Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: COC(=O)[CH2:4][N:5]([S:29]([C:32]1[CH:37]=[CH:36][C:35]([O:38]CC2C=CC=CC=2)=[CH:34][CH:33]=1)(=[O:31])=[O:30])[CH:6]([C:20]12[O:27][CH2:26][C:23]([CH3:28])([CH2:24][O:25]1)[CH2:22][O:21]2)[CH:7]([NH:9][C:10]([O:12]CC1C=CC=CC=1)=O)[CH3:8].C(N(CC)CC)C.[H][H]>C(O)C.[Pd]>[OH:38][C:35]1[CH:34]=[CH:33][C:32]([S:29]([N:5]2[CH:6]([C:20]34[O:27][CH2:26][C:23]([CH3:28])([CH2:22][O:21]3)[CH2:24][O:25]4)[CH:7]([CH3:8])[NH:9][C:10](=[O:12])[CH2:4]2)(=[O:31])=[O:30])=[CH:37][CH:36]=1
Reactant: COC(=O)CN(C(C(C)NC(=O)OCc1ccccc1)C12OCC(C)(CO1)CO2)S(=O)(=O)c1ccc(OCc2ccccc2)cc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCN(CC)CC
Solvent: CCO
Product: CC1NC(=O)CN(S(=O)(=O)c2ccc(O)cc2)C1C12OCC(C)(CO1)CO2
Yield: 75.3 %

Procedure:
A solution of {(4-benzyloxy-benzenesulfonyl)-[2-benzyloxycarbonylamino-1-(4-methyl-2,6,7-trioxa-bicyclo[2.2.2]oct-1-yl)-propyl]-amino}-acetic acid methyl ester (compound of formula LIII, 1.3 g, 2.0 mmol) in 75 ml of ethanol was treated with triethylamine (0.28 ml, 0.20 g, 2.0 mmol) and 0.2 g of 10% palladium on carbon. After stirring for about 2 hours under 1 atmosphere of hydrogen, the mixture was filtered through a pad of Celite® and concentrated in vacuo. The residue was dissolved in 10 ml of toluene, diluted with 3 ml of methanol and was refluxed for about 1.5 hours. Concentration of the mixture in vacuo afforded 0.6 g of 4-(4-hydroxy-benzenesulfonyl)-6-methyl-5-(4-methyl-2,6,7-trioxa-bicyclo[2.2.2]oct-1-yl)-piperazin-2-one (compound of formula LIV). A compound of the formula LI can be converted to a compound of the formula LIII by the method of Step 42 that, in turn, can be converted to a compound of Formula I according to the procedure of Step 43.
Reaction SMILES: [CH2:1]([C:5]([CH2:11][CH2:12][CH2:13][CH3:14])([CH2:8][O:9][CH3:10])[CH2:6][OH:7])[CH2:2][CH2:3][CH3:4].[CH2:15]([Si:17](Cl)([CH2:20][CH3:21])[CH2:18][CH3:19])[CH3:16]>>[CH2:1]([C:5]([CH2:11][CH2:12][CH2:13][CH3:14])([CH2:6][O:7][Si:17]([CH2:20][CH3:21])([CH2:18][CH3:19])[CH2:15][CH3:16])[CH2:8][O:9][CH3:10])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCC(CO)(CCCC)COC
Reactant: CC[Si](Cl)(CC)CC
Product: CCCCC(CCCC)(COC)CO[Si](CC)(CC)CC

