Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C@@H:1]1([N:10]2[C:20]3[N:19]=[C:17]([NH2:18])[NH:16][C:14](=[O:15])[C:13]=3[N:12]=[CH:11]2)[O:9][C@H:6]([CH2:7][OH:8])[C@@H:4]([OH:5])[C@H:2]1[OH:3].[C:21](Cl)(=[O:37])[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36]>CN(C1C=CN=CC=1)C.CN(C)C=O>[C:21]([C@@:1]1([N:10]2[C:20]3[N:19]=[C:17]([NH2:18])[NH:16][C:14](=[O:15])[C:13]=3[N:12]=[CH:11]2)[O:9][C@H:6]([CH2:7][OH:8])[C@@H:4]([OH:5])[C@H:2]1[OH:3])(=[O:37])[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36]
Reactant: CCCCCCCCCCCCCCCC(=O)Cl
Reactant: Nc1nc2c(ncn2[C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)c(=O)[nH]1
Agent: CN(C)c1ccncc1
Solvent: CN(C)C=O
Product: CCCCCCCCCCCCCCCC(=O)[C@@]1(n2cnc3c(=O)[nH]c(N)nc32)O[C@H](CO)[C@@H](O)[C@H]1O
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a 100 mL flask was added guanosine (2.0 g, 7.06 mmol) and N,N-dimethyl-4-aminopyridine (0.017 g, 0.14 mmol). N,N-dimethylformamide (25 mL) was added via cannula with stirring, the flask was purged with argon gas and pyridine (14 mL) was added via cannula. The slurry was allowed to cool 10 min. in an ice/NaCl bath and palmitoyl chloride (2.8 mL, 9.2 mmol) was added dropwise. The mixture was allowed to stir while it slowly warmed to 25° C. After 18 h, the mixture was poured into 300 mL of ice-cold 0.1 M sodium bicarbonate solution giving a white solid which was isolated by suction filtration, washed with 3×100 mL hot water, air dried, and recrystallized from hot 2-methoxyethanol.
Reaction SMILES: S(Cl)([Cl:3])=O.CN(C)C=O.[Cl:10][C:11]1[C:12]([CH3:29])=[C:13]([CH:22]2[CH2:27][NH:26][C:25](=[O:28])[CH2:24][O:23]2)[C:14]([O:20][CH3:21])=[C:15]([CH:17](O)[CH3:18])[CH:16]=1>C(Cl)Cl>[Cl:10][C:11]1[C:12]([CH3:29])=[C:13]([CH:22]2[CH2:27][NH:26][C:25](=[O:28])[CH2:24][O:23]2)[C:14]([O:20][CH3:21])=[C:15]([CH:17]([Cl:3])[CH3:18])[CH:16]=1
Reactant: O=S(Cl)Cl
Reactant: COc1c(C(C)O)cc(Cl)c(C)c1C1CNC(=O)CO1
Solvent: ClCCl
Solvent: CN(C)C=O
Product: COc1c(C(C)Cl)cc(Cl)c(C)c1C1CNC(=O)CO1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
A mixture of thionyl chloride (15 μL, 0.21 mmol) and N,N-dimethylformamide (10.0 μL) was stirred at room temperature for 10 minutes. A solution of 6-[3-chloro-5-(1-hydroxyethyl)-6-methoxy-2-methylphenyl]morpholin-3-one (19.0 mg, 0.0634 mmol) (racemic mixture of two diastereomers from step 5) in methylene chloride (1.0 mL) was added and the mixture was stirred at room temperature overnight. The mixture was diluted with methylene chloride, washed with saturated sodium bicarbonate, water, brine, dried over sodium sulfate, filtered and concentrated to give the desired compound as a racemic mixture of two diastereomers, 19 mg, 94%. LCMS calculated for C14H17ClNO3 (M-Cl)+: m/z=282.1; found: 282.1.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:13][C@H:12]([CH2:14][N:15]3[CH:19]=[CH:18][N:17]=[N:16]3)[O:11][C:10]2=[O:20])[CH:5]=[CH:6][C:7]=1I.C([Sn](CCCC)(CCCC)[C:26]1[O:30][N:29]=[C:28]([CH3:31])[CH:27]=1)CCC>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[F:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:13][C@H:12]([CH2:14][N:15]3[CH:19]=[CH:18][N:17]=[N:16]3)[O:11][C:10]2=[O:20])[CH:5]=[CH:6][C:7]=1[C:26]1[O:30][N:29]=[C:28]([CH3:31])[CH:27]=1
Reactant: O=C1O[C@@H](Cn2ccnn2)CN1c1ccc(I)c(F)c1
Reactant: CCCC[Sn](CCCC)(CCCC)c1cc(C)no1
Agent: Cl[Pd]Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1COCCO1
Product: Cc1cc(-c2ccc(N3C[C@H](Cn4ccnn4)OC3=O)cc2F)on1
Temperature: 100 °C
Reaction time: 16 h
Yield: 49.7 %

