Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:4]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=2)[CH:7]=[CH:6][N:5]=1)(=O)[CH3:2].[NH2:16][OH:17].C([O-])(=O)C.[Na+]>C(O)C.O>[C:1](=[N:16][OH:17])([C:4]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=2)[CH:7]=[CH:6][N:5]=1)[CH3:2]
Reactant: CC(=O)c1nccc(-c2ccccn2)n1
Reactant: NO
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CC(=NO)c1nccc(-c2ccccn2)n1
Yield: 91.1 %

Procedure:
A solution of 2-acetyl-4-(pyrid-2-yl)-pyrimidine (1.0 g), hydroxylamine (0.39 g) and sodium acetate (0.62 g) in a mixture of ethanol (10 ml) and water (2 ml) was heated to reflux for 1.5 hours. The reaction was then poured into water the precipitate filtered and washed with hexane to give 2-acetyl-4-(pyrid-2-yl)-pyrimidine oxime (0.98 g, 91% yield) as a white crystalline solid m.p. 196°-8° C.; 1H NMR: 2.50(3H,s); 7.42(1H,m); 7.88(1H,m); 8.30(1H,d); 8.59(1H,d); 8.74(1H,d); 8.90(1H,d); 10.85(1H,brs) ppm.
Reaction SMILES: [Br:1][C:2]1[CH:13]=[C:6]2[C:7](OC(=O)[NH:11][C:5]2=[CH:4][CH:3]=1)=[O:8].[CH3:14][NH:15][CH3:16].O1CCCC1>>[NH2:11][C:5]1[CH:4]=[CH:3][C:2]([Br:1])=[CH:13][C:6]=1[C:7]([N:15]([CH3:16])[CH3:14])=[O:8]
Reactant: O=c1[nH]c2ccc(Br)cc2c(=O)o1
Reactant: CNC
Solvent: C1CCOC1
Product: CN(C)C(=O)c1cc(Br)ccc1N
Temperature: 60 °C
Yield: 78.6 %

Procedure:
A 350 ml round bottomed pressure tube was charged with 5-bromoisatoic anhydride (15.0 g, 62.0 mmol) and 2 M dimethylamine in tetrahydrofuran (90 ml, 180 mmol). The vial was sealed and heated in an oil bath at 60° C. for 1 hour, then concentrated to dryness. The residue was dissolved in dichloromethane (100 ml). The organic layer was washed with saturated, aqueous sodium bicarbonate solution (25 ml), and water (25 ml), then dried over sodium sulfate and concentrated to obtain a yellow powder. The powder was re-crystallized from ether to obtain 11.8 g (78.6%) of 2-amino-5-bromo-N,N-dimethyl-benzamide. 1H-NMR (250 MHz, CDCl3) δ 7.20 (dd, J=8.5, 2.5 Hz, 1H), 7.10 (d, J=2.5 Hz, 1H), 6.65 (d, J=8.7 Hz, 1H), 5.34 (s, 2H), 2.91 (s, 6H); MS: m/z 243.1, 245.1 (M+H+).
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][N:14]1[CH2:23][CH2:22][C@H:21]2[C@@H:16]([C:17](=[O:30])[C:18]3[C:26]4[CH2:27][CH2:28][CH2:29][C:25]=4[NH:24][C:19]=3[CH2:20]2)[CH2:15]1.[CH3:31][C:32]([CH3:50])([CH2:36][CH2:37][O:38][C:39](=[O:49])[CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH3:48])[C:33](Cl)=[O:34]>O1CCCC1.CCCCCC>[CH3:50][C:32]([CH3:31])([CH2:36][CH2:37][O:38][C:39](=[O:49])[CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH3:48])[C:33]([N:24]1[C:19]2[CH2:20][C@@H:21]3[C@@H:16]([C:17](=[O:30])[C:18]=2[C:26]2[CH2:27][CH2:28][CH2:29][C:25]1=2)[CH2:15][N:14]([CH3:13])[CH2:23][CH2:22]3)=[O:34]
Reactant: CCCCCCCCCC(=O)OCCC(C)(C)C(=O)Cl
Reactant: CN1CC[C@@H]2Cc3[nH]c4c(c3C(=O)[C@H]2C1)CCC4
Agent: [Li]CCCC
Solvent: CC(C)NC(C)C
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CCCCCCCCCC(=O)OCCC(C)(C)C(=O)n1c2c(c3c1C[C@H]1CCN(C)C[C@@H]1C3=O)CCC2
Reaction time: 0.5 h
Yield: 46.9 %

