Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.Cl[C:10]([C:12]1[CH:13]=[C:14]([C:20]2[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=2)[N:15]2[C:19]=1[CH2:18][S:17][CH2:16]2)=[O:11].[OH-].[Na+].C>C(Cl)Cl.C(#N)C>[C:2]1([NH:1][C:10]([C:12]2[CH:13]=[C:14]([C:20]3[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=3)[N:15]3[C:19]=2[CH2:18][S:17][CH2:16]3)=[O:11])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(Cl)c1cc(-c2cccnc2)n2c1CSC2
Reactant: Nc1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CC#N
Solvent: ClCCl
Product: O=C(Nc1ccccc1)c1cc(-c2cccnc2)n2c1CSC2
Temperature: 20 °C
Reaction time: 16 h
Yield: 57.8 %

Procedure:
A solution of aniline (11.2 g) in methylene chloride (50 cc) is added over 15 minutes at a temperature of about 24° C. and 29° C. to a suspension of 7-chloroformyl-5-(3-pyridyl)-1H,3H-pyrrolo[1,2-c]thiazole hydrochloride (12 g) in methylene chloride (200 cc). The suspension obtained is stirred at a temperature of about 20° C. for 16 hours. Methylene chloride (300 cc) and distilled water (200 cc) are then added to the suspension. The insoluble material is separated off by filtration, washed 3 times with methylene chloride (75 cc in total) and 3 times with distilled water (75 cc in total). The mother-liquors from filtration and washing are combined; the organic phase is separated off, washed twice with distilled water (400 cc in total), once with a 2 N aqueous solution of sodium hydroxide (200 cc), then twice with distilled water (400 cc in total), dried over anhydrous magnesium sulphate, treated with decolourising charcoal (0.5 g) and filtered. A crude solution (625 cc) of product in methylene chloride is thus obtained. The insoluble material obtained earlier is taken up with a 5 N aqueous solution of sodium hydroxide (200 cc). The oil obtained is extracted 3 times with methylene chloride (750 cc in total). The organic extracts are combined, washed 3 times with distilled water (450 cc in total), dried over anhydrous magnesium sulphate, treated with decolourising charcoal (0.5 g) and filtered. The methylene chloride solution obtained is combined with the methylene chloride solution obtained earlier (625 cc) and the solvent is evaporated off under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about 60° C. A crude product (15.4 g) is thus obtained. This product is dissolved in boiling acetonitrile (210 cc). The solution obtained is treated with decolourising charcoal (0.5 g) and filtered hot. The filtrate is cooled at a temperature of about 4° C. for 2 hours. The crystals which have appeared are separated off by filtration, washed 3 times with acetonitrile (30 cc in total) cooled to a temperature of about 4° C. and 3 times with isopropyl ether (75 cc in total) and are then dried under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about 20° C. in the presence of potassium hydroxide pellets. N-phenyl-5-(3-pyridyl)-1H,3H-pyrrolo[1,2-c]thiazole-7-carboxamide (7.4 g) is thus obtained in the form of cream crystals melting at 188° C.
Reaction SMILES: [CH2:1]([CH2:3][NH2:4])[OH:2].[C:5]([O:11][CH3:12])(=[O:10])[CH2:6][C:7]([CH3:9])=O>>[CH3:12][O:11][C:5](=[O:10])[CH:6]=[C:7]([NH:4][CH2:3][CH2:1][OH:2])[CH3:9]
Reactant: NCCO
Reactant: COC(=O)CC(C)=O
Product: COC(=O)C=C(C)NCCO
Temperature: 0 °C
Yield: 91.2 %

Procedure:
To an ice-cooled sample of ethanolamine (6.1 g) was added methyl acetoacetate (11.6 g) dropwise. Compound (XXIII 14.5 g) was formed within 30 min (U.S. Pat. No. 1102800).
Reaction SMILES: [OH:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][C:8]2=[O:11])=[CH:4][CH:3]=1.Br[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.CCOC(C)=O>[CH2:13]([O:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][C:8]2=[O:11])=[CH:4][CH:3]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: BrCc1ccccc1
Reactant: O=C1CCc2ccc(O)cc21
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: O=C1CCc2ccc(OCc3ccccc3)cc21
Temperature: 25 °C
Reaction time: 23 h
Yield: 67 %

