Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:14]=[C:13]([CH2:15][C:16]2[C:23]([F:24])=[CH:22][C:19]([C:20]#[N:21])=[CH:18][C:17]=2[F:25])[CH:12]=[CH:11][CH:10]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:36][Si:37]([CH3:46])([CH3:45])[C:38]#[C:39][C:40](OCC)=[O:41]>C1COCC1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:14]=[C:13]([CH:15]([C:16]2[C:23]([F:24])=[CH:22][C:19]([C:20]#[N:21])=[CH:18][C:17]=2[F:25])[C:40](=[O:41])[C:39]#[C:38][Si:37]([CH3:46])([CH3:45])[CH3:36])[CH:12]=[CH:11][CH:10]=1
Reactant: CCOC(=O)C#C[Si](C)(C)C
Reactant: N#Cc1cc(F)c(Cc2cccc(-c3ccc(F)cc3F)n2)c(F)c1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: C[Si](C)(C)C#CC(=O)C(c1cccc(-c2ccc(F)cc2F)n1)c1c(F)cc(C#N)cc1F
Temperature: -78 °C
Yield: 84.2 %

Procedure:
To a solution of 4-{[6-(2,4-difluorophenyl)pyridin-2-yl]methyl}-3,5-difluorobenzonitrile (from Step E above, 6.10 g, 17.83 mmol) in THF (200 mL) was added lithium bis(trimethylsilyl)amide (53.49 mL, 1.0 M in THF) at −78° C. After stirring 1¼ h at −78° C., ethyl 3-(trimethylsilyl)prop-2-ynoate (4.01 mL, 21.37 mmol) was added to the reaction mixture. The reaction continued to stir at −78° C. for 1 hr and was warmed to −20° C. until the reaction was complete via LMCS. The reaction was quenched with aqueous NH4Cl and extracted with EtOAc (3×). The combined organic layers were washed with 1N HCl (1×), water, brine, dried over MgSO4, and condensed. The crude material was purified via silica gel chromatography (hexanes/methylene chloride) to give the title compound (7.0 g).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[O:15][C:16]1[C:17]([F:24])=[CH:18][C:19]([F:23])=[C:20]([CH:22]=1)[NH2:21].[C:25]([C:29]1[CH:33]=[C:32]([NH:34][C:35](=O)[O:36]C2C=CC=CC=2)[N:31]([C:44]2[CH:49]=[CH:48][C:47]([CH3:50])=[CH:46][CH:45]=2)[N:30]=1)([CH3:28])([CH3:27])[CH3:26]>>[C:25]([C:29]1[CH:33]=[C:32]([NH:34][C:35]([NH:21][C:20]2[CH:22]=[C:16]([O:15][C:6]3[C:5]4[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=4)[N:9]=[CH:8][N:7]=3)[C:17]([F:24])=[CH:18][C:19]=2[F:23])=[O:36])[N:31]([C:44]2[CH:49]=[CH:48][C:47]([CH3:50])=[CH:46][CH:45]=2)[N:30]=1)([CH3:28])([CH3:27])[CH3:26]
Reactant: COc1cc2ncnc(Oc3cc(N)c(F)cc3F)c2cc1OC
Reactant: Cc1ccc(-n2nc(C(C)(C)C)cc2NC(=O)Oc2ccccc2)cc1
Product: COc1cc2ncnc(Oc3cc(NC(=O)Nc4cc(C(C)(C)C)nn4-c4ccc(C)cc4)c(F)cc3F)c2cc1OC
Yield: 96.7 %

