Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1](N(C(C)C)CC)([CH3:3])[CH3:2].CC(C)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[CH3:28][C:29]1[CH:38]=[C:37]([CH2:39][C:40]2[CH:57]=[CH:56][C:43]([C:44]([NH:46][C@@H:47]3[CH2:51][NH:50][CH2:49][C@@H:48]3[C:52]([O:54][CH3:55])=[O:53])=[O:45])=[CH:42][CH:41]=2)[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[N:30]=1>ClCCl.C(OCC)(=O)C>[CH:1]([N:50]1[CH2:51][C@@H:47]([NH:46][C:44](=[O:45])[C:43]2[CH:42]=[CH:41][C:40]([CH2:39][C:37]3[C:36]4[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=4)[N:30]=[C:29]([CH3:28])[CH:38]=3)=[CH:57][CH:56]=2)[C@@H:48]([C:52]([O:54][CH3:55])=[O:53])[CH2:49]1)([CH3:3])[CH3:2]
Reactant: CCN(C(C)C)C(C)C
Reactant: COC(=O)[C@H]1CNC[C@H]1NC(=O)c1ccc(Cc2cc(C)nc3ccccc23)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: CC(C)=O
Product: COC(=O)[C@H]1CN(C(C)C)C[C@H]1NC(=O)c1ccc(Cc2cc(C)nc3ccccc23)cc1
Yield: 61.5 %

Procedure:
Diisopropylethylamine (28 mg, 38 μL, 0.22 mmol), acetone (6 mg, 8 μL) and NaBH(OAc)3 (23 mg, 0.11 mmol) were added to a solution of the TFA salt (403a) (46 mg, 0.073 mmol) in 1 mL of dichloromethane. The whole mixture was stirred until the reaction went to completion. The solution was diluted with ethyl acetate and washed with saturated NaHCO3, H2O and brine. The organic layer was dried over MgSO4. After filtration and concentration, the residue was purified on silica gel to provide methyl (3S,4S)-1-isopropyl-4-({4-[(2-methyl-4-quinolinyl)methyl]benzoyl}amino)-3-pyrrolidinecarboxylate (20 mg, 63%). MS (ES+): 446(M+1).
Reaction SMILES: C(=O)([O-])[O-].[Na+].[Na+].[N:7]1[CH:12]=[CH:11][C:10](B(O)O)=[CH:9][CH:8]=1.[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[C:29]3[CH:30]=[C:31](OS(C(F)(F)F)(=O)=O)[CH:32]=[CH:33][C:28]=3[N:27]3[C:42]([CH3:45])=[N:43][N:44]=[C:26]3[C@H:25]([CH2:46][C:47]([O:49][CH2:50][CH3:51])=[O:48])[N:24]=2)=[CH:19][CH:18]=1.O>COCCOC.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.C(OCC)(=O)C>[Cl:16][C:17]1[CH:18]=[CH:19][C:20]([C:23]2[C:29]3[CH:30]=[C:31]([C:10]4[CH:11]=[CH:12][N:7]=[CH:8][CH:9]=4)[CH:32]=[CH:33][C:28]=3[N:27]3[C:42]([CH3:45])=[N:43][N:44]=[C:26]3[C@H:25]([CH2:46][C:47]([O:49][CH2:50][CH3:51])=[O:48])[N:24]=2)=[CH:21][CH:22]=1
Reactant: CCOC(=O)C[C@@H]1N=C(c2ccc(Cl)cc2)c2cc(OS(=O)(=O)C(F)(F)F)ccc2-n2c(C)nnc21
Reactant: OB(O)c1ccncc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: COCCOC
Product: CCOC(=O)C[C@@H]1N=C(c2ccc(Cl)cc2)c2cc(-c3ccncc3)ccc2-n2c(C)nnc21
Temperature: 120 °C

