Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:6]=[CH:5][C:4]([C:7]([S:9][C:10]2[CH:18]=[CH:17][CH:16]=[CH:15][C:11]=2[C:12](O)=[O:13])=O)=[CH:3][CH:2]=1.C([N:27](CC)CC)C.ClC(OCC)=O.[N-]=[N+]=[N-].[Na+].C(P(CCCC)CCCC)CCC>CC(C)=O.O>[C:1]1([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:6]=[CH:5][C:4]([C:7]2[S:9][C:10]3[CH:18]=[CH:17][CH:16]=[CH:15][C:11]=3[C:12](=[O:13])[N:27]=2)=[CH:3][CH:2]=1
Reactant: O=C(Sc1ccccc1C(=O)O)c1ccc(-c2ccccc2)cc1
Reactant: CCN(CC)CC
Agent: CCCCP(CCCC)CCCC
Agent: CCOC(=O)Cl
Agent: [N-]=[N+]=[N-]
Solvent: CC(C)=O
Solvent: O
Product: O=c1nc(-c2ccc(-c3ccccc3)cc2)sc2ccccc12
Temperature: -10 °C
Yield: 62.5 %

Procedure:
2-[(1,1′-Biphenyl-4-ylcarbonyl)thio]benzoic acid (1.15 g, 3.4 mmol) was suspended in acetone (10 ml). While stirring under ice cooling, triethylamine (0.49 g, 4.8 mmol) and then ethyl chloroformate (0.52 g, 3.8 mmol) were dropwise added to the suspension. After stirring at the same temperature for an hour, an aqueous solution (10 ml) of sodium azide (0.34 g, 5.2 mmol) was dropwise added to the reaction mixture, followed by further stirring for an hour. The reaction mixture was diluted with water and the dilution was extracted with toluene (100 ml×2). The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and then filtered. The toluene solution was cooled to about −10° C. and tributylphosphine (0.84 g, 4.2 mmol) was dropwise added to the solution. After completion of the dropwise addition, the reaction temperature was reverted to room temperature and the mixture was heated under reflux for 15 minutes. The reaction solution was concentrated under reduced pressure and recrystallized from ethyl acetate-ethanol to give the title compound (0.67 g, 61%) as crystals.
Reaction SMILES: [CH3:1]C(C)([O-])C.[K+].[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:24]3=[C:25]4[C:20]([C:21](=O)[CH2:22][CH2:23]3)=[CH:19][CH:18]=[CH:17][N:16]4[CH:15]=2)=[CH:10][CH:9]=1.O>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCCC1>[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:24]3=[C:25]4[C:20]([C:21](=[CH2:1])[CH2:22][CH2:23]3)=[CH:19][CH:18]=[CH:17][N:16]4[CH:15]=2)=[CH:10][CH:9]=1
Reactant: CC(C)(C)[O-]
Reactant: O=C1CCc2c(-c3ccc(Cl)cc3)cn3cccc1c23
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: C=C1CCc2c(-c3ccc(Cl)cc3)cn3cccc1c23
Reaction time: 3 h

Procedure:
Methyltriphenylphosphonium bromide (3.8 g) was added to 25 ml of anhydrous tetrahydrofuran. To this mixture was added the solution of potassium t-butoxide (1.2 g) in 25 ml of tetrahydrofuran at ambient temperature. After stirring for 3 hours, to this solution was added the solution of 1-(4-chlorophenyl)-8,9-dihydro-7H-pyrrolo[3,2,1-ij]quinolin-7-one (1.5 g), which was obtained in example 2, in 15 ml of tetrahydrofuran. After stirring for 30 min., to this solution was added water and extracted with ethyl acetate. The organic solution was washed with brine and dried over anhydrous sodium sulfate. After removing drying agent by filtration and organic solvent by evaporation under reduced pressure, the residue was purified by alumina column chromatography, and the title compound was obtained as yellow crystals (1.1 g) .
Reaction SMILES: S(=O)(=O)(O)O.[NH:6]1[CH2:10][CH2:9][N:8]=[C:7]1[C:11]1[CH:25]=[CH:24][CH:23]=[CH:22][C:12]=1[C:13](C1C=CC(C)=CC=1)=[O:14].[OH-].[Na+]>>[N:6]1[CH:10]=[CH:9][N:8]2[CH:13]([OH:14])[C:12]3[C:11](=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:7]=12
Reactant: Cc1ccc(C(=O)c2ccccc2C2=NCCN2)cc1
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Product: OC1c2ccccc2-c2nccn21
Temperature: 0 °C

