Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][CH2:2][CH2:3][NH:4][C:5]([N:7]1[CH2:12][CH2:11][CH2:10][C@H:9]([NH:13][CH2:14][C:15]2[CH:24]=[C:23]3[C:18]([CH2:19][CH2:20][C:21](=[O:26])[N:22]3[CH3:25])=[CH:17][C:16]=2[O:27][CH3:28])[C@@H:8]1[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=S>C(O)C.[Hg]=O>[NH:4]1[CH2:3][CH2:2][N:1]=[C:5]1[N:7]1[CH2:12][CH2:11][CH2:10][C@H:9]([NH:13][CH2:14][C:15]2[CH:24]=[C:23]3[C:18]([CH2:19][CH2:20][C:21](=[O:26])[N:22]3[CH3:25])=[CH:17][C:16]=2[O:27][CH3:28])[C@@H:8]1[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1
Reactant: COc1cc2c(cc1CN[C@H]1CCCN(C(=S)NCCN)[C@H]1c1ccccc1)N(C)C(=O)CC2
Agent: O=[Hg]
Solvent: CCO
Product: COc1cc2c(cc1CN[C@H]1CCCN(C3=NCCN3)[C@H]1c1ccccc1)N(C)C(=O)CC2
Yield: 36.4 %

Procedure:
3-[(6-Methoxy-1-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-7-ylmethyl)-amino]-(2S,3S)-2-phenyl-piperidine-1-carbothioic acid (2-amino-ethyl)-amide (660 mg, 1.38 mmol) and mercury (II) oxide (600 mg, 2.75 mmol) were stirred in 30 mL of ethanol at reflux for 4 hours. The black reaction was filtered through Celite and the filtrate was concentrated. Silica gel chromatography using (9:1 chloroform/methanol) gave 225 mg (37% yield) of the title compound, a yellow oil. Rf=0.06 (9:1 chloroform/methanol). MS (M+H)+=448.2; 1H NMR (400 MHz, CD3OD): δ 1.79–2.00 (m, 4H), 2.49–2.53 (t, J=7.2 Hz, 2H), 2.80–2.84 (t, J=7.2 Hz, 2H), 3.19–3.23 (m, 1H), 3.25 (s, 3H), 3.28–3.31 (m, 1H), 3.48–3.54 (m, 1H), 3.61 (bs, 1H), 3.66 (s, 3H), 3.69 (s, 4H), 3.75–3.89 (m, 4H), 5.14–5.15 (d, J=5.6 Hz, 1H), 6.77 (s, 1H), 6.97 (s, 1H), 7.33–7.42 (m, 3H), 7.57–7.59 (d, J=7.3 Hz, 2H). 13C NMR (100 MHz, CD3OD): δ 24.0, 35.5, 26.1, 30.2, 32.6, 44.0, 44.2, 47.1, 562, 57.8, 61.6, 61.9, 111.5, 118.1, 127.5, 127.8, 129.5, 129.9, 130.1, 134.6, 137.0, 154.9, 161.3, 172.4. The dihydrochloride salt was prepared by the addition of 2 M HCl in ether to a solution of the product in ethyl acetate. Concentration gave a white solid.
Reaction SMILES: [NH2:1][C:2]1[CH:32]=[CH:31][C:5]([C:6]([NH:8][C:9]2[C:14]([CH3:15])=[CH:13][C:12]([C:16]([F:28])([C:21]([F:27])([F:26])[C:22]([F:25])([F:24])[F:23])[C:17]([F:20])([F:19])[F:18])=[CH:11][C:10]=2[CH2:29][CH3:30])=[O:7])=[CH:4][C:3]=1[Br:33].[Cl-].[Cl:35][C:36]1[C:40](Cl)=[S+:39][S:38][N:37]=1.N1C=CC=CC=1>O1CCCC1.ClCCl>[Br:33][C:3]1[CH:4]=[C:5]([CH:31]=[CH:32][C:2]=1[N:1]=[C:40]1[S:39][S:38][N:37]=[C:36]1[Cl:35])[C:6]([NH:8][C:9]1[C:14]([CH3:15])=[CH:13][C:12]([C:16]([F:28])([C:21]([F:26])([F:27])[C:22]([F:23])([F:24])[F:25])[C:17]([F:19])([F:20])[F:18])=[CH:11][C:10]=1[CH2:29][CH3:30])=[O:7]
Reactant: CCc1cc(C(F)(C(F)(F)F)C(F)(F)C(F)(F)F)cc(C)c1NC(=O)c1ccc(N)c(Br)c1
Reactant: Clc1ns[s+]c1Cl
Agent: [Cl-]
Solvent: C1CCOC1
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCc1cc(C(F)(C(F)(F)F)C(F)(F)C(F)(F)F)cc(C)c1NC(=O)c1ccc(N=c2ssnc2Cl)c(Br)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 85.3 %

