Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:11]=[C:10](Cl)[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH3:13])[CH:8]=2)[N:3]=1.[NH2:14][CH2:15][C:16]1([N:22](CC2C=CC=CC=2)CC2C=CC=CC=2)[CH2:19][S:18](=[O:21])(=[O:20])[CH2:17]1.[F:37][C:38]1([F:49])[C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][C:43]=2[CH2:42][NH:41][CH2:40][CH2:39]1>>[NH2:22][C:16]1([CH2:15][NH:14][C:10]2[C:9]3[C:4](=[CH:5][CH:6]=[C:7]([CH3:13])[CH:8]=3)[N:3]=[C:2]([N:41]3[CH2:40][CH2:39][C:38]([F:37])([F:49])[C:44]4[CH:45]=[CH:46][CH:47]=[CH:48][C:43]=4[CH2:42]3)[N:11]=2)[CH2:19][S:18](=[O:21])(=[O:20])[CH2:17]1
Reactant: NCC1(N(Cc2ccccc2)Cc2ccccc2)CS(=O)(=O)C1
Reactant: Cc1ccc2nc(Cl)nc(Cl)c2c1
Reactant: FC1(F)CCNCc2ccccc21
Product: Cc1ccc2nc(N3CCC(F)(F)c4ccccc4C3)nc(NCC3(N)CS(=O)(=O)C3)c2c1

Procedure:
The title compound was prepared in analogy to Example 116-1 in Scheme 57 by using 2,4-dichloro-6-methylquinazoline, 3-(aminomethyl)-N,N-dibenzyl(1,1-dioxido)thietan-3-amine and 5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepine. MS obsd. (ESI+) [(M+H)+] 474, 1H NMR (400 MHz, CD3OD) δ ppm 7.73 (s, 1 H), 7.65 (d, 1 H), 7.60 (d, 1 H), 7.29-7.45 (m, 4 H), 5.02 (s, 2 H), 4.04-4.62 (m, 2 H), 4.34 (t, 2 H), 4.12 (t, 2 H), 4.01-4.04 (m, 2 H), 2.47 (m, 2 H), 2.41 (s, 3 H).
Reaction SMILES: [CH:1]1([C:6]2[CH:7]=[C:8]([CH:11]=[CH:12][C:13]=2[O:14][CH3:15])[CH:9]=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:16][C:17]1[C:25]([Cl:26])=[CH:24][CH:23]=[C:22]2[C:18]=1[CH2:19][C:20](=[O:27])[NH:21]2>>[Cl:26][C:25]1[C:17]([CH3:16])=[C:18]2[C:22](=[CH:23][CH:24]=1)[NH:21][C:20](=[O:27])[C:19]2=[CH:9][C:8]1[CH:11]=[CH:12][C:13]([O:14][CH3:15])=[C:6]([CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)[CH:7]=1
Reactant: Cc1c(Cl)ccc2c1CC(=O)N2
Reactant: COc1ccc(C=O)cc1C1CCCC1
Product: COc1ccc(C=C2C(=O)Nc3ccc(Cl)c(C)c32)cc1C1CCCC1

Procedure:
3-Cyclopentyl-4-methoxybenzaldehyde was condensed with 4-methyl-5-chloro-2-oxindole to give 0.3 g of 5-Chloro-3-(3-cyclopentyl-4-methoxybenzylidene)-4-methyl-1,3-dihydroindol-2-one as a yellow-orange solid.
Reaction SMILES: [CH:1]([C:4]1[CH:5]=[C:6]([CH:9]=[C:10]([CH:13]([CH3:15])[CH3:14])[C:11]=1[OH:12])[CH:7]=O)([CH3:3])[CH3:2].[C:16]([CH2:18][C:19]([NH2:21])=[S:20])#[N:17]>>[NH2:21][C:19](/[C:18](=[CH:7]/[C:6]1[CH:5]=[C:4]([CH:1]([CH3:3])[CH3:2])[C:11]([OH:12])=[C:10]([CH:13]([CH3:15])[CH3:14])[CH:9]=1)/[C:16]#[N:17])=[S:20]
Reactant: CC(C)c1cc(C=O)cc(C(C)C)c1O
Reactant: N#CCC(N)=S
Product: CC(C)c1cc(/C=C(\C#N)C(N)=S)cc(C(C)C)c1O

