Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]([O:4][CH2:5][CH3:6])=[O:3].[OH:7][CH2:8][CH2:9][NH:10][N:11]=[CH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.N1C=CC=CC=1>C(OCC)(=O)C>[OH:7][CH2:8][CH2:9][N:10]([C:2]([O:4][CH2:5][CH3:6])=[O:3])[N:11]=[CH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: OCCNN=Cc1ccccc1
Reactant: CCOC(=O)Cl
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Product: CCOC(=O)N(CCO)N=Cc1ccccc1

Procedure:
This acylation is performed in the following manner: 1.08 g (10-2 moles) of ethyl chloroformate in 5 ml of anhydrous ethyl acetate are added dropwise to a solution containing 10-2 moles of benzaldehyde (2-hydroxyethyl)hydrazone and 0.79 g (10-2 moles) of anhydrous pyridine in 20 ml of anhydrous ethyl acetate, with stirring in the cold. The reaction mixture is left at 0° C. with stirring for 2 hours and then it is filtered. The product obtained is washed with 10 ml of water and then dried and recrystallized from a mixture of ethyl acetate and petroleum ether. It has a melting point of 69.5° C. The reaction yield is 62%.
Reaction SMILES: Cl.C(C1C=C2C(=CC=1)[CH:15]=[C:14]([C:19](N)=[NH:20])[CH:13]=C2)CCCCCC.Cl.[CH2:23]([O:28][C:29]1[CH:30]=[C:31]2[C:36](=[CH:37][CH:38]=1)[CH:35]=[C:34]([C:39]([NH2:41])=[NH:40])[CH:33]=[CH:32]2)[CH2:24][CH2:25][CH2:26][CH3:27]>>[CH2:23]([O:28][C:29]1[CH:38]=[CH:37][C:36]2[C:31](=[CH:32][CH:33]=[C:34]([C:39]3[N:41]=[CH:15][C:14]([C:19]#[N:20])=[CH:13][N:40]=3)[CH:35]=2)[CH:30]=1)[CH2:24][CH2:25][CH2:26][CH3:27]
Reactant: CCCCCOc1ccc2cc(C(=N)N)ccc2c1
Reactant: CCCCCCCc1ccc2cc(C(=N)N)ccc2c1
Agent: Cl
Product: CCCCCOc1ccc2cc(-c3ncc(C#N)cn3)ccc2c1

Procedure:
Operations were carried out as in Example 9 except that 6-heptyl-2-naphthalenecarboxamidine hydrochloride as a raw material was replaced by 6-pentyloxy-2-naphthalenecarboxamidine hydrochloride to produce 2-pentyloxy-6-(5-cyano-2-pyrimidinyl)naphthalene. This product exhibited a liquid crystalline phase, and its crystalline-nematic phase transition point (C-N point) was 134.8°-135.5° C. and its N-I point was 190.9°-191.1° C.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.C[O-].[Na+].[C:9]([O:13][C:14]([NH:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]Br)=[O:15])([CH3:12])([CH3:11])[CH3:10]>CN(C)C=O>[C:9]([O:13][C:14]([NH:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][N:1]1[CH:5]=[CH:4][N:3]=[CH:2]1)=[O:15])([CH3:12])([CH3:11])[CH3:10]
Reactant: c1c[nH]cn1
Reactant: CC(C)(C)OC(=O)NCCCCCCBr
Agent: C[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)NCCCCCCn1ccnc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Imidazole (70 mg) and 1.4 M sodium methoxide (1 ml) were added to N,N-dimethylformamide (3 ml) and the mixture was stirred at room temperature for 30 minutes. A solution of N-(tert-butoxycarbonyl)-6-bromo-hexylamine (280 mg) in N,N-dimethylformamide (1 ml) was added and after heating at 80-90° C. for 30 minutes stirring was continued overnight at room temperature. Evaporation in vacuo followed by stirring with acetone and fitration gave a filtrate which after evaporation was purified by chromatography on silica gel with ethyl acetate/methanol (4:1) as eluent to yield the title compound as a colourless oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=1.[C:23]([N:31]=[C:32]=[O:33])(=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C1(C)C=CC=CC=1>[C:23]([NH:31][C:32]([NH:22][C:19]1[CH:18]=[CH:17][C:16]([O:15][C:6]2[C:5]3[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=3)[N:9]=[CH:8][CH:7]=2)=[CH:21][CH:20]=1)=[O:33])(=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: COc1cc2nccc(Oc3ccc(N)cc3)c2cc1OC
Reactant: O=C=NC(=O)c1ccccc1
Solvent: Cc1ccccc1
Product: COc1cc2nccc(Oc3ccc(NC(=O)NC(=O)c4ccccc4)cc3)c2cc1OC
Yield: 15 %

