Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[C:10]([CH3:12])[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[Al].[Br:14]Br>C(OCC)C>[Br:14][C:9]1[C:10]([CH3:12])=[CH:11][C:2]([CH3:1])=[C:3]([CH:8]=1)[C:4]([O:6][CH3:7])=[O:5]
Reactant: COC(=O)c1ccc(C)cc1C
Reactant: BrBr
Agent: [Al]
Solvent: CCOCC
Product: COC(=O)c1cc(Br)c(C)cc1C
Temperature: 25 °C

Procedure:
To a mixture of the above methyl 2,4-dimethylbenzoate (19.75 g) and activated aluminum neutral oxide (120 g) was added dropwise bromine (9.25 ml) while stirring at room temperature. The mixture was stirred at room temperature for 8 hours, and diluted with diethyl ether (1000 ml). Insoluble materials were filtered off, and washed with diethyl ether (500 ml). The combined filtrate was washed successively with 10% aqueous sodium thiosulfate solution, a saturated aqueous sodium hydrogen carbonate solution and brine. The filtrate was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was crystallized from methanol (40 ml) to give methyl 5-bromo-2,4-dimethylbenzoate (6.34 g) as colorless crystals. APCI-Mass m/Z 243/245 (M+H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH:7]=[CH:8][C:9](=[O:13])[NH:10]2)=[CH:5][CH:4]=1.I[CH:15]1[CH2:18][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:16]1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.O>[C:22]([O:21][C:19]([N:17]1[CH2:18][CH:15]([N:10]2[C:11]3[C:6](=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[CH:12]=3)[CH:7]=[CH:8][C:9]2=[O:13])[CH2:16]1)=[O:20])([CH3:25])([CH3:23])[CH3:24]
Reactant: COc1ccc2ccc(=O)[nH]c2c1
Reactant: CC(C)(C)OC(=O)N1CC(I)C1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1ccc2ccc(=O)n(C3CN(C(=O)OC(C)(C)C)C3)c2c1
Temperature: 80 °C
Yield: 59.4 %

Procedure:
A mixture of 7-methoxy-2(1H)-quinolinone (commercial; 290 mg; 1.65 mmol) and tert-butyl 3-iodo-1-azetidinecarboxylate (commercial; 391 mg; 1.38 mmol) and Cs2CO3 (613 mg; 1.88 mmol) in DMF (2 mL) was heated at 80° C. for 4 h. The reaction mixture was diluted with water and extracted with EA. The combined org. layers were washed with water and brine, dried over MgSO4, concentrated under reduced pressure and purified by CC (Hept/EA 1:1), affording a pale yellow oil (271 mg, 65% yield).
Reaction SMILES: Cl[C:2]1[C:3]2[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[S:14][C:4]=2[N:5]=[C:6]([CH2:8][CH2:9][C:10]([O:12][CH3:13])=[O:11])[N:7]=1.[Cl:21][C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][C:29]=1[O:30][CH3:31])[CH2:25][NH2:26]>CN1CCCC1=O>[Cl:21][C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][C:29]=1[O:30][CH3:31])[CH2:25][NH:26][C:2]1[C:3]2[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[S:14][C:4]=2[N:5]=[C:6]([CH2:8][CH2:9][C:10]([O:12][CH3:13])=[O:11])[N:7]=1
Reactant: COC(=O)CCc1nc(Cl)c2c(n1)sc1ccccc12
Reactant: COc1ccc(CN)cc1Cl
Solvent: CN1CCCC1=O
Product: COC(=O)CCc1nc(NCc2ccc(OC)c(Cl)c2)c2c(n1)sc1ccccc12

