Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:41][CH3:42])=[C:6]([CH:40]=1)[CH2:7][C@H:8]1[C:14](=[O:15])[N:13]([C:16]([O:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[Cl:25])=[O:17])[CH2:12][C:11](=[O:26])[N:10](CC2C(OC)=CC(OC)=CC=2OC)[CH2:9]1.C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:41][CH3:42])=[C:6]([CH:40]=1)[CH2:7][C@H:8]1[C:14](=[O:15])[N:13]([C:16]([O:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[Cl:25])=[O:17])[CH2:12][C:11](=[O:26])[NH:10][CH2:9]1
Reactant: COc1cc(OC)c(CN2C[C@@H](Cc3cc(Cl)ccc3OC)C(=O)N(C(=O)Oc3ccccc3Cl)CC2=O)c(OC)c1
Solvent: Cc1ccccc1
Solvent: COc1ccccc1
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc(Cl)cc1C[C@@H]1CNC(=O)CN(C(=O)Oc2ccccc2Cl)C1=O
Temperature: 25 °C
Reaction time: 4.5 h
Yield: 56.1 %

Procedure:
To the compound S141C described in WO 06-059801A, that is, (6R)-2-chlorophenyl 6-(5-chloro-2-methoxybenzyl)-3,7-dioxo-4-(2,4,6-trimethoxybenzyl)-1,4-diazepan-1-carboxylate (996 mg), anisole (1.75 ml) and trifluoroacetic acid (10 ml) were added, and the mixture was stirred at room temperature for 4.5 hours. The reaction solution was diluted with toluene and concentrated in vacuo. This operation was repeated two times and excessive anisole was distilled off under reduced pressure of a vacuum pump. To the residue, ethyl acetate was added. The precipitated solid was collected by filtration to obtain the title compound (396 mg). Furthermore, the filtrate was concentrated, and the residue was purified by flash column chromatography (silica gel, hexane/ethyl acetate=2/1 to 1/3) to obtain the title compound (198 mg).
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10](Cl)(=[O:12])=[O:11])=[CH:6][CH:5]=1)([CH3:3])[CH3:2].[NH2:14][C:15]1[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=1[C:22]([C:24]1[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=1)=[O:23]>>[Br:21][C:18]1[CH:19]=[CH:20][C:15]([NH:14][S:10]([C:7]2[CH:8]=[CH:9][C:4]([CH:1]([CH3:3])[CH3:2])=[CH:5][CH:6]=2)(=[O:12])=[O:11])=[C:16]([C:22]([C:24]2[CH:25]=[CH:26][N:27]=[CH:28][CH:29]=2)=[O:23])[CH:17]=1
Reactant: CC(C)c1ccc(S(=O)(=O)Cl)cc1
Reactant: Nc1ccc(Br)cc1C(=O)c1ccncc1
Product: CC(C)c1ccc(S(=O)(=O)Nc2ccc(Br)cc2C(=O)c2ccncc2)cc1

Procedure:
The title compound was prepared according the general procedure for the synthesis of N-aryl-benzenesulfonamides using 4-isopropyl-benzenesulfonyl chloride and (2-amino-5-bromo-phenyl)-pyridin-4-yl-methanone and purified by HPLC. MS: m/z 460 (M++1).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([S:8][C:9]2[C:17]3[C:12](=[CH:13][C:14]([Cl:18])=[CH:15][CH:16]=3)[NH:11][C:10]=2[CH3:19])[CH:5]=[CH:6][CH:7]=1.Br[C:21]1[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=1>>[Br:1][C:2]1[CH:3]=[C:4]([S:8][C:9]2[C:17]3[C:12](=[CH:13][C:14]([Cl:18])=[CH:15][CH:16]=3)[N:11]([C:21]3[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=3)[C:10]=2[CH3:19])[CH:5]=[CH:6][CH:7]=1
Reactant: Cc1[nH]c2cc(Cl)ccc2c1Sc1cccc(Br)c1
Reactant: Brc1cccnc1
Product: Cc1c(Sc2cccc(Br)c2)c2ccc(Cl)cc2n1-c1cccnc1