Procedure:
4-amino-3-bromo-N-[2-ethyl-6-methyl-4-(1,1,1,2,3,3,4,4,4-nonafluorobutan-2-yl)phenyl]benzamide (0.254 g) was dissolved in tetrahydrofuran (20 ml). To the mixture was added 4,5-dichloro-1,2,3-dithiazol-1-ium chloride (0.106 g), and stirred at room temperature for 2 hours. To the reaction mixture was added pyridine (0.091 g) in dichloromethane, and stirred at room temperature for 1 hour. The solvent was removed under reduced pressure. To the residue was added water and extracted twice with ethyl acetate. The organic phases were combined and washed with water, and dried over anhydrous magnesium sulfate. The drying agent (anhydrous magnesium sulfate) was removed by filtration and the solvent was distilled off under the reduced pressure. The residue was purified by column chromatography to obtain 3-bromo-4-{[4-chloro-5H-1,2,3-dithiazol-5-ylidene]amino}-N-[2-ethyl-6-methyl-4-(1,1,1,2,3,3,4,4,4-nonafluorobutan-2-yl)phenyl]benzamide (0.270 g, 85%).
Reaction SMILES: [Na+:1].[NH2:2][C:3]1[C:4]([S:17]([O-:20])(=[O:19])=[O:18])=[CH:5][C:6]2[C:11]([CH:12]=1)=[CH:10][CH:9]=[C:8]([S:13]([OH:16])(=[O:15])=[O:14])[CH:7]=2.[C:21]([O-])(=O)[CH3:22].[Na+].[N+:26]([C:29]1[CH:30]=[C:31]([C:38](Cl)=[O:39])[CH:32]=[C:33]([C:35](Cl)=[O:36])[CH:34]=1)([O-:28])=[O:27]>O>[Na+:1].[Na+:1].[Na+:1].[Na+:1].[N+:26]([C:29]1[CH:30]=[C:31]([C:38]([NH:2][C:3]2[C:4]([S:17]([O-:20])(=[O:19])=[O:18])=[CH:5][C:6]3[C:21]([CH:22]=2)=[CH:10][CH:9]=[C:8]([S:13]([O-:16])(=[O:15])=[O:14])[CH:7]=3)=[O:39])[CH:32]=[C:33]([C:35]([NH:2][C:3]2[C:4]([S:17]([O-:20])(=[O:19])=[O:18])=[CH:5][C:6]3[C:11]([CH:12]=2)=[CH:10][CH:9]=[C:8]([S:13]([O-:16])(=[O:15])=[O:14])[CH:7]=3)=[O:36])[CH:34]=1)([O-:28])=[O:27]
Reactant: Nc1cc2ccc(S(=O)(=O)O)cc2cc1S(=O)(=O)[O-]
Reactant: CC(=O)[O-]
Reactant: O=C(Cl)c1cc(C(=O)Cl)cc([N+](=O)[O-])c1
Agent: [Na+]
Solvent: O
Product: O=C(Nc1cc2ccc(S(=O)(=O)[O-])cc2cc1S(=O)(=O)[O-])c1cc(C(=O)Nc2cc3ccc(S(=O)(=O)[O-])cc3cc2S(=O)(=O)[O-])cc([N+](=O)[O-])c1
Reaction time: 8 h

