Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([CH2:3][CH2:4][N:5]1[CH2:13][C@H:12]([OH:14])[CH2:11][C@H:6]1[C:7]([O:9]C)=O)#[N:2].N1C=CN=C1.[CH2:20]([Si:22](Cl)([CH2:25][CH3:26])[CH2:23][CH3:24])[CH3:21]>CN(C)C=O>[CH2:20]([Si:22]([CH2:25][CH3:26])([CH2:23][CH3:24])[O:14][C@H:12]1[CH2:13][N:5]2[CH2:4][CH2:3][CH2:1][NH:2][C:7](=[O:9])[C@@H:6]2[CH2:11]1)[CH3:21]
Reactant: COC(=O)[C@@H]1C[C@@H](O)CN1CCC#N
Reactant: CC[Si](Cl)(CC)CC
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: CC[Si](CC)(CC)O[C@@H]1C[C@H]2C(=O)NCCCN2C1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of the product from Example 1, Part B (0.33 g, 1.94 mmol) in anhydrous N,N-dimethylformamide (10 mL) was added imidazole (0.264 g, 3.88 mmol) and triethylsilyl chloride (0.488 mL, 2.91 mmol). The resulting solution was stirred at room temperature for 16 hours. The mixture was partitioned between ethyl acetate (50 mL) and water (2×50 mL), and the organic extract was dried over Na2SO4. The drying agent was removed by filtration, and the filtrate was concentrated in vacuo to give a crude product that was purified by column chromatography on silica gel using a solvent gradient of 0-10% methanol in dichloromethane. The title compound was obtained as a colorless solid (0.28 g, 51%).
Reaction SMILES: O[CH:2]([CH3:28])[CH2:3][NH:4][C:5](=[O:27])[CH2:6][N:7]1[C:25](=[O:26])[N:10]2[CH:11]=[C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=3)[CH:13]=[CH:14][C:9]2=[N:8]1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.O>C1COCC1>[CH3:28][C:2]1[O:27][C:5]([CH2:6][N:7]2[C:25](=[O:26])[N:10]3[CH:11]=[C:12]([C:15]4[CH:16]=[CH:17][C:18]([C:21]([F:22])([F:23])[F:24])=[CH:19][CH:20]=4)[CH:13]=[CH:14][C:9]3=[N:8]2)=[N:4][CH:3]=1
Reactant: CC(O)CNC(=O)Cn1nc2ccc(-c3ccc(C(F)(F)F)cc3)cn2c1=O
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: O
Solvent: C1CCOC1
Product: Cc1cnc(Cn2nc3ccc(-c4ccc(C(F)(F)F)cc4)cn3c2=O)o1
Reaction time: 1 h
Yield: 101.2 %

Procedure:
N-(2-Hydroxypropyl)-2-(3-oxo-6-(4-(trifluoromethyl)phenyl)-[1,2,4]triazolo[4,3-a]pyridin-2 (3H)-yl)acetamide (30.0 mg, 0.0761 mmol) was treated with Dess-Martin periodinane (64.6 mg, 0.1522 mmol, 2.0 equiv.) in THF (2 mL) at room temperature in a 50 mL round bottomed flask. After stirring for 1 h, water (30 mL) was added and the whole was extracted with EtOAc (30 mL×3). Combined organic layers were washed with sat. Na2S2O3 aq. solution (30 mL), sat. NaHCO3 aq. solution (30 mL) and brine (30 mL) successively. The organic layer was dried over Na2SO4. The solvent was removed under a reduced pressure to give the desired product as colorless crystals (2-(3-oxo-6-(4-(trifluoromethyl)phenyl)-[1,2,4]triazolo[4,3-a]pyridin-2 (3H)-yl)-N-(2-oxopropyl)acetamide, 30.3 mg, 0.077 mmol, >99%). LCMS (EI: 70 eV) 415 (M++Na), 393 (M++1).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[O:9][CH2:8][CH2:7][C:6]2=[O:13].[S:14]1[CH:18]=[CH:17][N:16]=[C:15]1[CH:19]=O>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[O:9][CH2:8][C:7](=[CH:19][C:15]1[S:14][CH:18]=[CH:17][N:16]=1)[C:6]2=[O:13]
Reactant: O=Cc1nccs1
Reactant: COc1ccc2c(c1)C(=O)CCO2
Product: COc1ccc2c(c1)C(=O)C(=Cc1nccs1)CO2

