Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([O:17]C)=[O:16])=[CH:11][C:10]=2[CH3:19])=[CH:5][C:4]=1[C:20]1[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][C:21]=1[CH2:30][N:31]1[C@@H:35]([CH3:36])[C@@H:34]([C:37]2[CH:42]=[CH:41][N:40]=[C:39]([CH3:43])[CH:38]=2)[O:33][C:32]1=[O:44].[Li+].[OH-].Cl>O1CCOCC1.O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([OH:17])=[O:16])=[CH:11][C:10]=2[CH3:19])=[CH:5][C:4]=1[C:20]1[CH:25]=[CH:24][C:23]([C:26]([F:28])([F:29])[F:27])=[CH:22][C:21]=1[CH2:30][N:31]1[C@@H:35]([CH3:36])[C@@H:34]([C:37]2[CH:42]=[CH:41][N:40]=[C:39]([CH3:43])[CH:38]=2)[O:33][C:32]1=[O:44]
Reactant: COC(=O)c1ccc(-c2ccc(OC)c(-c3ccc(C(F)(F)F)cc3CN3C(=O)O[C@H](c4ccnc(C)c4)[C@@H]3C)c2)c(C)c1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: COc1ccc(-c2ccc(C(=O)O)cc2C)cc1-c1ccc(C(F)(F)F)cc1CN1C(=O)O[C@H](c2ccnc(C)c2)[C@@H]1C
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of methyl 4′-methoxy-2-methyl-2″-{[(4S,5R)-4-methyl-5-(2-methylpyridin-4-yl)-2-oxo-1,3-oxazolidin-3-yl]methyl}-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate (30.1 mg, 0.050 mmol) in 1,4-dioxane (1.5 mL) and water (1.5 mL) was added 1M aqueous LiOH (0.498 mL, 0.498 mmol). The mixture was stirred at room temperature for 4 h. The mixture was acidified with 1N HCl. The aqueous layer was extracted with EtOAc (3×). The combined organic layers were dried (Na2SO4), filtered and the solvent was evaporated in vacuo. The crude material was purified by preparative HPLC reverse phase (C-18), eluting with MeCN/water. The fractions were collected and lyophilized to give 4′-methoxy-2-methyl-2″-{[(4S,5R)-4-methyl-5-(2-methylpyridin-4-yl)-2-oxo-1,3-oxazolidin-3-yl]methyl}-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylic acid. LCMS calc.=591.2; found=591.1 (M+1)+. 1H NMR (500 MHz, CDCl3, 1:1 mixture of atropisomers) δ 8.83 (s, 1H); 8.02 (s, 1H); 7.94 (t, J=10.0 Hz, 1H); 7.72 (s, 0.5H); 7.69 (t, J=6.0 Hz, 1H); 7.64 (s, 0.5H); 7.49-7.43 (m, 3H); 7.40 (d, J=5.2 Hz, 0.5H); 7.35 (d, J=5.4 Hz, 0.5H); 7.31 (m, 1H); 7.16 (dd, J=2.1, 6.0 Hz, 1H); 7.12 (t, J=8.8 Hz, 1H); 5.56 (d, J=8.1 Hz, 0.5H); 5.26 (d, J=8.2 Hz, 0.5H); 4.94 (dd, J=8.7, 15.7 Hz, 1H); 4.77 (br s, 1H); 4.20 (d, J=15.8 Hz, 0.5H); 4.00 (d, J=15.7 Hz, 0.5H); 3.90 (s, 1.5H); 3.89 (s, 1.5H); 3.89-3.81 (m, 1H); 2.82 (s, 1.5H); 2.81 (s, 1.5H); 2.41 (s, 1.5H); 2.36 (s, 1.5H); 0.62 (d, J=6.5 Hz, 1.5H); 0.49 (d, J=6.5 Hz, 1.5H).
Reaction SMILES: C([C:5](C)=[O:6])C(C)C.[C:8]1([CH3:14])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>>[CH2:8]([CH:13]([CH2:12][CH2:11][CH2:10][CH3:9])[CH2:5][OH:6])[CH3:14]
Reactant: CC(=O)CC(C)C
Reactant: Cc1ccccc1
Product: CCCCC(CC)CO
Yield: 0 %