Procedure:
Methyl 3-(4-chlorobenzothieno[2,3-d]pyrimidin-2-yl)propionate [obtainable by cyclization of methyl 2-amino-5,6,7,8-tetrahydrobenzothiophene-3-carboxylate with methyl 3-cyanopropionate, dehydrogenation with sulfur and subsequent chlorination with phosphorus oxychloride/dimethylamine] and 3-chloro-4-methoxybenzylamine (“A”) in N-methylpyrrolidone are stirred at 110° for 5 hours. The solvent is removed and the residue is worked up in the customary manner. Methyl 3-[4-(3-chloro-4-methoxybenzylamino)benzothieno-[2,3-d]pyrimidin-2-yl]propionate is obtained as a colourless oil.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:34]=[CH:33][C:12]([CH2:13][C:14]2[C:30]([CH3:31])=[CH:29][C:17]([O:18][Si](C(C)C)(C(C)C)C(C)C)=[CH:16][C:15]=2[CH3:32])=[CH:11][C:10]=1[S:35]([C:38]1[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=1)(=[O:37])=[O:36])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>ClC(Cl)C>[CH2:1]([O:8][C:9]1[CH:34]=[CH:33][C:12]([CH2:13][C:14]2[C:30]([CH3:31])=[CH:29][C:17]([OH:18])=[CH:16][C:15]=2[CH3:32])=[CH:11][C:10]=1[S:35]([C:38]1[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=1)(=[O:36])=[O:37])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Cc1cc(O[Si](C(C)C)(C(C)C)C(C)C)cc(C)c1Cc1ccc(OCc2ccccc2)c(S(=O)(=O)c2ccc(F)cc2)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: CC(Cl)Cl
Product: Cc1cc(O)cc(C)c1Cc1ccc(OCc2ccccc2)c(S(=O)(=O)c2ccc(F)cc2)c1

Procedure:
600 mg (9.95 mmol) of (4-{4-(benzyloxy)-3-[(4-fluorophenyl)sulphonyl]benzyl}-3,5-dimethylphenoxy)-(triisopropyl)silane (Example IX) are dissolved in 15 ml of dichloroethane. At room temperature, 359 mg (1.14 mmol) of tetrabutylammonium fluoride are added, and the mixture is stirred for thirty minutes. The solvent is then removed under reduced pressure and the product is purified by silica gel chromatography (mobile phase cyclohexane/ethyl acetate 9:1). This gives 180 mg (40% of theory) of 4-{4-(benzyloxy)-3-[(4-fluorophenyl)sulphonyl]benzyl}-3,5-dimethylphenol.
Reaction SMILES: S(C1C=CC(C)=CC=1)(O)(=O)=O.[NH2:12][C@:13]1([C:18]([O:20][CH3:21])=[O:19])[CH2:15][C@H:14]1[CH:16]=[CH2:17].[CH:22]1[N:26]=[CH:25][N:24]([C:27](N2C=NC=C2)=[O:28])[CH:23]=1>C1COCC1>[N:24]1([C:27]([NH:12][C@:13]2([C:18]([O:20][CH3:21])=[O:19])[CH2:15][C@H:14]2[CH:16]=[CH2:17])=[O:28])[CH:23]=[CH:22][N:26]=[CH:25]1
Reactant: C=C[C@@H]1C[C@]1(N)C(=O)OC
Reactant: O=C(n1ccnc1)n1ccnc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: C1CCOC1
Product: C=C[C@@H]1C[C@]1(NC(=O)n1ccnc1)C(=O)OC