Procedure:
A suspension of (5R)-3-(3-fluoro-4-iodophenyl)-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-2-one (Intermediate 6, 582 mg, 1.50 mmol) in 1,4-dioxane (14 ml) was placed under argon. Bis(triphenylphospine)palladium (II) chloride (42 mg, 0.060 mmol) was added, followed by the dropwise addition of 5-(tributylstannyl)-3-methylisoxazole (Sakamoto, T. et al; Tetrahedron, 1991, 47, 5111–5118; 0.84 g, 2.25 mmol) in 1,4-dioxane (1 ml). The mixture was heated at 100° C. After approximately 16 hours, the solution was concentrated under vacuum. The crude material was dissolved in acetonitrile and washed with hexanes (3×). The acetonitrile phase was concentrated under vacuum. Purification by chromatography on silica gel using EtOAc, followed by recrystallization from EtOAc/MeOH gave 256 mg of the title product.
Reaction SMILES: [Cl:1][C:2]1[C:7]([OH:8])=[C:6]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:4][N:3]=1.[CH3:12][Si](C=[N+]=[N-])(C)C>C(#N)C.CO>[Cl:1][C:2]1[C:7]([O:8][CH3:12])=[C:6]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:4][N:3]=1
Reactant: O=[N+]([O-])c1ccnc(Cl)c1O
Reactant: C[Si](C)(C)C=[N+]=[N-]
Solvent: CC#N
Solvent: CO
Product: COc1c([N+](=O)[O-])ccnc1Cl
Reaction time: 0.5 h
Yield: 67.8 %

Procedure:
To a solution of 2-chloro-4-nitro-pyridin-3-ol (1.05 g, 6.02 mmol) in acetonitrile (45 mL) and methanol (5 mL), trimethylsilyldiazomethane (2M in hexane, 3.9 mL, 7.8 mmol) were added slowly. After 30 minutes, mixture was concentrated and residue was purified by column chromatography on silica gel (hexane/ethyl acetate 5:1) to give 2-chloro-3-methoxy-4-nitro-pyridine as a white solid (0.77 g, 68%). 1HNMR (CDCl3, 400 MHz) δ 8.35-8.34 (d, J=5.1 Hz, 1H), 7.58-7.56 (d, J=5.2 Hz, 1H), 4.08 (s, 3H).
Reaction SMILES: [CH2:1]([C:8]1[C:9]([O:21]C)=[N:10][CH:11]=[C:12]([CH2:14][CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClCCCl.B(Br)(Br)Br.O>ClCCl>[CH2:1]([C:8]1[C:9]([OH:21])=[N:10][CH:11]=[C:12]([CH2:14][CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)CCc1cnc(OC)c(Cc2ccccc2)c1
Agent: BrB(Br)Br
Solvent: O
Solvent: ClCCl
Solvent: ClCCCl
Product: CCOC(=O)CCc1cnc(O)c(Cc2ccccc2)c1
Yield: 37.6 %

