Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:12])[CH:10]=[CH2:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:13]([NH:21][NH2:22])(=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C(O)(C)C>[C:13]([NH:21][NH:22][CH2:11][CH2:10][C:9]([O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:12])(=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: NNC(=O)c1ccccc1
Reactant: C=CC(=O)OCc1ccccc1
Solvent: CC(C)O
Product: O=C(CCNNC(=O)c1ccccc1)OCc1ccccc1
Temperature: 25 °C
Yield: 50.1 %

Procedure:
Benzylacrylate (1.13 ml, 7.34 mmol) was added to a stirred suspension of benzoylhydrazine (285) (1.0 g, 7.34 mmol) in isopropanol (28 ml). The mixture was refluxed for 20 h, cooled to room temperature then concentrated. The residue was purified by flash chromatography (20% EtOAc in CH2Cl2) to afford 259 (1.098 g, 50%) as an oil which crystallized on standing: mp 65° C.; IR (KBr) 3283, 1723, 1644, 1316, 1201, 1156; 1H NMR (CDCl3) δ 8.32-8.18 (1H, m), 7.81-7.70 (2H, m), 7.57-7.23 (8H, m), 5.36-4.92 (1H, brm), 5.11 (2H, s), 3.26 (2H, t, J=6.5), 2.59 (2H, t, J=6.5); 13C NMR (CDCl3) δ 172.12, 167.27, 135.65, 132.54, 131.66, 128.45, 128.10, 128.06, 126.84, 66.31, 47.33, 33.31; Anal. Calcd for C17H18N2O3: C, 68.44; H, 6.08; N, 9.39. Found: C, 68.42; H, 6.10; N, 9.38. MS (ES +) 321 (M+Na, 38%), 299 (M++1, 100).
Reaction SMILES: [C:1]([CH2:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=[O:10])=[CH:7][CH:6]=1)(=[S:3])[NH2:2].[Cl:14][CH2:15][C:16]([CH2:18]Cl)=O>C1COCC1>[Cl:14][CH2:15][C:16]1[N:2]=[C:1]([CH2:4][C:5]2[CH:13]=[CH:12][C:8]([C:9]([OH:11])=[O:10])=[CH:7][CH:6]=2)[S:3][CH:18]=1
Reactant: O=C(CCl)CCl
Reactant: NC(=S)Cc1ccc(C(=O)O)cc1
Solvent: C1CCOC1
Product: O=C(O)c1ccc(Cc2nc(CCl)cs2)cc1
Yield: 82.8 %

Procedure:
A solution of 250 (729 mg, 3.73 mmol) and 1,3-dichloroacetone (474 mg, 3.73 mmol) in THF (30 ml) was stirred at 40° C. during 48 h. The solvent was evaporated then the residue was dissolved in ethyl acetate, washed with brine, dried over anhydrous MgSO4, filtered and concentrated. The crude residue was purified by flash chromatography on silica gel (2-4% MeOH/CH2Cl2) to afford the title compound (827 mg, 83% yield) as a white solid. 1H NMR (DMSO) δ (ppm): 12.93 (bs, 1H), 7.91 (d, J=8.1 Hz, 2H), 7.63 (s, 1H), 7.46 (d, J=8.1 Hz, 2H), 4.78 (s, 2H), 4.42 (s, 2H).
Reaction SMILES: [C-:1]#[N:2].[K+].[C-]#N.[Na+].C1OCCOCCOCCOCCOCCOC1.Br[CH2:26][C@H:27]1[N:31]([CH3:32])[C:30](=[O:33])[CH2:29][CH2:28]1>CC#N>[CH3:32][N:31]1[C:30](=[O:33])[CH2:29][CH2:28][C@H:27]1[CH2:26][C:1]#[N:2]
Reactant: [C-]#N
Reactant: CN1C(=O)CC[C@H]1CBr
Agent: C1COCCOCCOCCOCCOCCO1
Agent: [K+]
Agent: [Na+]
Solvent: CC#N
Product: CN1C(=O)CC[C@H]1CC#N