Procedure:
The title compound was prepared from 5-(6,7-dimethoxyquinazolin-4-yloxy)-2,4-difluoroaniline (100 mg, 0.3 mmol) and phenyl 3-tert-butyl-1-p-tolyl-1H-pyrazol-5-ylcarbamate (140 mg, 0.4 mmol) using the procedure in Example 115C to give 1-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)-3-(5-(6,7-dimethoxyquinazolin-4-yloxy)-2,4-difluorophenyl)urea (170 mg, 0.29 mmol, 96%). 1H NMR (300 MHz, DMSO-d6) δ 9.15 (s, 1H), 8.86 (s, 1H), 8.58 (s, 1H), 8.22 (t, 1H), 7.61 (t, 1H), 7.58 (s, 1H), 7.42-7.34 (m, 5H), 6.35 (s, 1H), 4.01 (s, 3H), 4.00 (s, 3H), 2.39 (s, 3H), 1.28 (s, 9H); LC-MS (ESI) m/z 589 (M+H)+.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[C:9]1[O:13][C:12]([NH2:14])=[N:11][N:10]=1.C([O-])([O-])=O.[K+].[K+].Br.Br[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=1>C(#N)C>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[C:9]1[O:13][C:12]([NH:14][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=2)=[N:11][N:10]=1
Reactant: BrCc1ccccn1
Reactant: Cc1ccc(-c2nnc(N)o2)c(C)c1
Agent: Br
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: Cc1ccc(-c2nnc(NCc3ccccn3)o2)c(C)c1
Temperature: 90 °C
Reaction time: 8 h
Yield: 97 %

Procedure:
To a solution of 5-(2,4-dimethylphenyl)-1,3,4-oxadiazol-2-amine (Example 16a) (94.5 mg, 0.5 mmol) in 5 ml of dry acetonitrile was added K2CO3 (207 mg, 1.5 mmol). To the suspension was added 2-(bromomethyl)pyridine hydrobromide (127 mg, 0.5 mmol) and the mixture was stirred at 90° C. overnight. The solvent was removed under vacuum and the solid was dissolved in EtOAc, washed successively with aq. NaHCO3 and brine, dried over MgSO4 filtered and evaporated. The residue was purified on silica gel to give 5-(2,4-Dimethylphenyl)-N-(pyridin-2-ylmethyl)-1,3,4-oxadiazol-2-amine (136 mg, 97%) as a white solid. 1H NMR (300 MHz, CdCl3): δ 2.34 (s, 3H), 2.5 (s, 3H), 5.1 (s, 2H), 7.07-7.08 (m, 2H), 7.21-7.33 (m, 2H), 7.64-7.68 (m, 2H), 8.59-8.60 (d, 1H); MS (M+H, 281).
Reaction SMILES: [F:1][C:2]1([F:20])[CH2:5][N:4]([C:6]2[CH:7]=[CH:8][C:9]([C:17]([OH:19])=O)=[N:10][C:11]=2[O:12][CH2:13][CH2:14][O:15][CH3:16])[CH2:3]1.[NH2:21][C@@H:22]([CH2:26][CH:27]([CH3:29])[CH3:28])[C:23]([NH2:25])=[O:24]>>[C:23]([C@@H:22]([NH:21][C:17]([C:9]1[CH:8]=[CH:7][C:6]([N:4]2[CH2:3][C:2]([F:1])([F:20])[CH2:5]2)=[C:11]([O:12][CH2:13][CH2:14][O:15][CH3:16])[N:10]=1)=[O:19])[CH2:26][CH:27]([CH3:29])[CH3:28])(=[O:24])[NH2:25]
Reactant: CC(C)C[C@H](N)C(N)=O
Reactant: COCCOc1nc(C(=O)O)ccc1N1CC(F)(F)C1
Product: COCCOc1nc(C(=O)N[C@@H](CC(C)C)C(N)=O)ccc1N1CC(F)(F)C1

Procedure:
The title compound was synthesized in analogy to Example 1, using 5-(3,3-difluoro-azetidin-1-yl)-6-(2-methoxy-ethoxy)-pyridine-2-carboxylic acid and (2S)-2-amino-4-methyl-pentanamide (CAN 687-51-4) as starting materials, MS (EI): m/e=401.1 [M+H]+.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][C:5]([CH2:6][CH2:7]O)=[CH:4][CH:3]=1.C1(C)C=CC(S(Cl)(=O)=O)=CC=1.[CH2:22]([N:24](CC)[CH2:25][CH3:26])[CH3:23].Cl.N1CCCC1>ClCCl>[Br:1][C:2]1[CH:10]=[CH:9][C:5]([CH2:6][CH2:7][N:24]2[CH2:25][CH2:26][CH2:23][CH2:22]2)=[CH:4][CH:3]=1
Reactant: CCN(CC)CC
Reactant: OCCc1ccc(Br)cc1
Agent: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: Cl
Solvent: C1CCNC1
Solvent: ClCCl
Product: Brc1ccc(CCN2CCCC2)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 80 %

