Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2](=[CH2:12])[CH2:3][O:4]CC1C=CC=CC=1.[CH3:13][O:14][C:15]1[CH:16]=[C:17]([CH:28]=[CH:29][C:30]=1B1OC(C)(C)C(C)(C)O1)[C:18]([O:20]CC1C=CC=CC=1)=[O:19]>CN(C=O)C.Cl[Pd](Cl)([P+](C1CCCCC1)(C1CCCCC1)C1C=CC=CC=1)[P+](C(C)(C)C)(C(C)(C)C)C(C)(C)C.[Pd]>[OH:4][CH2:3][CH:2]([C:30]1[CH:29]=[CH:28][C:17]([C:18]([OH:20])=[O:19])=[CH:16][C:15]=1[O:14][CH3:13])[CH3:12]
Reactant: COc1cc(C(=O)OCc2ccccc2)ccc1B1OC(C)(C)C(C)(C)O1
Reactant: C=C(Br)COCc1ccccc1
Agent: CC(C)(C)[P+](C(C)(C)C)(C(C)(C)C)[Pd](Cl)(Cl)[P+](c1ccccc1)(C1CCCCC1)C1CCCCC1
Agent: [Pd]
Solvent: CN(C)C=O
Product: COc1cc(C(=O)O)ccc1C(C)CO
Temperature: 90 °C
Reaction time: 8 h

Procedure:
Dichloro-[dicyclohexyl(phenyl)phosphaniumyl]-tritert-butylphosphaniumyl-palladium (981 mg, 0.150 mmol) and 2-bromoallyloxymethylbenzene (341 mg, 1.50 mmol) were dissolved in DMF (1 mL). A solution of benzyl 3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (1.11 g, 3.00 mmol) in DMF (3 mL) was added the mixture was heated at 90° C. for 3 h. The mixture was then filtered through Celite using ethyl acetate. The filtrate was then washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue from step 1 was taken up in isopropanol (2 mL) and was added to 10% Pd/C (160 mg, 0.150 mmol). The vessel was purged with nitrogen and a balloon of hydrogen was added and the reaction mixture was allowed to stir overnight. The reaction mixture was filtered through Celite and the filtrate was concentrated. The residue was partitioned between aqueous 2M Na2CO3 and ethyl acetate. The layers were separated and the organic phase was discarded. To the aqueous phase was added 1M HCl until the solution was pH 3. The solution was then extracted with EtOAc (3×) and the combined organic layers were dried over sodium sulfate, filtered, and concentrated to provide 4-(1-hydroxypropan-2-yl)-3-methoxybenzoic acid. ESI-MS m/z calc 210.1, found 211.1 (M+1)+. Retention time: 1.19 minutes (3 min run).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([O:11][CH3:12])=[O:10])=[CH:4][C:3]=1[Br:13].[Br:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[N:21]=[C:22]=[O:23]>C1COCC1>[Br:13][C:3]1[CH:4]=[C:5]([CH2:8][C:9]([O:11][CH3:12])=[O:10])[CH:6]=[CH:7][C:2]=1[NH:1][C:22]([NH:21][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=1[Br:14])=[O:23]
Reactant: COC(=O)Cc1ccc(N)c(Br)c1
Reactant: O=C=Nc1ccccc1Br
Solvent: C1CCOC1
Product: COC(=O)Cc1ccc(NC(=O)Nc2ccccc2Br)c(Br)c1
Reaction time: 4 h
Yield: 72.6 %

