Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]([CH2:3][CH2:4][C:5]12[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH3:19])[CH:6]1[C:7]([NH:9][C:10]2=[O:11])=[O:8])=O.[CH3:20][NH:21][CH2:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=1>>[CH3:20][N:21]([CH2:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=1)[CH2:1][CH2:3][CH2:4][C:5]12[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH3:19])[CH:6]1[C:7]([NH:9][C:10]2=[O:11])=[O:8]
Reactant: COC1=C(OC)C2C(=O)NC(=O)C2(CCC=O)C=C1
Reactant: CNCCc1ccccn1
Product: COC1=C(OC)C2C(=O)NC(=O)C2(CCCN(C)CCc2ccccn2)C=C1

Procedure:
Prepared from 2-(2-formyl-ethyl)-5,6-dimethoxy-phthalimide and 2-(2-methylamino-ethyl)-pyridine analogously to Example 4.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]2[C@H:14]([N:15]([CH3:25])[C:16](=[O:24])[C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[CH2:13][CH2:12][NH:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].[C:26]([N:29]1[CH2:34][CH2:33][CH:32]([C:35](O)=[O:36])[CH2:31][CH2:30]1)(=[O:28])[CH3:27]>>[C:26]([N:29]1[CH2:30][CH2:31][CH:32]([C:35]([N:11]2[CH2:12][CH2:13][C@@H:14]([N:15]([CH3:25])[C:16](=[O:24])[C:17]3[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=3)[C@H:9]([C:4]3[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=3)[CH2:10]2)=[O:36])[CH2:33][CH2:34]1)(=[O:28])[CH3:27]
Reactant: CN(C(=O)c1ccc(F)cc1)[C@@H]1CCNC[C@H]1c1ccc(Cl)c(Cl)c1
Reactant: CC(=O)N1CCC(C(=O)O)CC1
Product: CC(=O)N1CCC(C(=O)N2CC[C@@H](N(C)C(=O)c3ccc(F)cc3)[C@H](c3ccc(Cl)c(Cl)c3)C2)CC1

Procedure:
Using the compound obtained in Example 26 and 1-acetylpiperidine-4-carboxylic acid, and by the reaction and purification in the same manner as in Example 3, the title compound was obtained.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][N:11]2[CH:15]=[CH:14][N:13]=[CH:12]2)=[CH:4][CH:3]=1.Cl[CH2:17][C:18]1[N:19]=[C:20]([C:23]2[CH:35]=[CH:34][C:33]3[C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[C:26](=[O:36])[C:25]=3[CH:24]=2)[O:21][CH:22]=1>>[CH:24]1[C:25]2[C:26](=[O:36])[C:27]3[C:32](=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:33]=2[CH:34]=[CH:35][C:23]=1[C:20]1[O:21][CH:22]=[C:18]([CH2:17][O:1][C:2]2[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][N:11]3[CH:15]=[CH:14][N:13]=[CH:12]3)=[CH:4][CH:3]=2)[N:19]=1
Reactant: Oc1ccc(CCCn2ccnc2)cc1
Reactant: O=C1c2ccccc2-c2ccc(-c3nc(CCl)co3)cc21
Product: O=C1c2ccccc2-c2ccc(-c3nc(COc4ccc(CCCn5ccnc5)cc4)co3)cc21
Yield: 86 %

Procedure:
In substantially the same manner as in Working Example 72, 1-[3-(4-hydroxyphenyl)propyl]imidazole was allowed to react with 4-chloromethyl-2-(9-fluorenone-2-yl)oxazole to give 2-(9-fluorenone-2-yl)-4-[4-[3-(1-imidazolyl)propyl]phenoxymethyl]oxazole. The yield was 86%. Recrystallization from ethanol gave yellow needles, mp 153-154° C.
Reaction SMILES: CON(C)[C:4](=[O:12])[CH2:5][C:6]1[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=1.[H-].C([Al+]CC(C)C)C(C)C>O1CCCC1>[N:8]1[CH:9]=[CH:10][CH:11]=[C:6]([CH2:5][CH:4]=[O:12])[CH:7]=1
Reactant: CON(C)C(=O)Cc1cccnc1
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: C1CCOC1
Product: O=CCc1cccnc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 64 %

