Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].C(O[CH2:26][CH:27]=[CH:28][CH2:29]OC(=O)C)(=O)C>O1CCCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:12]([N:11]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10])[CH2:26][CH:27]=[CH:28][CH2:29][N:11]([CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:29][CH2:28][CH2:27][CH3:26])[CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]
Reactant: CCCCCCCCCCNCCCCCCCCCC
Reactant: CC(=O)OCC=CCOC(C)=O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CCCCCCCCCCN(CC=CCN(CCCCCCCCCC)CCCCCCCCCC)CCCCCCCCCC
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of di-n-decylamine (10.9 g, 36.6 mmol) and 2-butene-1,4-diol diacetate (3.15 g, 18.3 mmol) in tetrahydrofuran (THF) (150 ml) is treated with tetrakis(triphenylphosphine)palladium(0) (1.0 g, 0.9 mmol) and stirred at room temperature overnight. The reaction mixture is concentrated in vacuo to a oil that is redissolved in THF (500 ml) and treated with 20% aqueous sodium hydroxide (250 ml). The mixture is stirred for one hour, concentrated, and extracted with ether. The ether extracts are dried and concentrated giving an orange oil which is purified by medium pressure chromatography (silica gel; 25% ethyl acetate in hexanes). The title compound is isolated as 5.8g (49% yield) of a clear oil.
Reaction SMILES: [F:1][C:2]1[C:11]2[C:6](=[C:7]([O:14]C)[CH:8]=[CH:9][C:10]=2[O:12]C)[C:5]([F:16])=[C:4]([F:17])[C:3]=1[F:18].[F:19][C:20]1[C:28]([F:29])=[C:27]([F:30])[C:26]([F:31])=[C:25]2[C:21]=1[C:22](=[O:33])O[C:24]2=[O:32]>>[F:31][C:26]1[C:25]2[C:24](=[O:32])[C:9]3[C:8](=[C:7]([OH:14])[C:6]4[C:11]([C:10]=3[OH:12])=[C:2]([F:1])[C:3]([F:18])=[C:4]([F:17])[C:5]=4[F:16])[C:22](=[O:33])[C:21]=2[C:20]([F:19])=[C:28]([F:29])[C:27]=1[F:30]
Reactant: COc1ccc(OC)c2c(F)c(F)c(F)c(F)c12
Reactant: O=C1OC(=O)c2c(F)c(F)c(F)c(F)c21
Product: O=C1c2c(F)c(F)c(F)c(F)c2C(=O)c2c1c(O)c1c(F)c(F)c(F)c(F)c1c2O

Procedure:
{1-1} First, 1,2,3,4,7,8,9,10-octafluoro-6,11-tetrahydroxynaphthacene-5,12-dione (7) was synthesized from 1,2,3,4-tetrafluoro-5,8-dimethoxynaphthalene (6) and 4,5,6,7-tetrafluoroisobenzofuran-1,3-dione (2).
Reaction SMILES: C(N(CC)CC)C.[OH:8][C@@H:9]([CH2:31][CH2:32][CH3:33])[CH:10]([C:21]([O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:22])[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12].[CH3:34][S:35](Cl)(=[O:37])=[O:36]>ClCCl>[CH3:34][S:35]([O:8][C@@H:9]([CH2:31][CH2:32][CH3:33])[CH:10]([C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])[C:21]([O:23][CH2:24][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)=[O:22])(=[O:37])=[O:36]
Reactant: CS(=O)(=O)Cl
Reactant: CCC[C@H](O)C(C(=O)OCc1ccccc1)C(=O)OCc1ccccc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCC[C@H](OS(C)(=O)=O)C(C(=O)OCc1ccccc1)C(=O)OCc1ccccc1
Reaction time: 0.5 h

