Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][Si:2]([CH3:31])([CH3:30])[CH2:3][CH2:4][O:5][CH2:6][N:7]1[CH:11]=[CH:10][N:9]=[C:8]1[CH2:12][CH:13]([CH2:16][C:17]1[N:18]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[CH:19]=[CH:20][N:21]=1)[CH2:14][OH:15].O[C:33]1[CH:40]=[CH:39][C:36]([CH:37]=[O:38])=[CH:35][CH:34]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>O.O1CCCC1>[CH3:31][Si:2]([CH3:1])([CH3:30])[CH2:3][CH2:4][O:5][CH2:6][N:7]1[CH:11]=[CH:10][N:9]=[C:8]1[CH2:12][CH:13]([CH2:16][C:17]1[N:18]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:28])([CH3:27])[CH3:29])[CH:19]=[CH:20][N:21]=1)[CH2:14][O:15][C:33]1[CH:40]=[CH:39][C:36]([CH:37]=[O:38])=[CH:35][CH:34]=1
Reactant: O=Cc1ccc(O)cc1
Reactant: C[Si](C)(C)CCOCn1ccnc1CC(CO)Cc1nccn1COCC[Si](C)(C)C
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: O
Product: C[Si](C)(C)CCOCn1ccnc1CC(COc1ccc(C=O)cc1)Cc1nccn1COCC[Si](C)(C)C
Temperature: 25 °C
Reaction time: 15 h
Yield: 58.7 %

Procedure:
To a tetrahydrofuran (2 mL) solution of the compound (120 mg) produced in Example 18 and a 4-hydroxybenzaldehyde (31 mg), triphenylphosphine (81 mg) and diethylazodicarboxylate (175 μL) were added in this order. The reaction solution was stirred at room temperature for 15 hours. To the reaction solution, water (20 mL) was added. The aqueous layer was extracted twice with ethyl acetate (50 mL). The combined organic layer was washed with saturated sodium chloride solution (50 mL) and then dried over anhydrous magnesium sulfate. After removing the anhydrous magnesium sulfate by filtration, the filtrate was concentrated. The residue was purified by silica gel chromatography (n-hexane:ethyl acetate=80:20→0:100→ethyl acetate:methanol:28% aqueous ammonia=100:0:0→80:20:2) to obtain the title compound (85 mg) having the following physical properties.
Reaction SMILES: [C:1]([O:5][CH2:6][CH3:7])(=[O:4])[CH:2]=O.[CH3:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([NH2:16])=[CH:12][CH:11]=1.[C:17]1([CH2:23][C:24](Cl)=[O:25])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.N(C1CNC1)=[N+]=[N-]>ClCCCl.ClC(Cl)C.C(N(CC)CC)C>[C:1]([CH:2]1[N:16]([C:13]2[CH:14]=[CH:15][C:10]([O:9][CH3:8])=[CH:11][CH:12]=2)[C:24](=[O:25])[CH:23]1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)([O:5][CH2:6][CH3:7])=[O:4]
Reactant: O=C(Cl)Cc1ccccc1
Reactant: COc1ccc(N)cc1
Reactant: CCOC(=O)C=O
Agent: [N-]=[N+]=NC1CNC1
Solvent: CCN(CC)CC
Solvent: ClCCCl
Solvent: CC(Cl)Cl
Product: CCOC(=O)C1C(c2ccccc2)C(=O)N1c1ccc(OC)cc1