Procedure:
KCN (886 mg, 13.6 mmols), NaCN (666 mg, 13.6 mmols) and 18-crown-6 (207 mg, 1.02 mmols) were added to a CH3CN (25 ml) solution of the (5S)-5-(bromomethyl)-1-methylpyrrolidin-2-one (1.31 g, 6.8 mmols), and the mixture was heated for 43 hours under reflux. The inorganic matter was filtered off, and the filtrate was diluted with AcOEt (50 ml). The dilution was washed with a saturated solution (30 ml) of NaCl, and dried over MgSO4. The solvent was distilled off under reduced pressure, and then the residue was subjected to silica gel column chromatography (SiO2 50 g, MeOH—CHCl3 1:9 v/v) to obtain 2-((2S)-1-methyl-5-oxopyrrolidin-2-yl)ethanenitrile as a mixture (1.05 g) with impurities difficult to separate: IR νmax (film) cm−1: 2246, 1685. 1H-NMR (CDCl3)δ: 3.85-3.76 (1H, m), 2.88 (3H, s), 2.68 (1H, dd, J=17.0, 4.4 Hz), 2.61 (1H, dd, J=17.0, 6.0 Hz), 2.62-2.48 (1H, m), 2.46-2.30 (2H, m), 2.00-1.86 (1H, m). MS m/z: 138 (M+), 98 (100%). HRMS: Calcd. for C7H10N2O: 138.0793 (M+). Found: 138.0794 (M+).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]2[O:8][CH2:9][C:10]([CH2:12][O:13][C:4]=2[CH:3]=1)=[O:11].[CH3:14][O:15][C:16]1[C:23]([O:24][CH3:25])=[C:22]([O:26][CH3:27])[CH:21]=[CH:20][C:17]=1[CH:18]=O>>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]2[O:8]/[C:9](=[CH:18]\[C:17]3[CH:20]=[CH:21][C:22]([O:26][CH3:27])=[C:23]([O:24][CH3:25])[C:16]=3[O:15][CH3:14])/[C:10](=[O:11])/[C:12](=[CH:18]/[C:17]3[CH:20]=[CH:21][C:22]([O:26][CH3:27])=[C:23]([O:24][CH3:25])[C:16]=3[O:15][CH3:14])/[O:13][C:4]=2[CH:3]=1
Reactant: COc1ccc(C=O)c(OC)c1OC
Reactant: Cc1ccc2c(c1)OCC(=O)CO2
Product: COc1ccc(/C=C2\Oc3ccc(C)cc3O/C(=C\c3ccc(OC)c(OC)c3OC)C2=O)c(OC)c1OC

Procedure:
Calone is reacted with 2,3,4-trimethoxybenzaldehyde analogously to the reaction conditions of Example 1, giving 7-methyl-2,4-bis[1-(2,3,4-tri-methoxyphenyl)meth-(Z)-ylidene]benzo[b]-1,4-dioxepin-3-one.
Reaction SMILES: [CH:1]12[CH2:7][CH:4]([NH:5][CH2:6]1)[CH2:3][N:2]2[C:8]1[N:13]2[CH:14]=[CH:15][N:16]=[C:12]2[CH:11]=[C:10]([C:17]2[CH:22]=[CH:21][N:20]=[C:19]([NH:23][CH:24]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH3:25])[CH:18]=2)[N:9]=1.[CH2:32]=O>CO.C(Cl)Cl>[CH3:32][N:5]1[CH2:6][C@@H:1]2[CH2:7][C@H:4]1[CH2:3][N:2]2[C:8]1[N:13]2[CH:14]=[CH:15][N:16]=[C:12]2[CH:11]=[C:10]([C:17]2[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C@H:24]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH3:25])[CH:18]=2)[N:9]=1
Reactant: C=O
Reactant: CC(Nc1cc(-c2cc3nccn3c(N3CC4CC3CN4)n2)ccn1)c1ccccc1
Solvent: ClCCl
Solvent: CO
Product: C[C@H](Nc1cc(-c2cc3nccn3c(N3C[C@@H]4C[C@H]3CN4C)n2)ccn1)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of 96 mg (0.23 mmol) {4-[5-(2,5-diaza-bicyclo[2.2.1]hept-2-yl)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine in 3 mL methanol was treated with 0.17 mL (2.3 mmol) formaldehyde (37% in water) and 150 mg (0.70 mmol) NaBH3(CN). The mixture was stirred at ambient temperature for 1 h when MS showed that all starting materials had converted to product. The reaction mixture was diluted with 50 mL DCM, washed with 50 mL satd. NaHCO3, and dried over anhydrous Na2SO4. After purification by HPLC, the title compound was obtained. MS (ES+): 426 (M+H)+.
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:6]=[C:7]([CH:13]2[CH2:18][C:17](=[O:19])[C:16]([C:20](=O)[CH2:21][CH2:22][CH3:23])=[C:15]([OH:25])[CH2:14]2)[CH:8]=[CH:9][C:10]=1[O:11][CH3:12])(=[O:3])[CH3:2].Cl.[CH2:27]([O:30][NH2:31])[CH:28]=[CH2:29].C(=O)(O)[O-].[Na+]>CO>[C:1]([NH:4][C:5]1[CH:6]=[C:7]([CH:13]2[CH2:18][C:17](=[O:19])[C:16]([C:20](=[N:31][O:30][CH2:27][CH:28]=[CH2:29])[CH2:21][CH2:22][CH3:23])=[C:15]([OH:25])[CH2:14]2)[CH:8]=[CH:9][C:10]=1[O:11][CH3:12])(=[O:3])[CH3:2]
Reactant: CCCC(=O)C1=C(O)CC(c2ccc(OC)c(NC(C)=O)c2)CC1=O
Reactant: C=CCON
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Product: C=CCON=C(CCC)C1=C(O)CC(c2ccc(OC)c(NC(C)=O)c2)CC1=O
Yield: 57.6 %