Procedure:
Twenty grams of the residue 9b-(p-tolyl)-1,2,3,9b-tetrahydro-1-(p-tolylsulfonyl)-1H-imidazo[2,1-a]isoindol-5-one are dissolved in 50 ml. of 80 percent sulfuric acid and stirred at room temperature for one hour. The reaction mixture which contains the sulfate salt of 2-(2-imidazolin-2-yl)-4'-methylbenzophenone is then cooled by the addition of ice water and made alkaline by the addition of a 10N sodium hydroxide solution. The precipitated solid is separated by decantation and recrystallized from dioxan to obtain crystalline 2,3-dihydro-5-(4-tolyl(-5H-imidazo[2,1-a]isoindol-5-ol, m.p. 208°-210°C.
Reaction SMILES: [OH-].[Na+].[CH3:3][N:4]([CH2:14][C:15]1[CH:16]=[C:17]([C:21]2[O:25][C:24]([CH:26]=[CH:27][C:28]([O-:30])=[O:29])=[CH:23][CH:22]=2)[CH:18]=[CH:19][CH:20]=1)[C:5](=[O:13])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].O1CCCC1.CO.O>C(O)(=O)C>[CH3:3][N:4]([CH2:14][C:15]1[CH:16]=[C:17]([C:21]2[O:25][C:24]([CH:26]=[CH:27][C:28]([OH:30])=[O:29])=[CH:23][CH:22]=2)[CH:18]=[CH:19][CH:20]=1)[C:5](=[O:13])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCCCCCC(=O)N(C)Cc1cccc(-c2ccc(C=CC(=O)[O-])o2)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Solvent: CC(=O)O
Product: CCCCCCCC(=O)N(C)Cc1cccc(-c2ccc(C=CC(=O)O)o2)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 57.9 %

Procedure:
300 mg (7.5 mmol, 12 eq) of sodium hydroxide are added to a solution of 250 mg (0.63 mmol, 1 eq) of 3-(5-{3-[(methyloctanoylamino)methyl]phenyl}furan-2-yl)acrylate in 4 mL of 9/1 tetrahydrofuran/methanol. The reaction mixture is stirred for two hours at room temperature. The reaction is stopped by adding 20 ml of water and 3 ml of acetic acid and is then extracted with ethyl acetate. The organic phases are combined and dried over sodium sulfate. The solvents are evaporated off and the residue is then chromatographed on silica gel (90/10 dichloromethane/methanol). The oil obtained is crystallized from pentane. 140 mg of 3-(5-{3-[(methyloctanoylamino)methyl]phenyl}furan-2-yl)acrylic acid are obtained. Yield=58%. m.p.=96-98° C.
Reaction SMILES: [CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[S:12][C:11]3=[N:13][CH:14]=[C:15](I)[N:10]3[N:9]=2)[CH:5]=[N:4]1)[CH3:2].CC1(C)C(C)(C)OB([C:25]2[CH:26]=[C:27]([C:32]([F:35])([F:34])[F:33])[C:28]([NH2:31])=[N:29][CH:30]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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>[CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[S:12][C:11]3=[N:13][CH:14]=[C:15]([C:25]4[CH:26]=[C:27]([C:32]([F:35])([F:34])[F:33])[C:28]([NH2:31])=[N:29][CH:30]=4)[N:10]3[N:9]=2)[CH:5]=[N:4]1)[CH3:2]
Reactant: CC1(C)OB(c2cnc(N)c(C(F)(F)F)c2)OC1(C)C
Reactant: CCn1cc(-c2nn3c(I)cnc3s2)cn1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Product: CCn1cc(-c2nn3c(-c4cnc(N)c(C(F)(F)F)c4)cnc3s2)cn1
Yield: 13.2 %