Procedure:
A 6.5 g portion of 3-amino-2,7-naphthalenedisulfonic acid monosodium salt is suspended in 100 ml of water and the pH is adjusted to 7.5-8.0 giving a solution. A 1.82 g portion of sodium acetate is added and dissolved and 2.75 g of 5-nitro-1,3-benzenedicarbonylchloride is added. A 100 ml portion of water is added to maintain solution and the reaction is allowed to stand overnight. The mixture is treated with activated carbon and concentrated to about 50 ml on a rotary evaporator. The solid which forms is redissolved by heating on a steam bath. Cooling produces crystals which are dried overnight in an Abderhalden under high vacuum and refluxing toluene to give 3,3'-[(5-nitro-1,3-phenylene)bis(carbonylimino)]bis[2,7-naphthalenedisulfonic acid] tetrasodium salt.
Reaction SMILES: [C:1]([O:5][C:6](=[O:19])[NH:7][C:8]([CH3:18])([CH3:17])[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12](Br)[CH:11]=1)([CH3:4])([CH3:3])[CH3:2].[C:20]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)(=[O:23])[CH:21]=[CH2:22].P(OC1C=CC(C)=CC=1)(OC1C=CC(C)=CC=1)OC1C=CC(C)=CC=1.C(N(CC)CC)C>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:25]([O:24][C:20](=[O:23])[CH:21]=[CH:22][C:12]1[CH:13]=[CH:14][CH:15]=[C:10]([CH2:9][C:8]([NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:19])([CH3:18])[CH3:17])[CH:11]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: CC(C)(Cc1cccc(Br)c1)NC(=O)OC(C)(C)C
Reactant: C=CC(=O)OCc1ccccc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccc(OP(Oc2ccc(C)cc2)Oc2ccc(C)cc2)cc1
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CC(C)(Cc1cccc(C=CC(=O)OCc2ccccc2)c1)NC(=O)OC(C)(C)C
Yield: 90 %

Procedure:
A mixture of [2-(3-bromophenyl)-1,1-dimethylethyl]carbamic acid tert-butyl ester (preparation 32), (2 g, 6.09 mmol), benzyl acrylate (2 g, 12.19), palladium (II) acetate (204 mg, 0.91 mmol), tri-p-tolyl phosphite (556 mg, 1.83 mmol) and triethylamine (2.12 mL, 15.22 mmol) in acetonitrile (100 mL) was heated under reflux for 48 hours. The reaction mixture was then concentrated in vacuo and the residue was purified by column chromatography on silica gel, eluting with ethyl acetate:pentane to afford the title compound as a pale yellow oil in 90% yield, 2.23 g.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][C:19]=1[F:20])[CH:5]=[N:6][C:7]1[CH:12]=[CH:11][C:10]([S:13](=[O:16])(=[O:15])[NH2:14])=[CH:9][CH:8]=1.C[Si]([C:25]#[N:26])(C)C>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]([NH:6][C:7]2[CH:12]=[CH:11][C:10]([S:13](=[O:16])(=[O:15])[NH2:14])=[CH:9][CH:8]=2)[C:25]#[N:26])[CH:17]=[CH:18][C:19]=1[F:20]
Reactant: NS(=O)(=O)c1ccc(N=Cc2ccc(F)c(F)c2)cc1
Reactant: C[Si](C)(C)C#N
Product: N#CC(Nc1ccc(S(N)(=O)=O)cc1)c1ccc(F)c(F)c1