Procedure:
A mixture of 6-hydroxy-2,3-dihydroinden-1-one (available from Aldrich) (5.0 g, 34 mmol), 1-(bromomethyl)benzene (1.1) (available from Aldrich) (4.4 mL, 37 mmol) and cesium carbonate (25 g, 78 mmol) in DMF were stirred at room temperature for 23 hours. The reaction mixture was diluted with EtOAc (400 mL). The mixture was washed with brine and dried over anhydrous sodium sulfate. After removing solvent by rotary evaporation, the residue was purified by column chromatography (1:4 EtOAc/hexane). Product 1.2 was obtained in 67% yield as a white solid.
Reaction SMILES: [O:1]([CH:8]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH2:9][CH2:10]Cl)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH3:18]>C(O)C>[O:1]([CH:8]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH2:9][CH2:10][NH2:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: ClCCC(Oc1ccccc1)c1ccccc1
Reactant: N
Solvent: CCO
Product: NCCC(Oc1ccccc1)c1ccccc1

Procedure:
Eight grams of 3-phenoxy-3-phenylpropylchloride were heated with 150 ml. of liquid ammonia in a high pressure reactor at 100° C. for 20 hours. The volatile constituents of the reaction mixture were evaporated, and the residue, comprising 3-phenoxy-3-phenylpropylamine formed in the above reaction, was dissolved in ethanol and the volatile constituents again removed by evaporation. The resulting residue was dissolved in a mixture of ether and 5 N aqueous sodium hydroxide. The ether layer was separated, and the alkaline aqueous layer extracted three more times with ether. The ether extracts were combined, and the combined extracts washed with water. The combined ether extracts were in turn extracted twice with 2 N aqueous hydrochloric acid, the primary amine passing into the acidic layer. The acidic extracts were combined and made basic by the addition of an excess of 5 N aqueous sodium hydroxide. The primary amine, being insoluble in the basic layer, separated and was extracted into ether. The ether extract was separated, and the basic solution extracted twice more with ether. The ether extracts were combined, the combined extracts washed with saturated aqueous sodium chloride and then dried. Evaporation of the ether in vacuo yielded 3-phenoxy-3-phenylpropylamine as an oil. The oxalate salt of the primary amine was prepared and melted at 170°-173° C.
Reaction SMILES: Cl.Cl.[N:3]1([CH2:9][CH2:10][CH2:11][O:12][C:13]2[CH:22]=[C:21]3[C:16]([CH2:17][CH2:18][NH:19][CH2:20]3)=[CH:15][CH:14]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.CCN(CC)CC.[CH:30]([S:33](Cl)(=[O:35])=[O:34])([CH3:32])[CH3:31]>>[N:3]1([CH2:9][CH2:10][CH2:11][O:12][C:13]2[CH:22]=[C:21]3[C:16]([CH2:17][CH2:18][N:19]([S:33]([CH:30]([CH3:32])[CH3:31])(=[O:35])=[O:34])[CH2:20]3)=[CH:15][CH:14]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1
Reactant: c1cc2c(cc1OCCCN1CCCCC1)CNCC2
Reactant: CC(C)S(=O)(=O)Cl
Agent: Cl
Solvent: CCN(CC)CC
Product: CC(C)S(=O)(=O)N1CCc2ccc(OCCCN3CCCCC3)cc2C1