Procedure:
To a solution of 17 ml of triethylamine and 5.0 g of the imine formed from ethyl glyoxalate and p-anisidine in 100 ml of refluxing 1,2-dichloroethane was added dropwise over 2 hours a solution of 16 ml of freshly distilled phenylacetyl chloride in 50 ml of dichloroethane. After refluxing for three hours the reaction was worked-up as per the 3-azidoazetidine. The crude residue was chromatographed to yield the cis and trans isomers of 4-carboethoxy-1-(p-methoxyphenyl)-3-phenylazetidin-2-one as oils; cis: NMR (CDCl3): δ 7.2 (m, 7H), 6.7 (d, J=9, 2H), 4.7 (s, 2H), 3.6 (s, 3H), 3.6 (q, J=7, 2H), 0.7 (t, J=7, 3H); trans: NMR (CDCl3): 7.3 (m, 7H), 6.8 (d, J=9, 2H), 4.5 (d, J=2, 1H), 4.45 (d, J=2, 1H), 4.1 (q, J =7, 2H), 3.6 (s, 3H), 1.2 (t, J=7, 3H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:4]=1[CH:5]=O.[ClH:13].[NH2:14][C:15]1[S:16][C:17](Cl)=[CH:18][N:19]=1.CCN(CC)CC.N1CCCCC1.[BH4-].[Na+]>C(Cl)Cl>[Cl:13][C:18]1[N:19]=[C:15]([NH:14][CH2:5][C:4]2[CH:7]=[CH:8][C:9]([O:11][CH3:12])=[CH:10][C:3]=2[O:2][CH3:1])[S:16][CH:17]=1
Reactant: Nc1ncc(Cl)s1
Reactant: COc1ccc(C=O)c(OC)c1
Reactant: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: ClCCl
Solvent: C1CCNCC1
Solvent: CCN(CC)CC
Product: COc1ccc(CNc2nc(Cl)cs2)c(OC)c1

Procedure:
2,4 Dimethoxybenzaldehyde (5 g, 30 mmol, 1 eq), 2-amino-5-chlorothiazole hydrochloride (5.15 g, 30 mmol, 1 eq), Et3N (3.04 g, 30 mmol, 1 eq) and piperidine (31 mg, 0.361 mmol, 0.012 eq) were combined in DCM (100 ml) and the reaction mixture heated to reflux over sieves for 18 hours. The sieves were removed by filtration and the reaction mixture diluted with MeOH (50 ml). Sodium borohydride (5.01 g, 132 mmol, 4.4 eq) was added portionwise and the reaction mixture heated to reflux for 1 hour. The mixture was cooled, quenched with water and the organic solvent evaporated in vacuo. The residue was extracted from water into ethyl acetate, dried over sodium sulphate, filtered and evaporated in vacuo. The crude material was triturated with isopropanol to yield the title compound as a cream solid.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[CH3:9][C:10]1(O)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1.CC#[N:19]>>[NH2:19][C:3]1[C:2]([F:1])=[CH:7][C:6]([C:10]2([CH3:9])[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)=[C:5]([OH:8])[CH:4]=1
Reactant: Oc1ccc(F)cc1
Reactant: CC1(O)CCCCC1
Reactant: CC#N
Product: CC1(c2cc(F)c(N)cc2O)CCCCC1

Procedure:
5-Amino-4-fluoro-2-(1-methylcyclohexyl)phenol (C-13) was synthesized following the general scheme above starting from 4-fluorophenol and 1-methylcyclohexanol. Overall yield (3%). HPLC ret. time 3.00 min, 10-99% CH3CN, 5 min run; ESI-MS 224.2 m/z (MH+).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[O:15][C:16]1[CH:17]=[C:18]([CH:20]=[CH:21][CH:22]=1)[NH2:19].[C:23]1([N:29]=[C:30]=[O:31])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[O:15][C:16]1[CH:17]=[C:18]([NH:19][C:30]([NH:29][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:31])[CH:20]=[CH:21][CH:22]=1
Reactant: COc1cc2ncnc(Oc3cccc(N)c3)c2cc1OC
Reactant: O=C=Nc1ccccc1
Solvent: C1CCOC1
Product: COc1cc2ncnc(Oc3cccc(NC(=O)Nc4ccccc4)c3)c2cc1OC
Temperature: 25 °C
Reaction time: 8 h
Yield: 50 %