Procedure:
6,7-Dimethoxy-4-(4-aminophenoxy)quinoline (52 mg) was dissolved in toluene (5 ml) with heat, benzoyl isocyanate (0.2 ml) was added, and the admixture was refluxed with heat for 50 minutes. The resulting residue was purified by column chromatography on silica gel eluting with chloroform/acetone (10/1) to obtain 11 mg of the title compound (yield: 15%).
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][CH:2]=1.[C:14](OC(=O)C)(=[O:16])[CH3:15].[Cl-].[Al+3].[Cl-].[Cl-]>>[C:14]([C:9]1[CH:8]=[CH:7][C:6]2[C:5]3[C:13](=[CH:1][CH:2]=[CH:3][CH:4]=3)[CH2:12][C:11]=2[CH:10]=1)(=[O:16])[CH3:15]
Reactant: c1ccc2c(c1)Cc1ccccc1-2
Reactant: CC(=O)OC(C)=O
Agent: [Al+3]
Agent: [Cl-]
Product: CC(=O)c1ccc2c(c1)Cc1ccccc1-2

Procedure:
Known in the present-day practice is a method of producing the bisulfite compound of 2-fluorenonyl-glyoxal, said method consisting in that fluorene is acylated by acetic anhydride in the presence of aluminum chloride to obtain 2-acetylfluorene at a yield of 60 weight percent. Then the thus-obtained 2-acetylfluorene is oxidized by sodium bichromate in an acetic-acid medium at 70°-75° C during 6 hours and 2-acetylfluorenon is isolated at a yield of 50 weight percent.
Reaction SMILES: [CH:1]1([C:4]2[C:13]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([N:21]4[CH:25]=[CH:24][CH:23]=[N:22]4)=[CH:17][CH:16]=3)=[C:12]([CH3:26])[C:11]3[C:10]([OH:27])=[CH:9][CH:8]=[C:7]([F:28])[C:6]=3[N:5]=2)[CH2:3][CH2:2]1.CN(C)C=O.C(=O)([O-])[O-].[K+].[K+].[CH3:40][O:41][C:42](=[O:46])[C@H:43](Cl)[CH3:44]>O>[CH3:40][O:41][C:42](=[O:46])[C@@H:43]([O:27][C:10]1[CH:9]=[CH:8][C:7]([F:28])=[C:6]2[C:11]=1[C:12]([CH3:26])=[C:13]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([N:21]3[CH:25]=[CH:24][CH:23]=[N:22]3)=[CH:17][CH:16]=1)[C:4]([CH:1]1[CH2:2][CH2:3]1)=[N:5]2)[CH3:44]
Reactant: Cc1c(Cc2ccc(-n3cccn3)cc2)c(C2CC2)nc2c(F)ccc(O)c12
Reactant: COC(=O)[C@@H](C)Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)[C@H](C)Oc1ccc(F)c2nc(C3CC3)c(Cc3ccc(-n4cccn4)cc3)c(C)c12
Temperature: 40 °C
Reaction time: 72 h
Yield: 41.9 %

