Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[CH:2]([CH3:16])[C:3](=[O:15])[C:4](=[N:10][O:11][CH2:12][CH2:13][CH3:14])[C:5]([O:7][CH2:8][CH3:9])=[O:6].[SH:17][CH2:18][CH2:19][OH:20].C(N(CC)CC)C>C(Cl)(Cl)Cl>[OH:20][CH2:19][CH2:18][S:17][CH:2]([CH3:16])[C:3](=[O:15])[C:4](=[N:10][O:11][CH2:12][CH2:13][CH3:14])[C:5]([O:7][CH2:8][CH3:9])=[O:6]
Reactant: OCCS
Reactant: CCCON=C(C(=O)OCC)C(=O)C(C)Cl
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: CCCON=C(C(=O)OCC)C(=O)C(C)SCCO
Temperature: 20 °C
Reaction time: 1.33 h
Yield: 85.1 %

Procedure:
Ethyl 4 chloro-3-oxo-2-n-propoxyiminovalerate (180.0 g.) was added to a stirred solution of 2-mercaptoethanol (71.6 g.) in chloroform (1.8 l.), and then a solution of triethylamine (93.1 g.) in chloroform (200 ml.) was added to the solution over 5 minutes. The solution was stirred at 20° C. for 80 minutes. After washing the resultant mixture with 10% hydrochloric acid twice, a saturated aqueous solution of sodium bicarbonate twice and water in turn, the solution was dried over magnesium sulfate and concentrated in vacuo to give ethyl 4-(2-hydroxyethylthio)-3-oxo-2-n-propoxyiminovalerate (178.7 g.).
Reaction SMILES: [C:1]([O:13]C)(=O)[C:2]1[CH:11]=[CH:10][CH:9]=[C:4]([C:5]([O:7][CH3:8])=[O:6])[CH:3]=1.[CH3:15][C:16]([CH3:18])=[O:17].[H-].[Na+].Cl>C1(C)C=CC=CC=1.O>[CH3:8][O:7][C:5](=[O:6])[C:4]1[CH:9]=[CH:10][CH:11]=[C:2]([C:1](=[O:13])[CH2:15][C:16](=[O:17])[CH3:18])[CH:3]=1
Reactant: CC(C)=O
Reactant: COC(=O)c1cccc(C(=O)OC)c1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: Cc1ccccc1
Product: COC(=O)c1cccc(C(=O)CC(C)=O)c1
Temperature: 100 °C
Yield: 13.1 %

Procedure:
A solution of dimethyl isophthalate (12 g, 61.85 mmole) and acetone (5 mL, 68 mmole) in a mixture of toluene/dimethoyethane (90 mL/30 mL) was added to a suspension of NaH 60% (2.97 g, 74.23 mmole) in dry toluene (30 mL) under argon. The mixture was heated at 100° C. for 4 hours. The reaction mixture was cooled to rt and 25 mL of water were added. The mixture was poured into water (250 mL) and the pH was adjusted to 3-4 with HCl 2N. The aqueous mixture was extracted with ethyl acetate (2×250 mL), washed with brine, dried over sodium sulphate and evaporated to afford a yellow solid which was purified by column cromatography (n-Hex/EtOAc 9:1 to 8:2) to afford the title compound (1.78 g, 11% yield) as a yellow solid.
Reaction SMILES: [F:1][C:2]([F:16])([F:15])[C:3]1[C:4]([NH2:14])=[C:5]([NH2:13])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.N1C=CC=CC=1.Cl[C:24](=[O:31])[CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27]>C(Cl)Cl>[NH2:14][C:4]1[C:3]([C:2]([F:15])([F:16])[F:1])=[CH:8][C:7]([C:9]([F:12])([F:11])[F:10])=[CH:6][C:5]=1[NH:13][C:24](=[O:31])[CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27]
Reactant: CCOC(=O)CC(=O)Cl
Reactant: Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1N
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCOC(=O)CC(=O)Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1N
Temperature: 0 °C
Reaction time: 3 h
Yield: 76.8 %

