Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:17][CH2:18][C:19]([O:21]C(C)(C)C)=[O:20])=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([S:14][CH2:15][CH3:16])=[CH:10][CH:9]=2)[CH:7]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:17][CH2:18][C:19]([OH:21])=[O:20])=[C:6]([C:8]2[CH:9]=[CH:10][C:11]([S:14][CH2:15][CH3:16])=[CH:12][CH:13]=2)[CH:7]=1
Reactant: CCSc1ccc(-c2cc(Cl)ccc2OCC(=O)OC(C)(C)C)cc1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCSc1ccc(-c2cc(Cl)ccc2OCC(=O)O)cc1

Procedure:
The title compound was prepared by stirring a mixture of the product from step (ii) (0.3 g) and trifluoroacetic acid (4 ml) in DCM (10 ml) at RT for 5 h. The solvent was evaporated under reduced pressure, the residue triturated with diethylether then purified by reverse phase HPLC. Yield 0.106 g
Reaction SMILES: [OH-].[Na+].Cl[C:4]1[N:9]=[C:8](Cl)[N:7]=[C:6](Cl)[N:5]=1.[CH2:12]([NH2:15])[CH2:13][CH3:14]>CC(C)=O.O>[CH2:12]([NH:15][C:4]1[N:9]=[C:8]([NH:15][CH2:12][CH2:13][CH3:14])[N:7]=[CH:6][N:5]=1)[CH2:13][CH3:14]
Reactant: Clc1nc(Cl)nc(Cl)n1
Reactant: CCCN
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(C)=O
Product: CCCNc1ncnc(NCCC)n1
Temperature: 50 °C
Yield: 100 %

Procedure:
A 2 M NaOH solution (82 mL, 162.68 mmol) was added in a dropwise manner to a suspension of 2,4,6-trichloro-1,3,5-triazine (XVIII) (15.00 g, 81.34 mmol) and n-propylamine (13.4 mL, 162.68 mmol) in acetone (300 mL) and water (15 mL) at 0° C. The reaction mixture was heated at 50° C. for 3 h and then cooled. Water (100 mL) was added to the reaction mixture; the resultant precipitate was filtered, washed with water, ethyl ether and dried to yield 2-chloro-N-(4,6-bis-(n-propylamino)-[1,3,5]triazine (XXXIV) (15.88 g, 85% yield).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([C:7]2[CH:8]=[C:9]([CH:13]=[CH:14][CH:15]=2)[C:10](O)=[O:11])=[CH:3][CH:2]=1.S(Cl)([Cl:18])=O>>[N:1]1[CH:6]=[CH:5][C:4]([C:7]2[CH:8]=[C:9]([CH:13]=[CH:14][CH:15]=2)[C:10]([Cl:18])=[O:11])=[CH:3][CH:2]=1
Reactant: O=C(O)c1cccc(-c2ccncc2)c1
Reactant: O=S(Cl)Cl
Product: O=C(Cl)c1cccc(-c2ccncc2)c1

Procedure:
Thionyl chloride (10 mL) was added to 3-(pyridin-4-yl)benzoic acid (1.5 g, 7.5 mmol) and the mixture was stirred under reflux overnight. The solvent was evaporated under reduced pressure and the residue was dried in vacuum giving 1.5 g of crude 3-(pyridin-4-yl)benzoyl chloride. To a solution of methyl 3-amino-2-hydroxybenzoate (950 g, 5.8 mmol) and pyridine (480 mg, 6 mmol) in toluene (50 mL) was added crude 3-(pyridin-4-yl)benzoyl chloride (1.5 g, 7 mmol) portion wise at 0° C. and then stirred at 70° C. for 4 h. The resulting mixture was extracted with ethyl acetate (100 mL×4), the organic phase was washed with water and saturated sodium bicarbonate, dried with anhydrous sodium sulfate and evaporated under reduced pressure to obtain methyl 2-hydroxy-3-(3-(pyridin-4-yl)benzamido)benzoate as a yellow solid (1.8 g, yield 85%). LC-MS (ESI) m/z: 349 (M+1)+.
Reaction SMILES: C([Li])CCC.C(NC(C)C)(C)C.[Li+].CC([N-]C(C)C)C.[CH3:21][C:22]1[CH:27]=[N:26][CH:25]=[CH:24][N:23]=1.Br[CH2:29][C:30]([O:32][C:33](C)(C)[CH3:34])=[O:31]>C1COCC1>[CH2:33]([O:32][C:30](=[O:31])[CH2:29][CH2:21][C:22]1[CH:27]=[N:26][CH:25]=[CH:24][N:23]=1)[CH3:34]
Reactant: Cc1cnccn1
Reactant: CC(C)(C)OC(=O)CBr
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Agent: [Li]CCCC
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Product: CCOC(=O)CCc1cnccn1
Temperature: 2.5 °C
Yield: 49.9 %