Procedure:
A similar four-necked flask was charged with 120 g of the allyl group-bearing epoxy resin produced above, 100 g of methyl isobutyl ketone, 200 g of toluene and 0.04 g of a 2-ethylhexanol-modified chloroplatinic acid solution having a platinum concentration of 2%. After one hour of azeotroping off water, 80 g of an organopolysiloxane blocked with hydrogen atoms at both ends represented by the following formula (7) was added dropwise over 30 minutes at the reflux temperature. Stirring was continued at the temperature for a further 4 hours for reaction. The resulting contents were washed with water and the solvent was distilled off in vacuum. The reaction product was a silicone-modified epoxy resin of the above formula (6) serving as Silicone stress-reducing agent 2.
Reaction SMILES: C(N[C:5]1[C:6]([N+:16]([O-:18])=[O:17])=[C:7]([C:11]([Cl:15])=[CH:12][C:13]=1[Cl:14])[C:8]([OH:10])=[O:9])(=O)C.[OH-:19].[K+].Cl>O.C(OCC)(=O)C>[Cl:14][C:13]1[CH:12]=[C:11]([Cl:15])[C:7]([C:8]([OH:10])=[O:9])=[C:6]([N+:16]([O-:18])=[O:17])[C:5]=1[OH:19]
Reactant: CC(=O)Nc1c(Cl)cc(Cl)c(C(=O)O)c1[N+](=O)[O-]
Reactant: [OH-]
Agent: Cl
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: O
Product: O=C(O)c1c(Cl)cc(Cl)c(O)c1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 89 %

Procedure:
3-Acetamido-4,6-dichloro-2-nitrobenzoic acid (1-5) (9.7 g, 0.033 mol) was added to a solution of KOH (18.7 g, 0.034 mol) in H2O (85 mL). The solution was heated under reflux for 18 h and cool to room temperature. Conc HCl was added to adjust the pH to 0. The mixture was diluted with ethyl acetate and H2O and left to stir at room temperature for 30 min. The layers were separated; the aqueous layer was extracted with ethyl acetate (3×), the extracts combined with the original organic layer, washed with brine, dried and concentrated to yield 4,6-dichloro-3-hydroxy-2-nitrobenzoic acid (1-6) as a dark red solid (7.4 g, 89%); m.p. 188-189° C. (lit.4 m.p. 186° C. (dec)).
Reaction SMILES: [NH2:1][CH2:2][C:3]1[NH:4][C:5](=[O:13])[C:6]2[CH:12]=[CH:11][CH:10]=[N:9][C:7]=2[N:8]=1.CCN(C(C)C)C(C)C.[F:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[CH2:30][CH2:31][S:32](Cl)(=[O:34])=[O:33]>C(Cl)Cl>[O:13]=[C:5]1[NH:4][C:3]([CH2:2][NH:1][S:32]([CH2:31][CH2:30][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[F:23])(=[O:33])=[O:34])=[N:8][C:7]2[N:9]=[CH:10][CH:11]=[CH:12][C:6]1=2
Reactant: NCc1nc2ncccc2c(=O)[nH]1
Reactant: O=S(=O)(Cl)CCc1ccccc1F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: O=c1[nH]c(CNS(=O)(=O)CCc2ccccc2F)nc2ncccc12
Temperature: 0 °C
Reaction time: 3 h
Yield: 12.1 %