Procedure:
To 3-(6,7-dimethoxyquinazolin-4-yloxy)aniline from Example 113A (89 mg, 0.3 mmol) in THF (3 mL) was added phenyl isocyanate (33 uL, 0.3 mmol) and the solution stirred at room temperature overnight. The reaction was concentrated in vacuo, diluted with EtOAc, and filtered to give 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-phenylurea (63 mg, 0.15 mmol, 50%). 1H NMR (300 MHz, DMSO-d6) δ 8.88 (s, 1H), 8.74 (s, 1H), 8.57 (s, 1H), 7.61-7.56 (m, 2H), 7.48-7.35 (m, 4H), 7.32-7.21 (m, 3H), 7.02-7.89 (m, 2H), 3.99 (s, 6H); LC-MS (ESI) m/z 417 (M+H)+.
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[C:10]([CH3:11])=[CH:9][C:8]([O:12][CH2:13][CH3:14])=[CH:7][C:6]=1[CH3:15])=O.[NH2:16][C:17]([NH2:19])=[S:18]>CCO>[CH2:13]([O:12][C:8]1[CH:9]=[C:10]([CH3:11])[C:5]([C:3]2[N:16]=[C:17]([NH2:19])[S:18][CH:2]=2)=[C:6]([CH3:15])[CH:7]=1)[CH3:14]
Reactant: CCOc1cc(C)c(C(=O)CBr)c(C)c1
Reactant: NC(N)=S
Solvent: CCO
Product: CCOc1cc(C)c(-c2csc(N)n2)c(C)c1
Yield: 71.9 %

Procedure:
A mixture of 2-bromo-1-(4-ethoxy-2,6-dimethylphenyl)ethanone (6.35 g, 23.4 mmol) and thiourea (1.78 g, 23.4 mmol) in 95% EtOH (33.5 mL) was heated at reflux for 60 min. The solution was concentrated and added with water (50 mL) and saturated aqueous Na2CO3 (5.0 mL). The resultant precipitate was filtered and recrystallized in toluene (30 mL). The solids were filtered and dried under vacuum to give 4-(4-ethoxy-2,6-dimethylphenyl)thiazol-2-amine (4.18 g) as white solids in 72% yield: 1H NMR (500 MHz, DMSO-d6) δ 6.84 (s, 2 H), 6.60 (s, 2 H), 6.27(s, 1 H), 3.99 (q, J=6.5 Hz, 2 H), 2.06 (s, 6 H), 1.31 (t, J=6.95 Hz, 3 H).
Reaction SMILES: [N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[CH:3]([C:9](Cl)=[O:10])[CH2:2]2.[NH2:12][C@H:13]1[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:14]1>>[C:20]1([CH2:19][CH2:18][N:15]2[CH2:16][CH2:17][CH:13]([NH:12][C:9]([C@H:3]3[CH:4]4[CH2:7][CH2:8][N:1]([CH2:6][CH2:5]4)[CH2:2]3)=[O:10])[CH2:14]2)[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: O=C(Cl)C1CN2CCC1CC2
Reactant: N[C@H]1CCN(CCc2ccccc2)C1
Product: O=C(NC1CCN(CCc2ccccc2)C1)[C@@H]1CN2CCC1CC2

Procedure:
1-Azabicyclo[2.2.2]octane-3-carbonyl chloride and (S)-3-amino-1-(2-phenylethyl)pyrrolidine were reacted under the same conditions as in Example 53 to give (S)-N-(1-(2-phenylethyl)pyrrolidin-3-yl)-1-azabicyclo[2.2.2]octane-3-carboxamide.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:10]=[CH:9][CH:8]=[CH:7][C:4]=1[CH2:5]Cl.[Cl:11][C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[NH:17][C:16](=[O:21])[C:15]2=[O:22]>>[Cl:11][C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[NH:17][C:16](=[O:21])[C:15]2([OH:22])[CH2:5][C:4]1[CH:7]=[CH:8][CH:9]=[CH:10][C:3]=1[O:2][CH3:1]
Reactant: COc1ccccc1CCl
Reactant: O=C1Nc2ccc(Cl)cc2C1=O
Product: COc1ccccc1CC1(O)C(=O)Nc2ccc(Cl)cc21
Yield: 30.2 %