Procedure:
500 ml of triethylamine are added to a solution of 236.9 g of 1 in 1.2 l of dichloromethane. With ice cooling, a solution of 83.6 ml of methanesulfonyl chloride in 200 ml of dichloromethane is added. The mixture is stirred at 5-100 for 30 minutes, the precipitated triethylamine hydrochloride is removed, and the product is subjected to conventional work-up, giving 2 as oil.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[S:13][C:14]([C:17]3[C:18]([CH2:35][CH3:36])=[C:19]([CH2:23][N:24]4[CH2:29][CH2:28][CH:27]([C:30]([O:32]CC)=[O:31])[CH2:26][CH2:25]4)[CH:20]=[CH:21][CH:22]=3)=[CH:15][N:16]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[OH-].[Na+]>C(O)(C)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[S:13][C:14]([C:17]3[C:18]([CH2:35][CH3:36])=[C:19]([CH2:23][N:24]4[CH2:25][CH2:26][CH:27]([C:30]([OH:32])=[O:31])[CH2:28][CH2:29]4)[CH:20]=[CH:21][CH:22]=3)=[CH:15][N:16]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10]
Reactant: CCOC(=O)C1CCN(Cc2cccc(-c3cnc(-c4ccc(OC(C)C)c(Cl)c4)s3)c2CC)CC1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(C)O
Product: CCc1c(CN2CCC(C(=O)O)CC2)cccc1-c1cnc(-c2ccc(OC(C)C)c(Cl)c2)s1
Temperature: 25 °C
Reaction time: 8 h
Yield: 48.2 %

Procedure:
To a solution of ethyl 1-{[3-(2-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]methyl}-4-piperidinecarboxylate (D85) (160 mg) in isopropanol (40 mL) and water (10 mL) stirred under nitrogen at room temperature was added a solution of NaOH (24.3 mg) in water in one charge. The reaction mixture was stirred at room temperature overnight. Isopropanol was removed in vacuo. The residue was dissolved in water and acidified with 1N HCl to pH=5. The solvent was removed in vacuo, the residue was dissolved in THF, and filtered. The filtrate was purified by Mass Directed AutoPrep to give 1-{[3-(2-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]methyl}-4-piperidinecarboxylic acid (E36) (73 mg) as a TFA salt (white solid). δH (DMSO-d6, 400 MHz): 1.02 (3H, t), 1.34 (6H, d), 1.78 (2H, m), 2.05 (2H, m), 2.54 (1H, m), 2.83 (2H, m), 3.18 (2H, m), 3.45 (2H, m), 4.42 (2H, m), 4.80 (1H, m), 7.32 (1H, d), 7.44 (2H, m), 7.63 (1H, d), 7.87 (2H, m), 7.99 (1H, d), 9.28 (1H, br s), 12.59 (1H, br s). δF (DMSO-d6, 376 MHz): −74.0. MS (ES): C27H31ClN2O3S requires 498. found 499.1 (M+H+).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:14]2[CH2:18][CH:17]([CH2:19][NH:20][C:21](=[O:23])[CH3:22])[O:16][N:15]=2)[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][S:11][CH2:10][CH2:9]1.I([O-])(=O)(=O)=[O:25].[Na+]>CO.O>[F:1][C:2]1[CH:3]=[C:4]([C:14]2[CH2:18][CH:17]([CH2:19][NH:20][C:21](=[O:23])[CH3:22])[O:16][N:15]=2)[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:9][CH2:10][S:11](=[O:25])[CH2:12][CH2:13]1
Reactant: CC(=O)NCC1CC(c2ccc(N3CCSCC3)c(F)c2)=NO1
Reactant: [O-][I+3]([O-])([O-])[O-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: CC(=O)NCC1CC(c2ccc(N3CCS(=O)CC3)c(F)c2)=NO1
Temperature: 25 °C
Reaction time: 48 h
Yield: 85.9 %

Procedure:
1.0 g (2.97 mmol) of N-({3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-4,5-dihydro-5-isoxazolyl}methyl)acetamide is suspended in 20 ml methanol/5 ml acetone in a 100 ml one neck round bottom flask. The suspension is treated with sodium meta periodate (666 mg, 3.12 mmole) in 20 ml water and the reaction mixture is stirred 48 hours at room temperature. The organics are removed in vacuo and the aqueous residue is filtered to remove a fine white solid. The solid is washed with water followed by diethyl ether to give 902 mg the title compound) as a solid. mp=204-205° C.
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])[CH2:9][NH:8][CH2:7][CH2:6]2.[CH:15]([O:18][C:19]1[CH:27]=[CH:26][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:24][C:20]=1[C:21](O)=[O:22])([CH3:17])[CH3:16]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[CH2:9][N:8]([C:21]([C:20]1[CH:24]=[C:25]([S:28]([CH3:31])(=[O:30])=[O:29])[CH:26]=[CH:27][C:19]=1[O:18][CH:15]([CH3:17])[CH3:16])=[O:22])[CH2:7][CH2:6]2
Reactant: CC(C)Oc1ccc(S(C)(=O)=O)cc1C(=O)O
Reactant: COc1cc2c(cc1OC)CNCC2
Product: COc1cc2c(cc1OC)CN(C(=O)c1cc(S(C)(=O)=O)ccc1OC(C)C)CC2