Procedure:
To a mixture of methyl 4-amino-3-bromophenylacetate (587 mg, 2.40 mmol) and 2-bromophenyl isocyanate (0.30 ml, 2.40 mmol) in THF (2 ml) was added Et3 N (33 ml, 0.24 mmol) at room temperature. After 4 h stirring, the reaction mixture was concentrated in vacuo. The residue was triturated by the addition of n-hexane to give methyl 3-bromo-4-[N′-(2-bromophenyl)ureido]phenylacetate (770 mg, 73%) as a pale brown powder. 1H-NMR (CDCl3) δ 3.55 (s, 2H), 3.70 (s, 3H), 6.97 (dd, J=7.3, 1.5 Hz, 1H), 7.22 (dd, J=8.5, 2.2 Hz, 1H), 7.29–7.33 (m, 2H), 7.48 (d, J=1.0, 2.2 Hz, 1H), 7.54 (dd, J=8.0, 1.2 Hz, 1H), 8.01 (m, 2H); MS (ESI) m/z 443 (M++1), 445 (M++3), 447 (M++5).
Reaction SMILES: [CH2:1]([N:5]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[S:22](=[O:29])(=[O:28])[NH:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:12][CH:11]=1)[C:6](Cl)=[O:7])[CH2:2][CH2:3][CH3:4].C(N(CC)C(C)C)(C)C.[NH:39]1[C:48]2[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=2)[CH2:42][CH2:41][CH2:40]1>C1(C)C=CC=CC=1>[CH2:1]([N:5]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[S:22](=[O:29])(=[O:28])[NH:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:12][CH:11]=1)[C:6]([N:39]1[C:48]2[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=2)[CH2:42][CH2:41][CH2:40]1)=[O:7])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCN(Cc1ccc(-c2ccccc2S(=O)(=O)NC(C)(C)C)cc1)C(=O)Cl
Reactant: c1ccc2c(c1)CCCN2
Solvent: Cc1ccccc1
Solvent: CCN(C(C)C)C(C)C
Product: CCCCN(Cc1ccc(-c2ccccc2S(=O)(=O)NC(C)(C)C)cc1)C(=O)N1CCCc2ccccc21

Procedure:
The title compound was prepared from N-butyl-N-[[2'-(N-t-butylsulfamoyl)biphenyl-4-yl]methyl]carbamoyl chloride (from Example 4, Step A), N,N-diisopropylethylamine, and 1,2,3,4-tetrahydroquinoline in toluene, according to the procedure of Example 4, Step A, to give 93% yield of the desired material after flash chromatography as a foam, homogeneous by TLC in 4:1 hexane-EtOAc; FAB-MS m/e 534 (M+1)+.
Reaction SMILES: [CH3:1][Si:2]([CH3:18])([CH3:17])[N:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]([Si:13]([CH3:16])([CH3:15])[CH3:14])[CH:5]=[CH:4]1.[C:19](#[N:22])[CH:20]=[CH2:21]>>[CH3:1][Si:2]([CH3:18])([CH3:17])[N:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([Si:13]([CH3:16])([CH3:15])[CH3:14])=[CH:5][CH:4]1[CH:20]([C:19]#[N:22])[CH3:21]
Reactant: C[Si](C)(C)C1C=CN([Si](C)(C)C)c2ccccc21
Reactant: C=CC#N
Product: CC(C#N)C1C=C([Si](C)(C)C)c2ccccc2N1[Si](C)(C)C
Temperature: 100 °C
Yield: 73.6 %