Procedure:
To a solution of 4-bromophenethyl alcohol (2.54 mmol) and p-toluenesulfonyl chloride (2.74 mmol) in anhydrous dichloromethane (5 mL) under nitrogen was added triethylamine (2.74 mmol) dropwise by syringe at room temperature. The reaction was stirred for 16 hours at room temperature. A white precipitate formed. 1N HCl solution (5 mL) was added to the suspension and the reaction became clear. The layers were separated and the organic layer was washed with saturated aqueous sodium bicarbonate solution (5 mL), dried over magnesium sulfate and concentrated in vacuo to give a white solid. To this crude product was added pyrrolidine (1 mL) under nitrogen and the reaction was stirred at 50° C. for 90 minutes. The reaction was cooled to room temperature and concentrated in vacuo. The resulting residue was dissolved in ethyl acetate (20 mL) and washed successively with water (20 mL) and saturated aqueous sodium bicarbonate solution (20 mL), dried over magnesium sulfate and concentrated in vacuo. Purification by silica gel chromatography (20-100% ethyl acetate/hexanes) afforded the title compound as a white solid (80%). ESMS [M+H]+: 254.2.
Reaction SMILES: [C:1]([O:4][CH2:5][C:6]1[C:11]([N:12]2[CH2:24][CH2:23][N:15]3[C:16]4[CH2:17][CH2:18][CH2:19][CH2:20][C:21]=4[CH:22]=[C:14]3[C:13]2=[O:25])=[CH:10][C:9]([F:26])=[CH:8][C:7]=1N1CCN2C3CCCCC=3C=C2C1=O)(=[O:3])[CH3:2].[N:41]1([CH2:45][C:46]2[N:50]([CH3:51])[N:49]=[C:48]([NH:52][C:53]3[C:54](=[O:61])[N:55]([CH3:60])[CH:56]=[C:57](Br)[CH:58]=3)[CH:47]=2)[CH2:44][CH2:43][CH2:42]1.C(=O)([O-])[O-].[Na+].[Na+]>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.COCCOC>[C:1]([O:4][CH2:5][C:6]1[C:11]([N:12]2[CH2:24][CH2:23][N:15]3[C:16]4[CH2:17][CH2:18][CH2:19][CH2:20][C:21]=4[CH:22]=[C:14]3[C:13]2=[O:25])=[CH:10][C:9]([F:26])=[CH:8][C:7]=1[C:57]1[CH:58]=[C:53]([NH:52][C:48]2[CH:47]=[C:46]([CH2:45][N:41]3[CH2:44][CH2:43][CH2:42]3)[N:50]([CH3:51])[N:49]=2)[C:54](=[O:61])[N:55]([CH3:60])[CH:56]=1)(=[O:3])[CH3:2]
Reactant: Cn1nc(Nc2cc(Br)cn(C)c2=O)cc1CN1CCC1
Reactant: CC(=O)OCc1c(N2CCn3c(cc4c3CCCC4)C2=O)cc(F)cc1N1CCn2c(cc3c2CCCC3)C1=O
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: COCCOC
Product: CC(=O)OCc1c(-c2cc(Nc3cc(CN4CCC4)n(C)n3)c(=O)n(C)c2)cc(F)cc1N1CCn2c(cc3c2CCCC3)C1=O
Temperature: 130 °C
Yield: 95.6 %

