Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][C:3]([C@:5]12[CH2:11][C@@H:8]3[CH2:9][C@H:10]1[C@H:6]2[C@@:7]3([NH:16][C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18])[C:12]([O:14]C)=[O:13])=[O:4].CO.Cl>O1CCCC1.[OH-].[Na+]>[CH2:20]([O:19][C:17]([NH:16][C@:7]1([C:12]([OH:14])=[O:13])[C@@H:8]2[CH2:11][C@@:5]3([C:3]([OH:4])=[O:2])[C@@H:10]([CH2:9]2)[C@@H:6]13)=[O:18])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: COC(=O)[C@]12C[C@@H]3C[C@H]1[C@H]2[C@@]3(NC(=O)OCc1ccccc1)C(=O)OC
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: O=C(N[C@]1(C(=O)O)[C@H]2C[C@H]3[C@@H]1[C@@]3(C(=O)O)C2)OCc1ccccc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 64.7 %

Procedure:
A suspension of 2.0 g (5.6 mmole) of (+/−)-(1R*,2R*,3R*,4S*,6S*)-3-benzyloxycarbonylamino-tricyclo[2.2.1.02,6]heptane-1,3-dicarboxylic acid dimethyl ester in a mixture of 30 mL of tetrahydrofuran and 30 mL of 1 N aqueous sodium hydroxide was stirred at room temperature for 24 hours. Because the starting material was unchanged, methanol was added until homogeneity was achieved and the solution was refluxed under nitrogen for 15 hours. The mixture was acidified with concentrated HCl and extracted with ethyl acetate (2×200 mL). The extract was washed with 200 mL portions of water and saturated brine, dried over sodium sulfate, filtered and concentrated in vacuum. The resulting residue was recrystallized from ethyl acetate/hexane to give 1.2 g of the title compound as a white solid, m.p. 205° C.
Reaction SMILES: C([O:8][CH:9]1[CH2:14][CH2:13][CH:12]([O:15][CH2:16][C:17]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=O)[CH:11]([F:25])[CH2:10]1)C1C=CC=CC=1.CCCCCC>[Pd].C(OCC)(=O)C>[F:25][CH:11]1[CH:12]([O:15][CH2:16][CH2:17][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:13][CH2:14][CH:9]([OH:8])[CH2:10]1
Reactant: O=C(COC1CCC(OCc2ccccc2)CC1F)c1ccccc1
Agent: [Pd]
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: OC1CCC(OCCc2ccccc2)C(F)C1
Yield: 92.2 %

Procedure:
To an ethyl acetate (100 mL) solution of (−) 2-{[4-(Benzyloxy)-2-fluorocyclohexyl]oxy}-1-phenylethanone (1.44 g, 4.18 mmol) was added 10% palladium on carbon (0.200 g). The resulting mixture was hydrogenated using a balloon. After 20 h the contents of the reaction flask were filtered through celite® and the filtrate evaporated under reduced pressure. Flash column chromatography (hexane:ethyl acetate, 60:40) gave 3-Fluoro-4-(2-phenylethoxy)cyclohexanol as a colorless oil (0.918 g, 92% yield).
Reaction SMILES: [NH2:1][C@H:2]([C:4]1[N:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1)[CH3:3].[C:11](Cl)(=[O:13])[CH3:12]>C1COCC1>[OH:10][C:7]1[CH:6]=[CH:5][C:4]([C@@H:2]([NH:1][C:11](=[O:13])[CH3:12])[CH3:3])=[N:9][CH:8]=1
Reactant: CC(=O)Cl
Reactant: C[C@H](N)c1ccc(O)cn1
Solvent: C1CCOC1
Product: CC(=O)N[C@@H](C)c1ccc(O)cn1
Reaction time: 2 h