Procedure:
A mixture of 240 mg of 3-benzyl-5-(2-ethoxycarbonylethyl)-2-methoxypyridine, 2.5 ml of 1,2-dichloroethane and a solution of 1.0 M boron tribromide in 0.39 ml of dichloromethane was stirred at 50° C. for 8 hours. Water and silica gel were added to the reaction solution, and the solvent was removed. The residue was subjected to silica gel column chromatography using 75% ethyl acetate/hexane, to give 86 mg of the target compound.
Reaction SMILES: [C:1]([O:5][C:6](=[O:34])[CH:7]([NH:17][C:18]([NH:20][CH:21]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:22][CH2:23][CH2:24][CH2:25][NH2:26])=[O:19])[CH2:8][CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])([CH3:4])([CH3:3])[CH3:2].[CH3:35][Sn:36]([CH3:46])([CH3:45])[C:37]1[CH:44]=[CH:43][C:40]([CH:41]=O)=[CH:39][CH:38]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[C:1]([O:5][C:6](=[O:34])[CH:7]([NH:17][C:18]([NH:20][CH:21]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:22][CH2:23][CH2:24][CH2:25][NH:26][CH2:41][C:40]1[CH:43]=[CH:44][C:37]([Sn:36]([CH3:35])([CH3:46])[CH3:45])=[CH:38][CH:39]=1)=[O:19])[CH2:8][CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C)(C)OC(=O)CCC(NC(=O)NC(CCCCN)C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Reactant: C[Sn](C)(C)c1ccc(C=O)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCCl
Product: CC(C)(C)OC(=O)CCC(NC(=O)NC(CCCCNCc1ccc([Sn](C)(C)C)cc1)C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Temperature: 40 °C
Reaction time: 8 h
Yield: 38.3 %

Procedure:
To a solution of 2-[3-(5-Amino-1-tert-butoxycarbonyl-pentyl)-ureido]-pentanedioic acid di-tert-butyl ester (150 mg, 0.31 mmol) in DCE (10 mL) was added 4-Trimethylstannanyl-benzaldehyde (82 mg, 0.31 mmol) followed by sodium triacetoxyborohydride (98 mg, 0.47 mmol) and the reaction was stirred overnight at 40° C. The reaction was concentrated and purified by column chromatography using hexanes/ethyl acetate as eluent to afford the desired product (88 mg, 38%) as a thick syrup which begins to solidify upon standing. 1H NMR (400 MHz, DMSO-d6) δ 7.48 (d, J=7.4 Hz, 2H), 7.30 (d, J=7.4 Hz, 2H), 6.27 (m, 2H, NH's), 3.96 (m, 4H), 2.74 (bm, 2H), 2.21 (m, 2H), 1.87 (m, 2H), 1.65-1.19 (m, 7H), 1.35 (m, 27H, t-Bu's), 0.23 (s, 9H). ESMS m/z: 742 (Sn-cluster).
Reaction SMILES: F[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:10]([CH:20]([OH:36])[C:21]2[CH:26]=[CH:25][C:24]([O:27][CH2:28][CH2:29][N:30]3[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]3)=[CH:23][CH:22]=2)=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH:15]=[C:14]([OH:19])[CH:13]=[CH:12]2.[H-].[Na+].O>CN(C=O)C>[F:8][C:6]1[CH:5]=[C:4]2[C:3](=[CH:2][CH:7]=1)[C:9]1[C:10](=[C:11]3[C:16](=[CH:17][CH:18]=1)[CH:15]=[C:14]([OH:19])[CH:13]=[CH:12]3)[CH:20]([C:21]1[CH:22]=[CH:23][C:24]([O:27][CH2:28][CH2:29][N:30]3[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]3)=[CH:25][CH:26]=1)[O:36]2
Reactant: Oc1ccc2c(C(O)c3ccc(OCCN4CCCCC4)cc3)c(-c3ccc(F)cc3F)ccc2c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: Oc1ccc2c3c(ccc2c1)-c1ccc(F)cc1OC3c1ccc(OCCN2CCCCC2)cc1
Temperature: 25 °C
Yield: 66.9 %