Procedure:
Butyl lithium (2.5M in hexane-2560 mL) was added within 2 hours into a 10 L flask charged with THF (3350 mL) and diisopropylamine (658 g) while the temperature was maintained at 0-5° C. with an ice bath. The LDA solution was then precooled to −50° C. and a mixture of methylpyrazine (606 g) and THF (590 mL) was added within 2 hours under vigorous stirring at −40 to −30° C. The deep red anion solution is then pumped to a cooled (−60° C.) mixture of tert-butyl bromoacetate (1255 g) and THF (3360 mL) in a 20 L reactor. During the addition of the anion solution, the temperature in the reaction vessel did not exceed −55° C. After the addition, the mixture is stirred for further 30 min at −55° C. and then transferred to a 30 L reactor (the transesterification and removal of solvents can be done for two runs at once). A solution of sodium ethylate (142 g) dissolved in EtOH (2200 mL) was then added to the orange mixture and about 12 L of solvents were distilled off until a temperature of 80° C. was reached in the distillation head and 100° C. in the boiling liquid. The mixture was cooled to approximately 30° C. and then toluene (840 mL), AcOEt (840 mL), and water (1180 mL) were added. After separation of the phases, the organic layer was extracted three times with AcOEt (420 mL) and toluene (170 mL) each. The combined organic phases were then concentrated in vacuo and the residue was distilled over a Vigreux column (bp 115 to 130° C. @ 0.07 mbar) giving the title compound (579 g).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([S:12]([N:15]([C:25]3[S:26][C:27]([F:30])=[CH:28][N:29]=3)CC3C=CC(OC)=CC=3)(=[O:14])=[O:13])=[CH:9][CH:10]=2)[CH:5]=[N:4][N:3]=1.[CH3:31][O:32][C:33]1[CH:38]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:36]=[CH:35][C:34]=1B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>O>[F:30][C:27]1[S:26][C:25]([NH:15][S:12]([C:8]2[CH:7]=[C:6]3[C:11](=[CH:10][CH:9]=2)[C:2]([C:34]2[CH:35]=[CH:36][C:37]([C:39]([F:42])([F:41])[F:40])=[CH:38][C:33]=2[O:32][CH3:31])=[N:3][N:4]=[CH:5]3)(=[O:13])=[O:14])=[N:29][CH:28]=1
Reactant: COc1ccc(CN(c2ncc(F)s2)S(=O)(=O)c2ccc3c(Cl)nncc3c2)cc1
Reactant: COc1cc(C(F)(F)F)ccc1B(O)O
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Product: COc1cc(C(F)(F)F)ccc1-c1nncc2cc(S(=O)(=O)Nc3ncc(F)s3)ccc12
Temperature: 90 °C
Reaction time: 0.5 h
Yield: 60.8 %

