Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([CH:17]3[CH2:22][CH2:21][N:20](C#N)[CH2:19][CH2:18]3)=[N:9]2)=[CH:4][CH:3]=1.OS(O)(=O)=O.[OH-].[Na+]>O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([CH:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)=[N:9]2)=[CH:4][CH:3]=1
Reactant: N#CN1CCC(c2nn(-c3ccc(F)cc3)c3ccccc23)CC1
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: Fc1ccc(-n2nc(C3CCNCC3)c3ccccc32)cc1
Yield: 76 %

Procedure:
A stirred mixture of 4-[1-(4-fluorophenyl)-1H-indazol-3-yl]piperidine-1-carbonitrile of Example 102 (30 g, 0.094 moles) and 25% H2SO4 (225 ml) was refluxed for 20 hours. The mixture was cooled, poured into H2O, and basified with a 25% NaOH solution. The product was extracted (dichloromethane), dried (MgSO4), and concentrated to yield 21 g (76% of 1-(4-fluorophenyl)-3-(4-piperidinyl)-1H-indazole as an oil. To a stirred suspension of the indazole (3.5 g, 0.012 moles) and triethylamine (3.3 ml, 0.024 moles) in toluene (50 ml) was added methyl chloroformate (1.0 ml, 0.013 moles). The mixture was stirred for 17 hours at ambient temperature and was then poured into H2O. The product was extracted (ethyl acetate), dried (MgSO4), and concentrated to yield 4.6 g of an oil. The product was purified on the HPLC (silica gel:ethyl acetate-hexane, 1:2) which produced 3.0 g (72%) of 4-[1-(4-fluorophenyl)-1H-indazol-3-yl]piperidine-1-carboxylic acid methyl ester, m.p. 95°-97° C.
Reaction SMILES: [CH3:1][N:2]1[CH2:6][CH2:5][C@@:4]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])([CH2:7][C:8]#[CH:9])[C:3]1=[O:18].I[C:20]1[N:25]=[C:24]([CH3:26])[CH:23]=[C:22]([C:27]2[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][CH:28]=2)[N:21]=1.C(NC(C)C)(C)C.O>COC(C)(C)C.[Cu](I)I.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>[CH3:1][N:2]1[CH2:6][CH2:5][C@@:4]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:15])([CH3:14])[CH3:16])([CH2:7][C:8]#[C:9][C:20]2[N:25]=[C:24]([CH3:26])[CH:23]=[C:22]([C:27]3[CH:28]=[CH:29][C:30]([C:33]([F:36])([F:34])[F:35])=[CH:31][CH:32]=3)[N:21]=2)[C:3]1=[O:18]
Reactant: C#CC[C@]1(NC(=O)OC(C)(C)C)CCN(C)C1=O
Reactant: Cc1cc(-c2ccc(C(F)(F)F)cc2)nc(I)n1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: I[Cu]I
Solvent: CC(C)NC(C)C
Solvent: COC(C)(C)C
Solvent: O
Product: Cc1cc(-c2ccc(C(F)(F)F)cc2)nc(C#CC[C@]2(NC(=O)OC(C)(C)C)CCN(C)C2=O)n1
Reaction time: 0.33 h
Yield: 88.4 %

Procedure:
In a 5 L three-necked flask with overhead paddle stirrer and a nitrogen inlet. tert-butyl N-[(3S)-1-methyl-2-oxo-3-prop-2-ynyl-pyrrolidin-3-yl]carbamate (which may be prepared as described in Description 4) (104.79 g, 415.32 mmol) was suspended in tert-Butyl methyl ether (2100 mL). 2-Iodo-4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidine (which may be prepared as described in Description 6) (166.34 g, 456.85 mmol) was added followed by diisopropylamine (174.63 mL, 1246 mmol) and the mixture was stirred over 20 mins. To the suspension was added copper iodide (1.58 g, 8.31 mmol) followed by bis(triphenyl-phosphine)palladium (II) dichloride (2.92 g, 4.15 mmol) and the mixture was stirred at room temperature for 3 hours. Water (1000 mL) was added and the mixture stirred for 30 mins. The phases were separated and the organic phase, washed with water (2×500 mL), dried over magnesium sulphate, filtered and evaporated to a tan foam, 230 g. The material was purified in three batches of approximately 75 g by column chromatography using an 800 g (Biotage 75 L) column and eluting with a gradient of acetone in iso-hexane. This gave the title compound (D7) (179.3 g) in good purity by NMR and consistent spectroscopically with that produced by Method 1.
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[C:12]2[C:7]([CH2:8][CH2:9][CH2:10][NH:11]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[Cl:14][CH2:15][C:16](Cl)=[O:17].C(OCC)(=O)C.CCCCCCC>C(OCC)(=O)C>[Cl:14][CH2:15][C:16]([N:11]1[C:12]2[C:7](=[CH:6][CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[CH:13]=2)[CH2:8][CH2:9][CH2:10]1)=[O:17]
Reactant: O=[N+]([O-])c1ccc2c(c1)NCCC2
Reactant: O=C(Cl)CCl
Solvent: CCCCCCC
Solvent: CCOC(C)=O
Product: O=C(CCl)N1CCCc2ccc([N+](=O)[O-])cc21
Temperature: 60 °C
Reaction time: 2 h

