Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[C:9]([C:17]3[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=3)[O:8][C:4]=2[N:5]=[CH:6][N:7]=1.[S:24]1[CH2:28][CH2:27][S:26][CH:25]1[CH2:29][NH2:30].CCN(C(C)C)C(C)C>C(O)CCC>[S:24]1[CH2:28][CH2:27][S:26][CH:25]1[CH2:29][NH:30][C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[C:9]([C:17]3[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=3)[O:8][C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: NCC1SCCS1
Reactant: Oc1ccc(-c2oc3ncnc(Cl)c3c2-c2ccccc2)cc1
Solvent: CCCCO
Solvent: CCN(C(C)C)C(C)C
Product: Oc1ccc(-c2oc3ncnc(NCC4SCCS4)c3c2-c2ccccc2)cc1

Procedure:
This compound was prepared by a method analogous to that for 70. Briefly, compound 79 was heated with C-[1,3]dithiolan-2-yl-methylamine and DIEA in 1-butanol to provide the title compound. MS: 422.1 (M+1). 1HNMR (DMSO-d6) ppm 9.86 (s, 1H), 8.33 (s, 1H), 7.59-7.51 (m, 5H), 7.26 (d, 2H, 7.00 Hz), 6.74 (d, 2H, 7.00 Hz), 5.35 (t, 1H), 4.69 (t, 1H, J=6.00 Hz), 3.64 (t, 2H, J=6.00 Hz), 3.13-3.05 (m, 4H).
Reaction SMILES: [C:1]1([S:7]([N@:10]2[CH2:12][CH:11]2[C:13]([N:15]2[CH2:20][CH2:19][N:18]([C:21]3[CH:26]=[C:25]([CH3:27])[CH:24]=[CH:23][C:22]=3[CH3:28])[CH2:17][CH2:16]2)=[O:14])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[I-].[Na+].[F:31][C:32]1[CH:37]=[CH:36][C:35]([N:38]=[C:39]=[O:40])=[CH:34][CH:33]=1>>[C:1]1([S:7]([N:10]2[CH2:12][C@@H:11]([C:13]([N:15]3[CH2:16][CH2:17][N:18]([C:21]4[CH:26]=[C:25]([CH3:27])[CH:24]=[CH:23][C:22]=4[CH3:28])[CH2:19][CH2:20]3)=[O:14])[N:38]([C:35]3[CH:36]=[CH:37][C:32]([F:31])=[CH:33][CH:34]=3)[C:39]2=[O:40])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: Cc1ccc(C)c(N2CCN(C(=O)C3C[N@@]3S(=O)(=O)c3ccccc3)CC2)c1
Reactant: O=C=Nc1ccc(F)cc1
Agent: [I-]
Agent: [Na+]
Product: Cc1ccc(C)c(N2CCN(C(=O)[C@@H]3CN(S(=O)(=O)c4ccccc4)C(=O)N3c3ccc(F)cc3)CC2)c1

Procedure:
In analogy to example 2, ((S)-1-benzenesulfonyl-aziridin-2-yl)-[4-(2,5-dimethyl-phenyl)-piperazin-1-yl]-methanone (example 21, step 3) was reacted with sodium iodide and 4-fluorophenylisocyanate to give the title compound as a colorless solid. MS: 537.2 ([M+H]+)
Reaction SMILES: [C:1]([NH2:5])([CH3:4])([CH3:3])[CH3:2].[Br:6][C:7]1[CH:8]=[C:9]([S:13](Cl)(=[O:15])=[O:14])[CH:10]=[CH:11][CH:12]=1>>[Br:6][C:7]1[CH:8]=[C:9]([S:13]([NH:5][C:1]([CH3:4])([CH3:3])[CH3:2])(=[O:15])=[O:14])[CH:10]=[CH:11][CH:12]=1
Reactant: CC(C)(C)N
Reactant: O=S(=O)(Cl)c1cccc(Br)c1
Product: CC(C)(C)NS(=O)(=O)c1cccc(Br)c1
Yield: 106.4 %