Procedure:
To a solution of diisopropylamine (0.15 g) in tetrahydrofuran (15 mL) was added n-butyllithium in hexane (0.75 mL, 2M solution) at -20° to -30° and the solution was stirred at -20° to -30° C. for 30 minutes. To the solution was added at -20° to -30° C. (in one portion) trans-1,3,4,4a,5,7,8,9,10,10a-decahydro-2-methyl-6H-cyclopenta[4,5]pyrrolo[2,3-g]isoquinolin-10(2H)-one (0.244 g) and the mixture was stirred at -20° C. for 2 hours. To the solution was added the crude 2,2-dimethyl-4-[(1-oxodecyl)oxy]butanoyl chloride (0.45 g) in tetrahydrofuran at -20° to -30° and the mixture was stirred at this temperature for an additional 1 hour. The mixture was poured onto ice water and extracted in the dichloromethane. The combined dichloromethane extracts were washed with brine dried sodium sulfate and evaporated. The crude product was chromatographed on silica gel eluting with 5% methanol in dichloromethane to give 0.24 g of oily material (47%), trans-1,3,4,4a,5,6,7,8,9,10a-Decahydro-6-[2,2-dimethyl-1-oxo-4-[(1-oxodecyl)oxy]butyl]-2-methylcyclopenta[4,5]pyrrolo[2,3-g]isoquinolin-10(2H)-one IR (CHCl3), 1778 (C=O) and 1657 (C=O); NMR (CDCl3), δ0.88 (t, 3, CH3); 1.2-1.4 (m, 20, CH2 and CH3) 2.41 (5, 3, CH3); 3.04 (br.d, 1, CH); 3.56 (br.d, 1, CH); 4.14 (t, 2, CH2); MS m/e 512 (M+).
Reaction SMILES: [F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8](=[O:33])[N:9]2[CH2:12][CH2:13][N:14]2[CH2:19][CH2:18][C@@H:17]([OH:20])[C@@H:16]([CH2:21][NH:22]C(=O)OCC3C=CC=CC=3)[CH2:15]2)=[CH:4][CH:3]=1>CCO.[OH-].[OH-].[Pd+2]>[NH2:22][CH2:21][C@@H:16]1[C@H:17]([OH:20])[CH2:18][CH2:19][N:14]([CH2:13][CH2:12][N:9]2[C:10]3[C:5](=[CH:4][CH:3]=[C:2]([F:1])[CH:11]=3)[CH:6]=[CH:7][C:8]2=[O:33])[CH2:15]1
Reactant: O=C(NC[C@H]1CN(CCn2c(=O)ccc3ccc(F)cc32)CC[C@H]1O)OCc1ccccc1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CCO
Product: NC[C@H]1CN(CCn2c(=O)ccc3ccc(F)cc32)CC[C@H]1O
Reaction time: 3 h
Yield: 95 %

Procedure:
A solution of phenylmethyl ({(3S,4R)-1-[2-(7-fluoro-2-oxo-1(2H)-quinolinyl)ethyl]-4-hydroxy-3-piperidinyl}methyl)carbamate (as prepared previously) (306 mg; 0.675 mmol) in EtOH (50 mL) was added 20% Pd(OH)2/C (70 mg). The mixture was hydrogenated at 1 atm of H2 at ambient temperature for 3 h. The crude product was filtered through Celite, washed with ethanol and concentrated under reduced pressure to obtain the product as a pale yellow oil (210 mg; 95%).
Reaction SMILES: [C:1]1([C:7]2([C:10]#N)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-:12].[K+].[OH-:14].[Na+]>C(O)C>[C:1]1([C:7]2([C:10]([OH:14])=[O:12])[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: [OH-]
Reactant: N#CC1(c2ccccc2)CC1
Agent: [K+]
Agent: [Na+]
Solvent: CCO
Product: O=C(O)C1(c2ccccc2)CC1
Yield: 95 %