Procedure:
3 g of 5-(3-acetylamino-4-methoxyphenyl)-2-butyryl-3-hydroxycyclohex-2-en-1-one were stirred together with 0.95 g of O-allylhydroxylamine hydrochloride and 0.8 g of sodium bicarbonate in 40 ml of methanol for 16 hours. The mixture was evaporated down, mixed with methylene chloride, washed thoroughly with water, dried and evaporated down again. The residue which remained was stirred with diisopropyl ether and the product was filtered off under suction. 2.0 g (57% yield) of 5-(3-acetylamino-4-methoxyphenyl)-2-(1-allyloxyiminobutyl)-3-hydroxycyclohex-2-en-1-one of melting point 136°-137° C. were obtained (compound No. 11).
Reaction SMILES: [ClH:1].[CH3:2][C:3]1[CH:15]=[CH:14][C:6]([CH2:7][CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:5][CH:4]=1.[CH2:16]([O:23][C:24]1[CH:33]=[CH:32][CH:31]=[CH:30][C:25]=1[O:26]CCBr)[C:17]1C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>>[ClH:1].[OH:26][C:25]1[CH:30]=[CH:31][CH:32]=[CH:33][C:24]=1[O:23][CH2:16][CH2:17][N:11]1[CH2:12][CH2:13][CH:8]([CH2:7][C:6]2[CH:5]=[CH:4][C:3]([CH3:2])=[CH:15][CH:14]=2)[CH2:9][CH2:10]1
Reactant: Cc1ccc(CC2CCNCC2)cc1
Reactant: BrCCOc1ccccc1OCc1ccccc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Product: Cc1ccc(CC2CCN(CCOc3ccccc3O)CC2)cc1

Procedure:
The title compound was prepared from 4-(4-methylbenzyl)piperidine hydrochloride (294 mg, 1.30 mmol), 2-(2-benzyloxyphenoxy)ethyl bromide (399 mg, 1.3 mmol) and potassium carbonate (449 mg, 3.2 mmol) in two steps as white-off solid (240 mg): mp 225-227° C. 1H NMR (CD3OD) 1.436 (m, 2 H), 1.758 (d, J=12.9 Hz, 3 H), 2.135 (s, 3 H), 2.443 (d, J=6.3 Hz, 2 H), 2.900 (m, 2 H), 3.388 (m, 2 H), 3.503 (m, 2 H), 4.172 (t, J=5.7 Hz, 2 H), 6.651-6.739 (m, 3 H), 6.818 (m, 1 H), 6.928 (m, 4 H).
Reaction SMILES: [F:1][C:2]1[C:27]([F:28])=[CH:26][C:5]2[N:6]([CH2:16][C:17]3[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][C:18]=3[F:25])[C:7]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[OH:15])=[N:8][C:4]=2[CH:3]=1.I[CH2:30][CH:31]1[CH2:35][CH2:34][CH2:33][CH2:32]1>>[CH:31]1([CH2:30][O:15][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[C:7]2[N:6]([CH2:16][C:17]3[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][C:18]=3[F:25])[C:5]3[CH:26]=[C:27]([F:28])[C:2]([F:1])=[CH:3][C:4]=3[N:8]=2)[CH2:35][CH2:34][CH2:33][CH2:32]1
Reactant: N#Cc1ccc(Cn2c(-c3ccccc3O)nc3cc(F)c(F)cc32)c(F)c1
Reactant: ICC1CCCC1
Product: N#Cc1ccc(Cn2c(-c3ccccc3OCC3CCCC3)nc3cc(F)c(F)cc32)c(F)c1