Procedure:
Compound BT was prepared according to Scheme 12. To a suspension of (1R,2S)-methyl 1-amino-2-vinylcyclopropanecarboxylate tosylate salt (25.0 g, 1 eq.) in THF (150 mL) at 50° C. were added CDI (14.24 g, 1.1 eq.) and TEA (12.27 mL, 1.1 eq.). The reaction mixture was then refluxed overnight. The solvent was removed under reduced pressure. The residue was dissolved in EtOAc, and washed with water. The organic layer was dried over sodium sulfate and concentrated. The residue was triturated in Et2O to afford compound BT (15.24 g, purity 80%) as a white solid. 1H NMR (CDCl3, 400 MHz): δ (ppm) 1.63 (dd, J=5.8 and 9.7 Hz, 1H), 1.96 (dd, J=5.8 and 8.4 Hz, 1H), 2.30 (q, J=8.9 Hz, 1H), 3.73 (s, 3H), 5.16 (d, J=10.0 Hz, 1H), 5.28 (d, J=17.0 Hz, 1H), 5.69-5.81 (m, 1H), 7.03 (s, 1H), 7.50 (s, 1H), 8.24 (s, 1H), 8.57 (s, 1H).
Reaction SMILES: [CH3:1][CH:2]([CH3:19])[CH:3]=[C:4]1[C:13](=O)[C:12]2[C:7](=[CH:8][C:9]([C:15]([O:17]C)=[O:16])=[CH:10][CH:11]=2)[O:6][CH2:5]1.Cl.[NH:21]([C:23]1[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[C:25]([CH3:31])[CH:24]=1)[NH2:22]>>[C:27]([C:26]1[CH:29]=[CH:30][C:23]([N:21]2[CH:3]([CH:2]([CH3:19])[CH3:1])[CH:4]3[CH2:5][O:6][C:7]4[CH:8]=[C:9]([C:15]([OH:17])=[O:16])[CH:10]=[CH:11][C:12]=4[C:13]3=[N:22]2)=[CH:24][C:25]=1[CH3:31])#[N:28]
Reactant: Cc1cc(NN)ccc1C#N
Reactant: COC(=O)c1ccc2c(c1)OCC(=CC(C)C)C2=O
Agent: Cl
Product: Cc1cc(N2N=C3c4ccc(C(=O)O)cc4OCC3C2C(C)C)ccc1C#N
Yield: 52 %

Procedure:
The title compound was prepared from methyl 3-(2-methylpropylidene)-4-oxochroman-7-carboxylate (Preparation 32; 260 mg, 1.0 mmol) and 4-hydrazinyl-2-methylbenzonitrile hydrochloride (Preparation 2; 275 mg, 1.5 mmol) according to Method B and Method C (yellow solid, 196 mg, 0.523 mmol, 52% yield, approximately 7:1 mixture of cis:trans diastereomers). 1H NMR (400 MHz, DMSO-d6) δ ppm 13.12 (br. s., 1H), 7.93 (d, J=8.2 Hz, 1H), 7.58 (dd, J=8.2, 1.6 Hz, 1H), 7.55 (d, J=8.6 Hz, 1H), 7.46 (d, J=1.6 Hz, 1H), 7.21 (d, J=1.6 Hz, 1H), 7.09 (dd, J=8.6, 2.3 Hz, 1H), 4.76-4.86 (m, 2H), 4.42 (dd, J=13.1, 10.4 Hz, 1H), 4.02 (ddd, J=13.2, 10.6, 5.9 Hz, 1H), 2.42 (s, 3H), 2.06-2.17 (m, 1H), 0.83 (d, J=7.4 Hz, 3H), 0.81 (d, J=7.4 Hz, 3H). ES-MS m/z 376 (M+H).
Reaction SMILES: [C:1]1([C:7]#[CH:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:9][SiH:10]([CH:12]([SiH:17]([Cl:19])[Cl:18])[Si:13]([Cl:16])([Cl:15])[Cl:14])[Cl:11]>C1C=CC=CC=1>[Cl:11][Si:10]1([Cl:9])[CH:8]=[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[Si:17]([Cl:18])([Cl:19])[CH:12]1[Si:13]([Cl:16])([Cl:14])[Cl:15]
Reactant: C#Cc1ccccc1
Reactant: Cl[SiH](Cl)C([SiH](Cl)Cl)[Si](Cl)(Cl)Cl
Solvent: c1ccccc1
Product: Cl[Si](Cl)(Cl)C1[Si](Cl)(Cl)C=C(c2ccccc2)[Si]1(Cl)Cl
Reaction time: 15 h
Yield: 43.9 %