Procedure:
A mixture of 2-cyclopropyl-8-fluoro-4-methyl-3-(4-pyrazol-1-ylbenzyl)quinolin-5-ol (0.064 g), N,N-dimethylformamide (0.86 mL), potassium carbonate (0.071 g) and (R)-2-chloropropionic acid methyl ester (0.032 g) was stirred at 40° C. for 3 days. The mixture was cooled to 0° C., diluted with water (40 mL) and extracted with ethyl acetate (3×10 mL). The combined extracts were washed saturated aqueous sodium chloride solution, dried over magnesium sulfate and concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel, eluting with a mixture of ethyl acetate and cyclohexane (0:1 to 4:6 by volume) gave title compound as a colourless oil (0.033 g).
Reaction SMILES: [C:1]1(P(C2C=CC=CC=2)C2C=CC=CC=2)[CH:6]=CC=C[CH:2]=1.N(C(OCC)=O)=NC(OCC)=O.[OH:32][C:33]1[C:42]2[C:37](=[N:38][CH:39]=[CH:40][CH:41]=2)[N:36]([CH2:43][CH2:44][CH:45]([CH3:47])[CH3:46])[C:35](=[O:48])[C:34]=1[C:49]1[NH:54][C:53]2[CH:55]=[CH:56][C:57]([NH:59][S:60](=[O:73])(=[O:72])[NH:61][C:62]([O:64][CH2:65][C:66]3[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=3)=[O:63])=[CH:58][C:52]=2[S:51](=[O:75])(=[O:74])[N:50]=1.C(O)CC.Cl>ClCCl>[OH:32][C:33]1[C:42]2[C:37](=[N:38][CH:39]=[CH:40][CH:41]=2)[N:36]([CH2:43][CH2:44][CH:45]([CH3:47])[CH3:46])[C:35](=[O:48])[C:34]=1[C:49]1[NH:54][C:53]2[CH:55]=[CH:56][C:57]([NH:59][S:60](=[O:73])(=[O:72])[N:61]([CH2:2][CH2:1][CH3:6])[C:62]([O:64][CH2:65][C:66]3[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=3)=[O:63])=[CH:58][C:52]=2[S:51](=[O:74])(=[O:75])[N:50]=1
Reactant: CC(C)CCn1c(=O)c(C2=NS(=O)(=O)c3cc(NS(=O)(=O)NC(=O)OCc4ccccc4)ccc3N2)c(O)c2cccnc21
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: Cl
Solvent: ClCCl
Solvent: CCCO
Product: CCCN(C(=O)OCc1ccccc1)S(=O)(=O)Nc1ccc2c(c1)S(=O)(=O)N=C(c1c(O)c3cccnc3n(CCC(C)C)c1=O)N2
Reaction time: 0.17 h

Procedure:
A solution of triphenylphosphine (1.5 eq) in dichloromethane is treated dropwise with diethyl azodicarboxylate (1.5 eq) at 25° C. The solution is allowed to stir for 10 min followed by the dropwise addition of a solution containing the product of Example 436 (1 eq) and n-propanol (1.1 eq) in dichloromethane. The resulting solution is stirred at 25° C. for 20 hours, followed by the addition of dichloromethane and 1N aqueous hydrochloric acid. The resulting organic layer is separated and dried over magnesium sulfate, and filtered to provide the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[Cl:11])[C:5](Cl)=[O:6].[NH:12]1[CH2:17][CH2:16][C:15](=[O:18])[CH2:14][C:13]1=[O:19].[C-]#N.[K+].C(N(CCOCCOC)CCOCCOC)COCCOC>C(#N)C.C(N(CC)CC)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[Cl:11])[C:5]([CH:14]1[C:15](=[O:18])[CH2:16][CH2:17][NH:12][C:13]1=[O:19])=[O:6]
Reactant: O=C1CCNC(=O)C1
Reactant: O=C(Cl)c1ccc(Cl)c(Cl)c1
Agent: COCCOCCN(CCOCCOC)CCOCCOC
Agent: [C-]#N
Agent: [K+]
Solvent: CC#N
Solvent: CCN(CC)CC
Product: O=C1CCNC(=O)C1C(=O)c1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 12.9 %