Procedure:
The phenylcyclopropanecarboxylic acid 43 used as a intermediate in preparing the thiazole containing C-aryl glucoside can be prepared by a method as shown in Scheme 8. The phenylacetonitrile β-39 is reacted with 1,2-dibromoethane in the presence of sodium hydroxide and a phase-transfer catalyst in toluene and water to provide a corresponding phenylcyclopropanecarbonitrile 42 in 71% yield. This carbonitrile 42 is treated with potassium hydroxide and sodium hydroxide in refluxed aqueous ethanol to provide cyclopropanecarboxylic acid 43 in 95% yield.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:9]=[C:8]([CH2:10][C:11]2[C:12]([NH2:18])=[N:13][C:14]([NH2:17])=[N:15][CH:16]=2)[CH:7]=[C:6]([O:19][CH2:20][CH3:21])[C:5]=1[C:22]1[CH:27]=[CH:26][C:25]([O:28]COC)=[CH:24][CH:23]=1)[CH3:2].Cl>CO>[NH2:17][C:14]1[N:13]=[C:12]([NH2:18])[C:11]([CH2:10][C:8]2[CH:7]=[C:6]([O:19][CH2:20][CH3:21])[C:5]([C:22]3[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=3)=[C:4]([O:3][CH2:1][CH3:2])[CH:9]=2)=[CH:16][N:15]=1
Reactant: CCOc1cc(Cc2cnc(N)nc2N)cc(OCC)c1-c1ccc(OCOC)cc1
Agent: Cl
Solvent: CO
Product: CCOc1cc(Cc2cnc(N)nc2N)cc(OCC)c1-c1ccc(O)cc1
Temperature: 56 °C
Reaction time: 0.5 h
Yield: 98.2 %

Procedure:
5-(2,6-Diethoxy-4′-methoxymethoxy-biphenyl-4-ylmethyl)-pyrimidine-2,4-diamine (10.06 g; 23.7 mmol) is dissolved in methanol (410 ml), and a 3 N hydrochloric acid solution in methanol (119.1 ml; 357.3 mmol) is added. The reaction mixture is stirred for 30 minutes at a temperature of 56° C. and concentrated. The grey residue is then stirred with water (400 ml), the pH is brought to 9 by addition of an aqueous saturated ammonia solution (approx. 8 ml) and the entire mixture is stirred for 15 minutes. The greyish suspension is filtered with suction and the residue is dried under a high vacuum. 8.85 g (98%) 4′-(2,4-diamino-pyrimidin-5-ylmethyl)-2′,6′-diethoxy-biphenyl-4-ol are obtained as a greyish powder.
Reaction SMILES: [Cl:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[N:6][N:5]=[C:4]2[N:14]([CH3:24])[N:15]=[C:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3Cl)[C:3]=12.[CH3:25][O:26]C1C=CC(C(CC#N)=O)=CC=1>>[Cl:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[N:6][N:5]=[C:4]2[N:14]([CH3:24])[N:15]=[C:16]([C:17]3[CH:22]=[CH:21][C:20]([O:26][CH3:25])=[CH:19][CH:18]=3)[C:3]=12
Reactant: Cn1nc(-c2ccccc2Cl)c2c(Cl)c(-c3ccccc3)nnc21
Reactant: COc1ccc(C(=O)CC#N)cc1
Product: COc1ccc(-c2nn(C)c3nnc(-c4ccccc4)c(Cl)c23)cc1

Procedure:
Compound 27 was synthesised following similar procedures outlined in Example 1 (Compound 37), using 4-methoxybenzoylacetonitrile instead of 2-chlorobenzoyl acetonitrile in Step 1.
Reaction SMILES: Cl[C:2]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:3].[NH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[N:13]=1.N1C=CC=CC=1.O>C1COCC1.C(OCC)(=O)C>[CH3:18][C:14]1[N:13]=[C:12]([NH:11][C:2](=[O:3])[O:4][C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH:17]=[CH:16][CH:15]=1
Reactant: Cc1cccc(N)n1
Reactant: O=C(Cl)Oc1ccccc1
Solvent: O
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: Cc1cccc(NC(=O)Oc2ccccc2)n1
Reaction time: 0.5 h
Yield: 52.4 %