Procedure:
To 1.00 g (5.73 mmol) (S)-6-(1-aminoethyl)pyridin-3-ol in 10 ml THF and 3.99 mL TEA (28.6 mmol) are slowly added 494 mg (6.30 mmol) acetyl chloride and stirring is continued for 2 h. The reaction is quenched by the addition of water and extracted several times with DCM. The org. layers are combined, dried over MgSO4, filtered and the solvent is removed in vacuo. The crude product is purified by column chromatography (silica gel, DCM/MeOH/NH3 90/9/1).
Reaction SMILES: [CH:1]1([S:4]([C:7]2[CH:22]=[CH:21][C:20]([N+:23]([O-])=O)=[CH:19][C:8]=2[CH2:9][N:10]([CH3:18])[C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])(=[O:6])=[O:5])[CH2:3][CH2:2]1>CO.CCOC(C)=O.[Pd]>[NH2:23][C:20]1[CH:21]=[CH:22][C:7]([S:4]([CH:1]2[CH2:2][CH2:3]2)(=[O:6])=[O:5])=[C:8]([CH:19]=1)[CH2:9][N:10]([CH3:18])[C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:14])[CH3:15]
Reactant: CN(Cc1cc([N+](=O)[O-])ccc1S(=O)(=O)C1CC1)C(=O)OC(C)(C)C
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CO
Product: CN(Cc1cc(N)ccc1S(=O)(=O)C1CC1)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 101.2 %

Procedure:
To Intermediate 8A (10.0 g, 27.0 mmol) in MeOH (250 ml) and EtOAc (150 ml) was added 10% Pd/C (0.5 g, 4.70 mmol) under a stream of nitrogen. The system was purged and degassed 3× with nitrogen, then the hydrogen balloon was introduced. The system was purged and degassed with hydrogen 3×. The mixture was stirred at rt overnight after addition of 0.5 mL of conc. HCl. The catalyst was filtered carefully over CELITE® under a stream of nitrogen and washed with methanol. The filtrate was concentrated and dried to give Intermediate 8B as an off-white solid (9.3 g). MS (ESI) (m/z) 341 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 0.85-1.08 (m, 4H) 1.38 (d, J=48.37 Hz, 9H) 2.67-2.78 (m, J=4.40 Hz, 1H) 2.84 (s, 3H) 4.68 (s, 2H) 5.94-6.30 (m, 2H) 6.39 (s, 1H) 7.44 (d, J=8.79 Hz, 1H).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:10]([OH:12])=[O:11])[CH:8]=2)[CH:3]=[N:2]1.[C:13](=O)([O-])[O-].[Na+].[Na+].IC.C(=O)(O)[O-].[Na+]>CN(C)C=O>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:10]([O:12][CH3:13])=[O:11])[CH:8]=2)[CH:3]=[N:2]1
Reactant: O=C([O-])[O-]
Reactant: O=C(O)c1ccc2cn[nH]c2c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CI
Solvent: CN(C)C=O
Product: COC(=O)c1ccc2cn[nH]c2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 90.5 %

Procedure:
To a solution of 1H-indazole-6-carboxylic acid (3.00 g, 18.5 mmol) in N,N-dimethylformamide (46 mL) was added sodium carbonate (2.06 g, 19.4 mmol), followed by iodomethane (2.75 g, 1.21 mL, 19.4 mmol) dropwise. The mixture was stirred at room temperature overnight. The mixture was poured into half saturated sodium bicarbonate and extracted with ethyl acetate three times. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to afford a brown oil. This residue was purified by flash column chromatography (12-100% ethyl acetate/heptanes) to afford methyl 1H-indazole-6-carboxylate as a yellow solid (2.95 g, 90%). 1H NMR (400 MHz, CDCl3, δ): 10.40 (br. s., 1 H), 8.26 (s, 1 H), 8.13 (s, 1 H), 7.84 (d, J=8.4 Hz, 1 H), 7.79 (d, J=8.4 Hz, 1 H), 3.96 (s, 3 H).
Reaction SMILES: Cl.Cl.[O:3]1[C:8]2=[CH:9][CH:10]=[CH:11][C:7]2=[CH:6][C:5]([CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][N:13]2[CH2:18][CH2:19][C@H:20]2[CH2:25][CH2:24][C@H:23]([NH2:26])[CH2:22][CH2:21]2)=[CH:4]1.[CH3:27][C:28]1[CH:32]=[C:31]([C:33](O)=[O:34])[O:30][N:29]=1>>[O:3]1[C:8]2=[CH:9][CH:10]=[CH:11][C:7]2=[CH:6][C:5]([CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][N:13]2[CH2:18][CH2:19][C@H:20]2[CH2:21][CH2:22][C@H:23]([NH:26][C:33]([C:31]3[O:30][N:29]=[C:28]([CH3:27])[CH:32]=3)=[O:34])[CH2:24][CH2:25]2)=[CH:4]1
Reactant: N[C@H]1CC[C@H](CCN2CCCCC2c2coc3cccc-3c2)CC1
Reactant: Cc1cc(C(=O)O)on1
Agent: Cl
Product: Cc1cc(C(=O)N[C@H]2CC[C@H](CCN3CCCCC3c3coc4cccc-4c3)CC2)on1