Procedure:
To an ice cooled suspension of 2-aminomethyl-3H-pyrido[2,3-d]pyrimidin-4-one (example 84.3; 50 mg, 0.28 mmol) in CH2Cl2 (2 ml) were added DIPEA (0.10 ml, 0.58 mmol) and 2-(2-fluoro-phenyl)-ethanesulfonyl chloride (78 mg, 0.35 mmol). The reaction mixture was stirred for 3 hours at 0° C. Unreacted 2-aminomethyl-3H-pyrido[2,3-d]pyrimidin-4-one was filtered off, the filtrate was evaporated to dryness and chromatographed (silica gel, EtOAc) to yield 2-(2-fluoro-phenyl)-ethanesulfonic acid (4-oxo-3,4-dihydro-pyrido[2,3-d]pyrimidin-2-ylmethyl)-amide (12 mg, 0.034 mmol; 12%) as a white solid. MS (m/e): 363.1 [M+H+].
Reaction SMILES: [CH2:1]([OH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:9](Cl)(=[O:20])[O:10][C:11]1[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][CH:12]=1>N1C=CC=CC=1>[C:9](=[O:20])([O:10][C:11]1[CH:12]=[CH:13][C:14]([N+:17]([O-:19])=[O:18])=[CH:15][CH:16]=1)[O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OCc1ccccc1
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Solvent: c1ccncc1
Product: O=C(OCc1ccccc1)Oc1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Benzyl alcohol was treated with phosgene or similar reagents, such as diphosgene or triphosgene, in the presence of a base, such as DIEA, at 0° C. for 30 min. The solvent was then removed via vacuum and the resulting intermediate carbonochloridate was dissolved in an organic solvent, such as DCM or EtOAc, and then treated with amine in the presence of base, such as Hunig's base or aqueous Na2CO3, to provide the desired carbamate. If required, hydrolysis under a basic condition, such as aqueous LiOH, was used to convert the carbamate to the final product. Alternatively, the benzyl alcohol was treated with 4-nitrophenyl carbonochloridate in the presence of base, such as pyridine, at 0° C. The reaction mixture was slowly warmed to room temperature where it was stirred overnight. After this time, the reaction was quenched with water. The organic layer washed with water and brine, dried over MgSO4 and concentrated in vacuum to provide the crude material. The crude material was purified by silica gel flash chromatography to afford the corresponding benzyl 4-nitrophenyl carbonate. The resulting benzyl 4-nitrophenyl carbonate was then treated with amine in the presence of a base, such as Hunig's base or aqueous Na2CO3, to get the desired carbamate. If required, hydrolysis under a basic condition, such as aqueous LiOH, was used to convert the carbamate to the final product.
Reaction SMILES: Br[CH:2]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:14][CH2:13][CH2:12]2)=[CH:7][CH:6]=1)=O.[F:29][C:30]([F:39])([F:38])[C:31]1[N:36]=[N:35][C:34]([NH2:37])=[CH:33][CH:32]=1.C(N(CC)C(C)C)(C)C>C(O)(C)C>[C:23]1([C:2]2[N:35]3[N:36]=[C:31]([C:30]([F:38])([F:29])[F:39])[CH:32]=[CH:33][C:34]3=[N:37][C:3]=2[C:5]2[CH:10]=[CH:9][C:8]([C:11]3([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:14][CH2:13][CH2:12]3)=[CH:7][CH:6]=2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: CC(C)(C)OC(=O)NC1(c2ccc(C(=O)C(Br)c3ccccc3)cc2)CCC1
Reactant: Nc1ccc(C(F)(F)F)nn1
Solvent: CC(C)O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)NC1(c2ccc(-c3nc4ccc(C(F)(F)F)nn4c3-c3ccccc3)cc2)CCC1
Yield: 34 %