Procedure:
A vial was charged with 1-chloro-N-(5-fluorothiazol-2-yl)-N-(4-methoxybenzyl)phthalazine-6-sulfonamide (Intermediate CCCC) (55.94 mg, 0.120 mmol), (2-methoxy-4-(trifluoromethyl)phenyl)boronic acid (Combi-Blocks, San Diego, Calif., 31.8 mg, 0.144 mmol), Pd(AmPhos)2Cl2 (4.26 mg, 6.02 μmol), potassium phosphate (77 mg, 0.361 mmol), 1,4-dioxane (451 μl), and water (150 μl). The vial was flushed with Ar (g), then sealed and heated in a microwave reactor for 30 min at 90° C. The mixture was extracted with EtOAc (3×), and the combined organic extracts were concentrated. The residue was dissolved in DCM (1 mL) and TFA (0.5 mL). After 30 min, the mixture was diluted with MeOH and concentrated, and the crude product was purified by chromatography on silica gel (12-g column, 0 to 7% MeOH/DCM) to give N-(5-fluorothiazol-2-yl)-1-(2-methoxy-4-(trifluoromethyl)phenyl)phthalazine-6-sulfonamide (35.18 mg, 0.073 mmol, 60.4% yield) as a cream-colored solid: 1H NMR (400 MHz, DMSO-d6) δ ppm=12.88 (s, 1H), 9.96 (s, 1H), 8.76 (d, J=1.9 Hz, 1H), 8.22 (dd, J=1.9, 8.7 Hz, 1H), 7.77 (d, J=8.7 Hz, 1H), 7.68 (d, J=7.7 Hz, 1H), 7.60-7.52 (m, 2H), 7.41 (s, 1H), 3.77 (s, 3H); m/z (ESI) 485.2 (M+H)+.
Reaction SMILES: Cl[C:2]([O:4][CH3:5])=[O:3].[F:6][C:7]1[CH:8]=[C:9]([NH:14][C:15]([C:17]2[CH:18]=[C:19]([C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=3[F:31])[CH:20]=[CH:21]C=2O)=[O:16])[CH:10]=[CH:11][C:12]=1[F:13].Cl>O1CCCC1.N1C=CC=CC=1>[F:31][C:25]1[CH:26]=[C:27]([F:30])[CH:28]=[CH:29][C:24]=1[C:19]1[CH:20]=[CH:21][C:5]2[O:4][C:2](=[O:3])[N:14]([C:9]3[CH:10]=[CH:11][C:12]([F:13])=[C:7]([F:6])[CH:8]=3)[C:15](=[O:16])[C:17]=2[CH:18]=1
Reactant: O=C(Nc1ccc(F)c(F)c1)c1cc(-c2ccc(F)cc2F)ccc1O
Reactant: COC(=O)Cl
Agent: Cl
Solvent: c1ccncc1
Solvent: C1CCOC1
Product: O=c1oc2ccc(-c3ccc(F)cc3F)cc2c(=O)n1-c1ccc(F)c(F)c1
Temperature: 25 °C
Reaction time: 10 h
Yield: 25 %

Procedure:
A solution of methyl chloroformate (1.2 mL, 12 mmol) was added drop wised to a stirred solution of compound 3 (1.44 g, 4 mmol) in dry anhydrous tetrahydrofuran/pyridine (30 mL) at 0° C. The mixture was refluxed for 3 h. After 10 h stirring at room temperature, the pH value of the mixture was adjusted to pH=6 by 5% HCl(aq). The mixture was cooled to obtain crystalline compound on an ice bath for 2-3 h. After cooling, precipitated crystals were filtered off and washed with diluted HCl and water. The crude product was purified by crystallization from hot ethanol to afford compound 15.
Reaction SMILES: Cl.[NH:2]([C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][C:12]=1[CH3:13])[C:7]([OH:9])=[O:8])[NH2:3].[CH2:14]([O:16][C:17](=[O:26])[C:18]([C:24]#[N:25])=[C:19](OCC)[CH3:20])[CH3:15].C(N(CC)CC)C>C(O)C>[CH2:14]([O:16][C:17]([C:18]1[C:19]([CH3:20])=[N:3][N:2]([C:4]2[CH:5]=[C:6]([C:7]([OH:9])=[O:8])[CH:10]=[CH:11][C:12]=2[CH3:13])[C:24]=1[NH2:25])=[O:26])[CH3:15]
Reactant: CCOC(=O)C(C#N)=C(C)OCC
Reactant: Cc1ccc(C(=O)O)cc1NN
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCO
Product: CCOC(=O)c1c(C)nn(-c2cc(C(=O)O)ccc2C)c1N
Temperature: 65 °C
Yield: 87.9 %