Procedure:
According to the procedure as described in Example 1,2,2-di-n-butyl-1-methoxy-3-[(triethylsilyl)oxy]propane was prepared from intermediate 2,2-di-n-butyl-3-methoxy-1-propanol and reagent triethylsilyl chloride.
Reaction SMILES: [C@H:1]12[NH:8][C@H:5]([CH2:6][CH2:7]1)[CH2:4][CH2:3][CH:2]2[C:9]([O:11][CH3:12])=[O:10].[F:13][C:14]1[CH:21]=[CH:20][CH:19]=[CH:18][C:15]=1[CH2:16]Br.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[F:13][C:14]1[CH:21]=[CH:20][CH:19]=[CH:18][C:15]=1[CH2:16][N:8]1[C@@H:5]2[CH2:6][CH2:7][C@H:1]1[CH:2]([C:9]([O:11][CH3:12])=[O:10])[CH2:3][CH2:4]2
Reactant: Fc1ccccc1CBr
Reactant: COC(=O)C1CC[C@H]2CC[C@@H]1N2
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)C1CC[C@H]2CC[C@@H]1N2Cc1ccccc1F
Reaction time: 1 h
Yield: 61 %

Procedure:
To (1S,5S)-methyl 8-azabicyclo[3.2.1]octane-2-carboxylate (185 mg, 1.1 mmol) dissolved in DCM (11 mL) was added 2-fluorobenzylbromide (206 mg, 1.1 mmol), followed by N,N-diisopropylethylamine (424 mg, 3.3 mmol). After stirring for 1 hour, the reaction mixture was quenched with water, and extracted with DCM. Dried and concentrated to give 186 mg of crude product. The crude was carried over the next step without further purification.
Reaction SMILES: [CH2:1]([N:3]1[CH2:8][CH2:7][N:6]([C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH:12]=[C:11]([C:19]3[CH:24]=[CH:23][C:22](O)=[CH:21][CH:20]=3)[N:10]=2)[CH2:5][CH2:4]1)[CH3:2].[CH2:26]([N:28]=[C:29]=[O:30])[CH3:27]>O1CCCC1>[CH2:1]([N:3]1[CH2:4][CH2:5][N:6]([C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH:12]=[C:11]([C:19]3[CH:24]=[CH:23][C:22]([C:29](=[O:30])[NH:28][CH2:26][CH3:27])=[CH:21][CH:20]=3)[N:10]=2)[CH2:7][CH2:8]1)[CH3:2]
Reactant: CCN=C=O
Reactant: CCN1CCN(c2nc(-c3ccc(O)cc3)cc3ccccc23)CC1
Solvent: C1CCOC1
Product: CCNC(=O)c1ccc(-c2cc3ccccc3c(N3CCN(CC)CC3)n2)cc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
1-(1-Ethylpiperazin-4-yl)-3-(4-hydroxyphenyl)isoquinoline (333 mg) was dissolved in tetrahydrofuran (5 ml), ethyl isocyanate (800 ml) was added thereto, and then the mixture was stirred at room temperature for 3 hr. The reaction mixture was evaporated. The resulting residue was purified by silica gel column chromatography (methylene chloride/methanol system), and then recrystallized from ethyl acetate/hexane, to give the free compound of the title compound. The free compound was converted into a hydrochloride in a conventional manner, which was then recrystallized (from ethanol/isopropyl ether), to give the hydrochloride of the title compound as yellow crystals (313 mg, yield; 70%).
Reaction SMILES: [Si:1]([O:8][C:9]1[CH:16]=[CH:15][C:12]([CH2:13][OH:14])=[CH:11][C:10]=1[CH:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1.CCCCCC.CCOC(C)=O>C(Cl)Cl>[Si:1]([O:8][C:9]1[CH:16]=[CH:15][C:12]([CH:13]=[O:14])=[CH:11][C:10]=1[CH:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc(CO)cc1C1CCCC1
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: CCCCCC
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: CC(C)(C)[Si](C)(C)Oc1ccc(C=O)cc1C1CCCC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 78.9 %