Procedure:
The title compound was prepared in analogy to Example 5, intermediate a, from 4-[5,6-difluoro-2-(2-hydroxy-phenyl)-benzoimidazol-1-ylmethyl]-3-fluoro-benzonitrile and iodomethyl-cyclopentane (CAS Reg. No. 27935-87-1). Off-white solid (51%). MS (Turbo Spray): m/z=462.2 (M+H).
Reaction SMILES: [N+:1]([C:4]1[CH:8]=[CH:7][N:6]([CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])[N:5]=1)([O-])=O.CO.[H][H]>C(OCC)(=O)C.[Pd]>[CH2:9]([N:6]1[CH:7]=[CH:8][C:4]([NH2:1])=[N:5]1)[CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]
Reactant: [H][H]
Reactant: CCCCCCn1ccc([N+](=O)[O-])n1
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CO
Product: CCCCCCn1ccc(N)n1
Temperature: 25 °C
Reaction time: 16 h
Yield: 87.7 %

Procedure:
3-Nitro-1-hexyl-1H-pyrazole (118 mg, 0.60 mmol) was dissolved in ethyl acetate (3 mL) and methanol (3 mL) was added. Palladium, 10 wt. % on activated carbon, wet (˜50 mg) was added to the reaction. The vial was charged with hydrogen gas (via balloon) and the reaction stirred for 16 h at 25° C. The mixture was passed through a plug of celite and concentrated in vacuo afforded 1-hexyl-1H-pyrazol-3-ylamine (88 mg, 88%) as a golden oil: ESI-LRMS m/e calcd for C9H17N3 [M+] 167.15, found 168.4 [M+H+].
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([F:9])[C:3]=1[F:10].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=1>C(#N)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)=[C:4]([F:9])[C:3]=1[F:10]
Reactant: COc1ccc(CCl)cc1
Reactant: Oc1ccc(Br)c(F)c1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: COc1ccc(COc2ccc(Br)c(F)c2F)cc1
Reaction time: 0.08 h
Yield: 96.3 %