Procedure:
Hydrosilation of phenylacetylene with bis(dichlorosilyl)trichlorosilylmethane in the presence of Pt(C2H4)(PPh3)2. Into the same apparatus as described in Example 1 were add 0.99 g of bis(dichlorosilyl)trichlorosilylmethane, 0.101 g of Pt(C2H4)(PPh3)2, and 25 ml of dried benzene forming a mixture. To this mixture at reflux was added 0.32 ml of phenylacetylene over a 10 minute period. The resulting mixture was stirred for an additional 15 hours at reflux temperature and then the solvent removed. The residue was vacuum distilled at 67 Pa to give a mixture comprising 0.58 g of 1,1,3,3-tetrachloro-2-trichlorosilyl-4-phenyl-1,3-disilacyclopent-4-ene (TCD-GC area 43.9%).
Reaction SMILES: FC(F)(F)C(O)=O.[C:8]([S:11][CH:12]1[CH2:17][CH2:16][NH:15][CH2:14]/[C:13]/1=[CH:18]\[C:19]1[N:20]=[N:21][N:22]([CH2:24][C:25]([O:27][CH3:28])=[O:26])[CH:23]=1)(=[O:10])[CH3:9].Br[CH:30]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1[F:42])[C:31]([CH:33]1[CH2:35][CH2:34]1)=[O:32].[ClH:43]>C(N(CC)CC)C>[ClH:43].[C:8]([S:11][CH:12]1[CH2:17][CH2:16][N:15]([CH:30]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=2[F:42])[C:31]([CH:33]2[CH2:34][CH2:35]2)=[O:32])[CH2:14]/[C:13]/1=[CH:18]\[C:19]1[N:20]=[N:21][N:22]([CH2:24][C:25]([O:27][CH3:28])=[O:26])[CH:23]=1)(=[O:10])[CH3:9]
Reactant: COC(=O)Cn1cc(/C=C2\CNCCC2SC(C)=O)nn1
Reactant: O=C(C1CC1)C(Br)c1ccccc1F
Agent: Cl
Solvent: CCN(CC)CC
Solvent: O=C(O)C(F)(F)F
Product: COC(=O)Cn1cc(/C=C2\CN(C(C(=O)C3CC3)c3ccccc3F)CCC2SC(C)=O)nn1
Yield: 56 %

