Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:9]=[CH:8][C:7]([C@H:10]2[CH2:15][CH2:14][CH2:13][N:12]([C:16]([C:18]3[S:22][C:21]([C:23]4[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=4)=[N:20][C:19]=3[CH3:33])=[O:17])[CH2:11]2)=[CH:6][C:3]=1[C:4]#[N:5].C[Sn]([N:38]=[N+:39]=[N-:40])(C)C>C1(C)C=CC=CC=1.C(OCC)C>[CH3:1][C:2]1[CH:9]=[CH:8][C:7]([CH:10]2[CH2:15][CH2:14][CH2:13][N:12]([C:16]([C:18]3[S:22][C:21]([C:23]4[CH:24]=[CH:25][C:26]([C:29]([F:32])([F:30])[F:31])=[CH:27][CH:28]=4)=[N:20][C:19]=3[CH3:33])=[O:17])[CH2:11]2)=[CH:6][C:3]=1[C:4]1[NH:40][N:39]=[N:38][N:5]=1
Reactant: C[Sn](C)(C)N=[N+]=[N-]
Reactant: Cc1ccc([C@H]2CCCN(C(=O)c3sc(-c4ccc(C(F)(F)F)cc4)nc3C)C2)cc1C#N
Solvent: CCOCC
Solvent: Cc1ccccc1
Product: Cc1ccc(C2CCCN(C(=O)c3sc(-c4ccc(C(F)(F)F)cc4)nc3C)C2)cc1-c1nnn[nH]1
Yield: 46 %

Procedure:
(R)-2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzonitrile (262 mg, 0.56 mmol) was dissolved in toluene (5 mL). Trimethyltin azide (230 mg, 1.12 mmol) was added and the mixture heated at reflux for 24 h. The mixture was diluted with diethyl ether (100 mL) and washed with 0.1 N HCl (100 mL). The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resultant oil was flash chromatographed with 7.5% methanol/chloroform (0.5% ammonium hydroxide modifier). The product fractions were combined and concentrated under reduced pressure. The resultant oil was taken up in 100 mL ethyl acetate and extracted with 0.1 N HCl (100 mL). The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to yield 132 mg (46%) of the desired {3-[4-methyl-3-(1H-tetrazol-5-yl)-phenyl]-piperidin-1-yl}-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-methanone as a clear oil.
Reaction SMILES: OS(O)(=O)=O.[N+:6]([O-:9])(O)=[O:7].[Br:10][C:11]1[S:15][N:14]=[CH:13][CH:12]=1>>[Br:10][C:11]1[S:15][N:14]=[CH:13][C:12]=1[N+:6]([O-:9])=[O:7]
Reactant: Brc1ccns1
Reactant: O=[N+]([O-])O
Agent: O=S(=O)(O)O
Product: O=[N+]([O-])c1cnsc1Br
Temperature: 70 °C
Reaction time: 1.5 h

Procedure:
To a solution of concentrated H2SO4 (15 mL) and HNO3 (6 mL) at 0° C. was added 5-bromoisothiazole (O) (5.0 g, 29.4 mmol). The mixture was then stirred at 70° C. for 1.5 hours. After cooling to room temperature, it was poured into stirring ice water (120 mL). The mixture was then extracted with ethyl acetate twice (150 mL×2). The combined organic phases were dried over Na2SO4 and concentrated in vacuo at room temperature (25° C.). The residue was purified with flash column (eluent: 5-20% ethyl acetate/petroleum ether) to afford the product 5-bromo-4-nitroisothiazole (P) (4.4 g, 21 mmol).
Reaction SMILES: C(=N[C@H](C)C(C1C=CC=CC=1OC)(C1C=CC=CC=1OC)O)C1C(=CC=CC=1)O.[CH3:30][C:31](=[CH:33][CH:34]=[C:35]([CH3:37])[CH3:36])[CH3:32].C1(NN)C=CC=CC=1.[N+](=[CH:48][C:49]([O:51][CH2:52][CH3:53])=[O:50])=[N-]>O.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH3:53][CH2:52][O:51][C:49]([CH:48]1[C:35]([CH3:37])([CH3:36])[CH:34]1[CH:33]=[C:31]([CH3:32])[CH3:30])=[O:50]
Reactant: CCOC(=O)C=[N+]=[N-]
Reactant: CC(C)=CC=C(C)C
Agent: [Cu+2]
Agent: CC(=O)[O-]
Agent: COc1ccccc1C(O)(c1ccccc1OC)[C@@H](C)N=Cc1ccccc1O
Solvent: NNc1ccccc1
Solvent: O
Product: CCOC(=O)C1C(C=C(C)C)C1(C)C
Temperature: 25 °C
Reaction time: 1 h
Yield: 90 %