Procedure:
A mixture of 2-(1-Ethyl-1H-pyrazol-4-yl)-5-iodo-imidazo[2,1-b][1,3,4]thiadiazole (110 mg, 0.319 mmol, 1 eq), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3-trifluoromethyl-pyridin-2-ylamine (119 mg, 0.414 mmol, 1.3 eq), Pd(PPh3)2Cl2 (45 mg, 0.064 mmol, 0.2 eq) and 2M aq Na2CO3 (1 mL) in dioxane (3 mL) was refluxed for 2 h. The solvent was evaporated and the residue was treated with water. The suspension was filtered off and washed with Et2O. The solid was purified by column chromatography (DCM/MeOH 9:1) to afford the desired product (16 mg, 13%). HPLC-MS (5-100% B in 8 min at 0.8 mL): tR=4.62 min, [M+H]+ m/z 380.1; 1H NMR (300 MHz, DMSO) δ 8.84 (s, 1H), 8.61 (s, 1H), 8.29 (d, J=2.0 Hz, 1H), 8.08 (s, 1H), 7.74 (s, 1H), 6.72 (s, 2H), 4.24 (q, J=7.3 Hz, 2H), 1.43 (t, J=7.3 Hz, 3H).
Reaction SMILES: [N:1]1([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:8][CH2:7][CH2:6][C@H:2]1[C:3]([OH:5])=O.Cl.[NH2:20][NH:21][C:22]([NH2:24])=[O:23].C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>CN(C=O)C.C(N(CC)CC)C>[N:1]1([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:8][CH2:7][CH2:6][C@H:2]1[C:3]([NH:20][NH:21][C:22]([NH2:24])=[O:23])=[O:5]
Reactant: NNC(N)=O
Reactant: O=C(O)[C@@H]1CCCN1C(=O)OCc1ccccc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: NC(=O)NNC(=O)[C@@H]1CCCN1C(=O)OCc1ccccc1

Procedure:
To a solution of Cbz-Pro (1.25 g), semicarbazide hydrochloride (5.5 g), and HOBt (6.75 g) in DMF (100 mL) is added triethylamine (7.5 mL) and DCC (10.5 g) at 0° C. with stirring. The reaction is stirred at 0° C. for 24 hours. The precipitate is filtered and the filtrate is concentrated in vacuo. The residue is triturated with saturated NaHCO3 solution, filtered, washed with water and dried to give Cbz-Pro-azaGlyNH2. Cbz-Pro-azaGlyNH2 (10 g) is catalytically hydrogenated in (1:1) methanol/DMF at pH 4.5 in the presence of Pd catalyst. At the end of the hydrogenation the catalyst is filtered and the filtrate is concentrated in vacuo to give H-Pro-azaGlyNH2.HCl. To a solution of H-Pro-azaGlyNH2.HCl (2.08 g), HOBt (1.63 g), and Boc-Lys(N,N-epsilon-isopropyl,Cbz)-OH (1.26 g) in DMF (40 mL), DCC (2.1 g) is added with stirring at 0° C. for 2 hours and then at 4° C. for 24 hours. After workup and trituration with ether Boc-Lys(N,N-epsilon-isopropyl,Cbz)-Pro-azaGlyNH2 is obtained.
Reaction SMILES: [O:1]1[C:6]2[CH:7]=[CH:8][C:9]([S:11][C:12]3[CH:17]=[CH:16][C:15](/[CH:18]=[CH:19]/[C:20]([N:22]4[CH2:27][CH2:26][CH:25]([C:28]([O:30]CC)=[O:29])[CH2:24][CH2:23]4)=[O:21])=[C:14]([Cl:33])[C:13]=3[Cl:34])=[CH:10][C:5]=2[O:4][CH2:3][CH2:2]1.[OH-].[K+].[OH-].[Na+]>CCOCC>[O:1]1[C:6]2[CH:7]=[CH:8][C:9]([S:11][C:12]3[CH:17]=[CH:16][C:15](/[CH:18]=[CH:19]/[C:20]([N:22]4[CH2:27][CH2:26][CH:25]([C:28]([OH:30])=[O:29])[CH2:24][CH2:23]4)=[O:21])=[C:14]([Cl:33])[C:13]=3[Cl:34])=[CH:10][C:5]=2[O:4][CH2:3][CH2:2]1
Reactant: CCOC(=O)C1CCN(C(=O)/C=C/c2ccc(Sc3ccc4c(c3)OCCO4)c(Cl)c2Cl)CC1
Agent: [K+]
Agent: [Na+]
Agent: [OH-]
Solvent: CCOCC
Product: O=C(O)C1CCN(C(=O)/C=C/c2ccc(Sc3ccc4c(c3)OCCO4)c(Cl)c2Cl)CC1