Procedure:
A solution of 3,4-dichlorobenzoyl chloride (2.1 g) in dry acetonitrile (10 ml) was added at ambient temperature to a stirred solution of piperidine-2,4-dione (1.13 g) and dry triethylamine (1.31 g) in dry acetonitrile (50 ml) and the mixture stirred at ambient temperature for 18 hours. Potassium cyanide (0.06 g) dry triethylamine (3.1 g) and tris-(3,6-dioxaheptyl)amine (0.5 ml) were added successively and the mixture stirred at ambient temperature for 24 hours. The mixture was evaporated under reduced pressure and the residue dissolved in dichloromethane (50 ml). The dichloromethane solution was washed successively with 2N hydrochloric acid (2×30 ml) and water (3×30 ml), dried over magnesium sulphate and evaporated under reduced pressure to give a brown solid which was purified by column chromatography to give 3-(3,4-dichlorobenzoyl)piperidine-2,4-dione (0.37 g) mp 171.5°-174.5° C., as a cream crystalline solid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:12](=[C:13]([F:15])[CH:14]=1)[NH:11][C:10]1[C:9](=[O:16])[CH2:8][CH2:7][CH2:6][C:5]2=1.[C:17]([Si](C)(C)C)([F:20])([F:19])[F:18].[F-].[Cs+]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:12](=[C:13]([F:15])[CH:14]=1)[NH:11][C:10]1[C:9]([C:17]([F:20])([F:19])[F:18])([OH:16])[CH2:8][CH2:7][CH2:6][C:5]2=1
Reactant: C[Si](C)(C)C(F)(F)F
Reactant: O=C1CCCc2c1[nH]c1c(F)cc(Cl)cc21
Agent: [Cs+]
Agent: [F-]
Solvent: C1CCOC1
Product: OC1(C(F)(F)F)CCCc2c1[nH]c1c(F)cc(Cl)cc21
Temperature: 0 °C
Reaction time: 6 h
Yield: 8.3 %

Procedure:
To a solution of 6-chloro-8-fluoro-2,3,4,9-tetrahydro-1H-carbazol-1-one (0.15 g, 0.63 mmol) in anhydrous THF (12 mL), cooled to 0° C., CF3TMS (1 mL, 6.3 mmol) followed by CsF (0.28 g, 1.8 mmol) were added. The reaction mixture was stirred at 0° C. for 6 h, quenched with saturated NH4Cl (10 mL) and extracted with EtOAc (2×15 mL). The combined organic extracts were dried over Na2SO4 and concentrated under reduced pressure to obtain the crude material which was purified by column chromatography [EtOAc-hexanes (3:22) as eluant] to give the title compound (0.016 g, 8%). 1H NMR (200 MHz, CDCl3, δ in ppm) 8.35 (bs, 1H), 7.30 (s, 1H), 7.00 (d, J=4.2 Hz, 1H), 2.82-2.79 (m, 1H), 2.70-2.68 (m, 1H), 2.47 (s, 1H), 2.28-2.24 (m, 1H), 2.12-2.10 (m, 2H), 2.03-2.02 (m, 1H).
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9]Br)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Li])(C)(C)C.[CH2:16]([O:23][C:24]1[CH:31]=[CH:30][C:27]([CH:28]=[O:29])=[CH:26][C:25]=1[O:32][CH3:33])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>CCOCC.CCCCC>[CH2:16]([O:23][C:24]1[CH:31]=[CH:30][C:27]([CH:28]([OH:29])[CH2:9][CH2:8][CH2:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[CH:26][C:25]=1[O:32][CH3:33])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: BrCCCc1ccccc1
Reactant: COc1cc(C=O)ccc1OCc1ccccc1
Agent: [Li]C(C)(C)C
Solvent: CCCCC
Solvent: CCOCC
Product: COc1cc(C(O)CCCc2ccccc2)ccc1OCc1ccccc1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
A solution of 20.0 g of 3-phenylpropyl bromide in 300 ml of ether is treated at -60° while stirring within 15 minutes with a solution of 71.8 ml of tert.butyllithium (1.4 molar) in pentane. After 10 minutes there is added dropwise at this temperature within 15 minutes a solution of 22.14 g of vanillin benzyl ether in 200 ml of ether, whereupon the mixture is stirred for an additional 2 hours. The mixture is poured into 1 l of ice-water and extracted three times with 500 ml of ethyl acetate each time. The organic phase is washed twice with 200 ml of water each time, dried over sodium sulfate and evaporated. The oil obtained is chromatographed on 1 kg of silica gel with methylene chloride. The crystals obtained are recrystallized from ether/pentane. There is obtained 4-(benzyloxy)-3-methoxy-α-(3-phenylpropyl)benzyl alcohol in the form of colorless crystals of m.p. 71°-73°.
Reaction SMILES: [BH4-].[Li+].C[O:4][C:5]([C:7]1[CH:8]=[CH:9][C:10]2[CH:15]([NH:16][C:17](=[O:40])[CH2:18][CH:19]([NH:26][S:27]([C:30]3[CH:39]=[CH:38][C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[CH:31]=3)(=[O:29])=[O:28])[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:14][S:13](=[O:42])(=[O:41])[N:12]([CH3:43])[C:11]=2[CH:44]=1)=O.CO>C1COCC1>[OH:4][CH2:5][C:7]1[CH:8]=[CH:9][C:10]2[CH:15]([NH:16][C:17](=[O:40])[CH2:18][CH:19]([NH:26][S:27]([C:30]3[CH:39]=[CH:38][C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[CH:31]=3)(=[O:29])=[O:28])[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:14][S:13](=[O:41])(=[O:42])[N:12]([CH3:43])[C:11]=2[CH:44]=1
Reactant: COC(=O)c1ccc2c(c1)N(C)S(=O)(=O)CC2NC(=O)CC(NS(=O)(=O)c1ccc2ccccc2c1)c1ccccc1
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CO
Product: CN1c2cc(CO)ccc2C(NC(=O)CC(NS(=O)(=O)c2ccc3ccccc3c2)c2ccccc2)CS1(=O)=O
Temperature: 50 °C
Reaction time: 20 h