Procedure:
Prepared by general procedure III from tert-butylamine (3.16 mL, 30 mmol) and commercially available 3-bromobenzenesulfonyl chloride (1.44 mL, 10 mmol) to give the title compound as a light yellow solid (3.11 g, 106%). MS (ISN) 290.1 [(M−H)−], 292.2 [(M+2−H)−].
Reaction SMILES: [OH:1][CH:2]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:16]=[C:15]([C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:18]=3[C:28]([F:31])([F:30])[F:29])[O:14][N:13]=2)=[CH:8][CH:7]=1)[C:3]([OH:5])=O.[CH3:32][O:33][CH2:34][C:35]1[N:39]=[C:38]([CH2:40][NH2:41])[O:37][N:36]=1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[OH:1][CH:2]([C:6]1[CH:7]=[CH:8][C:9]([C:12]2[N:16]=[C:15]([C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:18]=3[C:28]([F:29])([F:30])[F:31])[O:14][N:13]=2)=[CH:10][CH:11]=1)[C:3]([NH:41][CH2:40][C:38]1[O:37][N:36]=[C:35]([CH2:34][O:33][CH3:32])[N:39]=1)=[O:5]
Reactant: COCc1noc(CN)n1
Reactant: O=C(O)C(O)c1ccc(-c2noc(-c3onc(-c4ccccc4)c3C(F)(F)F)n2)cc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN1CCOCC1
Solvent: CN(C)C=O
Product: COCc1noc(CNC(=O)C(O)c2ccc(-c3noc(-c4onc(-c5ccccc5)c4C(F)(F)F)n3)cc2)n1
Reaction time: 1 h
Yield: 37 %

Procedure:
(R/S)-2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid (Int-V, 20 mg, 0.046 mmol), (3-(methoxymethyl)-1,2,4-oxadiazol-5-yl)methanamine (9.96 mg, 0.070 mmol), 4-methylmorpholine (18.76 mg, 0.185 mmol), and HATU (22.92 mg, 0.060 mmol) were dissolved in DMF (1 mL). This was stirred for 1 h before it was purified via preparative LC/MS with the following conditions: Column: Waters XBridge C18, 19×250 mm, 5-μm particles; Guard Column: Waters XBridge C18, 19×10 mm, 5-μm particles; Mobile Phase A: 5:95 methanol:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 methanol:water with 10-mM ammonium acetate; Gradient: 45-100% B over 25 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation to give (R/S)-2-hydroxy-N-((3-(methoxymethyl)-1,2,4-oxadiazol-5-yl)methyl)-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (9.7 mg, 0.017 mmol, 37.6% yield): LCMS=557.2 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.16 (2 H, d, J=8.53 Hz), 7.50-7.76 (8 H, m), 5.21 (1 H, s), 4.69 (2 H, d, J=7.53 Hz), 4.54 (2 H, s), 3.43 (3 H, s); HPLC peak RT=2.7 min (Method E).
Reaction SMILES: [CH2:1]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[OH:11])[CH:2]=[CH2:3].[O:12]=[CH:13]C(Cl)(Cl)Cl.C(=O)([O-])[O-].[Na+].[Na+]>O>[CH2:1]([O:4][C:5]1[CH:10]=[C:9]([CH:8]=[CH:7][C:6]=1[OH:11])[CH:13]=[O:12])[CH:2]=[CH2:3]
Reactant: O=CC(Cl)(Cl)Cl
Reactant: C=CCOc1ccccc1O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Product: C=CCOc1cc(C=O)ccc1O
Reaction time: 8 h