Procedure:
To a solution of N-methoxy-N-methyl-2-pyridin-3-yl-acetamide (279 mg in 5 mL dry tetrahydrofuran) at -30° C. was added 3.1 mL of a 1M diisobutylaluminum hydride solution in tetrahydrofuran and the mixture stirred at low temperature. After 30 minutes, the reaction was quenched by the careful addition of saturated aqueous sodium potassium tartarate. The resulting mixture was allowed to stir while warming to room temperature at which time the mixture was diluted with ethyl acetate and filtered through a pad of sodium sulfate. Purification of the concentrate by flash chromatography on silica gel (methylene chloride:methanol, 94:6) gave the title compound (120 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]([NH:11][C:12](=[O:16])[CH:13]([CH3:15])[CH3:14])[CH:8]=[CH:7][C:3]=1[C:4](Cl)=[O:5].[CH2:17]([NH:19][CH2:20][CH3:21])[CH3:18].O>C1COCC1>[Cl:1][C:2]1[CH:10]=[C:9]([NH:11][C:12](=[O:16])[CH:13]([CH3:15])[CH3:14])[CH:8]=[CH:7][C:3]=1[C:4]([N:19]([CH2:20][CH3:21])[CH2:17][CH3:18])=[O:5]
Reactant: CCNCC
Reactant: CC(C)C(=O)Nc1ccc(C(=O)Cl)c(Cl)c1
Solvent: C1CCOC1
Solvent: O
Product: CCN(CC)C(=O)c1ccc(NC(=O)C(C)C)cc1Cl
Reaction time: 8 h

Procedure:
The crude 2-chloro-4-(2'-methylpropionamido)benzoyl chloride from the preceding reaction in dry THF (10 ml) was added dropwise with stirring over 10-15 minutes to a solution of diethylamine (1.46 g) in dry THF (10 ml), at 0°-5° C. After stirring at 0°-10° C. the reaction mixture was stood overnight at room temperature, poured into cold water and extracted with ethyl acetate. This extract was dried and evaporated to give a viscous gum which crystallised slowly and was then recrystallised from ethyl acetate to give 2-chloro-4-(2'-methylpropionamido)-N,N-diethylbenzamide as white crystals (0.507 g).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3](/[CH:10]=[C:11]2\[O:12][C:13]3[C:20]([C:21]#[C:22][CH2:23][CH:24]4[CH2:29][CH2:28][N:27](C(OC(C)(C)C)=O)[CH2:26][CH2:25]4)=[C:19]([O:37][CH3:38])[CH:18]=[CH:17][C:14]=3[C:15]\2=[O:16])=[N:2]1.Cl>C(Cl)Cl.O1CCOCC1>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3](/[CH:10]=[C:11]2\[O:12][C:13]3[C:20]([C:21]#[C:22][CH2:23][CH:24]4[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]4)=[C:19]([O:37][CH3:38])[CH:18]=[CH:17][C:14]=3[C:15]\2=[O:16])=[N:2]1
Reactant: COc1ccc2c(c1C#CCC1CCN(C(=O)OC(C)(C)C)CC1)O/C(=C\c1n[nH]c3ccccc13)C2=O
Agent: Cl
Solvent: C1COCCO1
Solvent: ClCCl
Product: COc1ccc2c(c1C#CCC1CCNCC1)O/C(=C\c1n[nH]c3ccccc13)C2=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 52.2 %

Procedure:
A solution of tert-butyl (Z)-4-(3-{2-[(1H-indazol-3-yl)methylene]-6-methoxy-3-oxo-2,3-dihydrobenzofuran-7-yl}prop-2-ynyl)piperidine-1-carboxylate (0.0293 g, 0.0570 mmol) in methylene chloride (2 mL) was added with a 4 M solution of hydrogen chloride in 1,4-dioxane (2 mL), and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated, the resulting residue was added with saturated aqueous sodium hydrogencarbonate, and the precipitated solid was collected by filtration. The solid was washed with water, and then dried under reduced pressure to obtain (Z)-2-[(1H-indazol-3-yl)methylene]-6-methoxy-7-[3-(piperidin-4-yl)prop-1-ynyl]benzofuran-3(2H)-one (0.0123 g, 52%).
Reaction SMILES: [C:1]([C:5]1[CH:12]=[CH:11][C:8]([C:9]#N)=[C:7]([Cl:13])[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[H-].C([Al+]CC(C)C)C(C)C.C1(C)C=CC=CC=1.C([O:33]CC)C>>[C:1]([C:5]1[CH:12]=[CH:11][C:8]([CH:9]=[O:33])=[C:7]([Cl:13])[N:6]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CCOCC
Reactant: CC(C)(C)c1ccc(C#N)c(Cl)n1
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: Cc1ccccc1
Product: CC(C)(C)c1ccc(C=O)c(Cl)n1
Temperature: 25 °C
Yield: 95 %