Procedure:
Following a procedure similar to that described in Example 1(ii), but using N-(3,4-difluorobenzylidene)-4-sulfamoylaniline [prepared as described in step (i) above] and trimethylsilyl cyanide as starting materials, the title compound was obtained as a slightly yellow powder (yield 92%). Nuclear Magnetic Resonance Spectrum (270 MHz, hexadeuterated dimethyl sulfoxide) δ ppm:
Reaction SMILES: [OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([OH:12])=[CH:4][C:3]=1[C:13]([OH:15])=[O:14].C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(C)C=CC=CC=1.[CH2:34]([S:36]([CH2:39][CH2:40]O)(=[O:38])=[O:37])[CH3:35]>C(#N)C>[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][CH2:35][CH2:34][S:36]([CH2:39][CH3:40])(=[O:38])=[O:37])=[CH:4][C:3]=1[C:13]([OH:15])=[O:14]
Reactant: CCS(=O)(=O)CCO
Reactant: O=C(O)c1cc(O)c2ccccc2c1O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: CC#N
Product: CCS(=O)(=O)CCOc1cc(C(=O)O)c(O)c2ccccc12
Temperature: 95 °C
Yield: 53 %

Procedure:
20.4 g (0.1 mol) of 1,4-dihydroxy-2-naphthoic acid and 19 g (0.1 mol) of p-toluenesulfonic acid were added to 200 ml of dehydrated toluene. To the mixture, 27.6 g (0.2 mol) of β-ethylsulfonylethanol was added dropwise for 30 minutes under heating at 95° C. with stirring. After heating with stirring for 7 hours, the mixture was cooled to 20° to 30° C. 100 ml of acetonitrile was added to the mixture, the solid deposited was separated by filtration to obtain 17.2 g (53%) of 1-hydroxy-4-(β-ethylsulfonylethoxy)-2-naphthoic acid.
Reaction SMILES: [Cl:1][S:2]([OH:5])(=O)=[O:3].[CH3:6][N:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9][CH2:8]1>>[CH3:6][N:7]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([S:2]([Cl:1])(=[O:5])=[O:3])[CH:14]=2)[CH2:9][CH2:8]1
Reactant: O=S(=O)(O)Cl
Reactant: CN1CCc2ccccc21
Product: CN1CCc2ccc(S(=O)(=O)Cl)cc21
Temperature: 0 °C
Yield: 6.9 %

Procedure:
ClSO3H (400 g, 3.45 mol) was cooled to 0° C. and 1-methylindoline (35 g, 263.16 mmol) was added dropwise with stirring, maintaining the temperature at 0° C. The resulting solution was then warmed to room temperature and stirred for 20 hours. The reaction mixture was added carefully then dropwise to 3 L of iced water and the resulting solution was extracted using dichloromethane (3×400 mL). The organic layers were combined, dried (Na2SO4) and concentrated. The resulting residue was purified by column chromatography using a 1:30 ethyl acetate/petroleum ether solvent system. The collected fractions were combined and concentrated to give 4.2 g (7%) of 1-methylindoline-6-sulfonyl chloride as a brown solid. 1H NMR (CDCl3) δ 7.34 (d, 1H), 7.20 (d, 1H), 6.95 (s, 1H), 3.52 (t, 2H), 3.08 (t, 2H), 2.86 (s, 3H).
Reaction SMILES: [Al+3].[Cl-].[Cl-].[Cl-].[Br:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([OH:12])[C:7]=1C.[CH:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=[CH:16][C:15]=1[C:24](Cl)=[O:25].[CH:27](Cl)(Cl)Cl>>[Br:5][C:6]1[CH:7]=[C:8]([O:12][CH3:27])[CH:9]=[CH:10][C:11]=1[C:24]([C:15]1[CH:16]=[CH:17][C:18]2[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:14]=1)=[O:25]
Reactant: ClC(Cl)Cl
Reactant: O=C(Cl)c1ccc2ccccc2c1
Reactant: Cc1c(O)cccc1Br
Agent: [Al+3]
Agent: [Cl-]
Product: COc1ccc(C(=O)c2ccc3ccccc3c2)c(Br)c1
Yield: 47 %