Procedure:
149 g (1 mol) of o-allyloxyphenol and 180 g (1.22 mols) if chloral are fused by gentle warming, 100 g of finely powdered sodium carbonate are added at 25° C and the mixture is subsequently stirred for 8 hours. The resulting viscous mass is stored for 5 days at room temperature and then introduced into 500 ml of water. The whole is thoroughly stirred, the water is decanted and washing is repeated three more times, with 250 ml of water at a time. The viscous oil which remains is crude 2-allyloxy-4-(1-hydroxy-2-trichloro-ethyl)-phenol. This is introduced into a solution of 250 g of potassium hydroxide in 500 ml of methanol at 30° C over the course of 2-3 hours and the reaction mixture is left to stand for 3 hours. The alkali metal salts which have precipitated are filtered off and the filtrate is evaporated under reduced pressure. The oily residue is converted into a slurry with ice water, acidified with hydrochloric acid and extracted with chloroform. The chloroform extract is washed with water, dried over sodium sulphate and then filtered through a 3 cm thick layer of Merck silica gel (0.063-0.20). After washing with chloroform, evaporation of the filtrate under reduced pressure and crystallisation of the residue from hexane yields 3-allyloxy-4-hydroxy-benzaldehyde of melting point 66°-67° C.
Reaction SMILES: [O:1]=[C:2]1[CH2:10][C:9]2[C:4](=[CH:5][C:6]([C:11]([C:13]3[CH:14]=[C:15]([NH:19][C:20]([C:22]4[CH:23]=[N:24][N:25]([CH2:28][CH3:29])[C:26]=4[CH3:27])=[O:21])[CH:16]=[CH:17][CH:18]=3)=[O:12])=[CH:7][CH:8]=2)[NH:3]1.[CH:30](OCC)=[O:31].[O-]CC.[Na+].Cl>C(O)C>[OH:31][CH:30]=[C:10]1[C:9]2[C:4](=[CH:5][C:6]([C:11]([C:13]3[CH:14]=[C:15]([NH:19][C:20]([C:22]4[CH:23]=[N:24][N:25]([CH2:28][CH3:29])[C:26]=4[CH3:27])=[O:21])[CH:16]=[CH:17][CH:18]=3)=[O:12])=[CH:7][CH:8]=2)[NH:3][C:2]1=[O:1]
Reactant: CCn1ncc(C(=O)Nc2cccc(C(=O)c3ccc4c(c3)NC(=O)C4)c2)c1C
Reactant: CCOC=O
Agent: CC[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: CCn1ncc(C(=O)Nc2cccc(C(=O)c3ccc4c(c3)NC(=O)C4=CO)c2)c1C
Temperature: 78 °C
Yield: 79 %

Procedure:
1-Ethyl-5-methyl-1H-pyrazole-4-carboxylic acid [3-(2-oxo-2,3-dihydro-1H-indole-6-carbonyl)-phenyl]-amide (0.235 g, 0.605 mmol) and ethyl formate (0.145 mL, 1.80 mmol) were dissolved in anhydrous ethanol (5 mL). The resulting solution was treated in dropwise fashion with a 21 wt % solution of sodium ethoxide in ethanol (1.13 mL, 3.02 mmol). This reaction mixture was heated at 78° C. for 0.5 h, producing a black oil. Subsequently, the reaction mixture was cooled to room temperature, and then the reaction pH was adjusted to pH 1 with dropwise addition of 1M HCl(aq) causing the formation of a brown precipitate. The suspension was filtered and the solids were washed with 0° C. EtOH to afford the pure 1-Ethyl-5-methyl-1H-pyrazole-4-carboxylic acid [3-(3-hydroxymethylene-2-oxo-2,3-dihydro-1H-indole-6-carbonyl)-phenyl]-amide (0.199 g, 0.478 mmol, 79%).
Reaction SMILES: C([O:5][C:6]([C:8]1[CH:27]=[CH:26][CH:25]=[CH:24][C:9]=1[C:10]1[CH:15]=[CH:14][C:13]([CH2:16][NH:17][C:18](=[NH:23])[CH2:19][CH2:20][CH2:21][CH3:22])=[CH:12][CH:11]=1)=[O:7])(C)(C)C.F[C:29](F)(F)[C:30]([OH:32])=O>>[CH2:19]([C:18]1[N:17]([CH2:16][C:13]2[CH:12]=[CH:11][C:10]([C:9]3[CH:24]=[CH:25][CH:26]=[CH:27][C:8]=3[C:6]([OH:5])=[O:7])=[CH:15][CH:14]=2)[C:6](=[O:5])[CH:8]=[C:9]([O:32][CH2:30][CH3:29])[N:23]=1)[CH2:20][CH2:21][CH3:22]
Reactant: O=C(O)C(F)(F)F
Reactant: CCCCC(=N)NCc1ccc(-c2ccccc2C(=O)OC(C)(C)C)cc1
Product: CCCCc1nc(OCC)cc(=O)n1Cc1ccc(-c2ccccc2C(=O)O)cc1