Procedure:
Lithium borohydride (10.0 mL, 20 mmol, 2.0 M in THF) was added to a THF (50 mL) solution of 4-(3-(naphthalen-2-yl-sulfonylamino)-3-phenyl-propionylamino)-1-methyl-2,2-dioxo-1,2,3,4-tetrahydro-2λ6-benzo[c][1,2]thiazine-7-carboxylic acid methyl ester (Step C) (1.76 g, 2.9 mmol). Following addition of MeOH (0.3 mL, 8 mmol), the mixture was stirred for 20 h at 50° C. The reaction was quenched with acetone, MeOH and dilute HCl at 0° C. The mixture was diluted with CH2Cl2 (400 mL), washed with H2O, dried over MgSO4, filtered, and concentrated in vacuo. Chromatography on silica (0-5% MeOH in CH2Cl2) provided the title compound. MS (−APCI, m/z): 578 (M−H)−.
Reaction SMILES: [Br:1][C:2]1[C:3]([CH3:10])=[C:4]([C:7](O)=[O:8])[S:5][CH:6]=1.S(Cl)([Cl:13])=O>CN(C=O)C.ClCCCl>[Br:1][C:2]1[C:3]([CH3:10])=[C:4]([C:7]([Cl:13])=[O:8])[S:5][CH:6]=1
Reactant: O=S(Cl)Cl
Reactant: Cc1c(Br)csc1C(=O)O
Solvent: CN(C)C=O
Solvent: ClCCCl
Product: Cc1c(Br)csc1C(=O)Cl
Yield: 100.2 %

Procedure:
A slurry of 1.11 g (5 mmole) of 4-bromo-3-methyl-2-thiophenecarboxylic acid, 0.44 mL (6 mmole) of thionyl chloride, 5 drops of DMF, and 10 mL of 1,2-dichloroethane was heated at 80° C. for 1.5 h. The clear solution was cooled and concentrated on a roto-evaporator. The residue was dissolved in 5 mL of 1,2-dichloroethane and reconcentrated on a roto-evaporator to give 1.2 g of a tan solid, 97% pure (GC area). This acid chloride was used without further purification.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[C:10]([O:12][CH:13]2[CH2:18][CH2:17][N:16](C(OC(C)(C)C)=O)[CH2:15][CH2:14]2)[CH:9]=[CH:8][C:4]=1[C:5]([OH:7])=[O:6].Cl>C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:11]=[C:10]([O:12][CH:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)[CH:9]=[CH:8][C:4]=1[C:5]([OH:7])=[O:6]
Reactant: COc1cc(OC2CCN(C(=O)OC(C)(C)C)CC2)ccc1C(=O)O
Agent: Cl
Solvent: CCOC(C)=O
Product: COc1cc(OC2CCNCC2)ccc1C(=O)O
Reaction time: 0.5 h