Procedure:
Dissolve 6-(2,4-difluoro-phenyl)-5-{hydroxy-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methyl}-naphthalen-2-ol (3.4 g, 7.0 mmol) in dry DMF (70 mL). Slowly add sodium hydride (440 mg, 18 mmol) and plunge into a 140° C. oil bath for 30 minutes. Cool to room temperature and pour into water. Adjust the pH to 7 and extract three times with methylene chloride. Wash combined organic layers with water, dry with sodium sulfate, filter and concentrate. Triturate with ether to yield 2.2 g (69%) of the title compound: mass spectrum (ion spray) m/z=470.3 (M+H).
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[CH2:8][OH:9].[Li]CCCC.[NH:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=[C:16]1C(Cl)=O.Cl.C1C[O:31][CH2:30]C1>CCCCCC>[NH:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:17]([C:30]([O:9][CH2:8][CH:3]2[CH2:4][CH2:5][CH2:6][CH2:7][N:2]2[CH3:1])=[O:31])=[CH:16]1
Reactant: CN1CCCCC1CO
Reactant: O=C(Cl)c1cc2ccccc2[nH]1
Reactant: C1CCOC1
Agent: Cl
Agent: [Li]CCCC
Solvent: CCCCCC
Product: CN1CCCCC1COC(=O)c1c[nH]c2ccccc12

Procedure:
To a THF solution (17 ml) of 1-methyl-2-piperidinemethanol (1.70 g, 13.2 mmol) cooled in an ice-sodium chloride bath to -5° C. was dropwise added a 1.5M hexane solution of n-BuLi (8.7 ml, 13.0 mmol) over a period of 5 min. Stirring was continued under ice-cooling for 30 min. To a mixture was then dropwise added a THF solution (5 ml) of indolecarboxylic acid chloride (1.50 g, 8.35 mmol) over a period of 5 min. After stirring at room temperature for 5 hours, a reaction solution was poured onto diluted hydrochloric acid. The organic layer was separated, and the aqueous layer was extracted with EtOAc. The combined organic layers were then adjusted with saturated aqueous NaCO3 to a pH of >10 and again extracted with EtOAc. The basic extract was washed successively with water and saturated aqueous sodium chloride, then dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The pale yellow crystals thus produced were recrystallized from a chloroform-methanol mixture to give 1.20 g of the title compound as prisms. m.p. 168°-170° C.;
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[C:10]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)=[N:9][CH:8]=[CH:7][N:6]=1)=[O:4].[N+:19]([O-])([OH:21])=[O:20]>[N+](C)([O-])=O>[CH3:1][O:2][C:3]([C:5]1[C:10]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=2[N+:19]([O-:21])=[O:20])=[N:9][CH:8]=[CH:7][N:6]=1)=[O:4]
Reactant: COC(=O)c1nccnc1Nc1ccc(Cl)cc1
Reactant: O=[N+]([O-])O
Solvent: C[N+](=O)[O-]
Product: COC(=O)c1nccnc1Nc1ccc(Cl)cc1[N+](=O)[O-]
Reaction time: 0.75 h

Procedure:
A suspension of 2.6 g 3-(4-chlorophenylamino)-pyrazine-2-carboxylic acid methyl ester in 100 ml nitromethane is stirred and treated dropwise at 0° C. with 24 ml nitric acid (99%). Stirring is continued at 0° C. for further 45 minutes. The solution is poured on ice and extracted with methylene chloride. The organic phase is washed with saturated sodium bicarbonate solution, dried over sodium sulphate and evaporated to give the heading compound, m.p. 191°-192°.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[O:7][C:8]([CH3:30])=[C:9]([CH2:11][O:12][C:13]2[CH:29]=[CH:28][C:16]([CH2:17][O:18][C:19]3[C:24]([CH2:25][C:26]#N)=[CH:23][CH:22]=[CH:21][N:20]=3)=[CH:15][CH:14]=2)[N:10]=1.COCCO.[OH-:36].[K+].Cl.[OH2:39]>>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[O:7][C:8]([CH3:30])=[C:9]([CH2:11][O:12][C:13]2[CH:29]=[CH:28][C:16]([CH2:17][O:18][C:19]3[C:24]([CH2:25][C:26]([OH:39])=[O:36])=[CH:23][CH:22]=[CH:21][N:20]=3)=[CH:15][CH:14]=2)[N:10]=1
Reactant: O
Reactant: Cc1oc(-c2ccco2)nc1COc1ccc(COc2ncccc2CC#N)cc1
Reactant: [OH-]
Agent: Cl
Agent: [K+]
Solvent: COCCO
Product: Cc1oc(-c2ccco2)nc1COc1ccc(COc2ncccc2CC(=O)O)cc1
Yield: 63 %