Procedure:
M25 was prepared using 3,5-diisopropyl-4-hydroxybenzaldehyde and cyanothioacetamide under similar conditions as decribed for M11.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([CH2:8][CH:9]([C:11]2[S:12][CH:13]=[C:14]3[O:19][CH2:18][CH2:17][O:16][C:15]=23)O)[CH:5]=[CH:4][N:3]=1.O=P(Cl)(Cl)Cl.O>N1C=CC=CC=1>[Br:1][C:2]1[CH:7]=[C:6]([CH:8]=[CH:9][C:11]2[S:12][CH:13]=[C:14]3[O:19][CH2:18][CH2:17][O:16][C:15]=23)[CH:5]=[CH:4][N:3]=1
Reactant: OC(Cc1ccnc(Br)c1)c1scc2c1OCCO2
Solvent: c1ccncc1
Solvent: O=P(Cl)(Cl)Cl
Solvent: O
Product: Brc1cc(C=Cc2scc3c2OCCO3)ccn1
Temperature: -78 °C
Reaction time: 0.25 h
Yield: 50 %

Procedure:
Compound (9) (800 mg, 2.34 mmol) was dissolved in pyridine (2 mL). POCl3 (327 μL, 538 mg, 3.51 mmol) was added and the resulting mixture was cooled to −78° C. Upon addition of water (40 mL) the formation of a precipitate was observed. The cooling bath was removed and the mixture was stirred for 15 min. A precipitate was obtained which was collected upon filtration and washed with petroleum ether/ethyl acetate (20 mL, 1:1) affording pure (10) as a yellow solid (380 mg, 1.17 mmol, 50%), mp 127-129° C. 1H NMR (500 MHz, CDCl3) δ 8.27 (d, J=5.2 Hz, 1H), 7.51 (s, 1H), 7.34 (d, J=16.1 Hz, 1H), 7.25 (d, J=5.2 Hz, 1H), 6.70 (d, J=16.1 Hz, 1H), 6.38 (s, 1H), 4.35-4.33 (m, 2H), 4.27-4.25 (m, 2H).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:11]2[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=2)([CH3:10])[CH3:9])=[CH:4][CH:3]=1.[C:18]([O:21]C(=O)C)(=[O:20])[CH3:19]>>[C:18]([OH:21])(=[O:20])[CH3:19].[C:18]([OH:21])(=[O:20])[CH3:19].[OH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([C:11]2[CH:12]=[CH:13][C:14]([OH:17])=[CH:15][CH:16]=2)([CH3:10])[CH3:9])=[CH:6][CH:7]=1
Reactant: CC(=O)OC(C)=O
Agent: CC(C)(c1ccc(O)cc1)c1ccc(O)cc1
Product: CC(=O)O
Temperature: 135 °C
Reaction time: 4 h