Procedure:
A solution of 1.94 g of 4-((tert-butyldimethylsilyl)oxy)-3-cyclopentylbenzyl alcohol in 70 mL of anhydrous CH2Cl2 was treated with 2.05 g of pyridinium chlorochromate (Aldrich) and was stirred at RT under nitrogen. After 30 min, tlc (SiO2, 85:15 hexane:EtOAc) indicated no remaining starting material and a major new component at Rf=0.80. The mixture was filtered to remove solids and the filtrate was washed with 5% aqueous citric acid (4×50 mL) followed by 5% aqueous NaHCO3 (4×50 mL). The CH2Cl2 solution was dried over anhydrous MgSO4 and concentrated in vacuo to give a brown oil. This material was purified by flash chromatography on silica gel (9:1 hexane:EtOAc) to afford 1.52 g (79%) of 4-((tert-butyldimethylsilyl)oxy)-3-cyclopentylbenzaldehyde as a clear oil.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][N:8]2[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]2)[CH:2]=1.Cl.[NH2:16][OH:17]>>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][N:8]2[CH2:13][CH2:12][C:11](=[N:16][OH:17])[CH2:10][CH2:9]2)[CH:2]=1
Reactant: O=C1CCN(Cc2cccnc2)CC1
Reactant: NO
Agent: Cl
Product: ON=C1CCN(Cc2cccnc2)CC1

Procedure:
1-(3-Pyridinylmethyl)-4-piperidone oxime is prepared from 1-(3-pyridinylmethyl)-4-piperidone and hydroxylamine hydrochloride essentially as described above in Example 38, Scheme C, step b.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[CH:4][C:3]=1[CH3:11].[CH3:12][NH2:13]>C1COCC1>[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:13][CH3:12])=[O:7])=[CH:4][C:3]=1[CH3:11]
Reactant: Cc1cc(C(=O)O)ccc1Br
Reactant: CN
Solvent: C1CCOC1
Product: CNC(=O)c1ccc(Br)c(C)c1
Temperature: 5 °C
Reaction time: 2.5 h

Procedure:
4-Bromo-3-methylbenzoic acid (20 g) was added to a suspension of 1,1-carbonyldiimidazole (18.1 g) in dry THF (250 ml) at 5° C. and the resulting suspension stirred for 2.5 h at 5° C. Methylamine (33% w/v, solution in methanol 50 ml) was added dropwise over 5 min and the resultant mixture stirred at 23° for 15 h. The solution was evaporated and the residue treated with aqueous 2M-hydrochloric acid (150 ml). The mixture was extracted with ether (4×150 ml) and the combined, dried organic extracts were evaporated. The residue crystallised from hot ethyl acetate (~50 ml) to give the title compound as white crystals (8.7 g),
Reaction SMILES: C[O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[NH:9][C:10]1[CH:14]=[CH:13][N:12]([CH3:15])[N:11]=1.C(=O)(O)[O-].[Na+].[ClH:21]>ClCCl>[ClH:21].[CH3:15][N:12]1[CH:13]=[CH:14][C:10]([NH:9][C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[OH:2])=[N:11]1
Reactant: COc1ccccc1Nc1ccn(C)n1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: Cn1ccc(Nc2ccccc2O)n1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
The pyrazole from step (a) (1.7 g) was dissolved in dichloromethane (30 ml) under an atmosphere of nitrogen. Brown tribromide (8 ml) in dichloromethane was added dropwise and the mixture stirred at room temperature for 24 hours. After addition of dilute sodium bicarbonate, the organic phase was removed, dried and evaporated to give a pale oil, which was converted to the hydrochloride salt of the title compound, by trituration with ethereal HCl, to give an off-white solid, 0.75 g, mp 162°-164°.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[CH2:16][CH2:15][N:14]([C:17]([C:19]2[N:20]=[CH:21][N:22]([CH2:24][C:25]([O:27]C)=[O:26])[CH:23]=2)=[O:18])[CH2:13][CH2:12]1)([CH3:4])([CH3:3])[CH3:2].[Li+].[OH-].Cl>O1CCCC1>[C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[CH2:16][CH2:15][N:14]([C:17]([C:19]2[N:20]=[CH:21][N:22]([CH2:24][C:25]([OH:27])=[O:26])[CH:23]=2)=[O:18])[CH2:13][CH2:12]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: COC(=O)Cn1cnc(C(=O)N2CCN(c3ccccc3C(C)(C)C)CC2)c1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Product: CC(C)(C)c1ccccc1N1CCN(C(=O)c2cn(CC(=O)O)cn2)CC1
Temperature: 0 °C
Reaction time: 2 h
Yield: 105.5 %