Procedure:
A mixture of crude tert-butyl (1-{4-[bromo(phenyl)acetyl]phenyl}cyclobutyl)carbamate that was prepared in a manner analgous to that described for Intermediate Example Int-1-A (1.85 g, ˜80% purity, 3.45 mmol, 1.0 eq), 6-(trifluoromethyl)pyridazin-3-amine (CAS-Nr. 935777-24-5, 0.674 g, 4.14 mmol, 1.2 eq), N,N-diisopropylethylamine (0.60 mL, 6.89 mmol, 1.0 eq) and activated 3 Å molecular sieves in isopropanol (10.5 mL) was heated for 7 hours under reflux. On cooling, the mixture was partitioned between DCM and water, stirred vigorously and filtered through a silicone coated filter paper. The filtrate was concentrated in vacuo. The crude mixture was purified via MPLC (Biotage Isolera; 100 g SNAP cartridge: hexane→hexane/ethyl acetate 2/1) to give 680 mg (34% yield) of the title compound.
Reaction SMILES: [OH:1][C@H:2]1[CH2:19][CH2:18][C@@:17]2([CH3:20])[C:4](=[CH:5][CH2:6][C@@H:7]3[C@@H:16]2[CH2:15][CH2:14][C@@:12]2([CH3:13])[C@H:8]3[CH2:9][CH2:10][C:11]2=[O:21])[CH2:3]1.[O:22]=[O:23]>>[O:22]([C@:4]12[CH2:3][C@@H:2]([OH:1])[CH2:19][CH2:18][C@:17]1([CH3:20])[C@@H:16]1[C@H:7]([C@H:8]3[C@@:12]([CH2:14][CH2:15]1)([CH3:13])[C:11](=[O:21])[CH2:10][CH2:9]3)[CH:6]=[CH:5]2)[OH:23]
Reactant: C[C@]12CC[C@H](O)CC1=CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
Reactant: O=O
Product: C[C@]12CC[C@H]3[C@@H](C=C[C@@]4(OO)C[C@@H](O)CC[C@]34C)[C@@H]1CCC2=O

Procedure:
3β-Hyroxyandrost-5-en-17-one (DHEA) 1 reacts with singlet oxygen to yield 5α-hydroperoxy-3β-hydroxyandrost-6-en-17one 2. This hydroperoxide undergoes a rearrangement when in chloroform solution to yield 7α-hydroperoxy-3β-hydroxyandrost-5-en-17-one, 3. Treatment of the hydroperoxide with zinc and acetic acid yields 3β,7α-dihydroxy-androst-5-en-17-one, 4. ##STR43##
Reaction SMILES: [CH:1]([CH:13]1[CH2:18][C:17](=[O:19])[O:16][C:14]1=[O:15])=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]CCCC.[CH2:20]([NH:23][CH2:24][CH:25]=[CH2:26])[CH:21]=[CH2:22].C1(C)C=CC=CC=1>O>[CH2:20]([N:23]([CH2:24][CH:25]=[CH2:26])[C:17](=[O:19])[CH2:18][CH:13]([CH:1]=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])[C:14]([OH:16])=[O:15])[CH:21]=[CH2:22]
Reactant: CCCCCCCCCCC=CC1CC(=O)OC1=O
Reactant: C=CCNCC=C
Solvent: O
Solvent: Cc1ccccc1
Product: C=CCN(CC=C)C(=O)CC(C=CCCCCCC)C(=O)O
Temperature: 25 °C
Reaction time: 0.75 h

Procedure:
A 500 ml, two-neck flask was charged with 105.2 g (500 mmol) dodecenylsuccinic anhydride 100 ml toluene. The flask was equipped with a thermometer and immersed in a water bath. Diallylamine (48.6 g, 500 mmol) was then dripped into the magnetically stirred anhydride plus toluene solution over a 15-minute period. Ice was added to the water bath as required to prevent temperature of the reaction mixture from getting above 35° C. The mixture was then stirred for another 45 minutes at room temperature. The toluene was then removed via rotary evaporator and air sparge to yield 153.4 g (99.8% of theory) of a red, oily liquid. An FTIR trace on this compound was found to have significant absorptions at 2924, 1726, 1605, 1440, 1221, 1174, 972, and 922 wavenumbers.
Reaction SMILES: [CH3:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]#[N:10])=[CH:4][N:3]=1.Br[CH2:12][CH2:13][O:14][CH2:15][CH2:16]Br.CC([O-])(C)C.[K+]>O1CCOCC1>[CH3:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2([C:9]#[N:10])[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[CH:4][N:3]=1
Reactant: BrCCOCCBr
Reactant: Cc1ncc(CC#N)cn1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1COCCO1
Product: Cc1ncc(C2(C#N)CCOCC2)cn1
Temperature: 80 °C
Yield: 9.020515659967313e+19 %