Procedure:
22.6 mg (0.05 mmol) of copper complex prepared from 9.98 mg (0.05 mmol) of copper acetate-mono hydrate and 21.5 mg of (R)-N-salicylidene-2-amino-1,1-di(2-methoxyphenyl)propanol, and 6.0 g (55 mmol) of 2,5dimethyl-2,4-hexadiene were charged in a 50 ml Schlenk's tube wherein the atmosphere is substituted with nitrogen, followed by the addition of 5.4 mg of phenylhydrazine, and 1.14 g (10 mmol) of ethyl diazoacetate was added dropwise at 80° C. over 2 hours. After the completion of the dropwise addition of ethyl diazoacetate, the mixture was further stirred at 25° C. for 1 hour. The amount of chrysanthemic acid ethyl ester formed was determined by gas chromatography. As a result, it was 1.76 g and the yield was 90.0% based on ethyl diazoacetate and, furthermore, the trans/cis ratio was 58/42. After 2,5-dimethyl-2,4-hexadiene (boiling point: 51° C./30 mmHg) was distilled off from the reaction mixture, 1 g of the concentrated solution was taken out. Then, 10 ml of an aqueous 1N sodium hydroxide solution and 5 ml of ethanol were added and alkali hydrolysis was performed by stirring at 100° C. for 1 hour. The resulting chrysanthemic acid was reacted with I-menthol and the formed diastereomer was analyzed by gas chromatography. As a result, the optical purity of the (+)-trans isomer was 63% e.e., whereas, the optical purity of the (+)-cis isomer was 63% e.e.
Reaction SMILES: Cl[CH:2]([C:8]([CH3:10])=[O:9])[C:3]([O:5][CH2:6][CH3:7])=[O:4].C(=O)([O-])O.[Na+].[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([SH:23])=[CH:19][CH:18]=1.O>COCCOC>[CH2:6]([O:5][C:3](=[O:4])[CH:2]([S:23][C:20]1[CH:21]=[CH:22][C:17]([Cl:16])=[CH:18][CH:19]=1)[C:8](=[O:9])[CH3:10])[CH3:7]
Reactant: Sc1ccc(Cl)cc1
Reactant: CCOC(=O)C(Cl)C(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: COCCOC
Solvent: O
Product: CCOC(=O)C(Sc1ccc(Cl)cc1)C(C)=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 54.9 %

Procedure:
To a solution of ethyl 2-chloroacetoacetate (1.58 g, 9.61 mmol) in ethylene glycol dimethyl ether (30 mL) was added sodium hydrogencarbonate (ca. 15 g) and 4-chlorothiophenol (1.39 g, 9.61 mmol). The suspension was heated to reflux and stirred for 3 hours. The reaction mixture was allowed to cool to room temperature, and water (100 mL) was added. The mixture was extracted with ethyl ether (75 mL), and the organic extract was washed with brine (150 mL). The organic phase was dried (magnesium sulfate), filtered, and concentrated to afford a yellow oil. Flash chromatography over silica (ethyl acetate/hexanes) provided 1.44 g (55%) of the product as a colorless oil: 1H NMR (CDCl3) δ 13.8 (s, 1H), 7.26-7.21 (m, 2H), 7.06-7.04 (m, 2H), 4.21 (q, J=7.1 Hz, 2H), 2.33 (s, 3H), 1.20 (t, J=7.1 Hz, 3H).
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[CH:9][NH:10]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:19]([O:21][C:22](=[O:30])[C:23]1[CH:28]=[CH:27][C:26](F)=[CH:25][CH:24]=1)[CH3:20].O>CN(C)C=O>[CH2:19]([O:21][C:22](=[O:30])[C:23]1[CH:28]=[CH:27][C:26]([N:10]2[C:11]3[C:7](=[CH:6][CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[CH:12]=3)[CH:8]=[CH:9]2)=[CH:25][CH:24]=1)[CH3:20]
Reactant: CCOC(=O)c1ccc(F)cc1
Reactant: O=[N+]([O-])c1ccc2cc[nH]c2c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)c1ccc(-n2ccc3ccc([N+](=O)[O-])cc32)cc1
Temperature: 75 °C
Reaction time: 8 h
Yield: 66.9 %