Procedure:
Sodium carbonate (66.3 mg), 4-pyridinylboronic acid (22.5 mg) and bis(triphenylphosphine)palladium(II) chloride (19.1 mg) were added to a 2-5 ml microwave vial. A solution of ethyl ((4S)-6-(4-chlorophenyl)-1-methyl-8-{[(trifluoromethyl)sulfonyl]oxy}-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl)acetate (for a preparation see intermediate 2) (147.5 mg) in DME (3 ml) and water (1 ml) was added to the microwave vial. The reaction mixture was heated at 120° C. for 90 min (microwave). Ethyl acetate (2 ml) was added and the water layer was separated and acidified with glacial acetic acid. The aqueous was extracted with ethyl acetate (3×5 ml), the organic fractions dried and the solvent evaporated. The residue was chromatographed (0-10% methanol:DCM) and then further purified by MDAP (formate modifier) to give ethyl [(4S)-6-(4-chlorophenyl)-1-methyl-8-(4-pyridinyl)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]acetate as a white solid (5.5 mg).
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([N:11]2[C:15](=[O:16])[NH:14][C:13]([CH:17]([C:31]3[CH:36]=[C:35]([O:37][CH3:38])[CH:34]=[C:33]([O:39][CH2:40][CH2:41][F:42])[C:32]=3[F:43])[NH:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]4[N:29]=[C:28]([CH3:30])[O:27][N:26]=4)=[CH:21][CH:20]=3)=[N:12]2)[N:6]=1)=[O:4].C1COCC1.[OH-].[Na+].C(O)(=O)C>CO>[F:43][C:32]1[C:33]([O:39][CH2:40][CH2:41][F:42])=[CH:34][C:35]([O:37][CH3:38])=[CH:36][C:31]=1[CH:17]([NH:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[N:29]=[C:28]([CH3:30])[O:27][N:26]=2)=[CH:21][CH:20]=1)[C:13]1[NH:14][C:15](=[O:16])[N:11]([C:7]2[N:6]=[C:5]([C:3]([OH:4])=[O:2])[CH:10]=[CH:9][CH:8]=2)[N:12]=1
Reactant: COC(=O)c1cccc(-n2nc(C(Nc3ccc(-c4noc(C)n4)cc3)c3cc(OC)cc(OCCF)c3F)[nH]c2=O)n1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: COc1cc(OCCF)c(F)c(C(Nc2ccc(-c3noc(C)n3)cc2)c2nn(-c3cccc(C(=O)O)n3)c(=O)[nH]2)c1
Temperature: 25 °C
Reaction time: 15 h
Yield: 49.7 %

Procedure:
After dissolving 167 mg of 6-(3-{[2-fluoro-3-(2-fluoroethoxy)-5-methoxyphenyl]-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl)pyridine-2-carboxylic acid methyl ester in 6 ml of a methanol:THF=2:1 mixed solvent, there was added 562 μl of a 5N aqueous sodium hydroxide solution and the mixture was stirred at room temperature for 15 hours. The mixture was adjusted to acidic with acetic acid and then concentrated under reduced pressure. The residue was dissolved in methanol, and the solution was filtered through celite and then purified by reverse-phase high performance liquid chromatography (acetonitrile-water, 0.1% trifluoroacetic acid) to give the title compound (81 mg) as a light yellow solid.
Reaction SMILES: Br[C:2]1[N:6]2[C@@H:7]([CH3:15])[CH2:8][N:9]([CH:12]([CH3:14])[CH3:13])[C:10](=[O:11])[C:5]2=[C:4]([O:16][CH3:17])[C:3]=1[C:18]([O:20][CH2:21][CH3:22])=[O:19].N.O.[CH3:25][N:26](C)C=O>>[C:25]([C:2]1[N:6]2[C@@H:7]([CH3:15])[CH2:8][N:9]([CH:12]([CH3:14])[CH3:13])[C:10](=[O:11])[C:5]2=[C:4]([O:16][CH3:17])[C:3]=1[C:18]([O:20][CH2:21][CH3:22])=[O:19])#[N:26]
Reactant: CN(C)C=O
Reactant: CCOC(=O)c1c(OC)c2n(c1Br)[C@@H](C)CN(C(C)C)C2=O
Agent: N
Solvent: O
Product: CCOC(=O)c1c(OC)c2n(c1C#N)[C@@H](C)CN(C(C)C)C2=O
Temperature: 110 °C
Reaction time: 2 h
Yield: 80 %