Procedure:
To a diethyl ether (17 ml) solution of 6-tert-butyl-2-chloronicotinonitrile (Tetrahedron 1965, 21, 2453-2467, 1.0 g, 5.4 mmol) was added 0.94 M diisobutylaluminum hydride in toluene solution (8.6 ml, 8.0 mmol) at −78° C. and the reaction was allowed to warm to room temperature over 2 hours with stirring. Then the reaction was quenched with 10% potassium sodium tartrate tetrahydrate aqueous solution and the whole was extracted with EtOAc, and washed with 2M sodium hydroxide aqueous solution and brine. The organic layer was evaporated and purified by silica gel column chromatography, eluting with hexane/EtOAc (5:1), to give 6-tert-butyl-2-chloronicotinaldehyde (1.0 g, 95%). To a THF (24 ml) suspension of methyltriphenylphosphonium bromide (5.3 g, 14.8 mmol) was added 1.60 M n-butyllithium (9.3 ml, 14.8 mmol) in hexane solution at 0° C. and the reaction was stirred for 30 minutes. Then to this mixture was added a THF (5 ml) solution of the 6-tert-butyl-2-chloronicotinaldehyde (1.0 g, 5.2 mmol) at 0° C., and the reaction was stirred for 2 hours at room temperature. The reaction was quenched with saturated ammonium chloride aqueous solution, and the whole was extracted with EtOAc, and dried over magnesium sulfate. The organic layer was evaporated and purified by silica gel column chromatography, eluting with hexane/EtOAc (10:1), to give the title compound (735 mg, 71%).
Reaction SMILES: [CH:1]1[C:13]2[CH2:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][C:2]=1[CH2:14][CH2:15][CH:16]([OH:18])[CH3:17].[C:19](OC(=O)C)(=[O:21])[CH3:20]>N1C=CC=CC=1>[C:19]([O:18][CH:16]([CH2:15][CH2:14][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=3)[CH2:12][C:13]=2[CH:1]=1)[CH3:17])(=[O:21])[CH3:20]
Reactant: CC(=O)OC(C)=O
Reactant: CC(O)CCc1ccc2c(c1)Cc1ccccc1-2
Solvent: c1ccncc1
Product: CC(=O)OC(C)CCc1ccc2c(c1)Cc1ccccc1-2
Yield: 90 %

Procedure:
To 4.72 grams of 4-(2-fluorenyl)-butan-2-ol were added 1.74 grams of pyridine and 2.24 grams of acetic anhydride and the mixture was heated to reflux for 25 hours. An excess of acetic anhydride and pyridine was removed by evaporation, the residue was subjected to a silica gel column chromatography, the column was eluted with a 4:1 mixture of n-hexane and ethyl acetate, and the resulting crystals were recrystallized from n-hexane to give 5 grams of 4-(2-fluorenyl)-butan-2-ol acetate, white crystals, m.p. 63°-64.5° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([Mg]Br)=[CH:4][C:3]=1[CH3:10].[CH2:11]([O:13][P:14]([CH2:19][CH:20]1[CH2:22][O:21]1)(=[O:18])[O:15][CH2:16][CH3:17])[CH3:12].[Cl-].[NH4+]>C1COCC1>[CH2:16]([O:15][P:14]([CH2:19][CH:20]([OH:21])[CH2:22][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[C:3]([CH3:10])[CH:4]=1)(=[O:18])[O:13][CH2:11][CH3:12])[CH3:17]
Reactant: Cc1cc([Mg]Br)ccc1F
Reactant: CCOP(=O)(CC1CO1)OCC
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CCOP(=O)(CC(O)Cc1ccc(F)c(C)c1)OCC
Temperature: -150 °C
Reaction time: 0.17 h
Yield: 86.6 %