Procedure:
A mixture consisting of 27.5 g (0.1 mol) of 1,4-bis-(trimethylsilyl)-1,4-dihydroquinoline and 6 g (0.1 mol) of acrylonitrile is heated in an inert atmosphere at 100°C for 150 hours. Fractional distillation yields 24.2 g (72%) of 1,4-bis-(trimethylsilyl)-2-(1-cyanoethyl)-1,2-dihydroquinoline: yellow-green oil, b.p. 106°-108°C/0.001 mm.
Reaction SMILES: [N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][C:2]=1[S:10]([CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[N:21]([CH2:23][CH3:24])[CH2:20][CH:19]([C:25]([O:27]CC)=[O:26])[CH2:18]2)=[O:11].[OH-].[Na+]>CO>[N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][C:2]=1[S:10]([CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[N:21]([CH2:23][CH3:24])[CH2:20][CH:19]([C:25]([OH:27])=[O:26])[CH2:18]2)=[O:11]
Reactant: CCOC(=O)C1Cc2cccc(CS(=O)c3nc4ccccc4[nH]3)c2N(CC)C1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CCN1CC(C(=O)O)Cc2cccc(CS(=O)c3nc4ccccc4[nH]3)c21
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 8-(2-benzimidazolyl)sulfinylmethyl-1-ethyl-3-ethoxycarbonyl-1,2,3,4-tetrahydroquinoline(0.4 g) in methanol (80 ml) was added sodium hydroxide (0.2 g) and the mixture was stirred for 2 hours at room temperature and furthermore refluxed for 3 hours. The solvent was distilled off under reduced pressure The resulting residue was dissolved in water, and the solution was adjusted to acidic with acetic acid. The precipitate was collected by filtration and recrystallized from methanol to give 8-(2-benzimidazolyl)sulfinylmethyl-1-ethyl-1,2,3,4-tetrahydroquinoline-3-carboxylic acid.1/2 hydrate (0.2 g).
Reaction SMILES: Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:3]=1[CH3:12].CC1C=CC2C(=CC=CC=2)C=1B(O)[OH:25].B(O)O.OO>>[CH3:12][C:3]1[CH:4]=[CH:5][C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:2]=1[OH:25]
Reactant: Cc1ccc2ccccc2c1Br
Reactant: Cc1ccc2ccccc2c1B(O)O
Agent: OBO
Agent: OO
Product: Cc1ccc2ccccc2c1O
Yield: 51 %

Procedure:
Yarboro, T. L.; Karr, C.; J. Org. Chem. 1959, 24, 1141 disclose a process wherein 1-bromo-2-methyl naphthalene is convened into 2-methyl-1-naphthalene boronic acid via Grignard reaction. The boronic acid is oxidized by 30% hydrogen peroxide to produce 2-methyl-1-naphthol in 51% yield. This prior art process is disadvantageous in that it involves 4 steps and is not economical.
Reaction SMILES: [CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][C:8]([N+:12]([O-])=O)=[CH:9][CH:10]=2)[CH:5]=[C:4]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[F:21])[CH3:2]>[Pd].C(O)C>[CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][C:8]([NH2:12])=[CH:9][CH:10]=2)[CH:5]=[C:4]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[F:21])[CH3:2]
Reactant: CCn1c(-c2ccccc2F)cc2cc([N+](=O)[O-])ccc21
Agent: [Pd]
Solvent: CCO
Product: CCn1c(-c2ccccc2F)cc2cc(N)ccc21
Reaction time: 4 h
Yield: 114.4 %

Procedure:
To a suspension containing 1-ethyl-2-(2-fluorophenyl)-5-nitro-1H-indole (0.78 g; 2.75 mmol) in 95° ethanol (100 ml) was added 10% Pd/C (0.1 g; 0.1 mmol) and the mixture underwent hydrogenation in a Parr hydrogenator (30 psi) for 4 hours. The mixture was filtered and the solution was evaporated under reduced pressure to give 1-ethyl-2-(2-fluorophenyl)-1H-indol-5-amine (0.8 g), which was used without any further purification.
Reaction SMILES: [CH2:1]([C:4]1[CH:5](O)[C:6](=[O:9])[O:7][CH:8]=1)[CH2:2][CH3:3].C(OCC)(=[O:13])C>[Pd]>[OH:13][C:8]1[O:7][C:6](=[O:9])[CH2:5][C:4]=1[CH2:1][CH2:2][CH3:3]
Reactant: CCOC(C)=O
Reactant: CCCC1=COC(=O)C1O
Agent: [Pd]
Product: CCCC1=C(O)OC(=O)C1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
5-hydroxy-4-propyl-5H-furan-2-one 373 (15 g, 0.1 mol), ethyl acetate (260 ml) and Pd/C 5% are placed in a Parr apparatus. The mixture is degassed, and hydrogen is introduced at a pressure of 35 psi. This mixture is then stirred vigorously at 25° C. for 2 h. After filtration on celite, the solvent is removed under reduced pressure at 50° C. to give the 5-hydroxy-4-propyl-furan-2-one as a crude product (100% yield). LC/MS: 145 (MH+).
Reaction SMILES: [Sn](Cl)Cl.[N:4]12[CH2:11][CH2:10][CH:7]([CH2:8][CH2:9]1)[C@@H:6]([NH:12][C:13]([C:15]1[O:16][C:17]3[C:23]([N+:24]([O-])=O)=[CH:22][CH:21]=[CH:20][C:18]=3[CH:19]=1)=[O:14])[CH2:5]2>CN(C=O)C>[N:4]12[CH2:9][CH2:8][CH:7]([CH2:10][CH2:11]1)[C@@H:6]([NH:12][C:13]([C:15]1[O:16][C:17]3[C:23]([NH2:24])=[CH:22][CH:21]=[CH:20][C:18]=3[CH:19]=1)=[O:14])[CH2:5]2
Reactant: O=C(N[C@H]1CN2CCC1CC2)c1cc2cccc([N+](=O)[O-])c2o1
Agent: Cl[Sn]Cl
Solvent: CN(C)C=O
Product: Nc1cccc2cc(C(=O)N[C@H]3CN4CCC3CC4)oc12
Reaction time: 8 h