Procedure:
Prepared according to the procedure described in Example 27, Step 1, using the following starting materials: 3-(3-bromo-phenylsulfanyl)-6-chloro-2-methyl-1H-indole and 3-bromopyridine.
Reaction SMILES: [CH2:1]([N:6]([CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])[C:7]([N:9]1[CH2:14][CH2:13][N:12]([C:15](=[O:29])[N:16]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@H:11]([C:30](O)=[O:31])[CH2:10]1)=[O:8])[CH2:2][CH2:3][CH2:4][CH3:5].B>C1COCC1>[CH2:33]([N:6]([CH2:1][CH2:2][CH2:3][CH2:4][CH3:5])[C:7]([N:9]1[CH2:14][CH2:13][N:12]([C:15](=[O:29])[N:16]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@H:11]([CH2:30][OH:31])[CH2:10]1)=[O:8])[CH2:34][CH2:35][CH2:36][CH3:37]
Reactant: CCCCCN(CCCCC)C(=O)N1CCN(C(=O)N(c2ccccc2)c2ccccc2)[C@H](C(=O)O)C1
Agent: B
Solvent: C1CCOC1
Product: CCCCCN(CCCCC)C(=O)N1CCN(C(=O)N(c2ccccc2)c2ccccc2)[C@H](CO)C1
Temperature: 0 °C
Reaction time: 24 h
Yield: 97.8 %

Procedure:
1.24 g (2.44 mmole) of (S)-4-(dipentylcarbamoyl)-1-(diphenylcarbamoyl)piperazine-2-carboxylic acid dissolved in 6 ml of THF was cooled to 0° C. in an ice bath. To this 9 ml (9 mmole) of 1.0M borane solution in THF was slowly added during a 15 min. period. The resulting mixture was stirred for 24 hr at 25°. The excess hydride was destroyed carefully with 20 ml of a 1:1 mixture of THF and water. The aqueous phase was saturated with anhydrous potassium carbonate. The THF layer was separated and aqueous layer was extracted with ether. The combined organic phase was dried over magnesium sulfate. The solvents were removed on a rotary evaporator to yield 1.18 g (98%) of (S)-4-(dipentylcarbamoyl)-1-(diphenylcarbamoyl)-2-(hydroxymethyl)piperazine as a white solid, mp 133°-134°.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][NH:10][C:11](=[O:13])[CH3:12])=[CH:5][CH:4]=1.[CH3:14][N:15]([CH3:30])[C:16]1[CH:21]=[C:20]([O:22][CH3:23])[N:19]=[C:18]([N:24]2[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)[N:17]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[CH3:30][N:15]([CH3:14])[C:16]1[CH:21]=[C:20]([O:22][CH3:23])[N:19]=[C:18]([N:24]2[CH2:25][CH2:26][N:27]([CH2:2][C:3]3[CH:8]=[CH:7][C:6]([CH2:9][NH:10][C:11](=[O:13])[CH3:12])=[CH:5][CH:4]=3)[CH2:28][CH2:29]2)[N:17]=1
Reactant: COc1cc(N(C)C)nc(N2CCNCC2)n1
Reactant: CC(=O)NCc1ccc(CCl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1cc(N(C)C)nc(N2CCN(Cc3ccc(CNC(C)=O)cc3)CC2)n1
Yield: 104.7 %