Procedure:
The title compound is prepared from N-(2'-t-butoxycarbonylbiphen-4-yl)methylvaleramidine and ethyl 3,3-diethocyacrylate (Aldrich) similarly to that in Example 16. The t-butyl ester is hydrolyzed in neat trifluoroacetic acid to give the title compound.
Reaction SMILES: [C:1]([C:3]1([CH2:9][C:10]([OH:12])=[O:11])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1)#[N:2].[H][H]>CO.[Rh].[Pd]>[NH2:2][CH2:1][C:3]1([CH2:9][C:10]([OH:12])=[O:11])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1
Reactant: N#CC1(CC(=O)O)CCCCC1
Reactant: [H][H]
Agent: [Pd]
Agent: [Rh]
Solvent: CO
Product: NCC1(CC(=O)O)CCCCC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 79.7 %

Procedure:
One gram of 10% rhodium on carbon, containing 1% palladium, (Pearlman, W. M., Tetrahedron Letters, pages 1663-1664 (1967)) is slurried in 30 ml methanol and reduced under hydrogen in a Parr shaker. 1-Cyanocyclohexaneacetic acid (16.7 g, 0.1 mol) is dissolved in 40 ml methanol and combined with the reduced catalyst. The mixture is placed under 50 pounds per square inch gauge (psig) hydrogen and shaken for two hours at room temperature. The catalyst is removed by filtration, and the filtrate is condensed to a volume of 25 ml by vacuum distillation. Isopropanol, 100 ml, is added and an additional 25 to 50 ml of solvent is removed by vacuum distillation. The resultant slurry is cooled at 0 to 5° C. for 24 hours and filtered and dried to give 13.65 g (79% of theory) of 1-(aminomethyl)-cyclohexaneacetic acid; mp 162-163° C.
Reaction SMILES: P(Cl)(Cl)([Cl:3])=O.O=[C:7]1[C:12]([C:13]#[N:14])=[CH:11][C:10]([CH3:15])=[C:9]([CH3:16])[NH:8]1>>[Cl:3][C:7]1[C:12]([C:13]#[N:14])=[CH:11][C:10]([CH3:15])=[C:9]([CH3:16])[N:8]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: Cc1cc(C#N)c(=O)[nH]c1C
Product: Cc1cc(C#N)c(Cl)nc1C
Temperature: 25 °C
Reaction time: 1 h
Yield: 66.7 %

Procedure:
Phosphorus oxychloride (15 mL) was added to 2-oxo-1,2-dihydro-5,6-dimethyl pyridine-3-carbonitrile (2.00 g, 13.5 mmol) in a two neck 50 mL round bottom flask, and this mixture was stirred at RT for 1 h, and then refluxed for 12 h. Afterwards, the excess phosphorous oxychloride was distilled off, and the residue was poured into ice cooled water. The aqueous solution was basified with saturated sodium bicarbonate solution, and the precipitate that formed was filtered off to afford the title compound (1.50 g), yield: 66.7%.
Reaction SMILES: [NH:1](C(OCC1C=CC=CC=1)=O)[C@H:2]([C:8]([NH:10][NH:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:9])[CH2:3][CH2:4][C:5](=[O:7])[NH2:6].[H][H]>CO.[Pd]>[NH2:1][C@H:2]([C:8]([NH:10][NH:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:9])[CH2:3][CH2:4][C:5](=[O:7])[NH2:6]
Reactant: [H][H]
Reactant: CC(C)(C)OC(=O)NNC(=O)[C@H](CCC(N)=O)NC(=O)OCc1ccccc1
Agent: [Pd]
Solvent: CO
Product: CC(C)(C)OC(=O)NNC(=O)[C@@H](N)CCC(N)=O