Procedure:
1.78 g of 7-nitro-1,2,3,4-tetrahydroquinoline (0.01 mol) are dissolved in 15 ml of ethyl acetate. This solution is run into a mixture of 15 ml of ethyl acetate and 0.80 ml of chloroacetyl chloride. A white precipitate forms immediately, and stirring is continued at 30° C. for 2 h (the reaction is monitored by thin layer chromatography (90/10 ethyl acetate/heptane)). After 2 h, since the reaction is incomplete, 0.2 equivalent of chloroacetyl chloride is added and the temperature is raised to 60° C.; the solid formed undergoes dissolution. When the reaction has finished, the mixture is cooled and the solvent is evaporated off. 2.46 g of a beige product which corresponds to the expected compound are recovered.
Reaction SMILES: C([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C:13]#[CH:14])(OC(C)(C)C)=O.[CH2:15]([O:17][C:18]([C:20]1[C:24]([CH3:25])=[C:23](/[CH:26]=[C:27]2\[C:28](=[O:38])[NH:29][C:30]3[C:35]\2=[C:34](I)[C:33]([F:37])=[CH:32][CH:31]=3)[NH:22][CH:21]=1)=[O:19])[CH3:16]>CN(C=O)C.CCN(CC)CC.CCOC(C)=O.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>[CH2:15]([O:17][C:18]([C:20]1[C:24]([CH3:25])=[C:23](/[CH:26]=[C:27]2\[C:28](=[O:38])[NH:29][C:30]3[C:35]\2=[C:34]([C:14]#[C:13][C@@H:9]2[CH2:10][CH2:11][CH2:12][NH:8]2)[C:33]([F:37])=[CH:32][CH:31]=3)[NH:22][CH:21]=1)=[O:19])[CH3:16]
Reactant: CCOC(=O)c1c[nH]c(/C=C2\C(=O)Nc3ccc(F)c(I)c32)c1C
Reactant: C#C[C@@H]1CCCN1C(=O)OC(C)(C)C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: CCOC(=O)c1c[nH]c(/C=C2\C(=O)Nc3ccc(F)c(C#C[C@@H]4CCCN4)c32)c1C
Reaction time: 2 h

Procedure:
Using Method C above, (S)-N-Boc-2-Ethynyl-pyrrolidine (106 mg, 0.55 mmol) (Example 87B) was coupled with (Z)-5-(5-fluoro-4-iodo-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester (80 mg, 0.18 mmol) (Example 116B) using (Ph3P)4Pd (21 mg, 0.02 mmol) and a catalytic amount of Cul in a mixture of DMF (5 mL) and Et3N (5 mL) as solvent at 80° C. for 5 hrs. Upon completion, the reaction mixture was diluted with EtOAc and extracted with H2O. The organic layer was dried over Na2SO4, concentrated and the residue was chromatographed on a silica gel column with a 0-40% EtOAc in hexanes gradient. The resulting intermediate was dissolved in 5 mL of a 50% trifluoroacetic acid in CH2Cl2 solution that contained 0.5 mL of H2O at 0° C. and stirred for 2 hrs. Upon completion, the reaction mixture was diluted with EtOAc and extracted with ammonium hydroxide. The organic layer was dried over Na2SO4 and concentrated. (S)-(Z)-5-[[5-Fluoro-2-oxo-4-[(pyrrolidin-2-yl)ethynyl]-1,2-dihydro-indol-3-ylidene]methyl]-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester was obtained after silica gel column chromatography with a 0-100% EtOAc in hexanes-30% THF in EtOAc gradient and precipitation out of THF with excess of hexanes. (Yield 21 mg, 28%).
Reaction SMILES: [O:1]1[C:6]2[CH:7]=[CH:8][C:9](C=O)=[CH:10][C:5]=2[O:4][CH2:3][CH2:2]1.C1C=C(Cl)C=C(C(OO)=[O:21])C=1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[O:1]1[C:6]2[CH:7]=[CH:8][C:9]([OH:21])=[CH:10][C:5]=2[O:4][CH2:3][CH2:2]1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: O=Cc1ccc2c(c1)OCCO2
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: Oc1ccc2c(c1)OCCO2
Temperature: 50 °C
Reaction time: 2 h
Yield: 96.7 %