Procedure:
To a stirred solution of 4-bromo-2,3-difluorophenol (5 g, 23.92 mmol) in acetonitrile (50 mL) was added potassium carbonate (3.31 g, 23.92 mmol) at room temperature and the reaction mixture was stirred for 5 min followed by the addition of 1-(chloromethyl)-4-methoxybenzene (3.75 g, 23.92 mmol) dropwise then the reaction mixture was stirred at room temperature for 16 h. After the completion of reaction, the volatiles were removed under reduced pressure. Water (100 mL) was added and the solution extracted with ethyl acetate (2×120 mL). The combined organic layers were washed with brine (100 mL), dried over sodium sulphate, filtered and concentrated under reduced pressure to afford 1-bromo-2,3-difluoro-4-((4-methoxybenzyl)oxy)benzene (7.58 g, 23.03 mmol, 96% yield) as a pale brown solid. The product was carried on without further purification. LCMS (ESI) m/e 329.1 [(M)−, calcd for C14H10BrF2O2 329.0]; LC/MS retention time (Method G): tR=1.20 min.
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[S:10]([NH2:13])(=[O:12])=[O:11].C(OC(=O)C)(=O)C.[N:21]1[CH:26]=[CH:25][CH:24]=CC=1>>[N:21]1[CH:24]=[CH:25][C:26]=1[NH:13][S:10]([C:2]1[S:1][C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=1)(=[O:12])=[O:11]
Reactant: NS(=O)(=O)c1nc2ccccc2s1
Reactant: c1ccncc1
Solvent: CC(=O)OC(C)=O
Product: O=S(=O)(NC1=NC=C1)c1nc2ccccc2s1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
2-Benzothiazolesulfonamide (1.0g., 0047 mol) was dissolved in 30 ml of pyridine and stirred at room temperature for 15 minutes. Freshly distilled acetic anhydride (2 ml) was added to this solution and the reaction stirred over night at room temperature. The reaction was poured into a 300 ml beaker containing 25 ml of concentrated HC1 and 250 of crushed ice. The reaction was allowed to stand at room temperature until the ice melted and then vacuum filtered to yield 0.2 g of product (quantitative yield). The product was purified by adding the crude product to 25 ml of 10% Ha2CO3.H2O solution, filtering the sodium salt of N-acetyl-2-benzothiazolesulfonamide and dissolving it into water followed by careful acidification and hydrochloric acid. m.p. 197° -199° C.; NMR(DMSO-D6) δ8.4-7.5 (m, 5H), 2.1 (2, 3H). Elemental Analyses: C9H8N2O3S2. Calculated: C 42.18%, H 3.15%, N 1-0.93%. Found: C 42.27%, H 3.14%, N 10.86%.
Reaction SMILES: [CH3:1][C:2]1[C:9]([CH3:10])=[CH:8][C:5]([C:6]#[N:7])=[C:4]([N+:11]([O-])=O)[CH:3]=1>C(O)(=O)C.[Fe]>[CH3:1][C:2]1[C:9]([CH3:10])=[CH:8][C:5]([C:6]#[N:7])=[C:4]([NH2:11])[CH:3]=1
Reactant: Cc1cc(C#N)c([N+](=O)[O-])cc1C
Agent: [Fe]
Solvent: CC(=O)O
Product: Cc1cc(N)c(C#N)cc1C

Procedure:
0.41 g Sodium nitrite in water is added to 1 g 4,5-dimethyl-2-nitroaniline in 3 mL conc. HCl and stirred for 1 hour at +4° C. This solution is added to a mixture of 0.67 g copper (I) cyanide, 0.98 g sodium cyanide, 0.32 g sodium carbonate, 25 mL of water and 3 mL toluene. The mixture is stirred for 12 hours at room temperature and worked up to give 0.45 g 4,5-dimethyl-2-nitrobenzonitrile. 4,5-Dimethyl-2-nitrobenzonitrile is reduced with iron powder in acetic acid to yield 4,5-dimethyl-2-aminobenzonitrile. 4,5-Dimethyl-2-aminobenzonitrile is heated at reflux for 12 hours in conc. HCl to give 4,5-dimethyl-2-aminobenzoic acid. 4,5-Dimethyl-2-aminobenzoic acid is reacted with trimethylsilyl-diazomethane to yield methyl 4,5-dimethyl-2-aminobenzoate (Chem. Pharm. Bull. Vol. 29, 1475 (1981)).
Reaction SMILES: Cl[C:2]1[CH:7]=[N:6][CH:5]=[C:4]([Cl:8])[N:3]=1.[CH3:9][C:10]([CH3:13])([O-:12])[CH3:11].[K+]>O1CCCC1>[C:10]([O:12][C:2]1[CH:7]=[N:6][CH:5]=[C:4]([Cl:8])[N:3]=1)([CH3:13])([CH3:11])[CH3:9]
Reactant: CC(C)(C)[O-]
Reactant: Clc1cncc(Cl)n1
Agent: [K+]
Solvent: C1CCOC1
Product: CC(C)(C)Oc1cncc(Cl)n1
Temperature: 25 °C
Reaction time: 5.5 h
Yield: 89.9 %