Procedure:
Prepared in analogy to example 1.1 from 6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline (CA [1745-07-9]) and 2-isopropoxy-5-methanesulfonyl-benzoic acid (Example 2.1).
Reaction SMILES: [CH3:1][O:2][C:3]1[N:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][C:7]([C:13]([OH:15])=[O:14])=[CH:6]2.CO[C:18]([C@H:20]1[CH2:25][CH2:24][C@H:23]([NH:26][CH2:27][CH2:28][S:29][C:30]2[S:31][CH:32]=[CH:33][CH:34]=2)[CH2:22][CH2:21]1)=O>>[S:31]1[CH:32]=[CH:33][CH:34]=[C:30]1[S:29][CH2:28][CH2:27][NH:26][C@H:23]1[CH2:24][CH2:25][C@H:20]([CH2:18][O:14][C:13]([C:7]2[CH:8]=[N:9][C:10]3[C:5]([CH:6]=2)=[N:4][C:3]([O:2][CH3:1])=[CH:12][CH:11]=3)=[O:15])[CH2:21][CH2:22]1
Reactant: COc1ccc2ncc(C(=O)O)cc2n1
Reactant: COC(=O)[C@H]1CC[C@H](NCCSc2cccs2)CC1
Product: COc1ccc2ncc(C(=O)OC[C@H]3CC[C@H](NCCSc4cccs4)CC3)cc2n1

Procedure:
The title compound is prepared as an off-white viscous oil following Scheme 2 and in analogy to Example 28 using 6-methoxy-[1,5]naphthyridine-3-carboxylic acid and trans-4-[2-(thiophen-2-ylsulfanyl)-ethylamino]-cyclohexanecarboxylic acid methyl ester as starting materials.
Reaction SMILES: [OH:1][CH:2]([C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=1)[CH3:3].[CH:14]1[C:19](O)=[CH:18][CH:17]=[C:16]([CH3:21])[CH:15]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OC(N=NC(OC(C)C)=O)=O)(C)C>O1CCCC1>[C:16]1([CH3:21])[CH:17]=[CH:18][C:19]([O:1][CH:2]([C:4]2[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=2)[CH3:3])=[CH:14][CH:15]=1
Reactant: Cc1ccc(O)cc1
Reactant: COC(=O)c1ccc(C(C)O)cc1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COC(=O)c1ccc(C(C)Oc2ccc(C)cc2)cc1
Temperature: 20 °C
Yield: 37 %

Procedure:
A mixture of methyl 4-(1-hydroxyethyl)benzoate (180 mg, 1.0 mmol), p-cresol (130 mg, 1.2 mmol), triphenylphosphine (393 mg, 1.5 mmol) and tetrahydrofuran (15 mL) were stirred at 20° C. for half an hour. Then azodicarboxylic acid diisopropyl ester (303 mg, 1.5 mmol) was added. The mixture was stirred at 20° C. for 12 hours. The resultant mixture was washed with water (20 mL×3). The organic phase was separated, dried over sodium sulfate, filtered, and concentrated to give a residue. The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=5:1) to furnish methyl 4-(1-(p-tolyloxy)ethyl)benzoate as a colorless oil (100 mg, 37%).
Reaction SMILES: [OH:1][CH2:2][CH2:3][C@@H:4]1[O:8][C:7]([CH3:10])([CH3:9])[O:6][C:5]1=[O:11].N1C=CN=C1.[C:17]([Si:21]([CH3:24])([CH3:23])Cl)([CH3:20])([CH3:19])[CH3:18].O>CN(C)C=O>[C:17]([Si:21]([CH3:24])([CH3:23])[O:1][CH2:2][CH2:3][C@@H:4]1[O:8][C:7]([CH3:9])([CH3:10])[O:6][C:5]1=[O:11])([CH3:20])([CH3:19])[CH3:18]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: CC1(C)OC(=O)[C@H](CCO)O1
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: O
Product: CC1(C)OC(=O)[C@H](CCO[Si](C)(C)C(C)(C)C)O1
Temperature: 25 °C
Reaction time: 18 h
Yield: 74.6 %