Procedure:
Into a glass lined reactor was charged 880 grams of bisphenol-A and 1000 grams of acetic anhydride. The reaction was heated to about 135° C. and held at this temperature for about 4 hours. Vacuum was then slowly applied to distill acetic acid and excess acetic anhydride. At maximum vacuum, the material temperature was allowed to rise to 150° C. and held until no further distillation was evident (approximately 30 minutes). Analysis of the crude product showed that conversion to bisphenol-A diacetate was 99.9% complete. The material also contained some residual acetic anhydride (less than 600 ppm based on weight of bisphenol-A diacetate as measured by titration with morpholine as described in Siggia and Hana, "Quantitative Organic Analysis via Functional Groups", Fourth Edition, Wiley-Interscience, 1979, pages 231 to 235).
Reaction SMILES: [N:1]1([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([N:21]4[C:26](=[O:27])[CH:25]=[CH:24][CH:23]=[N:22]4)=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:5][CH2:4][C@@H:3]2[CH2:6][NH:7][CH2:8][C@H:2]12.[CH:28](=O)[CH3:29].CC(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.C([O-])(O)=O.[Na+]>[CH2:28]([N:7]1[CH2:6][C@@H:3]2[C@@H:2]([N:1]([C:9]3[CH:14]=[CH:13][C:12]([C:15]4[CH:20]=[CH:19][C:18]([N:21]5[C:26](=[O:27])[CH:25]=[CH:24][CH:23]=[N:22]5)=[CH:17][CH:16]=4)=[CH:11][CH:10]=3)[CH2:5][CH2:4]2)[CH2:8]1)[CH3:29]
Reactant: O=c1cccnn1-c1ccc(-c2ccc(N3CC[C@@H]4CNC[C@@H]43)cc2)cc1
Reactant: CC=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(Cl)Cl
Solvent: CC(=O)O
Product: CCN1C[C@H]2CCN(c3ccc(-c4ccc(-n5ncccc5=O)cc4)cc3)[C@H]2C1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
The product from Example 85B (0.050 g, 0.140 mmol) and acetaldehyde (10.0 μL, 0.140 mmol) were combined in 5 mL of dichloroethane containing 3 drops of HOAc and stirred at ambient temperature for 10 minutes. Sodium triacetoxyborohydride (0.039 g, 0.182 mmol) was added and the mixture was stirred for 3 hours. The mixture was diluted with 20 mL of aqueous NaHCO3 and extracted three times with 25 mL of 5% n-propanol in CHCl3 and the combined extracts were dried over Na2SO4, filtered, and absorbed on silica gel. The crude material was chromatographed, eluting with 1% aqueous NH4OH in EtOAc/MeOH (9:1), to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.91 (d, J=2.0 Hz, 1H), 7.63 (s, 4H), 7.50 (d, J=8.5 Hz, 2H), 7.23 (d, J=3.7 Hz, 1H), 7.07 (d, J=9.2 Hz, 1H), 6.65 (d, J=8.8 Hz, 2H), 4.11-4.25 (m, 1H), 3.47-3.60 (m, 1H), 3.24-3.39 (m, 1H), 2.88-3.05 (m, 1H), 2.78 (dd, J=9.5, 6.4 Hz, 1H), 2.56-2.70 (m, 2H), 2.35-2.56 (m, 3H), 2.10-2.25 (m, 1H), 1.85-2.02 (m, 1H), 1.26 (s, 1H), 1.09 (t, J=7.1 Hz, 2H). MS (ESI+) m/z 387 (M+H)+.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][CH2:10][CH2:9]2.I[C:16]1[CH:28]=[CH:27][C:26]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:19]([CH3:30])([CH3:29])[C:18]=2[CH:17]=1.C(=O)([O-])[O-].[K+].[K+]>[Cu].CN(C)C=O>[CH3:29][C:19]1([CH3:30])[C:20]2[CH:21]=[C:22]([N:11]3[C:12]4[C:8](=[CH:7][C:6]([C:2]5[S:1][CH:5]=[CH:4][CH:3]=5)=[CH:14][CH:13]=4)[CH2:9][CH2:10]3)[CH:23]=[CH:24][C:25]=2[C:26]2[C:18]1=[CH:17][CH:16]=[CH:28][CH:27]=2
Reactant: CC1(C)c2ccccc2-c2ccc(I)cc21
Reactant: c1csc(-c2ccc3c(c2)CCN3)c1
Agent: [Cu]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC1(C)c2ccccc2-c2ccc(N3CCc4cc(-c5cccs5)ccc43)cc21