Procedure:
2-Methoxy-4-(1-Boc-4-piperidyloxy)benzoic acid (0.79 g, 2.24 mmol) was dissolved in ethyl acetate (15 ml). The solution was cooled in ice and saturated with HCl gas, then stirred 30 min in the cold. The mixture was evaporated in vacuo and the residue concentrated from ether three times to give 2-methoxy-4-(4-piperidyloxy)benzoic acid.
Reaction SMILES: [CH2:1]1[CH:14]2[CH:5]([C:6](=[O:16])[C:7]3[C:12]([C:13]2=[O:15])=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH2:4][CH:3]=[CH:2]1>[Pd]>[CH:8]1[C:7]2[C:6](=[O:16])[C:5]3[C:14](=[CH:1][CH:2]=[CH:3][CH:4]=3)[C:13](=[O:15])[C:12]=2[CH:11]=[CH:10][CH:9]=1
Reactant: O=C1c2ccccc2C(=O)C2CC=CCC12
Agent: [Pd]
Product: O=C1c2ccccc2C(=O)c2ccccc21
Yield: 18.3 %

Procedure:
20 g of 1,4,4a,9a-tetrahydro-anthraquinone and 2 g of palladium at 5% on charcoal are heated under an atmosphere of nitrogen for one hour at 130° C. After cooling, the solid mixture is washed with 250 ml of acetone. After a similar treatment to that of the preceding Examples 1 and 2, 3.6 g of anthraquinone and 16 g of a mixture of 1,2,3,4-tetrahydro-9,10-anthracenediol and 1,2,3,4-tetrahydro-anthraquinone (Mixture C) are obtained.
Reaction SMILES: S1C2C=CC=CC=2N=C1N(COCC[Si](C)(C)C)C(C1C=CC=C2C=1CN(C1SC(C3C=CC(CO)=CC=3)=C(C(OCC)=O)N=1)CC2)=O.OCC1C=CC(B(O)O)=CC=1.Br[C:61]1[C:62]([C:66]#[N:67])=[CH:63][S:64][CH:65]=1.CC1(C)C(C)(C)OB([C:76]2[CH:81]=[CH:80][C:79]([OH:82])=[CH:78][CH:77]=2)O1>>[OH:82][C:79]1[CH:80]=[CH:81][C:76]([C:61]2[C:62]([C:66]#[N:67])=[CH:63][S:64][CH:65]=2)=[CH:77][CH:78]=1
Reactant: CC1(C)OB(c2ccc(O)cc2)OC1(C)C
Reactant: N#Cc1cscc1Br
Agent: CCOC(=O)c1nc(N2CCc3cccc(C(=O)N(COCC[Si](C)(C)C)c4nc5ccccc5s4)c3C2)sc1-c1ccc(CO)cc1
Agent: OCc1ccc(B(O)O)cc1
Product: N#Cc1cscc1-c1ccc(O)cc1

Procedure:
Compound 51A was prepared in a similar manner to the synthesis of compound 34D by substituting compound 34C and 4-(hydroxymethyl)phenylboronic acid with 4-bromothiophene-3-carbonitrile and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol, respectively: 1H NMR (DMSO-d6): δ 9.68 (s, 1H), 8.62 (d, J=3.38 Hz, 1H), 7.73 (d, J=3.07 Hz, 1H), 7.44 (d, J=8.59 Hz, 2H), 6.86 (d, J=8.59 Hz, 2H). MS (ESI(+)): m/z 200 (M−H).
Reaction SMILES: [CH2:1]([O:8][CH2:9][C@H:10]([C@H:13]([O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])[CH3:14])[CH2:11]O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:23]([N:31]1[C:36](=[O:37])[C:35]([CH3:38])=[CH:34][NH:33][C:32]1=[O:39])(=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[CH2:1]([O:8][CH2:9][C@@H:10]([CH2:11][N:33]1[CH:34]=[C:35]([CH3:38])[C:36](=[O:37])[N:31]([C:23](=[O:30])[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:32]1=[O:39])[C@H:13]([O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])[CH3:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C[C@@H](O[Si](C)(C)C(C)(C)C)[C@H](CO)COCc1ccccc1
Reactant: Cc1c[nH]c(=O)n(C(=O)c2ccccc2)c1=O
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: Cc1cn(C[C@H](COCc2ccccc2)[C@@H](C)O[Si](C)(C)C(C)(C)C)c(=O)n(C(=O)c2ccccc2)c1=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 81 %