Procedure:
To a mixture of 2-[2-[4-[[2-(2-furyl)-5-methyl-4-oxazolyl]methoxy]benzyloxy]-3-pyridyl]acetonitrile (0.60 g) and 2-methoxyethanol (2 mL) was added a 4N aqueous potassium hydroxide solution (2 mL) and the mixture was heated under reflux for 4 hrs. 1N Hydrochloric acid (8 mL) and water were added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated to give crystals (0.40 g, 63%) of 2-[2-[4-[[2-(2-furyl)-5-methyl-4-oxazolyl]methoxy]benzyloxy]-3-pyridyl]acetic acid. Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 151-152° C.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([C:11]([F:14])([F:13])[F:12])=[C:6]([CH:10]=1)[C:7](Cl)=[O:8].[CH:15]1([CH2:18][CH2:19][NH:20][C:21]([C:23]2[N:24]=[N:25][C:26]([N:29]3[CH2:35][CH2:34][CH2:33][NH:32][CH2:31][CH2:30]3)=[CH:27][CH:28]=2)=[O:22])[CH2:17][CH2:16]1>>[CH:15]1([CH2:18][CH2:19][NH:20][C:21]([C:23]2[N:24]=[N:25][C:26]([N:29]3[CH2:35][CH2:34][CH2:33][N:32]([C:7](=[O:8])[C:6]4[CH:10]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=4[C:11]([F:14])([F:13])[F:12])[CH2:31][CH2:30]3)=[CH:27][CH:28]=2)=[O:22])[CH2:16][CH2:17]1
Reactant: O=C(Cl)c1cc(F)ccc1C(F)(F)F
Reactant: O=C(NCCC1CC1)c1ccc(N2CCCNCC2)nn1
Product: O=C(NCCC1CC1)c1ccc(N2CCCN(C(=O)c3cc(F)ccc3C(F)(F)F)CC2)nn1

Procedure:
Following the procedure of Example 3, making variations only as required to use 5-fluoro-2-trifluoromethylbenzoyl chloride in place of isoxazole-5-carbonyl chloride to react with 6-[1,4]diazepan-1-ylpyridazine-3-carboxylic acid (2-cyclopropylethyl)amide, the title compound was obtained as a white solid (60% yield).
Reaction SMILES: [H-].[Na+].[OH:3][CH2:4][CH:5]1[CH2:7][CH2:6]1.[Br:8][CH2:9][CH2:10][CH2:11][CH2:12]Br.O>C1(C)C=CC=CC=1>[Br:8][CH2:9][CH2:10][CH2:11][CH2:12][O:3][CH2:4][CH:5]1[CH2:7][CH2:6]1
Reactant: BrCCCCBr
Reactant: OCC1CC1
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O
Product: BrCCCCOCC1CC1
Temperature: 100 °C
Reaction time: 15 h