Procedure:
An ice-cold solution of 3,5-bis(trifluoromethyl)-1,2-phenylenediamine (880 mg, 3.6 mmol) and pyridine (104 mg, 1.3 mmol) in methylene chloride (20 mL) was treated with ethyl 3-chloro-3-oxopropionate (181 mg, 1.2 mmol). The mixture was stirred at 0° C. for 3 h, then allowed to warm to room temperature and stirred for four days. The solution was diluted to 100 mL with methylene chloride, washed with saturated NH4Cl (3×20 mL), water (20 mL), and brine (20 mL), then dried over sodium sulfate and concentrated in-vacuo. The residue was purified over silica gel, eluting with 20%-30%-40% EtOAc/heptane, to yield 330 mg of a white solid as product. 1H NMR (500 MHz, DMSO) δ ppm 1.22 (t, J=7.15 Hz, 3 H) 3.52 (s, 2 H) 4.14 (q, J=7.15 Hz, 2 H) 6.16 (s, 2 H) 7.54 (s, 1 H) 7.71 (m, 1 H) 9.60 (s, 1 H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]=[C:12]([N+]([O-])=O)[CH3:13])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].C.CO.S(=O)(=O)(O)[OH:21]>[Pd].O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][C:12](=[O:21])[CH3:13])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]
Reactant: COc1ccc(C=C(C)[N+](=O)[O-])cc1OC
Reactant: O=S(=O)(O)O
Agent: [Pd]
Solvent: O
Solvent: CO
Product: COc1ccc(CC(C)=O)cc1OC

Procedure:
(3,4-Dimethoxyphenyl)-2-nitropropene (11) (200 g, 0.90 mol), palladium 10%/charcoal (10.0 g, either fresh or recycled), methanol (750 ml), water (220 ml) and sulfuric acid (96%, 28 ml) are charged to a steel autoclave thermostatted at 15° C.
Reaction SMILES: [C:1]([O:5][C:6](=[O:35])[C:7]([S:10][C:11]1[S:12][CH:13]=[C:14]([CH2:16][CH2:17][N:18]([CH2:27][C:28]2[CH:33]=[CH:32][C:31]([NH2:34])=[CH:30][CH:29]=2)[C:19]2[N:24]=[CH:23][C:22]([CH2:25][CH3:26])=[CH:21][N:20]=2)[N:15]=1)([CH3:9])[CH3:8])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[C:43](Cl)(=[O:46])[CH2:44][CH3:45]>O1CCCC1>[C:1]([O:5][C:6](=[O:35])[C:7]([S:10][C:11]1[S:12][CH:13]=[C:14]([CH2:16][CH2:17][N:18]([C:19]2[N:24]=[CH:23][C:22]([CH2:25][CH3:26])=[CH:21][N:20]=2)[CH2:27][C:28]2[CH:29]=[CH:30][C:31]([NH:34][C:43](=[O:46])[CH2:44][CH3:45])=[CH:32][CH:33]=2)[N:15]=1)([CH3:8])[CH3:9])([CH3:2])([CH3:3])[CH3:4]
Reactant: CCC(=O)Cl
Reactant: CCc1cnc(N(CCc2csc(SC(C)(C)C(=O)OC(C)(C)C)n2)Cc2ccc(N)cc2)nc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CCC(=O)Nc1ccc(CN(CCc2csc(SC(C)(C)C(=O)OC(C)(C)C)n2)c2ncc(CC)cn2)cc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
2-[(4-{2-[(4-Aminobenzyl)(5-ethylpyrimidin-2-yl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl ester (120 mg) synthesized in Example 439-2 was dissolved in tetrahydrofuran (2.5 mL), triethylamine (40 mL) and propionyl chloride (22 μL) were added thereto, and the mixture was stirred at room temperature for 30 min. The reaction solution was concentrated under reduced pressure, the residue was directly purified by silica gel chromatography (elution solvent; hexane:ethyl acetate=1:1) to give the title compound (100 mg) as a colorless oil.
Reaction SMILES: OCCCN1C=C(C2C=CC(N[C:22]3[C:27]([C:28]([F:31])([F:30])[F:29])=[CH:26][N:25]=[C:24]([NH:32][C:33]4[CH:47]=[CH:46][C:36]([CH2:37][P:38](=[O:45])([O:42][CH2:43][CH3:44])[O:39][CH2:40][CH3:41])=[CH:35][C:34]=4[O:48][CH3:49])[N:23]=3)=C3C=2CN(C)C3=O)C=N1.[NH2:50][C:51]1[C:52]([C:67]([NH:69][CH3:70])=[O:68])=[N:53][C:54]([C:57]2[C:58]([Cl:66])=[N:59][N:60]([CH2:62][CH2:63][CH2:64][OH:65])[CH:61]=2)=[CH:55][CH:56]=1>>[Cl:66][C:58]1[C:57]([C:54]2[N:53]=[C:52]([C:67](=[O:68])[NH:69][CH3:70])[C:51]([NH:50][C:26]3[C:27]([C:28]([F:29])([F:30])[F:31])=[CH:22][N:23]=[C:24]([NH:32][C:33]4[CH:47]=[CH:46][C:36]([CH2:37][P:38](=[O:45])([O:42][CH2:43][CH3:44])[O:39][CH2:40][CH3:41])=[CH:35][C:34]=4[O:48][CH3:49])[N:25]=3)=[CH:56][CH:55]=2)=[CH:61][N:60]([CH2:62][CH2:63][CH2:64][OH:65])[N:59]=1
Reactant: CCOP(=O)(Cc1ccc(Nc2ncc(C(F)(F)F)c(Nc3ccc(-c4cnn(CCCO)c4)c4c3C(=O)N(C)C4)n2)c(OC)c1)OCC
Reactant: CNC(=O)c1nc(-c2cn(CCCO)nc2Cl)ccc1N
Product: CCOP(=O)(Cc1ccc(Nc2ncc(C(F)(F)F)c(Nc3ccc(-c4cn(CCCO)nc4Cl)nc3C(=O)NC)n2)c(OC)c1)OCC
Yield: 59 %