Procedure:
A mixture of methyl (4-{[4-(2-tert-butylphenyl)piperazin-1-yl]carbonyl}-1H-imidazol-1-yl)acetate (Example 187, 0.34 g, 0.87 mmol) and 1M LiOH solution (5 mL, 5.0 mmol) in tetrahydrofuran (5 mL) was stirred at 0° C. for 2 h. The reaction mixture was acidified with 1 M HCl solution and extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give the title compound (0.34 g, quant.) as a white powder.
Reaction SMILES: C([N:8]1[CH2:14][CH2:13][C:12]2[C:15](Cl)=[N:16][C:17]([CH:19]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH3:20])=[N:18][C:11]=2[CH2:10][CH2:9]1)C1C=CC=CC=1>C(OCC)(=O)C.[Pd]>[C:21]1([CH:19]([C:17]2[N:16]=[CH:15][C:12]3[CH2:13][CH2:14][NH:8][CH2:9][CH2:10][C:11]=3[N:18]=2)[CH3:20])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: CC(c1ccccc1)c1nc(Cl)c2c(n1)CCN(Cc1ccccc1)CC2
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CC(c1ccccc1)c1ncc2c(n1)CCNCC2
Reaction time: 41 h
Yield: 2 %

Procedure:
Palladium (10% on carbon) (40 mg) was added to a solution of 7-benzyl-4-chloro-2-(1-phenylethyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine (368 mg, 0.97 mmol) of Preparation 30, Step B, in ethyl acetate (5 ml) and hydrogenated at 50° C., 60 psi for 41 h. The reaction mixture was filtered through Arbocel then the filtrate was concentrated in vacuo. The residue was purified by HPLC (Phenomenex column, acetonitrile:water:formic acid gradient) to afford the title compound as an oil in 2% yield, 5 mg.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[N:7]1[C:14]2[C@H:13]3[CH2:15][C@H:12]3[CH2:11][C:10]=2[C:9]([C:16]([OH:18])=O)=[N:8]1.Cl.[F:20][C:21]([F:28])([F:27])[C:22]1([NH2:26])[CH2:25][CH2:24][CH2:23]1>>[F:20][C:21]([F:28])([F:27])[C:22]1([NH:26][C:16]([C:9]2[C:10]3[CH2:11][C@@H:12]4[CH2:15][C@@H:13]4[C:14]=3[N:7]([C:2]3[CH:3]=[N:4][CH:5]=[CH:6][N:1]=3)[N:8]=2)=[O:18])[CH2:25][CH2:24][CH2:23]1
Reactant: NC1(C(F)(F)F)CCC1
Reactant: O=C(O)c1nn(-c2cnccn2)c2c1C[C@@H]1C[C@H]21
Agent: Cl
Product: O=C(NC1(C(F)(F)F)CCC1)c1nn(-c2cnccn2)c2c1C[C@@H]1C[C@H]21