Procedure:
To a solution of 2,3-dihydro-benzo[1,4]dioxin-6-carboxaldehyde (30.0 g, 183 mmol) in 500 ml CH2Cl2 was added mCPBA (37.85 g, 219 mmol). The suspension was heated to 50° C. After 16 h saturated NaHCO3 was added and the mixture was extracted with CH2Cl2 The combined organics were concentrated in vacuo and taken up in MeOH and 200 ml 4M NaOH was added. After 2 h the mixture was acidified with 4M HCl and extracted with ethyl acetate. The combined organics were washed with saturated NaHCO3, washed with brine, concentrated in vacuo, and taken up in CH2Cl2. The solution was filtered to remove the precipitate. The resulting solution was stirred with saturated NaHCO3 for 1 h, separated, dried over MgSO4, filtered and concentrated in vacuo to give 2,3-dihydro-benzo[1,4]dioxin-6-ol (26.92 g, 94%).
Reaction SMILES: [CH3:1][O:2][N:3]=[CH:4][C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[C:7]([OH:14])[CH:6]=1.N1C=CN=C1.[CH:20]([Si:23](Cl)([CH:27]([CH3:29])[CH3:28])[CH:24]([CH3:26])[CH3:25])([CH3:22])[CH3:21].C(OCC)(=O)C>CN(C)C=O.CCOCC>[CH3:1][O:2][N:3]=[CH:4][C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[C:7]([O:14][Si:23]([CH:27]([CH3:29])[CH3:28])([CH:24]([CH3:26])[CH3:25])[CH:20]([CH3:22])[CH3:21])[CH:6]=1
Reactant: CC(C)[Si](Cl)(C(C)C)C(C)C
Reactant: CON=Cc1ccc([N+](=O)[O-])c(O)c1
Agent: c1c[nH]cn1
Solvent: CCOC(C)=O
Solvent: CCOCC
Solvent: CN(C)C=O
Product: CON=Cc1ccc([N+](=O)[O-])c(O[Si](C(C)C)(C(C)C)C(C)C)c1
Temperature: 25 °C
Yield: 93 %

Procedure:
An amount of 3.0 g (15.39 mmol) of 3-hydroxy-4-nitrobenzaldehyde O-methyloxime is stirred in N,N-dimethylformamide (8 mL), followed by addition of imidazole (3.14 g, 46.17 mmol) and 4.89 mL (23.1 mmol) of triisopropylsilyl chloride. The reaction mixture is stirred at room temperature over night. 1:1 ethyl acetate: ether (300 mL) is added and extracted 3× with water, followed by additional washing with brine, dried over magnesium sulfate, evaporated, to afford 5.02 g (93% yield) as a yellow crystals.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([CH3:12])[C:10]=1[OH:11])[C:5]([OH:7])=[O:6].O[N:14]1[C:18](=[O:19])[CH2:17][CH2:16][C:15]1=[O:20].C1(N=C=NC2CCCCC2)CCCCC1.C(O)(=O)C>CN(C)C=O.C(OCC)C>[CH3:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([CH3:12])[C:10]=1[OH:11])[C:5]([O:7][N:14]1[C:18](=[O:19])[CH2:17][CH2:16][C:15]1=[O:20])=[O:6]
Reactant: Cc1cc(C(=O)O)cc(C)c1O
Reactant: O=C1CCC(=O)N1O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: CN(C)C=O
Solvent: CCOCC
Solvent: CC(=O)O
Product: Cc1cc(C(=O)ON2C(=O)CCC2=O)cc(C)c1O
Temperature: 0 °C
Reaction time: 2 h