Procedure:
Prepared analogously to Compound 1B using 3-amino-6-[3-chloro-1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-N-methylpyridine-2-carboxamide (Compound 49C, 365 mg, 1.18 mmol) to afford 480 mg of the title compound (59%). 1H NMR (400 MHz, CD3OD) δ 9.06 (br. s., 1H), 8.51 (s, 1H), 8.35 (s, 1H), 7.89 (d, J=9.1 Hz, 1H), 7.82 (d, J=8.1 Hz, 1H), 7.04 (t, J=2.0 Hz, 1H), 6.91 (td, J=2.3, 8.1 Hz, 1H), 4.26 (t, J=6.9 Hz, 2H), 4.00-4.11 (m, 4H), 3.89 (s, 3H), 3.59 (t, J=6.1 Hz, 2H), 3.35 (s, 1H), 3.23 (s, 1H), 2.98 (s, 3H), 2.11 (quin, J=6.5 Hz, 2H), 1.22-1.29 (m, 6H). MS (ESI): m/z=727.38/729.32 [M+H]+. UPLC: tR=1.35 min (UPLC-TOF: polar—2 min).
Reaction SMILES: [CH3:1][C:2]([C:5]1[CH:10]=[C:9]([SH:11])[CH:8]=[C:7]([C:12]([CH3:15])([CH3:14])[CH3:13])[C:6]=1[OH:16])([CH3:4])[CH3:3].[O:17]=[C:18]([N:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1)[CH:19]=[CH2:20].C(N(CC)CC)C>CO>[CH3:4][C:2]([C:5]1[CH:10]=[C:9]([S:11][CH2:20][CH2:19][C:18]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=[O:17])[CH:8]=[C:7]([C:12]([CH3:15])([CH3:14])[CH3:13])[C:6]=1[OH:16])([CH3:1])[CH3:3]
Reactant: CC(C)(C)c1cc(S)cc(C(C)(C)C)c1O
Reactant: C=CC(=O)N1CCOCC1
Solvent: CO
Solvent: CCN(CC)CC
Product: CC(C)(C)c1cc(SCCC(=O)N2CCOCC2)cc(C(C)(C)C)c1O
Temperature: 25 °C
Reaction time: 12 h