Procedure:
A solution of N-(4-chloromethylphenylmethyl)acetamide (0.9 g), 1-(4-dimethylamino-6-methoxypyrimidin-2-yl)piperazine (1.1 g) and potassium carbonate (1.0 g) in dimethylformamide (10 ml) was stirred at 80° C. for 8.5 hr. The reaction mixture was poured into water (100 ml) and extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated to give a brown oil (1.9 g). The obtained brown oil was purified by silica gel column chromatography (developing solvent; chloroform:methanol=9:1) to give a yellow oil (1.6 g). The obtained yellow oil was crystallized from ethyl acetate/hexane (1:1, 20 ml) to give the title compound (1.0 g) as pale-yellow crystals.
Reaction SMILES: [CH2:1]([NH:3][C:4]([C:6]1[CH:11]=[CH:10][C:9]([N:12]2[C:16]([CH2:17][CH2:18][CH2:19][CH2:20][F:21])=[C:15]([C:22]([OH:24])=O)[N:14]=[N:13]2)=[CH:8][CH:7]=1)=[O:5])[CH3:2].C1C=C[C:28]2N(O)N=[N:31][C:29]=2[CH:30]=1.C1(N)CC1.CCN=C=NCCCN(C)C>C(#N)C.CN(C=O)C.C(=O)([O-])[O-].[Na+].[Na+].O>[CH:29]1([NH:31][C:22]([C:15]2[N:14]=[N:13][N:12]([C:9]3[CH:8]=[CH:7][C:6]([C:4]([NH:3][CH2:1][CH3:2])=[O:5])=[CH:11][CH:10]=3)[C:16]=2[CH2:17][CH2:18][CH2:19][CH2:20][F:21])=[O:24])[CH2:30][CH2:28]1
Reactant: On1nnc2ccccc21
Reactant: CCNC(=O)c1ccc(-n2nnc(C(=O)O)c2CCCCF)cc1
Agent: CCN=C=NCCCN(C)C
Agent: NC1CC1
Agent: O=C([O-])[O-]
Solvent: CN(C)C=O
Solvent: O
Solvent: CC#N
Product: CCNC(=O)c1ccc(-n2nnc(C(=O)NC3CC3)c2CCCCF)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 176.1 %

Procedure:
1-{4-[(Ethylamino)carbonyl]phenyl}-5-(4-fluorobutyl)-1H-1,2,3-triazole-4-carboxylic acid (375 mg, 1.12 mmol) obtained in Example 108b), HOBt (76.5 mg, 0.561 mmol, 0.5 eq.) and cyclopropylamine (0.104 ml, 1.46 mmol, 1.3 eq.) were dissolved in acetonitrile-DMF (2:1, 4.5 ml), WSC (263 mg, 1.35 mmol, 1.2 eq.) was added, and the mixture was stirred at room temperature for 4 hr. The reaction mixture was diluted with 2% aqueous sodium carbonate solution (5 ml) and water (10 ml), and the mixture was stirred at room temperature. The precipitate was collected by filtration, washed with water and dried to give the title compound as a white powder (369 mg, 0.988 mmol, 88.2%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6]([C:8](=[O:10])[CH3:9])[CH:7]=1.CO[CH:14](OC)[N:15]([CH3:17])[CH3:16]>CC(O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6]([C:8](=[O:10])/[CH:9]=[CH:14]/[N:15]([CH3:17])[CH3:16])[CH:7]=1
Reactant: CC(=O)c1cc(Cl)ccc1O
Reactant: COC(OC)N(C)C
Solvent: CC(C)O
Product: CN(C)/C=C/C(=O)c1cc(Cl)ccc1O
Temperature: 45 °C
Reaction time: 18 h
Yield: 93.8 %

Procedure:
1-(5-chloro-2-hydroxyphenyl)ethanone, (165 g, 0.967 mol) was slurried in 2-propanol (1000 mL) then 1,1-dimethoxy-N,N-dimethylmethanamine (258.28 mL, 1.93 mol) was added and the resulting yellow solution was stirred at 45° C. for 18 hours. The resulting suspension was cooled to room temperature and stirred for a further 48 hours. The solid was filtered off, washed with 2-propanol (2×200 mL) and then tert-butylmethyl ether (200 mL) then dried to give the title compound as a bright yellow solid, (204.59 g).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([CH3:13])[CH2:9][SiH:10]([Cl:12])[Cl:11]>C(O)(C)C.[H+].[H+].Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl>[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([CH3:13])[CH2:9][Si:10]([CH:6]([Si:10]([Cl:12])([Cl:11])[CH2:9][CH:8]([C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[CH3:1])[CH3:13])[CH2:7][CH2:2][CH2:3][CH2:4][CH3:5])([Cl:12])[Cl:11]
Reactant: Cc1ccccc1C(C)C[SiH](Cl)Cl
Agent: Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl
Agent: [H+]
Solvent: CC(C)O
Product: CCCCCC([Si](Cl)(Cl)CC(C)c1ccccc1C)[Si](Cl)(Cl)CC(C)c1ccccc1C
Yield: 93.4 %