Procedure:
To a solution of 6-nitro-1H-indole (0.5 g) in N,N-dimethylformamide (10 mL) were added cesium carbonate (1.2 g) and 4-fluoro benzoic acid ethyl ester (0.62 g), and this mixture was stirred at 75° C. overnight. This reaction mixture was poured into water and the precipitated solid was collected by filtration, and washed with water and n-hexane, dried under reduced pressure to give the title compound (0.64 g).
Reaction SMILES: C(P(CCCC)CCCC)CCC.[CH3:14][O:15][C:16](=[O:30])[CH2:17][C:18]1[C:22]2[C:23]([Cl:28])=[CH:24][C:25]([OH:27])=[CH:26][C:21]=2[S:20][C:19]=1[CH3:29].[CH3:31][N:32]1[C:36]([CH2:37]O)=[CH:35][C:34]([C:39]([F:42])([F:41])[F:40])=[N:33]1.C1CCN(C(N=NC(N2CCCCC2)=O)=O)CC1>C1COCC1>[CH3:14][O:15][C:16](=[O:30])[CH2:17][C:18]1[C:22]2[C:23]([Cl:28])=[CH:24][C:25]([O:27][CH2:37][C:36]3[N:32]([CH3:31])[N:33]=[C:34]([C:39]([F:42])([F:40])[F:41])[CH:35]=3)=[CH:26][C:21]=2[S:20][C:19]=1[CH3:29]
Reactant: COC(=O)Cc1c(C)sc2cc(O)cc(Cl)c12
Reactant: Cn1nc(C(F)(F)F)cc1CO
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: C1CCOC1
Product: COC(=O)Cc1c(C)sc2cc(OCc3cc(C(F)(F)F)nn3C)cc(Cl)c12
Temperature: 25 °C
Reaction time: 1 h
Yield: 90.9 %

Procedure:
To a mixture of tri-n-butylphosphine (0.415 mL), methyl(4-chloro-6-hydroxy-2-methyl-1-benzothiophen-3-yl)acetate (150 mg) and (1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanol (105 mg) in THF (4.0 mL) was added ADDP (419 mg) at room temperature. The mixture was stirred at room temperature under nitrogen atmosphere for 1 h. The mixture was concentrated. To the residue was added IPE and the precipitate was filtered off and the filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (NH, EtOAc/hexane) and silica gel column chromatography (EtOAc/hexane) to give the title compound (218 mg) as a colorless solid. The solid was crystallized from EtOAc-hexane.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[NH:15][C:14](=[O:19])/[C:13]/3=[CH:20]\[C:21]2[NH:22][CH:23]=[CH:24][CH:25]=2)=[CH:4][CH:3]=1.[C:26](C1C=C2C(=CC=1)NC(=O)/C/2=C\C1NC=CC=1)#C.IC1C=CC(OC)=CC=1.C(N(CC)CC)C>[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CN(C=O)C>[CH3:26][O:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[NH:15][C:14](=[O:19])/[C:13]/3=[CH:20]\[C:21]2[NH:22][CH:23]=[CH:24][CH:25]=2)=[CH:4][CH:3]=1
Reactant: O=C1Nc2ccc(C#Cc3ccc(O)cc3)cc2/C1=C/c1ccc[nH]1
Reactant: C#Cc1ccc2c(c1)/C(=C/c1ccc[nH]1)C(=O)N2
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Agent: COc1ccc(I)cc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COc1ccc(C#Cc2ccc3c(c2)/C(=C/c2ccc[nH]2)C(=O)N3)cc1