Procedure:
Phenyl chloroformate (232 mL, 1.84 mol) was added dropwise (1.5 h) to a cooled (0° C.) solution of 2-amino-6-picoline (200 g, 1.84 mol) and pyridine (448 mL, 5.55 mol) in THF (1.6 L). The reaction was stirred, with continued cooling for 15 h. Water (500 mL) was added slowly (30 min) and then the mixture was diluted with ethyl acetate (2 L). The layers were separated and the organic layer was washed with 1 N hydrochloric acid (3×1 L), 1 N aqueous sodium hydroxide solution (500 mL) and brine (500 mL). The organic layer was then dried over sodium sulfate and concentrated under reduced pressure. The residue was suspended in hexane (500 mL) for 30 min and then filtered to afford the desired product (220 g, 52%) containing some trace impurities. 1H-NMR (300 MHz, DMSO-d6) δ 10.68 (s, 1H), 6.93-7.74 (m, 8H), 2.42 (s, 3H); ES-MS m/z 229.4 (MH)+; HPLC RT (Method A) 2.94 min.
Reaction SMILES: [CH:1]1([CH2:6][CH2:7][C:8](Cl)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:11][C:12]1[C:20]([C:21]([O:23][CH3:24])=[O:22])=[C:15]2[N:16]=[CH:17][CH:18]=[CH:19][N:14]2[N:13]=1.CO>C(Cl)Cl.N1C=CC=CC=1>[CH:1]1([CH2:6][CH2:7][C:8]([NH:11][C:12]2[C:20]([C:21]([O:23][CH3:24])=[O:22])=[C:15]3[N:16]=[CH:17][CH:18]=[CH:19][N:14]3[N:13]=2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=C(Cl)CCC1CCCC1
Reactant: COC(=O)c1c(N)nn2cccnc12
Solvent: CO
Solvent: ClCCl
Solvent: c1ccncc1
Product: COC(=O)c1c(NC(=O)CCC2CCCC2)nn2cccnc12
Reaction time: 4 h

Procedure:
A solution of 3-cyclopentylpropionyl chloride (0.58 mL, 3.8 mmol) in CH2Cl2 (0.5 mL) was added to a suspension of the product from Example 125A (300 mg, 1.56 mmol) in pyridine (5 mL) at room temperature. After 4 hours, methanol (10 mL) was added to quench the excess acyl chloride, and the mixture was stirred for 15 minutes, and then concentrated under vacuum. The residue was crystallized from 86% methanol-water (24 mL) to provide the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.01-1.22 (m, 2H) 1.39-1.69 (m, 6H) 1.68-1.88 (m, 3H) 2.46-2.54 (m, 2H) 3.81 (s, 3H) 7.25 (dd, J=6.9, 4.2 Hz, 1H) 8.75 (dd, J=4.4, 1.6 Hz, 1H) 9.18 (dd, J=6.9, 1.8 Hz, 1H) 10.04 (s, 1H); MS (ESI) m/z 317 (M+H)+; Anal. Calculated for C16H20N4O3: C, 60.75; H, 6.37; N, 17.71. Found: C, 60.71; H, 5.85; N, 17.48.
Reaction SMILES: [Cl-].[C:2]1([N+:8]#[N:9])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.NC1C=CC=CC=1.[NH2:17][C:18]1[N:19]=[C:20]([CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[NH:21][C:22](=[O:24])[CH:23]=1.[OH-].[Na+]>O>[NH2:17][C:18]1[N:19]=[C:20]([CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[NH:21][C:22](=[O:24])[C:23]=1[N:9]=[N:8][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: N#[N+]c1ccccc1
Reactant: Nc1cc(=O)[nH]c(Cc2ccccc2)n1
Agent: [Cl-]
Agent: [Na+]
Agent: [OH-]
Solvent: Nc1ccccc1
Solvent: O
Product: Nc1nc(Cc2ccccc2)[nH]c(=O)c1N=Nc1ccccc1
Reaction time: 1 h