Procedure:
Following the procedure of Example 4, 2,6-bis-(1,1-dimethylethyl)4-mercaptophenol (2.38 g, 0.01 mole) and (1-oxo-2-propenyl)morpholine(1.41 g, 0.01 mole) in methanol (75 ml) were combined with triethylamine (1.5 ml) and stirred for 12 hours at room temperature. The solvent was evaporated under a nitrogen stream leaving an orange oil which was chromatographed over silica. The product was recrystallized from a mixture of hexane, ethyl ether and methanol and the resu-ting white solid dried to yield the title compound, m.p. about 136.5°-137.5° C.
Reaction SMILES: C(=O)([O-])O.[Na+].[I:6]N1C(=O)CCC1=O.[CH2:14]([N:21]1[C:25]2[N:26]=[C:27]([C:33]3[CH:38]=[CH:37][C:36]([F:39])=[C:35]([C:40]([O:42][CH3:43])=[O:41])[CH:34]=3)[CH:28]=[C:29]([C:30]([OH:32])=[O:31])[C:24]=2[CH:23]=[N:22]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>O1CCOCC1>[CH2:14]([N:21]1[C:25]2[N:26]=[C:27]([C:33]3[CH:38]=[CH:37][C:36]([F:39])=[C:35]([C:40]([O:42][CH3:43])=[O:41])[CH:34]=3)[CH:28]=[C:29]([C:30]([OH:32])=[O:31])[C:24]=2[C:23]([I:6])=[N:22]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: COC(=O)c1cc(-c2cc(C(=O)O)c3cnn(Cc4ccccc4)c3n2)ccc1F
Reactant: O=C1CCC(=O)N1I
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1COCCO1
Product: COC(=O)c1cc(-c2cc(C(=O)O)c3c(I)nn(Cc4ccccc4)c3n2)ccc1F
Temperature: 25 °C
Reaction time: 24 h
Yield: 57.9 %

Procedure:
Sodium hydrogen carbonate (11.39 g/0.136 mol) and N-iodosuccinimide (30.51 g/0.136 mol) are added portionwise to a suspension of 1-benzyl-6-[4-fluoro-3-(methoxycarbonyl)phenyl]-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (14.25 g/45.2 mmol) in 410 mL of dioxane. The reaction mixture is stirred for 24 h at ambient temperature. The reaction medium is run into a saturated aqueous solution of NaHCO3. The aqueous phase is washed with EtOAc and then acidified to pH=2-3 using a solution of KHSO4 (1 M), and extracted with EtOAc. The organic phase is washed with water, with a solution of sodium thiosulphate (0.1 M) and with a saturated aqueous solution of NaCl, dried over sodium sulphate and then concentrated to dryness to give 13.9 g of a yellow powder (yield: 70%).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH3:8].[Mg].[C:10]([P:14](Cl)[C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:13])([CH3:12])[CH3:11].S(=O)(=O)(O)O>O1CCCC1.[Cu]Cl.C1(C)C=CC=CC=1>[C:10]([P:14]([C:15]([CH3:18])([CH3:17])[CH3:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH3:8])([CH3:13])([CH3:12])[CH3:11]
Reactant: Cc1ccccc1Br
Reactant: CC(C)(C)P(Cl)C(C)(C)C
Agent: Cl[Cu]
Agent: O=S(=O)(O)O
Agent: [Mg]
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: Cc1ccccc1P(C(C)(C)C)C(C)(C)C
Reaction time: 4 h
Yield: 91 %