Procedure:
(S)-ethyl 6-bromo-2-isopropyl-8-methoxy-4-methyl-1-oxo-1,2,3,4-tetrahydro-pyrrolo[1,2-a]pyrazine-7-carboxylate (1.2 mol) and Cu(I)CN (2.4 mol) were dissolved in dimethylformamide (DMF; 2.2 l) at 20° C. under N2. The mixture was stirred for 2 h at 110° C. Concentrated NH3.H2O (650 ml) was added at 60° C. The mixture was stirred for 30 min at 60° C. and then cooled to 20° C. The mixture was filtered off. Ethyl acetate (3000 ml) and H2O (2000 ml) were added and the organic layer was separated. The aqueous layer was extracted with ethyl acetate (3×1000 ml). The combined organic layers were washed with brine, dried and concentrated in vacuo. The crude product and a small batch of an earlier preparation were combined and washed with methyl tert-butyl ether to give a solid. Yield: 350 g of Intermediate I-3 (95% purity, 80% yield total).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:20])[C:7]=1[S:8][C:9]1[S:13][C:12]([C:14](Cl)=[O:15])=[CH:11][C:10]=1[N+:17]([O-:19])=[O:18].[Cl:21][C:22]1[CH:28]=[C:27]([Cl:29])[CH:26]=[CH:25][C:23]=1[NH2:24]>>[Cl:21][C:22]1[CH:28]=[C:27]([Cl:29])[CH:26]=[CH:25][C:23]=1[NH:24][C:14]([C:12]1[S:13][C:9]([S:8][C:7]2[C:2]([Cl:1])=[CH:3][N:4]=[CH:5][C:6]=2[Cl:20])=[C:10]([N+:17]([O-:19])=[O:18])[CH:11]=1)=[O:15]
Reactant: Nc1ccc(Cl)cc1Cl
Reactant: O=C(Cl)c1cc([N+](=O)[O-])c(Sc2c(Cl)cncc2Cl)s1
Product: O=C(Nc1ccc(Cl)cc1Cl)c1cc([N+](=O)[O-])c(Sc2c(Cl)cncc2Cl)s1

Procedure:
Prepared according to the procedure described for example 50 from 5-[(3,5-dichloro-4-pyridyl)sulfanyl]-4-nitro-thiophene-2-carbonyl chloride (120 mg, 0.33 mmol) and 2,4-dichloroaniline (62 mg, 0.39 mmol). The title compound was obtained as a solid (85 mg, 52% yield). 1H NMR (400 MHz, d6-DMSO) δ: 10.58 (1H, s), 8.99 (2H, m), 8.69 (1H, s), 7.74 (1H, m), 7.48 (2H, m). MS m/z: 491.96, 493.96, 495.97 [M+H]+.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[CH:8][C:7]([N+:10]([O-])=O)=[CH:6][C:5]=1[Cl:13]>[Fe]>[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[CH:8][C:7]([NH2:10])=[CH:6][C:5]=1[Cl:13]
Reactant: COC(=O)c1ccc([N+](=O)[O-])cc1Cl
Agent: [Fe]
Product: COC(=O)c1ccc(N)cc1Cl

Procedure:
Compound of example 161 (50 g, 232 mmol) was subjected to reduction using iron.
Reaction SMILES: [CH3:1][C:2]1([CH2:10][C:11]([NH2:13])=O)[CH2:7][CH2:6][CH2:5][C:4]([CH3:9])([CH3:8])[CH2:3]1.COCCO[AlH2-]OCCOC.[Na+]>C1COCC1>[NH2:13][CH2:11][CH2:10][C:2]1([CH3:1])[CH2:7][CH2:6][CH2:5][C:4]([CH3:9])([CH3:8])[CH2:3]1
Reactant: CC1(C)CCCC(C)(CC(N)=O)C1
Agent: COCCO[AlH2-]OCCOC
Agent: [Na+]
Solvent: C1CCOC1
Product: CC1(C)CCCC(C)(CCN)C1
Temperature: 0 °C
Reaction time: 2.5 h