Procedure:
With 4.50 g of 2-methoxybenzyl chloride and 4.34 g of 5-chloroisatin as starting materials, 2.19 g of the title compound (orange red solid) was obtained by a similar method to Step 21-1.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][N:6]=[C:5]2[OH:12].[F:13][C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[CH:16][CH:15]=1.C([O-])([O-])=O.[K+].[K+].C(O)(=O)C>O1CCOCC1.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>[F:13][C:14]1[CH:19]=[CH:18][C:17]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[CH:7][N:6]=[C:5]3[OH:12])=[CH:16][CH:15]=1
Reactant: OB(O)c1ccc(F)cc1
Reactant: Oc1ncnc2ccc(Br)cc12
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: [K+]
Solvent: CC(=O)O
Solvent: O
Solvent: C1COCCO1
Product: Oc1ncnc2ccc(-c3ccc(F)cc3)cc12
Temperature: 25 °C
Yield: 89.5 %

Procedure:
A mixture of 6-bromo-4-hydroxy-quinazoline (2.4 g, 10 mmol), 4-fluorophenylboronic acid (1.54 g, 11 mmol), K2CO3 (4.15 g, 30 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.5 g, 0.43 mmol) in dioxane (150 ml) and water (50 ml) was heated under reflux for 12 hours. After cooling to room temperature, the reaction mixture was neutralized with acetic acid to pH 6-7. The precipitate was collected by filtration, washed with water and diethyl ether to yield the crude product. The crude residue was purified by silica gel flash chromatography, the mobile phase being a mixture of methanol and dichloromethane (in a ratio of 1:40), yielding the pure title compound as a white solid (2.15 g, yield: 95%) which was characterized by its mass spectrum as follows: MS (m/z): 241 ([M+H]+, 100).
Reaction SMILES: [OH-].[K+].[CH3:3]I.[CH2:5]([N:8]1[C@H:22]2[C@@H:12]([C:13]3[CH:14]=[CH:15][CH:16]=[C:17]4[C:23]=3[C:20]([CH2:21]2)=[CH:19][NH:18]4)[CH2:11][C@H:10]([NH:24][C:25]2[CH:26]=[CH:27][C:28]3[O:32][CH2:31][CH2:30][C:29]=3[CH:33]=2)[CH2:9]1)[CH2:6][CH3:7].O>CS(C)=O>[CH3:3][N:18]1[C:17]2[C:23]3[C:20]([CH2:21][C@@H:22]4[C@@H:12]([C:13]=3[CH:14]=[CH:15][CH:16]=2)[CH2:11][C@H:10]([NH:24][C:25]2[CH:26]=[CH:27][C:28]3[O:32][CH2:31][CH2:30][C:29]=3[CH:33]=2)[CH2:9][N:8]4[CH2:5][CH2:6][CH3:7])=[CH:19]1
Reactant: CCCN1C[C@@H](Nc2ccc3c(c2)CCO3)C[C@@H]2c3cccc4[nH]cc(c34)C[C@H]21
Reactant: CI
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CS(C)=O
Product: CCCN1C[C@@H](Nc2ccc3c(c2)CCO3)C[C@@H]2c3cccc4c3c(cn4C)C[C@H]21
Reaction time: 5 h