Procedure:
Under the atmosphere of nitrogen, a mixed solution made of 2 parts of 2-thiopheneboric acid, 3 mL of ethanol and 10 mL of 2M sodium carbonate was dropwise added to a mixed solution of 2 parts of 5-bromoindoline and 20 parts of toluene, and the reactive components were caused to react for 1 hour. Thereafter, thereto was added 0.3 part of tetra-triphenylphosphine palladium (0), and the reactive components were caused to react at 80° C. for 12 hours. After the reaction, the reaction solution was extracted with water/ethyl acetate, and the ethyl acetate phase was dried over magnesium sulfate. Ethyl acetate was distilled off, and the residue was separated and purified by column chromatography (hexane/ethyl acetate) to yield 2 parts of a precursor of the compound (311), 5-(thiophene-2-yl)indoline as a colorless crystal. Next, under the atmosphere of nitrogen, 2 parts of this 5-(thiophene-2-yl)indoline, 6 parts of 2-iodo-9,9-dimethyl-9H-fluorene, 30 parts of dimethylformamide (DMF), 10 parts of potassium carbonate, and 1 part of copper powder (200 mesh) were stirred at 160° C. for 10 hours. After the reaction, the resultant was extracted with water/ethyl acetate, and the ethyl acetate phase was dried over magnesium sulfate. Ethyl acetate was distilled off, and the residue was separated and purified by column chromatography to yield 2 parts of 1-(9,9-dimethyl-9H-fluorene-2-yl)-5-(thiophene-2-yl)indoline, which is a precursor of the compound (311) in the same manner, as a colorless crystal. Next, 1.7 parts of phosphorus oxychloride were dropwise added to 10 parts of DMF, the temperature of which was adjusted to 5° C., while the temperature of the reaction solution was kept at 10° C. or lower. The reaction solution was then stirred at 5° C. for 1 hour. Thereafter, 2 parts of 1-(9,9-dimethyl-9H-fluorene-2-yl)-5-(thiophene-2-yl)indoline described above were added thereto, and then the reactive components were caused to react at 25° C. for 1 hour. The reaction solution was then stirred at 70° C. for 1 hour. Thereafter, a 20% solution of sodium hydroxide in water was added to the reaction solution until the pH turned to 12. The precipitated crystal was filtrated, and the resultant crystal was washed with water. The crystal was then separated by column chromatography (hexane/ethyl acetate), and recrystallized from ethanol to yield 2 parts of the compound (311) as a yellow crystal.
Reaction SMILES: [OH:1][C:2]1[C:7]([CH3:8])=[N:6][N:5]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[N+:16]([O-:18])=[O:17])[C:4](=[O:19])[C:3]=1[C:20]([O:22]CC)=O.[H-].[Na+].[N+:27](C1C=CC=CC=1CBr)([O-])=O.Cl.CC[O:41][C:42]([CH3:44])=[O:43]>CN(C)C=O.O>[OH:1][C:2]1[C:7]([CH3:8])=[N:6][N:5]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[N+:16]([O-:18])=[O:17])[C:4](=[O:19])[C:3]=1[C:20]([NH:27][CH2:44][C:42]([OH:41])=[O:43])=[O:22]
Reactant: CCOC(=O)c1c(O)c(C)nn(Cc2ccccc2[N+](=O)[O-])c1=O
Reactant: CCOC(C)=O
Reactant: O=[N+]([O-])c1ccccc1CBr
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1nn(Cc2ccccc2[N+](=O)[O-])c(=O)c(C(=O)NCC(=O)O)c1O
Reaction time: 0.75 h
Yield: 50 %