Procedure:
A solution of 2-(2-methylpyrimidin-5-yl)acetonitrile (4 g, 0.03 amol) and 1-bromo-2-(2-bromoethoxy)ethane (7.66 g, 0.033 mol) in 1,4-dioxane (60 mL) was added t-BuOK (66 mL, 0.066 mol, 1M in THF) and heated to 80° C. for 4 h. The reaction mixture was cooled to room temperature, quenched by sat.NH4Cl. The 1,4-dioxane was removed under reduced pressure. The residue aqueous layer was extracted with EtOAc (3×150 mL). The organic layer was dried over Na2SO4 and concentracted to give 4-(2-methylpyrimidin-5-yl)tetrahydro-2H-pyran-4-carbonitrile (5.5 g, yield: 90.5%). 1H NMR (CDCl3 400 MHz): δ8.75 (s, 2H), 4.15-4.05 (m, 2H), 3.95-3.85 (m, 2H), 2.75 (s, 3H), 2.15-2.00 (m, 4H).
Reaction SMILES: [O:1]=[C:2]1[C:6]2([CH2:11][CH2:10][NH:9][CH2:8][CH2:7]2)[N:5]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:4][N:3]1[CH2:18][C:19]1[CH:20]=[C:21]([CH:26]=[CH:27][CH:28]=1)[C:22]([O:24][CH3:25])=[O:23].I[CH2:30][CH2:31][CH2:32][N:33]1[C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=2[N:35]([CH3:42])[C:34]1=[O:43].C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>O>[CH3:42][N:35]1[C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=2[N:33]([CH2:32][CH2:31][CH2:30][N:9]2[CH2:10][CH2:11][C:6]3([N:5]([C:12]4[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=4)[CH2:4][N:3]([CH2:18][C:19]4[CH:20]=[C:21]([CH:26]=[CH:27][CH:28]=4)[C:22]([O:24][CH3:25])=[O:23])[C:2]3=[O:1])[CH2:7][CH2:8]2)[C:34]1=[O:43]
Reactant: COC(=O)c1cccc(CN2CN(c3ccccc3)C3(CCNCC3)C2=O)c1
Reactant: Cn1c(=O)n(CCCI)c2ccccc21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: O
Product: COC(=O)c1cccc(CN2CN(c3ccccc3)C3(CCN(CCCn4c(=O)n(C)c5ccccc54)CC3)C2=O)c1
Temperature: 65 °C
Yield: 78.2 %

Procedure:
A mixture of methyl 3-((4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate (400 mg, 0.962 mmol, 1 equiv), 1-(3-iodopropyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one (304.8 mg, 0.962 mmol, 1 equiv), and potassium carbonate (399 mg, 2.88 mmol, 3 equiv) was heated at 65° C. for 16 h. The reaction was cooled to ambient temperature and worked up using ethyl acetate and water. The organic layer was dried over MgSO4, filtered and concentrated in vacuo. The crude residue was purified using preparatory thin layer chromatography in 5% methanol in dichloromethane to afford the title compound as an oil (427 mg, 78%); 1H NMR (400 MHz, DMSO-d6): δ 1.61 (d, 2H, J=13.2 Hz), 1.85 (t, 2H, J=7.2 and 6.8 Hz); 2.34 (d, 2H, J=6.4 Hz); 2.64-2.66 (m, 2H); 2.89 (s, 3H); 3.843 (s, 3H); 3.91 (t, 2H, J=6.4 and 6.8 Hz); 4.58 (s, 2H); 4.62 (s, 2H); 6.78 (t, 1H, J=7.2 Hz); 6.86 (d, 2H, J=8.8 Hz); 7.01-7.07 (m, 2H); 7.13-7.14 (m, 1H); 7.21-7.26 (m, 3H); 7.52-7.58 (m, 2H); 7.88 (s, 1H); 7.90 (s, 1H); MS for C33H37N5O4 m/z 568.13 (M+H)+.
Reaction SMILES: [O:1]1[CH2:22][CH:2]1[CH2:3][O:4][C:5]1[CH:14]=[C:13]2[C:8]([C:9](=[O:21])[CH:10]=[C:11]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[O:12]2)=[CH:7][CH:6]=1.[CH2:23]([NH2:25])[CH3:24].[ClH:26].CCO>CO>[ClH:26].[CH2:23]([NH:25][CH2:22][CH:2]([OH:1])[CH2:3][O:4][C:5]1[CH:14]=[C:13]2[C:8]([C:9](=[O:21])[CH:10]=[C:11]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[O:12]2)=[CH:7][CH:6]=1)[CH3:24]
Reactant: CCN
Reactant: O=c1cc(-c2ccccc2)oc2cc(OCC3CO3)ccc12
Agent: Cl
Solvent: CCO
Solvent: CO
Product: CCNCC(O)COc1ccc2c(=O)cc(-c3ccccc3)oc2c1
Yield: 36 %