Procedure:
696 mg finely powdered KOH and 0.77 ml methyliodide are added to 4.1 g 6-n-propyl-8α-(2,3-dihydro-5-benzofuranylamino)-ergoline (example 9) in 25 ml dimethylsulfoxide. The reactive mixture is stirred for 5 hours, poured onto 150 ml H2O, extracted with ethyl acetate, dried over Na2SO4 and concentrated. The residue is chromatographed on 100 g silica gel using methylene chloride/methanol (98:2) as eluant. M.P.=137°-138° C.
Reaction SMILES: Cl[CH:2]([Cl:4])C.[CH3:5][C:6]1[CH:14]=[CH:13][C:9]([C:10](Cl)=[O:11])=[CH:8][CH:7]=1.[O:15]1CCCOO1>[Cl-].[Cl-].[Cl-].[Cl-].[Zr+4].O>[CH3:5][C:6]1[CH:14]=[CH:13][C:9]([C:10]([O:15][CH2:2][Cl:4])=[O:11])=[CH:8][CH:7]=1
Reactant: CC(Cl)Cl
Reactant: C1COOOC1
Reactant: Cc1ccc(C(=O)Cl)cc1
Agent: [Zr+4]
Agent: [Cl-]
Solvent: O
Product: Cc1ccc(C(=O)OCCl)cc1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
To 10 ml of dichloroethane were added 1.36 g of zirconium tetrachloride and 1 g of 4-methylbenzoyl chloride, and the mixture was stirred at room temperature for 20 minutes. The mixture was cooled to 0° C., 0.22 g of trioxane was added, and the mixture was stirred at room temperature for 1 hour. Water was added slowly at 0° C., the resultant solution was extracted with chloroform three times, and the organic layers were combined, washed with an aqueous saturated sodium bicarbonate solution and an aqueous saturated sodium chloride solution, dried with anhydrous magnesium sulfate, and concentrated to obtain 0.7 g of chloromethyl 4-methylbenzoate.
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([NH:17][C:18]3[N:23]=[C:22](Cl)[N:21]=[CH:20][N:19]=3)=[CH:14][CH:15]=2)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[NH2:34][C:35]1[CH:36]=[C:37]([NH:41][C:42](=[O:45])[CH:43]=[CH2:44])[CH:38]=[CH:39][CH:40]=1>>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([NH:17][C:18]3[N:19]=[CH:20][N:21]=[C:22]([NH:34][C:35]4[CH:36]=[C:37]([NH:41][C:42](=[O:45])[CH:43]=[CH2:44])[CH:38]=[CH:39][CH:40]=4)[N:23]=3)=[CH:14][CH:15]=2)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C=CC(=O)Nc1cccc(N)c1
Reactant: Clc1ncnc(Nc2ccc3c(cnn3Cc3ccccc3)c2)n1
Solvent: CCN(C(C)C)C(C)C
Product: C=CC(=O)Nc1cccc(Nc2ncnc(Nc3ccc4c(cnn4Cc4ccccc4)c3)n2)c1
Temperature: 100 °C

Procedure:
To a slurry of (1-benzyl-1H-indazol-5-yl)-(4-chloro-[1,3,5]triazin-2-yl)-amine (Step 3) (50.0 mg, 0.148 mmol) in IpOH (2.5 ml) was added DIEA (0.039 mL, 0.222 mmol) and N-(3-aminophenyl)acrylamide (26.5 mg, 0.163 mmol). The mix was heated at 100° C. for 18 h. The solution was then cooled to RT. A precipitate fell out of solution and was filtered off and dried under reduced pressure to give N-{3-[4-(1-benzyl-1H-indazol-5-ylamino)-[1,3,5]triazin-2-ylamino]-phenyl}-acrylamide: MS m/z=463[M+H]+. Calc'd for C26H22N8O: 462.19.
Reaction SMILES: Cl.Cl.[CH2:3]([N:10]([CH2:18][C:19]1([NH:22][CH3:23])[CH2:21][CH2:20]1)[C:11]1[CH:12]=[N:13][C:14]([Cl:17])=[CH:15][CH:16]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH2:24]=O.Cl>C(O)=O.C(O)C.CCOCC>[ClH:17].[CH2:3]([N:10]([CH2:18][C:19]1([N:22]([CH3:24])[CH3:23])[CH2:20][CH2:21]1)[C:11]1[CH:12]=[N:13][C:14]([Cl:17])=[CH:15][CH:16]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: C=O
Reactant: CNC1(CN(Cc2ccccc2)c2ccc(Cl)nc2)CC1
Agent: Cl
Solvent: CCOCC
Solvent: O=CO
Solvent: CCO
Product: CN(C)C1(CN(Cc2ccccc2)c2ccc(Cl)nc2)CC1
Temperature: 70 °C