Procedure:
After dissolving 3.00 g of 2,6-dichloropyrazine in 40 ml of tetrahydrofuran, 2.26 g of potassium tert-butoxide was added and the mixture was stirred for 5.5 hours at room temperature. The reaction solution was distilled off under reduced pressure, ethyl acetate was added to the residue and filtration was performed with NH silica gel and silica gel. The solvent was distilled off under reduced pressure to obtain the title compound (3.38 g, 90% yield).
Reaction SMILES: [F:1][C:2]1[C:3](=[O:9])[NH:4][C:5](=[O:8])[NH:6][CH:7]=1.[CH3:10][O:11][C:12]1[CH:13]=[C:14]([N:22]=[C:23]=[O:24])[CH:15]=[C:16]([O:20][CH3:21])[C:17]=1[O:18][CH3:19].N1C=CC=CC=1>ClCCl>[CH3:10][O:11][C:12]1[CH:13]=[C:14]([NH:22][C:23]([N:6]2[CH:7]=[C:2]([F:1])[C:3](=[O:9])[NH:4][C:5]2=[O:8])=[O:24])[CH:15]=[C:16]([O:20][CH3:21])[C:17]=1[O:18][CH3:19]
Reactant: O=c1[nH]cc(F)c(=O)[nH]1
Reactant: COc1cc(N=C=O)cc(OC)c1OC
Solvent: ClCCl
Solvent: c1ccncc1
Product: COc1cc(NC(=O)n2cc(F)c(=O)[nH]c2=O)cc(OC)c1OC
Temperature: 90 °C
Yield: 47.2 %

Procedure:
A mixture of 3.9 g of 5-fluorouracil, 6.27 g of 3, 4, 5-trimethoxyphenylisocyanate and 15 ml of pyridine was heated at 90° C. for 2 hr and, after evaporating pyridine, 100 ml of dichloromethane and 200 ml of hydrochloric acid water were added to it. The insoluble substance produced was combined with the substance dissolved in the dichloromethane. The combined substances were washed with water and then with ethanol, and 4.8 g of 1-(3, 4, 5-trimethoxyphenylcarbamoy)-5-fluorouracil (melting point: 168°-170° C.) was obtained (Compound No. 6). NMR: 3.76 (3H s OCH3) 3.84 (6H s OCH3) 6.64-7.0 (2H b C6H2).
Reaction SMILES: [CH:1]1([C:6]2[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][CH:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:13]([CH:15]1[O:17][CH2:16]1)Cl>>[CH:1]1([C:6]2[CH:7]=[CH:8][C:9]([O:12][CH2:13][CH:15]3[CH2:16][O:17]3)=[CH:10][CH:11]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: ClCC1CO1
Reactant: Oc1ccc(C2CCCC2)cc1
Product: c1cc(C2CCCC2)ccc1OCC1CO1

Procedure:
The title compound was prepared from 4-cyclopentyl-phenol and epichlorohydrin employing the procedures as set forth in Step 1 of Example 2.
Reaction SMILES: [N:1]1([S:7]([C:10]2[CH:11]=[C:12]([CH:16]=[CH:17][CH:18]=2)[C:13]([OH:15])=O)(=[O:9])=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:19]1([C:22]2[NH:26][N:25]=[C:24]([NH2:27])[CH:23]=2)[CH2:21][CH2:20]1>>[CH:19]1([C:22]2[CH:23]=[C:24]([NH:27][C:13](=[O:15])[C:12]3[CH:16]=[CH:17][CH:18]=[C:10]([S:7]([N:1]4[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]4)(=[O:8])=[O:9])[CH:11]=3)[NH:25][N:26]=2)[CH2:21][CH2:20]1
Reactant: Nc1cc(C2CC2)[nH]n1
Reactant: O=C(O)c1cccc(S(=O)(=O)N2CCCCC2)c1
Product: O=C(Nc1cc(C2CC2)n[nH]1)c1cccc(S(=O)(=O)N2CCCCC2)c1