Procedure:
By the method of Example 1, 6-methoxy-4-chromanone (3.97 g, 0.0223 mol) and 2-thiazolecarbaldehyde (3.00 g, 0.0265 mol) were converted to present title product which was recrystallized from methanol, 1.20 g (20%), m.p. 130-132° C., tlc (1:19 CH3OH:CH2Cl2) Rf 0.67.
Reaction SMILES: [C:1]([N:4]1[CH:8](O)[CH2:7][CH:6]([CH2:10][CH3:11])[C:5]1([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:12]([O:14][CH2:15][CH3:16])=[O:13])(=[O:3])[CH3:2].C([SiH](CC)CC)C.FC(F)(F)C(O)=O>C(Cl)Cl>[C:1]([N:4]1[CH2:8][CH2:7][CH:6]([CH2:10][CH3:11])[C:5]1([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:12]([O:14][CH2:15][CH3:16])=[O:13])(=[O:3])[CH3:2]
Reactant: CCOC(=O)C1(C(=O)OCC)C(CC)CC(O)N1C(C)=O
Agent: CC[SiH](CC)CC
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCOC(=O)C1(C(=O)OCC)C(CC)CCN1C(C)=O
Temperature: 25 °C
Yield: 137.6 %

Procedure:
To a solution of diethyl 1-acetyl-5-hydroxy-3-ethylpyrrolidine-2,2-dicarboxylate (287 g, 0.95 mol) and triethylsilane (228 mL, 1.43 mol) in CH2Cl2 (3 L) under argon was added trifluoroacetic acid (735 mL, 9.53 mol) dropwise with stirring while maintaining the internal temperature at 25° C. by means of an ice bath. After stirring for 3 h at 23° C., the solution was concentrated in vacuo,, the residue diluted with CH2Cl2 (1.5 L), then treated with H2O (1 L) and solid Na2CO3 with vigorous stirring until the solution was basic. The organic layer was separated, dried (Na2SO4), filtered, then concentrated to give the title compound as a yellow oil (373 g) which was used without further purification.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH:5]=[CH:6][CH:7]=1.[CH3:16][N:17]([CH3:22])[CH2:18][C:19](O)=[O:20].Cl.C(N=C=NCCCN(C)C)C>CN(C)C1C=CN=CC=1.ClCCl>[CH3:16][N:17]([CH3:22])[CH2:18][C:19]([NH:1][C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:14])[CH3:13])[CH:5]=[CH:6][CH:7]=1)=[O:20]
Reactant: CC(C)(C)OC(=O)Nc1cccc(N)c1
Reactant: CN(C)CC(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Product: CN(C)CC(=O)Nc1cccc(NC(=O)OC(C)(C)C)c1

Procedure:
A 250 mL round bottom flask with stir bar was charged with tert-butyl 3-aminophenylcarbamate (5.315 g, 25.5 mmol), 2-(dimethylamino)acetic acid (2.94 g, 28.5 mmol), 1-ethyl-3-[3-(dimethylamino)propyl]-carbodiimide hydrochloride (5.17 g, 27.0 mmol) and 4-dimethylaminopyridine (0.09 g, 0.737 mmol) in dichloromethane (100 ml). The solution was stirred at ambient temperature for 2 hours. The reaction mixture was washed into a separatory funnel with an additional 100 mL dichloromethane and washed with 100 mL saturated sodium bicarbonate. The organics were dried over magnesium sulfate, filtered, and concentrated to provide the title compound. MS ESI+) m/e 294.0 (M+H)+.
Reaction SMILES: [N:1]1([S:7]([N:10]2[CH2:15][CH2:14][O:13][C:12]3[N:16]=[CH:17][C:18]([C:20]([OH:22])=O)=[CH:19][C:11]2=3)(=[O:9])=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C([Cl:26])=O.CN(C=O)C.CO>ClCCCl>[N:1]1([S:7]([N:10]2[CH2:15][CH2:14][O:13][C:12]3[N:16]=[CH:17][C:18]([C:20]([Cl:26])=[O:22])=[CH:19][C:11]2=3)(=[O:9])=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=C(Cl)C(=O)Cl
Reactant: O=C(O)c1cnc2c(c1)N(S(=O)(=O)N1CCCCC1)CCO2
Solvent: ClCCCl
Solvent: CO
Solvent: CN(C)C=O
Product: O=C(Cl)c1cnc2c(c1)N(S(=O)(=O)N1CCCCC1)CCO2
Temperature: 50 °C
Reaction time: 16 h