Procedure:
In the same apparatus and procedures as EXAMPLE 1, 20.8 g (0.089 mole) 3-(methylphenyl)-1,1-dichloro-1-silabutane and 90 μl of 1% chloroplatinic acid solution in isopropanol were placed and then 3.0 g (0.036 mole) of 1, 5-hexadiene was added dropwise for 3 min. The solution was reacted for 13 hours at reflux under the dry nitrogen atmosphere. Vacuum distillation gave 15.2 g (189°-191° C./0.03 mmHg) of bis[{2-(methylphenyl)propyl}dichlorosilyl]hexane in 77.2% yield.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[C:6]([Br:8])[CH:7]=1.[C:10]1(B(O)O)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(=O)([O-])[O-].[K+].[K+].Cl>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.O.C1(C)C=CC=CC=1>[Br:8][C:6]1[CH:5]=[C:4]([OH:9])[CH:3]=[C:2]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:7]=1
Reactant: OB(O)c1ccccc1
Reactant: Oc1cc(Br)cc(Br)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: Cc1ccccc1
Solvent: O
Product: Oc1cc(Br)cc(-c2ccccc2)c1
Temperature: 90 °C

Procedure:
Toluene (400 mL) and water (20 mL) were added to a mixture of 3-,5-dibromophenol (5.088 g, 19.85 mmol), phenylboronic acid (2.42 g, 19.85 mmol) and potassium carbonate (5.48 g, 39.7 mmol) in a round bottom flask. This was followed by addition of 1.149 g of tetrakis(triphenylphosphine)palladium(0) under a atmosphere of nitrogen. This mixture was stirred at heated overnight at 90° C. At this time, HCl (2 N aq) was added to the reaction mixture until pH=˜2 and the subsequent two phases were separated; the aqueous phase was extracted and washed three time with ethyl acetate. The combined organic phases were dried with MgSO4, filtered and washed with ethyl acetate. The filtrate was concentrated in vacuo to provide an orange oil. Analysis of the oil by LC/MS indicated a mixture of desired product, starting material and the bis-phenyl coupling product The mixture was carried on to the next aryl boronic acid coupling step 2.
Reaction SMILES: C[O:2][C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[C@@H:14]([O:15][CH2:16][C:17]3[CH:18]=[CH:19][C:20]4[O:25][CH2:24][CH2:23][N:22]([CH2:26][CH2:27][CH2:28][O:29][CH3:30])[C:21]=4[CH:31]=3)[CH2:13][N:12]([S:32]([C:35]3[CH:40]=[CH:39][C:38]([CH3:41])=[CH:37][CH:36]=3)(=[O:34])=[O:33])[C@H:11]([CH2:42][C:43]([CH3:48])([CH3:47])[C:44]([OH:46])=[O:45])[CH2:10]2)=[CH:5][CH:4]=1.C([S-])C.[Na+]>CN(C)C=O.Cl>[OH:2][C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[C@@H:14]([O:15][CH2:16][C:17]3[CH:18]=[CH:19][C:20]4[O:25][CH2:24][CH2:23][N:22]([CH2:26][CH2:27][CH2:28][O:29][CH3:30])[C:21]=4[CH:31]=3)[CH2:13][N:12]([S:32]([C:35]3[CH:36]=[CH:37][C:38]([CH3:41])=[CH:39][CH:40]=3)(=[O:34])=[O:33])[C@H:11]([CH2:42][C:43]([CH3:48])([CH3:47])[C:44]([OH:46])=[O:45])[CH2:10]2)=[CH:5][CH:4]=1
Reactant: COCCCN1CCOc2ccc(CO[C@H]3CN(S(=O)(=O)c4ccc(C)cc4)[C@H](CC(C)(C)C(=O)O)C[C@@H]3c3ccc(OC)cc3)cc21
Agent: CC[S-]
Agent: Cl
Agent: [Na+]
Solvent: CN(C)C=O
Product: COCCCN1CCOc2ccc(CO[C@H]3CN(S(=O)(=O)c4ccc(C)cc4)[C@H](CC(C)(C)C(=O)O)C[C@@H]3c3ccc(O)cc3)cc21
Temperature: 95 °C