Procedure:
The title compound was prepared by the procedures described in Example 155, substituting the ethyl ester from Example 137 with the ethyl ester from Example 328, and KOH with NaOH, to produce a white solid. 1H NMR (d6-DMSO, 300 MHz) δ 1.33-1.55 (m, 2H), 1.62-1.78 (m, 2H), 1.93-2.07 (m, 1H), 2.90 (brt, J=10.5 Hz, 1H), 3.16 (brt, J=10.5 Hz, 1H), 3.96 (br d, J=13.5 Hz, 1H), 4.09 (br d, J=13.5 Hz, 1H), 4.26-4.42 (m, 4H), 6.60 (d, J=9.0 Hz, 1H), 7.04-7.08 (m, 2H), 7.13 (d, J=1.5 Hz, 1H), 7.22 (d, J=15.3 Hz, 1H), 7.70 (d, J=15.3 Hz, 1H), 7.86 (d, J=9.0 Hz, 1H). MS (ESI+) (M+H)+ at m/z 516, 518, 520. Anal. Calcd for C23H20Cl2N1NaO5S.0.36 Et2O: C, 54.06; H, 4.38; N, 2.58. Found: C, 53.99; H, 4.37; N, 2.22.
Reaction SMILES: [N:1]1[C:8](Cl)=[N:7][C:5](Cl)=[N:4][C:2]=1[Cl:3].[Cl-].[Al+3].[Cl-].[Cl-].Cl.[C:15]1([CH3:21])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>ClC1C=CC=CC=1Cl>[Cl:3][C:2]1[N:4]=[C:5]([C:18]2[CH:19]=[CH:20][C:15]([CH3:21])=[CH:16][CH:17]=2)[N:7]=[C:8]([C:18]2[CH:19]=[CH:20][C:15]([CH3:21])=[CH:16][CH:17]=2)[N:1]=1
Reactant: Cc1ccccc1
Reactant: Clc1nc(Cl)nc(Cl)n1
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: Clc1ccccc1Cl
Product: Cc1ccc(-c2nc(Cl)nc(-c3ccc(C)cc3)n2)cc1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
To a stirring mixture of 1 eq of cyanuric chloride and 3 eq of aluminum chloride in o-dichlorobenzene at ice bath temperature was added concentrated HCl (13 wt % based on cyanuric chloride). After 10 minutes, 1.9 eq of toluene was added and the reaction mixture was stirred at ice bath temperature for 30 minutes. The cooling bath was removed, the reaction mixture was allowed to warm to room temperature, and stirred for 21 h. HPLC analysis indicated about 95% cyanuric chloride conversion to 2-chloro-4,6-bis(4-methylphenyl)-1,3,5-triazine and the isomer 2-chloro-4-(4-methylphenyl)-6-(2-methylphenyl)-1,3,5-triazine
Reaction SMILES: [F:1][C:2]1[CH:9]=[C:8]([OH:10])[C:7]([O:11][CH3:12])=[CH:6][C:3]=1[CH:4]=[O:5].[H-].[Na+].Cl[CH2:16][C:17]1[N:21]([CH3:22])[C:20]2[CH:23]=[CH:24][CH:25]=[CH:26][C:19]=2[N:18]=1.O>CN(C)C(=O)C>[F:1][C:2]1[CH:9]=[C:8]([O:10][CH2:16][C:17]2[N:21]([CH3:22])[C:20]3[CH:23]=[CH:24][CH:25]=[CH:26][C:19]=3[N:18]=2)[C:7]([O:11][CH3:12])=[CH:6][C:3]=1[CH:4]=[O:5]
Reactant: COc1cc(C=O)c(F)cc1O
Reactant: Cn1c(CCl)nc2ccccc21
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CC(=O)N(C)C
Product: COc1cc(C=O)c(F)cc1OCc1nc2ccccc2n1C
Temperature: 80 °C
Yield: 267.3 %