Procedure:
In a 500 ml four-necked flask thoroughly purged with nitrogen, a Grignard reagent solution previously prepared from 20.5 g (0.12 mol) of 2-bromotoluene and 3.1 g (0.13 mol) of metallic magnesium in a mixed solvent of 100 ml of tetrahydrofuran and 40 ml of toluene, and 0.05 g (0.0005 mol (corresponding to 0.5% by mol)) of copper(I) chloride were placed. To the contents of the flask, a solution of 18.1 g (0.10 mol) of di-tert-butylphosphinous chloride in 30 ml of tetrahydrofuran was dropwise added over a period of 1 hour with maintaining the temperature at 25° C. to 30° C. After the dropwise addition was completed, stirring was conducted at 50° C. for 4 hours. After the temperature of the reaction solution was returned to room temperature, disappearance of di-tert-butylphosphinous chloride was confirmed by gas chromatography. Thereafter, 30 ml of a 5% sulfuric acid aqueous solution was added to the reaction solution to perform liquid separation. Then, the organic layer was washed with water and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, followed by further distillation. Then, fractions given by distillation at 112° C. to 114° C. under reduced pressure of 3 Torr were collected. As a result, 21.5 g (purity: 99.0%) of the aimed di-tert-butyl(2-methylphenyl)phosphine was obtained. The yield was 91.0%.
Reaction SMILES: [CH3:1][S:2]([CH3:5])(=[O:4])=[O:3].[H-].[Na+].CS(C)=O.C[O:13][C:14](=O)[C:15]1[CH:20]=[C:19]([O:21][CH3:22])[C:18]([NH:23][C:24](=[O:26])[CH3:25])=[C:17]([O:27][CH3:28])[CH:16]=1>O>[CH3:22][O:21][C:19]1[CH:20]=[C:15]([C:14](=[O:13])[CH2:1][S:2]([CH3:5])(=[O:4])=[O:3])[CH:16]=[C:17]([O:27][CH3:28])[C:18]=1[NH:23][C:24](=[O:26])[CH3:25]
Reactant: COC(=O)c1cc(OC)c(NC(C)=O)c(OC)c1
Reactant: CS(C)(=O)=O
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: COc1cc(C(=O)CS(C)(=O)=O)cc(OC)c1NC(C)=O
Temperature: 25 °C
Reaction time: 20 h

Procedure:
A suspension of 30.1 g. of dimethylsulfone and 11.5 g. of sodium hydride (50% dispersion in oil) in 80 ml. of dimethylsulfoxide was stirred at 50° C. for 3 hours with the exclusion of moisture. Then, 20.3 g. of 4-acetamido-3,5-dimethoxy-benzoic acid methyl ester were added and the mixture was stirred at room temperature for an additional 20 hours. Thereafter, the solution was diluted with 1 liter of water and extracted with three 1 liter portions of ethyl acetate. The ethyl acetate extracts were washed with two 300 ml. portions of water, combined, dried over magnesium sulfate and evaporated to dryness under vacuum. Recrystallization of the residue from ethyl acetate gave 2',6'-dimethoxy-4'-[(methylsulfonyl-acetyl)]-acetanilide having a melting point of 206°-207° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4](F)[C:3]=1[N+:10]([O-])=O.[CH3:13][NH:14][CH3:15]>C1COCC1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([N:14]([CH3:15])[CH3:13])[C:3]=1[NH2:10]
Reactant: O=[N+]([O-])c1c(F)cc(F)cc1F
Reactant: CNC
Solvent: C1CCOC1
Product: CN(C)c1cc(F)cc(F)c1N
Temperature: 0 °C
Reaction time: 0.75 h
Yield: 50 %

Procedure:
To a solution of 2,4,6-trifluoronitrobenzene (2.58 g, 0.0145 mol) in THF (20.0 ml) was added a solution of N,N-dimethylamine in THF (8.5 mL of 2M soln) and stirred for 45 min at 0° C. It was then stirred at room temperature for 30 min and concentrated to dryness. The resulting material was dissolved in EtOH (25 mL), added Pd/C (10%, 0.6 g) and hydrogenated at 50 psi for 4 h. The catalyst was removed by filtration, and the filtrate was concentrated to dryness under reduced pressure. The residue was partitioned between sod. bicarbonate (10%, 25 mL) and EtOAc (30 mL). The organic phase was washed with water, dried (Na2SO4), and concentrated to dryness to afford the title compound (1.3 g, 50%) as a dark colored solid: 1H NMR (CDCl3/400 MHz) δ6.52 (m, 2H), 3.64 (br, 2H), and 2.65 (s, 6H); ES-HRMS m/z 172.0772 (M+C8H10N2F2 requires 172.0810).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:30]=[C:31](F)[CH:32]=1)[C:5]([NH:7][C:8]1[CH:9]=[CH:10][C:11]([CH3:29])=[C:12]([NH:14][C:15](=[O:28])[C:16]2[CH:21]=[CH:20][C:19]([CH2:22][N:23]([CH2:26][CH3:27])[CH2:24][CH3:25])=[CH:18][CH:17]=2)[CH:13]=1)=[O:6].[NH:34]1[CH2:38][CH:37]=[CH:36][CH2:35]1>>[F:1][C:2]1[CH:3]=[C:4]([CH:30]=[C:31]([N:34]2[CH2:38][CH:37]=[CH:36][CH2:35]2)[CH:32]=1)[C:5]([NH:7][C:8]1[CH:9]=[CH:10][C:11]([CH3:29])=[C:12]([NH:14][C:15](=[O:28])[C:16]2[CH:17]=[CH:18][C:19]([CH2:22][N:23]([CH2:26][CH3:27])[CH2:24][CH3:25])=[CH:20][CH:21]=2)[CH:13]=1)=[O:6]
Reactant: CCN(CC)Cc1ccc(C(=O)Nc2cc(NC(=O)c3cc(F)cc(F)c3)ccc2C)cc1
Reactant: C1=CCNC1
Product: CCN(CC)Cc1ccc(C(=O)Nc2cc(NC(=O)c3cc(F)cc(N4CC=CC4)c3)ccc2C)cc1
Yield: 58 %