Procedure:
Ethyl 5-hydroxy-6-methyl-2-[(2-nitrophenyl)methyl]-3-oxo-2,3-dihydro-4-pyridazinecarboxylate. Sodium hydride (50 mg, 1.26 mmol) was added to a solution of the compound from example 28b) (100 mg, 0.50 mmol) in N,N-Dimethylformamide (DMF) (2 mL) at 0° C. The reaction was brought to room temperature and stirred for 45 minutes. The temperature was then reduced to 0° C. and 2-nitrobenzyl bromide (109 mg, 0.50 mmol) was added. The reaction was brought to room temperature and stirred for 3 hours followed by the addition of 1N HCl. The solution was diluted with EtOAc and H2O and the layers separated. The aqueous layer was backextracted with EtOAc several times. The combined organic layers were washed with Brine, dried (MgSO4), filtered and concentrated. The product was purified by column chromatography (SiO2, 0-6% MeOH/CH2Cl2) to give the title compound as an orange oil (83 mg, 50%). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.28 (s, 1H) 8.08 (dd, J=8.08, 1.26 Hz, 1H) 7.70 (td, J=7.64, 1.39 Hz, 1H) 7.53-7.61 (m, 1H) 7.18 (dd, J=7.71, 0.88 Hz, 1H) 5.45 (s, 2H) 4.26 (q, J=7.24 Hz, 2H) 2.20 (s, 3H) 1.25 (t, J=7.07 Hz, 3H).
Reaction SMILES: [N:1]([CH:4]([C:6]1[N:7]=[C:8]2[S:16][CH:15]=[C:14]([CH3:17])[N:9]2[C:10](=[O:13])[C:11]=1Br)[CH3:5])=[N+:2]=[N-:3].[C:18]1(B(O)O)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.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>[N:1]([CH:4]([C:6]1[N:7]=[C:8]2[S:16][CH:15]=[C:14]([CH3:17])[N:9]2[C:10](=[O:13])[C:11]=1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH3:5])=[N+:2]=[N-:3]
Reactant: OB(O)c1ccccc1
Reactant: Cc1csc2nc(C(C)N=[N+]=[N-])c(Br)c(=O)n12
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Solvent: O
Product: Cc1csc2nc(C(C)N=[N+]=[N-])c(-c3ccccc3)c(=O)n12
Temperature: 100 °C
Yield: 44.4 %

Procedure:
To a mixture of 7-(1-azidoethyl)-6-bromo-3-methyl-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one (0.100 g, 0.318 mmol) and phenylboronic acid (46.6 mg, 0.382 mmol) in 1,4-dioxane (2 mL) was added a 1M solution of sodium carbonate (40.5 mg, 0.382 mmol) in water (0.38 mL) and tetrakis(triphenylphosphine)palladium (0) (18.4 mg, 0.0159 mmol). The reaction mixture was heated at 100° C. overnight. After cooling to rt, the mixture was diluted with EtOAc, washed with water, brine, dried over MgSO4, and concentrated. The residue was purified on silica gel, eluting with 0 to 50% EtOAc in hexane, to provide the desired product (44 mg, 44.4%). LCMS calculated for C15H14N5OS (M+H)+: m/z=312.1. Found: 312.3.
Reaction SMILES: [CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:37])[CH2:15][CH2:16][CH2:17][CH2:18][O:19][Si:20]([C:33]([CH3:36])([CH3:35])[CH3:34])([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C[C@H]2N(C[C@H]3[C@@H]4CCCCN4C[C@@H]2C3)CC1.[CH:55](=[O:64])/[CH:56]=[CH:57]/[C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1>C(Cl)Cl.[Ti](Cl)(Cl)(Cl)Cl>[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:37])[C@H:15]([CH2:16][CH2:17][CH2:18][O:19][Si:20]([C:33]([CH3:34])([CH3:36])[CH3:35])([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)[C@H:55]([OH:64])[CH:56]=[CH:57][C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)[Si](OCCCCC(=O)N1C(=O)OC[C@H]1Cc1ccccc1)(c1ccccc1)c1ccccc1
Reactant: O=C/C=C/c1ccccc1
Agent: Cl[Ti](Cl)(Cl)Cl
Agent: C1CCN2C[C@@H]3C[C@@H](CN4CCCC[C@@H]34)[C@H]2C1
Solvent: ClCCl
Product: CC(C)(C)[Si](OCCC[C@@H](C(=O)N1C(=O)OC[C@H]1Cc1ccccc1)[C@H](O)C=Cc1ccccc1)(c1ccccc1)c1ccccc1
Reaction time: 0.08 h
Yield: 83.2 %