Procedure:
Step C A mixture of (S)-5-(2-hydroxy-ethyl)-2,2-dimethyl-[1,3]dioxolan-4-one (6.8 g, 42 mmol) and imidazole (7.5 g, 107 mmol) in dimethylformamide (40 mL) was added tert-butyldimethylchlorosilane (7 g, 45 mmol). The reaction mixture was stirred at room temperature for 18 h. Water was added. The organic layer was separated, the aqueous layer was then extracted with ethyl acetate twice. The combined organic layers were washed with brine, dried over MgSO4, concentrated to give (S)-5-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2,2-dimethyl-[1,3]dioxolan-4-one as a colorless oil (8.6 g, 74%).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.C(N=C=NCCCN(C)C)C.[CH3:19][O:20][C:21]1[C:22](=[O:43])[C:23]([CH3:42])=[C:24]([CH2:30][C:31]2[CH:32]=[CH:33][C:34]([O:40][CH3:41])=[C:35]([CH:39]=2)[C:36](O)=[O:37])[C:25](=[O:29])[C:26]=1[O:27][CH3:28]>C(Cl)Cl>[CH3:19][O:20][C:21]1[C:22](=[O:43])[C:23]([CH3:42])=[C:24]([CH2:30][C:31]2[CH:32]=[CH:33][C:34]([O:40][CH3:41])=[C:35]([CH:39]=2)[C:36]([N:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)=[O:37])[C:25](=[O:29])[C:26]=1[O:27][CH3:28]
Reactant: C1CCNCC1
Reactant: COC1=C(OC)C(=O)C(Cc2ccc(OC)c(C(=O)O)c2)=C(C)C1=O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Product: COC1=C(OC)C(=O)C(Cc2ccc(OC)c(C(=O)N3CCCCC3)c2)=C(C)C1=O
Temperature: 25 °C
Reaction time: 12 h
Yield: 26.6 %

Procedure:
Piperidine (0.027 g, 0.318 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.091 g, 0.477 mmol) were added to a methylene chloride solution (5 ml) of 5-(5,6-dimethoxy-3-methyl-1,4-benzoquinon-2-yl)methyl-2-methoxybenzoic acid (0.055 g, 0.159 mmol) and the resulting solution was stirred at room temperature for 12 hours. The reaction solution was poured into ice water and then extracted with methylene chloride. The extract was washed with water and then dried, and the solvent was removed by distillation. The obtained residue was purified by preparative thin-layer chromatography (ethyl acetate) to obtain the titled compound (0.0175 g, 0.0423 mmol, 27%).
Reaction SMILES: [C:1]1(Cl)[CH:6]=[CH:5][CH:4]=[C:3]([CH3:7])[C:2]=1[CH3:8].O.O.B(F)(F)F.S(=O)(=O)(O)O>C1C=CC=CC=1>[CH2:7]([C:3]1[CH:4]=[CH:5][CH:6]=[CH:1][C:2]=1[CH3:8])[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: Cc1cccc(Cl)c1C
Agent: FB(F)F
Agent: O=S(=O)(O)O
Solvent: c1ccccc1
Solvent: O
Product: Cc1ccccc1Cc1ccccc1
Reaction time: 6 h
Yield: 91.1 %

Procedure:
A solution of 70 parts of xylyl chloride in 240 parts of benzene is added to a mixture of 60 parts of boron fluoride dihydrate and 250 parts of 75 per cent strength by weight sulfuric acid at from 75° to 78° C, whilst stirring vigorously. After 6 hours, the organic phase is separated off and 82 parts (91.1% of theory) of o-benzyl-toluene boiling at 98° C at 0.2 mm Hg are isolated by distillation.
Reaction SMILES: [CH2:1]([O:8][C@@H:9]1[C@@H:13]([C@@H:14]([CH2:23][OH:24])[O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[O:12][C@@H:11]([N:25]2[CH:33]=[C:31]([CH3:32])[C:29](=[O:30])[NH:28][C:26]2=[O:27])[C@@H:10]1[OH:34])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:35]1([CH3:45])[CH:40]=[CH:39][C:38]([S:41](Cl)(=[O:43])=[O:42])=[CH:37][CH:36]=1>ClCCl>[CH2:1]([O:8][C@@H:9]1[C@@H:13]([C@@H:14]([CH2:23][O:24][S:41]([C:38]2[CH:39]=[CH:40][C:35]([CH3:45])=[CH:36][CH:37]=2)(=[O:43])=[O:42])[O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[O:12][C@@H:11]([N:25]2[CH:33]=[C:31]([CH3:32])[C:29](=[O:30])[NH:28][C:26]2=[O:27])[C@@H:10]1[O:34][S:41]([C:38]1[CH:39]=[CH:40][C:35]([CH3:45])=[CH:36][CH:37]=1)(=[O:43])=[O:42])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Cc1cn([C@@H]2O[C@H]([C@@H](CO)OCc3ccccc3)[C@@H](OCc3ccccc3)[C@H]2O)c(=O)[nH]c1=O
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)OC[C@@H](OCc2ccccc2)[C@H]2O[C@@H](n3cc(C)c(=O)[nH]c3=O)[C@H](OS(=O)(=O)c3ccc(C)cc3)[C@@H]2OCc2ccccc2)cc1
Temperature: 0 °C
Reaction time: 3 h