Procedure:
To a suspension of 1-(piperidin-1-ylsulfonyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-7-carboxylic acid (110 mg, 0.336 mmol) in DCE (5 mL) was added oxalyl chloride (293 μL, 3.36 mmol) and DMF (5 μL, 0.065 mmol). The reaction was heated to 50° C. and stirred at that temperature for 16 h. The reaction was concentrated in vacuo and used without further purification. The reaction yield was assumed to be 100% for calculation purposes only. LCMS (methanol adduct, i.e. the methyl ester; +ESI) m/z=342.1 [M+H]+.
Reaction SMILES: [CH3:1][O:2][C@H:3]1[CH2:8][CH2:7][C@H:6]2[C@H:9]3[C@H:19]([CH2:20][CH2:21][C@:4]12[CH3:5])[C@:17]1([CH3:18])[C@@H:12]([CH2:13][C:14](=[O:22])[CH2:15][CH2:16]1)[CH2:11][CH2:10]3.[H-].C(O[Al](OC(C)(C)C)OC(C)(C)C)(C)(C)C.[Li+]>C1COCC1.C(Cl)Cl>[OH:22][C@@H:14]1[CH2:15][CH2:16][C@@:17]2([CH3:18])[C@H:12]([CH2:11][CH2:10][C@@H:9]3[C@@H:19]2[CH2:20][CH2:21][C@@:4]2([CH3:5])[C@H:6]3[CH2:7][CH2:8][C@@H:3]2[O:2][CH3:1])[CH2:13]1
Reactant: CO[C@H]1CC[C@H]2[C@@H]3CC[C@@H]4CC(=O)CC[C@]4(C)[C@H]3CC[C@]12C
Agent: CC(C)(C)O[Al](OC(C)(C)C)OC(C)(C)C
Agent: [H-]
Agent: [Li+]
Solvent: ClCCl
Solvent: C1CCOC1
Product: CO[C@H]1CC[C@H]2[C@@H]3CC[C@@H]4C[C@H](O)CC[C@]4(C)[C@H]3CC[C@]12C
Temperature: -75 °C
Reaction time: 3 h
Yield: 83.1 %

Procedure:
A solution of 17β-methoxy-5β-androstan-3-one (130 mg, 0.42 mmol) in dry THF (15 mL) was treated with lithium tri(tert-butoxy)aluminum hydride (1 mL, 1M in THF, 1 mmol) at −73° C. After stirring the mixture at −75° C. for 3 hr and then at −10° C. for 1.5 hr, the mixture was quenched with NaOH solution (1N, 2 mL). The solvents were removed and the residue was extracted with EtOAc. The organic layer was washed with water, and brine. After drying over anhyd. MgSO4 the solution was filtered and evaporated to yield the crude product. This crude product was then dissolved in a small amount of CH2Cl2 and poured on a column of silica gel. Elution with toluene:acetone mixture (9:1) gave 3α-hydroxy-17β-methoxy-5β-androstane (107 mg); mp 151-156° C.; TLC Rf (hexane:acetone 7:3)=0.18.
Reaction SMILES: [OH-:1].[Na+].[OH:3][C:4]1[CH:5]=[C:6]([C:11]2([C:14]#N)[CH2:13][CH2:12]2)[CH:7]=[CH:8][C:9]=1[OH:10].Cl.[OH2:17]>>[OH:3][C:4]1[CH:5]=[C:6]([C:11]2([C:14]([OH:17])=[O:1])[CH2:13][CH2:12]2)[CH:7]=[CH:8][C:9]=1[OH:10]
Reactant: N#CC1(c2ccc(O)c(O)c2)CC1
Reactant: [OH-]
Reactant: O
Agent: Cl
Agent: [Na+]
Product: O=C(O)C1(c2ccc(O)c(O)c2)CC1
Temperature: 25 °C