Procedure:
A cold solution of benzenediazonium chloride (prepared by the method well known in the art, from 2 g. aniline) was added dropwise with stirring to a solution of 4-amino-2-benzylpyrimid-6-one (4 g.) and sodium hydroxide (1.6 g.) in water (50 ml.) at 5° C. After stirring for a further 1 hour, the solid was filtered off and recrystallised from a mixture of dimethylformamide and water (4:1 v/v) to give 4-amino-2-benzyl-5-phenylazopyrimid-6-one (3.8 g.) in the form of orange needles, which decomposed at 256°-257° C.
Reaction SMILES: N#N.[NH2:3][CH2:4][C:5]([OH:7])=O.[Cl:8][C:9]1[CH:21]=[CH:20][C:12]2[N:13](C)[C:14](=O)[O:15][C:16](=O)[C:11]=2[CH:10]=1>CC(O)=O>[Cl:8][C:9]1[CH:21]=[CH:20][C:12]2[N:13]([CH3:14])[C:5](=[O:7])[CH2:4][NH:3][C:16](=[O:15])[C:11]=2[CH:10]=1
Reactant: NCC(=O)O
Reactant: Cn1c(=O)oc(=O)c2cc(Cl)ccc21
Agent: N#N
Solvent: CC(=O)O
Product: CN1C(=O)CNC(=O)c2cc(Cl)ccc21
Temperature: 130 °C
Reaction time: 0.33 h
Yield: 44 %

Procedure:
In a 2 L RBF equipped with mechanical stir, condenser and N2 inlet, glycine (38 g, 0.506 mol) was added to crude 6-chloro-1-methyl-1H-benzo[d][1,3]oxazine-2,4-dione (107 g, 0.506 mol) followed by the addition of AcOH (500 mL). Reaction flask was heated in a 130° C. oil bath for 7 h. Solvent was evaporated under suction with heating (50-60° C.). To the thick syrupy crude product was added 1 L of EtOAc followed by the slow addition of aqueous NaHCO3 (saturated) to adjust the pH to ˜7. Then 10 mL of 2 M NaOH was added to adjust the pH to ˜9-10. The mixture gave a solid along with organic and aqueous layers. Solid was filtered to give product containing some impurity. Solid was partitioned between 400 mL DCM and 200 mL NaHCO3 and the slurry was stirred for 20 min, then filtered to remove the insoluble impurity. The DCM layer was separated and washed with 3% NaHCO3 and then brine (200 mL). The DCM layer was dried (MgSO4), filtered and concentrated to give 50 g of pure product. EtOAc layer was concentrated to give 67 g of solid product with some impurity. Aqueous layer was extracted with EtOAc (2×400 mL). Combined organics were dried over Na2SO4, filtered and concentrated to give an additional 6.7 g of crude product. Total of 123.4 g of product was obtained, 50 g of which was very clean. 1H NMR (300 MHz, CDCl3) δ 3.2 (s, 3H), 3.5 (m, 1 H), 3.8 (m, 1H), 7.35 (d, 1H), 7.6 (m, 2H), 8.8 (t, 1H).
Reaction SMILES: [CH3:1]/[C:2](/[CH2:6][CH2:7]/[CH:8]=[C:9](\[CH3:16])/[CH2:10][CH2:11][CH:12]=[C:13]([CH3:15])[CH3:14])=[CH:3]\[CH2:4][OH:5].CC(C)[O-].[Al+3].CC(C)[O-].CC(C)[O-].[N+](C1C=C(C=CC=1)C=O)([O-])=O.Cl>C1CCCCC1.CCCCCC>[CH3:1]/[C:2](/[CH2:6][CH2:7]/[CH:8]=[C:9](\[CH3:16])/[CH2:10][CH2:11][CH:12]=[C:13]([CH3:15])[CH3:14])=[CH:3]\[CH:4]=[O:5]
Reactant: CC(C)=CCC/C(C)=C/CC/C(C)=C/CO
Agent: CC(C)[O-]
Agent: Cl
Agent: O=Cc1cccc([N+](=O)[O-])c1
Solvent: CCCCCC
Solvent: C1CCCCC1
Product: CC(C)=CCC/C(C)=C/CC/C(C)=C/C=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 96 %