Procedure:
3.1 g of the base of the compound of Example 17 are dissolved in 60 ml of formic acid. 60 ml of 37% aqueous formaldehyde solution are added and the mixture is heated for 4 hours at 70° C. Concentration to dryness is carried out, and the residue is taken up in 50% aqueous potassium carbonate solution and extraction is carried out with dichloromethane. The organic phase is dried over sodium sulphate, concentration is carried out, and the residue is chromatographed on silica gel (dichloromethane/acetone: 96/4). A fraction consisting of 0.48 g of base of the expected compound is isolated which, after dissolution in 5 ml of ethanol and addition of hydrochloric acid solution in ether, allows, after filtering off a precipitate and drying, 0.4 g of the expected compound to be obtained.
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:32])[CH:10]([CH2:19][CH2:20][N:21]1[C:25](=[O:26])[C:24]2=[CH:27][CH:28]=[CH:29][CH:30]=[C:23]2[C:22]1=[O:31])[NH:11]C(OC(C)(C)C)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OC(=O)C(CCN1C(=O)C2=CC=CC=C2C1=O)NC(OC(C)(C)C)=O)C=C.[N:61]1[CH:66]=[CH:65][C:64]([O:67][C:68]2[CH:73]=[CH:72][C:71]([S:74]([Cl:77])(=[O:76])=[O:75])=[CH:70][CH:69]=2)=[CH:63][CH:62]=1>>[O:67]([C:68]1[CH:73]=[CH:72][C:71]([S:74]([Cl:77])(=[O:76])=[O:75])=[CH:70][CH:69]=1)[C:64]1[CH:65]=[CH:66][CH:1]=[CH:62][CH:63]=1.[CH2:1]([O:8][C:9](=[O:32])[CH:10]([CH2:19][CH2:20][N:21]1[C:22](=[O:31])[C:23]2=[CH:30][CH:29]=[CH:28][CH:27]=[C:24]2[C:25]1=[O:26])[NH:11][S:74]([C:71]1[CH:70]=[CH:69][C:68]([O:67][C:64]2[CH:65]=[CH:66][N:61]=[CH:62][CH:63]=2)=[CH:73][CH:72]=1)(=[O:75])=[O:76])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)NC(CCN1C(=O)c2ccccc2C1=O)C(=O)OCc1ccccc1
Reactant: O=S(=O)(Cl)c1ccc(Oc2ccncc2)cc1
Agent: C=CCOC(=O)C(CCN1C(=O)c2ccccc2C1=O)NC(=O)OC(C)(C)C
Product: O=C(OCc1ccccc1)C(CCN1C(=O)c2ccccc2C1=O)NS(=O)(=O)c1ccc(Oc2ccncc2)cc1
Product: O=S(=O)(Cl)c1ccc(Oc2ccccc2)cc1
Yield: 13 %

Procedure:
In a similar manner to the procedures described in Example 1(2)-a and b, reactions were carried out using (±)-N-(tert-butoxycarbonyl)-2-(2-phthalimidoethyl)glycine benzyl ester, instead of (±)-N-(tert-butoxycarbonyl)-2-(2-phthalimidoethyl)glycine allyl ester, and using 4-(pyridin-4-yl)oxybenzensulfonyl chloride, instead of 4-phenoxybenzenesulfonyl chloride, to afford the desired compound (yield 13%) as a white amorphous solid.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][C@H:18]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=4)[C@@H:19]([NH2:21])[CH3:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[C:30](O)(=[O:36])[CH2:31][NH:32][C:33]([NH2:35])=[O:34]>>[C:33]([NH:32][CH2:31][C:30]([NH:21][C@@H:19]([CH3:20])[C@H:18]([O:17][C:13]1[CH:12]=[C:11]2[C:16](=[CH:15][CH:14]=1)[N:8]([C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)[N:9]=[CH:10]2)[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=1)=[O:36])(=[O:34])[NH2:35]
Reactant: NC(=O)NCC(=O)O
Reactant: COc1cccc([C@@H](Oc2ccc3c(cnn3-c3ccc(F)cc3)c2)[C@H](C)N)c1
Product: COc1cccc([C@@H](Oc2ccc3c(cnn3-c3ccc(F)cc3)c2)[C@H](C)NC(=O)CNC(N)=O)c1