Procedure:
The product from Step 2 (5.0 mmol) was added as a THF solution over 0.1 hour to a refluxing THF solution of RED-Al (20 mmol) and refluxing was continued for 2.5 hours. The reaction was then cooled to 0° C. and quenched with a saturated solution of potassium sodium tartrate and then this was stirred at 25° C. for 18 hours. The reaction was diluted with ethyl acetate, washed successively with water and saturated sodium chloride, dried with sodium sulfate and evaporated.1H-NMR (CDCl3): 2.6 (m, 2H); 1.5 (m, 3H); 1.2 (m, 8H); 0.9 (m, 9H).
Reaction SMILES: [Cl:1][C:2]1[N:18]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([N+:25]([O-])=O)[CH:20]=2)[C:5]2[N:6]=[CH:7][N:8]=[C:9]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[C:4]=2[C:3]=1[C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=1.[NH4+].[Cl-].O.CCO>C1COCC1.C(Cl)Cl.[Fe].CO>[NH2:25][C:21]1[CH:20]=[C:19]([N:18]2[C:5]3[N:6]=[CH:7][N:8]=[C:9]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:14])([CH3:15])[CH3:16])[C:4]=3[C:3]([C:28]3[CH:29]=[CH:30][C:31]([Cl:34])=[CH:32][CH:33]=3)=[C:2]2[Cl:1])[CH:24]=[CH:23][CH:22]=1
Reactant: CC(C)(C)OC(=O)Nc1ncnc2c1c(-c1ccc(Cl)cc1)c(Cl)n2-c1cccc([N+](=O)[O-])c1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CO
Solvent: CCO
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)Nc1ncnc2c1c(-c1ccc(Cl)cc1)c(Cl)n2-c1cccc(N)c1
Temperature: 50 °C
Yield: 34.4 %

Procedure:
A suspension of 6-chloro-5-(4-chlorophenyl)-7-(3-nitrophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylcarbamate (20) (1.3 g, 2.6 mmol), iron powder (2.9 g, 52.1 mmol) and NH4Cl (1.4 g, 26.0 mmol) in a mixture of THF (30 mL), H2O (15 mL) and EtOH (3 mL) was purged with N2 before heated to 50° C. for 8 hrs. The reaction was then cooled down to r.t. and was filtered through Celite pad. The filter cake was thoroughly washed with DCM. The filtrate was washed with H2O, brine, dried over Na2SO4 and concentrated. The crude product was purified by column chromatographic (silica gel, with 0 to 50% EA in a mixture of PE & DCM (1:1) and then 0 to 10% MeOH in DCM) to afford tert-butyl 7-(3-aminophenyl)-6-chloro-5-(4-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylcarbamate (21) (421 mg, 35% yield) as a yellow solid. LC-MS (ESI): m/z (M/M+2) 468.6/470.6.
Reaction SMILES: [CH:1]([C:3]1[CH:10]=[CH:9][C:6]([C:7]#[N:8])=[CH:5][CH:4]=1)=O.[C:11]([NH:14][CH2:15][C:16]([OH:18])=[O:17])(=O)[CH3:12].C([O-])(=O)C.[Na+].C(OC(=O)C)(=O)C>CC(C)=O>[CH3:12][C:11]1[O:18][C:16](=[O:17])[C:15](=[CH:1][C:3]2[CH:10]=[CH:9][C:6]([C:7]#[N:8])=[CH:5][CH:4]=2)[N:14]=1
Reactant: CC(=O)NCC(=O)O
Reactant: N#Cc1ccc(C=O)cc1
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CC(=O)OC(C)=O
Solvent: CC(C)=O
Product: CC1=NC(=Cc2ccc(C#N)cc2)C(=O)O1
Temperature: 50 °C