Procedure:
Using an analogous procedure to that described in Example 67 except that the reaction mixture was heated to 100° C. for 16 hours rather than for 6 days, N-[5-(3,5-difluorobenzamido)-2-methylphenyl]-4-diethylaminomethylbenzamide was reacted with 3-pyrroline. There was thus obtained the title compound in 58% yield; NMR Spectrum: (DMSOd6) 1.0 (t, 6H), 2.2 (s, 3H), 2.5 (m, 4H), 3.6 (s, 2H), 4.15 (s, 4H), 6.05 (m, 1H), 6.45-6.55 (m, 1H), 6.9 (s, 1H), 6.97 (m, 1H), 7.22 (m, 1H), 7.45 (d, 2H), 7.57 (m, 1H), 7.8 (m, 1H), 7.95 (d, 2H), 9.8 (s, 1H), 10.12 (broad s, 1H); Mass Spectrum: M+H+501.
Reaction SMILES: [F:1][C:2]1[C:7]([CH:8]2[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]2)=[CH:6][CH:5]=[CH:4][N:3]=1.[CH3:15][Si](C=[N+]=[N-])(C)C.O>C(Cl)Cl>[F:1][C:2]1[C:7]([CH:8]2[CH2:15][CH2:9][CH2:10][C:11](=[O:14])[CH2:12][CH2:13]2)=[CH:6][CH:5]=[CH:4][N:3]=1
Reactant: O=C1CCC(c2cccnc2F)CC1
Reactant: C[Si](C)(C)C=[N+]=[N-]
Solvent: ClCCl
Solvent: O
Product: O=C1CCCC(c2cccnc2F)CC1

Procedure:
To a solution of boron trifluoride-diethyl etherate (0.64 g, 4.50 mmol) and 4-(2-fluoropyridin-3-yl)cyclohexanone (0.79 g, 4.09 mmol) in DCM (8 mL) at −25° C. under argon was added (trimethylsilyl)diazomethane (2.25 mL, 5.18 mmol, 2.0 M in hexanes). The reaction was stirred for 2 h at that temperature, water was added, and the mixture was extracted with DCM (2×). The combined organic extracts were washed with 10:1 saturated ammonium chloride/ammonium hydroxide mixture (1×), water (1×), saturated aqueous sodium chloride (1×), and dried over anhydrous magnesium sulfate. The mixture was filtered and the filtrate concentrated in vacuo. The resulting oil was purified by silica gel chromatography to give 4-(2-fluoropyridin-3-yl)cycloheptanone. MS (ESI, pos. ion) m/z: 208.1 (M+1).
Reaction SMILES: [CH3:1][CH:2]([C:8]([C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[CH2:15][CH:14]([NH:19][S:20]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)(=[O:22])=[O:21])[CH2:13]2)=[O:9])[CH2:3][C:4]([O:6]C)=[O:5].[OH-].[Na+]>>[CH3:1][CH:2]([C:8]([C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[CH2:15][CH:14]([NH:19][S:20]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)(=[O:22])=[O:21])[CH2:13]2)=[O:9])[CH2:3][C:4]([OH:6])=[O:5]
Reactant: COC(=O)CC(C)C(=O)c1ccc2c(c1)CC(NS(=O)(=O)c1ccccc1)C2
Agent: [Na+]
Agent: [OH-]
Product: CC(CC(=O)O)C(=O)c1ccc2c(c1)CC(NS(=O)(=O)c1ccccc1)C2