Procedure:
6.0 ml (12 mmol) of a 2 M tin(II) chloride solution in DMF are added to N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-nitro-1-benzofuran-2-carboxamide (1340 mg, 4.25 mmol). The mixture is stirred overnight. The solvent is removed under reduced pressure using a rotary evaporator. The crude product is taken up in methanol and, together with acidic ion exchange resin (Dowex WX2-200), shaken for about 1 h. The loaded ion exchanger is washed with methanol, then with water, again with methanol, with DMF, again with methanol, with THF, again with methanol, with dichloromethane and finally once more with methanol. The product is eluted with methanol/triethylamine 95:5. The solvent is removed under reduced pressure using a rotary evaporator. 1200 mg (98% of theory) of the title compound are obtained.
Reaction SMILES: [Na+].[Na+].[NH2:3][C:4]1[CH:5]=[C:6]([S:22]([OH:25])(=[O:24])=[O:23])[CH:7]=[C:8]2[C:13]=1[C:12]([S:14]([O-:17])(=[O:16])=[O:15])=[CH:11][C:10]([S:18]([O-:21])(=[O:20])=[O:19])=[CH:9]2.[OH-].[Na+]>O>[NH2:3][C:4]1[CH:5]=[C:6]([S:22]([OH:25])(=[O:24])=[O:23])[CH:7]=[C:8]2[C:13]=1[C:12]([S:14]([OH:17])(=[O:16])=[O:15])=[CH:11][C:10]([S:18]([OH:21])(=[O:19])=[O:20])=[CH:9]2
Reactant: Nc1cc(S(=O)(=O)O)cc2cc(S(=O)(=O)[O-])cc(S(=O)(=O)[O-])c12
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: Nc1cc(S(=O)(=O)O)cc2cc(S(=O)(=O)O)cc(S(=O)(=O)O)c12
Temperature: 25 °C
Yield: 100.1 %

Procedure:
A solution of 51.2 g of 8-amino-1,3,6-naphthalenetrisulfonic acid disodium salt in 120 ml of water containing 21.0 ml of 5N sodium hydroxide was warmed and filtered. The filtrate was slowly diluted with 400 ml of ethanol, stirred and allowed to cool to room temperature. The solid was collected, washed with ethanol, then ether and dried, giving 46.0 g of 8-amino-1,3,6-naphthalenetrisulfonic acid, trisodium salt.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([CH2:24][CH3:25])[C:13]3[C:18]([C:19]=2[C:20]#[N:21])=[CH:17][CH:16]=[C:15]([O:22][CH3:23])[CH:14]=3)=[CH:7][CH:6]=1.CCN(CC)CC.[C:33](Cl)(=[O:35])[CH3:34]>C1COCC1>[C:20]([C:19]1[C:18]2[C:13](=[CH:14][C:15]([O:22][CH3:23])=[CH:16][CH:17]=2)[N:12]([CH2:24][CH3:25])[C:11]=1[C:8]1[CH:9]=[CH:10][C:5]([O:4][CH2:3][CH2:2][NH:1][C:33](=[O:35])[CH3:34])=[CH:6][CH:7]=1)#[N:21]
Reactant: CCn1c(-c2ccc(OCCN)cc2)c(C#N)c2ccc(OC)cc21
Reactant: CC(=O)Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CCn1c(-c2ccc(OCCNC(C)=O)cc2)c(C#N)c2ccc(OC)cc21
Temperature: 25 °C
Reaction time: 2 h
Yield: 97.1 %