Procedure:
2.8 g of a 60% suspension of sodium hydride in mineral oil are added in portions to a solution of 5.0 g of hydroxymethylcyclopropane in 25 ml of toluene at room temperature. The mixture is then heated at 100° C. for 2 hours. After this, it is allowed to reach room temperature and a solution of 14.9 g of 1,4-dibromobutane in 15 ml of toluene is added. The mixture is left to stir at 100° C. for a further 15 hours. Then, at room temperature, 10 ml of water are added, the phases are separated, and the toluene is removed in a rotary evaporator. The product is isolated by vacuum distillation.
Reaction SMILES: [CH2:1]([Cl:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:9]([C:11]1([CH3:35])[CH:16]([CH3:17])[CH:15]([OH:18])[CH2:14][C:13]([CH2:20][CH3:21])([CH3:19])[N:12]1[O:22][C:23]([CH3:34])([CH3:33])[C:24]([NH:26][CH2:27][CH2:28][CH2:29][N:30]([CH3:32])[CH3:31])=[O:25])[CH3:10]>C(#N)C>[Cl-:8].[CH2:1]([N+:30]([CH2:29][CH2:28][CH2:27][NH:26][C:24](=[O:25])[C:23]([O:22][N:12]1[C:13]([CH2:20][CH3:21])([CH3:19])[CH2:14][CH:15]([OH:18])[CH:16]([CH3:17])[C:11]1([CH2:9][CH3:10])[CH3:35])([CH3:34])[CH3:33])([CH3:32])[CH3:31])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: ClCc1ccccc1
Reactant: CCC1(C)CC(O)C(C)C(C)(CC)N1OC(C)(C)C(=O)NCCCN(C)C
Solvent: CC#N
Product: CCC1(C)CC(O)C(C)C(C)(CC)N1OC(C)(C)C(=O)NCCC[N+](C)(C)Cc1ccccc1
Product: [Cl-]
Temperature: 25 °C
Reaction time: 19 h
Yield: 102.8 %

Procedure:
Benzylchloride (0.87 g, 0.0069 mol) is added to a solution of 2-(2,6-diethyl-4-hydroxy-2,3,6-trimethyl-piperidine-1-yloxy)-N-(3-dimethylamino-propyl)-2-methyl-propionamide (2.2 g, 0.0057 mol, compound 110) in acetonitrile (3 ml). The mixture is stirred for 19 h at room temperature and is then evaporated. The residue is triturated with diethylether to remove the excess of benzylchloride, the solid is filtered off and dried to afford 3.0 g of the title compound as a colorless amorphous solid.
Reaction SMILES: C(C1(CCCCCCCC)C2C=CC=CC=2C2C1=CC=CC=2)CCCCCCC.[C:30]1([O:36][CH3:37])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.[CH3:38][O:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=1OC.[CH2:48]1[N:53]([N+:54]([O-:56])=[O:55])[CH2:52][N:51]([N+:57]([O-:59])=[O:58])[CH2:50][N:49]1[N+:60]([O-:62])=[O:61].[CH2:63]([O:80][N+:81]([O-:83])=[O:82])[C:64]([CH2:75][O:76][N+:77]([O-:79])=[O:78])([CH2:70][O:71][N+:72]([O-:74])=[O:73])[CH2:65][O:66][N+:67]([O-:69])=[O:68]>C1COCC1.C(#N)C>[C:30]1([O:36][CH3:37])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.[CH2:50]1[N:49]([N+:60]([O-:62])=[O:61])[CH2:48][N:53]([N+:54]([O-:56])=[O:55])[CH2:52][N:51]1[N+:57]([O-:59])=[O:58].[CH2:75]([O:76][N+:77]([O-:79])=[O:78])[C:64]([CH2:65][O:66][N+:67]([O-:69])=[O:68])([CH2:63][O:80][N+:81]([O-:83])=[O:82])[CH2:70][O:71][N+:72]([O-:74])=[O:73].[N+:54]([C:43]1[CH:44]=[CH:45][C:40]([O:39][CH3:38])=[CH:41][CH:42]=1)([O-:56])=[O:55]
Reactant: COc1ccccc1OC
Agent: CCCCCCCCC1(CCCCCCCC)c2ccccc2-c2ccccc21
Agent: O=[N+]([O-])N1CN([N+](=O)[O-])CN([N+](=O)[O-])C1
Agent: O=[N+]([O-])OCC(CO[N+](=O)[O-])(CO[N+](=O)[O-])CO[N+](=O)[O-]
Solvent: COc1ccccc1
Solvent: C1CCOC1
Solvent: CC#N
Product: COc1ccc([N+](=O)[O-])cc1
Yield: 1 %