Procedure:
To a stirred solution of 3-hydrazino-4-methylbenzoic acid hydrochloride (Example 3A, 353 mg, 1.74 mmol, 1.0 eq) in 15 mL of ethanol were added 2-cyano-3-ethoxy-but-2-enoic acid ethyl ester (prepared as described by Xia et al., J. Med. Chem., 1997, 40, 4372) (319 mg, 1.746 mmol, 1.0 eq) and triethylamine (242 μL, 1.74 mmol, 1.0 eq) and the mixture was heated at 65° C. overnight. The mixture was cooled to room temperature and concentrated. The crude residue was purified by flash chromatography on silica gel (loaded with CH2Cl2, and packed and eluted with gradient from 6/4 hexanes/EtOAc to elute byproducts followed by 8/2 EtOAc/hexanes and 8/2 EtOAc/MeOH to elute product) to provide the product as a brown solid (464 mg, 68%). HPLC (4 minute 10-95 gradient) tR1.97 min; MS m/z 304.1 [M+H]+
Reaction SMILES: [CH:1]([C:4]1[N:5]=[C:6]([NH2:9])[S:7][CH:8]=1)([CH3:3])[CH3:2].[CH:10]1[N:14]=[CH:13][N:12]([C:15](N2C=NC=C2)=[S:16])[CH:11]=1>C(#N)C>[CH:1]([C:4]1[N:5]=[C:6]([NH:9][C:15]([N:12]2[CH:11]=[CH:10][N:14]=[CH:13]2)=[S:16])[S:7][CH:8]=1)([CH3:3])[CH3:2]
Reactant: CC(C)c1csc(N)n1
Reactant: S=C(n1ccnc1)n1ccnc1
Solvent: CC#N
Product: CC(C)c1csc(NC(=S)n2ccnc2)n1
Temperature: 50 °C
Reaction time: 18 h
Yield: 55.3 %

Procedure:
To 4-isopropylthiazol-2-amine (1.04 g, 7.31 mmol) in acetonitrile (30 mL) was added 1,1-thiocarbonyldiimidazole (1.7 g, 9.5 mmol). The reaction was stirred at 50° C. for 18 hours. The reaction was cooled to room temperature and the precipitate was filtered and washed with acetonitrile (2×50 mL). The yellow powder was dried in a vacuum oven (40° C.) for 2 hours. The product, N-(4-isopropylthiazol-2-yl)-1H-imidazole-1-carbothioamide (1.02 g, 4.04 mmol, 55.3% yield), was taken directly to the next step without any further purification.
Reaction SMILES: [CH:1]1[CH:2]=[CH:3][C:4]2[C:11](=[O:12])[CH:10]=[CH:9][C:7](=[O:8])[C:5]=2[CH:6]=1.[CH2:13]=[CH:14][CH:15]=[CH2:16]>>[CH2:13]1[C:10]2[C:11](=[O:12])[C:4]3[C:5](=[CH:6][CH:1]=[CH:2][CH:3]=3)[C:7](=[O:8])[C:9]=2[CH2:16][CH2:15][CH2:14]1
Reactant: O=C1C=CC(=O)c2ccccc21
Reactant: C=CC=C
Product: O=C1C2=C(CCCC2)C(=O)c2ccccc21

Procedure:
A process has now been found for the isolation of purified anthraquinone from the crude anthraquinone which has been obtained by oxidation of naphthalene to give naphthoquinone, reaction of the oxidation product with butadiene to give tetrahydroanthraquinone, oxy-dehydrogenation of this reaction product with molecular oxygen to give a crude anthraquinone and optionally removal of naphthalene, phthalic anhydride and low-boiling substances from this crude anthraquinone, which is characterised in that the crude anthraquinone is treated with an oxygen compound of the elements of the first and/or second main group of the periodic system at an elevated temperature, optionally in the presence of a solvent, and purified anthraquinone is then isolated by subliming the anthraquinone present at a temperature of about 190° to about 290° C. and a pressure of about 1 to about 90 mm Hg and then desubliming it under the same pressure, or by vaporising the pretreated anthraquinone at a temperature of about 290° to about 380° C. and a pressure of about 90 to about 760 mm Hg and condensing the vapour under a pressure of about 90 to about 760 mm Hg.
Reaction SMILES: [CH3:1][C:2]1[CH:8]=[C:7]([S:9](=[O:12])(=[O:11])[NH2:10])[CH:6]=[CH:5][C:3]=1[NH2:4].[Cl:13][CH2:14][C:15](Cl)=[O:16]>>[Cl:13][CH2:14][C:15]([NH:4][C:3]1[CH:5]=[CH:6][C:7]([S:9](=[O:12])(=[O:11])[NH2:10])=[CH:8][C:2]=1[CH3:1])=[O:16]
Reactant: O=C(Cl)CCl
Reactant: Cc1cc(S(N)(=O)=O)ccc1N
Product: Cc1cc(S(N)(=O)=O)ccc1NC(=O)CCl