Procedure:
To a solution of NaOH (20 g, 0.50 mol) in H2O (20 mL) was added. 1-(3,4-dihydroxy-phenyl)-cyclopropanecarbonitrile (4.4 g, 25 mmol). The mixture was heated at reflux for 3 h before being cooled to room temperature. The mixture was neutralized with HCl (0.5 N) to pH 3-4 and extracted with ethyl acetate (20 mL×3). The combined organic layers were washed with water, brine, dried over anhydrous MgSO4, and concentrated under vacuum to obtain 1-(3,4-dihydroxy-phenyl)-cyclopropanecarboxylic acid (4.5 g crude). From 900 mg crude, 500 mg pure 1-(3,4-dihydroxy-phenyl)-cyclopropanecarboxylic acid was obtained by preparatory HPLC. H NMR (DMSO, 300 MHz) δ 12.09 (br s, 1 H), 8.75 (br s, 2 H), 6.50-6.67 (m, 3 H), 1.35-1.31 (m, 2 H), 1.01-0.97 (m, 2 H).
Reaction SMILES: [F:1][S:2]([O:5][CH3:6])(=[O:4])=[O:3].[CH3:7][N:8]([CH3:27])[C:9]([C@@H:11]1[CH2:15][C@H:14]([S:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)[CH2:13][N:12]1[CH3:26])=[O:10]>C(Cl)Cl>[F:1][S:2]([O-:5])(=[O:4])=[O:3].[CH3:7][N:8]([CH3:27])[C:9]([C@@H:11]1[CH2:15][C@H:14]([S:16][CH2:17][C:18]2[CH:19]=[CH:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=2)[CH2:13][N+:12]1([CH3:6])[CH3:26])=[O:10]
Reactant: COc1ccc(CS[C@H]2C[C@@H](C(=O)N(C)C)N(C)C2)cc1
Reactant: COS(=O)(=O)F
Solvent: ClCCl
Product: COc1ccc(CS[C@H]2C[C@@H](C(=O)N(C)C)[N+](C)(C)C2)cc1
Product: O=S(=O)([O-])F
Temperature: 25 °C
Reaction time: 2 h

Procedure:
139 μl of methyl fluorosulfonate were added, whilst ice-cooling, to a solution of 190 mg of (2S, 4S)-2-(N,N-dimethylcarbamoyl)-4-(4-methoxybenzylthio)-1-methylpyrrolidine [prepared as described in step (5) or (11) above] dissolved in 3.8 ml of methylene chloride, and the mixture was stirred at room temperature for 2 hours. At the end of this time, the solvent was distilled off under reduced pressure. The residue was repeatedly washed by decantation with hexane and dried under reduced pressure, to give 356 mg of the title compound as an oil.
Reaction SMILES: [CH2:1]([NH:3][CH2:4][C:5]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[CH:7][C:6]=1[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([CH2:21][C:22]([OH:24])=[O:23])[CH:16]=1)[CH3:2].[CH3:25][CH2:26]O>S(=O)(=O)(O)O>[CH2:25]([O:23][C:22](=[O:24])[CH2:21][C:17]1[CH:16]=[C:15]([C:6]2[CH:7]=[CH:8][C:9]([C:11]([F:13])([F:12])[F:14])=[CH:10][C:5]=2[CH2:4][NH:3][CH2:1][CH3:2])[CH:20]=[CH:19][CH:18]=1)[CH3:26]
Reactant: CCNCc1cc(C(F)(F)F)ccc1-c1cccc(CC(=O)O)c1
Reactant: CCO
Agent: O=S(=O)(O)O
Product: CCNCc1cc(C(F)(F)F)ccc1-c1cccc(CC(=O)OCC)c1
Temperature: 50 °C
Reaction time: 8 h