Procedure:
Following Example 121b, 4-fluoro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate 210d (202 mg, 0.42 mmol), 3-(5-(azetidin-1-ylmethyl)-1-methyl-1H-pyrazol-3-ylamino)-5-bromo-1-methylpyridin-2(1H)-one 200c (105 mg, 0.3 mmol), 1M sodium carbonate solution (1.2 mL, 1.2 mmol), tetrakis(triphenylphosphine)palladium(0) (18 mg, 0.015 mmol) and 1,2-Dimethoxyethane (3 mL) were heated at 130° C. for 10 minutes in the microwave reactor. Work-up and the resulting residue was purified by flash column chromatography (silica, 3:1 methylene chloride/methanol) to give 180 mg compound 200d (quant., contain 3% 200) as a yellow residue: MS (ESI+) m/z 628.1 (M+H).
Reaction SMILES: [CH2:1]([OH:7])[C:2]1[O:6][CH:5]=[CH:4][CH:3]=1.[Na].[CH:9]([Si:11](Cl)(Cl)Cl)=[CH2:10]>C1(C)C=CC=CC=1>[CH:9]([Si:11]([O:7][CH2:1][C:2]1[O:6][CH:5]=[CH:4][CH:3]=1)([O:7][CH2:1][C:2]1[O:6][CH:5]=[CH:4][CH:3]=1)[O:7][CH2:1][C:2]1[O:6][CH:5]=[CH:4][CH:3]=1)=[CH2:10]
Reactant: OCc1ccco1
Reactant: C=C[Si](Cl)(Cl)Cl
Agent: [Na]
Solvent: Cc1ccccc1
Product: C=C[Si](OCc1ccco1)(OCc1ccco1)OCc1ccco1
Temperature: 100 °C

Procedure:
To a solution of 86.5 ml. furfuryl alcohol in 200 ml. toluene was slowly added 23 g. sodium metal. An additional 10 ml. furfuryl alcohol was added and the solution was heated to 100° C. with stirring to convert all the sodium. The solution was cooled to ice temperature and 43.5 ml. vinyltrichlorosilane dissolved in 50 ml. toluene was slowly added. After the addition was complete, the mixture was heated at 95° C. for 0.5 hr. The colloidal sodium chloride by-product was extracted with water. The organic phase was filtered and the toluene removed by vacuum evaporation. The residue was distilled at 2 mmHg and the product recovered at 182°-184° C.
Reaction SMILES: [F:1][C:2]1[CH:8]=[C:7]([S:9][C:10]([F:15])([F:14])[CH:11]([F:13])[F:12])[CH:6]=[CH:5][C:3]=1[NH2:4].[F:16][C:17]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:18]=1[C:19]([N:21]=[C:22]=[O:23])=[O:20]>C1(C)C=CC=CC=1>[F:16][C:17]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:18]=1[C:19]([NH:21][C:22]([NH:4][C:3]1[CH:5]=[CH:6][C:7]([S:9][C:10]([F:15])([F:14])[CH:11]([F:12])[F:13])=[CH:8][C:2]=1[F:1])=[O:23])=[O:20]
Reactant: O=C=NC(=O)c1c(F)cccc1F
Reactant: Nc1ccc(SC(F)(F)C(F)F)cc1F
Solvent: Cc1ccccc1
Product: O=C(NC(=O)c1c(F)cccc1F)Nc1ccc(SC(F)(F)C(F)F)cc1F
Reaction time: 0.5 h
Yield: 85.6 %

Procedure:
In 20 ml of toluene was dissolved 1.0 g of 2-fluoro-4-(1,1,2,2-tetrafluoroethylthio)aniline, and 0.8 g of 2,6-difluorobenzoyl isocyanate was added dropwise to the solution at room temperature (20° to 25° C.). After the reaction was allowed to proceed at the same temperature for 30 minutes, the crystals, which separated out, were recovered by filtration and washed with toluene to give 1.5 g of N-(2,6-difluorobenzoyl)-N'-[2-fluoro-4-(1,1,2,2-tetrafluoro-ethylthio)phenyl]urea (Compound No. 1), m.p. of 177°-179° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9](=O)[CH2:10][C:11]#[N:12])=[CH:4][CH:3]=1.C(N(CC)CC)C.Cl.[C:22]([NH:26][NH2:27])([CH3:25])([CH3:24])[CH3:23]>C(O)C>[C:22]([N:26]1[C:11]([NH2:12])=[CH:10][C:9]([CH2:8][C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)=[N:27]1)([CH3:25])([CH3:24])[CH3:23]
Reactant: N#CCC(=O)Cc1ccc(Cl)cc1
Reactant: CC(C)(C)NN
Agent: Cl
Solvent: CCO
Solvent: CCN(CC)CC
Product: CC(C)(C)n1nc(Cc2ccc(Cl)cc2)cc1N
Temperature: 25 °C
Reaction time: 96 h
Yield: 115.6 %