Procedure:
This compound was also prepared in a manner analogous to the preparation of (Z)-1,3-dihydro-5-(4-hydroxyphenyl)ethynyl-3-[(1H-pyrrol-2-yl)methylene]-2H-indol-2-one in Example 83 above. In this example, (Z)-1,3-dihydro-5-ethynyl-3-[(1H-pyrrol-2-yl)methylene]-2H-indol-2-one (60 mg, 0.26 mmol) (Example 82) was coupled with 4-iodoanisole (30 mg, 0.34 mmol) (Aldrich) using CuI (6 mg, 0.031 mmol) (Aldrich) and (Ph3P)2PdCl2 (14 mg, 0.020 mmol) (Aldrich) as catalyst in 1 mL DMF and 2 mL triethylamine at 70° C. for 16 hours to give (Z)-1,3-dihydro-5-(4-methoxyphenyl)ethynyl-3-[(1H-pyrrol-2-yl)-methylene]-2H-indol-2-one as a yellow powder. (Yield 63 mg, 71%).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Al](C)C.C([O:14][C:15](=O)[CH2:16][N:17]1[C:21]([C:22]([F:25])([F:24])[F:23])=[C:20]([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)[C:19]([C:33]2[CH:38]=[CH:37][C:36]([S:39]([CH3:42])(=[O:41])=[O:40])=[CH:35][CH:34]=2)=[N:18]1)C>C(Cl)Cl>[C:2]1([NH:1][C:15](=[O:14])[CH2:16][N:17]2[C:21]([C:22]([F:25])([F:23])[F:24])=[C:20]([C:26]3[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=3)[C:19]([C:33]3[CH:38]=[CH:37][C:36]([S:39]([CH3:42])(=[O:41])=[O:40])=[CH:35][CH:34]=3)=[N:18]2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOC(=O)Cn1nc(-c2ccc(S(C)(=O)=O)cc2)c(-c2ccc(F)cc2)c1C(F)(F)F
Reactant: Nc1ccccc1
Agent: C[Al](C)C
Solvent: ClCCl
Product: CS(=O)(=O)c1ccc(-c2nn(CC(=O)Nc3ccccc3)c(C(F)(F)F)c2-c2ccc(F)cc2)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 69.6 %

Procedure:
Aniline (0.07 g, 0.75 mmol) was added to a methylene chloride solution of trimethyl aluminum (0.38 mL, 0.75 mmol, 2.0M in hexanes) at 25° C. under nitrogen. After gas evolution had ceased (approx. 30 minutes), ethyl[4-(4-fluorophenyl)-3-[4-(methylsulfonyl)phenyl]-5-(trifluoromethyl)-1H-pyrazol-1-yl]acetate (Example 8) (0.25 g, 0.5 mmol) was added and the mixture stirred for 24 hours at 25° C. The reaction was quenched with dilute aqueous HCl and extracted with two portions ethyl acetate and the extracts washed with brine, dried over MgSO4 and concentrated in vacuo. Recrystallization from chloroform/acetone gave N-phenyl-[4-(4-fluorophenyl)-3-[4-(methylsulfonyl)phenyl]-5-(trifluoromethyl)-1H-pyrazol-1-yl]acetamide as a white crystalline solid (0.18 g, 68% yield). Elemental analysis for C25H19N3F4SO3Calc'd: C, 58.02, H, 3.70, N, 8.12, S, 6.20. Found: C, 57.48, H, 3.78, N, 8.03, S, 6.46.
Reaction SMILES: [CH2:1]([N:4]1[C:12]2C(=CC=[CH:10][CH:11]=2)[C:6](=[O:13])[C:5]1=O)[CH2:2]C.[Cl:15][C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[NH:21][C:20](=[O:25])[C:19]2=[O:26].BrCCCN1CCOCC1>>[Cl:15][C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[N:21]([CH2:10][CH2:11][CH2:12][N:4]1[CH2:1][CH2:2][O:13][CH2:6][CH2:5]1)[C:20](=[O:25])[C:19]2=[O:26]
Reactant: CCCN1C(=O)C(=O)c2ccccc21
Reactant: O=C1Nc2ccc(Cl)cc2C1=O
Agent: BrCCCN1CCOCC1
Product: O=C1C(=O)N(CCCN2CCOCC2)c2ccc(Cl)cc21