Procedure:
The title compound, off-white solid (89 mg, 82%), MS (ISP) m/z=436.3 [(M+H)+], mp 178° C., was prepared in accordance with the general method of example 1 from trans-4-[2-(4-benzofuran-3-yl-piperidin-1-yl)-ethyl]-cyclohexylamine dihydrochloride (intermediate A) (100 mg, 0.25 mmol) and 3-methyl-isoxazole-5-carboxylic acid.
Reaction SMILES: Cl.[NH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13](=[O:22])[C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=2)=[CH:8][C:7]=1[C:23]1[N:27]([CH3:28])[N:26]=[CH:25][CH:24]=1.C(N(CC)CC)C.Cl[C:37]([O:39][CH2:40][CH3:41])=[O:38]>ClCCl>[CH2:40]([O:39][C:37](=[O:38])[NH:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13](=[O:22])[C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=2)=[CH:8][C:7]=1[C:23]1[N:27]([CH3:28])[N:26]=[CH:25][CH:24]=1)[CH3:41]
Reactant: CCOC(=O)Cl
Reactant: COc1cccc(C(=O)Nc2ccc(OCCN)c(-c3ccnn3C)c2)c1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCOC(=O)NCCOc1ccc(NC(=O)c2cccc(OC)c2)cc1-c1ccnn1C
Reaction time: 0.25 h
Yield: 52.4 %

Procedure:
The N-(4-(2-aminoethoxy)-3-(1-methyl-1H-pyrazol-5-yl)phenyl)-3-methoxybenzamide hydrochloride (30.0 mg, 74.5 μmol) and triethylamine (31.1 μL, 3.0 eq) were taken up in 2 mL of dichloromethane and stirred for 15 mins. To this was added ethyl chloroformate (8.58 μL, 1.2 eq) and the reaction was stirred at room temperature for 18 hrs. The solvents were evaporated under a stream of nitrogen and it was purified by HPLC. The proper fractions were collected and lyophilized to afford the title compound as a white solid in 52.4% yield. LCMS m/z (%)=439 (M+H, 100). 1H NMR (400 MHz, CDCl3) δ ppm 1.23 (t, J=7.07 Hz, 3 H), 3.44-3.51 (m, 2 H), 3.85 (s, 3 H), 3.88 (s, 3 H), 3.94-4.21 (m, 5 H), 6.38 (d, J=2.53 Hz, 1 H), 7.03 (d, J=9.60 Hz, 1 H), 7.11 (dt, J=4.67, 2.27 Hz, 1 H), 7.36-7.46 (m, 3 H), 7.62-7.72 (m, 2 H), 7.83 (s, 1 H)
Reaction SMILES: C([O:3][C:4]1[CH:5]([CH2:13][CH:14]([CH2:18][C:19]2[CH:28]=[CH:27][C:26]3[C:21](=[C:22]([O:29][CH2:30][CH2:31][O:32][CH3:33])[CH:23]=[CH:24][CH:25]=3)[CH:20]=2)[CH:15]([CH3:17])[CH3:16])[N:6]=C(OCC)CN=1)C.Cl.[C:35](=[O:38])(O)[O-].[Na+].[C:40](#N)C>>[NH2:6][CH:5]([CH2:13][CH:14]([CH2:18][C:19]1[CH:28]=[CH:27][C:26]2[C:21](=[C:22]([O:29][CH2:30][CH2:31][O:32][CH3:33])[CH:23]=[CH:24][CH:25]=2)[CH:20]=1)[CH:15]([CH3:16])[CH3:17])[C:4]([O:38][CH2:35][CH3:40])=[O:3]
Reactant: O=C([O-])O
Reactant: CCOC1=NC(CC(Cc2ccc3cccc(OCCOC)c3c2)C(C)C)C(OCC)=NC1
Reactant: CC#N
Agent: Cl
Agent: [Na+]
Product: CCOC(=O)C(N)CC(Cc1ccc2cccc(OCCOC)c2c1)C(C)C
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
A solution of 1.57 g of 3,6-diethoxy-2-{2-[8-(2-methoxyethoxy)naphthalen-2-ylmethyl]-3-methylbutyl}-2,5-dihydropyrazine in 14 ml of acetonitrile at room temperature is admixed with 14 ml of 1N HCl. After 30 minutes, the reaction mixture is poured into a stirred mixture of 15 ml of saturated aqueous sodium bicarbonate solution and 15 g of ice, and the mixture is extracted with dichloromethane (3×). The combined organic phases are washed with water (3×), dried with sodium sulphate and concentrated by evaporation. The crude title compound is identified on the basis of the Rf value from the residue.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH2:5].C(N(CC)CC)C.ClC(OCC)=O.Cl.[C:24](=S)=[S:25]>C(Cl)(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([N:5]=[C:24]=[S:25])[CH:6]=[CH:7][C:8]=1[F:9]
Reactant: S=C=S
Reactant: Nc1ccc(F)c(F)c1
Agent: CCOC(=O)Cl
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: Fc1ccc(N=C=S)cc1F
Temperature: 25 °C
Yield: 70.2 %