Procedure:
To probe the scope of the photonitration reaction, the nitration of 9,9-dioctylfluorene, anisole and 1,2-dimethoxybenzene by RDX and PETN was investigated. Extended photolysis (5 h) of a mixture of 9,9-dioctylfluorene and either RDX or PETN in 1:1 acetonitrile:THF at either 254, 313, 334, or 356 nm did not generate any observable products and 9,9-dioctylfluorene was recovered in ca. 90% yield. Photolysis of anisole with RDX or PETN yielded only trace amounts of 4-nitroanisole (<1% GC yield) after 4 hours. Photolysis of 1,2-dimethoxybenzene with either RDX or PETN yielded 1,2-dimethoxy-4-nitrobenzene in only ca. 8% yield after 2 hours; moreover this reaction did not proceed cleanly and numerous polar photoproducts were observed. Based on this set of experiments, anilines were selected as candidates for potential indicators. To create fluorogenic indicators based on the facile nitration reaction between aromatic amines and the photofragmentation products of RDX and PETN, 9,9-disubstituted 9,10-dihydroacridines (DHAs) were targeted as chemosensory.
Reaction SMILES: CS(C)=O.[CH2:5]([OH:7])[CH3:6].[H-].[Na+].[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][N:20]([C:23](=[O:49])[C:24]2[CH:29]=[CH:28][C:27]([C:30]3[CH:31]=[N:32][C:33]([NH2:48])=[C:34]([O:36][CH:37]([C:39]4[C:44]([Cl:45])=[CH:43][CH:42]=[C:41](F)[C:40]=4[Cl:47])[CH3:38])[CH:35]=3)=[CH:26][CH:25]=2)[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11]>O>[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][N:20]([C:23](=[O:49])[C:24]2[CH:29]=[CH:28][C:27]([C:30]3[CH:31]=[N:32][C:33]([NH2:48])=[C:34]([O:36][CH:37]([C:39]4[C:44]([Cl:45])=[CH:43][CH:42]=[C:41]([O:7][CH2:5][CH3:6])[C:40]=4[Cl:47])[CH3:38])[CH:35]=3)=[CH:26][CH:25]=2)[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11]
Reactant: CCO
Reactant: CC(Oc1cc(-c2ccc(C(=O)N3CCN(C(=O)OC(C)(C)C)CC3)cc2)cnc1N)c1c(Cl)ccc(F)c1Cl
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: CCOc1ccc(Cl)c(C(C)Oc2cc(-c3ccc(C(=O)N4CCN(C(=O)OC(C)(C)C)CC4)cc3)cnc2N)c1Cl
Temperature: 40 °C

Procedure:
To 4 mL of DMSO was added 0.124 ml ethanol followed by 32 mg NaH. After stirring for 30 minutes 250 mg of 250 mg 4-(4-{6-Amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-benzoyl)-piperazine-1-carboxylic acid tert-butyl ester was added and the reaction was heated to 40° C. After three hours the reaction was cooled and poured into water to precipitate. After neutralization to pH 6, 200 mg of a tan solid was isolated, 77%.
Reaction SMILES: Br[CH2:2][C:3]1([CH3:16])[CH2:7][C:6]2[C:8]([CH3:15])=[C:9]([NH2:14])[C:10]([CH3:13])=[C:11]([CH3:12])[C:5]=2[O:4]1.[CH2:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:20][CH2:19][NH:18]1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C(=O)C.O>[CH3:16][C:3]1([CH2:2][N:18]2[CH2:19][CH2:20][C:21]3[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH2:17]2)[CH2:7][C:6]2[C:8]([CH3:15])=[C:9]([NH2:14])[C:10]([CH3:13])=[C:11]([CH3:12])[C:5]=2[O:4]1
Reactant: Cc1c(C)c2c(c(C)c1N)CC(C)(CBr)O2
Reactant: c1ccc2c(c1)CCNC2
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC(=O)N(C)C
Product: Cc1c(C)c2c(c(C)c1N)CC(C)(CN1CCc3ccccc3C1)O2