Procedure:
Prepared analogously to Example 2 from methyl 3-methyl-4-(2-benzenesulphonamido-indan-5-yl)-4-oxobuty rate by hydrolysis with sodium hydroxide.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[C:5]([CH3:9])=[N+:6]([O-])[CH:7]=1.P(Cl)(Cl)([Cl:16])=O.CN(C=O)C>C1(C)C=CC=CC=1>[Cl:16][C:7]1[N:6]=[C:5]([CH3:9])[C:4]([C:10]([O:12][CH3:13])=[O:11])=[N:3][C:2]=1[Cl:1]
Reactant: COC(=O)c1nc(Cl)c[n+]([O-])c1C
Reactant: O=P(Cl)(Cl)Cl
Solvent: CN(C)C=O
Solvent: Cc1ccccc1
Product: COC(=O)c1nc(Cl)c(Cl)nc1C
Temperature: 25 °C
Reaction time: 1 h
Yield: 67.5 %

Procedure:
To a solution of 5-chloro-3-(methoxycarbonyl)-2-methylpyrazine 1-oxide (8.83 g, 43.6 mmol) in toluene (100 mL) at 0° C. was added phosphorus oxychloride (10 ml, 109 mmol) and DMF (1 ml, 12.91 mmol). The reaction mixture was stirred at room temperature for 1 h, and then was heated to 85° C. fort 8 h. The mixture was cooled to RT and concentrated. The residue was diluted with EtOAc and washed with saturated NaHCO3 solution. The combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. The crude mixture was purified with ISCO (0% to 10% EtOAc/Hexanes) to afford the desired methyl 5,6-dichloro-3-methylpyrazine-2-carboxylate (6.51 g, 68% yield). 1H NMR (300 MHz, CDCl3) δ ppm 4.00 (3H, s), 2.83 (3H, s)
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]=[C:11]([C:13]3[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=3)[NH:10][N:9]=2)=[CH:4][CH:3]=1.[C:19](OC(=O)C)(=[O:21])[CH3:20]>>[C:19]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]=[C:11]([C:13]3[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=3)[NH:10][N:9]=2)=[CH:4][CH:3]=1)(=[O:21])[CH3:20]
Reactant: CC(=O)OC(C)=O
Reactant: Nc1ccc(-c2n[nH]c(-c3ccncc3)n2)cc1
Product: CC(=O)Nc1ccc(-c2n[nH]c(-c3ccncc3)n2)cc1
Reaction time: 0.5 h

Procedure:
To 3-(p-aminophenyl)-5-(4-pyridyl)-1,2,4-triazole (1 g.) is added acetic anhydride (20 ml.) and the resulting suspension is heated 18 hours on a steam bath. The excess acetic anhydride is removed under reduced pressure and water (25 ml.) is added to the residue. After stirring 0.5 hour, the solid is filtered and recrystallized to yield 3-(p-acetylaminophenyl)-5-(4-pyridyl)-1,2,4-triazole.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([O:14][CH3:15])[C:10]=1[N+:11]([O-])=O)[C:5]([OH:7])=[O:6].CC(O)=O.[H][H]>CO>[NH2:11][C:10]1[C:9]([O:14][CH3:15])=[CH:8][C:4]([C:5]([OH:7])=[O:6])=[CH:3][C:2]=1[F:1]
Reactant: COc1cc(C(=O)O)cc(F)c1[N+](=O)[O-]
Reactant: [H][H]
Solvent: CO
Solvent: CC(=O)O
Product: COc1cc(C(=O)O)cc(F)c1N

Procedure:
A solution of 3-fluoro-5-methoxy-4-nitrobenzoic acid (obtained above), HOAc (5 mL) and MeOH (5 mL) was hydrogenated using a hydrogen balloon overnight. The solution was then filtered through celite and concentrated to a red solid (590 mg, 66%). [M+H] calc'd for C8H8FNO3, 186. found 186.
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][CH:5]=1)=[O:3].[BH4-].[Na+].[NH3:15]>C(OCC)(=O)C>[NH2:15][CH2:1][CH:2]([OH:3])[C:4]1[CH:5]=[CH:6][C:7]([N+:10]([O-:12])=[O:11])=[CH:8][CH:9]=1
Reactant: N
Reactant: CC(=O)c1ccc([N+](=O)[O-])cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCOC(C)=O
Product: NCC(O)c1ccc([N+](=O)[O-])cc1