Procedure:
Acetone (80.0 l) was introduced into a mixture of 4-formylbenzonitrile (15.0 kg, 114.5 mol), N-acetylglycine (19.2 kg, 162.4 mol) and anhydrous sodium acetate (9.4 kg, 114.5 mol) followed by introduction, with stirring, of acetic anhydride (35.0 l, 370.5 mol). The reaction mixture was stirred under reflux for 1 h. The resulting thin yellow suspension was cooled to 50° C. and ice-water (200 l) was added as quickly as possible, with stirring and cooling. The mixture was stirred at 20° C. for another 1 h. To isolate the product, the yellow suspension was pressed onto a centrifuge and washed with deionized water (75 l), isopropanol (40 l) and methyl-tert-butylether (75 l). The product was dried under reduced pressure at 40° C. Yield 18.17 kg (85.7 mol, 75.2% of theory). M.p.: 192–193° C.; MS (DCl): m/z=213 [M+H+]; 1H-NMR (DMSO-d6): δ=2.42 (s, 3H), 7.30 (s, 1H), 7.96 (d, 2H), 8.33 (d, 2H).
Reaction SMILES: C[O:2][C:3]1[CH:11]=[CH:10][C:6]2[N:7]=[CH:8][S:9][C:5]=2[CH:4]=1.O.C(=O)([O-])O.[Na+]>Br>[OH:2][C:3]1[CH:11]=[CH:10][C:6]2[N:7]=[CH:8][S:9][C:5]=2[CH:4]=1
Reactant: COc1ccc2ncsc2c1
Agent: Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Product: Oc1ccc2ncsc2c1
Reaction time: 6 h
Yield: 95.6 %

Procedure:
The product of Step 1 (1.2 g) in hydrobromic acid (10 ml, 48%) was heated at 120° C. with stirring for 6 hours then stored at ambient temperature for 2 days. The hot, pale yellow solution produced a suspension on cooling. The suspension was dissolved by the addition of water then the solution was adjusted to pH 6 by addition of sodium hydrogen carbonate and the solid that precipitated was filtered from solution, washed with water and sucked to dryness. The solid was dissolved in ethyl acetate, the solution dried over magnesium sulphate and evaporated to give 6-hydroxybenzothiazole as a colourless solid (1.05 g).
Reaction SMILES: Cl[C:2](=[O:8])[C:3]([O:5][CH2:6][CH3:7])=[O:4].[Br:9][C:10]1[CH:11]=[C:12]([CH:17]=[C:18]([Br:21])[C:19]=1[OH:20])[C:13](=[N:15]O)[NH2:14]>N1C=CC=CC=1>[Br:9][C:10]1[CH:11]=[C:12]([C:13]2[N:15]=[C:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])[O:8][N:14]=2)[CH:17]=[C:18]([Br:21])[C:19]=1[OH:20]
Reactant: CCOC(=O)C(=O)Cl
Reactant: NC(=NO)c1cc(Br)c(O)c(Br)c1
Solvent: c1ccncc1
Product: CCOC(=O)c1nc(-c2cc(Br)c(O)c(Br)c2)no1
Temperature: 25 °C
Reaction time: 1 h
Yield: 14.6 %

Procedure:
Ethyl 2-chloro-2-oxoacetate (12.3 g, 82 mmol) was added dropwise to a stirred solution of 3,5-dibromo-N′,4-dihydroxybenzimidamide (25.5 g, 82 mmol) in pyridine (120 mL) and the mixture was stirred at room temperature for 1 hour and then at 60° C. for 2 hours. The resulting suspension was poured onto water (1.5 L) and extracted with ethyl acetate (2×400 mL). The combined extracts were washed with saturated sodium chloride, dried (MgSO4) and evaporated in vacuo to give an oily solid that was purified by flash chromatography to give a colourless powder. Crystallisation from toluene (400 mL) gave the title compound (I 4.7 g, 46%) as colourless crystals. 1H NMR δ (ppm) (DMSO-d6): 1.14 (3H, t), 4.49 (2H, q), 8.14 (2H, s), 10.93 (1H, br s).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][OH:4].[N:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[CH:11]=O>>[N:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[CH2:11][NH:1][CH2:2][CH2:3][OH:4]
Reactant: O=Cc1ccccn1
Reactant: NCCO
Product: OCCNCc1ccccn1