Procedure:
To a solution of (2′-ethylaminomethyl-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid (0.34 mmol) in EtOH (7 mL) was added sulfuric acid (34 drops), and the reaction was stirred at 50° C. overnight. Once no starting material was seen by analytical LCMS, the mixture was filtered over a pad of Celite and rinsed with EtOH. The filtrate was concentrated to give the title compound.
Reaction SMILES: [OH:1][N:2]1[C:11](=[O:12])[C:10]2[CH:13]=[C:14]([OH:16])[CH:15]=[C:8]3[C:9]=2[C:4](=[CH:5][CH:6]=[CH:7]3)[C:3]1=[O:17].[CH2:18]=O.[NH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1>O1CCOCC1>[OH:1][N:2]1[C:11](=[O:12])[C:10]2[C:13]([CH3:18])=[C:14]([OH:16])[C:15]([N:20]3[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]3)=[C:8]3[C:9]=2[C:4](=[CH:5][CH:6]=[CH:7]3)[C:3]1=[O:17]
Reactant: O=C1c2cccc3cc(O)cc(c23)C(=O)N1O
Reactant: C=O
Reactant: C1CCNCC1
Solvent: C1COCCO1
Product: Cc1c(O)c(N2CCCCC2)c2cccc3c2c1C(=O)N(O)C3=O
Temperature: 25 °C
Reaction time: 40 h
Yield: 67.3 %

Procedure:
To a suspension of 150 mg (0.66 mmol) of 2,5-dihydroxy-benzo[de]isoquinoline-1,3-dione (from Example 3) in 4 mL dioxane was added 0.6 mL (7.4 mol) of 37% aqueous formaldehyde, and then 168 mg (2.0 mmol) of piperidine. The reaction mixture was stirred at room temperature 40 hours and quenched with 25 mL water. The precipitate was isolated, washed with water, and dried to yield 145 mg of the title compounds, mp 224-225° C.
Reaction SMILES: [CH3:1][C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[C:9]([CH2:12][C:13]([OH:15])=O)[CH:8]=[CH:7][CH:6]=2.[F:16][C:17]([F:27])([F:26])[C:18]1[CH:25]=[CH:24][C:21]([CH2:22][NH2:23])=[CH:20][CH:19]=1.FC(F)(F)OC1C=CC(CN)=CC=1>>[CH3:1][C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[C:9]([CH2:12][C:13]([NH:23][CH2:22][C:21]1[CH:20]=[CH:19][C:18]([C:17]([F:16])([F:26])[F:27])=[CH:25][CH:24]=1)=[O:15])[CH:8]=[CH:7][CH:6]=2
Reactant: Cc1cc2c(CC(=O)O)cccc2cn1
Reactant: NCc1ccc(C(F)(F)F)cc1
Agent: NCc1ccc(OC(F)(F)F)cc1
Product: Cc1cc2c(CC(=O)NCc3ccc(C(F)(F)F)cc3)cccc2cn1

Procedure:
The title compound was prepared using the procedure described in Example 222B using (3-methyl-5-isoquinolinyl)acetic acid and 4-(trifluoromethyl)benzylamine instead of 5-isoquinolinylacetic acid and 4-(trifluoromethoxy)benzylamine. MS (ESI+) m/z 359 (M+H)+; MS (ESI−) m/z 357 (M−H)−; 1H NMR (DMSO, 300 MHz) δ 2.77 (s, 3H), 4.12 (s, 2H), 4.37 (d, J 6.1, 2H), 7.47 (d, J 7.8, 2H), 7.68 (d, J 8.1, 2H), 7.86 (t, J 7.4, 1H), 8.03 (d, J 6.4, 1H), 8.36 (m, 2H), 9.03 (t, J 5.8, 1H), 9.77 (s, 1H); Anal. Calcd for C20H17F3N2O+1.85 HCl: C, 56.44; H, 4.57. Found: C, 56.41; H, 4.46.
Reaction SMILES: [OH:1][CH:2]1[CH:7]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH:6]=[C:5]([C:16]2[CH:21]=[CH:20][N:19]=[CH:18][C:17]=2[N+:22]([O-:24])=[O:23])[CH2:4][CH:3]1[CH3:25].[CH3:26][C:27](OC(C)=O)=[O:28]>N1C=CC=CC=1>[C:27]([O:1][CH:2]1[CH:3]([CH3:25])[CH2:4][C:5]([C:16]2[CH:21]=[CH:20][N:19]=[CH:18][C:17]=2[N+:22]([O-:24])=[O:23])=[CH:6][CH:7]1[NH:8][C:9]([O:10][C:11]([CH3:12])([CH3:13])[CH3:14])=[O:15])(=[O:28])[CH3:26]
Reactant: CC(=O)OC(C)=O
Reactant: CC1CC(c2ccncc2[N+](=O)[O-])=CC(NC(=O)OC(C)(C)C)C1O
Solvent: c1ccncc1
Product: CC(=O)OC1C(C)CC(c2ccncc2[N+](=O)[O-])=CC1NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 94 %