Procedure:
To a cold (ice/water bath) solution of (2R,3R)-2-((benzyloxy)methyl)-3-(tert-butyldimethylsiloxy)butan-1-ol (4) (W.-H. Ham et al. J. Org. Chem. 2000, 65, 8372-8374) 1.5 g, 4.6 mmol), 3-benzoylthymine (1.5 g, 6.5 mmol) and triphenylphosphine (1.71 g, 6.5 mmol) in 50 ml of anhydrous THF was added dropwise via syringe with stirring (1.26 ml, 6.5 mmol) of diisopropylazodicarboxylate. The reaction was removed from the bath and stirred at room temperature for 2 hrs and then concentrated. The reaction was diluted with ether (50 ml) and hexane (50 ml) to precipitate some of triphenylphosphine oxide and the DIPADC by-product. The solids were filtered off and the filtrate concentrated. The resultant crude product, which still contained some Ph3PO, was chromatographed on silica eluting with 20% ethyl acetate in hexane. Concentration of the pure product fractions afforded 2.0 g (81%) of 5 as a colorless viscous srup. 1H NMR (CDCl3): δ 7.85 (d, J=8.4 Hz, 2H), 7.58 (t, J=7.5 Hz, 1H), 7.42 (t, J=7.8 Hz, 2H), 7.35-7.25 (m, 5H), 7.06 (d, J=1.2 Hz, 1H), 4.42 (s, 2H), 3.98 (m, 2H), 3.61 (m, 1H), 3.46 (d, J=5.7 Hz, 2H), 2.08 (m, 1H), 1.83 (s, 3H), 1.16 (d, J=6.6 Hz, 3H), 0.84 (s, 9H), 0.02 (s, 3H), 0.00 (s, 3H).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[C:7]([O:12][CH3:13])=[CH:6][C:5]=1[S:14](Cl)(=[O:16])=[O:15].C(N(CC)CC)C.[NH2:26][CH2:27][C:28]([O:30][CH3:31])=[O:29]>C(Cl)Cl.C(OCC)(=O)C.Cl>[CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[C:7]([O:12][CH3:13])=[CH:6][C:5]=1[S:14](=[O:16])(=[O:15])[NH:26][CH2:27][C:28]([O:30][CH3:31])=[O:29]
Reactant: COC(=O)CN
Reactant: COC(=O)c1cc(OC)c(OC)cc1S(=O)(=O)Cl
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: COC(=O)CNS(=O)(=O)c1cc(OC)c(OC)cc1C(=O)OC
Reaction time: 2 h
Yield: 78 %

Procedure:
To a solution of 2-Chlorosulfonyl-4,5-dimethoxy-benzoic acid methyl ester (0.100 g, 0.339 mmol) in methylene chloride (5 mL) was added triethylamine (0.28 mL, 2.012 mmol) and methyl glycinate.HCl (0.128 g, 1.02 mmol). The mixture was stirred for 2 hours and then diluted with ethyl acetate (50 mL) and 1N HCl (50 mL). The organic fraction was washed with brine and dried over MgSO4. Crystallization from methylene chloride hexane affords the title compound (0.092 g, 78%);
Reaction SMILES: Cl[CH:2](Cl)[C:3]1[CH:4]=[N:5][N:6]([CH3:11])[C:7]=1[N+:8]([O-:10])=[O:9].C([OH:15])C>O.[N+]([O-])([O-])=O.[Ag+]>[CH3:11][N:6]1[C:7]([N+:8]([O-:10])=[O:9])=[C:3]([CH:2]=[O:15])[CH:4]=[N:5]1
Reactant: CCO
Reactant: Cn1ncc(C(Cl)Cl)c1[N+](=O)[O-]
Agent: [Ag+]
Agent: O=[N+]([O-])[O-]
Solvent: O
Product: Cn1ncc(C=O)c1[N+](=O)[O-]
Temperature: 25 °C
Yield: 41 %