Procedure:
(2E,6E)-3,7,11-Trimethyl-2,6,10-dodecatrien-1-ol (445 mg, 2.0 mmol) was dissolved in cyclohexane (1 mL), added with aluminum isopropoxide (40 mg, 0.1 eq, 0.2 mmol) and 3-nitrobenzaldehyde (393 mg, 1.3 eq, 2.6 mmol) and stirred at room temperature for 2 hours. The reaction mixture was added with hexane, then made acidic with addition of 1 N hydrochloric acid and extracted twice with ethyl acetate. Subsequently, the organic layer was washed with saturated brine and dried over magnesium sulfate. The solvent was evaporated in vacuo, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1) to obtain 427 mg (yield: 96%, E:Z=99:1) of the title compound as yellow oil.
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]([CH3:34])=[C:5]([C:21]([O:23][CH2:24]/[CH:25]=[CH:26]/[C:27]2[CH:32]=[CH:31][C:30]([OH:33])=[CH:29][CH:28]=2)=[O:22])[CH:6]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=2)[C:7]=1[C:8]([O:10][CH3:11])=[O:9].[C:35](OC(=O)C)(=[O:37])[CH3:36]>N1C=CC=CC=1>[CH3:1][C:2]1[NH:3][C:4]([CH3:34])=[C:5]([C:21]([O:23][CH2:24]/[CH:25]=[CH:26]/[C:27]2[CH:28]=[CH:29][C:30]([O:33][C:35](=[O:37])[CH3:36])=[CH:31][CH:32]=2)=[O:22])[CH:6]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=2)[C:7]=1[C:8]([O:10][CH3:11])=[O:9]
Reactant: CC(=O)OC(C)=O
Reactant: COC(=O)C1=C(C)NC(C)=C(C(=O)OC/C=C/c2ccc(O)cc2)C1c1cccc([N+](=O)[O-])c1
Solvent: c1ccncc1
Product: COC(=O)C1=C(C)NC(C)=C(C(=O)OC/C=C/c2ccc(OC(C)=O)cc2)C1c1cccc([N+](=O)[O-])c1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
0.5 Gram of methyl 3-(4-hydroxyphenyl)-2(E)-propenyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-pyridine-3,5-dicarboxylate was dissolved in 5 ml of pyridine, then to this solution was added 0.5 ml of acetic anhydride under an ice-cooling condition. The reaction mixture was allowed to stand overnight, then poured into an ice-water, and extracted with ether. The ether layer was washed with a diluted hydrochloric acid, 10%-sodium bicarbonate aqueous solution and water in this order, then dried with anhydrous sodium sulfate. The ether extract was concentrate, and the residue thus obtained was purified by means of a silica gel column chromatography (eluent: methanol:chloroform=1:100) to yield 0.4 g of methyl 3(4-acetyloxyphenyl)-2(E)-propenyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-pyridine-3,5-dicarboxylate in the form of light yellow indefinite form crystals.
Reaction SMILES: Cl[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[C:7]([OH:12])[CH:6]=1)=O.[C:13](=[S:16])([S-:15])[NH2:14].[NH4+]>CO>[OH:12][C:7]1[CH:6]=[C:5]([C:3]2[N:14]=[C:13]([SH:16])[S:15][CH:2]=2)[CH:10]=[CH:9][C:8]=1[OH:11]
Reactant: O=C(CCl)c1ccc(O)c(O)c1
Reactant: NC(=S)[S-]
Agent: [NH4+]
Solvent: CO
Product: Oc1ccc(-c2csc(S)n2)cc1O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 72.9 %