Procedure:
To a solution of (+/−)-tert-butyl 6-hydroxy-5-methyl-3-(3-nitropyridin-4-yl)cyclohex-2-enylcarbamate (1.0 equiv.) in pyridine (0.1 M) was added Ac2O (2.0 equiv.) and the reaction was stirred at room temperature overnight. Upon completion, the reaction was concentrated to dryness, then worked-up with ethyl acetate and water. The organic phase was dried with brine, then sodium sulfate, filtered, and concentrated to give (+/−)-2-(tert-butoxycarbonylamino)-6-methyl-4-(3-nitropyridin-4-yl)cyclohex-3-enyl acetate in 94% yield. LC/MS=392.2 (M+H), Rt=0.94 min.
Reaction SMILES: [CH2:1]([C:13]1[C:14](=[O:25])[C:15]2[C:20]([C:21](=[O:24])[C:22]=1[OH:23])=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].C(N(CC)CC)C.[C:33](Cl)(=[O:35])[CH3:34].C(Cl)Cl>O>[C:33]([O:23][C:22]1[C:21](=[O:24])[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14](=[O:25])[C:13]=1[CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])(=[O:35])[CH3:34]
Reactant: CC(=O)Cl
Reactant: CCCCCCCCCCCCC1=C(O)C(=O)c2ccccc2C1=O
Solvent: O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCCCCCCCCCCC1=C(OC(C)=O)C(=O)c2ccccc2C1=O
Temperature: 25 °C
Reaction time: 30 h

Procedure:
A mixture of 2.0 parts of 2-n-dodecyl-3-hydroxy-1,4-naphthoquinone, 0.81 parts of triethylamine, 0.63 parts of acetyl chloride and 50 parts of methylene chloride was stirred at room temperature for 30 hours. The resulting mixture was distributed between methylene chloride and water. The methylene chloride layer was separated, dried over magnesium sulfate, then filtered and evaporated under reduced pressure. The residue was crystallized from petroleum ether (b.p. 30°-60°) to give 1.2 parts of 3-acetoxy-2-n-dodecyl-1,4-naphthoquinone, m.p.57°-58° C.
Reaction SMILES: C(N(CC)CC)C.ON1C2C=CC=CC=2N=N1.[CH:18]1[C:30]2[CH:29]([C:31](O)=[O:32])[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:22]=2[CH:21]=[CH:20][CH:19]=1.Cl.[NH2:35][CH2:36][C:37]([O:39][CH3:40])=[O:38]>C(Cl)Cl.O>[CH:18]1[C:30]2[CH:29]([C:31]([NH:35][CH2:36][C:37]([O:39][CH3:40])=[O:38])=[O:32])[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:22]=2[CH:21]=[CH:20][CH:19]=1
Reactant: COC(=O)CN
Reactant: O=C(O)C1c2ccccc2-c2ccccc21
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)CNC(=O)C1c2ccccc2-c2ccccc21
Reaction time: 20 h
Yield: 93.2 %

Procedure:
1.2 ml of triethylamine and 1.31 g of 1-hydroxybenzotriazole were successively added, under ice-cooling, to a solution of 1.5 g of fluorene-9-carboxylic acid and 0.90 g of methyl glycinate hydrochloride in 50 ml of methylene chloride, followed by further adding 10 minutes later 1.64 g of water-soluble carbodiimide hydrochloride. The resultant mixture was stirred at 0° C. for 0.5 hour and, then at room temperature for 20 hours. The reaction mixture was washed with 5% hydrochloric acid, saturated sodium bicarbonate, and saturated saline, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by a silica gel column chromatography (eluting solution: chloroform-methanol) to give 1.87 g of methyl N-(9-fluorenylcarbonyl)glycinate.
Reaction SMILES: [C:1]([O:4][C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([O:18][C:19](=[O:21])[CH3:20])[C:13]=1[O:14][C:15](=[O:17])[CH3:16])[C:8](O)=[O:9])(=[O:3])[CH3:2].C(Cl)(=O)C([Cl:25])=O.CN(C)C=O>C(Cl)Cl>[C:1]([O:4][C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([O:18][C:19](=[O:21])[CH3:20])[C:13]=1[O:14][C:15](=[O:17])[CH3:16])[C:8]([Cl:25])=[O:9])(=[O:3])[CH3:2]
Reactant: O=C(Cl)C(=O)Cl
Reactant: CC(=O)Oc1cc(C(=O)O)cc(OC(C)=O)c1OC(C)=O
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CC(=O)Oc1cc(C(=O)Cl)cc(OC(C)=O)c1OC(C)=O
Reaction time: 2 h