Procedure:
A hot solution of silver nitrate (4.7 g, 27.4 mmol) in ethanol (15 mL) and water (4 mL) was added to a stirring solution of 4-dichloromethyl-1-methyl-5-nitro-1H-pyrazole (1.44 g, 6.85 mmol) in ethanol (50 mL) at 50° C. The mixture was stirred vigorously under reflux for 1 h, cooled to room temperature, and diluted with water (14 mL). The aqueous layer was extracted with chloroform and filtered through a layer of celite. Concentration and chromatography on a silica gel column with hexane and ethyl acetate (6:1) gave 1-methyl-5-nitro-1H-pyrazole-4-carbaldehyde (0.42 g, 41%): 1H NMR (300 MHz, CDCl3) δ 9.93 (s, 1H), 8.08 (s, 1H), 4.36 (s, 3H).
Reaction SMILES: [CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[NH:4][C:3]=1[C:11]([O:13][CH2:14]C)=[O:12].[Mg].ClCCl.[NH4+].[Cl-]>CO>[CH3:1][CH:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[NH:4][CH:3]1[C:11]([O:13][CH3:14])=[O:12]
Reactant: CCOC(=O)c1[nH]c2ccccc2c1C
Agent: [Cl-]
Agent: [Mg]
Agent: [NH4+]
Solvent: CO
Solvent: ClCCl
Product: COC(=O)C1Nc2ccccc2C1C
Temperature: 25 °C

Procedure:
Ethyl 3-methylindole-2-carboxylate (4.06 g, 20 mmol) was dissolved in methanol (50 ml) and magnesium shavings (2.431 g, 100 mmol) were then added with stirring, at room temperature under a nitrogen atmosphere. After the reaction started, a water bath was used to maintain the reaction temperature between 15-20° C. After the end of the reaction, dichloromethane (200 ml) was added to the mixture, followed by NH4Cl solution (200 ml). The organic phase was separated out and the aqueous phase was extracted with dichloromethane (3×50 ml). The combined organic phases were dried over magnesium sulphate and the solvent was removed to give a brown oil.
Reaction SMILES: C([O:3][C:4]([CH:6]([C:9]1[CH:14]=[CH:13][C:12]([NH:15][C@H:16]([C:22]([OH:24])=[O:23])[CH2:17][CH2:18][C:19](=[O:21])[NH2:20])=[CH:11][CH:10]=1)[CH2:7][CH3:8])=[O:5])C.[OH-].[Na+]>CO.O>[C:4]([CH:6]([C:9]1[CH:10]=[CH:11][C:12]([NH:15][C@H:16]([C:22]([OH:24])=[O:23])[CH2:17][CH2:18][C:19](=[O:21])[NH2:20])=[CH:13][CH:14]=1)[CH2:7][CH3:8])([OH:5])=[O:3]
Reactant: CCOC(=O)C(CC)c1ccc(N[C@@H](CCC(N)=O)C(=O)O)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CCC(C(=O)O)c1ccc(N[C@@H](CCC(N)=O)C(=O)O)cc1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 76 %

Procedure:
In 10 ml of methanol was suspended 1.68 g (0.005 mole) of N-[4-(1-ethoxycarbonyl-n-propyl)phenyl]-L-glutamine and a solution of 0.42 g of sodium hydroxide in 20 ml of water was added thereto and stirred for 1.5 hours at room temperature. The solvent was then distilled off in vacuo to about a half volume and the remaining solution was acidified to pH 4 with 5% hydrochloric acid. The precipitated crystals were collected by filtration, washed with cold water and dried in vacuo to give 1.16 g (0.0038 mole, 75% yield) of N-[4-(1-carboxy-n-propyl)phenyl]-L-glutamine, m.p. 166.5°-167.0° C.