Procedure:
2-[4-(2-Aminoethoxy)phenyl]-1-ethyl-6-methoxy-1H-indole-3-carbonitrile (30 mg, 0.09 mmol), prepared as in example 1BB, step B, is dissolved in THF (400 μL), and Et3N (24 μL, 0.17 mmol). Acetyl chloride (10 μL, 0.14 mmol) is added, and the reaction mixture is stirred at room temperature for 2 h. The reaction mixture is partitioned between EtOAc and H2O. The organic layer is dried and concentrated. Purification by silica gel chromatography (EtOAc) yields N-{2-[4-(3-cyano-1-ethyl-6-methoxy-1H-indol-2-yl)phenoxy]ethyl}acetamide (33 mg, 97%) as a white solid.
Reaction SMILES: [CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:25])[CH2:15][CH2:16][C:17]1[CH:22]=[C:21]([F:23])[CH:20]=[C:19]([F:24])[CH:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B(OS(C(F)(F)F)(=O)=O)(CCCC)CCCC.CCN(C(C)C)C(C)C.[C:52]([O:56][C:57]([N:59]1[C@@H:68]([C:69](O)=[O:70])[CH2:67][C:66]2[C:61](=[CH:62][CH:63]=[CH:64][CH:65]=2)[CH2:60]1)=[O:58])([CH3:55])([CH3:54])[CH3:53]>C(Cl)Cl.CO>[F:24][C:19]1[CH:18]=[C:17]([CH:22]=[C:21]([F:23])[CH:20]=1)[CH2:16][C@H:15]([C:14]([N:9]1[C@@H:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:12][O:11][C:10]1=[O:13])=[O:25])[C@@H:69]([C@H:68]1[CH2:67][C:66]2[C:61](=[CH:62][CH:63]=[CH:64][CH:65]=2)[CH2:60][N:59]1[C:57]([O:56][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:58])[OH:70]
Reactant: O=C(CCc1cc(F)cc(F)c1)N1C(=O)OC[C@@H]1Cc1ccccc1
Reactant: CC(C)(C)OC(=O)N1Cc2ccccc2C[C@@H]1C(=O)O
Agent: CCCCB(CCCC)OS(=O)(=O)C(F)(F)F
Solvent: CO
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)N1Cc2ccccc2C[C@@H]1[C@@H](O)[C@H](Cc1cc(F)cc(F)c1)C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1
Temperature: -78 °C
Reaction time: 0.33 h
Yield: 77.8 %

Procedure:
To a solution of (S)-4-benzyl-3-(3-(3,5-difluorophenyl)propanoyl)oxazolidin-2-one (preparation D, 1.3 g, 3.77 mmol) in CH2Cl2 (50 mL) at −78° C. was added Bu2BOTf (4.90 ml, 4.90 mmol, 1M in CH2Cl2) and Hunig's base (972 mg, 7.54 mmol). The resulting mixture was brought up to 0° C. and stirred for 20 min. The mixture was cooled back to −78° C. and a solution of (R)-tert-butyl 3-formyl-3,4-dihydroisoquinoline-2(1H)-carboxylate (Step A (3), 1.10 g, 4.20 mmol) in CH2Cl2 (50 mL) was added dropwise. When the addition was complete, the mixture was allowed to warm to rt. After stirring at rt for 1 h, MeOH was added and the mixture was concentrated in vacuo. The crude mixture was purified by silica gel Flash chromatography to give 1.78 g (78% yield) of the title compound. MS (ESI)(M+H)+ 607.20.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.C([Li])CCC.[O:13]1[CH2:18][CH2:17][C:16](=[O:19])[CH2:15][CH2:14]1>C1COCC1>[OH:19][C:16]1([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=2)[CH2:17][CH2:18][O:13][CH2:14][CH2:15]1
Reactant: O=C1CCOCC1
Reactant: Brc1ccccn1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: OC1(c2ccccn2)CCOCC1
Temperature: -78 °C
Reaction time: 0.17 h
Yield: 61.2 %