Procedure:
According to Method B, the title compound was synthesized from the reaction of 7-(2,3-epoxypropoxy) flavone and 70% aqueous ethylamine followed by treatment with HCl/EtOH, as white prisms, m.p. 244°-46° (MeOH) in 36% yield. The free base was obtained after column purification as white crystals, m.p. 164°-65° (MeOH/ehter), yield 39%.
Reaction SMILES: [CH2:1]([N:8]1[C:12]2=[C:13]([N:20]3[CH2:29][CH2:28][C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[CH2:21]3)[N:14]=[C:15]([C:17](O)=[O:18])[CH:16]=[C:11]2[CH:10]=[C:9]1[CH3:30])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:31]([N:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1)[CH3:32]>>[CH2:1]([N:8]1[C:12]2=[C:13]([N:20]3[CH2:29][CH2:28][C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[CH2:21]3)[N:14]=[C:15]([C:17]([N:36]3[CH2:37][CH2:38][N:33]([CH2:31][CH3:32])[CH2:34][CH2:35]3)=[O:18])[CH:16]=[C:11]2[CH:10]=[C:9]1[CH3:30])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Cc1cc2cc(C(=O)O)nc(N3CCc4ccccc4C3)c2n1Cc1ccccc1
Reactant: CCN1CCNCC1
Product: CCN1CCN(C(=O)c2cc3cc(C)n(Cc4ccccc4)c3c(N3CCc4ccccc4C3)n2)CC1

Procedure:
In accordance with the same procedures as in Step 1 of Example 756, except for using 1-benzyl-7-(3,4-dihydro-1H-isoquinolin-2-yl)-2-methyl-1H-pyrrolo[2,3-c]pyridin-5-carboxylic acid prepared in Step 1 of Example 925 and 1-ethylpiperazine, the titled compound was obtained as a white solid. (Yield: 63%) The product was used in the subsequent step without further purification.
Reaction SMILES: [Cl:1][C:2]1[C:7]([NH:8][NH:9]C(OC(C)(C)C)=O)=[C:6]([F:17])[C:5]([CH2:18][NH:19][C:20](=[O:25])[C:21]([CH3:24])([CH3:23])[CH3:22])=[CH:4][CH:3]=1.[F:26][C:27]1[CH:37]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:35]=[CH:34][C:28]=1[C:29]([N:31]=[C:32]=[O:33])=O.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:18][NH:19][C:20](=[O:25])[C:21]([CH3:24])([CH3:22])[CH3:23])=[C:6]([F:17])[C:7]=1[N:8]1[C:32](=[O:33])[NH:31][C:29]([C:28]2[CH:34]=[CH:35][C:36]([C:38]([F:41])([F:40])[F:39])=[CH:37][C:27]=2[F:26])=[N:9]1
Reactant: CC(C)(C)OC(=O)NNc1c(Cl)ccc(CNC(=O)C(C)(C)C)c1F
Reactant: O=C=NC(=O)c1ccc(C(F)(F)F)cc1F
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC(C)(C)C(=O)NCc1ccc(Cl)c(-n2nc(-c3ccc(C(F)(F)F)cc3F)[nH]c2=O)c1F