Procedure:
2-methyl-4-sulphamoylaniline (18,6 g) and α-chloroacetyl chloride (30g) were refluxed together 30 min. and the mixture worked up as in Example 2(a) to yield 11 g, m.p. 193°-194°
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[OH:12])[O:8][CH2:7][CH2:6]C2(O[Si](C)(C)C)C#N.[C:20]([OH:23])(=[O:22])[CH3:21]>Cl.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[OH:12])[O:8][CH2:7][CH2:6][CH:21]2[C:20]([OH:23])=[O:22]
Reactant: C[Si](C)(C)OC1(C#N)CCOc2cc(O)c(Cl)cc21
Reactant: CC(=O)O
Agent: Cl
Solvent: CCOC(C)=O
Product: O=C(O)C1CCOc2cc(O)c(Cl)cc21
Reaction time: 12 h
Yield: 100 %

Procedure:
A solution of 6-chloro-7-hydroxy-4-(trimethylsilyloxy)chroman-4-carbonitrile (129 g, 433 mmol) and SnCl2 dihydrate (293 g, 1299 mmol) in concentrated HCl (435 ml) and glacial acetic acid (435 ml) was heated to 125° C. and stirred for 12 hours. The reaction was taken up in ethyl acetate (500 ml) and washed with water (3×500 ml), dried over magnesium sulfate, filtered and concentrated to give the desired compound (99 g, 100%).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH:18]2[CH2:22][CH2:21][O:20][CH2:19]2)=[N:9][NH:10]C(OC(C)(C)C)=O)=[C:4](F)[CH:3]=1.N12CCCN=C1CCCCC2>O1CCCC1>[Br:1][C:2]1[CH:7]=[C:6]2[C:5]([C:8]([CH:18]3[CH2:22][CH2:21][O:20][CH2:19]3)=[N:9][NH:10]2)=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)NN=C(c1ccc(Br)cc1F)C1CCOC1
Solvent: C1CCOC1
Solvent: C1CCC2=NCCCN2CC1
Product: Brc1ccc2c(C3CCOC3)n[nH]c2c1
Temperature: 150 °C
Yield: 53.4 %

Procedure:
A mixture of 1,1-dimethylethyl 2-[(4-bromo-2-fluorophenyl)(tetrahydro-3-furanyl)methylidene]hydrazinecarboxylate (Intermediate 8, 1.1 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (424 μL) in tetrahydrofuran (12 mL) in a sealed vial was heated in a microwave oven at 150° C. for 30 min. The reaction mixture was partitioned between ethyl acetate (15 mL) and water (15 mL) and the organic layer was dried using a hydrophobic filter tube and concentrated under vacuum. The residue was purified by chromatography on a silica column, eluting with a cyclohexane:ethyl acetate gradient, to give the title compound as a colourless glass (405 mg).
Reaction SMILES: [OH:1][CH:2]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:3][N:4]1[C:9](=[O:10])[C:8]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)=[C:7]([C:18]2[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:20][CH:19]=2)[CH:6]=[N:5]1.I[CH3:35].[H-].[Na+]>CN(C=O)C>[CH3:35][O:1][CH:2]([C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)[CH2:3][N:4]1[C:9](=[O:10])[C:8]([C:11]2[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=2)=[C:7]([C:18]2[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:20][CH:19]=2)[CH:6]=[N:5]1
Reactant: CS(=O)(=O)c1ccc(-c2cnn(CC(O)c3ccccc3)c(=O)c2-c2ccc(F)cc2)cc1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(Cn1ncc(-c2ccc(S(C)(=O)=O)cc2)c(-c2ccc(F)cc2)c1=O)c1ccccc1
Yield: 34.8 %