Procedure:
7-(3-Piperidin-1-yl-propoxy)-2-(propane-2-sulfonyl)-1,2,3,4-tetrahydro-isoquinoline is prepared from 7-(3-piperidin-1-yl-propoxy)-1,2,3,4-tetrahydro-isoquinoline dihydrochloride (175 mg, 0.5 mmol), NEt3 (0.25 mL, 1.8 mmol), and isopropylsulfonyl chloride (0.07 mL, 0.60 mmol) via a procedure substantially analogous to Procedure F except that an additional SCX column purification step is performed to give the product (93 mg, 49% yld). MS(ES+) 381.1(M+H)+.
Reaction SMILES: [H-].[Na+].[CH2:3]([N:10]1[CH:14]=[C:13]([CH:15]=O)[C:12]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[N:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C(OP([CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])(OCC)=O)C.CN(C)C=O>O>[CH2:3]([N:10]1[CH:14]=[C:13](/[CH:15]=[CH:33]/[C:34]([O:36][CH2:37][CH3:38])=[O:35])[C:12]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[N:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: CCOC(=O)CP(=O)(OCC)OCC
Reactant: O=Cc1cn(Cc2ccccc2)nc1OCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)/C=C/c1cn(Cc2ccccc2)nc1OCc1ccccc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 91 %

Procedure:
Sodium hydride (60%, oily, 1.94 g) was added to a mixture of 1-benzyl-3-benzyloxy-1H-pyrazole-4-carbaldehyde (12.90 g), ethyl diethylphosphonoacetate (9.60 ml), and N,N-dimethylformamide (200 ml) at 0° C., and the mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into water, which was extracted with ethyl acetate. The ethyl acetate layer was washed with diluted hydrochloric acid and then with saturated aqueous sodium chloride solution, dried (MgSO4), and then concentrated. The crystals obtained were collected by filtration to yield ethyl(E)-3-(1-benzyl-3-benzyloxy-1H-pyrazol-4-yl)propenoate (14.50 g, yield: 91%). This was recrystallized from ethyl acetate-hexane. Melting point: 88–89° C.
Reaction SMILES: C([O-])([O-])=O.[K+].[K+].C(O)CO.C1(O)C=CC=CC=1.[I:18]C1C=C2C(=CC=1)NC=C2.[CH:28]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[SH:37])([CH3:30])[CH3:29].IC1C=CC=CC=1C>C(O)(C)C.[Cu]I>[CH:28]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[I:18])([CH3:30])[CH3:29].[CH:28]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[SH:37])([CH3:30])[CH3:29]
Reactant: Ic1ccc2[nH]ccc2c1
Agent: [Cu]I
Agent: CC(C)c1ccccc1S
Agent: Cc1ccccc1I
Solvent: Oc1ccccc1
Solvent: CC(C)O
Solvent: OCCO
Product: CC(C)c1ccccc1I

Procedure:
Thus, a system comprising 5 mol % of CuI, 2 equiv of K2CO3 and 2 equiv of ethylene glycol in isopropanol (without pre-drying and degassing) at 80° C. under argon was applied for the coupling of various functionalized aryl iodides with thiols. Both aromatic and aliphatic NH2 groups, phenol, carboxylic acid, ketone, ester, amide and aldehyde functional groups are tolerated under these reaction conditions. No deleterious effect is observed when heterocyclic substrates, such as 5-iodoindole, are used. This protocol is also applicable to ortho-substituted substrates; for example, the sterically hindered 2-isopropylthiophenol can be coupled with 2-iodotoluene in 88% yield at 80° C. A 91% yield was obtained when the highly sterically hindered 2-isopropyliodobenzene and 2-isopropylthiophenol were coupled at 100° C. The presence of functional groups in the ortho position of the aryl iodide substrates are tolerated including a hydroxymethyl group and a free NH2 group. As can be seen from the results in FIG. 2, a thiophenol with an ortho carboxymethyl group can be coupled in good yield. In addition, alkyl thiols were also found to be effective nucleophiles. Aryl bromides can be used for the arylation of thiols if the aryl bromide is first converted into the corresponding aryl iodide using CuI (10 mol %), a 1,2-diaminoalkane ligand (e.g., 20 mol % of N,N′-dimethylethylenediamine) and sodium iodide (2 equiv) before the addition of the thiol starting material. In summary, we have developed a general and efficient Cu-catalyzed arylation method for both aryl and alkyl thiols under mild conditions that tolerate a wide variety of functional groups.
Reaction SMILES: [C:1]([C:3]1[CH:12]=[C:11]2[C:6]([NH:7][C:8](=[O:15])[C:9](=[O:14])[N:10]2[OH:13])=[CH:5][C:4]=1[C:16]([F:19])([F:18])[F:17])#[N:2].C(N(CC)CC)C.Cl[C:28]([O:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:29]>O1CCCC1>[C:1]([C:3]1[CH:12]=[C:11]2[C:6]([NH:7][C:8](=[O:15])[C:9](=[O:14])[N:10]2[O:13][C:28]([O:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[O:29])=[CH:5][C:4]=1[C:16]([F:19])([F:17])[F:18])#[N:2]
Reactant: N#Cc1cc2c(cc1C(F)(F)F)[nH]c(=O)c(=O)n2O
Reactant: O=C(Cl)Oc1ccccc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: N#Cc1cc2c(cc1C(F)(F)F)[nH]c(=O)c(=O)n2OC(=O)Oc1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 82.9 %