Procedure:
To a stirred, cooled solution of 2-bromopyridine (5 g, 31.65 mmol) in THF (75 mL) at −78° C. was added n-butyl lithium (2.5 M in hexanes, 12.66 mL, 31.65 mmol) dropwise and the solution stirred at −78° C. for 10 minutes. After this time, tetrahydro-4H-pyran-4-one (3.49 g, 34.81 mmol) was added, the reaction warmed to ambient temperature and stirred overnight. The reaction was then quenched with saturated aqueous ammonium chloride solution and the THF removed in vacuo. The resultant aqueous phase was twice extracted with ethyl acetate and the combined organic phases dried (magnesium sulfate) and filtered. After concentration in vacuo, purification by column chromatography (SiO2, eluting with 2:1 hexanes:ethyl acetate) gave a residue which was triturated from hexane to yield the title compound (3.47 g, 61%) as a white solid; NMR δH (400 MHz, CDCl3) 8.49 (1H, m), 7.81 (1H, td, J 7.8 Hz, 1.8 Hz), 7.68 (1H, m), 7.25 (1H, ddd, J 7.5 Hz, 4.9 Hz, 1.1 Hz), 3.85 (4H, m), 3.30 (1H, m), 2.30 (2H, td, J 13.3 Hz, 5.3 Hz), 1.54 (1H, dd, J 13.8 Hz, 1.9 Hz); LC-MS Retention time 0.51 min, (M+H)+ 180.
Reaction SMILES: C[O:2][C:3](=[O:26])[CH2:4][CH2:5][CH2:6][C:7]#[C:8][CH2:9][C:10]#[C:11][CH2:12][C:13]#[C:14][CH2:15][C:16]#[C:17][CH2:18][O:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.O1CCCCC1OC1CCCCO1.C(O)(=O)C(O)=O>C(OCC)(=O)C>[O:19]([CH2:18][C:17]#[C:16][CH2:15][C:14]#[C:13][CH2:12][C:11]#[C:10][CH2:9][C:8]#[C:7][CH2:6][CH2:5][CH2:4][C:3]([OH:26])=[O:2])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: COC(=O)CCCC#CCC#CCC#CCC#CCOc1ccccc1
Agent: C1CCC(OC2CCCCO2)OC1
Agent: O=C(O)C(=O)O
Solvent: CCOC(C)=O
Product: O=C(O)CCCC#CCC#CCC#CCC#CCOc1ccccc1