Procedure:
A solution of 3,5-dimethyl-4-hydroxybenzoic acid (5.0 g, 30.0 mmol) in N,N-dimethylformamide (150 ml) was cooled to 0° C. and treated with N-hydroxysuccinimide (3.45 g, 30.0 mmol) and 1,3-dicyclohexylcarbodiimide (6.81 g, 33.0 mmol). The solution was stirred under nitrogen at 0° C. for 2 hours and then at 25° C. for 16 hours. The resulting mixture was stirred with 0.5 ml of acetic acid for 15 minutes, and then filtered to remove the insoluble urea. The filtrate was evaporated under reduced pressure to dryness. The dried material was washed with diethyl ether (100 ml) and suspended in boiling ethyl acetate (200 ml). The suspension, when hot, was filtered to remove insoluble impurities. The filtrate was concentrated and suspended in hot ethyl acetate/methylene chloride (1:1, 200 ml) and cooled to give an off-white powder in 2.91 g (37%). Rf 0.6 (silica gel, diethyl ether).
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[N:11]=[C:10]([C:12]([OH:14])=O)[CH:9]=[CH:8][C:7]=2[N:15]2[CH2:18][C:17]([F:20])([F:19])[CH2:16]2)[CH2:3][CH2:2]1.Cl.[CH3:22][C:23]1([CH3:31])[CH2:27][NH:26][CH:25]([C:28]([NH2:30])=[O:29])[CH2:24]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C>>[CH:1]1([CH2:4][O:5][C:6]2[N:11]=[C:10]([C:12]([N:26]3[CH2:27][C:23]([CH3:31])([CH3:22])[CH2:24][CH:25]3[C:28]([NH2:30])=[O:29])=[O:14])[CH:9]=[CH:8][C:7]=2[N:15]2[CH2:18][C:17]([F:20])([F:19])[CH2:16]2)[CH2:2][CH2:3]1
Reactant: CC1(C)CNC(C(N)=O)C1
Reactant: O=C(O)c1ccc(N2CC(F)(F)C2)c(OCC2CC2)n1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Product: CC1(C)CC(C(N)=O)N(C(=O)c2ccc(N3CC(F)(F)C3)c(OCC3CC3)n2)C1

Procedure:
In analogy to the procedure described in Example 47 b), 6-cyclopropylmethoxy-5-(3,3-difluoro-azetidin-1-yl)-pyridine-2-carboxylic acid (Example 1 b)) was reacted with 4,4-dimethyl-pyrrolidine-2-carboxylic acid amide hydrochloride (Example 90 d)) in the presence of TBTU and DIEA to obtain the title compound as colorless oil; MS (EI): m/e=380.6 [MH+].
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]([OH:9])=O.C1N=CN(C(N2C=NC=C2)=O)C=1.Cl.[CH3:23][NH:24][O:25][CH3:26].C(N(C(C)C)CC)(C)C>C(Cl)Cl>[CH3:26][O:25][N:24]([CH3:23])[C:7]([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=1)=[O:9]
Reactant: CNOC
Reactant: O=C(O)c1ccccn1
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CON(C)C(=O)c1ccccn1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Picolinic acid (12.3 g, 100 mmol), N,N-carbonyldiimidazole (17.8 g, 110 mmol) and anhydrous CH2Cl2 (150 mL) were combined and stirred at room temperature for 60 minutes. To the reaction mixture was added a solution of N,O-dimethylhydroxylamine hydrochloride (10.7 gr, 0.11 mole), anhydrous CH2Cl2 (50 mL) and diisopropylethylamine (20 mL), and stirring continued overnight. The reaction mixture was concentrated in vacuo and purified by flash chromatography (silica gel 60, MeOH/CH2Cl2, 9:1) to afford pyridine-2-carboxylic acid methoxy-methyl-amide (a pale yellow liquid, 15.9 g, 95%); ESI) m/z 167.
Reaction SMILES: [Cl:1][S:2]([OH:5])(=O)=[O:3].[CH3:6][C:7]1[CH:8]=[N:9][C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[CH:12][CH:11]=2.S(Cl)(Cl)=O>C(Cl)(Cl)Cl>[CH3:6][C:7]1[CH:8]=[N:9][C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[CH:12][C:11]=2[S:2]([Cl:1])(=[O:5])=[O:3]
Reactant: Cc1cnc2ccccc2c1
Reactant: O=S(=O)(O)Cl
Solvent: ClC(Cl)Cl
Solvent: O=S(Cl)Cl
Product: Cc1cnc2c(S(=O)(=O)Cl)cccc2c1
Temperature: 25 °C
Reaction time: 5 h
Yield: 34.3 %