Procedure:
A solution of 0.4 g (1.48 mmol) 7-cyano-1-hydroxy-6-trifluoromethylquinoxaline -2,3(1H,4H)-dione in 50 ml dry tetrahydrofuran was added 0.225 ml (1.63 mmol) dry triethylamine and 0.2 ml (1.58 mmol) phenyl chloroformate. The mixture was stirred at 25° C. for 30 min., and then filtered and evaporated in vacuo. The residue was stirred with ether to give 0.48 g (83%) of 7-cyano-1-phenoxycarbonyloxy-6-trifluoromethylquinoxaline-2,3-(1H,4H)-dione. M.p. 190° C. decomp. 1H-NMR (DMSO-d6): 8.43 (1H,s), 7.63 (1H, s), 7.3 (5H, broad s).
Reaction SMILES: [C:1]([N:4]1[CH:9]=[CH:8][N:7]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[C:6](=[O:18])[CH2:5]1)(=[O:3])[CH3:2]>C(O)C.[Pd]>[C:1]([N:4]1[CH2:9][CH2:8][N:7]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[C:6](=[O:18])[CH2:5]1)(=[O:3])[CH3:2]
Reactant: CC(=O)N1C=CN(Cc2ccc(F)cc2)C(=O)C1
Agent: [Pd]
Solvent: CCO
Product: CC(=O)N1CCN(Cc2ccc(F)cc2)C(=O)C1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 4-acetyl-1-(4-fluorobenzyl)-3,4-dihydropyrazin-2(1H)-one (141 g, 0.57 mol) and 5% Pd/C (10.4 g) in ethanol (500 mL) was stirred under an atmosphere of hydrogen (1 atm) at room temperature overnight. The product mixture was filtered through a pad of Celite, and concentrated under vacuum to provide the title compound. Residual ethanol was removed by co-evaporation with toluene (3×) under vacuum. The resultant oil solidify on standing and was used in the next step without further purification.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([S:11][CH3:12])=[N:9][CH:10]=2)[CH:7]=1.O.C(=O)(O)[O-].[Na+].[I:19]I>C(O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([S:11][CH3:12])=[N:9][C:10]=2[I:19])[CH:7]=1
Reactant: II
Reactant: CSc1ncc2ccc(F)cn12
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: CSc1nc(I)c2ccc(F)cn12
Temperature: 25 °C
Reaction time: 8 h
Yield: 40.6 %