Procedure:
A solution of 4-(4-chloro-phenyl)-3-oxo-butyronitrile (500 mg, 2 mmol, 1.0 equiv), triethylamine (1.16 mL, 8.3 mmol, 3.2 equiv), and tert-butylhydrazine hydrochloride (1.03 g, 8.3 mmol, 3.2 equiv) in 10 mL of ethanol was heated at 100° C. in a sealed tube. After 4 d, the reaction mixture was cooled to ambient temperature and concentrated in vacuo. The residue was purified via automated flash chromatography (40 g SiO2, gradient from hexanes to ethyl acetate) to afford the product as a yellow oil (610 mg, 70%).
Reaction SMILES: [Cl:1][C:2]1[N:11]=[CH:10][C:9]2[NH:8][C:7](=[O:12])[C@H:6]([CH2:13][CH3:14])[N:5]([CH:15]([CH3:17])[CH3:16])[C:4]=2[N:3]=1.[C:18]1(C)C=CC(S(OC)(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH3:18])[C:7](=[O:12])[C@H:6]([CH2:13][CH3:14])[N:5]([CH:15]([CH3:16])[CH3:17])[C:4]=2[N:3]=1
Reactant: CC[C@H]1C(=O)Nc2cnc(Cl)nc2N1C(C)C
Reactant: COS(=O)(=O)c1ccc(C)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CC[C@H]1C(=O)N(C)c2cnc(Cl)nc2N1C(C)C
Reaction time: 12 h
Yield: 81 %

Procedure:
The crude compound (7S)-2-chloro-8-isopropyl-7-ethyl-5,7-dihydropteridin-6-one 43c (7.17 g, 28.21 mmol), methyl p-toluenesulfonate (5.77 g, 31.03 mmol) and potassium carbonate (11.70 g, 84.60 mmol) were dissolved in 40 mL of acetone. The reaction solution was stirred for 12 hours and the precipite was filtered. The filter cake was washed with dichloromethane (100 mL). The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography with elution system B to obtain (7S)-2-chloro-8-isopropyl-7-ethyl-5-methyl-7H-pteridin-6-one 43d (6.14 g, yield: 81.0%) as a white solid.
Reaction SMILES: FC1C=CC(C[N:7]2C(=O)N(C3SC(C(O)=O)=C(C)N=3)C=N2)=CC=1.[CH3:24][C:25]1[N:26]=[C:27]([N:33]2[CH2:37][CH2:36][N:35]([CH2:38][C:39]3[CH:44]=[CH:43][C:42]([C:45]([F:48])([F:47])[F:46])=[CH:41][CH:40]=3)[C:34]2=[O:49])[S:28][C:29]=1[C:30](O)=[O:31]>>[CH3:24][C:25]1[N:26]=[C:27]([N:33]2[CH2:37][CH2:36][N:35]([CH2:38][C:39]3[CH:40]=[CH:41][C:42]([C:45]([F:47])([F:46])[F:48])=[CH:43][CH:44]=3)[C:34]2=[O:49])[S:28][C:29]=1[C:30]([NH2:7])=[O:31]
Reactant: Cc1nc(N2CCN(Cc3ccc(C(F)(F)F)cc3)C2=O)sc1C(=O)O
Reactant: Cc1nc(-n2cnn(Cc3ccc(F)cc3)c2=O)sc1C(=O)O
Product: Cc1nc(N2CCN(Cc3ccc(C(F)(F)F)cc3)C2=O)sc1C(N)=O
Yield: 23 %