Procedure:
To 9.0 mL (135 mmol, Fisher) of chlorosulfonic acid was added dropwise with stirring at room temperature 5.00 g (35.0 mmol, Lancaster) of 3-methyl-quinoline over ~5 minutes. The addition was exothermic. The resulting dark solution was heated to 140°-145°, stirring for 5 h, then cooled to 125°. To the cooled reaction mixture was added dropwise over 15 rain 3.3 mL (45 mmol, Mallinckrodt) of thionyl chloride, and the reaction mixture was then heated to 1400 for 1 h. The reaction mixture was cooled to room temperature, then cooled in an ice-bath and added slowly to 50 g of ice. Chloroform (50 mL) was added to the resulting slurry and stirred until the ice melted to give two layers. The aqueous layer was separated and extracted with 30 mL of chloroform. The chloroform layers were combined, washed with two-50 mL portions of 5% aqueous sodium bicarbonate solution, 50 mL of water, dried (sodium sulfate) and concentrated in vacuo to give 4.6 g of a crude light brown solid. The crude material was recrystallized (~20 mL toluene), and the crystals were washed with hexane and dried in vacuo to afford 2.89 g (12.0 mmol, 34%) of title compound as small pale brown crystals, mp 158°-159°.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:8]=[C:9]([CH:13]=[CH:14][CH:15]=2)[C:10](Cl)=[O:11])[CH2:3][CH2:2]1.[CH3:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[CH:19][C:18]=1[N+:24]([O-:26])=[O:25].C(N(CC)CC)C>C(Cl)Cl>[CH3:16][C:17]1[CH:23]=[CH:22][C:20]([NH:21][C:10](=[O:11])[C:9]2[CH:13]=[CH:14][CH:15]=[C:7]([N:4]3[CH2:5][CH2:6][O:1][CH2:2][CH2:3]3)[CH:8]=2)=[CH:19][C:18]=1[N+:24]([O-:26])=[O:25]
Reactant: Cc1ccc(N)cc1[N+](=O)[O-]
Reactant: O=C(Cl)c1cccc(N2CCOCC2)c1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1ccc(NC(=O)c2cccc(N3CCOCC3)c2)cc1[N+](=O)[O-]
Reaction time: 18 h
Yield: 19.3 %

Procedure:
3-Morpholinobenzoyl chloride (6.22 g) was added to a solution of 4-methyl-3-nitroaniline (4.20 g) and triethylamine (11.0 ml) in methylene chloride (150 ml) at ambient temperature under argon. The reaction mixture was stirred for 18 hours then diluted to 250 ml with methylene chloride. The mixture was washed with water (3×150 ml) and saturated sodium bicarbonate solution (2×100 ml), dried and evaporated to give a dark brown oil. The oil was triturated with diethyl ether and the solid collected and dried to yield N-(4-methyl-3-nitrophenyl)-3-morpholinobenzamide (1.82g); NMR: (CDCl3) 2.53 (s, 3H), 3.22 (t, 4H), 3.83 (t, 4H), 7.06 (dd, 1H), 7.23 (d, 1H), 7.37 (m, 2H), 7.42 (d, 1H), 7.88 (dd, 1H), 7.97 (s, 1H), 8.21 (d, 1H); m/z 340 (MH+); m.p. 149-150° C.
Reaction SMILES: [CH3:1][O:2]S([O-])(=O)=O.[CH3:7][C:8]1[CH:9]=[CH:10][CH:11]=[C:12]2[C:21]=1[N:20]=[C:19]1[C:14](C=[CH:16][CH:17]=[CH:18]1)=[NH+:13]2.C(=O)([O-])[O-].[Na+].[Na+]>O>[O:2]=[C:1]1[C:14]2[C:19](=[N:20][C:21]3[C:12]([N:13]=2)=[CH:11][CH:10]=[CH:9][C:8]=3[CH3:7])[CH:18]=[CH:17][CH2:16]1
Reactant: Cc1cccc2[nH+]c3ccccc3nc12
Reactant: COS(=O)(=O)[O-]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Product: Cc1cccc2nc3c(nc12)C=CCC3=O
Reaction time: 24 h
Yield: 35.9 %