Procedure:
A suspension of 2-bromomethyl-2,3-dihydro-2,4,6,7-tetramethyl-5-benzofuranamine (1.4 g), 1,2,3,4-tetrahydroisoquinoline (1.3 g), and potassium carbonate (1.4 g) in N,N-dimethylacetamide (10 mL) was refluxed under nitrogen gas for 15 hours. This reaction mixture was diluted with water and extracted with 2 portions of ethyl acetate. The pooled organic layer was washed with water and saturated aqueous NaCl, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=3:1) to provide 2,3-dihydro-2,4,6,7-tetramethyl-2-[(1,2,3,4-tetrahydroisoquinolin-2-yl)methyl]-5-benzofuranamine. This product was dissolved in ethanol, followed by addition of 1 equivalent of oxalic acid solution in ethanol. This mixture was heated and the resulting solution was concentrated under reduced pressure. The crystals that separated out were collected to provide 1.5 g of the title compound. Yield 68%.
Reaction SMILES: [NH2:1][NH:2][C:3]([NH2:5])=[S:4].[CH3:6][NH:7][C:8](=[O:19])[CH2:9][CH2:10][C:11](=O)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.Cl.O>CO>[NH2:5][C:3]([NH:2][N:1]=[C:11]([C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)[CH2:10][CH2:9][C:8]([NH:7][CH3:6])=[O:19])=[S:4]
Reactant: CNC(=O)CCC(=O)c1ccccc1
Reactant: NNC(N)=S
Agent: Cl
Solvent: CO
Solvent: O
Product: CNC(=O)CCC(=NNC(N)=S)c1ccccc1
Yield: 98.9 %

Procedure:
Thiosemicarbazide (2.60 g, 28.5 mmol) was added to a solution of N-methyl4-oxo-4-phenyl-butyramide (3.33 g, 17.4 mmol), prepared in the previous step, in 60 ml of methanol plus 4.7 ml of 1 N HCl plus 4.7 ml of water and the reaction stirred at room temperature for 22 hours. The reaction was submerged in an ice bath and a solid precipitated. The solid was collected by filtration and dried to give 4.55 g of a white solid. The solid was triturated with water and then dried to give the title compound (4.10 g, 89%) as a white solid, mp 205-207° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][CH2:10][CH2:11][CH2:12][C:13]2([S:20]([C:23]3[CH:28]=[CH:27][C:26]([I:29])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[S:17][C:16](=[O:18])[NH:15][C:14]2=[O:19])=[CH:4][CH:3]=1.[N+:30]([C:33]1[CH:40]=[CH:39][C:36]([CH2:37]Br)=[CH:35][CH:34]=1)([O-:32])=[O:31].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][CH2:10][CH2:11][CH2:12][C:13]2([S:20]([C:23]3[CH:24]=[CH:25][C:26]([I:29])=[CH:27][CH:28]=3)(=[O:21])=[O:22])[S:17][C:16](=[O:18])[N:15]([CH2:37][C:36]3[CH:39]=[CH:40][C:33]([N+:30]([O-:32])=[O:31])=[CH:34][CH:35]=3)[C:14]2=[O:19])=[CH:4][CH:3]=1
Reactant: O=[N+]([O-])c1ccc(CBr)cc1
Reactant: O=C1NC(=O)C(CCCC#Cc2ccc(Cl)cc2)(S(=O)(=O)c2ccc(I)cc2)S1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=C1SC(CCCC#Cc2ccc(Cl)cc2)(S(=O)(=O)c2ccc(I)cc2)C(=O)N1Cc1ccc([N+](=O)[O-])cc1

Procedure:
5-[5-(4-Chlorophenyl)pent-4-ynyl]-5-(4-iodobenzenesulfonyl)-thiazolidine-2,4-dione is reacted with 4-nitrobenzyl bromide and potassium carbonate in DMF to give the title compound as a light tan solid, mp 172-175° C.