Procedure:
540 mg of 16-phenoxyhexadeca-5,8,11,14-tetraynoic acid methyl ester weretreated with 64 ml of a pH 6.7 buffer solution (disodium hydrogen phosphate-potassium dihydrogen phosphate) obtained as described in Example1. The emulsion was vigorously stirred and 6.17 g of Sigma Lipase, Type VII, from Candida cylindracea was added, stirring for 8 hours at room temperature. The reaction mixture was then transferred to a separatory funnel with ethyl acetate (100 ml), and then acidified with saturated solution of oxalic acid. The organic phase was separated, dried over sodium sulfate and the solvent removed under vacuo. The residue was purified by TLC on silica gel with a Chromatotron using hexane:ethyl acetate:acetic acid (60:40:1) as the eluant. The crude product was crystallized from benzene-hexane, to yield 16-phenoxyhexadeca-5,8,11,14-tetraynoic acid. M.P. 74°-76° C. (dec.). The product was stored in dry ice.
Reaction SMILES: [I-].C[S+](C)(C)=O.[H-].[Na+].O1CCC[CH2:10]1.[Cl:14][CH:15]([F:34])[C:16]([F:33])([F:32])[O:17][C:18]1[CH:23]=[CH:22][C:21]([CH:24]=[CH:25][C:26]([C:28]2([Cl:31])[CH2:30][CH2:29]2)=[O:27])=[CH:20][CH:19]=1>CS(C)=O>[Cl:31][C:28]1([C:26]2([CH:25]=[CH:24][C:21]3[CH:22]=[CH:23][C:18]([O:17][C:16]([F:32])([F:33])[CH:15]([Cl:14])[F:34])=[CH:19][CH:20]=3)[CH2:10][O:27]2)[CH2:29][CH2:30]1
Reactant: C1CCOC1
Reactant: O=C(C=Cc1ccc(OC(F)(F)C(F)Cl)cc1)C1(Cl)CC1
Agent: C[S+](C)(C)=O
Agent: [H-]
Agent: [I-]
Solvent: CS(C)=O
Product: FC(Cl)C(F)(F)Oc1ccc(C=CC2(C3(Cl)CC3)CO2)cc1
Temperature: 0 °C
Yield: 89 %

Procedure:
A solution of 6.35 g (0.031 mole) of trimethylsulphoxonium iodide in 20 ml of dimethyl sulphoxide is added at -15° C. with stirring to a suspension of 0.75 g (0.031 mole) of sodium hydride in 25 ml of a mixture of dimethyl sulphoxide: tetrahydrofuran =3:2. After warming the reaction mixture to 0° C., a solution of 9.6 g (0.028 mole) of 1-chloro-cyclopropyl 4-(2-chloro-1,1,2-trifluoroethoxy)-phenyl-ethenyl ketone in 15 ml of dimethyl sulphoxide is added dropwise with stirring. The mixture is subsequently stirred at 0° C. for 15 minutes and at room temperature for 45 minutes. The reaction mixture is then poured into 100 ml of ice water and the mixture is extracted three times with cyclohexane. The combined organic phases are washed once with water, dried over sodium sulphate and then concentrated under reduced pressure. 8.89 g (89% of theory) of 2-(1-chloro-cyclopropyl)-2-[4-(2-chloro-1,1,2-trifluoroethoxy)-phenylethenyl]-oxirane are obtained in this way in the form of an oily product which is reacted further without additional purification. ##STR38##
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH2:10][OH:11])[CH:8]=2)[CH:3]=[CH:2]1.[CH3:12]I>CN(C)C=O>[CH3:12][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH2:10][OH:11])[CH:8]=2)[CH:3]=[CH:2]1
Reactant: CI
Reactant: OCc1ccc2cc[nH]c2c1
Solvent: CN(C)C=O
Product: Cn1ccc2ccc(CO)cc21
Temperature: 0 °C
Reaction time: 1 h
Yield: 75 %

Procedure:
NaH(8.2mm) in N,N-dimethylformamide ("DMF") (20 mL) was cooled to 0° C., then treated with a solution of the known 1H-indole-6-methanol (1 g,6.8 mm) in DMF(8 mL). After stirring for 1 hour at 0° C., methyl iodide ("MeI") (0.51 mL, 8.2 mm) dissolved in DMF (2 mL) was added, and the mixture was stirred at 0° C. overnight, then poured into ice/H2O (250 ml) and extracted with EtOAc(50 mL×3). The organic fraction was dried over MgSO4, filtered, evaporated and purified by flash column chromatography to afford 1-methyl-1H-indole-6-methanol (0.82 g. 75%). This product (1-methyl-1H-indole-6-methanol, 1 g, 6.2 mm) was dissolved in a mixture of pyridine (5 mL) and acetic anhydride (Ac2O) (5 mL) and stirred at room temperature overnight. The solvent was evaporated, and the residue purified by flash column chromatography to afford 1.09 g of Acetic acid 1-methyl-1H-indol-6-yl methyl ester.
Reaction SMILES: C(OC([N:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:11]([C:18]2[CH:23]=[CH:22][C:21]([N:24]3[CH2:29][CH2:28][N:27]([CH2:30][CH:31]([CH3:33])[CH3:32])[CH2:26][CH2:25]3)=[CH:20][N:19]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl.O1CCOCC1.[OH-].[Na+]>ClCCl>[CH2:30]([N:27]1[CH2:28][CH2:29][N:24]([C:21]2[CH:22]=[CH:23][C:18]([N:11]3[C:12]4[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=4)[NH:8][CH2:9][CH2:10]3)=[N:19][CH:20]=2)[CH2:25][CH2:26]1)[CH:31]([CH3:33])[CH3:32]
Reactant: CC(C)CN1CCN(c2ccc(N3CCN(C(=O)OC(C)(C)C)c4ccccc43)nc2)CC1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: ClCCl
Product: CC(C)CN1CCN(c2ccc(N3CCNc4ccccc43)nc2)CC1
Temperature: 25 °C
Reaction time: 18 h
Yield: 89.3 %