Procedure:
To a stirred solution of 1.1 g of 3-[(2S,4R,5R)-4-(4-methoxy-phenyl)-5-[4-(3-methoxy-propyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]-1-(toluene-4-sulfonyl)-piperidin-2-yl]-2,2-dimethyl-propionic acid (from example 65b) in 10 ml N,N-dimethylformamide are added 1.35 g of sodium ethanethiolate and the reaction mixture is heated to 95° C. for 2 days. The reaction mixture is diluted with 1N hydrochloric acid solution and extracted with tert-butyl methyl ether. The organic phases are combined, dried and concentrated under reduced pressure to afford the crude title compound. The residue is purified by flash chromatography (SiO2 60 F) to afford the title compound as a colourless oil. Rf=0.10 (EtOAc-heptane 1:1); Rt=4.67.
Reaction SMILES: C([O:5][C:6]([C:8]1[S:12][C:11]([N:13]2[CH2:18][CH2:17][N:16]([S:19]([C:22]3[CH:27]=[CH:26][C:25]([O:28][C:29]([F:32])([F:31])[F:30])=[CH:24][CH:23]=3)(=[O:21])=[O:20])[C@@H:15]([C:33](=[O:45])[NH:34][CH2:35][C:36]3[CH:37]=[N:38][C:39]([CH:42]([CH3:44])[CH3:43])=[CH:40][CH:41]=3)[CH2:14]2)=[N:10][C:9]=1[CH3:46])=[O:7])(C)(C)C>FC(F)(F)C(O)=O>[CH:42]([C:39]1[N:38]=[CH:37][C:36]([CH2:35][NH:34][C:33]([C@@H:15]2[N:16]([S:19]([C:22]3[CH:23]=[CH:24][C:25]([O:28][C:29]([F:32])([F:30])[F:31])=[CH:26][CH:27]=3)(=[O:21])=[O:20])[CH2:17][CH2:18][N:13]([C:11]3[S:12][C:8]([C:6]([OH:7])=[O:5])=[C:9]([CH3:46])[N:10]=3)[CH2:14]2)=[O:45])=[CH:41][CH:40]=1)([CH3:44])[CH3:43]
Reactant: Cc1nc(N2CCN(S(=O)(=O)c3ccc(OC(F)(F)F)cc3)[C@@H](C(=O)NCc3ccc(C(C)C)nc3)C2)sc1C(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Product: Cc1nc(N2CCN(S(=O)(=O)c3ccc(OC(F)(F)F)cc3)[C@@H](C(=O)NCc3ccc(C(C)C)nc3)C2)sc1C(=O)O
Yield: 85.2 %