Procedure:
Prepared as described in Example 269 from (1R,2S)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)-1-(3-methoxyphenyl)propan-2-amine (6a, 200 mg, 0.51 mmol) and hydantoic acid (60 mg, 0.51 mmol).
Reaction SMILES: [CH:1]1([CH2:7][CH2:8][CH2:9][CH2:10][N:11]2[CH2:16][CH2:15][C:14](=[C:17]3[C:23]4C=[CH:25][CH:26]=[CH:27][C:22]=4C=C[C:19]4[CH:28]=[CH:29][CH:30]=[CH:31][C:18]3=4)[CH2:13][CH2:12]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C[N+]1([O-])CC[O:36]CC1.[CH3:40][C:41]([CH3:43])=[O:42]>[Os](=O)(=O)(=O)=O>[CH:1]1([CH2:7][CH2:8][CH2:9][CH2:10][N:11]2[CH2:16][CH2:15][C:14](=[C:17]3[C:23]4[CH:22]=[CH:27][CH:26]=[CH:25][C:43]=4[C:41]([OH:42])=[C:40]([OH:36])[C:19]4[CH:28]=[CH:29][CH:30]=[CH:31][C:18]3=4)[CH2:13][CH2:12]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: C1=Cc2ccccc2C(=C2CCN(CCCCC3CCCCC3)CC2)c2ccccc21
Reactant: C[N+]1([O-])CCOCC1
Reactant: CC(C)=O
Agent: O=[Os](=O)(=O)=O
Product: OC1=C(O)c2ccccc2C(=C2CCN(CCCCC3CCCCC3)CC2)c2ccccc21
Temperature: 25 °C

Procedure:
A osmium tetraoxide (0.4 mmol) in acetone was added to the 50% aqueous solution of acetone dissolved in 1-Cyclohexyl-4-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)butane (4.8 mmol) and N-methylmorpholine-N-oxide (7.2 mmol). The mixture was stirred for over night at ambient temperature.
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC1C=C(C)C=C(C)C=1[O-].[K+].[C:19](=[O:21])=[O:20]>>[OH:7][C:1]1[CH:6]=[CH:5][C:4]([C:19]([OH:21])=[O:20])=[CH:3][CH:2]=1
Reactant: Oc1ccccc1
Reactant: O=C=O
Agent: Cc1cc(C)c([O-])c(C)c1
Agent: [K+]
Product: O=C(O)c1ccc(O)cc1
Yield: 73.1 %

Procedure:
A pressure vessel was charged with 4.70 g of phenol, 17.42 g of potassium 2,4,6-trimethylphenolate being in a dry powder form and 38 ml of NeoSK 1400. With stirring, reaction was carried out at a carbon dioxide pressure of 5 kg/cm2 (G) and at 260° C. for 10 min. An analysis of the reaction mixture after conversion to acid form showed a para-hydroxybenzoic acid yield of 73.1% on the basis of phenol.
Reaction SMILES: [C:1]1(/[C:7](/[C:18]2[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH2:26]Br)=[CH:20][CH:19]=2)=[C:8](/[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)\[CH2:9][CH2:10][OH:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH3:28]>C(O)C>[C:1]1(/[C:7](/[C:18]2[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH2:26][NH2:28])=[CH:20][CH:19]=2)=[C:8](/[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)\[CH2:9][CH2:10][OH:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: OCC/C(=C(\c1ccccc1)c1ccc(OCCBr)cc1)c1ccccc1
Reactant: N
Solvent: CCO
Product: NCCOc1ccc(/C(=C(/CCO)c2ccccc2)c2ccccc2)cc1
Temperature: 90 °C
Reaction time: 3 h