Procedure:
AlCl3 (17.48 g; 131.1 mmol) was added portionwise to a mixture of 3-bromocresol (16.04 g; 87.4 mmol) and 2-naphthoyl chloride (25.00 g; 131.1 mmol) in 50 mL of CHCl3 gave 14.0 g (47%) of the title compound.
Reaction SMILES: [CH3:1][C@H:2]1[CH2:19][C@@:17]2([CH3:18])[C@@H:13]([CH2:14][CH2:15][C:16]2=[O:20])[C@H:12]2[C@H:3]1[C@@H:4]1[C:9]([CH2:10][CH2:11]2)=[CH:8][C:7](=[O:21])[CH2:6][CH2:5]1.O1CCO[CH2:24][CH2:23]1.C(OCC)(OCC)OCC.C(=O)([O-])O.[Na+]>C(O)C.N1C=CC=CC=1>[CH2:23]([O:21][C:7]1[CH2:6][CH2:5][C@H:4]2[C:9](=[CH:10][CH2:11][C@@H:12]3[C@@H:3]2[C@@H:2]([CH3:1])[CH2:19][C@@:17]2([CH3:18])[C@H:13]3[CH2:14][CH2:15][C:16]2=[O:20])[CH:8]=1)[CH3:24]
Reactant: C1COCCO1
Reactant: C[C@H]1C[C@]2(C)C(=O)CC[C@H]2[C@@H]2CCC3=CC(=O)CC[C@@H]3[C@H]21
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(OCC)OCC
Solvent: c1ccncc1
Solvent: CCO
Product: CCOC1=CC2=CC[C@@H]3[C@H]([C@@H](C)C[C@]4(C)C(=O)CC[C@@H]34)[C@H]2CC1

Procedure:
—Pyridinium p-toluenesulfonate (1.65 g) was added to a solution of (11β)-11-methylestr-4-ene-3,17-dione [van den Broek, A. J. et al, Steroids 30, 481 (1977); 16.86 g] in a mixture of ethanol (110 ml), dioxane (220 ml) and triethyl orthoformate (35.0 ml). After 4 h stirring at room temperature pyridine was added and the reaction mixture was poured into a saturated aqueous solution of sodium hydrogencarbonate. The product was extracted into ethyl acetate; the combined organic phases were washed with water and brine, dried over magnesium sulfate and concentrated under reduced pressure, to give (11β)-3-ethoxy-11-methylestra-3,5-dien-17-one (21.84 g). The product was used in the following step without further purification.
Reaction SMILES: O[CH:2]([C:7]1[CH:8]=[C:9]([CH:19]2[CH2:21][CH:20]2[C:22]2[CH:31]=[C:30]3[C:25]([CH2:26][CH2:27][N:28]=[C:29]3[CH:32]([CH3:34])[CH3:33])=[CH:24][CH:23]=2)[CH:10]=[C:11]2[C:16]=1[CH:15]=[C:14]([C:17]#[N:18])[CH:13]=[CH:12]2)[CH2:3][CH:4]([CH3:6])[CH3:5].C1(C)C=CC(S(O)(=O)=O)=CC=1>C(OCCOCC)C>[CH:32]([C:29]1[C:30]2[C:25](=[CH:24][CH:23]=[C:22]([CH:20]3[CH2:21][CH:19]3[C:9]3[CH:10]=[C:11]4[C:16](=[C:7](/[CH:2]=[CH:3]/[CH:4]([CH3:6])[CH3:5])[CH:8]=3)[CH:15]=[C:14]([C:17]#[N:18])[CH:13]=[CH:12]4)[CH:31]=2)[CH2:26][CH2:27][N:28]=1)([CH3:34])[CH3:33]
Reactant: CC(C)CC(O)c1cc(C2CC2c2ccc3c(c2)C(C(C)C)=NCC3)cc2ccc(C#N)cc12
Agent: CCOCCOCC
Agent: Cc1ccc(S(=O)(=O)O)cc1
Product: CC(C)/C=C/c1cc(C2CC2c2ccc3c(c2)C(C(C)C)=NCC3)cc2ccc(C#N)cc12
Temperature: 185 °C
Reaction time: 3 h