Procedure:
A solution of the compound (55 mg) obtained in Step 7 in trifluoroacetic acid (330 μl) was stirred at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure, chloroform was added to the residue, and the mixture was concentrated again under reduced pressure. The residue was purified by thin layer chromatography (methanol:chloroform=1:10) to give the title compound (43 mg).
Reaction SMILES: [CH3:1][C:2]1[CH:8]=[C:7]([OH:9])[C:6]([CH3:10])=[C:5]([CH3:11])[C:3]=1[OH:4].[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([CH:19](O)[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25]([OH:27])=[O:26])=[CH:15][CH:14]=1>B(F)(F)F.CCOCC.C1(C)C=CC=CC=1>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([CH:19]([C:8]2[C:7](=[O:9])[C:6]([CH3:10])=[C:5]([CH3:11])[C:3](=[O:4])[C:2]=2[CH3:1])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25]([OH:27])=[O:26])=[CH:15][CH:14]=1
Reactant: O=C(O)CCCCCC(O)c1ccc(Cl)cc1
Reactant: Cc1cc(O)c(C)c(C)c1O
Agent: FB(F)F
Solvent: Cc1ccccc1
Solvent: CCOCC
Product: CC1=C(C)C(=O)C(C(CCCCCC(=O)O)c2ccc(Cl)cc2)=C(C)C1=O
Temperature: 60 °C
Yield: 78.2 %

Procedure:
Toluene (15 ml) was added to 0.76 g (5.0 mmole) of 2,5,6-trimethylhydroquinone and 1.28 g (5.0 mmole) of 7-(4-chlorophenyl)-7-hydroxyheptanoic acid, and the mixture was warmed at 60° C. and stirred. 0.19 ml (5.0×0.3 mmole) of boron trifluoride ethyl etherate was added to the mixture, followed by stirring at 60° C. for 15 hours. After the conclusion of the reaction, a large amount of the toluene was distilled off, and the residue was dissolved in tetrahydrofuran (20 ml). An aqueous solution (10 ml) of ferric chloride (2.7 g, 10.0 mmole was added to the solution, followed by stirring at room temperature for 20 minutes. The tetrahydrofuran was distilled off, and ethyl acetate was added to the residue to extract the reaction product. The organic layer was separated out, washed with aqueous sodium chloride solution and dried (magnesium sulfate). The ethyl acetate solution was chromatographed on a short silica gel (10 g) column, and elution was performed with ethyl acetate. The fractions containing the object compound were collected and concentrated under reduced pressure, and the residue was recrystallized from ethyl acetate/isopropyl ether to give 1.52 g (78%) of 7-(4-chlorophenyl)-7-(3,5,6-trimethyl-1,4-benzoquinon-2-yl)heptanoic acid.
Reaction SMILES: [CH2:1]([C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:15][CH3:16])=[C:10]([O:13][CH3:14])[CH:11]=2)[CH:6]=[C:5]([OH:17])[N:4]=1)[CH3:2].Cl.Cl[CH2:20][C:21]1[CH:22]=[N:23][C:24]2[C:29]([CH:30]=1)=[CH:28][C:27]([O:31][CH3:32])=[CH:26][CH:25]=2.[Li+].[OH-]>C1COCC1>[CH2:1]([C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:15][CH3:16])=[C:10]([O:13][CH3:14])[CH:11]=2)[C:6]([CH2:20][C:21]2[CH:22]=[N:23][C:24]3[C:29]([CH:30]=2)=[CH:28][C:27]([O:31][CH3:32])=[CH:26][CH:25]=3)=[C:5]([OH:17])[N:4]=1)[CH3:2]
Reactant: COc1ccc2ncc(CCl)cc2c1
Reactant: CCc1nc(O)cc2cc(OC)c(OC)cc12
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Product: CCc1nc(O)c(Cc2cnc3ccc(OC)cc3c2)c2cc(OC)c(OC)cc12
Temperature: 25 °C