Procedure:
10.0 g (53.6 mmol) of 2-chloro-3'4'-dihydroxy-acetophenone was dissolved in 100 ml of methanol, and then 5.90 g (53.6 mmol) of ammonium dithiocarbamate was added thereto. The mixture was stirred at room temperature for 30 minutes. The solvent was distilled off under reduced pressure. To the residue, water was added to adjust the mixture to pH2.0, and then the mixture was extracted twice with ethyl acetate. The extract was dried over anhydrous sodium sulfate and-then concentrated. The crystal residue was washed with diethyl ether to obtain 8.80 g (yield: 72.9%) of the above-identified compound.
Reaction SMILES: [CH2:1]([NH:3][C:4]([N:6]1[CH2:12][CH2:11][C:10]2[CH:13]=[CH:14][C:15]([S:17]([NH2:20])(=[O:19])=[O:18])=[CH:16][C:9]=2[CH2:8][CH2:7]1)=[O:5])[CH3:2].[CH:21]1([N:27]=[C:28]=[O:29])[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1>>[CH:21]1([NH:27][C:28]([NH:20][S:17]([C:15]2[CH:14]=[CH:13][C:10]3[CH2:11][CH2:12][N:6]([C:4](=[O:5])[NH:3][CH2:1][CH3:2])[CH2:7][CH2:8][C:9]=3[CH:16]=2)(=[O:18])=[O:19])=[O:29])[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1
Reactant: O=C=NC1CCCCC1
Reactant: CCNC(=O)N1CCc2ccc(S(N)(=O)=O)cc2CC1
Product: CCNC(=O)N1CCc2ccc(S(=O)(=O)NC(=O)NC3CCCCC3)cc2CC1

Procedure:
By the reaction of 3-ethylcarbamoyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7-sulfonamide with cyclohexylisocyanate in a manner analogous to that described in Example 1, there is obtained 1-cyclohexyl-3-[(3-ethylcarbamoyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)sulfonyl]urea, m.p. 158°-160° C.
Reaction SMILES: O.[NH2:2][C:3]1[C:8]2[CH2:9][C:10]([CH3:13])([CH3:12])[O:11][C:7]=2[C:6]([OH:14])=[CH:5][CH:4]=1.[CH:15](=O)[C:16]1[C:17](=[CH:19][CH:20]=[CH:21][CH:22]=1)[OH:18]>C(OCC)(=O)C>[CH3:13][C:10]1([CH3:12])[CH2:9][C:8]2[C:3]([N:2]=[CH:15][C:16]3[CH:22]=[CH:21][CH:20]=[CH:19][C:17]=3[OH:18])=[CH:4][CH:5]=[C:6]([OH:14])[C:7]=2[O:11]1
Reactant: CC1(C)Cc2c(N)ccc(O)c2O1
Reactant: O=Cc1ccccc1O
Solvent: O
Solvent: CCOC(C)=O
Product: CC1(C)Cc2c(N=Cc3ccccc3O)ccc(O)c2O1
Temperature: 25 °C
Yield: 73.3 %

Procedure:
To a 500 milliliter round bottom flask equipped with a water collector, water condenser, magnetic stirrer and drying tube was added 5.38 grams (0.030 moles) of 4-amino-2,3-dihydro-2,2-dimethyl-7-hydroxybenzofuran, 3.91 grams (0.032 moles) of salicylaldehyde and 300 milliliters of ethyl acetate. The resulting reaction mixture was heated to reflux with removal of the first 50 milliliters of distillate, and the remaining mixture allowed to reflux for 1 additional hour with continuous stirring. After the stirring and refluxing period, the reaction mixture was cooled to room temperature, filtered, dried over magnesium sulfate and concentrated under reduced pressure to give 6.15 grams (0.022 moles) of 2,3-dihydro-2,2-dimethyl-4-(2-hydroxybenzylideneamino)benzofuran-7-ol in the form of a dark red oil.
Reaction SMILES: CN(C)CCC[OH:6].[OH-].[K+].Cl/[C:11](/[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[CH:12]\[C:13]1[C:18]([C:19]#[N:20])=[C:17]([C:21]2[CH:26]=[CH:25][C:24]([O:27]C)=[CH:23][CH:22]=2)[N:16]=[C:15]2[NH:29][N:30]=[C:31]([CH3:32])[C:14]=12.B(Br)(Br)Br>CS(C)=O.O>[OH:27][C:24]1[CH:23]=[CH:22][C:21]([C:17]2[N:16]=[C:15]3[NH:29][N:30]=[C:31]([CH3:32])[C:14]3=[C:13]([CH2:12][C:11](=[O:6])[C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:18]=2[C:19]#[N:20])=[CH:26][CH:25]=1
Reactant: COc1ccc(-c2nc3[nH]nc(C)c3c(/C=C(\Cl)c3ccccc3)c2C#N)cc1
Reactant: CN(C)CCCO
Agent: BrB(Br)Br
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CS(C)=O
Product: Cc1n[nH]c2nc(-c3ccc(O)cc3)c(C#N)c(CC(=O)c3ccccc3)c12
Temperature: 25 °C
Reaction time: 3 h
Yield: 54.3 %