Procedure:
To a solution of 4-fluoro-3-methylphenylmagnesium bromide (0.5M in Et2O, 15.5 mL, 7.75 mmol) in THF (10 mL) at −30° C. was added Cul (196 mg, 1.03 mmol) and the reaction mixture was stirred for 10 minutes. The reaction mixture was warmed to −150° C. and oxiranylmethyl-phosphonic acid diethyl ester (1 g, 5.2 mmol) in THF (10 mL) was added. The reaction mixture was stirred at 0° C. for 2 h. Saturated aqueous ammonium chloride was added and the product was extracted into EtOAc. The organic solution was dried (MgSO4), filtered and concentrated. Purification by medium pressure chromatography (20% EtOAc in hexanes to 70% EtOAc in hexanes) provided [3-(4-fluoro-3-methyl-phenyl)-2-hydroxy-propyl]-phosphonic acid diethyl ester (1.37 g).
Reaction SMILES: [OH:1][NH:2][C:3](=[NH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[O:11]1[C:15]2([CH2:20][CH2:19][N:18]([C:21]#N)[CH2:17][CH2:16]2)[O:14][CH2:13][CH2:12]1>O1CCCC1.C(OCC)(=O)C.[Cl-].[Zn+2].[Cl-]>[C:4]1([C:3]2[N:10]=[C:21]([N:18]3[CH2:19][CH2:20][C:15]4([O:11][CH2:12][CH2:13][O:14]4)[CH2:16][CH2:17]3)[O:1][N:2]=2)[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: N#CN1CCC2(CC1)OCCO2
Reactant: N=C(NO)c1ccccc1
Agent: [Cl-]
Agent: [Zn+2]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: c1ccc(-c2noc(N3CCC4(CC3)OCCO4)n2)cc1
Temperature: 50 °C
Reaction time: 3 h

Procedure:
A 0.5 M solution of zinc chloride in tetrahydrofuran (18.00 mL) is added dropwise at room temperature to a mixture of N-hydroxy-benzamidine (817 mg) and 1,4-dioxa-8-aza-spiro[4.5]decane-8-carbonitrile (1.00 g) in ethyl acetate (20 mL). The reaction mixture is stirred at 50° C. for 3 h and cooled to room temperature. The precipitate is filtered off and heated to 100° C. for 1 h in a mixture of ethanol (10 mL) and glacial acetic acid (5 mL). The solvents are evaporated and the crude product is purified by HPLC. TLC: rf=0.88 (silica gel, CH2Cl2/MeOH 9:1); Mass spectrum (ESI+): m/z=288 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[N:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.C(N(CC)CC)C.C[C:23]1[C:24]([NH2:28])=[N:25][O:26][N:27]=1>ClCCl>[Cl:1][C:2]1[N:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[CH:7][C:3]=1[C:4]([NH:28][C:24]1[CH:23]=[N:27][O:26][N:25]=1)=[O:6]
Reactant: O=C(O)c1ccc(C(F)(F)F)nc1Cl
Reactant: Cc1nonc1N
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(Nc1cnon1)c1ccc(C(F)(F)F)nc1Cl
Temperature: 25 °C
Reaction time: 14 h

Procedure:
239 mg (1.06 mmol) of 2-chloro-6-(trifluoromethyl)nicotinic acid and 1.6 g (2.0 mmol) of Mukaiyama reagent on polymer (1.25 mmol/g) are admixed with 15 ml of dichloromethane (abs.) and 0.31 g (3.03 mmol) of triethylamine. Then 100 mg (1.01 mmol) of 4-methyl-1,2,5-oxadiazol-3-ylamine are added. The reaction mixture is stirred at room temperature (RT) for 14 h. Subsequently, the solid is removed by means of a frit and washed with 10 ml of dichloromethane. The filtrate is concentrated and purified by chromatography using a silica gel column with heptane/ethyl acetate. Yield: 52 mg (16%).
Reaction SMILES: [F:1][CH:2]([C:7]([O:9]C)=O)[C:3](OC)=[O:4].Cl.[NH2:12][C:13]([NH2:15])=[NH:14]>>[OH:9][C:7]1[C:2]([F:1])=[C:3]([OH:4])[N:14]=[C:13]([NH2:15])[N:12]=1
Reactant: COC(=O)C(F)C(=O)OC
Reactant: N=C(N)N
Agent: Cl
Product: Nc1nc(O)c(F)c(O)n1