Procedure:
To a solution of 1-ethyl-6,7-dimethoxyisoquinolin-3-ol SLA 28136 (288 mg, 1.18 mmol) in THF (13 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added 3-(chloromethyl)-6-methoxyquinoline hydrochloride SLA 47088B (275 mg, 1.18 mmol) and a 2 N aq. LiOH solution (1.20 mL, 2.40 mmol) and the mixture was stirred at 160° C. for 1.5 h under microwave irradiation. After cooling to RT, THF was then removed at 40° C. under vacuum and the solution was extracted with CH2Cl2 (50 mL), washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated under vacuum. Purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 94:6) followed by a new purification by column chromatography (RP 18, eluent CH3CN:H2O=100:0 to 34:66) gave 1-ethyl-6,7-dimethoxy-4-((6-methoxyquinolin-3-yl)methyl)isoquinolin-3-ol. This free base was dissolved in MeOH (2 mL) in a 10 mL round-bottomed flask equipped with a magnetic stirrer before addition of a 0.149 M HCl solution in MeOH (3.0 mL). The reaction mixture was stirred for 5 min at RT and concentrated at 40° C. under vacuum to afford 1-ethyl-6,7-dimethoxy-4-((6-methoxyquinolin-3-yl)methyl)isoquinolin-3-ol dihydrochloride 85 as a brown solid (46.5 mg, 8% yield).
Reaction SMILES: [N+:1]([C:4]1[CH:10]=[C:9]([S:11]([C:14]([F:17])([F:16])[F:15])(=[O:13])=[O:12])[CH:8]=[CH:7][C:5]=1[NH2:6])([O-:3])=[O:2].[Cl:18]Cl>C(O)(=O)C>[N+:1]([C:4]1[CH:10]=[C:9]([S:11]([C:14]([F:17])([F:15])[F:16])(=[O:13])=[O:12])[CH:8]=[C:7]([Cl:18])[C:5]=1[NH2:6])([O-:3])=[O:2]
Reactant: Nc1ccc(S(=O)(=O)C(F)(F)F)cc1[N+](=O)[O-]
Reactant: ClCl
Solvent: CC(=O)O
Product: Nc1c(Cl)cc(S(=O)(=O)C(F)(F)F)cc1[N+](=O)[O-]
Yield: 95.3 %

Procedure:
In analogy to Example 14, 27 g of 2-nitro-4-trifluoromethylsulphonyl-aniline in 100 ml of acetic acid were chlorinated with 10 g of chlorine. 29 g of 2-nitro-4-trifluoromethylsulphonyl-6-chloro-aniline resulted; melting point 138°-139° C.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:18][CH2:19][CH2:20][CH3:21])=[C:6]([C:8]2[N:16]=[C:15]3[C:11](=[N:12][N:13]=[N:14]3)[C:10](=[O:17])[N:9]=2)[CH:7]=1.C(O[C:25]1[CH2:29][CH2:28][CH2:27][C:26]=1[C:30]([O:32][CH2:33][CH3:34])=[O:31])C.S1(CCCC1)(=O)=O>Cl>[CH2:33]([O:32][C:30]([C:26]1[CH2:27][CH2:28][CH2:29][C:25]=1[NH:1][C:2]1[CH:3]=[CH:4][C:5]([O:18][CH2:19][CH2:20][CH3:21])=[C:6]([C:8]2[N:16]=[C:15]3[C:11](=[N:12][N:13]=[N:14]3)[C:10](=[O:17])[N:9]=2)[CH:7]=1)=[O:31])[CH3:34]
Reactant: CCCOc1ccc(N)cc1C1=NC(=O)C2=NN=NC2=N1
Reactant: CCOC(=O)C1=C(OCC)CCC1
Agent: Cl
Solvent: O=S1(=O)CCCC1
Product: CCCOc1ccc(NC2=C(C(=O)OCC)CCC2)cc1C1=NC(=O)C2=NN=NC2=N1
Yield: 28.3 %