Procedure:
10.0 g of Z-1,2-diphenyl-1-[4-(bromoethoxy)phenyl]-1-buten-4-ol is added to200 ml of ethanol saturated with ammonia gas. The solution is stirred for 3hours at 90° C. in an autoclave. The solvent is evaporated and the residue is dissolved in ethyl acetate in the presence of 2M sodium hydroxide solution by warming the solution on a water bath. The organic layer is washed with water. The precipitated product is filtered off. The yield is 5.1 g (60%).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:21])[CH2:5][N:6]1[C:15]2[C:10](=[C:11]([N+:16]([O-])=O)[CH:12]=[CH:13][CH:14]=2)[C:9](=[O:19])[C:8]([CH3:20])=[CH:7]1)[CH3:2]>C(O)C.ClCCl.[Pd]>[NH2:16][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]2[C:10]=1[C:9](=[O:19])[C:8]([CH3:20])=[CH:7][N:6]2[CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:21]
Reactant: CCOC(=O)Cn1cc(C)c(=O)c2c([N+](=O)[O-])cccc21
Agent: [Pd]
Solvent: ClCCl
Solvent: CCO
Product: CCOC(=O)Cn1cc(C)c(=O)c2c(N)cccc21

Procedure:
A solution of (3-Methyl-5-nitro-4-oxo-4H-quinolin-1-yl)-acetic acid ethyl ester (Compound 301B, 250 mg, 0.86 mmol) in ethanol and dichloromethane (10 mL/20 mL) was cautiously treated with palladium on charcoal (10%) (30 mg) and hydrogenated at atmospheric pressure for 1 hr. The mixture was filtered and the filtrate was concentrated to a residue which upon trituration with t-butyl methyl ether gave the desired product as 150 mg of a light yellow solid (67%). 1H NMR of compound C (CDCl3, 300 MHz): δ 1.24 (t, 3H, J=7.5 Hz), 2.04 (s, 3H), 4.22 (q, 2H, J=7.5 Hz), 4.58 (s, 2H), 6.18 (d, J=8.4 Hz, 1H), 6.35 (d, J=8.5 Hz, 1H), 7.24 (m, 3H).
Reaction SMILES: N1C=CC=CC=1.[OH:7][CH2:8][C:9]#[C:10][C:11]1[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][CH:12]=1.[C:20]1([CH3:30])[CH:25]=[CH:24][C:23]([S:26](Cl)(=[O:28])=[O:27])=[CH:22][CH:21]=1.Cl>ClCCl>[C:20]1([CH3:30])[CH:25]=[CH:24][C:23]([S:26]([O:7][CH2:8][C:9]#[C:10][C:11]2[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][CH:12]=2)(=[O:28])=[O:27])=[CH:22][CH:21]=1
Reactant: O=[N+]([O-])c1ccc(C#CCO)cc1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)OCC#Cc2ccc([N+](=O)[O-])cc2)cc1
Temperature: 0 °C

Procedure:
4.4 ml (54 mmol) of pyridine are added dropwise to a solution of 5.8 g (33 mmol) of 4-(3-hydroxyprop-1-ynyl)-nitrobenzene and 5.2 g (27 mmol) of p-toluenesulphonic acid chloride in 50 ml of dichloromethane at 0° C. After 2 hours at 0° C. about 25 g of ice and 8 ml of conc. hydrochloric acid are added. The organic phase is separated off and washed with water. After removal of the solvent in vacuo and chromatography of the residue on silica gel (dichloromethane/methanol=1:1) the product is obtained as an oil.