Procedure:
Commercially available dimethyl fluoromalonate (1) (or the diethyl ester) is condensed with guanidine hydrochloride (2) to yield 4,6-dihydroxy-5-fluoro-2-pyrimidineamine (3). This product (3) was converted to the dichloride (4) with POCl3 /2-picoline. Introduction of the 4-amino group was carried out undersealed tube conditions to give (5). Oxidation of (5) with MCPBA formed the N-oxide (6) which was smoothly converted to the 5-fluoro minoxidil with piperidine in refluxing ethanol.
Reaction SMILES: C([NH:8][C@H:9]([C:20]([OH:22])=O)[CH2:10][C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[NH:13][CH:12]=1)(OC(C)(C)C)=O.ON1C2C=CC=CC=2N=N1.[ClH:33].CN(C)CCCN=C=NCC.[F:45][C:46]([F:60])([F:59])[C:47]1[CH:48]=[C:49]([CH:52]=[C:53]([C:55]([F:58])([F:57])[F:56])[CH:54]=1)[CH2:50][NH2:51]>CN(C)C=O.ClCCl.Cl>[ClH:33].[F:45][C:46]([F:59])([F:60])[C:47]1[CH:48]=[C:49]([CH:52]=[C:53]([C:55]([F:58])([F:56])[F:57])[CH:54]=1)[CH2:50][NH:51][C:20](=[O:22])[C@H:9]([CH2:10][C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[NH:13][CH:12]=1)[NH2:8]
Reactant: NCc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: ClCCl
Product: N[C@@H](Cc1c[nH]c2ccccc12)C(=O)NCc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reaction time: 16 h

Procedure:
To a stirred solution of N-Boc-L-tryptophan (5 g) and 1-hydroxybenzotriazole (2.48 g) in dimethyl formamide (85 ml) was added 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride (3.15 g) at 0° C. After 30 minutes 3,5-bistrifluoromethylbenzylamine (4.43 g) was added and stirring continued for 16 hours at 25° C. The reaction mixture was diluted with dichloromethane and washed with sodium bicarbonate solution, water and dried (Na2SO4). The solvents were evaporated in vacuo to give a white solid which was dissolved in methanolic hydrogen chloride and allowed to stand for 16 hours. Concentration under reduced pressure afforded the title compound as a solid.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH3:14])[CH2:9][CH2:10][C:11]([OH:13])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:16][NH:17][O:18][CH3:19].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C=O)C>[CH3:19][O:18][N:17]([CH3:16])[C:11](=[O:13])[CH2:10][CH2:9][N:8]([CH3:14])[C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4]
Reactant: CN(CCC(=O)O)C(=O)OC(C)(C)C
Reactant: CNOC
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CON(C)C(=O)CCN(C)C(=O)OC(C)(C)C
Temperature: 25 °C
Yield: 99 %

Procedure:
To a stirred solution of 3-[(tert-butoxycarbonyl)(methyl)amino]-propanoic acid (5.0 g, 24.6 mmol), N,O-dimethylhydroxylamine hydrochloride (3.1 g, 32.0 mmol) and HBTU (11.2 g, 29.5 mmol) in DMF (50 mL) at 0° C. was added triethylamine (10.2 mL, 73.8 mmol). The mixture was stirred at room temperature over night and the solvent was removed under reduced pressure. The residue was taken up in ethyl acetate (300 mL), washed with water (100 mL) and 0.6 N NaOH solution (100 mL). The aqueous phases were back extracted with ethyl acetate (100 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (120 g column, 0% ethyl acetate in hexanes to 100% ethyl acetate in hexanes) to give product (6.0 g, 99%). 1H NMR (CDCl3) 3.69 (s, 3H), 3.52 (t, J=6.2 Hz, 2H), 3.18 (s, 3H), 2.88 (s, 3H), 2.66 (brs, 2H), 1.45 (s, 9H); MS EI m/z 269 (M+Na)+.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][CH2:8][NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13].ClC1C=CC=C(C(OO)=[O:25])C=1>C(OCC)(=O)C>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][CH2:8][NH+:9]([O-:25])[C:10](=[O:16])[O:11][C:12]([CH3:13])([CH3:15])[CH3:14]
Reactant: CC(C)(C)OC(=O)NCCc1ccccn1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)[NH+]([O-])CCc1ccccn1
Temperature: 25 °C
Reaction time: 15 h
Yield: 99.1 %