Procedure:
To a solution of 2-fluoro-4-hydroxy-5-methoxy-benzaldehyde (39, 3.0 g, 5 mmol) in N,N-dimethylacetamide (120 mL) was added sodium hydride (60% dispersion in mineral oil, 0.8 g, 19 mmol) portion wise. After the addition was complete, the reaction was stirred for 30 minutes after which 2-chloromethyl-1-methyl-1H-benzoimidazole (212, 2.9 g, 16 mmol) was added and then heated at 80° C. overnight. The reaction mixture was then poured into water (1 L) with stirring and the precipitated solid was filtered, washed with water and dried to give the desired compound (213, 4.2 g, 84% yield).
Reaction SMILES: [ClH:1].[CH2:2]([N:9]1[CH2:14][CH:13]=[C:12]([CH:15]=[CH:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)[CH2:11][CH2:10]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:25]1(=[O:31])[O:30][C:28](=[O:29])[CH:27]=[CH:26]1.C(OC(=O)C)(=O)C.C1(C=CC(O)=CC=1)O>C(O)(=O)C>[ClH:1].[CH2:2]([N:9]1[CH2:10][CH2:11][C:12]2[CH:13]([CH:26]3[C:25](=[O:31])[O:30][C:28](=[O:29])[CH:27]3[CH:16]([C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=3)[CH:15]=2)[CH2:14]1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1
Reactant: COc1ccc(C=CC2=CCN(Cc3ccccc3)CC2)cc1
Reactant: O=C1C=CC(=O)O1
Agent: Cl
Agent: Oc1ccc(O)cc1
Solvent: CC(=O)OC(C)=O
Solvent: CC(=O)O
Product: COc1ccc(C2C=C3CCN(Cc4ccccc4)CC3C3C(=O)OC(=O)C23)cc1

Procedure:
A solution of 21 g (0.06 moles) 1-benzyl-1,2,3,6-tetrahydro-4-(p-methoxystyryl)-pyridine, hydrochloride, from example 6, 37.8 g ground maleic anhydride, 135 ml. glacial acetic acid, 135 ml. acetic anhydride and 20 mg hydroquinone is refluxed under nitrogen for 1/2 hour. The solution is allowed to cool and evaporate to an oil. The crude Diels-Alder adduct (quantitative yield of 2-benzyl-1,2,3,4,6,7,8,8a-octahydro-6-(p-methoxyphenyl)-7,8-isoquinoline-dicarboxylic acid anhydride hydrochloride) is dissolved in 500 ml. methanol and 20 ml. hydrochloric acid in isopropanol and refluxed for 18 hours. The solution is allowed to cool and evaporated. The residue is triturated in ether and solid filtered to afford a quantitative yield of 2-benzyl-1,2,3,4,6,7,8,8a-octahydro-6-(p-methoxyphenyl)-7,8-isoquinoline-dicarboxylic acid, dimethyl ester, hydrochloride. After recrystallization from acetone-ether the mp is 200° to 209°C with decomposition.
Reaction SMILES: C[O:2][C:3](=[O:19])[C:4]1[CH:16]=[C:15]([CH:17]=[CH2:18])[CH:14]=[C:6]([C:7]([N:9]([CH3:13])[CH2:10][CH2:11][CH3:12])=[O:8])[CH:5]=1.[OH-].[Li+]>C1COCC1>[CH3:13][N:9]([CH2:10][CH2:11][CH3:12])[C:7](=[O:8])[C:6]1[CH:5]=[C:4]([CH:16]=[C:15]([CH:17]=[CH2:18])[CH:14]=1)[C:3]([OH:19])=[O:2]
Reactant: C=Cc1cc(C(=O)OC)cc(C(=O)N(C)CCC)c1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Product: C=Cc1cc(C(=O)O)cc(C(=O)N(C)CCC)c1
Yield: 70.1 %