Procedure:
4-Nitroacetophenone is brominated in the α-position, the product obtained is redcuced by means of sodium borohydride to the corresponding bromohydrin and this is treated with ammonia. Rac.-α-(aminomethyl)-4-nitrobenzyl alcohol, m.p. 138°-139° (from ethyl acetate) is obtained.
Reaction SMILES: [C:1]([OH:9])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:10]1([CH3:17])[CH:15]=[CH:14][CH:13]=[C:12]([CH3:16])[CH:11]=1>[Zn]>[CH3:17][C:10]1[CH:11]=[C:12]([CH3:16])[CH:13]=[CH:14][C:15]=1[C:1]([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:9]
Reactant: O=C(O)c1ccccc1
Reactant: Cc1cccc(C)c1
Agent: [Zn]
Product: Cc1ccc(C(=O)c2ccccc2)c(C)c1
Temperature: 25 °C

Procedure:
Benzoic acid (0.31 g, 2.5 mmol), m-xylene (0.53 g, 5.0 mmol), [bmim][NTf2] (0.50 g) and M(NTf2)2 (M=Co (0.14 g, 0.25 mmol), or Zn (0.15 g, 0.25 mmol) were placed in flasks equipped with stirrers and condensers. The contents of the flask were heated under reflux (ca 140-150 ° C.) for 2 days, then cooled to room temperature. The products were analysed by gas chromatographic analysis and found to give 93 and 87% conversions (for Co and Zn bis-triflimide reactions respectively) to 2,4-dimethylbenzophenone and, it is believed to be, 2,6-dimethylbenzophenone (11:1 isomer ratio in both cases). The results show that zinc and cobalt bis-triflimide have been found to catalyse the benzoylation of m-xylene with benzoic acid. The reaction is slower that the corresponding reaction with benzoyl chloride. The catalyst was recycled and the reaction was repeated. The results of the repeat experiment are shown in Table 4.
Reaction SMILES: [CH3:1][C:2]1[CH:34]=[CH:33][C:5]2[CH:6]([C:16]3[C:17](=[S:32])[NH:18][C:19](=[O:31])[N:20]([CH2:22][C:23]4[O:24][CH:25]=[C:26]([C:28](O)=[O:29])[N:27]=4)[CH:21]=3)[C:7]3[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][C:8]=3[CH:9]=[CH:10][C:4]=2[CH:3]=1.[CH3:35][NH2:36]>CN(C)C=O.O1CCCC1>[CH3:1][C:2]1[CH:34]=[CH:33][C:5]2[CH:6]([C:16]3[C:17](=[S:32])[NH:18][C:19](=[O:31])[N:20]([CH2:22][C:23]4[O:24][CH:25]=[C:26]([C:28]([NH:36][CH3:35])=[O:29])[N:27]=4)[CH:21]=3)[C:7]3[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][C:8]=3[CH:9]=[CH:10][C:4]=2[CH:3]=1
Reactant: Cc1ccc2c(c1)C=Cc1cc(C)ccc1C2c1cn(Cc2nc(C(=O)O)co2)c(=O)[nH]c1=S
Reactant: CN
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: CNC(=O)c1coc(Cn2cc(C3c4ccc(C)cc4C=Cc4cc(C)ccc43)c(=S)[nH]c2=O)n1

Procedure:
N,N'-Carbonyldiimidazole (0.073 g) and the product of example 37(0.2 g) in N,N-dimethylformamide (3 ml) was stirred at room temperature. After 0.5 h Methylamine (0.6 ml of a 2M solution in tetrahydrofuran) was added. After a further 0.5 h the solution was partitioned between water and ethyl acetate. The organic solution was washed with water and brine, dried (MgSO4) and evaporated under reduced pressure. Purification was by chromatography eluting with 20% ethyl acetate in iso-hexane. Yield 0. lg.