Procedure:
A solution of Example 8G (120 mg, 0.27 mmol) in 1,2 diethoxyethane was treated with para-toluenesulfonic acid (253 mg,1.3 mmol) and 3 Å molecular sieves (500 mg), heated to 185° C., and stirred for 3 hours. The mixture was cooled to room temperature, quenched with saturated NaHCO3, and extracted with ethyl acetate. The combined extracts were washed with water, dried (Na2SO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 25% ethyl acetate/hexanes to provide the desired product.
Reaction SMILES: [C:1]1([C:7]2[O:8][C:9]3[CH:15]=[CH:14][C:13]([NH2:16])=[CH:12][C:10]=3[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:17]1([CH2:23][CH2:24][C:25](Cl)=[O:26])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(N(C(C)C)CC)(C)C>ClCCl>[C:17]1([CH2:23][CH2:24][C:25]([NH:16][C:13]2[CH:14]=[CH:15][C:9]3[O:8][C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)=[N:11][C:10]=3[CH:12]=2)=[O:26])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: Nc1ccc2oc(-c3ccccc3)nc2c1
Reactant: O=C(Cl)CCc1ccccc1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: O=C(CCc1ccccc1)Nc1ccc2oc(-c3ccccc3)nc2c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 74.4 %

Procedure:
To a solution of 2-phenylbenzo[d]oxazol-5-amine (50 mg, 0.24 mmol) in dichloromethane (2 mL) at room temperature was added 3-phenylpropanoyl chloride (44.1 mg, 0.26 mmol) followed immediately by diisopropylethylamine (82 μL, 0.48 mmol). The resulting mixture was stirred at room temperature for 16 h. Dichloromethane was added and the organic layer was washed with saturated aqueous Na2CO3. The combined organic layers were dried over anhydrous MgSO4 and evaporated. The resulting solid was dissolved in methanol, passed through an acidic scavenger column (silica-based quaternary amine SPE-AX from Biotage®) and then evaporated to afford 61.1 mg (75%) of the title compound (LCMS RT=6.45 min, MH+ 343.2)
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:8]2[N:16]([CH2:17][C:18]([OH:20])=O)[C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[NH:33]1[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1>O1CCCC1>[Br:1][C:2]1[CH:3]=[C:4]([C:8]2[N:16]([CH2:17][C:18](=[O:20])[N:33]3[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]3)[C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)Cn1c(-c2cccc(Br)c2)nc2cccnc21
Reactant: C1CCNCC1
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Product: O=C(Cn1c(-c2cccc(Br)c2)nc2cccnc21)N1CCCCC1
Temperature: 25 °C
Reaction time: 4 h
Yield: 65.6 %

Procedure:
Under nitrogen bubbling, a mixture of 2-(3-bromophenyl)-3H-imidazo [4,5-b]pyridine-3-acetic acid (4.98 g, 0.015 mole) and 1,1'-carbonyldiimidazole (2.59 g, 0.016 mole) in 120 ml of tetrahydrofuran was stirred at room temperature for 4 hrs. The piperidine (2.55 g, 0.03 mole) was added and the reaction mixture was allowed to stir at room temperature overnight. The reaction mixture was filtered and the filtrate was evaporated to dryness, then placed under high vacuum for 3 hrs. The solid was treated with water, collected by filtration, washed with water, and dried at 50° C. under high vacuum over the weekend to give 3.93 g (66%) of title compound, mp 157°-58° C.
Reaction SMILES: [CH2:1]([S:7][C:8]1[N:13]=[C:12]([CH:14]=O)[CH:11]=[C:10]([C:16]([F:19])([F:18])[F:17])[N:9]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[NH:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1.C(O)(=O)C>C(O)C>[CH2:1]([S:7][C:8]1[N:13]=[C:12]([CH2:14][N:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[CH:11]=[C:10]([C:16]([F:19])([F:18])[F:17])[N:9]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: C1COCCN1
Reactant: CCCCCCSc1nc(C=O)cc(C(F)(F)F)n1
Solvent: CCO
Solvent: CC(=O)O
Product: CCCCCCSc1nc(CN2CCOCC2)cc(C(F)(F)F)n1