Procedure:
This compound was prepared in a similar method as 1-propylindoline-2,3-dione by reacting commercially available 5-chloro isatin (purchase from Fisher Scientific) with the 4-(3-bromopropyl)morpholine. 1H NMR δ 7.57 (m, 2H), 6.98 (d, 1H), 3.82 (t, 2H), 3.64 (m, 4H), 2.41 (m, 6H), 1.87 (m, 2H).
Reaction SMILES: [OH:1][CH:2]1[NH:6][C:5](=[O:7])[CH2:4][CH2:3]1.[CH2:8](O)[CH2:9][CH2:10][CH2:11][CH3:12]>>[CH2:8]([O:1][CH:2]1[NH:6][C:5](=[O:7])[CH2:4][CH2:3]1)[CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCCCO
Reactant: O=C1CCC(O)N1
Product: CCCCCOC1CCC(=O)N1

Procedure:
2.5 g of 5-hydroxy-pyrrolidin-2-one and 1.25 g of Amberlite IR 120H are heated to 65° C. for 3 hours in 55 cm3 of 1-pentanol. The resin is filtered off, and the remainder is distilled under reduced pressure at a temperature of 22° C./24° C. under 0.5 mbar. The residue is chromatographed on silica (eluent: ethyl acetate), and 2.68 g of the expected product is obtained. m.p. 42°-43° C.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:16])[CH:4]=[CH:5][C:6]1[CH:11]=[CH:10][C:9](Cl)=[C:8]([N+:13]([O-:15])=[O:14])[CH:7]=1.[C:17]([NH:24][CH2:25][CH2:26][NH2:27])([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18].C(N(CC)CC)C>O1CCOCC1>[CH3:1][O:2][C:3](=[O:16])[CH:4]=[CH:5][C:6]1[CH:11]=[CH:10][C:9]([NH:27][CH2:26][CH2:25][NH:24][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[C:8]([N+:13]([O-:15])=[O:14])[CH:7]=1
Reactant: COC(=O)C=Cc1ccc(Cl)c([N+](=O)[O-])c1
Reactant: CC(C)(C)OC(=O)NCCN
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Product: COC(=O)C=Cc1ccc(NCCNC(=O)OC(C)(C)C)c([N+](=O)[O-])c1
Temperature: 80 °C