Procedure:
prepared by reaction of 2-amino-ethanol with pyridine-2-carbaldehyde
Reaction SMILES: [C:1](O)(=O)[CH2:2][CH2:3][CH2:4][CH2:5][C:6]([OH:8])=[O:7].C1(=O)[O:16][C:14](=[O:15])[C:13]2=CC=CC=C12>>[C:6]([OH:8])(=[O:7])[C:5]1[C:13](=[CH:1][CH:2]=[CH:3][CH:4]=1)[C:14]([OH:16])=[O:15]
Reactant: O=C(O)CCCCC(=O)O
Reactant: O=C1OC(=O)c2ccccc21
Product: O=C(O)c1ccccc1C(=O)O
Yield: 200 %

Procedure:
At a temperature of from 150° to 160° C., 490 parts by weight of the glycide ester of branched monocarboxylic acids (2 moles) having an average carbon number of about 13* are added to 146 parts by weight of adipic acid (1 mole). Subsequently, at the same temperature, 296 parts by weight of phthalic anhydride (2 moles) are added to the formed dihydric ester alcohol. When the acid number of 120 is reached the ester chain length is extended by adding 490 parts by weight of the same glycide ester of branched monocarboxylic acids previously added above (2 moles) to the formed ester dicarboxylic acid to give the corresponding ester diol to which 296 parts by weight of phthalic acid (2 moles) are then added. As soon as the acid number is 65, the temperature is lowered to 130° C., and 88 parts by weight of ethylene oxide are added to the formed ester dicarboxylic acid to yield the corresponding ester diol.
Reaction SMILES: [N+:1]([C:4]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:5]=1[C:6](=[O:19])[C:7]1[CH2:8][CH2:9][CH2:10][CH2:11][C:12]=1[C:13]2=[O:18])([O-])=O.[OH-].[Na+].[H][H]>[Pd]>[NH2:1][C:4]1[C:5]2[C:6](=[O:19])[C:7]3[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=3)[C:13](=[O:18])[C:14]=2[CH:15]=[CH:16][CH:17]=1
Reactant: O=C1C2=C(CCCC2)C(=O)c2c1cccc2[N+](=O)[O-]
Reactant: [H][H]
Agent: [Pd]
Agent: [Na+]
Agent: [OH-]
Product: Nc1cccc2c1C(=O)c1ccccc1C2=O
Temperature: 25 °C
Yield: 94.1 %

Procedure:
2.6 Grams (0.01 mol) of 5-nitrotetrahydroanthraquinone, 52 grams (0.013 mol) of a 1% aqueous sodium hydroxide solution, and 0.052 grams of a 5% palladium on carbon catalyst were introduced into an electromagnetic agitation-type glass reactor having an inner volume of 200 ml. Then, the atmosphere in the reactor was replaced by hydrogen, followed by hydrogenation while agitating at room temperature. When 0.015 mol of hydrogen was absorbed, the hydrogen in the system was replaced by nitrogen and then by air for oxidizing the resultant over-reduced compound while agitating for 30 minutes. The resultant reaction product was separated together with the catalyst by filtration and was dissolved in N,N-dimethylformamide for separating the catalyst by filtration. To the resultant filtrate was added water for dilution to obtain 2.1 grams of 1-aminoanthraquinone (at a yield of 93.1%). The purity of the 1-aminoanthraquinone was 98%.
Reaction SMILES: [CH2:1]([S:8][CH2:9][CH2:10][Cl:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].ClC1C=CC=C(C(OO)=[O:20])C=1.S(S([O-])=O)([O-])(=O)=O.[Na+].[Na+].C(=O)([O-])O.[Na+]>C(Cl)Cl>[CH2:1]([S:8]([CH2:9][CH2:10][Cl:11])=[O:20])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CCCCCCCSCCCl
Agent: O=C([O-])O
Agent: O=S([O-])S(=O)(=O)[O-]
Agent: [Na+]
Solvent: ClCCl
Product: CCCCCCCS(=O)CCCl
Temperature: -20 °C
Reaction time: 3 h
Yield: 111 %