Procedure:
2-Hexylsulfanyl-6-trifluoromethyl-pyrimidine-4-carbaldehyde (0.5 g, 1.7 mmol) and morpholine (0.16 mL, 1.9 mmol) were dissolved in ethanol (5 mL) and acetic acid (0.5 mL) and treated with borane-pyridine complex (0.19 mL, 1.9 mmol) for 4 h at 20° C. The reaction mixture was evaporated to dryness. Extraction: 2×AcOEt, 1×10% aqueous Na2CO3. One obtained a mixture of the expected product and the reduced aldehyde which was more polar. This mixture was separated by chromatography on Si-amine from Silicycle with a gradient of heptane/ethyl acetate from 10:1 up to 1:1. Gave 220 mg (35%) of a colorless oil. MS: m/z=364 (M+H).
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[C:8]([CH:10]([CH3:12])[CH3:11])[CH:7]=[C:6]([CH:13]([CH3:15])[CH3:14])[C:5]=1[SH:16])([CH3:3])[CH3:2].[CH3:17][CH2:18][O-:19].[Na+].C(OC(OCC)CBr)C.Cl>CC(C)=O.O.C(O)C>[CH:13]([C:6]1[CH:7]=[C:8]([CH:10]([CH3:12])[CH3:11])[CH:9]=[C:4]([CH:1]([CH3:3])[CH3:2])[C:5]=1[S:16][CH2:17][CH:18]=[O:19])([CH3:15])[CH3:14]
Reactant: CC[O-]
Reactant: CC(C)c1cc(C(C)C)c(S)c(C(C)C)c1
Agent: CCOC(CBr)OCC
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: CCO
Solvent: CC(C)=O
Product: CC(C)c1cc(C(C)C)c(SCC=O)c(C(C)C)c1
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
Na (0.35 g, 15 mmol) was added in small pieces under Ar to dry ethanol (7 mL). A solution of 2,4,6-triisopropylthiophenol (3.55 g, 15 mmol) was added to the solution of NaOEt and the resulting mixture stirred for 5 min at RT. Bromoacetaldehyde diethylacetal (2.5 mL, 16.5 mmol, Aldrich) was added dropwise to the solution of Na thiolate and the resulting mixture refluxed for 2 h. After that, it was poured into H2O (100 mL), extracted with CH2Cl2 (3×50 mL), the extracts dried (MgSO4), filtered and evaporated (aspirator). The NMR showed the presence of the product and ca. 15% of bromoacetaldehyde diethylacetal impurity. The crude reaction mixture was refluxed with 2% aq. HCl (20 mL) and acetone (30 mL) for 2 h 10 min. The reaction mixture was extracted with CH2Cl2 (3×50 mL), the extracts were dried (MgSO4), filtered and evaporated. Distillation of the product gave a clear liquid, bp 108–114C/0.5 mm, 3.58 g (85.6%). 1H NMR (CD2Cl2) 9.57 (t, 1H; J=3.4 Hz); 7.00 (s, 2H); 3.86 (septet, 2H; J=7.1 Hz); 3.33 (d, 2H; J=3.4 Hz); 2.87 (septet, 1H; J=7.0 Hz); 1.23 (d, 6H; J=7.0 Hz); 1.22 (d, 12H; J=7.1 Hz).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]#[C:9][C:10]2[CH:15]=[CH:14][N:13]=[C:12]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH:11]=2)[CH:5]=[CH:6][CH:7]=1>CO.C(Cl)Cl.[Pd]>[NH2:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][N:13]=[C:12]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:21])([CH3:20])[CH3:22])[CH:11]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)Nc1cc(C#Cc2cccc(N)c2)ccn1
Agent: [Pd]
Solvent: ClCCl
Solvent: CO
Product: CC(C)(C)OC(=O)Nc1cc(CCc2cccc(N)c2)ccn1
Yield: 98.1 %