Procedure:
A mixture of 3-(4-chloro-3-nitro-phenyl)-acrylic acid methyl ester (Ia, 0.243 g, 1.00 mmol), N-Boc-ethylenediamine (0.316 mL, 2.0 mmol) and triethylamine (0.50 mL, 3.59 mmoL) in dioxane (7 mL) was heated at 80° C. for about 80 h. The solution was evaporated and the residue was added MeOH. The resulting solid was filtered and washed with MeOH. 3-[4-(2-tert-Butoxycarbonylamino-ethylamino)-3-nitro-phenyl]-acrylic acid methyl ester (IIIa1) was obtained as bright yellow solid (0.193 g, 52.6%). HPLC purity at 254 nm: 96.0˜98.1%; tR=3.27 min. LCMS (ESI) m/z: 366 ([M+H]+), 310 (M+H-56), 266 (M+H-Boc). 1H NMR (CDCl3) δ 8.41 (1H, br t like, NHAr), 8.31 (1H, d, J=1.8 Hz), 7.63 (1H, dd, J=9.0, 1.7 Hz), 7.57 (1H, d, J=16.0 Hz), 6.98 (1H, d, J=8.9 Hz), 6.30 (1H, d, J=15.9 Hz), 3.80 (3H, s), 3.52 (2H, m), 3.45 (2H, m), 1.45 (9H, s); 13C NMR (CDCl3) δ 166.9, 155.7, 145.8, 142.3, 134.1, 131.5, 127.1, 121.8, 115.4, 113.9, 79.5, 51.2, 42.7, 39.1, 27.9.
Reaction SMILES: [F:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([OH:10])[CH:3]=1.[CH3:11][N:12]([CH3:16])[C:13](Cl)=[O:14].C(N(CC)CC)C>ClCCl>[C:6]([C:5]1[CH:8]=[CH:9][C:2]([F:1])=[CH:3][C:4]=1[O:10][C:13](=[O:14])[N:12]([CH3:16])[CH3:11])#[N:7]
Reactant: N#Cc1ccc(F)cc1O
Reactant: CN(C)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CN(C)C(=O)Oc1cc(F)ccc1C#N
Yield: 67 %

Procedure:
Under N2, a stirred solution of 4-fluoro-2-hydroxybenzonitrile (685 mg, 5.00 mmol), dimethylcarbamoyl chloride, and triethylamine (606 mg, 6 mmol) in dichloromethane (10 mL) was heated at reflux for 20 hrs. The cooled mixture was diluted with dichloromethane (10 mL) washed with water, and brine. The organic layer was separated, dried (Na2SO4), concentrated, and the residue purified by column chromatography (SiO2, 5% ethyl acetate-CH2Cl2) to provide 700 mg (Yield 67%) of the title compound as a white crystalline solid: 1H NMR (CDCl3, 500 MHz) δ ppm: 3.03 (3H, s, NMe), 3.15 (3H, s, NMe), 6.99 (1H, dt, J=2.5 Hz, 8.5 Hz, Ar—H), 7.23 (1H, dd, J=2.5 Hz, 9.5 Hz, Ar—H), 7.61 (1H, dd, J=9 Hz, 6 Hz, Ar—H); 13C NMR (CDCl3, 125.77 Hz) δ ppm: 36.76, 37.06, 102.84, 102.86, 111.59, 111.79, 113.24, 113.42, 114.99, 134.36, 134.45, 152.54, 155.06, 155.16, 164.26, 166.31. HRMS (ESI) calcd for C10H10N2O2F (M+H) 209.0726, found 209.0722.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH:9]=[C:8]([C:14]#[N:15])[C:7]2=O)([O-:3])=[O:2].P(Cl)(Cl)([Cl:19])=O>>[Cl:19][C:7]1[C:6]2[C:11](=[CH:12][CH:13]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)[N:10]=[CH:9][C:8]=1[C:14]#[N:15]
Reactant: N#Cc1c[nH]c2ccc([N+](=O)[O-])cc2c1=O
Reactant: O=P(Cl)(Cl)Cl
Product: N#Cc1cnc2ccc([N+](=O)[O-])cc2c1Cl

Procedure:
A mixture of 31.3 g (0.147 mol) of 6-nitro-4-oxo-1,4-dihydro-3-quinolinecarbonitrile and 160 mL of phosphorous oxychloride was refluxed for 5.5 h. The phosphorous oxychloride was removed in vacuo and the residue was poured over ice and neutralized with sodium bicarbonate. The product was collected, washed with water and dried in vacuo (500° C.). There was obtained 33.5 g of tan solid; solid: mass spectrum (electrospray, m/e): M+H 234.
Reaction SMILES: [CH2:1]([NH2:3])[CH3:2].Cl[C:5]1[C:10]([C:11]([NH:13][C:14]2[C:15]([Cl:25])=[N:16][C:17]([CH3:24])=[CH:18][C:19]=2[C:20]([F:23])([F:22])[F:21])=[O:12])=[CH:9][CH:8]=[CH:7][N:6]=1>C1(C)C(C)=CC=CC=1.C(OCC)(=O)C>[Cl:25][C:15]1[C:14]([NH:13][C:11]([C:10]2[C:5]([NH:3][CH2:1][CH3:2])=[N:6][CH:7]=[CH:8][CH:9]=2)=[O:12])=[C:19]([C:20]([F:23])([F:22])[F:21])[CH:18]=[C:17]([CH3:24])[N:16]=1
Reactant: Cc1cc(C(F)(F)F)c(NC(=O)c2cccnc2Cl)c(Cl)n1
Reactant: CCN
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1C
Product: CCNc1ncccc1C(=O)Nc1c(C(F)(F)F)cc(C)nc1Cl
Temperature: 160 °C
Yield: 37.5 %