Procedure:
Following the procedure as described in EXAMPLE 1, making variations as required to replace 2-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methylthiazole-5-carboxylic acid with 4-methyl-2-(2-oxo-3-(4-(trifluoromethyl)benzyl)-imidazolidin-1-yl)thiazole-5-carboxylic acid, the title compound was obtained as a colorless solid in 23% yield: mp 216-217° C. (hexanes/ethyl acetate); 1H NMR (300 MHz, DMSO-d6) δ 7.74 (d, J=8.2 Hz, 2H), 7.55 (d, J=8.2 Hz, 2H), 7.32 (s, 2H), 4.54 (s, 2H), 4.02 (dd, J=9.0, 7.3 Hz, 2H), 3.49 (dd, J=9.0, 7.3 Hz, 2H), 2.46 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 163.5, 157.4, 155.2, 150.7, 141.5 (d, JC-F=1.2 Hz), 128.5, 128.1 (q, 2JC-F=31.6 Hz), 125.5 (q, 3JC-F=3.8 Hz), 124.3 (q, 1JC-F=272.2 Hz), 118.5, 46.5, 42.0, 41.8, 17.0; MS (ES+) m/z 384.9 (M+1).
Reaction SMILES: [C:1]1([CH3:30])[CH:6]=[CH:5][C:4]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:27]=[CH:26][C:17]([NH:18][C:19]4[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=4)=[C:16]([CH3:28])[CH:15]=3)=[CH:10][C:9]=2[CH3:29])=[CH:3][CH:2]=1.[CH2:31]([C:33]1[CH:38]=[CH:37][C:36]([C:39]2[CH:44]=[CH:43][C:42](I)=[CH:41][CH:40]=2)=[CH:35][CH:34]=1)[CH3:32]>>[C:1]1([CH3:30])[CH:2]=[CH:3][C:4]([N:7]([C:42]2[CH:43]=[CH:44][C:39]([C:36]3[CH:37]=[CH:38][C:33]([CH2:31][CH3:32])=[CH:34][CH:35]=3)=[CH:40][CH:41]=2)[C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:27]=[CH:26][C:17]([N:18]([C:4]4[CH:5]=[CH:6][C:1]([CH3:30])=[CH:2][CH:3]=4)[C:19]4[CH:24]=[CH:23][C:22]([C:25]5[CH:13]=[CH:12][C:11]([CH2:14][CH3:15])=[CH:10][CH:9]=5)=[CH:21][CH:20]=4)=[C:16]([CH3:28])[CH:15]=3)=[CH:10][C:9]=2[CH3:29])=[CH:5][CH:6]=1
Reactant: CCc1ccc(-c2ccc(I)cc2)cc1
Reactant: Cc1ccc(Nc2ccc(-c3ccc(Nc4ccc(C)cc4)c(C)c3)cc2C)cc1
Product: CCc1ccc(-c2ccc(N(c3ccc(C)cc3)c3ccc(-c4ccc(N(c5ccc(C)cc5)c5ccc(-c6ccc(CC)cc6)cc5)c(C)c4)cc3C)cc2)cc1
Yield: 23.7 %

Procedure:
According to the same manner as that described in Synthesis Example 1, 14.9 g of N,N'-diacetyl-3,3'-dimethylbenzidine was reacted with 21.8 g of para-iodobenzene to give N,N'-di-p-tolyl-3,3'-dimethylbenzidine. Further, 12.0 g of N,N'-di-p-tolyl-3,3'-dimethylbenzidine was reacted with 15.4 g of 4-ethyl-4'-iodobiphenyl according to the same manner as that described in Synthesis Example 1 to give N,N'-di-p-tolyl-N,N'-di(4'-ethylbiphenyl-4-yl)-3,3'-dimethylbenzidine (hereinafter referred to as 6-c) (8.82 g, yield: 23.7%).
Reaction SMILES: [O:1]=[C:2]([C:9]1[CH:14]=[CH:13][C:12]([O:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:11][CH:10]=1)[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].[H-].[Na+].[F:24][C:25]([F:35])([F:34])[C:26]1[CH:33]=[CH:32][C:29]([CH2:30]Br)=[CH:28][CH:27]=1.O>COCCOC>[O:1]=[C:2]([C:9]1[CH:14]=[CH:13][C:12]([O:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:11][CH:10]=1)[CH:3]([CH2:30][C:29]1[CH:28]=[CH:27][C:26]([C:25]([F:24])([F:34])[F:35])=[CH:33][CH:32]=1)[C:4]([O:6][CH2:7][CH3:8])=[O:5]
Reactant: CCOC(=O)CC(=O)c1ccc(Oc2ccccc2)cc1
Reactant: FC(F)(F)c1ccc(CBr)cc1
Agent: [H-]
Agent: [Na+]
Solvent: COCCOC
Solvent: O
Product: CCOC(=O)C(Cc1ccc(C(F)(F)F)cc1)C(=O)c1ccc(Oc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 75 %