Procedure:
The title compound was prepared by following the procedure as described for Example-83 by using tert-butyl 2-(6-chloro-2-fluoro-3-(pivalamidomethyl)phenyl)hydrazinecarboxylate (Intermediate-57, 0.050 g, 0.13 mmol), 2-fluoro-4-(trifluoromethyl)benzoyl isocyanate (Intermediate-56, 0.10 g, 0.26 mmol), DCM (10 mL) and TFA (3 mL) to afford 0.030 g of pure product. 1H NMR (400 MHz, CDCl3): δ 1.20 (s, 9H), 4.48 (d, J=5.7 Hz, 2H), 6.13 (m, 1H), 7.31 (d, J=8.5 Hz, 1H), 7.41-7.51 (m, 3H), 8.12 (t, J=7.9 Hz, 1H); MS (m/z): 489.20 (M+H+).
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]=[C:7]([O:9][CH:10]2[CH2:27][CH:26]3[CH:12]([C:13](=[O:33])[N:14]([CH3:32])[CH2:15][CH2:16][CH2:17][CH2:18][CH:19]=[CH:20][CH:21]4[C:23]([C:29](O)=[O:30])([NH:24][C:25]3=[O:28])[CH2:22]4)[CH2:11]2)[CH:6]=[C:5]([C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([O:40][CH3:41])[CH:35]=2)[N:4]=1.[CH3:42][C:43]1([S:46]([NH2:49])(=[O:48])=[O:47])[CH2:45][CH2:44]1>>[CH3:1][O:2][C:3]1[N:8]=[C:7]([O:9][CH:10]2[CH2:27][CH:26]3[CH:12]([C:13](=[O:33])[N:14]([CH3:32])[CH2:15][CH2:16][CH2:17][CH2:18][CH:19]=[CH:20][CH:21]4[C:23]([C:29]([NH:49][S:46]([C:43]5([CH3:42])[CH2:45][CH2:44]5)(=[O:48])=[O:47])=[O:30])([NH:24][C:25]3=[O:28])[CH2:22]4)[CH2:11]2)[CH:6]=[C:5]([C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([O:40][CH3:41])[CH:35]=2)[N:4]=1
Reactant: CC1(S(N)(=O)=O)CC1
Reactant: COc1cccc(-c2cc(OC3CC4C(=O)NC5(C(=O)O)CC5C=CCCCCN(C)C(=O)C4C3)nc(OC)n2)c1
Product: COc1cccc(-c2cc(OC3CC4C(=O)NC5(C(=O)NS(=O)(=O)C6(C)CC6)CC5C=CCCCCN(C)C(=O)C4C3)nc(OC)n2)c1
Yield: 50.8 %

Procedure:
The acid 25 (150 mg, 0.26 mmol) was reacted with methylcyclopropane sulphonamide (72 mg, 0.53 mmol) according to the procedure described in Example 16 step g, which gave the title compound (90 mg, 50%), MS [M+1] 682.
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[C:6]([CH3:17])=[N:7][O:8][C:9]=1[C:10]1[CH:15]=[CH:14][C:13]([Br:16])=[CH:12][CH:11]=1)=[O:4].[F:18][C:19]([F:23])([F:22])[CH2:20][SH:21]>>[Br:16][C:13]1[CH:14]=[CH:15][C:10]([C:9]2[O:8][N:7]=[C:6]([CH3:17])[C:5]=2[C:3](=[O:4])[CH2:2][S:21][CH2:20][C:19]([F:23])([F:22])[F:18])=[CH:11][CH:12]=1
Reactant: Cc1noc(-c2ccc(Br)cc2)c1C(=O)CBr
Reactant: FC(F)(F)CS
Product: Cc1noc(-c2ccc(Br)cc2)c1C(=O)CSCC(F)(F)F