Procedure:
3,4-Difluoroaniline (600 g) and 1410 g of triethylamine were mixed and, with ice cooling and stirring, 389 g of carbon disulfide was dropped in during 2.5 hours. The mixture was stirred at the same temperature for 2 hours more whereupon crystals gradually appeared. The mixture was gradually warmed up to the room temperature, stirred for 2 hours, and kept in a refrigerator for two nights. Chloroform (2 liters) was added to the reaction mixture in which crystals were solidified, the mixture was stirred to make it suspended, and ethyl chloroformate was dropped in at 10° C. (inner temperature) during 2 hours. The mixture was stirred 3.5 hours more at room temperature. After the reaction, the reaction solution was poured over into ice water, the mixture was made weakly acidic with concentrated hydrochloric acid, and the chloroform layer was collected. This was washed with water, dried and concentrated and the residue was purified by a column chromatography (n-hexane/silica gel) to give 558.6 g of 3,4-difluorophenyl isothiocyanate in colorless oil.
Reaction SMILES: [C:1]([O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)(=[O:21])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]([O-:20])=[O:19].C1COCC1.CCN(C(C)C)C(C)C.[B-](F)(F)(F)F.CN(C(O[N:57]1[C:62](=[O:63])[CH2:61][CH2:60][C:58]1=[O:59])=[N+](C)C)C>CN(C=O)C>[C:18]([O:20][N:57]1[C:62](=[O:63])[CH2:61][CH2:60][C:58]1=[O:59])(=[O:19])[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][C:1]([O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:21]
Reactant: O=C([O-])CCCCCCCCCCCCCCCCC(=O)OCc1ccccc1
Reactant: CN(C)C(ON1C(=O)CCC1=O)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: O=C(CCCCCCCCCCCCCCCCC(=O)ON1C(=O)CCC1=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 100 %