Procedure:
In a round-bottomed flask, 6-fluoro-3-methylsulfanyl-imidazo[1,5-a]pyridine (178 mg, 0.88 mmol) was dissolved in ethanol (1.6 ml). Water (0.8 ml), sodium bicarbonate (278 mg, 3.31 mmol) and iodine (312 mg, 1.23 mmol) were added. The dark brown suspension was stirred at room temperature overnight then quenched with 10% aqueous Na2S2O3 and extracted with EtOAc (2×). The combined organic layers were washed with 10% aqueous Na2S2O3, water, and brine then dried over sodium sulfate, filtered and concentrated. The residue was absorbed on silica gel and chromatographed with EtOAc/hexanes (gradient 0-10% EtOAc) to afford 110 mg (41%) of 6-fluoro-1-iodo-3-methylsulfanyl-imidazo[1,5-a]pyridine as a brown solid.
Reaction SMILES: [C:1](=[O:13])([O:6][CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)[O:2][CH:3](Cl)[CH3:4].[OH:14][C@H:15]([CH2:35][NH:36][C:37]([CH3:50])([CH3:49])[CH2:38][C:39]1[CH:48]=[CH:47][C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[CH:40]=1)[CH2:16][O:17][CH:18]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[C:26]1[CH:31]=[CH:30][C:29]([C:32]([OH:34])=[O:33])=[CH:28][CH:27]=1)[CH3:19].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CN(C)C=O.O>[OH:14][C@H:15]([CH2:35][NH:36][C:37]([CH3:49])([CH3:50])[CH2:38][C:39]1[CH:48]=[CH:47][C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[CH:40]=1)[CH2:16][O:17][CH:18]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[C:26]1[CH:27]=[CH:28][C:29]([C:32]([O:34][CH:3]([O:2][C:1]([O:6][CH:7]2[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]2)=[O:13])[CH3:4])=[O:33])=[CH:30][CH:31]=1)[CH3:19]
Reactant: CC(Cl)OC(=O)OC1CCCCC1
Reactant: CC(OC[C@H](O)CNC(C)(C)Cc1ccc2ccccc2c1)c1ccccc1-c1ccc(C(=O)O)cc1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(OC(=O)OC1CCCCC1)OC(=O)c1ccc(-c2ccccc2C(C)OC[C@H](O)CNC(C)(C)Cc2ccc3ccccc3c2)cc1
Temperature: 60 °C
Reaction time: 24 h
Yield: 94.6 %

Procedure:
1-Chloroethyl cyclohexyl carbonate (149 mg) obtained in Step 1 was dissolved in N,N-dimethylformamide (5.0 ml), 2′-[1-[(2R)-2-hydroxy-3-[[2-methyl-1-(naphthalen-2-yl)propan-2-yl]amino]propoxy]ethyl]biphenyl-4-carboxylic acid (300 mg) obtained in Step 2, potassium carbonate (99 mg) and potassium iodide (50 mg) were successively added and the mixture was stirred at 60° C. for 1 day. Water was added to the reaction mixture and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed successively with water (3 times) and brine, and dried over sodium sulfate. The organic layer was concentrated under reduced pressure and the obtained residue was purified by silica gel column chromatography (chloroform:methanol=15:1) to give the title compound (381 mg).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2([CH3:17])[NH:14][CH:13]([C:15]#[N:16])[CH2:12][O:11][CH2:10]2)=[CH:5][CH:4]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2([CH3:17])[NH:14][CH:13]([CH2:15][NH2:16])[CH2:12][O:11][CH2:10]2)=[CH:7][CH:8]=1
Reactant: COc1ccc(C2(C)COCC(C#N)N2)cc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: COc1ccc(C2(C)COCC(CN)N2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of 2.25 mmol of 5-(4-methoxyphenyl)-5-methylmorpholin-3-carbonitrile (Example 3f2) in 10 ml of tetrahydrofuran is cooled to 0-5° C. in an ice bath. 6.75 mmol of lithium aluminium hydride are added in portions, and the reaction mixture is then stirred at room temperature for 1 hour. The reaction mixture is quenched with 0.5 ml of methanol and mixed with 40 ml of dichloromethane and 0.060 g of solid potassium carbonate, and 0.60 ml of water. The suspension is filtered through Hyflo and the filter cake is washed with dichloromethane. The filtrate is evaporated. The title compound is obtained as a colourless oil from the residue by flash chromatography (SiO2 60F). Rf=0.26 (dichloromethane-methanol-25% aqueous ammonia solution 200:20:1), Rt=2.13 (gradient I)
Reaction SMILES: [CH:1]1[CH2:8][CH2:7]C=CCCC=1.[C]=O.[CH2:11]([O:13][SiH:14]([O:18][CH2:19][CH3:20])[O:15][CH2:16][CH3:17])[CH3:12].[CH2:21]([NH2:24])[CH:22]=[CH2:23]>[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Rh].[Rh].[Rh].[Rh].C1(C)C(C)=CC=CC=1>[CH2:21]([NH2:24])[CH:22]=[CH2:23].[NH2:24][CH:8]([CH3:7])[CH2:1][Si:14]([O:18][CH2:19][CH3:20])([O:15][CH2:16][CH3:17])[O:13][CH2:11][CH3:12]
Reactant: CCO[SiH](OCC)OCC
Reactant: C1=CCCC=CCC1
Agent: [Rh]
Agent: [C-]#[O+]
Agent: [C]=O
Solvent: Cc1ccccc1C
Solvent: C=CCN
Product: CCO[Si](CC(C)N)(OCC)OCC
Temperature: 120 °C
Reaction time: 2.5 h