Procedure:
2 g (0.011 mol) of 9-methylphenazinium methylsulphate are dissolved in 2 l of distilled water and then exposed for 24 hours to UV-radiation (from a source having a power 1.5 kW, at a distance of 30-40 cm) at the temperature of 40° C. in a closed quartz flask, then added with a 0.1M solution of sodium carbonate to the pH of 9.0. Then the irradiation is continued for additional 4 hours. The solution is filtered, added with 40 ml of a 10% solution of sodium carbonate and extracted four times with 200 ml portions of chloroform. The extracts are combined, dried with potassium carbonate and evaporated to the volume of 70 ml, then 250 ml of hot hexane are added and the mixture is cooled. The formed precipitate is filtered off, washed with 200 ml of hexane, recrystallized from 50 ml of water to give 0.83 g of 4-keto-9-methylphenazine (61%) in the form of blue crystals melting at 133°-135° C.
Reaction SMILES: O.[OH-].[Na+].[CH:4]1[CH:9]=[C:8]2[CH:10]=[CH:11][C:12]3[C:17]([C:18](=[O:19])[C:7]2=[CH:6][CH:5]=1)=[CH:16][CH:15]=[CH:14][CH:13]=3.[BH4-].[Na+]>CO>[CH:9]1[C:8]2[CH:10]=[CH:11][C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:17]=3[CH:18]([OH:19])[C:7]=2[CH:6]=[CH:5][CH:4]=1
Reactant: O=c1c2ccccc2ccc2ccccc12
Agent: [BH4-]
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: OC1c2ccccc2C=Cc2ccccc21
Reaction time: 8 h

Procedure:
4 ml of water, 0.45 ml of 1 N aqueous sodium hydroxide solution and 20 ml of a suspension of 1.50 g (7.27 mmol) of dibenzosuberenone in methanol were added to 200 mg (5.29 mmol) of sodium borohydride, and they were stirred overnight. Crystals thus precipitated were taken by the filtration, washed with water and dissolved in ethyl acetate. After drying over anhydrous magnesium sulfate, the solvent was evaporated under reduced pressure to obtain the title compound.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[H-].[Na+].[C:8]1([C:14](Cl)([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>CN(C=O)C>[C:14]([N:1]1[CH:5]=[CH:4][N:3]=[CH:2]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: c1c[nH]cn1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: c1ccc(C(c2ccccc2)(c2ccccc2)n2ccnc2)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 82.9 %

Procedure:
Imidazole (10.0 g, 146.9 mmol) was added to sodium hydride (60% dispersion in mineral oil, pre-washed in hexane, 6.5 g, 161.6 mmol) in DMF (200 ml), triphenylmethylchloride (41.0 g, 146.9 mmol) was then added and the reaction mixture stirred at room temperature for 18 h. The mixture was poured onto ice and the solid precipitate formed filtered off and partitioned between water and dichloromethane. The organic phase was washed with brine and dried over sodium sulphate and concentrated in vacuo to give the title compound (37.8 g, 83%). 1H NMR (CDCl3) δ 7.42-7.03 (1H, m). MS (ES) m/e 311 [M+H]+.
Reaction SMILES: [O:1]=[C:2]1[CH2:5][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:3]1.[CH2:13]1COCC1.C[Mg]Br.C1COCC1.O>CCOC(C)=O>[OH:1][C:2]1([CH3:13])[CH2:5][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:3]1
Reactant: CC(C)(C)OC(=O)N1CC(=O)C1
Reactant: C1CCOC1
Agent: C[Mg]Br
Solvent: O
Solvent: CCOC(C)=O
Product: CC1(O)CN(C(=O)OC(C)(C)C)C1
Reaction time: 1 h