Procedure:
Mono-benzyl octadecandioate was dissolved in DMF (3.5 mL) and THF (7 mL) and cooled with ice bath. DIEA (0.103 mL) and TSTU were added and the mixture was stirred 1 h at ice bath and at RT overnight. The solvent was evaporated in vacuo and the residue was dissolved in AcOEt and washed twice with 0.2 N HCl, saturated NaHCO3, dried, filtered and evaporated to dryness to give succinimidyl mono-benzyl octadecandioate (0.25 g, 100%).
Reaction SMILES: [CH3:1][NH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.CCCCCC.[Li+].CCC[CH2-].[CH2:20](Br)[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37].Cl>O>[CH3:1][N:2]([CH2:37][CH2:36][CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH3:20])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: CNc1ccccc1
Reactant: CCCCCCCCCCCCCCCCCCBr
Agent: Cl
Agent: [CH2-]CCC
Agent: [Li+]
Solvent: O
Solvent: CCCCCC
Product: CCCCCCCCCCCCCCCCCCN(C)c1ccccc1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
Add 23.6 g (0.22 mol) N-methylaniline into 92 g (0.2 mol) 14% hexane solution of N-butyllithium and stir it for 10-20 minutes. Drop 33.3 g (0.1 mol) octadecylbromide into the above solution, while stirring it. Add 200 ml water into the solution, after heating and refluxing the solution for about 17 hours and cooling it down to room temperature. Add 6N hydrochloric acid to the solution after concentrating the solution extracted by 300 ml diethyl ether and deposit it. 32.3 g (0.09 mol) N, N-methyloctadecylaniline is obtained by refinement through crystalization with ethyl alcohol and water. Dissolve the obtained 32.3 g (0.09 mol) N, N-methyloctadecylaniline into 250 ml concentrated sulfuric acid. Add 30 ml concentrated nitric acid into the solution while stirring it in an ice water bath. Leave it about one hour after adding the nitric acid. Add the solution into ice water filter off the deposit from it, and refine it by crystalization with ethyl alcohol and water. With the above step, 14.5 g (0.036 mol) N, N-octadecylmethyl-o-nitroaniline is obtained. Add 100 ml 2N hydrochloric acid into this 14.5 g (0.036 mol) N, N-octadecylmethyl-o-nitroaniline which is dissolved into 200 ml ethyl alcohol. 11.7 g (0.031 mol) N, N-octadecylmethyl-o-phenylene-diamine is obtained after adding 11.75 (0.18 mol) zinc dust into the above solution to be heated and refluxed for one hour.
Reaction SMILES: C(Cl)(Cl)Cl.[OH:5][CH2:6][CH2:7][N:8]([CH:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1)[C:9]([CH2:11][CH2:12][CH2:13][O:14][C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][CH:24]=1)[NH:21][C:20](=[O:25])[CH:19]=[CH:18]2)=[O:10].C(N(CC)CC)C.[C:39](Cl)(=[O:46])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>C(Cl)(Cl)Cl.CO>[C:39]([O:5][CH2:6][CH2:7][N:8]([CH:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1)[C:9]([CH2:11][CH2:12][CH2:13][O:14][C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][CH:24]=1)[NH:21][C:20](=[O:25])[CH:19]=[CH:18]2)=[O:10])(=[O:46])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1
Reactant: O=C(CCCOc1ccc2[nH]c(=O)ccc2c1)N(CCO)C1CCCCC1
Reactant: O=C(Cl)c1ccccc1
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Solvent: CO
Product: O=C(OCCN(C(=O)CCCOc1ccc2[nH]c(=O)ccc2c1)C1CCCCC1)c1ccccc1

Procedure:
Into 100 ml of chloroform were added 3.7 g of 6-{3-[N-(2-hydroxyethyl)-N-cyclohexylaminocarbonyl]propoxy}carbostyril and 1.8 ml of triethylamine and the outside of the reaction vessel containing said mixture was ice-cooled. Then 1.4 ml of benzoyl chloride was added dropwise to the mixture under stirring condition. After the addition operation the reaction mixture was further stirred at room temperature for 1 hour. Then the reaction mixture was washed with 5% NaHCO3 aqueous solution, diluted hydrochloric acid and water in this order, then dried with anhydrous sodium sulfate. The drying agent was removed by filtration and the mother liquor is concentrated. The residue thus obtained is treated by a silica-gel column chromatography [the solvent used was a mixture of chloroform:methanol 30:1 (v/v)] and the elute was recrystallized from chloroform-petroleum ether to obtain 3.0 g of 6-{3-[N-(2-benzoyloxyethyl)-N-cyclohexylaminocarbonyl]propoxy}carbostyril as in the form of colorless needle-like crystals. Melting point: 94°-96° C.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]([CH:11]=[CH:12][C:13]=1[OH:14])[C:7]([O:9][CH3:10])=[O:8])(=[O:3])[CH3:2].[CH2:15]([O:22][C:23]1[CH:32]=[CH:31][CH:30]=[CH:29][C:24]=1[C:25](OC)=[O:26])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[H-].[Na+]>O1CCOCC1>[OH:14][C:13]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:5][C:4]=1[C:1]([CH2:2][C:25](=[O:26])[C:24]1[CH:29]=[CH:30][CH:31]=[CH:32][C:23]=1[O:22][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:3]
Reactant: COC(=O)c1ccc(O)c(C(C)=O)c1
Reactant: COC(=O)c1ccccc1OCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: C1COCCO1
Product: COC(=O)c1ccc(O)c(C(=O)CC(=O)c2ccccc2OCc2ccccc2)c1
Reaction time: 5 h
Yield: 65.8 %