Procedure:
3,4,5-Triacetoxybenzoic acid (296.23 g, 1 mol) was slurried in a 2 L flask in CH2Cl2 (1.0 L), and oxalyl chloride (113 mL, 1.3 mol) as added, followed by slow, dropwise addition of N,N-dimethylformamide (1.5 mL). After 2 hours at RT, gas evolution had ceased, and 3,4,5-triacetoxybenzoyl chloride was isolated by evaporation under reduced pressure.
Reaction SMILES: [OH:1][C:2]1([C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)[CH2:7][CH2:6][CH2:5][CH2:4][C:3]1=[O:8].C(O[CH:20](N(C)C)[N:21]([CH3:23])[CH3:22])(C)(C)C>>[CH3:20][N:21]([CH3:23])/[CH:22]=[C:4]1\[CH2:5][CH2:6][CH2:7][C:2]([OH:1])([C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)[C:3]\1=[O:8]
Reactant: O=C1CCCCC1(O)c1cccnc1
Reactant: CN(C)C(OC(C)(C)C)N(C)C
Product: CN(C)/C=C1\CCCC(O)(c2cccnc2)C1=O

Procedure:
2-Hydroxy-2-pyridin-3yl-cyclohexanone (394 mg, 2 mmol) was reacted with tert.-butoxy-bis-(dimethylamino)-methane using in analogous manner the procedure described in example 45a) to give crude title compound (582 mg) as a brown oil which was used directly in the next step. MS ISP (m/e): 247.2 (100) [(M+H)+].
Reaction SMILES: [Cl:1][C:2]1[CH2:7][C:6]([N+:15]([O-:17])=[O:16])(C2C=CC(O)=CC=2)[CH:5]=[CH:4][C:3]=1[N:18]=[N:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.Br[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33].[C:34](=[O:37])([O-])[O-].[K+].[K+].[I-].[Na+]>C(O)C>[Cl:1][C:2]1[CH:7]=[C:6]([N+:15]([O-:17])=[O:16])[CH:5]=[CH:4][C:3]=1[N:18]=[N:19][C:20]1[CH:25]=[CH:24][C:23]([C:2]2[CH:7]=[CH:6][C:34]([O:37][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])=[CH:4][CH:3]=2)=[CH:22][CH:21]=1
Reactant: O=C([O-])[O-]
Reactant: CCCCCCCBr
Reactant: O=[N+]([O-])C1(c2ccc(O)cc2)C=CC(N=Nc2ccccc2)=C(Cl)C1
Agent: [I-]
Agent: [K+]
Agent: [Na+]
Solvent: CCO
Product: CCCCCCCOc1ccc(-c2ccc(N=Nc3ccc([N+](=O)[O-])cc3Cl)cc2)cc1
Reaction time: 22 h
Yield: 104.5 %