Procedure:
tert-Butyl 3-oxoazetidine-1-carboxylate (1 g) and THF (20 ml), which had been cooled to 0° C., were mixed, and a 1.12 M methylmagnesium bromide/THF solution (10 ml) was added thereto, followed by stirring at the same temperature for 1 hour. Water and EtOAc were added to the reaction mixture, the organic layer was dried over Na2SO4, and the solvent was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/EtOAc) to obtain tert-butyl 3-hydroxy-3-methylazetidine-1-carboxylate (1.0 g).
Reaction SMILES: C([O:8][C@H:9]1[C@H:13]([O:14]CC2C=CC=CC=2)[C@@H:12]([CH2:22][O:23]CC2C=CC=CC=2)[O:11][C@H:10]1[N:31]1[CH:39]=[N:38][C:37]2[C:32]1=[N:33][C:34]([F:41])=[N:35][C:36]=2[NH2:40])C1C=CC=CC=1.C(=O)(O)[O-].[Na+].C>C(Cl)Cl.C(O)C>[C@@H:10]1([N:31]2[CH:39]=[N:38][C:37]3[C:32]2=[N:33][C:34]([F:41])=[N:35][C:36]=3[NH2:40])[O:11][C@H:12]([CH2:22][OH:23])[C@@H:13]([OH:14])[C@@H:9]1[OH:8]
Reactant: Nc1nc(F)nc2c1ncn2[C@@H]1O[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@@H]1OCc1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCO
Product: Nc1nc(F)nc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O
Reaction time: 8 h

Procedure:
Boron trichloride gas was bubbled in methylene chloride (610 ml.) at 0° in a 2-l., 3-necked flask equipped with a thermometer, magnetic stirrer, and addition funnel and the stirred solution then cooled to -72° (dry ice-acetone) before the dropwise addition (1 hour) of a cold solution of 9-(2,3,5-tri-O-benzyl-β-D-arabinofuranosyl)-2-fluoroadenine (6, 7.0 g., 12.5 mmoles) in methylene chloride (70 ml.). After a total reaction time of 2.75 hours, the cooling bath was removed and the solvent and gas removed in vacuo. The residue was dissolved in cold methylene chloride (40 ml.) and the solution evaporated to dryness (6 times) or until a solid white residue was obtained, before adding 450 ml. of cold 5% sodium bicarbonate followed by solid sodium bicarbonate to adjust the pH to 6-7. The mixture was diluted with ethanol, heated to boiling, treated with charcoal, filtered through Celite, and then allowed to stand at room temperature overnight. It was then chilled and the solid collected by filtration, washed with cold water and then ether, and dried in vacuo; yield 3.23 g. (91%); m.p. 259°-260°; homogeneous according to tlc (19:1) and hplc (23 water:2 acetonitrile); nmr: 3.7 (m, H4' and 2H5'), 4.15 (m, H2' and H3'), 5.1 (t, 5'--OH), 5.55 and 5.65 (2d, 2'-13 OH and 3'--OH), 6.14 (d, J'2' 3 Hz, H1'), 7.8 (broad s, NH2), 8.2 (s, H8); uv: pH 1-262 (13.2); pH 7, 13-261 (15.3).
Reaction SMILES: C[O-].[Na+].[C:4]1([SH:10])[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[C:11]1(=[O:16])[O:15][CH2:14][CH2:13][CH2:12]1>C(O)C>[C:4]1([S:10][CH2:14][CH2:13][CH2:12][C:11]([OH:16])=[O:15])[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: Sc1ccccc1
Reactant: O=C1CCCO1
Agent: C[O-]
Agent: [Na+]
Solvent: CCO
Product: O=C(O)CCCSc1ccccc1
Temperature: 25 °C
Yield: 52 %

Procedure:
Sodium methoxide (1.2 equivalent) was added to 60 ml of ethanol, in one portion, and the suspension was stirred at room temperature. Thiophenol (1 equivalent) was added to the above suspension and stirred at room temperature for 30 minutes. Butyrolactone (1.1 equivalent) was added to the reaction mixture and the resulting mixture was stirred at reflux temperature for 6 hours, cooled to room temperature and concentrated in vacuo. The resulting solid was washed with 200 ml hexane/ether 2:1, v/v. The solid was suspended into ice cold 2N HCl solution and stirred for 15 minutes. The resulting solid was filtered, washed with 100 ml hexane/ether and dried under reduced pressure at room temperature to give 4-(phenylsulfanyl)butanoic acid as tan solid: 52% yield; 1H NMR (CDCl3) δ 7.32-7.12 (m, 5H), 2.94 (t, 2H, J=7.2 Hz), 2.41 (t, 2H, J=7.2 Hz), 1.85 (p, 2H, J=7.2 Hz); Anal. Calc. For C10H12S1O2 : C, 61.22; H, 6.12. Found: C, 61.16; H, 6.28.