Procedure:
Prepared according to the procedure described in Example 3, Step 7, using 2-bromo-1-[5-(4-bromo-phenyl)-3-methyl-isoxazol-4-yl]-ethanone and 2,2,2-trifluoro-ethanethiol.
Reaction SMILES: [CH3:1][C:2]([O:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[N:12]([CH2:16][CH2:17][CH3:18])[C:11]([CH3:19])=[C:10]2[C:20]1[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=1)([CH3:5])[CH2:3][OH:4].[OH-].[Na+].[Mn]([O-])(=O)(=O)=[O:29].[K+]>O1CCOCC1.O>[CH3:1][C:2]([O:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[N:12]([CH2:16][CH2:17][CH3:18])[C:11]([CH3:19])=[C:10]2[C:20]1[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=1)([CH3:5])[C:3]([OH:29])=[O:4]
Reactant: CCCn1c(C)c(-c2ccncc2)c2cc(OC(C)(C)CO)ccc21
Reactant: O=[Mn](=O)(=O)[O-]
Agent: [K+]
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: O
Product: CCCn1c(C)c(-c2ccncc2)c2cc(OC(C)(C)C(=O)O)ccc21
Reaction time: 12 h

Procedure:
An amount of 3.38 g (10 m mole) of 2-methyl-2-[2-methyl-1-propyl-3-(4-pyridyl)-1H-indole-5-yloxy]propanol in 50 ml of dioxane was successively mixed with 300 mg of sodium hydroxide in 5 ml of water and then with 3.4 g of potassium permanganate dissolved in 30 ml of water. After stirring for 12 hours, the reaction mixture was filtered, evaporated, and neutralized with dilute sulfuric acid. After extraction with chloroform, the organic phase was dried over sodium sulfate and evaporated. The evaporation residue was recrystallized from ethanol.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3](/[CH:10]=[CH:11]/[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[NH:18][C:19]([C:21]2[S:22][C:23]([N+:27]([O-])=O)=[CH:24][C:25]=2[CH3:26])=[O:20])=[N:2]1.[Cl-].[NH4+].C(O)C>[Fe].O>[NH2:27][C:23]1[S:22][C:21]([C:19]([NH:18][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2/[CH:11]=[CH:10]/[C:3]2[C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[NH:1][N:2]=2)=[O:20])=[C:25]([CH3:26])[CH:24]=1
Reactant: Cc1cc([N+](=O)[O-])sc1C(=O)Nc1ccccc1/C=C/c1n[nH]c2ccccc12
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCO
Solvent: O
Product: Cc1cc(N)sc1C(=O)Nc1ccccc1/C=C/c1n[nH]c2ccccc12
Temperature: 50 °C
Reaction time: 1 h
Yield: 31.6 %

Procedure:
(E)-N-{2-[2-(1H-indazol-3-yl)vinyl]phenyl}-3-methyl-5-nitrothiophene-2-carboxamide (90 mg, 0.22 mmol), iron powder (621 mg, 11.13 mmol) and ammonium chloride (59 mg, 1.10 mmol) were added with ethanol (1.0 mL) and water (1.0 mL) at room temperature, stirred at 50° C. for 1 hour and then the reaction mixture was filtered through Celite. The filtrate was extracted with ethyl acetate and the organic layer was sequentially washed with water and saturated brine, dried over anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure. The residue was triturated in ethyl acetate to obtain Compound 67 (26 mg, 32%).
Reaction SMILES: [OH:1][C:2]1[CH:24]=[CH:23][C:22](I)=[CH:21][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:10]=[C:9]([C:17]([F:20])([F:19])[F:18])[CH:8]=1)=[O:5].[S:26]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27]1>>[OH:1][C:2]1[CH:24]=[CH:23][C:22]([C:28]2[CH:29]=[CH:30][S:26][CH:27]=2)=[CH:21][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:10]=[C:9]([C:17]([F:20])([F:19])[F:18])[CH:8]=1)=[O:5]
Reactant: O=C(Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1)c1cc(I)ccc1O
Reactant: OB(O)c1ccsc1
Product: O=C(Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1)c1cc(-c2ccsc2)ccc1O
Yield: 38.7 %

Procedure:
Using 2-hydroxy-5-iodo-N-[3,5-bis(trifluoromethyl)phenyl]-benzamide(compound of Example 81(1)) and 3-thiopheneboronic acid as the raw materials, the same operation as the Example 81(2) gave the title compound.