Procedure:
A mixture of 1.3 g of crude 2-chloro-4-nitro-4-(4-hydroxyphenyl)azobenzene, 20 ml of ethanol, 0.658 g of 1-bromoheptane, 0.528 g of potassium carbonate and a spatula tip of sodium iodide was boiled at reflux while stirring for 22 hours. The brown suspension was subsequently concentrated in vacuo and the residue was chromatographed on silica gel with toluene/hexane as the eluent. Recrystallization from methylene chloride/hexane, yielded 0.863 g of 2-chloro-4-nitro-4'-(4-heptyloxyphenyl)-azobenzene as orange crystals; m.p. (C-N) 83.1°-83.7° C., cl.p. (N-I) 179.4°-179.8° C.; E300 =11580, E406 =25910.
Reaction SMILES: [CH3:1][C:2]1([CH3:22])[C:10]2=[CH:11][C:12]3[NH:13][C:14]4[C:19]([C:20]=3[CH:21]=[C:9]2[C:8]2[C:3]1=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:18][CH:17]=[CH:16][CH:15]=4.[H-].[Na+].[C:25]([C:29]1[CH:34]=[CH:33][C:32]([C:35]2[N:40]=[C:39]([C:41]3[CH:46]=[CH:45][C:44]([C:47]([CH3:50])([CH3:49])[CH3:48])=[CH:43][CH:42]=3)[N:38]=[C:37](Cl)[N:36]=2)=[CH:31][CH:30]=1)([CH3:28])([CH3:27])[CH3:26]>CN(C)C=O.C1COCC1>[C:25]([C:29]1[CH:30]=[CH:31][C:32]([C:35]2[N:40]=[C:39]([C:41]3[CH:42]=[CH:43][C:44]([C:47]([CH3:50])([CH3:49])[CH3:48])=[CH:45][CH:46]=3)[N:38]=[C:37]([N:13]3[C:12]4[CH:11]=[C:10]5[C:2]([CH3:22])([CH3:1])[C:3]6[C:8]([C:9]5=[CH:21][C:20]=4[C:19]4[C:14]3=[CH:15][CH:16]=[CH:17][CH:18]=4)=[CH:7][CH:6]=[CH:5][CH:4]=6)[N:36]=2)=[CH:33][CH:34]=1)([CH3:28])([CH3:27])[CH3:26]
Reactant: CC1(C)c2ccccc2-c2cc3c(cc21)[nH]c1ccccc13
Reactant: CC(C)(C)c1ccc(-c2nc(Cl)nc(-c3ccc(C(C)(C)C)cc3)n2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: CC(C)(C)c1ccc(-c2nc(-c3ccc(C(C)(C)C)cc3)nc(-n3c4ccccc4c4cc5c(cc43)C(C)(C)c3ccccc3-5)n2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
12.5 g (44 mmol) of 12,12-dimethyl-10,12-dihydro-10-azaindeno[2,1-b]-fluorene are dissolved in 200 ml of dimethylformamide under a protective-gas atmosphere, and 2.1 g of 60% NaH in mineral oil (52.7 mmol) are added. After 1 h at room temperature, a solution of 2,4-bis(4-tert-butylphenyl)-6-chloro-1,3,5-triazine (20 g, 52.7 mmol) in 100 ml of THF is added dropwise. The reaction mixture is stirred at room temperature for 12 h. After this time, the reaction mixture is poured onto ice and extracted three times with dichloromethane. The combined organic phases are dried over Na2SO4 and evaporated. The residue is extracted with hot toluene, recrystallised from toluene and finally sublimed in a high vacuum. Yield: 17 g, 60%. The purity is 99.9%.
Reaction SMILES: [CH:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][C:7]([C:13]#[N:14])=[C:6]2[O:15][CH2:16][CH2:17][O:18][CH3:19])=O.COC1C=CC(/C=[C:35]2/[C:36]([NH:38][C:39]([S:41]/2)=[NH:40])=[O:37])=CC=1OC1CCCC1.C([O-])(=O)C.[Na+]>C(O)(=O)C>[NH2:40][C:39]1[S:41]/[C:35](=[CH:1]\[C:3]2[CH:4]=[C:5]3[C:10](=[CH:11][CH:12]=2)[N:9]=[CH:8][C:7]([C:13]#[N:14])=[C:6]3[O:15][CH2:16][CH2:17][O:18][CH3:19])/[C:36](=[O:37])[N:38]=1
Reactant: COc1ccc(/C=C2\SC(=N)NC2=O)cc1OC1CCCC1
Reactant: COCCOc1c(C#N)cnc2ccc(C=O)cc12
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CC(=O)O
Product: COCCOc1c(C#N)cnc2ccc(/C=C3\SC(N)=NC3=O)cc12

Procedure:
Similar procedure as described in example 28c was used, starting from 6-formyl-4-(2-methoxy-ethoxy)-quinoline-3-carbonitrile (example 77b), pseudothiohydantoin, sodium acetate and acetic acid to give 6-[2-amino-4-oxo-4H-thiazol-(5Z)-ylidenemethyl]-4-(2-methoxy-ethoxy)-quinoline-3-carbonitrile. LC-MS m/e 355 (MH+).