Procedure:
A 200 ml. flask equipped with a stirrer, thermometer, dropping funnel, CO inlet tube and reflux condenser having a CO outlet tube, was flushed with carbon monoxide and charged with 1.9 milligrams of tetrarhodium dodecacarbonyl (2.5×10-6 mole), 0.027 gram of 1,5-cyclooctadiene (2.5×10-4 mole) and 60 ml. of xylene. While passing carbon monooxide through the flask at a rate of 10 ml./min., the mixture was heated to a temperature of 120° C. under stirring. To the mixture a mixture of 41 grams of triethoxy silane (0.25 mole) and 14 grams of allylamine (0.25 mole) was dropwise added over a period of 30 minutes. After the addition of the reactants, the reaction was carried out at a temperature of 120° C. for 2.5 hours under CO flush and stirring. It was revealed by gas chromatography that gamma-aminopropyl triethoxy silane was obtained in a yield of 75% on an allylamine basis, while the yield of beta-aminopropyl triethoxy silane was 7.5% on an allylamine basis.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[C:8]([N+:10]([O-])=O)[CH:7]=[CH:6][C:5]=1[O:13][C:14]1[CH:19]=[CH:18][C:17]([N+:20]([O-])=O)=[CH:16][C:15]=1[N+:23]([O-])=O)([O-])=O.[H][H]>C(OCC)(=O)C.C(O)C.[Pd]>[NH2:23][C:15]1[CH:16]=[C:17]([NH2:20])[CH:18]=[CH:19][C:14]=1[O:13][C:5]1[CH:6]=[CH:7][C:8]([NH2:10])=[CH:9][C:4]=1[NH2:1]
Reactant: O=[N+]([O-])c1ccc(Oc2ccc([N+](=O)[O-])cc2[N+](=O)[O-])c([N+](=O)[O-])c1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CCO
Product: Nc1ccc(Oc2ccc(N)cc2N)c(N)c1
Yield: 24 %

Procedure:
The dinitro compound obtained from Example 7 (22.1 g, 0.035 mole) was mixed with 10% Pd/C. (2.2 g) in ethyl acetate/ethanol (6/4 by volume, 88 g) solvent. Hydrogenation was carried out with 50-60 psi of hydrogen pressure at ambient temperature for about 6 hrs. After reaction, the solution was filtered to remove the metal residue and the solvent was removed in vacuo. The final diamino product was purified by distillation, 4.75 g of (24% yield) clear, viscous liquid was obtained. Bp. 120° C./0.02 mm. H1NMR (CDCl3): δ7.61 (d, J=8.0 Hz, 1H), 6.08 (d, J=2.0 Hz, 1H), 6.02 (dd, J=2 Hz, 8 Hz, 1H), 4.11 (t, J=13.5 Hz, 2H), 3.55 (s, br, 4H, --NH2); F19NMR (CDCl3): -71.3 (m, 2F), - 77.5 (m, 1F), -80.2 (m, 3F), -82.3 to -86.0 (m, 4F), -124.0 (m, 2F), -146.2 (m, 1F).
Reaction SMILES: NC1C=CC(OC2C=C3C(=CC=2)OC(C2C=CC=CC=2)CC3)=NC=1.[F:25][C:26]1[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=1[CH:33]1[CH2:42][CH2:41][C:40]2[C:35](=[CH:36][CH:37]=[C:38]([O:43][C:44]3[CH:49]=[CH:48][C:47]([N+:50]([O-])=O)=[CH:46][N:45]=3)[CH:39]=2)[O:34]1>>[F:25][C:26]1[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=1[CH:33]1[CH2:42][CH2:41][C:40]2[C:35](=[CH:36][CH:37]=[C:38]([O:43][C:44]3[N:45]=[CH:46][C:47]([NH2:50])=[CH:48][CH:49]=3)[CH:39]=2)[O:34]1
Reactant: O=[N+]([O-])c1ccc(Oc2ccc3c(c2)CCC(c2cc(F)ccc2F)O3)nc1
Agent: Nc1ccc(Oc2ccc3c(c2)CCC(c2ccccc2)O3)nc1
Product: Nc1ccc(Oc2ccc3c(c2)CCC(c2cc(F)ccc2F)O3)nc1