Procedure:
Ethylamine (0.4 g) was added to a suspension of 1.3 g of 2-chloro-N-(2-chloro-6-methyl-4-trifluoromethyl-3-pyridinyl)-3-pyridinecarboxamide in 5 ml of xylene, and the resulting mixture heated in a pressure tube for 30 min. at 160° C. The cooled mixture was diluted with ethyl acetate, washed, dried, and concentrated. Column chromatography over silica gel (ethyl acetate/hexane, 1:1) gave 0.5 g of the title compound.
Reaction SMILES: [CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]1[CH3:12])[CH3:2].[C:13](Cl)(=O)[CH3:14]>O>[CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:4]([C:5]2[C:6]3[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=3)[N:3]([CH2:1][CH3:2])[C:13]=2[CH3:14])=[CH2:12])=[C:4]1[CH3:12])[CH3:2]
Reactant: CC(=O)Cl
Reactant: CCn1c(C)cc2ccccc21
Solvent: O
Product: C=C(c1c(C)n(CC)c2ccccc12)c1c(C)n(CC)c2ccccc12
Temperature: 25 °C
Reaction time: 20 h

Procedure:
A mixture of 1-ethyl-2-methylindole (15.9 g, 0.1 mole) and acetyl chloride (9.4 g, 0.12 mole) was stirred at room temperature for 20 hours. Then, water (100 ml) was added to the reaction mixture and the resulting grains were filtered and dried. The dried product was recrystallized from toluene/methanol. Yield: 13.0 g (77.0%). M.P.: 183°-185° C. IR (KBr) spectrum was identical to that of the product in Example 1.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[C:5]2[F:11].CC1C=CC(S(O)(=O)=O)=CC=1.[O:23]1[CH:28]=[CH:27][CH2:26][CH2:25][CH2:24]1>ClCCl>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:24]1[CH2:25][CH2:26][CH2:27][CH2:28][O:23]1)[N:6]=[C:5]2[F:11]
Reactant: Fc1n[nH]c2ccc(Br)cc12
Reactant: C1=COCCC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: ClCCl
Product: Fc1nn(C2CCCCO2)c2ccc(Br)cc12
Temperature: 25 °C
Reaction time: 18 h
Yield: 74.3 %