Procedure:
4-[5-(4-Isobutylpiperazin-1-yl)pyridin-2-yl]-3,4-dihydro-2H-quinoxaline-1-carboxylic acid tert-butyl ester (0.39 g, 0.86 mmol) is placed in 1.7 ml of dichloromethane and then 4N HCl in dioxane (3.24 ml, 12.95 mmol) is added. The reaction medium is stirred at ambient temperature for 18 h. After hydrolysis with a 1N aqueous sodium hydroxide solution up to a pH of 10, extraction is carried out with dichloromethane. The organic phase is washed with a saturated aqueous sodium chloride solution and then dried over MgSO4 and concentrated to dryness. The crude product obtained is chromatographed on silica gel, elution being carried out with a gradient of methanol in dichloromethane varying from 0% to 10%. 0.27 g of 1-[5-(4-isobutylpiperazin-1-yl)pyridin-2-yl]-1,2,3,4-tetrahydroquinoxaline is obtained.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]2[C:9]([C:22]3[CH:23]=[C:24]([NH:28][S:29]([C:32]4[CH:37]=[C:36]([F:38])[CH:35]=[CH:34][C:33]=4[F:39])(=[O:31])=[O:30])[CH:25]=[CH:26][CH:27]=3)=[N:10][N:11](CC3C=CC(OC)=CC=3)[CH:12]=2)[CH:5]=[CH:4][N:3]=1.C(OCC)C>FC(F)(F)C(O)=O>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[C:9]([C:22]3[CH:23]=[C:24]([NH:28][S:29]([C:32]4[CH:37]=[C:36]([F:38])[CH:35]=[CH:34][C:33]=4[F:39])(=[O:30])=[O:31])[CH:25]=[CH:26][CH:27]=3)=[N:10][NH:11][CH:12]=2)[CH:5]=[CH:4][N:3]=1
Reactant: COc1ccc(Cn2cc(-c3ccnc(N)n3)c(-c3cccc(NS(=O)(=O)c4cc(F)ccc4F)c3)n2)cc1
Solvent: CCOCC
Solvent: O=C(O)C(F)(F)F
Product: Nc1nccc(-c2c[nH]nc2-c2cccc(NS(=O)(=O)c3cc(F)ccc3F)c2)n1
Temperature: 70 °C
Reaction time: 2 h
Yield: 16.7 %

Procedure:
80 mg (0.14 mmol) of N-{3-[4-(2-aminopyrimidin-4-yl)-1-(4-methoxybenzyl)-1H-pyrazol-3-yl]phenyl}-2,5-difluorobenzenesulfonamide were dissolved in 5 ml of trifluoroacetic acid and the resulting solution was heated at 70° C. under stirring for 2 hours. The solvent was removed in vacuo and the residue taken up with dichloromethane and washed with aqueous sodium hydrogenocarbonate. The organic phase was then dried over sodium sulphate and evaporated, giving, after trituration with diethylether, 10 mg (17%) of the title compound.