Procedure:
The title compound was prepared in a manner similar to that described in Method UU using Intermediate 4 and 1-(trifluoromethyl)cyclobutanamine hydrochloride. LCMS m/z=364.4 [M+H]+; 1H NMR (400 MHz, CDCl3) δ 0.47 (td, J=4.6, 3.2 Hz, 1H), 1.23-1.29 (m, 1H), 2.04-2.14 (m, 2H), 2.27-2.33 (m, 1H), 2.64-2.70 (m, 4H), 2.74-2.80 (m, 1H), 2.93 (d, J=16.9. Hz, 1H), 3.02 (dd, J=16.6 and 6.2 Hz, 1H), 6.99 (s, 1H), 8.42 (dd, J=2.5 and 1.5 Hz, 1H), 8.52 (d, J=2.5 Hz, 1H), 9.26 (d, J=1.4 Hz, 1H).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[O:8][CH:7]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:6][C:5]2=[O:19].[F:20][C:21]1[C:26](B(O)O)=[CH:25][CH:24]=[CH:23][N:22]=1.C([O-])([O-])=O.[Na+].[Na+].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.CCO.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:12][C:11]1[CH:10]=[C:9]2[C:4]([C:5](=[O:19])[CH2:6][CH:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[O:8]2)=[CH:3][C:2]=1[C:26]1[C:21]([F:20])=[N:22][CH:23]=[CH:24][CH:25]=1
Reactant: O=C1CC(c2ccccc2)Oc2cc(F)c(Br)cc21
Reactant: OB(O)c1cccnc1F
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: Cc1ccccc1
Product: O=C1CC(c2ccccc2)Oc2cc(F)c(-c3cccnc3F)cc21
Temperature: 110 °C
Reaction time: 0.33 h
Yield: 23.3 %

Procedure:
A mixture of 6-bromo-7-fluoro-2-phenylchroman-4-one (318 mg, 0.994 mmol), 2-fluoropyridin-3-ylboronic acid (210 mg, 1.5 mmol), Na2CO3 (318 mg, 2.98 mmol), PPh3 (34 mg) and Pd(PPh3)2Cl2 (59 mg, 0.1 mmol) in toluene/EtOH (v/v=1/1, 10.5 mL) was degassed and stirred at 110° C. for 20 minutes. The reaction mixture was concentrated in vacuo to give the residue, which was purified by preparative TLC to give 7-fluoro-6-(2-fluoropyridin-3-yl)-2-phenylchroman-4-one (78 mg, 23%).
Reaction SMILES: [Br:1][C:2]1[CH:13]=[CH:12][C:5]([C:6](N(OC)C)=[O:7])=[CH:4][CH:3]=1.[S:14]1[CH:18]=[CH:17][CH:16]=[C:15]1[Li].[Cl-].[NH4+]>C1COCC1>[Br:1][C:2]1[CH:13]=[CH:12][C:5]([C:6]([C:15]2[S:14][CH:18]=[CH:17][CH:16]=2)=[O:7])=[CH:4][CH:3]=1
Reactant: [Li]c1cccs1
Reactant: CON(C)C(=O)c1ccc(Br)cc1
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: O=C(c1ccc(Br)cc1)c1cccs1
Temperature: 0 °C
Reaction time: 1 h
Yield: 33.5 %

Procedure:
To a stirred solution of 4-bromobenzoyl chloride (20.0 g, 91.1 mmol) in dichloromethane (300 mL) at −78° C. was added triethylamine (28.0 mL, 200.0 mmol), and O,N-dimethylhydroxylamine hydrochloride (9.33 g, 95.6 mmol). The resulting solution was allowed to warm to room temperature, stirred for 1.5 hours, and then concentrated. The residue was triturated in acetone and the resulting solid was dissolved in ethyl acetate washed with water and brine. The organic layer was dried over magnesium sulfate, filtered, and concentrated to give 4-bromo-N-methoxy-N-methylbenzamide (18.6 g, 84%). To a solution of 4-bromo-N-methoxy-N-methylbenzamide (3.0 g, 12.29 mmol) in THF (30 mL) at 0° C. under nitrogen was added 2-thienyllithium (1.0 M in THF, 15 mL, 15 mmol) slowly over 10 minutes. The solution was stirred at 0° C. for 1 hour, poured into a saturated aqueous ammonium chloride solution (150 mL), and extracted several times with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated. The residue was triturated with ether to give (4-bromophenyl)(thien-2-yl)methanone as a brown solid (1.1 g, 34%). MS (ES) m/z 266.9.
Reaction SMILES: [F:1][C:2]([F:18])([F:17])[O:3][C:4]1[CH:5]=[C:6]([CH2:10][CH2:11][C:12]([O:14]CC)=[O:13])[CH:7]=[CH:8][CH:9]=1.[OH-].[Li+]>C(O)C.O.O>[F:1][C:2]([F:17])([F:18])[O:3][C:4]1[CH:5]=[C:6]([CH2:10][CH2:11][C:12]([OH:14])=[O:13])[CH:7]=[CH:8][CH:9]=1
Reactant: CCOC(=O)CCc1cccc(OC(F)(F)F)c1
Agent: [Li+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: O=C(O)CCc1cccc(OC(F)(F)F)c1
Temperature: 15 °C
Reaction time: 2 h