Procedure:
The entitled compound was produced according to the method of Example 92 but using 3-(piperidin-1-ylsulfonyl)benzoic acid and 5-cyclopropyl-1H-pyrazole-3-amine as the starting materials.
Reaction SMILES: [C:1]([Si:5]([CH3:18])([CH3:17])[O:6][C:7]([C:10]([CH3:16])([CH:14]=[CH2:15])[C:11]([OH:13])=[O:12])([CH3:9])[CH3:8])([CH3:4])([CH3:3])[CH3:2].Br[C:20]1[CH:29]=[C:28]2[C:23]([CH:24]=[CH:25][C:26]([C@H:30]([O:32][C:33](=[O:35])[CH3:34])[CH3:31])=[N:27]2)=[CH:22][CH:21]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:33]([O:32][C@@H:30]([C:26]1[CH:25]=[CH:24][C:23]2[C:28](=[CH:29][C:20](/[CH:15]=[CH:14]/[C:10]([C:7]([O:6][Si:5]([C:1]([CH3:4])([CH3:3])[CH3:2])([CH3:18])[CH3:17])([CH3:8])[CH3:9])([CH3:16])[C:11]([OH:13])=[O:12])=[CH:21][CH:22]=2)[N:27]=1)[CH3:31])(=[O:35])[CH3:34]
Reactant: CC(=O)O[C@H](C)c1ccc2ccc(Br)cc2n1
Reactant: C=CC(C)(C(=O)O)C(C)(C)O[Si](C)(C)C(C)(C)C
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CC(=O)O[C@H](C)c1ccc2ccc(/C=C/C(C)(C(=O)O)C(C)(C)O[Si](C)(C)C(C)(C)C)cc2n1
Temperature: 100 °C
Reaction time: 0.33 h
Yield: 65 %

Procedure:
A solution of 2-[1-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-2-methyl-but-3-enoic acid (258 mg, 0.95 mmol), acetic acid (R)-1-(7-bromo-quinolin-2-yl)-ethyl ester (279 mg, 0.95 mmol), palladium(II) acetate (43 mg, 0.19 mmol), tris-(o-tolyl)phosphine (87 mg, 0.29 mmol) in anhydrous acetonitrile (3 mL) was treated with triethylamine (265 μL, 1.90 mmol). After stirring at 100° C. under microwave for 20 min, the reaction was cooled to room temperature and the volatiles were removed in vacuo. The residue was partitioned between dichloromethane and a saturated potassium hydrogen sulfate solution. The organics were combined and the volatiles were removed in vacuo. The residue was purified by silica gel chromatography using a 25 g Biotage cartridge eluted with a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 0:1 to afford the title compound (300 mg, 65%) as a colourless oil. 1H NMR (300 MHz, CDCl3) δ 0.20 (s, 3H), 0.22 (s, 3H), 0.94 (s, 9H), 1.44 (s, 3H), 1.45 (s, 3H), 1.50 (s, 3H), 1.68 (d, J=6.7 Hz, 3H), 2.17 (s, 3H), 6.06 (q, J=6.7 Hz, 1H), 6.76 (m, 2H), 7.43 (d, J=8.5 Hz, 1H), 7.62 (d, J=8.5 Hz, 1H), 7.74 (d, J=8.7 Hz, 1H), 8.03 (s, 1H), 8.11 (d, J=8.5 Hz, 1H). LCMS (m/z) 486.3 [M+H], Tr=3.64 min.
Reaction SMILES: S(Cl)(Cl)=O.[Br:5][C:6]1[CH:7]=[C:8]([CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]([OH:19])=O)[CH:9]=[CH:10][CH:11]=1.[Cl-].[Cl-].[Cl-].[Al+3]>C(=S)=S>[Br:5][C:6]1[CH:11]=[CH:10][C:9]2[C:17](=[O:19])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][C:8]=2[CH:7]=1
Reactant: O=C(O)CCCCCc1cccc(Br)c1
Agent: [Al+3]
Agent: [Cl-]
Solvent: S=C=S
Solvent: O=S(Cl)Cl
Product: O=C1CCCCCc2cc(Br)ccc21
Temperature: 60 °C
Reaction time: 20 h
Yield: 67.4 %