Procedure:
To a stirring solution of (R)-4-benzyl-3-[5-(tert-butyl-diphenyl-silanyloxy)-pentanoyl]-oxazolidin-2-one (1.64 g, 3.19 mmol) in dry methylene chloride (15.9 mL) in a flame dried round bottom flask under N2 at 0° C. was added titanium(IV) chloride (386 μL, 3.51 mmol). After 5 min, (−)-sparteine (1.83 mL, 7.97 mmol) was added. After 20 min, trans-cinnamaldehyde (442 μL, 3.51 mmol) was added dropwise to the purple suspension, and the resulting pale green-yellow solution was stirred for 1 h . The reaction was quenched by the addition of 50% saturated ammonium chloride (50 mL), diluted with water (100 mL), and then extracted with methylene chloride (3×30 mL). The organic layers were combined, washed with brine, dried over sodium sulfate, and concentrated in vacuo to a colorless oil. The oil was purified by flash chromatography (SiO2, 15-30% ethyl acetate in hexanes) to yield 1.72 g (83.1%) of the desired product as a white solid. MS (APCI), m+/z: (M+H)+=648.
Reaction SMILES: O.[C:2]([O:8]CC)(=O)[CH2:3][C:4]([CH3:6])=[O:5].C1(C)C(C)=CC=CC=1.[NH2:19][C:20]1[CH:21]=[C:22]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:24][CH:25]=1>CCCCCC>[F:27][C:26]([F:28])([F:29])[C:22]1[CH:21]=[C:20]([CH:25]=[CH:24][CH:23]=1)[NH:19][C:2](=[O:8])[CH2:3][C:4]([CH3:6])=[O:5]
Reactant: Nc1cccc(C(F)(F)F)c1
Reactant: CCOC(=O)CC(C)=O
Solvent: O
Solvent: Cc1ccccc1C
Solvent: CCCCCC
Product: CC(=O)CC(=O)Nc1cccc(C(F)(F)F)c1
Reaction time: 4 h
Yield: 55.7 %

Procedure:
A two-liter reaction flask fitted with a magnetic stirrer, heating mantle, dropping funnel, thermometer, water-cooled condenser and Dean Stark trap was charged with 156.2 g (1.2 moles) of ethyl acetoacetate and 400 ml of xylene. The dropping funnel contained 161 g (1.0 mole) of 3-aminobenzotrifluoride and 320 ml xylene. The solution in the reaction pot was heated to 135° and the contents of the dropping funnel were added dropwise over a period of three hours. The low-boiling liquid which accumulated in the Dean Stark trap was periodically drained in order to maintain a reaction temperature of about 135°. After four hours, the reaction was judged to be completed and the reaction solution was cooled. There was added 650 ml of hexane. Cooling in an ice bath yielded a white crystalline precipitate. The product was collected on a vacuum filter and dried in an oven. There was obtained 136.6 g (55.7%) of 3'-trifluoromethylacetoacetanilide, m.p. 109°-10°. N.M.R. (CDCl3) ∂ 2.2 (CH3, keto), 3.5 (CH2), 7.2-7.9 (aromatic), 1.8 (CH3, enol).
Reaction SMILES: [O:1]=[C:2]1[CH2:6][CH2:5][CH2:4][CH:3]1[CH2:7][C:8]([OH:10])=[O:9].OS(O)(=O)=O.[CH2:16](O)[CH3:17]>>[O:1]=[C:2]1[CH2:6][CH2:5][CH2:4][CH:3]1[CH2:7][C:8]([O:10][CH2:16][CH3:17])=[O:9]
Reactant: O=C(O)CC1CCCC1=O
Reactant: CCO
Agent: O=S(=O)(O)O
Product: CCOC(=O)CC1CCCC1=O