Procedure:
To a mixture of 158d (11.0 g, 42 mmol) in ethanol/water (150 mL/100 mL) was added lithium hydroxide (8.8 g, 210 mmol). See FIG. 4. The resulting mixture was stirred at 15° C. for 2 h. The mixture was diluted with water and extracted with EtOAc (200 mL×3). The organic layers were dried over anhydrous sodium sulfate and concentrated to afford 3-(3-(trifluoromethoxy)phenyl)propanoic acid 158e as a colorless oil.
Reaction SMILES: [H-].C([Al+]CC(C)C)C(C)C.[OH:11][CH2:12][C:13]1[NH:14][C:15]2[C:20]([C:21]=1[CH2:22][CH2:23][CH2:24][CH2:25][N:26]1[CH2:31][CH:30]=[C:29]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH2:28][CH2:27]1)=[CH:19][CH:18]=[C:17]([O:38]C)[CH:16]=2>C1(C)C=CC=CC=1>[OH:11][CH2:12][C:13]1[NH:14][C:15]2[C:20]([C:21]=1[CH2:22][CH2:23][CH2:24][CH2:25][N:26]1[CH2:27][CH:28]=[C:29]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH2:30][CH2:31]1)=[CH:19][CH:18]=[C:17]([OH:38])[CH:16]=2
Reactant: COc1ccc2c(CCCCN3CC=C(c4ccccc4)CC3)c(CO)[nH]c2c1
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: Cc1ccccc1
Product: OCc1[nH]c2cc(O)ccc2c1CCCCN1CC=C(c2ccccc2)CC1
Temperature: 25 °C

Procedure:
A solution of 1.5 g of diisobutylaluminiumhydride in 15 ml of toluene is added with cooling and stirring to a suspension of 3.9 g of 2-hydroxymethyl-3-[4-(4-phenyl-1,2,3,6-tetrahydropyridyl)-butyl]-6-methoxy-indole in 400 ml of toluene. The mixture is warmed to room temperature, refluxed for 3 hours with stirring, cooled and worked up in the usual manner. 2-Hydroxymethyl-3-[4-(4-phenyl-1,2,3,6-tetrahydropyridyl)-butyl]-6-hydroxy-indole is obtained.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]([C:14]3[C:19]4[CH:20]=[C:21]([C:24]#[N:25])[CH:22]=[CH:23][C:18]=4[O:17][C:16]([CH3:27])([CH3:26])[CH:15]=3)=[N:12][CH:13]=2)=[CH:4][CH:3]=1.C(OCC)(=[O:30])C>>[C:24]([C:21]1[CH:22]=[CH:23][C:18]2[O:17][C:16]([CH3:27])([CH3:26])[CH:15]=[C:14]([C:11]3[CH:10]=[CH:9][C:8]([C:5]4[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=4)=[CH:13][N+:12]=3[O-:30])[C:19]=2[CH:20]=1)#[N:25]
Reactant: CCOC(C)=O
Reactant: Cc1ccc(-c2ccc(C3=CC(C)(C)Oc4ccc(C#N)cc43)nc2)cc1
Product: Cc1ccc(-c2ccc(C3=CC(C)(C)Oc4ccc(C#N)cc43)[n+]([O-])c2)cc1