Procedure:
16.00 Grams of Z-Gln-NHNHBoc was suspended in 100 ml of methanol, a small amount of palladium black was added thereto and stirred for 18 hours under the condition of introducing hydrogen gas. After completion of the reaction, the catalyst was removed by suction filtration, the filtrate was subjected to distillation under a reduced pressure, the residue thus obtained was dried under a reduced pressure in a desiccator to obtain the desired product.
Reaction SMILES: [NH2:1][C:2]1([CH2:9][C:10]#[CH:11])[CH2:6][CH2:5][N:4]([CH3:7])[C:3]1=[O:8].I[C:13]1[N:18]=[C:17]([CH3:19])[CH:16]=[C:15]([C:20]2[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=2)[N:14]=1.C(NC(C)C)(C)C>COC(C)(C)C.[Cu](I)I.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:1][C:2]1([CH2:9][C:10]#[C:11][C:13]2[N:18]=[C:17]([CH3:19])[CH:16]=[C:15]([C:20]3[CH:21]=[CH:22][C:23]([C:26]([F:29])([F:27])[F:28])=[CH:24][CH:25]=3)[N:14]=2)[CH2:6][CH2:5][N:4]([CH3:7])[C:3]1=[O:8]
Reactant: Cc1cc(-c2ccc(C(F)(F)F)cc2)nc(I)n1
Reactant: C#CCC1(N)CCN(C)C1=O
Agent: I[Cu]I
Agent: c1ccc([P]([Pd][P](c2ccccc2)(c2ccccc2)c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CC(C)NC(C)C
Solvent: COC(C)(C)C
Product: Cc1cc(-c2ccc(C(F)(F)F)cc2)nc(C#CCC2(N)CCN(C)C2=O)n1
Temperature: 25 °C
Reaction time: 120 h
Yield: 80.3 %

Procedure:
To a stirred solution of 3-amino-1-methyl-3-prop-2-ynyl-pyrrolidin-2-one (which may be prepared as described in Description 3) (2.3 g, 15.11 mmol) in tert-butyl methyl ether (50 mL) was added 2-iodo-4-methyl-6-[4-(trifluoromethyl)-phenyl]pyrimidine (which may be prepared as described in Description 12) (6.05 g, 16.62 mmol). diisopropylamine (6.35 mL, 45.34 mmol) was then added, followed by copper iodide (57.56 mg, 0.300 mmol) and bis(triphenylphosphine)palladium (II) dichloride (106.07 mg, 0.1500 mmol). The reaction was then stirred at room temperature for 5 days. The reaction mixture was transferred to a separating funnel and the flask washed with an additional quantity of tert-butyl methyl ether (15 ml). The organic solution was washed with water (2×50 mL) and brine (50 mL). The organic phase was dried over magnesium sulphate, filtered, and then the magnesium sulphate washed with dichloromethane (30 ml). The filtrate was concentrated at reduced pressure to give a yellow foam. The product was purified by silica gel chromatography eluting with ethyl acetate followed by an increasing percentage of a solution of 10% 0.880 ammonia in methanol, to give the title compound (D14b) as a yellow foam (4.71 g). This racemate was consistent by NMR and mass spectroscopy with the R isomer prepared in Description 14.
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:23]=[CH:22][C:7]([O:8][CH2:9][C:10]([OH:21])([C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:11][N:12]2[CH:16]=[N:15][CH:14]=[N:13]2)=[C:6]([CH3:24])[CH:5]=1.I[CH3:26]>O1CCOCC1>[Cl:3][C:4]1[CH:23]=[CH:22][C:7]([O:8][CH2:9][C:10]([O:21][CH3:26])([C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:11][N:12]2[CH:16]=[N:15][CH:14]=[N:13]2)=[C:6]([CH3:24])[CH:5]=1
Reactant: CI
Reactant: Cc1cc(Cl)ccc1OCC(O)(Cn1cncn1)C(C)(C)C
Agent: [H-]
Agent: [Na+]
Solvent: C1COCCO1
Product: COC(COc1ccc(Cl)cc1C)(Cn1cncn1)C(C)(C)C
Temperature: 25 °C
Reaction time: 4 h
Yield: 53.3 %