Procedure:
To a solution of ethyl 3-oxo-3-(4-phenoxyphenyl)propionate (12 g, 42.2 mmol) in 1,2-dimethoxyethane (80 ml) was added sodium hydride (60% in oil, 1.69 g, 42.2 mmol) under ice-cooling, and the mixture was stirred at room temperature for 30 min. To the reaction solution was dropwise added a solution of 4-trifluoromethylbenzyl bromide (10.1 g, 42.2 mmol) in 1,2-dimethoxyethane (50 ml), and the reaction solution was stirred at room temperature for 4 hrs. The reaction solution was poured into water (200 ml), and extracted with ethyl acetate (200 ml×2). The extract was washed with water and saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was recrystallized from ethyl acetate-hexane to give ethyl 3-oxo-3-(4-phenoxyphenyl)-2-((4-(trifluoromethyl)phenyl)methyl)propionate (14.0 g, 75%).
Reaction SMILES: [K].[Cl:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[C:8]([OH:13])[CH:7]=[CH:6]2.F[C:15]1[CH:16]=[CH:17][C:18]([N+:24]([O-:26])=[O:25])=[C:19]([CH:23]=1)[C:20]([O-:22])=[O:21].Cl>CS(C)=O.O>[Cl:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[C:8]([O:13][C:15]1[CH:16]=[CH:17][C:18]([N+:24]([O-:26])=[O:25])=[C:19]([CH:23]=1)[C:20]([OH:22])=[O:21])[CH:7]=[CH:6]2
Reactant: O=C([O-])c1cc(F)ccc1[N+](=O)[O-]
Reactant: Oc1ccc2cc(Cl)ccc2n1
Agent: Cl
Agent: [K]
Solvent: O
Solvent: CS(C)=O
Product: O=C(O)c1cc(Oc2ccc3cc(Cl)ccc3n2)ccc1[N+](=O)[O-]
Temperature: 100 °C
Reaction time: 16 h

Procedure:
A reactor is charged with 4.34 grams (0.02 mole) of the potassium salt of 6-chloro-2-hydroxyquinoline (Formula II Compound) in 25 milliliters of dimethylsulfoxide. To this mixture is added 4.46 grams (0.02 mole) of the potassium salt of 5-fluoro-2-nitrobenzoate (Formula III Compound). After stirring at about 100° C. for about 16 hours, the reaction mixture is poured into 200 milliliters of water and acidified with concentrated hydrochloric acid. Filtration and air drying affords 5-(6-chloro-2-quinolinoxy)-2-nitrobenzoic acid (Formula IV Compound).
Reaction SMILES: C1CO[CH:20]2[CH:3]([CH2:4][C:5]3[C@H:18]([CH2:19]2)[C@@H:17]2[C@H:8]([C@H:9]4[C@@:13]([CH2:15][C@@H:16]2[F:23])([CH3:14])[C@@H:12]([OH:24])[CH2:11][CH2:10]4)[C@H:7]([CH3:25])[CH:6]=3)[O:2]1.C(O)(=O)C(O)=O.O.C(=O)(O)[O-].[Na+]>CO>[F:23][C@H:16]1[CH2:15][C@@:13]2([CH3:14])[C@@H:9]([CH2:10][CH2:11][C@@H:12]2[OH:24])[C@H:8]2[C@H:17]1[C:18]1[CH2:19][CH2:20][C:3](=[O:2])[CH2:4][C:5]=1[CH2:6][C@H:7]2[CH3:25]
Reactant: C[C@@H]1C=C2CC3OCCOC3C[C@@H]2[C@@H]2[C@@H]1[C@@H]1CC[C@H](O)[C@@]1(C)C[C@@H]2F
Agent: O=C(O)C(=O)O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: O
Product: C[C@@H]1CC2=C(CCC(=O)C2)[C@@H]2[C@@H]1[C@@H]1CC[C@H](O)[C@@]1(C)C[C@@H]2F
Yield: 42.2 %

