([OH:14])[CH:11]=[CH:10][C:8]=2[OH:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1(C)C=CC=CC=1>C(O)(=O)C>[C:1]1([C:7]2[C:8](=[O:9])[CH:10]=[CH:11][C:12](=[O:14])[CH:13]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: Oc1ccc(O)c(-c2ccccc2)c1
Solvent: CC(=O)O
Solvent: Cc1ccccc1
Product: O=C1C=CC(=O)C(c2ccccc2)=C1

Procedure:
The procedure described in Example 3 is repeated using 3.8 g (0.02 mole) of phenylhydroquinone as the aromatic diol reactant and 10 mL toluene and 40 mL acetic acid as the solvent. The yield of phenyl-p-benzoquinone obtained is 60%.
Reaction SMILES: C(N[C:5]1[C:14]2[C:9](=[CH:10][C:11]([O:15][CH3:16])=[CH:12][CH:13]=2)[C:8]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[C:7]([C:23]#[N:24])[N:6]=1)C=C.[NH:25]1[CH2:29][CH2:28][C@@H:27]([OH:30])[CH2:26]1>>[OH:30][C@@H:27]1[CH2:28][CH2:29][N:25]([C:5]2[C:14]3[C:9](=[CH:10][C:11]([O:15][CH3:16])=[CH:12][CH:13]=3)[C:8]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[C:7]([C:23]#[N:24])[N:6]=2)[CH2:26]1
Reactant: C=CCNc1nc(C#N)c(-c2ccccc2)c2cc(OC)ccc12
Reactant: O[C@@H]1CCNC1
Product: COc1ccc2c(N3CC[C@@H](O)C3)nc(C#N)c(-c3ccccc3)c2c1

Procedure:
Following the procedure for 1-(allylamino)-6-methoxy-4-phenylisoquinoline-3-carbonitrile, using (R)-3-pyrrolidinol in place of allylamine, the title compound was synthesized.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[O:6][C:5]2=O.O.[NH2:14][NH2:15]>C(O)(C)C>[CH3:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[NH:15][NH:14][C:5]2=[O:6]
Reactant: NN
Reactant: Cc1ccc2c(c1)C(=O)OC2=O
Solvent: O
Solvent: CC(C)O
Product: Cc1ccc2c(=O)[nH][nH]c(=O)c2c1
Yield: 71.9 %

Procedure:
A mixture of 5-methyl-isobenzofuran-1,3-dione (6.0 g, 34.1 mmol) and hydrazine hydrate (2.48 mL, 51.1 mmol) in isopropanol (120 mL) was heated at reflux for 4 h. The mixture was allowed to cool and the precipitate was filtered and washed with water (50 mL). The filter cake was dried to afford the title compound (4.32 g, 72%) as a white solid. m/z (M+1)=177.18