Procedure:
tert-Butyl 2-(2-pyridyl)ethylcarbamate (18.5 g, 83 mmol) and 3-chloroperbenzoic acid (77%, 24.5 g, 109 mmol) were dissolved in ethyl acetate (200 ml), and the mixture was stirred at room temperature for 15 hrs. The solvent was evaporated, and the residue was subjected to a silica gel column chromatography. The fractions eluted with methanol-ethyl acetate (1:4, v/v) were collected and concentrated to give the titled compound (19.6 g, 99%).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[N+:14]([O-])=O)=[CH:4][CH:3]=1>CO.[Pd]>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[NH2:14])=[CH:6][CH:7]=1
Reactant: Cc1ccc(-c2ccccc2[N+](=O)[O-])cc1
Agent: [Pd]
Solvent: CO
Product: Cc1ccc(-c2ccccc2N)cc1
Yield: 93.1 %

Procedure:
A solution of 15 g (70 mmol) of 4-methyl-2'-nitro-1,1'-biphenyl in 160 mL of methanol containing 900 mg of 5% palladium on carbon was hydrogenated for 1.5 hours at 40 psi. The reaction mixture was filtered through Celite and the filtrate evaporated under vacuum to yield 11.94 g (65.2 mmol, 93%) of the product. FAB-MS: calculated for C13H13N 183; found 184 (M+1).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:16]2[C:20]([CH2:21][N:22]([CH3:24])[CH3:23])=[N:19][N:18]=[C:17]2[CH2:25]O)=[C:6]([CH:15]=1)[C:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:8].CS(Cl)(=O)=O.[CH:32]1([CH2:35][NH2:36])[CH2:34][CH2:33]1>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:16]2[C:20]([CH2:21][N:22]([CH3:24])[CH3:23])=[N:19][N:18]=[C:17]2[CH2:25][NH:36][CH2:35][CH:32]2[CH2:34][CH2:33]2)=[C:6]([CH:15]=1)[C:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:8]
Reactant: CN(C)Cc1nnc(CO)n1-c1ccc(Br)cc1C(=O)c1ccccc1
Reactant: NCC1CC1
Agent: CS(=O)(=O)Cl
Product: CN(C)Cc1nnc(CNCC2CC2)n1-c1ccc(Br)cc1C(=O)c1ccccc1

Procedure:
In the manner given in Example 47, 5-bromo-2-[3-(hydroxymethyl)-5-[(dimethylamino)methyl]-4H-1,2,4-triazol-4-yl]benzophenone is treated first with methanesulfonyl chloride followed by (cyclopropylmethyl)-amine to give 5-bromo-2-[3-[[(cyclopropylmethyl)amino]-methyl]-5-[(dimethylamino)methyl]-4H-1,2,4-triazol-4-yl]-benzophenone.
Reaction SMILES: [CH:1]([C:3]1[N:7]2[CH:8]=[CH:9][CH:10]=[C:11]([OH:12])[C:6]2=[N:5][C:4]=1[CH3:13])=[O:2].C(N([CH2:19][CH3:20])CC)C>CO>[CH:1]([C:3]1[N:7]2[CH:8]=[CH:9][CH:10]=[C:11]([O:12][C@H:10]3[C:19]4[C:20](=[CH:1][CH:3]=[CH:4][CH:13]=4)[CH2:6][C@@H:11]3[OH:12])[C:6]2=[N:5][C:4]=1[CH3:13])=[O:2]
Reactant: Cc1nc2c(O)cccn2c1C=O
Reactant: CCN(CC)CC
Solvent: CO
Product: Cc1nc2c(O[C@H]3c4ccccc4C[C@@H]3O)cccn2c1C=O
Yield: 52.3 %