Procedure:
Thionyl chloride (13.2 mL, 181 mmol) was added (neat) to Example 2a, 6-(3-bromophenyl)hexanoic acid (16 g, 59.2 mmol) in a 1 L round-bottomed flask under a nitrogen atmosphere. The mixture was warmed to 60° C. for 2 h, excess reagent was removed in vacuo, and the residue was subjected to azeotropic conditions (benzene 3×). The acid chloride was dissolved in carbon disulfide (550 mL) and cannulated into a solution of aluminum trichloride (26.3 g, 198 mmol) in carbon disulfide (1315 mL) heated at reflux. The reaction was stirred 20 h, cooled, decanted, concentrated, and the resultant solids were stirred in diethyl ether/THF (1:1, 1 L), and 1N HCl (500 mL) for 1.5 hours. The organic layer was filtered, washed with water, and brine to give Example 3c, 2-bromo-7,8,9,10-tetrahydrobenzo[8]annulen-5(6H)-one 10.1 g (66%) as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 7.55 (d, J=8.4 Hz, 1H), 7.38 (dd, J=8.4 Hz, 1.8 Hz, 1H), 7.33 (d, J=1.8 Hz, 1H), 2.99 (t, J=6.6 Hz, 2H), 2.89 (t, J=6.6 Hz, 2H), 1.85-1.73 (m, 4H), 1.52-1.44 (m, 2H). RT=2.8 minutes (condition 2); LRMS: Anal. Calcd. for C12H13BrO: 253.02. found: 253.15 (M+H).
Reaction SMILES: [Cl:1][C:2]1[N:3]=[CH:4][C:5]2[NH:14][C:13](=[O:15])[CH2:12][C@@H:11]3[N:7]([CH2:8][CH2:9][CH2:10]3)[C:6]=2[N:16]=1.[C:17](=O)([O-])[O-].[Cs+].[Cs+].IC>CN(C)C=O>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[N:14]([CH3:17])[C:13](=[O:15])[CH2:12][C@@H:11]3[N:7]([CH2:8][CH2:9][CH2:10]3)[C:6]=2[N:16]=1
Reactant: O=C([O-])[O-]
Reactant: O=C1C[C@H]2CCCN2c2nc(Cl)ncc2N1
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CI
Product: CN1C(=O)C[C@H]2CCCN2c2nc(Cl)ncc21
Reaction time: 8 h
Yield: 81.5 %

Procedure:
To a solution of 0.4 g (0.0017 mole) of (R)-9-chloro-2,3,3a,4-tetrahydro-1H,6H-6,8,10,10b-tetraaza-benzo[e]azulen-5-one (VI-102) in 10 mL of dimethylformamide was added 1.1 g (0.0034 mole) of cesium carbonate, followed by 0.32 mL (0.0051 mole) of iodomethane. After stirring overnight, the mixture was filtered and the filtrate concentrated under reduced pressure. Purification of the residue by silica gel chromatography, eluting with hexanes-ethyl acetate (40:60-0:100) gave 0.35 g of (R)-9-chloro-6-methyl-2,3,3a,4-tetrahydro-1H,6H-6,8,10,10b-tetraaza-benzo[e]azulen-5-one (VII-102) as a light yellow solid.
Reaction SMILES: [Cl:1][C:2]1[CH:12]=[CH:11][CH:10]=[C:9]([Cl:13])[C:3]=1[C:4]([N:6]=[C:7]=[O:8])=[O:5].[Cl:14][C:15]1[CH:16]=[C:17]([CH:19]=[CH:20][C:21]=1[Cl:22])[NH2:18]>C1C=CC=CC=1>[Cl:1][C:2]1[CH:12]=[CH:11][CH:10]=[C:9]([Cl:13])[C:3]=1[C:4]([NH:6][C:7]([NH:18][C:17]1[CH:19]=[CH:20][C:21]([Cl:22])=[C:15]([Cl:14])[CH:16]=1)=[O:8])=[O:5]
Reactant: Nc1ccc(Cl)c(Cl)c1
Reactant: O=C=NC(=O)c1c(Cl)cccc1Cl
Solvent: c1ccccc1
Product: O=C(NC(=O)c1c(Cl)cccc1Cl)Nc1ccc(Cl)c(Cl)c1

Procedure:
35 g of 2,6-dichlorobenzoylisocyanate in 100 ml of dry benzene are added drop by drop, with stirring and cooling, to a solution of 24.3 g of 3,4-dichloroaniline in 200 ml of dry benzene. Much heat is evolved and a precipitate is formed which is drawn off while hot and then is washed with hot benzene. The resulting N-(2,6-dichlorobenzoyl)-N'-(3,4-dichlorophenyl)-urea is pure, as is shown by thin layer chromatography (with ethylacetate as the solvent). If desired, the product may be recrystallized from acetonitrile. Melting point 238° K.