Procedure:
A mixture of the product from Example 441, 2-(2-hydroxy-2-phenylethyl)-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (210 mg, 0.45 mmol), iodomethane (56 μL, 0.90 mmol), and an 80% oil dispersion of sodium hydride (18 mg, 0.59 mmol) in anhydrous DMF (16 mL) was stirred at room temperature for 18 hours. The reaction mixture was partitioned between ethyl acetate and 2 N aqueous hydrochloric acid. The organic layer was washed with brine, dried over MgSO4, and filtered. The filtrate was concentrated in vacuo to provide a yellow oil which was purified by column chromatography (silica gel, 70:30 hexanes/ethyl acetate). Fractions containing product were combined and concentrated in vacuo, and the residue was triturated with hexanes to provide the title compound (yield: 75 mg, 34.7%). mp 135-137° C. 1H NMR (300 MHz, CDCl3) δ 3.07 (s, 3H), 3.26 (s, 3H), 4.33-4.52 (m, 2H), 4.91 (dd, J=9 Hz, 3 Hz, 1H), 6.99 (t, J=9 Hz, 2H), 7.20 (dd, J=9 Hz, 3 Hz, 2H), 7.31-7.50 (m, 7H), 7.87 (s, 1H), 7.89 (d, J=9 Hz, 2H). MS (DCI/NH3) m/z 479 (M+H)+. Anal. calc. for C26H23FN2O4S: C, 65.25; H, 4.84; N, 5.85. Found: C, 64.98; H, 4.83; N, 5.81.
Reaction SMILES: [OH:1][C:2]1[C:3]([CH3:15])=[C:4]2[C:9](=[C:10]([CH3:13])[C:11]=1[CH3:12])[O:8][C:7](=[O:14])[CH2:6][CH2:5]2.[CH:16]([Si:19](Cl)([CH:23]([CH3:25])[CH3:24])[CH:20]([CH3:22])[CH3:21])([CH3:18])[CH3:17].N1C=CN=C1>CN(C=O)C.C(OCC)(=O)C>[CH3:15][C:3]1[C:2]([O:1][Si:19]([CH:23]([CH3:25])[CH3:24])([CH:20]([CH3:22])[CH3:21])[CH:16]([CH3:18])[CH3:17])=[C:11]([CH3:12])[C:10]([CH3:13])=[C:9]2[C:4]=1[CH2:5][CH2:6][C:7](=[O:14])[O:8]2
Reactant: CC(C)[Si](Cl)(C(C)C)C(C)C
Reactant: Cc1c(C)c2c(c(C)c1O)CCC(=O)O2
Agent: c1c[nH]cn1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Cc1c(C)c2c(c(C)c1O[Si](C(C)C)(C(C)C)C(C)C)CCC(=O)O2
Yield: 58.3 %

Procedure:
A solution of 6-hydroxy-5,7,8-trimethyl-chroman-2-one (1.22 g), triisopropylsilyl chloride (1.71 g) and imidazole (806 mg, 11.84 mmol) in anhydrous DMF (2 mL) was stirred at room temperature for two days. The solution was diluted with ethyl acetate, washed with water and brine. Evaporation and chromatography (silica gel, hexane-ethyl acetate) gave 1.25 g of 5,7,8-trimethyl-6-triisopropylsilanyloxy-chroman-2-one.
Reaction SMILES: [C:1]1([C:7]2[CH:11]=[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[NH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:18]1(S(O)(=O)=O)C=CC=CC=1.CO>>[CH3:18][N:8]1[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[CH:11][C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[N:9]1
Reactant: c1ccc(-c2cc(-c3ccccc3)[nH]n2)cc1
Reactant: O=S(=O)(O)c1ccccc1
Solvent: CO
Product: Cn1nc(-c2ccccc2)cc1-c1ccccc1
Yield: 900.5 %