Procedure:
Dissolve 2-chloroethyl heptyl sulfide (1.0 g, 5.13 mmol) in methylene chloride (50 mL), cool to -20° C. and place under nitrogen atmosphere. Add, by dropwise addition, a solution of meta-chlorperbenzoic acid (1.25 g, 6.0 mmol) in methylene chloride. Stir at -20° C. for 3 hours, then allow to warm to room temperature. Treat with saturated sodium meta bisulfite (until negative starch-iodide test) and basify with saturated sodium hydrogen carbonate. Extract with methylene chloride (2×25 mL), dry (MgSO4) and evaporate in vacuo to yield 1.2 g of 2chloroethyl heptyl sulfoxide as white crystals; MS (CI/CH4) m/z 211(M+1).
Reaction SMILES: [O:1]1[CH2:3][C@@H:2]1[CH2:4][OH:5].[CH3:6][O:7][C:8]1[CH:9]=[CH:10][C:11]([N+:15]([O-:17])=[O:16])=[C:12](O)[CH:13]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[CH3:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[C:10]([CH:9]=1)[O:5][CH2:4][C@H:2]1[CH2:3][O:1]1
Reactant: OC[C@H]1CO1
Reactant: COc1ccc([N+](=O)[O-])c(O)c1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COc1ccc([N+](=O)[O-])c(OC[C@H]2CO2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 72.2 %

Procedure:
To a mixture of (2S)-oxiran-2-ylmethanol (296.3 mg, 4.0 mmol), 5-methoxy-2-nitrophenol (676.6 mg, 4.0 mmol) and triphenyl phosphine (1.05 g, 4.0 mmol) in THF (10 mL) was added diethyl azodicarboxylate (DEAD, 704.6 mg, 4.0 mmol) in THF (5 mL) dropwise at room temperature. After addition was completed the reaction mixture was stirred at room temperature overnight. The volatiles were removed in vacuo and the residue was purified by silica gel flash chromatography (040% ethyl acetate in petroleum spirit) to give the subtitled compound (650 mg).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:44])[CH:15]([OH:43])[CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][C:24]3[CH:29]=[CH:28][C:27]([NH:30][C:31](=[O:42])[C:32]4[CH:37]=[CH:36][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:34][CH:33]=4)=[CH:26][N:25]=3)=[CH:19][CH:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:44])[C:15](=[O:43])[CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][C:24]3[CH:29]=[CH:28][C:27]([NH:30][C:31](=[O:42])[C:32]4[CH:33]=[CH:34][C:35]([C:38]([F:39])([F:41])[F:40])=[CH:36][CH:37]=4)=[CH:26][N:25]=3)=[CH:19][CH:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCN(C(=O)C(O)Cc2ccc(Oc3ccc(NC(=O)c4ccc(C(F)(F)F)cc4)cn3)cc2)CC1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCN(C(=O)C(=O)Cc2ccc(Oc3ccc(NC(=O)c4ccc(C(F)(F)F)cc4)cn3)cc2)CC1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of 4-(2-hydroxy-3-{4-[5-(4-trifluoromethylbenzoylamino)pyridin-2-yloxy]phenyl}propionyl)piperazine-1-carboxylic acid t-butyl ester (0.58 g, 0.94 mmol) in dichloromethane (4 mL) was added a Dess-Martin reagent (0.8 g, 1.89 mmol), and the resulting solution was then stirred under a nitrogen gas flow for 4 hours at room temperature. The reaction solution was concentrated under reduced pressure. To the residue was added 1 N aqueous sodium hydroxide (50 mL), and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated. The residue was purified by silica gel chromatography (dichloromethane:methanol=50:1), to thereby yield 0.31 g of the title compound.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH3:8])[CH:5]=[CH:6][CH:7]=1.[N+:9]([O-])([OH:11])=[O:10]>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N+:9]([O-:11])=[O:10])=[C:4]([CH3:8])[CH:3]=1
Reactant: Cc1cccc(F)c1
Reactant: O=[N+]([O-])O
Product: Cc1cc(F)ccc1[N+](=O)[O-]
Temperature: 0 °C
Reaction time: 8 h