Procedure:
Stir a solution of N-methyl-N-propyl-5-vinyl-isophthalamic acid methyl ester (78 mg, 0.3 mmol), 1 N lithium hydroxide (1.5 mL, 1.5 mmol), and THF (1.5 mL) at room temperature overnight. Add water and extract with ethyl acetate. Acidify the aqueous with 5 N HCl, extract with ethyl acetate, dry (magnesium sulfate) and concentrate to give the title compound (52 mg, 70%).
Reaction SMILES: [CH3:1][C:2]1[CH2:3][C@H:4]([OH:11])[CH2:5][C:6]([CH3:10])([CH3:9])[C:7]=1[CH3:8].N1C=CC=CC=1.FC(F)(F)S(O[Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])(=O)=O.O>C(Cl)Cl>[Si:24]([O:11][C@@H:4]1[CH2:5][C:6]([CH3:10])([CH3:9])[C:7]([CH3:8])=[C:2]([CH3:1])[CH2:3]1)([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25]
Reactant: CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F
Reactant: CC1=C(C)C(C)(C)C[C@@H](O)C1
Solvent: ClCCl
Solvent: O
Solvent: c1ccncc1
Product: CC1=C(C)C(C)(C)C[C@@H](O[Si](C)(C)C(C)(C)C)C1
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
0.8 g (5.2 mmol) of the (1S)-3,4,5,5-tetramethyl-3-cyclohexen-1-ol obtained in Example 2B was dissolved in 5 ml of absolute methylene chloride, 0.5 ml of pyridine was added to the solution, and the mixture was cooled to 0° C. Subsequently 1.54 g (5.7 mmol) of tert-butyldimethylsilyl trifluorome-thanesulfonate were added and the mixture was stirred at 0° C. for 15 min and then poured into 10 ml of water. After extraction with 10 ml of methylene chloride, the organic phase was washed with 10 ml of 0.1 M H2SO4, 10 ml of saturated NaHCO3 solution and 10 ml of water, dried over MgSO4 and concentrated to result in 1.3 g (92% of theory) of the abovementioned product.
Reaction SMILES: [I-:1].[CH2:2]([N+:9]1[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[S:11][C:10]=1[CH3:18])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[CH3:19][N:20]([CH3:33])[C:21]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24]([CH:31]=O)=[CH:23][CH:22]=1>C(OC(=O)C)(=O)C>[I-:1].[CH3:19][N:20]([CH3:33])[C:21]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24](/[CH:31]=[CH:18]/[C:10]2[S:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[N+:9]=2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])=[CH:23][CH:22]=1
Reactant: CN(C)c1ccc(C=O)c2ccccc12
Reactant: CCCCCCC[n+]1c(C)sc2ccccc21
Agent: [I-]
Solvent: CC(=O)OC(C)=O
Product: CCCCCCC[n+]1c(/C=C/c2ccc(N(C)C)c3ccccc23)sc2ccccc21