Procedure:
27 g (0.9 mol) of 80% strength sodium hydride were introduced in portions into a solution of 290 g (0.86 mol) of 2-(4-chloro-2-methyl-phenoxy-methyl)-3,3-dimethyl-1-(1,2,4-triazol-1-yl)-2-butanol in 1,600 ml of absolute dioxane at room temperature. The mixture was subsequently stirred at room temperature for 4 hours, and 141.9 g (1 mol) of iodomethane were then added dropwise. The reaction mixture was stirred at 40° C. for 12 hours and another 10 g (0.33 mol) of 80% strength sodium hydride were then added in portions. After the mixture hadbeen stirred at room temperature for three hours, 57 g (0.4 mol) of iodomethane were added and the reaction mixture was subsequently stirred at room temperature for 72 hours. The suspension was filtered, the filtrate was concentrated, the oily residue was taken up in methylene chloride and the methylene chloride mixture was washed twice with water, dried over sodium sulphate and concentrated. 1,5-Naphthalenedisulphonic acid was added to the residue, in acetone, the salt which precipitated wasfiltered off with suction, washed with acetone and suspended in methylene chloride, and saturated sodium bicarbonate solution was added. The organicphase was separated off, washed and concentrated. 155 g (54% of theory) of 2-(4-chloro-2-methyl-phenoxymethyl)-3,3-dimethyl-2-methoxy- 1-(1,2,4-triazol-1-yl)butane were obtained as a light yellow oil of refractive index nD20 =1.5390.
Reaction SMILES: N[C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:6]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:5]=[C:4]([CH3:18])[N:3]=1.N([O-])=[O:20].[Na+]>Cl.O>[CH2:11]([O:10][C:8]([C:7]1[C:2](=[O:20])[NH:3][C:4]([CH3:18])=[CH:5][C:6]=1[C:13]([O:15][CH2:16][CH3:17])=[O:14])=[O:9])[CH3:12]
Reactant: O=N[O-]
Reactant: CCOC(=O)c1cc(C)nc(N)c1C(=O)OCC
Agent: Cl
Agent: [Na+]
Solvent: O
Product: CCOC(=O)c1cc(C)[nH]c(=O)c1C(=O)OCC
Temperature: 25 °C
Reaction time: 1 h

Procedure:
In 90 ml of 2% hydrochloric acid was dissolved 2.52 g (10 mmol) of 2-amino-3,4-diethoxycarbonyl-6-methylpyridine. A solution of 0.83 g (1.2 eq.) of sodium nitrite dissolved in 3 ml of water was added dropwise to the solution. The mixture was stirred at room temperature for 1 hour and left standing in a refrigerator overnight. The resulting crystals were collected by filtration. The crystals were recrystallized from ethyl acetate to give colorless plates.
Reaction SMILES: [C:1]1([N:7]=[C:8]=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:10][S:11][C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][C:20]=1[C:21]([F:24])([F:23])[F:22])[NH:17][CH2:16][CH2:15]2>>[C:1]1([NH:7][C:8]([N:17]2[C:18]3[C:14](=[CH:13][C:12]([S:11][CH3:10])=[C:20]([C:21]([F:22])([F:24])[F:23])[CH:19]=3)[CH2:15][CH2:16]2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CSc1cc2c(cc1C(F)(F)F)NCC2
Reactant: O=C=Nc1ccccc1
Product: CSc1cc2c(cc1C(F)(F)F)N(C(=O)Nc1ccccc1)CC2
Yield: 34 %

Procedure:
This was prepared from phenyl isocyanate and 5-methylthio-6-trifluoromethyl indoline in 34% yield m.p. 163-165° C.
Reaction SMILES: [CH2:1]([N:7]1[CH:12]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:10]([CH3:19])=[C:9]([N+:20]([O-])=O)[C:8]1=[O:23])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]>C(OCC)(=O)C.[Pd]>[NH2:20][C:9]1[C:8](=[O:23])[N:7]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])[CH:12]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:10]=1[CH3:19]
Reactant: CCCCCCn1cc(-c2ccccc2)c(C)c([N+](=O)[O-])c1=O
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CCCCCCn1cc(-c2ccccc2)c(C)c(N)c1=O
Reaction time: 4 h
Yield: 97.3 %

Procedure:
A mixture of 1-hexyl-4-methyl-3-nitro-5-phenyl-2-pyridone (0.093 g, 0.30 mmol) and 10% Pd/C in ethyl acetate (100 mL) was hydrogenated at 45 psi in a Parr apparatus for 4 hours. The catalyst was removed by filtration, and the solvent was evaporated to give 3-amino-1-hexyl-4-methyl-5-phenyl-2-pyridone (0.083 g, 97%).