Procedure:
To a solution of 2-(2-oxocyclopentyl)acetic acid (23.6 g, 166 mmol) in absolute ethanol (400 mL) was added H2SO4 (16.28 g, 166 mmol). The resultant solution was heated under reflux overnight. The reaction mixture was concentrated and the liquid residue was added into ice-water (200 mL). The aqueous mixture was extracted with DCM (3×200 mL). The combined organic layers were washed with H2O (300 mL), brine (300 mL), dried over Na2SO4, decanted, concentrated and dried under vacuum to afford the title compound as a light yellow liquid (27.2 g). LCMS m/z=171.3 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 1.19 (t, J=7.14 Hz, 3 H), 1.50-1.62 (m, 1 H), 1.65-1.80 (m, 1 H), 1.92-2.02 (m, 1 H), 2.12 (dd, J=16.7, 8.86 Hz, 1 H), 2.19-2.29 (m, 2 H), 2.30-2.44 (m, 2 H), 2.65 (dd, J=15.12, 2.6 Hz, 1H), 4.07 (q, J=7.14 Hz, 2H).
Reaction SMILES: [C:1]1([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[C:27](OC(=O)C)(=[O:29])[CH3:28].Cl>O1CCCC1>[C:1]1([CH:11]([C:27](=[O:29])[CH3:28])[C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: CCOC(=O)Cc1cccc2ccccc12
Reactant: CC(=O)OC(C)=O
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: Cl
Agent: [Li+]
Solvent: C1CCOC1
Product: CCOC(=O)C(C(C)=O)c1cccc2ccccc12
Temperature: -78 °C
Reaction time: 1 h

Procedure:
To a solution of ethyl 2-(naphthalen-1-yl)acetate (1 g, 4.7 mmol) in tetrahydrofuran (20 mL) at −78° C. was added LiHMDS (1M THF, 9.4 mL, 9.4 mmol) and the reaction mixture stirred at −78° C. for 1 hour. Acetic anhydride was then added (0.54 mL, 5.64 mmol) dropwise and the reaction allowed to warm to room temperature and stirred for 30 minutes. Aqueous HCl solution (1N, 25 mL) was added to the reaction mixture and then extracted with ethyl acetate, dried over sodium sulfate and concentrated to give compound ethyl 2-(naphthalen-1-yl)-3-oxobutanoate as a light yellow oil, that was used in the next step without further purification.
Reaction SMILES: [CH3:1][C@:2]12[C@@:19]3([CH3:20])[C@@H:10]([C@:11]4([CH3:33])[C@@H:16]([CH2:17][CH2:18]3)[C:15]([CH3:22])([CH3:21])[C:14]([C:23]3C=CC(C(OC)=O)=[CH:25][CH:24]=3)=[CH:13][CH2:12]4)[CH2:9][CH2:8][C@@H:7]1[C@H:6]1[C@H:34]([C:37]([CH3:39])=[CH2:38])[CH2:35][CH2:36][C@:5]1([NH:40][CH2:41][CH2:42][N:43]1[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1)[CH2:4][CH2:3]2.[C:49]([OH:54])(=[O:53])[CH2:50][CH2:51][CH3:52]>>[C:49]([N:46]1[CH2:45][CH2:44][N:43]([CH2:42][CH2:41][NH:40][C@:5]23[CH2:36][CH2:35][C@@H:34]([C:37]([CH3:39])=[CH2:38])[C@@H:6]2[C@@H:7]2[C@@:2]([CH3:1])([CH2:3][CH2:4]3)[C@@:19]3([CH3:20])[C@@H:10]([C@:11]4([CH3:33])[C@@H:16]([CH2:17][CH2:18]3)[C:15]([CH3:22])([CH3:21])[C:14]([C:23]3[CH:24]=[CH:25][C:50]([C:49]([OH:54])=[O:53])=[CH:51][CH:52]=3)=[CH:13][CH2:12]4)[CH2:9][CH2:8]2)[CH2:48][CH2:47]1)(=[O:53])[CH2:50][CH2:51][CH3:52]
Reactant: CCCC(=O)O
Reactant: C=C(C)[C@@H]1CC[C@]2(NCCN3CCNCC3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)OC)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Product: C=C(C)[C@@H]1CC[C@]2(NCCN3CCN(C(=O)CCC)CC3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12