Procedure:
A solution of methyl 3-acetyl-4-hydroxy-benzoate (54 g) and methyl 2-benzyloxy-benzoate (135 g) in dioxane (400 ml) was slowly added under stirring at room temperature to a suspension of sodium hydride 50% (40 g) in dioxane (150 ml). The mixture was kept for 5 hours at 70° C., then cooled and diluted with petroleum ether, and subsequently filtered. The collected precipitate was dissolved in water, acidified with acetic acid and extracted with ethylacetate. The organic phase was washed with potassium carbonate 5% and water, then evaporated to dryness. After crystallisation from methanol, (2-hydroxy-5-carbomethoxy-benzoyl)--(2-benzyloxy-benzoyl)-methane (74 g; m.p. 95°-97° C.) was obtained, which was then refluxed for 24 hours with formic acid 99% (500 ml). After cooling and dilution with ethanol (500 ml), the precipitate obtained was filtered and washed with ethanol to give 6-carbomethoxy-2'-hydroxy-flavone (31 g; m.p. 290°-291° C.) which was then reacted in dimethylformamide (150 ml) with 1-chloro-2-benzoyloxy-propane (26 g) and potassium carbonate (18 g) at 70° C. for 16 hours. The mixture was cooled, diluted in water (600 ml), filtered, then washed with water to obtain 6-carbomethoxy-2'-(2-benzoyloxy-propoxy)-flavone (45 g), which was hydrolysed with a solution of potassium hydroxide 1% (1. 1,250) in ethanol (95%) at reflux temperature for an hour. After cooling, acidification with acetic acid, concentration to small volume under vacuum and dilution in water, the precipitate obtained was filtered, then washed with water to give, after crystallisation with methylene chloride/ethylacetate, 6-carboxy-2'-(2-hydroxy-propoxy)-flavone (18.5; m.p. 211°-213° C.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([CH2:7][NH:8][C:9]2[CH:28]=[CH:27][CH:26]=[CH:25][C:10]=2[C:11]([NH:13][O:14][CH2:15][C:16]2[CH:17]=[C:18]([CH:22]=[CH:23][CH:24]=2)[C:19](O)=[O:20])=[O:12])=[CH:3][CH:2]=1.[CH3:29][N:30]([CH3:34])[CH2:31][CH2:32][NH2:33]>>[CH3:29][N:30]([CH3:34])[CH2:31][CH2:32][NH:33][C:19]([C:18]1[CH:17]=[C:16]([CH:24]=[CH:23][CH:22]=1)[CH2:15][O:14][NH:13][C:11](=[O:12])[C:10]1[CH:25]=[CH:26][CH:27]=[CH:28][C:9]=1[NH:8][CH2:7][C:4]1[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=1)=[O:20]
Reactant: CN(C)CCN
Reactant: O=C(O)c1cccc(CONC(=O)c2ccccc2NCc2ccncc2)c1
Product: CN(C)CCNC(=O)c1cccc(CONC(=O)c2ccccc2NCc2ccncc2)c1

Procedure:
Prepared by a similar procedure as described for preparation of Example 405. Starting materials: 3-{2-[(Pyridin-4-ylmethyl)-amino]-benzoylaminooxymethyl}-benzoic acid (see Example 403) and 2-dimethylaminoethylamine. 13C-NMR (DMSO-d6) δ 165.8, 149.5, 148.9, 148.2, 136.1, 134.6, 132.4, 131.4, 128.2, 128.0, 127.7, 126.8, 121.9, 114.8, 113.3, 111.4, 76.5, 58.1, 45.2, 44.8, 37.3.
Reaction SMILES: [NH2-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([CH2:11][C:12]#[N:13])[CH:7]=[CH:8][C:9]=1[Cl:10].Cl[CH2:15][CH2:16][CH2:17][N:18]([CH3:20])[CH3:19].O>CCOCC>[Cl:3][C:4]1[CH:5]=[C:6]([CH:11]([CH2:15][CH2:16][CH2:17][N:18]([CH3:20])[CH3:19])[C:12]#[N:13])[CH:7]=[CH:8][C:9]=1[Cl:10]
Reactant: N#CCc1ccc(Cl)c(Cl)c1
Reactant: CN(C)CCCCl
Agent: [NH2-]
Agent: [Na+]
Solvent: O
Solvent: CCOCC
Product: CN(C)CCCC(C#N)c1ccc(Cl)c(Cl)c1
Yield: 63 %