Procedure:
To a mixture of tert-butyl {4-[(3-aminophenyl)ethynyl]pyridin-2-yl}carbamate (328 mg, 1.06 mmol) in methanol (8 mL) and methylene chloride (8 mL) was added 10% palladium on carbon (100 mg, 0.09 mmol). The resultant mixture was hydrogenated at 30 psi for 18 hours. The reaction mixture was filtered, washed with MeOH/DCM and concentrated to give the desired product (326 mg, 98%) as a light brown powder. LCMS for C18H24N3O2 (M+H)+: m/z=314.1.
Reaction SMILES: [H-].[Na+].[OH:3][CH2:4][C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([S:14]([F:19])([F:18])([F:17])([F:16])[F:15])[CH:13]=1)[C:8]([OH:10])=[O:9].I[CH3:21].Cl>C1COCC1.O.CCCCC>[CH3:21][O:3][CH2:4][C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([S:14]([F:19])([F:15])([F:16])([F:17])[F:18])[CH:13]=1)[C:8]([OH:10])=[O:9]
Reactant: O=C(O)c1cc(CO)cc(S(F)(F)(F)(F)F)c1
Reactant: CI
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCCCC
Solvent: O
Product: COCc1cc(C(=O)O)cc(S(F)(F)(F)(F)F)c1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
108 mg (2.70 mmol) of sodium hydride (as a 60% strength suspension in mineral oil) were deoiled with pentane and then suspended in 5 ml of anhydrous THF. At 0° C., a solution of 250 mg (0.899 mmol) of the compound of Example 37A in 2.5 ml of anhydrous THF was slowly added dropwise to this suspension. After 30 min of stirring at 0° C., 170 μl (2.70 mmol) of iodomethane were added and the cooling bath was removed. Since, according to analytical HPLC, conversion was still incomplete after 6 h at RT, the mixture was once more cooled to 0° C., and a further 560 μl (9.0 mmol) of iodomethane and 36 mg (0.897 mmol) of sodium hydride (60% strength suspension in mineral oil) were added in succession. After 2 h of stirring at RT, about 75 ml of water were added carefully and the reaction mixture was acidified by addition of 1 M hydrochloric acid. The mixture was extracted three times with in each case about 25 ml of ethyl acetate. The combined organic extracts were washed successively with in each case about 30 ml of water and saturated sodium chloride solution. After drying over anhydrous magnesium sulphate, filtration and removal of the solvent on a rotary evaporator, the residue obtained was triturated with pentane. The crude product obtained in this manner was purified by preparative HPLC (Method 32). Pooling of the product fractions, removal of the solvent on a rotary evaporator and drying under high vacuum gave 153 mg (58% of theory) of the title compound.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][CH:12]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[N+:20](C1C=CC(CC2C=CC([N+]([O-])=O)=CC=2)=CC=1)([O-])=[O:21].[N+](C1C=CC(C(C2C=CC([N+]([O-])=O)=CC=2)=O)=CC=1)([O-])=O>O.C(O)(=O)C>[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10](=[N:20][OH:21])[C:11]2[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][CH:12]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1ccc(Cc2ccc([N+](=O)[O-])cc2)cc1
Agent: O=C(c1ccc([N+](=O)[O-])cc1)c1ccc([N+](=O)[O-])cc1
Solvent: CC(=O)O
Solvent: O
Product: O=[N+]([O-])c1ccc(C(=NO)c2ccc([N+](=O)[O-])cc2)cc1
Temperature: 25 °C

Procedure:
The title compound was prepared by modification of procedures previously reported in the literature (Chapman and Fidler (1936) J. Chem. Soc, 448; Kulin and Leffek (1973) Can. J. Chem., 51: 687). A solution of chromic anhydride (20 g, 200 mmol) in 125 ml of H2O was added dropwise over 4 hours, to a suspension of bis(4-nitrophenyl)methane (25 g, 97 mmol) in 300 ml of acetic acid heated to reflux. The reaction mixture was heated at reflux for 1 hour, cooled to room temperature, and poured into water. The solid was collected by filtration, washed with H2O, 5% sodium bicarbonate, H2O, and air-dryed to provide a 1:1 mixture of bis(4-nitrophenyl)methane/4,4'-dinitrobenzophenone via 1H NMR. This material was oxidized with a second portion of chromic anhydride (20 g, 200 mmol), followed by an identical work-up procedure to provide the crude product. Trituration with 200 ml of benzene heated to reflux for 16 hours provided 4,4'-dinitrobenzophenone (20.8 g, 79%) as a yellow powder.