Procedure:
To a stirred solution of nucleoside 16 (0.60 g, 1.28 mmol) in dichloromethane (70 cm3) at room temperature was added 4—N,N-(dimethylamino)pyridine (0.63g, 5.12 mmol) and p-toluenesulphonyl chloride (0.73 g, 3.84 mmol). After stirring for 3 h, ice-cold H2O (50 cm3) was added and extraction was performed using dichloromethane (3×75 cm3). The combined organic phase was dried (Na2SO4) and evaporated to dryness under reduced pressure. The residue was purified by silica gel column chromatography using dichloromethane/methanol (99.5:0.5, v/v) as eluent to give nucleoside 17 as white solid material (0.71 g, 71%) after evaporation of the solvents under reduced pressure.
Reaction SMILES: Cl.[O:2]([NH2:4])[CH3:3].[C:5]([C:8]1[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=1)(=O)[CH3:6].C(=O)([O-])[O-].[K+].[K+]>CO.O>[CH3:3][O:2][N:4]=[C:5]([C:8]1[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=1)[CH3:6]
Reactant: CC(=O)c1cccnc1
Reactant: CON
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Product: CON=C(C)c1cccnc1

Procedure:
6.85 g of methoxylamine hydrochloride is added to 10 g of 3-acetyl pyridine in 50 cm3 of methanol and the whole is heated to reflux for 3 hours. The solvent is eliminated under reduced pressure, the residue is taken up in water, alkanlized with potassium carbonate and extracted with ethyl acetate. After evaporating, 11 g of the expected product is recovered. (b.p.: 115°-118° C. under 18 mm Hg).
Reaction SMILES: C[O:2][C:3](=[O:14])[C@H:4]([CH3:13])[NH:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>O>[CH2:6]([NH:5][C@H:4]([C:3]([OH:14])=[O:2])[CH3:13])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: COC(=O)[C@H](C)NCc1ccccc1
Solvent: O
Product: C[C@H](NCc1ccccc1)C(=O)O

Procedure:
333 g (1.72 mmol) of N-benzylalanine methyl ester (J. Chem. Soc. 4374 (1952)) are heated under reflux overnight with 860 ml of water. Product which has deposited is filtered off with suction and the filtrate is extracted once with tert.butyl methyl ether. The aqueous solution is concentrated and the crystals obtained are dried over phosphorus pentoxide in a desiccator with the first crystal fraction.
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[CH:7][C:5](N)=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].N([O-])=O.[Na+].S(=O)(=O)(O)O.[C:22]([OH:26])(=[O:25])[CH:23]=[CH2:24]>>[Cl:1][C:2]1[CH:8]=[CH:7][C:5]([CH:24]=[CH:23][C:22]([OH:26])=[O:25])=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10]
Reactant: Nc1ccc(Cl)c(C(F)(F)F)c1
Reactant: C=CC(=O)O
Agent: O=N[O-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Product: O=C(O)C=Cc1ccc(Cl)c(C(F)(F)F)c1