Procedure:
A solution of 170 mg of product (C), obtained under 3a), in 22.5 ml of methanol was stirred with 300 mg of oxalic acid and 3 ml of water for 24 hours at room temperature. Then, it was mixed with sodium bicarbonate solution, extracted three times with ethyl acetate, washed neutral, dried on sodium sulfate, concentrated by evaporation in a vacuum and chromatographed on silica gel with hexane/ethyl acetate. 62.7 mg of pure 11β-fluoro-17β-hydroxy-7α-methyl-estr-5(10)-en-3-one (I″) was obtained. Crystallization from hexane yielded 47.6 mg of compound I″ with a melting point of 169.9° C. ([α]D20=+134.4° (c=0.56% chloroform)).
Reaction SMILES: C([O:5][C:6](=[O:30])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[N:18]3[CH:19]=[CH:20][C:21]([C:23]4[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=4)=[CH:22][C:17]3=[N:16][CH:15]=2)=[CH:10][C:9]=1[F:29])(C)(C)C.[ClH:31]>O.O1CCOCC1>[ClH:31].[ClH:31].[F:29][C:9]1[CH:10]=[C:11]([C:14]2[N:18]3[CH:19]=[CH:20][C:21]([C:23]4[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=4)=[CH:22][C:17]3=[N:16][CH:15]=2)[CH:12]=[CH:13][C:8]=1[CH2:7][C:6]([OH:30])=[O:5]
Reactant: CC(C)(C)OC(=O)Cc1ccc(-c2cnc3cc(-c4ccncc4)ccn23)cc1F
Agent: Cl
Solvent: C1COCCO1
Solvent: O
Product: O=C(O)Cc1ccc(-c2cnc3cc(-c4ccncc4)ccn23)cc1F
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Suspend [2-fluoro-4-(7-pyridin-4-yl-imidazo[1,2-a]pyridin-3-yl)-phenyl]-acetic acid tert-butyl ester (1.36 g, 3.369 mmol) in water (8 mL) and 4N hydrochloric acid in dioxane (40 mL) and stir at ambient temperature for 3 hours. Concentration under vacuum quantitatively provides the title compound (1.42 g, 3.69 mmol). MS(ES), m/z 348 (M+1).
Reaction SMILES: [C:1]([O-:17])(=[O:16])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]([O-:15])=[O:14].[K+].[K+].[C:20]([O-])(=O)[CH2:21]CCCCCCCCCCCCCCCC.[Al+3].C([O-])(=O)CCCCCCCCCCCCCCCCC.C([O-])(=O)CCCCCCCCCCCCCCCCC>>[C:1]1(=[O:17])[O:16][CH2:21][CH2:20][O:15][C:13](=[O:14])[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=C([O-])CCCCCCCCCCCC(=O)[O-]
Reactant: CCCCCCCCCCCCCCCCCC(=O)[O-]
Agent: [Al+3]
Agent: [K+]
Product: O=C1CCCCCCCCCCCC(=O)OCCO1
Yield: 81.6 %

Procedure:
A mixed metal catalyst comprised of potassium brassylate and aluminum stearate (1:1 molar ratio of K:Al) was employed for the depolymerization of poly(ethylene brassylate) at a 1.8 weight percent level. An 81.6 percent yield of ethylene brassylate was obtained. Comparable yields are obtained when this mixed metal catalyst is used for the depolymerization of poly(ethylene sebacate) and poly(3-oxa-pentamethylene azelate).