Procedure:
The title compound (1.2 mg) was prepared from methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((2-(piperazin-1-yl)ethyl)amino)-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoate following the general procedure as described above using butyric acid as the acylating agent. LCMS: m/e 712.8 (M+H)+, 4.97 min (method 15). 1H NMR (500 MHz, METHANOL-d4) δ 7.89 (d, J=8.2 Hz, 2H), 7.16 (d, J=8.2 Hz, 2H), 5.30 (d, J=4.6 Hz, 1H), 4.78 (s, 1H), 4.68 (s, 1H), 3.79-3.55 (m, 4H), 3.12-2.98 (m, 1H), 2.97-2.82 (m, 2H), 2.78 (td, J=10.9, 5.0 Hz, 1H), 2.71-2.61 (m, 3H), 2.60-2.54 (m, 1H), 2.52-2.44 (m, 1H), 2.40 (t, J=7.5 Hz, 2H), 2.19-1.80 (m, 6H), 1.75 (s, 3H), 1.73-1.04 (m, 18H), 1.23 (s, 3H), 1.11 (s, 3H), 1.05 (s, 3H), 0.99 (t, J=7.5 Hz, 3H), 0.97 (s, 3H), 0.97 (s, 3H).
Reaction SMILES: [Na].[CH3:2][CH:3]([SH:6])[CH2:4][CH3:5].Cl[C:8]1[C:16]2[NH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[N:13][C:12]=2[C:11]([N+:21]([O-:23])=[O:22])=[CH:10][C:9]=1[N+:24]([O-:26])=[O:25].O>C(O)C>[CH:3]([S:6][C:8]1[C:16]2[NH:15][C:14]([C:17]([F:19])([F:20])[F:18])=[N:13][C:12]=2[C:11]([N+:21]([O-:23])=[O:22])=[CH:10][C:9]=1[N+:24]([O-:26])=[O:25])([CH2:4][CH3:5])[CH3:2]
Reactant: CCC(C)S
Reactant: O=[N+]([O-])c1cc([N+](=O)[O-])c2nc(C(F)(F)F)[nH]c2c1Cl
Agent: [Na]
Solvent: CCO
Solvent: O
Product: CCC(C)Sc1c([N+](=O)[O-])cc([N+](=O)[O-])c2nc(C(F)(F)F)[nH]c12

Procedure:
In 200 milliliters of ethanol, 1 gram of sodium (0.04 mole) was reacted with 3.6 grams of 2-butanethiol (0.04 mole). The mixture was stirred for one-half hour. Then 4-chloro-5,7-dinitro-2-trifluoromethylbenzimidazole (6.2 grams; 0.02 mole) was added, and the resulting reaction mixture was stirred overnight, poured into water, acidified, and filtered to separate the desired 4-sec-butylthio-5,7-dinitro-2-trifluoromethylbenzimidazole. It was recrystallized twice from a mixture of benzene and an aliphatic hydrocarbon fraction boiling at 60°-80° C., m.p., 111°-15° C.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[S:11]([NH:14][C:15]2[CH:25]=[CH:24][C:18]([C:19]([O:21]CC)=[O:20])=[CH:17][CH:16]=2)(=[O:13])=[O:12])[CH:4]=[CH:3][CH:2]=1.[Li+].[OH-]>C1COCC1.O>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[S:11]([NH:14][C:15]2[CH:25]=[CH:24][C:18]([C:19]([OH:21])=[O:20])=[CH:17][CH:16]=2)(=[O:13])=[O:12])[CH:4]=[CH:3][CH:2]=1
Reactant: CCOC(=O)c1ccc(NS(=O)(=O)c2cccc3cccnc23)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)c1ccc(NS(=O)(=O)c2cccc3cccnc23)cc1
Temperature: 25 °C
Yield: 89.8 %

Procedure:
Ethyl 4-(quinoline-8-sulfonamido)benzoate (90, 10 g, 28.08 mmol) was dissolved in a mixture of THF-water (100:100 ml) and maintained at room temperature. To this solution was added LiOH (5.89 g, 14.0 mmol) and the resultant solution was refluxed overnight. The reaction mixture was then washed with ethyl acetate (3×50 ml) and then acidified with dilute HCl. The resultant suspension was filtered and residue was co-distilled with toluene. This product was then dried under vacuum to yield carboxylic acid 91 (8.28 g, 90%) as an off-white solid.