Procedure:
4-Chloro-3-trifluoromethyl aniline was converted to the diazonium salt with sodium nitrite and sulfuric acid and this was reacted with acrylic acid (Meerwein reaction) to give 4-chloro-3-trifluoromethyl cinnamic acid. This acid was hydrogenated, reduced with lithium aluminum hydride to the alcohol and reacted with phosphorus tribromide to give 3(4-chloro-3-trifluoromethylphenyl)propyl bromide.
Reaction SMILES: [Cl:1][C:2]1[C:3]([CH:8]([C:17]2[CH:26]=[C:25]3[C:20]([CH:21]=[CH:22][C:23]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)=[N:24]3)=[CH:19][CH:18]=2)[NH:9][C:10]([CH:12]2[CH2:15][C:14](=[CH2:16])[CH2:13]2)=O)=[N:4][CH:5]=[CH:6][N:7]=1.CN(C=O)C>O=P(Cl)(Cl)Cl>[Cl:1][C:2]1[C:3]2[N:4]([C:10]([CH:12]3[CH2:15][C:14](=[CH2:16])[CH2:13]3)=[N:9][C:8]=2[C:17]2[CH:26]=[C:25]3[C:20]([CH:21]=[CH:22][C:23]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)=[N:24]3)=[CH:19][CH:18]=2)[CH:5]=[CH:6][N:7]=1
Reactant: C=C1CC(C(=O)NC(c2ccc3ccc(-c4ccccc4)nc3c2)c2nccnc2Cl)C1
Solvent: CN(C)C=O
Solvent: O=P(Cl)(Cl)Cl
Product: C=C1CC(c2nc(-c3ccc4ccc(-c5ccccc5)nc4c3)c3c(Cl)nccn23)C1
Temperature: 55 °C

Procedure:
N-[(3-Chloropyrazin-2-yl)(2-phenylquinolin-7-yl)methyl]-3 methylenecyclobutanecarboxamide (0.02 mmol, 10 g) was dissolved in 150 mL POCl3 in a 250 mL rbf, charged with 0.1 mL DMF and heated to 55° C. under a consistent N2 flow for 1 h (the reaction was vented with a needle). The excess POCl3 was removed under reduced pressure and the residue was quenched with 2 N NH3 in isopropanol (250 mL) at 0° C. and water. The aqueous layer was washed with DCM (100 mL×2) and the combined organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (flash column) eluting with 20-50% EtOAc in hexane. Concentration in vacuo of the product-rich fractions afforded the desired product as yellow solid; MS (ES, Pos.): m/z 423 (100) [MH+]; 1H NMR (CDCl3, 400 MHz) δ 3.28-3.31 (m, 2H), 3.39-3.42 (m, 2H), 3.85-3.93 (m, 1H), 4.94 (p, J=2.4 Hz, 2H), 7.38 (d, J=4.9 Hz, 1H), 7.42-7.57 (m, 4H), 7.89-7.92 (m, 3H), 8.18-8.21 (m, 2H), 8.27 (dd, J=8.6 Hz, 0.8 Hz, 1H), 8.53 (s, 1H).
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][NH2:5].Cl[C:7]1[C:16](=[O:17])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9](=[O:18])[C:8]=1[NH:19][C:20](=[O:22])[CH3:21].O>C1C=CC=CC=1>[CH3:1][O:2][CH2:3][CH2:4][NH:5][C:7]1[C:16](=[O:17])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9](=[O:18])[C:8]=1[NH:19][C:20](=[O:22])[CH3:21]
Reactant: CC(=O)NC1=C(Cl)C(=O)c2ccccc2C1=O
Reactant: COCCN
Solvent: c1ccccc1
Solvent: O
Product: COCCNC1=C(NC(C)=O)C(=O)c2ccccc2C1=O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
2-Methoxyethylamine (0.8 ml) was added to a solution of N-(3-chloro-1,4-dihydro-1,4-dioxo-2-naphthalenyl)acetamide (1.0 g) in benzene (20 ml) and the mixture was stirred at room temperature for 1 hour. Water was added to the reaction solution and the mixture was extracted with chloroform. The organic layer was washed with water and brine and then dried over anhydrous sodium sulfate. The solvent was evaporated and the residue was recrystallized from ethyl acetate to give N-[3-(2-methoxyethyl)amino-1,4-dihydro-1,4-dioxo-2-naphthalenyl]acetamide (0.87 g) as a red powder.
Reaction SMILES: O1[C:3]23[C@:16]([CH3:21])([CH:17]=[CH:18][C:19](=[O:20])[CH:2]12)[C@@H:15]1[C@H:6]([C@H:7]2[C@@:11]([CH2:13][CH2:14]1)([CH3:12])[C:10](=[O:22])[CH2:9][CH2:8]2)[CH2:5][C:4]3=[CH2:23].B(F)(F)[F:25].CCOCC>C(OCC)C>[F:25][C:2]1[C:19](=[O:20])[CH:18]=[CH:17][C@@:16]2([CH3:21])[C:3]=1[C:4](=[CH2:23])[CH2:5][C@@H:6]1[C@@H:15]2[CH2:14][CH2:13][C@@:11]2([CH3:12])[C@H:7]1[CH2:8][CH2:9][C:10]2=[O:22]
Reactant: FB(F)F
Reactant: C=C1C[C@H]2[C@@H]3CCC(=O)[C@@]3(C)CC[C@@H]2[C@@]2(C)C=CC(=O)C3OC132
Solvent: CCOCC
Product: C=C1C[C@@H]2[C@H](CC[C@]3(C)C(=O)CC[C@@H]23)[C@@]2(C)C=CC(=O)C(F)=C12