Procedure:
6-[2-(2,5-Difluorophenyl)chroman-6-yloxy]-pyridin-3-ylamine was prepared as described for 5-amino-2-(2-phenylchroman-6-yloxy)pyridine in Example 26 starting from 830 mg of 2-[2-(2,5-Difluorophenyl)chroman-6-yloxy]-5-nitropyridine (Example 14(d)). 1H NMR (300 MHz, d6-DMSO) δ: 7.51 (d, 1H, J 2.9 Hz), 7.36-7.25 (m, 3H), 7.05 (dd, 1H, J 8.6, 2.9 Hz), 6.84-6.68 (m, 4H), 5.29 (d, 1H, J 8.6), 4.99 (s, 2H), 2.96 (m, 1H), 2.72 (m, 1H), 2.14 (m, 1H), 2.01 (m, 1H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C@H:11]2[CH2:16][CH2:15][CH2:14][CH2:13][C@H:12]2[NH:17][C:18](=O)[C:19]2[CH:24]=[CH:23][C:22]([C:25]([O:27][CH3:28])=[O:26])=[CH:21][CH:20]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].O(Cl)Cl.C(=O)(O)[O-].[Na+]>C(#N)C>[CH3:10][O:9][C:8]1[CH:7]=[C:6]2[C:5](=[CH:4][C:3]=1[O:2][CH3:1])[C@H:11]1[C@H:12]([CH2:13][CH2:14][CH2:15][CH2:16]1)[N:17]=[C:18]2[C:19]1[CH:24]=[CH:23][C:22]([C:25]([O:27][CH3:28])=[O:26])=[CH:21][CH:20]=1
Reactant: COC(=O)c1ccc(C(=O)N[C@@H]2CCCC[C@@H]2c2ccc(OC)c(OC)c2)cc1
Agent: ClOCl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC#N
Product: COC(=O)c1ccc(C2=N[C@H]3CCCC[C@H]3c3cc(OC)c(OC)cc32)cc1

Procedure:
1.8 g of (+/−)-cis-N-[2-(3,4-dimethoxyphenyl)cyclohexyl]-4-methoxycarbonylbenzamide are dissolved in 50 ml of acetonitrile and 1.0 ml of phoshorus oxychloride and stirred at 50° C. for 8 h. The reaction mixture is poured into 100 ml of saturated sodium bicarbonate solution and extracted with ethyl acetate. The organic phase is washed with sodium bicarbonate solution and water, dried with sodium sulfate and concentrated. The residue is recrystallized from ethyl acetate/petroleum ether. This gives 660 mg (38.6% of Th.) of the title compound of m.p.: 121.5-122.5° C.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:14]=[CH:15][CH:16]=1)[CH:12]=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C@@H:17]1([NH2:27])[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:20][CH2:19][CH2:18]1>>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:14]=[CH:15][CH:16]=1)[CH2:12][NH:27][C@@H:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:20][CH2:19][CH2:18]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=Cc1cccc(OCc2ccccc2)c1
Reactant: N[C@H]1CCCc2ccccc21
Product: c1ccc(COc2cccc(CN[C@H]3CCCc4ccccc43)c2)cc1

Procedure:
3-(Benzyloxy)benzaldehyde and (1S)-1,2,3,4-tetrahydro-1-naphthalenylamine were processed as described in Example 1A to provide the title compound.