Procedure:
3.30 g of 3-formyl-8-hydroxy-2-methyl-imidazo[1,2-a]pyridine and 1.40 g (-)-1R,2S-indenoxide are reacted, analogously to the method described in Example 21, with 1.90 g of triethylamine in 425 ml of aqueous methanol (350 ml methanol+75 g water) at 50° C. After 8 hours the solution is evaporated and the residue dissolved in 150 ml water. 4 g of sodium carbonate is added and extracted with 4×100 ml ethyl acetate. The organic phases are washed with 2×200 ml sodium carbonate solution and 4×200 ml water, dried over magnesium sulfate and evaporated. The solid residue is mixed in 100 ml cyclohexane filtered and dried. 1.51 g of the title compound m.p. 187°- 192° C. is isolated [α]D22 =+112° (c=0.5, chloroform).
Reaction SMILES: [NH2:1][C@@H:2]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[CH2:10][C@@H:9]([NH:14][C:15](=[O:29])[C:16]1[CH:21]=[CH:20][C:19]([O:22][CH2:23][C@@H:24]3[CH2:28][CH2:27][CH2:26][O:25]3)=[CH:18][CH:17]=1)[CH2:8][CH2:7]2)[CH3:3].Br[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36]Br.C(N(C(C)C)C(C)C)C>C(#N)C>[N:1]1([C@@H:2]([C:4]2[CH:5]=[C:6]3[C:11](=[CH:12][CH:13]=2)[CH2:10][C@@H:9]([NH:14][C:15](=[O:29])[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH2:23][C@@H:24]4[CH2:28][CH2:27][CH2:26][O:25]4)=[CH:18][CH:17]=2)[CH2:8][CH2:7]3)[CH3:3])[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1
Reactant: BrCCCCCCBr
Reactant: C[C@@H](N)c1ccc2c(c1)CC[C@H](NC(=O)c1ccc(OC[C@@H]3CCCO3)cc1)C2
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: C[C@H](c1ccc2c(c1)CC[C@H](NC(=O)c1ccc(OC[C@@H]3CCCO3)cc1)C2)N1CCCCCC1
Temperature: 40 °C

Procedure:
A mixture of N-[(S)-6-((R)-1-aminoethyl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-[(S)-1-(tetrahydrofuran-2-yl)methoxy]benzamide (50 mg), 1,6-dibromohexane (31 mg), ethyldiisopropylamine (0.10 ml) and acetonitrile (1 ml) was heated to 40° C. for 8 hours. The cooled reaction mixture was concentrated and the residue was purified by preparative HPLC. The product was thus obtained with the molecular weight of 476.66 (C30H40N2O3); MS (ESI): 477 (M+H+).
Reaction SMILES: [CH2:1]1[C:11]2=[C:12]3[C:7](=[CH:8][CH:9]=[CH:10]2)[CH:6]=[CH:5][CH:4]=[C:3]3[CH2:2]1.[H][H]>[Ni]>[CH2:1]1[CH:11]2[CH:12]3[CH:7]([CH2:8][CH2:9][CH2:10]2)[CH2:6][CH2:5][CH2:4][CH:3]3[CH2:2]1
Reactant: [H][H]
Reactant: c1cc2c3c(cccc3c1)CC2
Agent: [Ni]
Product: C1CC2CCCC3CCC(C1)C23
Reaction time: 7 h
Yield: 100 %

Procedure:
A shaking autoclave having an internal volume of about 60 ml was charged with 5 grams of acenaphthene and 0.2 gram of a 50% Ni/kieselguhr catalyst and with hydrogen at an initial pressure of 200 kg/cm2 gauge. Reaction was effected at 200° C. for 7 hours. Perhydroacenaphthene was produced in a yield of 100%, and the combined selectivity of Nos. 1 and 3 trans-isomers was 96%.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[O:8][CH3:9].C[CH2:11][O:12]CC>C(Cl)Cl.[Ti](Cl)(Cl)(Cl)Cl>[F:1][C:2]1[CH:7]=[C:6]([CH:5]=[CH:4][C:3]=1[O:8][CH3:9])[CH:11]=[O:12]
Reactant: CCOCC
Reactant: COc1ccccc1F
Agent: Cl[Ti](Cl)(Cl)Cl
Solvent: ClCCl
Product: COc1ccc(C=O)cc1F
Temperature: 15 °C
Reaction time: 1 h

Procedure:
To a solution of o-fluoroanisole, 101 g (0.80 mol) in 500 ml dry methylene chloride is added dropwise over 30 minutes a solution of titanium tetrachloride, 182 g (0.96 mol, 1.2 equiv.) and α,α-dichloromethylmethyl ether, 110 g (0.96 mol) in an equal volume of methylene chloride. The temperature is maintained at 10-20° C. with an ice-bath. The mixture is stirred at room temperature for 1 hour longer and then poured over crushed ice-water with stirring. Ether (1) is added, and the mixture stirred under nitrogen until solution occurs. The organic layer is extracted with water (3×), sodium bicarbonate solution (3×) and dried (MgSO4). The solvent is evaporated off at 30° C. to give crude product as an oil. The oil is vacuum distilled through a jacketed Vigreux column when it gives 3-fluoro-4-methoxybenzaldehyde, B.P. 120-121° C., at 10 mm Hg; Rf 0.6 on a silica-gel G plate with methylene chloride.