Procedure:
A mixture of 5-bromo-3-fluoro-1H-indazole (6.0 g, 27.9 mmol), p-TsOH (530.7 mg, 2.79 mmol) and 3,4-dihydro-2H-pyran (3.05 g, 36.3 mmol) in dichloromethane (80 mL) was stirred at room temperature for 18 h. The reaction mixture was diluted with dichloromethane (370 mL) and washed with water (230 mL). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified on a silica gel column using EtOAc in petroleum ether (1:100 to 1:15) to afford the title compound as a yellow solid (6.2 g, yield 74.3%). 1H NMR (DMSO-d6, 400 MHz): δ 7.96 (s, 1H), 7.70 (d, 1H), 7.60 (d, 1H), 5.76 (dd, 1H), 3.84-3.80 (m, 1H), 3.71-3.64 (m, 1H), 2.20-2.15 (m, 1H), 1.97-1.87 (m, 2H), 1.69-1.64 (m, 1H), 1.53-1.47 (m, 2H).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([C:11]([F:40])([F:39])[C:12]([F:38])([F:37])[O:13][C:14]([F:36])([F:35])[C:15]([F:34])([F:33])[O:16][C:17]([F:32])([F:31])[C:18]([F:30])([F:29])[C:19]2[CH:24]=[CH:23][C:22]([OH:25])=[C:21]([N+:26]([O-])=O)[CH:20]=2)[CH:7]=[CH:8][C:9]=1[OH:10])([O-])=O.Cl.[H][H]>C(O)C.[Pd]>[NH2:26][C:21]1[CH:20]=[C:19]([C:18]([F:29])([F:30])[C:17]([F:31])([F:32])[O:16][C:15]([F:33])([F:34])[C:14]([F:35])([F:36])[O:13][C:12]([F:37])([F:38])[C:11]([F:40])([F:39])[C:6]2[CH:7]=[CH:8][C:9]([OH:10])=[C:4]([NH2:1])[CH:5]=2)[CH:24]=[CH:23][C:22]=1[OH:25]
Reactant: [H][H]
Reactant: O=[N+]([O-])c1cc(C(F)(F)C(F)(F)OC(F)(F)C(F)(F)OC(F)(F)C(F)(F)c2ccc(O)c([N+](=O)[O-])c2)ccc1O
Agent: [Pd]
Agent: Cl
Solvent: CCO
Product: Nc1cc(C(F)(F)C(F)(F)OC(F)(F)C(F)(F)OC(F)(F)C(F)(F)c2ccc(O)c(N)c2)ccc1O
Reaction time: 8 h
Yield: 53 %

Procedure:
A solution of 1,8-bis(3-nitro-4-hydroxyphenyl)perfluoro-3,6-dioxaoctane (6.10 g, 0.010 mole) in 185 ml of ethanol was deoxygenated by passing nitrogen through the boiling solution for 14 minutes. Concentrated hydrochloric acid (37 ml, 0.44 mole) and 10% Pd/C(0.75 g) were added to the cooled solution and the catalytic reduction was run overnight at room temperature and 50 psi of hydrogen. The catalyst was filtered off and the water white solution reduced to dryness under water aspirator pressure. The light tan residue (6.1 g) was slurried in a water-ether mixture. After careful neutralization with solid sodium bicarbonate, the product dissolved in the ether layer, which was washed several times with water, dried over magnesium sulfate and evaporated to dryness. The soluble portion of the filtrate was taken up in 6 liters of boiling heptane, the solution treated with charcoal and reduced in volume to 3 liters to give upon cooling 2.9 g (53% yield) of slightly off-white product, mp 150°-152° C.
Reaction SMILES: [C:1]([O:5][C:6](=[O:16])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([CH3:14])=[C:10]([OH:15])[CH:9]=1)([CH3:4])([CH3:3])[CH3:2].Br[C:18]1[CH:19]=[CH:20][C:21]([N+:24]([O-:26])=[O:25])=[N:22][CH:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)C=O>O>[C:1]([O:5][C:6](=[O:16])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([CH3:14])=[C:10]([O:15][C:18]2[CH:23]=[N:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][CH:19]=2)[CH:9]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: Cc1ccc(NC(=O)OC(C)(C)C)cc1O
Reactant: O=[N+]([O-])c1ccc(Br)cn1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1ccc(NC(=O)OC(C)(C)C)cc1Oc1ccc([N+](=O)[O-])nc1
Temperature: 25 °C
Reaction time: 15 h
Yield: 46 %

Procedure:
A mixture of tert-butyl(3-hydroxy-4-methylphenyl)carbamate (3.14 g, 14.1 mmol), 5-bromo-2-nitropyridine (2.38 g, 11.7 mmol), cesium carbonate (5.72 g, 17.6 mmol) and N,N-dimethylformamide (25 mL) was stirred at room temperature for 15 hr. The reaction mixture was diluted with water, and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (basic silica gel, hexane/ethyl acetate=80/20→0/100) to give the title compound (1.86 g, 44%) as a colorless oil.