Procedure:
As in Example 2, a melt of 10 g (0.0455 mol) of 3,5-diphenylpyrazole and 0.72 g (0.00455 mol) of benzenesulfonic acid was introduced and reacted over the course of 4.5 hours with 245 g (7.66 mol) of gaseous methanol (vaporized at 160° C.). 9.6 g (88.5%) of 1-methyl-3,5-diphenylpyrazole were obtained, boiling point 190° C./3 mbar, with a content of 98.2% (GC).
Reaction SMILES: C(OP([CH2:9][C:10]#[N:11])(=O)OCC)C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:22][O:23][C:24]1[CH:25]=[C:26]([C:32]([C:34]2[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=2)=O)[CH:27]=[C:28]([O:30][CH3:31])[CH:29]=1>C1COCC1>[CH3:22][O:23][C:24]1[CH:25]=[C:26]([C:32]([C:34]2[CH:35]=[CH:36][C:37]([O:40][CH3:41])=[CH:38][CH:39]=2)=[CH:9][C:10]#[N:11])[CH:27]=[C:28]([O:30][CH3:31])[CH:29]=1
Reactant: COc1ccc(C(=O)c2cc(OC)cc(OC)c2)cc1
Reactant: CCOP(=O)(CC#N)OCC
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: COc1ccc(C(=CC#N)c2cc(OC)cc(OC)c2)cc1
Temperature: 25 °C
Reaction time: 0.67 h

Procedure:
To a stirred solution of cyanomethylphosphonic acid diethyl ester (2.15 ml, 13.66 mmol) in anhydrous THF (10 ml) in an ice bath was added lithium bis(trimethylsilyl)amide (1.0 M solution in THF, 13.66 ml, 13.66 mmol) slowly. The mixture was stirred in rt for 40 min. To the mixture, a solution of (3,5-dimethoxyphenyl)-(4-methoxyphenyl)methanone (5193-23-B, 1.86 g, 6.83 mmol) in anhydrous THF (20 ml) was added. The mixture was refluxed overnight. The solution was poured into ice water (20 ml) and the two phases were separated. The THF phase was evaporated and combined with the aqueous phase, which were then extracted with CH2Cl2 (2×40 ml), washed with water (50 ml), dried over MgSO4, filtered and concentrated in vacuo to an oil, which was purified via flash column chromatography (20% EtOAc in hexane) to give 3-(3,5-Dimethoxy-phenyl)-3-(4-methoxy-phenyl)-acrylonitrile as a yellow oil which was solidified slowly (1.97 g, 98%): mp, 79-81° C.; 1HNMR (DMSO-d6) δ 7.35-7.31 (m, 2H, Ar), 7.07-6.96 (m, 2H, Ar), 6.65-6.62 (m, 1H, Ar), 6.46-6.44 (m, 2H, Ar), 6.23 (s, 0.43H, double bond H of one isomer), 6.20 (s, 0.58H, double bond H of the other isomer),3.82-3.68 (multiple singlets, 9H, OCH3); 13C NMR (CDCl3) 162.8, 162.6, 161.7, 161.3, 160.9, 160.8, 141.7, 139.2, 131.5, 131.0, 130.1, 129.3, 118.4, 118.2, 114.2, 114.0, 107.8, 107.2, 102.2, 102.1, 93.8, 93.0, 55.6, 55.5, 55.5; Anal. Calcd. for C18H17NO3+0.05H2O: C, 72.92; H, 5.89; N, 4.65. Found: C, 72.90; H, 5.52; N, 4.67.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([CH3:8])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][CH:3]=1.CO[CH:14](OC)[N:15]([CH3:17])[CH3:16]>CN(C)C=O.C(N(CC)CC)C>[CH3:14][N:15]([CH3:17])[CH:16]=[CH:8][C:6]1[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][CH:3]=[C:2]([Cl:1])[N:7]=1
Reactant: Cc1nc(Cl)ccc1[N+](=O)[O-]
Reactant: COC(OC)N(C)C
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CN(C)C=Cc1nc(Cl)ccc1[N+](=O)[O-]
Temperature: 100 °C