Procedure:
A solution of 4,5-epoxy-6-methylenandrost-1-ene-3,17-dione (1.0 g) in diethyl ether (100 ml) was treated with boron trifluoride etherate (1.4 ml) for 3 hours at room temperature. Then the solution was washed with 5% sodium carbonate solution, water, dried (Na2SO4) and evaporated in vacuo. The residue was dissolved in pyridine (20 ml) and 0.4 ml of thionyl chloride were added at 0° C. After 5 minutes water was added and the product isolated with ether. The ether extracts were washed with 2N hydrochloric acid, water, dried (Na2SO4) and evaporated. The resulting raw product was chromatographed on silica gel using hexane/ethyl acetate as eluant to yield 0.6 g of pure 4-fluoro-6-methylenandrosta-1,4-diene-3,17-dione.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:24]=[C:25]([O:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:26]=1)[C:12]1[O:13][C:14]2[C:19]([C:20](=[O:22])[CH:21]=1)=[CH:18][CH:17]=[C:16]([OH:23])[CH:15]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH2:37]([CH:39]1[O:41][CH2:40]1)Cl>CN(C)C=O>[CH2:28]([O:27][C:25]1[CH:24]=[C:11]([CH:10]=[C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH:26]=1)[C:12]1[O:13][C:14]2[C:19]([C:20](=[O:22])[CH:21]=1)=[CH:18][CH:17]=[C:16]([O:23][CH2:37][CH:39]1[O:41][CH2:40]1)[CH:15]=2)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1
Reactant: ClCC1CO1
Reactant: O=c1cc(-c2cc(OCc3ccccc3)cc(OCc3ccccc3)c2)oc2cc(O)ccc12
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=c1cc(-c2cc(OCc3ccccc3)cc(OCc3ccccc3)c2)oc2cc(OCC3CO3)ccc12
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a well-stirred solution of 3′,5′-dibenzyloxy-7-hydroxy-flavone, 22 (8 g, 17.8 mmol) in dry dimethyl formamide (200 mL) was added 50% sodium hydride (3 g, 125 mmol) at 0-5° C. and after 30 minutes, excess of epichlorohydrin (8.3 mL, 107 mmol) was added and stirred at room temperature for overnight. The reaction mixture was concentrated under reduced pressure, diluted with water and extracted with chloroform. The combined organic layers were dried over sodium sulphate, filtered and evaporated to dryness. The crude product was purified by column chromatography to afford 28. Yield 7.1 g (79%); mp 172-173° C.; MS (FAB) 507 (M++1); IR (KBr) 1640; 1H NMR (200 MHz, CDCl3) δ 8.13 (d, J=8.7 Hz, 1H), 7.47-7.34 (m, 10H), 7.11 (d, J=2.2 Hz, 2H), 7.00 (dd, J=10.9 Hz, 2.1 Hz, 1H), 6.97 (d, J=1.9 Hz, 1H), 6.77 (d, J=2.0 Hz, 1H), 6.69 (s, 3H), 5.10 (s, 4H), 4.38 (dd, J=11.1 Hz, 2.8 Hz, 1H), 4.04 (dd, J=11.1 Hz, 5.8 Hz, 1H), 3.41-3.40 (m, 1H), 2.95 (t, J=4.5 Hz, 4.5 Hz, 1H), 2.80 (dd, J=4.8 Hz, 2.6 Hz, 1H); 13C NMR δ 177.9, 163.8, 162.9, 160.7, 158.1, 136.7, 133.9, 129.1, 128.6, 127.9, 127.5, 118.2, 115.1, 108.1, 106.0, 105.4, 101.7, 70.8, 69.7, 50.2, 44.9.