Procedure:
36 g (350 mmol) of 3-(dimethylamino)propan-1-ol and 12 g (21.4 mmol) of potassium hydroxide are added to 12 g (30 mmol) of Z-4-(2-chloro-2-phenylvinyl)-6-(4-methoxyphenyl)-3-methyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile dissolved in 100 ml of dimethylsulfoxide and 36 ml of water. The reaction mixture is carried at 120° C. for 3 hours. The reaction medium is cooled to room temperature and then poured over crushed ice. The product is extracted with ethyl acetate. The organic phases are dried on sodium sulfate, filtered and then concentrated. The residue is purified immediately by silica gel chromatography (eluent: 95:5 dichloromethane/methanol). The product is then dissolved in 100 ml of dichloromethane. The reaction medium is cooled in an ice bath before 36 ml (376.5 mmol) of boron tribromide is added slowly. The reaction medium is stirred at room temperature for 3 hours and then added slowly to crushed ice. The solid is filtered, rinsed with water, dried and then purified by silica gel chromatography (eluent: 5:5 cyclohexane/ethyl acetate) to yield 6 g (54%) of 6-(4-hydroxyphenyl)-3-methyl-4-(2-oxo-2-phenylethyl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile in the form of a yellow solid.
Reaction SMILES: [CH3:1][N:2]([CH3:12])[CH:3]=[CH:4][C:5](=[O:11])[C:6]([O:8]CC)=O.[C:13]1(C(=O)C(=O)C)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(OC(OCC)N(C)C)C>>[CH3:12][N:2]([CH3:1])[CH:3]=[CH:4][C:5](=[O:11])[C:6]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:8]
Reactant: CCOC(=O)C(=O)C=CN(C)C
Reactant: CC(=O)C(=O)c1ccccc1
Agent: CCOC(OCC)N(C)C
Product: CN(C)C=CC(=O)C(=O)c1ccccc1

Procedure:
The procedure is as in Example 2 for the preparation of ethyl 4-dimethylamino-2-oxo-3-butenoate, starting with 1-phenyl-1,2-propanedione (25 g) and N,N-dimethylformamide diethyl acetal (28.3 g). After purification by chromatography on a silica column with ethyl acetate as eluent, 4-dimethylamino-1-phenyl-3-butene-1,2-dione (9.3 g), m.p. 88° C., is obtained.
Reaction SMILES: [OH:1]/[N:2]=[C:3](/[C:9](=[O:11])[CH3:10])\[C:4]([O:6][CH2:7][CH3:8])=[O:5].Br[CH:13]1[CH2:17][CH2:16][S:15][CH2:14]1>>[S:15]1[CH2:16][CH2:17][CH:13]([O:1]/[N:2]=[C:3](/[C:9](=[O:11])[CH3:10])\[C:4]([O:6][CH2:7][CH3:8])=[O:5])[CH2:14]1
Reactant: CCOC(=O)/C(=N\O)C(C)=O
Reactant: BrC1CCSC1
Product: CCOC(=O)/C(=N\OC1CCSC1)C(C)=O
Yield: 68 %

Procedure:
Ethyl (Z)-2-hydroxyimino-3-oxobutyrate (1.68 g) was treated with 3-bromotetrahydrothiophene as described in Example 4a, method 2, to give the title compound (1.7 g, 68%) as a colourless liquid; [Found M+ 245.0719, C10H15NO4S requires M 245.0722]. νmax (film) 2890, 2940, 1745, 1695, and 1600 cm-1. δH (CDCl3) 1.33 (3H, t), 2.02 (1H, m), 2.41 (3H, s), 2.47 (1H, m), 2.89 (2H, m), 3.13 (2H, m), 4.35 (2H, q), and 5.14 (1H, m). δc (CDCl3) 14.1, 25.2, 28.6, 35.7, 62.0, 88.3, 150.8, 60.7, and 192.6.