Procedure:
A mixture of 3-heptyl-2-methylbenzothiazolium iodide (0.50 g, 1.33 mmol) and 4-dimethylamino-1-naphthaldehyde (0.40 g, 2.01 mmol) in 5 mL of acetic anhydride under nitrogen was heated. Upon refluxing, the mixture turned purple and all solids seemed to be in solution. The solution was refluxed for 15 minutes and on cooling, solid formed. The mixture was filtered and washed with ethyl acetate to give (E)-2-[2-(4-dimethylaminonaphthalen-1-yl)vinyl]-3-heptylbenzothiazol-3-ium iodide as a dark brown solid, mp 195-197° C.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH3:11])[C:5]([OH:7])=[O:6].C(=O)([O-])[O-].[K+].[K+].[CH2:18](Br)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.O>CN(C=O)C>[CH2:18]([O:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH3:11])[C:5]([O:7][CH2:5][C:4]1[CH:8]=[CH:9][CH:10]=[CH:2][CH:3]=1)=[O:6])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: Cc1ccc(C(=O)O)cc1O
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1ccc(C(=O)OCc2ccccc2)cc1OCc1ccccc1
Reaction time: 3 h
Yield: 196.8 %

Procedure:
To a mixture of 3-hydroxy-4-methylbenzoic acid (2.00 g) and potassium carbonate (5.40 g) in DMF (20 mL) was added dropwise benzyl bromide (4.50 g) at room temperature, and the mixture was stirred for 3 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give the title compound (4.30 g) as a colorless oil. This compound was used for the next step without further purification.
Reaction SMILES: [C:1]([O:18][CH:19]([CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[CH2:20][C:21]([NH:23][CH2:24][C:25]([OH:27])=O)=[O:22])(=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].[NH2:43][C@H:44]([C:55]([OH:57])=[O:56])[CH2:45][C:46]1[C:54]2[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=2)[NH:48][CH:47]=1>>[C:1]([O:18][CH:19]([CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[CH2:20][C:21]([NH:23][CH2:24][C:25]([NH:43][C@H:44]([C:55]([OH:57])=[O:56])[CH2:45][C:46]1[C:54]2[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=2)[NH:48][CH:47]=1)=[O:27])=[O:22])(=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: CCCCCCCCCCCCCCCC(=O)OC(CCCCCCCCCCCCCCC)CC(=O)NCC(=O)O
Reactant: N[C@@H](Cc1c[nH]c2ccccc12)C(=O)O
Product: CCCCCCCCCCCCCCCC(=O)OC(CCCCCCCCCCCCCCC)CC(=O)NCC(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)O
Yield: 48.1 %

Procedure:
N-(3-hexadecanoyloxyoctadecanoyl)glycine (1.3 g) prepared by the method described in Example 27 and L-tryptophan (1.45 g), N-[N-(3-hexadecanoyloxyoctadecanoyl)glycyl]-L-tryptophan (820 mg) was obtained as powders according to a similar manner to that of Example 29.
Reaction SMILES: N[C:2]1[CH:17]=[CH:16][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([C:13](=[O:15])[CH3:14])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.S(=O)(=O)(O)O.N([O-])=O.[Na+].[I-:27].[Na+]>C(COC)OC.O.C(OCC)(=O)C>[I:27][C:2]1[CH:17]=[CH:16][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([C:13](=[O:15])[CH3:14])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1
Reactant: CC(=O)c1ccc(Oc2ccc(N)cc2)cc1
Reactant: [I-]
Agent: O=N[O-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: COCCOC
Solvent: O
Solvent: CCOC(C)=O
Product: CC(=O)c1ccc(Oc2ccc(I)cc2)cc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 76.1 %