Procedure:
A solution of 5 gm (29 mMol) 6-chloro-3-nitro-2-picoline in 40 mL dimethylformamide was treated with 5.83 mL (44 mMol) dimethylformamide dimethylacetal and the resulting mixture heated at 100° C. for 1.5 hours. At this point, 2 drops of triethylamine followed by 1.9 mL dimethylformamide dimethylacetal were added and heating continued for 2 more hours. The reaction mixture was concentrated under reduced pressure to provide the desired compound.
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([C:9](=[O:20])[C:10](=[CH:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:11][CH3:12])[CH:5]=[CH:4][C:3]=1[O:21][CH3:22]>FC(F)(F)C(O)=O>[CH2:11]([CH:10]1[CH:13]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:5]2[C:6](=[C:7]([Cl:8])[C:2]([Cl:1])=[C:3]([O:21][CH3:22])[CH:4]=2)[C:9]1=[O:20])[CH3:12]
Reactant: CCC(=Cc1ccccc1)C(=O)c1ccc(OC)c(Cl)c1Cl
Solvent: O=C(O)C(F)(F)F
Product: CCC1C(=O)c2c(cc(OC)c(Cl)c2Cl)C1c1ccccc1

Procedure:
2,3-Dichloro-4-(2-benzylidenebutyryl)anisole (111.0 g., 0.331 mole) and trifluoroacetic acid (350 ml.) are heated at gentle reflux for 70 hours. The trifluoroacetic acid is removed, the oily residue triturated with ether to give 88.1 g. (80%) of 2-ethyl-3-phenyl-6,7-dichloro-5-methoxy-1-indanone which on crystallization from benzene melts at 141°-143° C.
Reaction SMILES: [CH:1]1[CH:6]=[C:5]2[C:7]([N:9]([CH2:12][C:13](Cl)=[O:14])[C:10](=[O:11])[C:4]2=[CH:3][CH:2]=1)=[O:8].[Cl:16][C:17]1[CH:31]=[CH:30][C:20]2[O:21][C:22]3[CH:29]=[CH:28][CH:27]=[CH:26][C:23]=3[CH2:24][NH:25][C:19]=2[CH:18]=1.C(N(CC)CC)C.Cl>C1(C)C=CC=CC=1>[Cl:16][C:17]1[CH:31]=[CH:30][C:20]2[O:21][C:22]3[CH:29]=[CH:28][CH:27]=[CH:26][C:23]=3[CH2:24][N:25]([C:13](=[O:14])[CH2:12][N:9]3[C:7](=[O:8])[C:5]4[C:4](=[CH:3][CH:2]=[CH:1][CH:6]=4)[C:10]3=[O:11])[C:19]=2[CH:18]=1
Reactant: Clc1ccc2c(c1)NCc1ccccc1O2
Reactant: O=C(Cl)CN1C(=O)c2ccccc2C1=O
Agent: Cl
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: O=C1c2ccccc2C(=O)N1CC(=O)N1Cc2ccccc2Oc2ccc(Cl)cc21

Procedure:
1,3-dihydro-1,3-dioxo-2H-isoindole-2-acetyl chloride (4.00 grams), 8-chloro-10,11-dihydrodibenz[b,f][1,4]oxazepine (4.16 grams) and triethylamine (2.8 mL) were refluxed in toluene (100 mL) under nitrogen for 3 hours. The resulting mixture was poured into 1N HCl at 0° C., and the biphasic mixture was shaken vigorously. The insoluble product was collected by filtration, washed with toluene and ethyl ether, and dried in vacuo at 56° C. The yield of the title compound was 6.36 grams (85%). Mp: 184°-185° C.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[C:11]1[CH2:12][CH2:13][N:14]([CH3:17])[CH2:15][CH:16]=1.[CH3:18][O:19][C:20]1[CH:28]=[CH:27][C:23]([C:24](Cl)=[O:25])=[CH:22][CH:21]=1>>[CH3:18][O:19][C:20]1[CH:28]=[CH:27][C:23]([C:24]([NH:1][C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][CH:6]=[C:5]3[C:11]2[CH2:12][CH2:13][N:14]([CH3:17])[CH2:15][CH:16]=2)=[O:25])=[CH:22][CH:21]=1
Reactant: CN1CC=C(c2c[nH]c3ccc(N)cc23)CC1
Reactant: COc1ccc(C(=O)Cl)cc1
Product: COc1ccc(C(=O)Nc2ccc3[nH]cc(C4=CCN(C)CC4)c3c2)cc1
Yield: 20.3 %

Procedure:
Beginning with 1.13 gm (5.0 mMol) 5-amino-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole and 0.853 gm (5.0 mMol) 4-methoxybenzoyl chloride, 0.367 gm (20.4%) of the title compound were recovered as a light yellow solid.