Procedure:
3.9 g of sodium amide are added in small portions to a solution of 18.6 g of 3,4-dichlorophenylacetonitrile in 200 ml of anhydrous ether. The mixture is refluxed for 2 hours, 12.1 g of 3-chlorodimethylaminopropane are added and refluxing is continued for 2 and a half hours. The mixture is cooled, water is added and the organic phase is decanted. It is washed with water and extracted with 10% hydrochloric acid. The aqueous phase is then neutralized with 30% sodium hydroxide and extracted with ether and the solvent is evaporated off to give 17 g of the expected product.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=2[F:16])[CH:5]=[CH:4][C:3]=1[C:17]([C:19]1[CH:24]=[C:23]([C:25]#[C:26][Si](C)(C)C)[CH:22]=[CH:21][C:20]=1[CH3:31])=[O:18].C([O-])([O-])=O.[K+].[K+].CCOC(C)=O.O>CO>[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=2[F:16])[CH:5]=[CH:4][C:3]=1[C:17]([C:19]1[CH:24]=[C:23]([C:25]#[CH:26])[CH:22]=[CH:21][C:20]=1[CH3:31])=[O:18]
Reactant: Cc1ccc(C#C[Si](C)(C)C)cc1C(=O)c1ccc(Nc2ccc(F)cc2F)cc1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CO
Solvent: O
Product: C#Cc1ccc(C)c(C(=O)c2ccc(Nc3ccc(F)cc3F)cc2Cl)c1

Procedure:
A solution of compound 406 (426 mg, 0.94 mmol) and K2CO3 (195 mg, 1.41 mmol) in methanol (4.0 mL) were stirred at RT for 5 h. The reaction mixture was poured into a mixture of EtOAc/water. The organic phase was washed with water, brine and then dried (MgSO4), filtered and concentrated in vacuo to give the crude title compound. The product was used without any further purification.
Reaction SMILES: [CH:1]1([CH:6]([C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=2)[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:5][CH2:4][CH2:3][CH2:2]1.N(C(C)(C)C#N)=NC(C)(C)C#N.[Br:33]N1C(=O)CCC1=O>ClC(Cl)(Cl)Cl>[Br:33][CH2:20][C:17]1[CH:18]=[CH:19][C:14]([CH:6]([CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)[C:7]([O:9][C:10]([CH3:12])([CH3:11])[CH3:13])=[O:8])=[CH:15][CH:16]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1ccc(C(C(=O)OC(C)(C)C)C2CCCC2)cc1
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: ClC(Cl)(Cl)Cl
Product: CC(C)(C)OC(=O)C(c1ccc(CBr)cc1)C1CCCC1
Temperature: 0 °C

Procedure:
27.4 g (0.1 mol) of the compound from Example XXI are dissolved in 200 ml of tetrachloromethane and the solution is heated to boiling. After addition of 0.82 g of azobisisobutyronitrile, 18.7 g (0.105 mol) of N-bromosuccinimide are added in portions and the mixture is then refluxed for 1 h, cooled to 0° C. and succinimide is filtered off. After concentrating the filtrate the product precipitates. It is washed With petroleum ether (40/60) and dried.
Reaction SMILES: [C:1]([OH:4])(=[O:3])[CH3:2].C([C:7]1[N:8]=[C:9]([CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[S:10][CH:11]=1)C.[OH-].[K+].Cl>C(O)C.C(OCC)(=O)C>[CH2:12]([C:9]1[S:10][CH:11]=[C:7]([CH2:2][C:1]([OH:4])=[O:3])[N:8]=1)[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24]
Reactant: CCCCCCCCCCCCCc1nc(CC)cs1
Reactant: CC(=O)O
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CCO
Product: CCCCCCCCCCCCCc1nc(CC(=O)O)cs1

Procedure:
Ethyl-2-tridecyl-thiazole acetate (2.13 g, 6.35 mmol) and potassium hydroxide (0.39 g, 6.98 mmol) were refluxed overnight in ethanol (200 mL). The mixture was then acidified with 1M HCl and the precipitate filtered to give a solid which was dissolved in ethyl acetate and washed with brine, dried (MgSO4), filtered concentrated, and triturated with hexanes. The solid was filtered and air dried to yield 0.75 g, 37%. %C,H,N(found): C, 66.16; H, 9.50; N 3.99.