Procedure:
A solution of 200 g of 3-fluorotoluene and 670 ml of concentrated nitric acid was heated at 50°-55° for 8 hours; after standing overnight, the reaction mixture was poured into 1200 ml of ice-water. The organic layer was separated, and the aqueous layer was extracted three times with ether; the organic fraction and the ethereal extracts were combined, washed once with water and saturated sodium chloride solution. The combined organic fraction was dried over magnesium sulfate, filtered, and evaporated under reduced pressure to give a yellow oil. This crude product was distilled using a 30-cm vacuum-jacketed column filled with glass helices to yield 192.7 g of 5-fluoro-2-nitrotoluene, bp 74.5°-77°/4 mm.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][OH:8])[CH:2]=1.C(N(CC)CC)C.[CH3:16][N:17]([C:21]1[CH:26]=[CH:25][C:24]([S:27][CH3:28])=[CH:23][CH:22]=1)[C:18](Cl)=[O:19]>C1C=CC=CC=1>[CH3:16][N:17]([C:21]1[CH:26]=[CH:25][C:24]([S:27][CH3:28])=[CH:23][CH:22]=1)[C:18](=[O:19])[O:8][CH2:7][C:3]1[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=1
Reactant: OCc1cccnc1
Reactant: CSc1ccc(N(C)C(=O)Cl)cc1
Solvent: c1ccccc1
Solvent: CCN(CC)CC
Product: CSc1ccc(N(C)C(=O)OCc2cccnc2)cc1
Yield: 40.5 %

Procedure:
A solution of 3-pyridylcarbinol (2.4 g., 0.0222 mole) in triethylamine (2.24 g., 0.0222 mole) was added dropwise to a solution of N-methyl-(4-methylthiophenyl)carbamoyl chloride in 150 ml. of benzene. The reaction mixture was heated to reflux temperature for about 1 hr. then allowed to stand over night at room temperature. The reaction mixture was washed with water and the benzene layer separated, dried over magnesium sulfate and concentrated in vacuo to give an oil which solidified. The product was recrystallized from methylcyclohexane to give 2.6 g. of solid melting at 100°-102° C. This was a 40.5% yield of 3-pyridylmethyl N-methyl-N-(4-methylthiophenyl)carbamate.
Reaction SMILES: [CH3:1][N:2]1[C:7](=[O:8])[NH:6][CH:5](SC)[N:4]([NH2:11])[C:3]1=[O:12].C(O)(=O)C.[CH3:17][NH2:18]>C(O)(C)C>[CH3:1][N:2]1[C:7](=[O:8])[NH:6][CH:5]([NH:18][CH3:17])[N:4]([NH2:11])[C:3]1=[O:12]
Reactant: CN
Reactant: CSC1NC(=O)N(C)C(=O)N1N
Solvent: CC(C)O
Solvent: CC(=O)O
Product: CNC1NC(=O)N(C)C(=O)N1N
Reaction time: 10 h
Yield: 88 %

Procedure:
18.8 g (0.1 mole) of 1-methyl-3-amino-4-methylmercaptotetrahydro-1,3,5-triazine-2,6-dione (prepared according to Example 2) were idssolved in 200 ml of isopropanol with addition of 6 g of glacial acetic acid and a pinch of ptoluenesulphonic acid and the mixture was saturated with methylamine gas at room temperature. The batch was left to stand for about 10 hours and was evaporated in vacuo, and the resudue was recrystallized from isopropanol. 15 g (88%) of 1-methyl-3-amino-4-methylamino-tetrahydro-1,3,5-triazine2,6-dione were obtained as a colorless powder; melting point 225°-227° C.