Procedure:
A stirred mixture of 2-(5-amino-2-propoxyphenyl)-8-azapurin-6-one (2.02 g), ethyl 2-ethoxy-1-cyclopentenecarboxylate (1.43 g) and dry sulpholane (20 ml) was heated at 125°-130° C. for 2 hours. The solution was then cooled and poured into dilute hydrochloric acid (200 ml; 2 N) and the yellow solid obtained was filtered off and recrystallised from a mixture of petroleum ether (b.p. 60°-80° C.) and ethyl acetate to give 2-[5-(2-ethoxycarbonylcyclopent-1-enylamino)-2-propoxyphenyl]-8-azapurin-6-one (0.85 g), m.p. 164°-165° C.
Reaction SMILES: [C:1]([OH:12])(=[O:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[CH2:13](O)[C:14]1[CH:22]=[CH:21][C:19]([OH:20])=[C:16]([O:17][CH3:18])[CH:15]=1.O>CCCCCC>[C:1]([O:12][CH2:13][C:14]1[CH:22]=[CH:21][C:19]([OH:20])=[C:16]([O:17][CH3:18])[CH:15]=1)(=[O:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: COc1cc(CO)ccc1O
Reactant: CCCCCCCCCC(=O)O
Solvent: O
Solvent: CCCCCC
Product: CCCCCCCCCC(=O)OCc1ccc(O)c(OC)c1
Temperature: 50 °C
Reaction time: 48 h
Yield: 100.5 %

Procedure:
Decanoic acid (25.0 g, 145 mmol), vanillyl alcohol (21.7 g, 141 mmol), and Novozym 435 (723 mg) were measured and placed in a flask (25 ml). The mixture in the flask free of a plug was heated with stirring in an oil bath at 50° C. for 48 hours. After 2 to 3 hours of stirring with heating, attachment of water on the wall of the upper part of the flask was observed. The flask was returned to room temperature, hexane (100 ml) was added to the reaction mixture, and the mixture was stirred for 1 hour. The immobilized enzyme and a small amount of precipitated vanillyl alcohol were removed by filtration. Hexane (100 ml) and 10% aqueous citric acid solution (200 ml) was added to the filtrate to allow partitioning. The aqueous layer was further extracted with hexane (150 ml), and the combined hexane layer was washed with 10% aqueous citric acid solution (100 ml), water (100 ml) and saturated brine (100 ml). The hexane layer was dried over anhydrous magnesium sulfate. Magnesium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure to give the mixture (43.7 g) of vanillyl decanoate and decanoic acid. As a result of the analysis, the yield of vanillyl decanoate was 97.0% and the purity was 98.6 area % by HPLC. The mixture contained 3.94 wt % of decanoic acid relative to vanillyl decanoate.
Reaction SMILES: [CH3:1][C:2](/[CH:9]=[CH:10]/[C:11]1[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=1)=[CH:3][C:4](OCC)=[O:5].[H-].C([Al+]CC(C)C)C(C)C.C1(C)C=CC=CC=1>C1(C)C=CC=CC=1>[CH3:1]/[C:2](/[CH:9]=[CH:10]/[C:11]1[CH:12]=[CH:13][C:14]([C:17]([F:18])([F:19])[F:20])=[CH:15][CH:16]=1)=[CH:3]\[CH2:4][OH:5]
Reactant: CCOC(=O)C=C(C)/C=C/c1ccc(C(F)(F)F)cc1
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: Cc1ccccc1
Product: CC(/C=C/c1ccc(C(F)(F)F)cc1)=C\CO
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 70.1 %

Procedure:
After a solution in which 150 mg (0.53 mmol) of ethyl (4E)-3-methyl-5-[4-(trifluoromethyl)phenyl]-2,4-pentadienoate ((2E)/(2Z)=5/1) as described in Reference example 8 were dissolved in 2 ml of toluene was stirred at 0° C., 0.7 ml (1.06 mmol) of a 1.5M diisobutyl aluminum hydride-toluene solution were added to the solution. After 20 minutes, ice-water was added to the reaction mixture and the mixture was stirred for 10 minutes. The insolubles were removed by filtration using Celite and the filtrate was extracted with ethyl acetate and dried, followed by evaporation of the solvent to obtain an oil. The oil was subjected to column chromatography using 5 g of silica gel and eluted with a mixed solvent of 30 to 40% ethyl acetate-hexane to obtain 90 mg of the title compound as an oil.