Procedure:
In an analogous manner to that described in the first paragraph of Example 6, from 4-[5-(4-methylphenyl)-2pyridyl]-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile there was obtained 2-(6-cyano-2,2-dimethyl-2H-1-benzopyran-4-yl)-5-(4-methylphenyl)pyridine N-oxide of melting point 173°-175° C. (decomposition) (from ethyl acetate).
Reaction SMILES: [OH:1][C@H:2]([C:16]1[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=1)[C@@H:3]([N:5]1C(=O)C2C(=CC=CC=2)C1=O)[CH3:4]>CO.CN>[NH2:5][C@@H:3]([CH3:4])[C@@H:2]([C:16]1[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=1)[OH:1]
Reactant: C[C@@H]([C@H](O)c1ccc(O)cc1)N1C(=O)c2ccccc2C1=O
Agent: CN
Solvent: CO
Product: C[C@H](N)[C@H](O)c1ccc(O)cc1
Yield: 53.3 %

Procedure:
To a suspension of (1S,2R)-2-[2-hydroxy-2-(4-hydroxy-phenyl)-1-methylethyl]isoindol-1,3-dione (1.0 g) in methanol (1.7 mL), methylamine in methanol (40% w/v; 3.5 mL) was added. The mixture was heated under reflux in argon atmosphere for 12 hours. After removing the solvent in vacua, the resulting residue was dissolved in tetrahydrofuran (3 mL) under heating. This solution was cooled and kept at room temperature. After removing the resulting precipitate by filtration, the mother liquor was concentrated in vacua. The resulting residue was recrystallized from ethyl acetate/methanol to obtain (1R, 2S)-2-amino-1-(4-hydroxyphenyl)propan-1-ol (0.30 g: 54% yield, optical purity 100% e.e.).
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].[C:7]([N:15]1[CH2:20][CH2:19][C:18]2[S:21][C:22]([C:24](OCC)=[O:25])=[CH:23][C:17]=2[CH2:16]1)(=O)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>C1COCC1>[CH2:7]([N:15]1[CH2:20][CH2:19][C:18]2[S:21][C:22]([CH2:24][OH:25])=[CH:23][C:17]=2[CH2:16]1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: CCOC(=O)c1cc2c(s1)CCN(C(=O)c1ccccc1)C2
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: OCc1cc2c(s1)CCN(Cc1ccccc1)C2

Procedure:
To stirred suspension of LAH (2.0 gms) a solution of ethyl 5-benzoyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxylate (6.0 g, 19 mmol) in THF was added slowly at 0° C. After addition reaction mixture was stirred for 30 minutes and quenched with saturated NH4Cl. It was diluted with CHCl3 and filtered. The filtrate was washed with saturated brine solution and dried over anhydrous MgSO4. It was filtered and taken to next step with out purifications. Yield: 4.5 g 91%. Yellow liquid.
Reaction SMILES: [Cl:1][C:2]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[C:17]([Cl:25])[C:3]=1[O:4][C:5]1[CH:6]=[C:7]([CH:14]=[CH:15][CH:16]=1)[O:8][CH:9]([CH3:13])[C:10]([OH:12])=[O:11].C(=O)([O-])[O-].[K+].[K+].Br[CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35]>C(#N)C>[Cl:1][C:2]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[C:17]([Cl:25])[C:3]=1[O:4][C:5]1[CH:6]=[C:7]([CH:14]=[CH:15][CH:16]=1)[O:8][CH:9]([CH3:13])[C:10]([O:12][CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])=[O:11]
Reactant: CCOC(=O)CBr
Reactant: CC(Oc1cccc(Oc2c(Cl)cc(C(F)(F)F)cc2Cl)c1)C(=O)O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCOC(=O)COC(=O)C(C)Oc1cccc(Oc2c(Cl)cc(C(F)(F)F)cc2Cl)c1