Procedure:
To a solution of 1-(4-(4-aminophenoxy)phenyl)ethanone (6.0 g, 26.43 mmol), in dimethoxyethane (80 mL), was added a solution of sulphuric acid (10.9 mL, 206.19 mmol) in water (54.5 mL) dropwise. The resulting reaction mixture was cooled to 0° C. and a solution of sodium nitrite (2.74 g, 39.64 mmol) in water (18 mL) was added dropwise. The reaction mixture was stirred at 0-5° C. for additional 30 min and a solution of sodium iodide (19.81 g, 132.15 mmol) in water (54 mL) was added dropwise. The reaction mixture was stirred for additional 30 min. After the completion of reaction as confirmed by TLC, the reaction mixture was diluted with ethyl acetate (300 mL). The organic layer was separated, washed with water (100 mL), dried over Na2SO4 and concentrated in vacuo to afford crude product which was purified by column chromatography (silica gel, 3:7 EtOAc:Pet Ether) to afford the title compound (6.8 g, 76%) as a white solid.
Reaction SMILES: [N:1]([CH:4]([CH2:11][O:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)[CH2:5][N:6]1[CH:10]=[CH:9][N:8]=[CH:7]1)=[N+]=[N-].[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[NH2:1][CH:4]([CH2:11][O:12][CH2:13][C:14]1[CH:15]=[CH:16][C:17]([O:20][CH3:21])=[CH:18][CH:19]=1)[CH2:5][N:6]1[CH:10]=[CH:9][N:8]=[CH:7]1
Reactant: COc1ccc(COCC(Cn2ccnc2)N=[N+]=[N-])cc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: COc1ccc(COCC(N)Cn2ccnc2)cc1

Procedure:
A solution of 1-[2-azido-3-[(4-methoxyphenyl)methoxy]propyl]-1H-imidazole (5.1 g, 0.018 mol) in dry tetrahydrofuran (10 ml) was added dropwise to a stirred slurry of lithium aluminium hydride (0.68 g, 0.018 mol) in dry tetrahydrofuran (40 ml) at room temperature under a stream of dry nitrogen. When the addition was complete the reaction mixture was heated under reflux for 18 hours. The solvent was evaporated off under reduced pressure and the residue was extracted with ethyl acetate, washed with saturated aqueous ammonium chloride solution and dried (MgSO4). The solvent was evaporated off under reduced pressure to give 1-[2-amino-3-[(4-methoxyphenyl)methoxy]propyl]-1H-imidazole as an oil which was used directly without further purification.
Reaction SMILES: C[O:2][C:3](=[O:26])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([NH:10][C:11](=[O:25])[CH2:12][C:13]2[C:18]([O:19][CH3:20])=[CH:17][C:16]([O:21][CH3:22])=[CH:15][C:14]=2[O:23][CH3:24])[CH:5]=1.[Li+].[OH-].Cl>C1COCC1>[CH3:20][O:19][C:18]1[CH:17]=[C:16]([O:21][CH3:22])[CH:15]=[C:14]([O:23][CH3:24])[C:13]=1[CH2:12][C:11]([NH:10][C:6]1[CH:5]=[C:4]([CH:9]=[CH:8][CH:7]=1)[C:3]([OH:26])=[O:2])=[O:25]
Reactant: COC(=O)c1cccc(NC(=O)Cc2c(OC)cc(OC)cc2OC)c1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Product: COc1cc(OC)c(CC(=O)Nc2cccc(C(=O)O)c2)c(OC)c1
Yield: 99.5 %

Procedure:
Dissolve 3-[2-(2,4,6-Trimethoxy-phenyl)-acetylamino]-benzoic acid methyl ester (16) (140 mg, 0.39 mmol) in THF (25.0 mL) at rt and add 1M aqu LiOH (2.0 mL, 2.0 mmol). Stir reaction mixture 40 h at rt. Quench reaction mixture (cooling bath) with 2M aqu. HCl. Extract the mixture with EtOAc (3×), wash the combined organic layer with brine and dry with Na2SO4 to obtain 3-[2-(2,4,6-Trimethoxy-phenyl)-acetylamino]-benzoic acid (17) (134 mg, 99%) as a beige solid. 1H NMR (400 MHz, CD3OD): 3.71 (s, 2H); 3.84 (s, 3H); 3.85 (s, 6H); 6.29 (s, 2H); 7.43 (t, 1H, J=7.8 Hz); 7.76 (d, 1H, J=7.8 Hz); 7.83 (d, 1H, J=8.1 Hz); 8.19 (br.s, 1H).