Procedure:
A mixture of 41.0 g (0.104 mol) of the R enantiomer of 2-[3-(2,6-dichloro-4-trifluoromethyl-phenoxy)phenoxy]-propionic acid, 15.8 g (0.114 mol) of potassium carbonate and 17.4 g (0.104 mol) of ethyl bromoacetate in 104 ml of acetonitrile was heated under reflux for 1 hour. Thereafter, working-up was carried out by filtering the reaction mixture under suction, evaporating down the filtrate, taking up the remaining residue in methylene chloride, and washing this solution once with water, drying it and then evaporating it down. The remaining residue was freed from residues of volatile constituents by gentle heating in a high vacuum. In this manner, 34.9 g (70% of theory) of the R enantiomer of (ethoxycarbonyl)-methyl 2-[3-(2,6-dichloro-4-trifluoromethylphenoxy)-phenoxy]-propionate were obtained in the form of a liquid having a refractive index nD20 =1.5190.
Reaction SMILES: [CH2:1]([N:4]([CH2:18][CH2:19][CH3:20])[CH2:5][C:6]1(O)[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:15][CH3:16])[CH:13]=2)[CH2:8][CH2:7]1)[CH2:2][CH3:3].Cl.[H][H]>CO.[Pd].O>[CH2:18]([N:4]([CH2:1][CH2:2][CH3:3])[CH2:5][CH:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:15][CH3:16])[CH:13]=2)[CH2:8][CH2:7]1)[CH2:19][CH3:20]
Reactant: CCCN(CCC)CC1(O)CCc2ccc(OC)cc21
Reactant: [H][H]
Agent: [Pd]
Agent: Cl
Solvent: CO
Solvent: O
Product: CCCN(CCC)CC1CCc2ccc(OC)cc21

Procedure:
12 g of N,N-dipropyl-1-hydroxy-6-methoxy-1-indanmethylamine were dissolved in 100 milliliters of methanol and 7 milliliters of concentrated hydrochloric acid and reduced catalytically with hydrogen at 3 atmospheres and 50 degrees Centigrade for 20 hours with 10 g of 5% palladium on carbon black containing 50% of water as a catalyst. After filtration of the catalyst and evaporation of the methanol 13 grams of product were obtained. The oxalate was precipitated from acetone. M.P. 124°-130° C.
Reaction SMILES: [CH:1]1([CH2:7][C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([O:17][C:18]4[C:25]([C:26]([F:29])([F:28])[F:27])=[CH:24][C:21]([CH2:22]Br)=[CH:20][C:19]=4[C:30]([F:33])([F:32])[F:31])[CH:15]=3)[NH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C-:34]#[N:35].[Na+].C1(C)C=CC=CC=1>CN(C)C=O.O>[CH:1]1([CH2:7][C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([O:17][C:18]4[C:25]([C:26]([F:29])([F:28])[F:27])=[CH:24][C:21]([CH2:22][C:34]#[N:35])=[CH:20][C:19]=4[C:30]([F:33])([F:32])[F:31])[CH:15]=3)[NH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: [C-]#N
Reactant: FC(F)(F)c1cc(CBr)cc(C(F)(F)F)c1Oc1ccc2[nH]cc(CC3CCCCC3)c2c1
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Solvent: Cc1ccccc1
Product: N#CCc1cc(C(F)(F)F)c(Oc2ccc3[nH]cc(CC4CCCCC4)c3c2)c(C(F)(F)F)c1

Procedure:
Preparation is carried out in analogy to the procedure of Example VIII from 0.85 g (1.59 mmol) of benzyl bromide from Example XXII with 0.1 g (1.99 mmol) of sodium cyanide in 5 ml of dimethylformamide and 0.5 ml of water at 50° C. in 1.5 hours. The chromatography of the crude product is carried out on silica gel 60 by means of toluene.