Procedure:
Following a procedure similar to that described in Example 150-(g), (E)-4-(acetylsulfanyl)-3-{[1-(methoxycarbonylmethyl)-1H-1,2,3-triazol-4-yl]methylidene}piperidine hydrogen trifluoroacetate (550 mg) was subjected to the reaction with 2-bromo-2-(2-fluorophenyl)-1-cyclopropylethanone and triethylamine, and the free base that was obtained by chromatographic purification on silica gel was treated with hydrogen chloride to yield the title compound (380 mg, yield: 56%) as a pale yellow amorphous solid.
Reaction SMILES: [CH:1]1[C:4]2[CH:5]=[CH:6][C:7]([N:9]3[C:13](=[O:14])[C:12]4=[CH:15][C:16]([C:19]#[C:20][Si](C)(C)C)=[CH:17][CH:18]=[C:11]4[C:10]3=[O:25])=[CH:8][C:3]=2[CH:2]=1.C(=O)([O-])[O-].[K+].[K+]>>[CH:1]1[C:4]2[CH:5]=[CH:6][C:7]([N:9]3[C:13](=[O:14])[C:12]4=[CH:15][C:16]([C:19]#[CH:20])=[CH:17][CH:18]=[C:11]4[C:10]3=[O:25])=[CH:8][C:3]=2[CH:2]=1
Reactant: C[Si](C)(C)C#Cc1ccc2c(c1)C(=O)N(c1ccc3c(c1)C=C3)C2=O
Agent: O=C([O-])[O-]
Agent: [K+]
Product: C#Cc1ccc2c(c1)C(=O)N(c1ccc3c(c1)C=C3)C2=O
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A mixture of N-4-benzocyclobutenyl 4-trimethylsilylethynyl phthalimide (3.95 g, 11.4 mmol) and potassium carbonate (0.50 g, 3.62 mmol) was stirred in 100 ml of anhydrous methol under N2 at room temperature for about 3 hours. The solvent was then removed, and the residue was treated with 75 ml of H2O and 50 ml CH2Cl2. The methylene chloride layer was separated and the aqueous layer was extracted with CH2Cl2 (2×50 ml). The combined extract was dried over MgSO4, and then filtered through a bed of silica gel (10 g). Slow evaporation of the filtrate led to the isolation of light yellow crystals. Yield: 2.85 g (91%) m.p.=191°-192° . Calc. for C18H11NO2 : 79.10% C; 4.06% H; 5.12% N, Found: 78.98% C; 4.01% H; 5.09% N. Mass Spectroscopy: 273 (M+ 100 %). Proton NMR (CDCl3): 3.25 (singlet, alicyclic protons); 3.37 (singlet,≡CH); 7.08-7.31, 7.94-8.08 (complex, aromatic protons). IR(KBr): 3272s (≡CH stretch); 2943m (alicyclic CH stretch); 1710 ms, 1773 vs (symmetric and asymmetric stretches of imide group).
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:41])[N:10]([CH:12]([C:14](=[O:40])[NH:15][CH:16]([C:21]([N:23]1[CH2:27][CH2:26][CH:25]2[NH:28][CH2:29][CH:30]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=3)[CH:24]12)=[O:22])[C:17]([CH3:20])([CH3:19])[CH3:18])[CH3:13])[CH3:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:42]([N:49]=[C:50]=[O:51])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.CO.[NH4+].[OH-]>C(Cl)Cl>[CH2:1]([O:8][C:9](=[O:41])[N:10]([CH:12]([C:14](=[O:40])[NH:15][CH:16]([C:21]([N:23]1[CH2:27][CH2:26][CH:25]2[N:28]([C:50](=[O:51])[NH:49][CH2:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)[CH2:29][CH:30]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=3)[CH:24]12)=[O:22])[C:17]([CH3:19])([CH3:18])[CH3:20])[CH3:13])[CH3:11])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C(=O)NC(C(=O)N1CCC2NCC(OCc3ccc(F)cc3)C21)C(C)(C)C)N(C)C(=O)OCc1ccccc1
Reactant: O=C=NCc1ccccc1
Agent: [NH4+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CO
Product: CC(C(=O)NC(C(=O)N1CCC2C1C(OCc1ccc(F)cc1)CN2C(=O)NCc1ccccc1)C(C)(C)C)N(C)C(=O)OCc1ccccc1
Reaction time: 3 h
Yield: 121 %

Procedure:
Bicyclic amine 49 (300 mg, 0.53 mmol) and TEA (150 μL) were dissolved in DCM (5 mL) at ambient temperature and benzyl isocyanate (135 μL, 1.06 mmol) was added. After 3 h, MeOH (20 mL) and 30% NH4OH (1 mL) were added and the solution was stirred for 15 min before being concentrated in vacuo. The residue was dissolved in EtOAc and washed successively with 1N HCl, water, aqueous NaHCO3, water, and brine. The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated to afford 450 mg of 50 as an amorphous solid which was used without further purification. Mass spectrum, m/z [702.3] (M+Na)+.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[N:4][C:5](Cl)=[CH:6][CH:7]=1.[CH2:9]([NH2:13])[CH2:10][CH2:11][NH2:12].C(=O)([O-])[O-].[Na+].[Na+]>C(O)C>[Cl:1][C:2]1[N:3]=[N:4][C:5]([NH:12][CH2:11][CH2:10][CH2:9][NH2:13])=[CH:6][CH:7]=1
Reactant: NCCCN
Reactant: Clc1ccc(Cl)nn1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Product: NCCCNc1ccc(Cl)nn1
Yield: 66.1 %

Procedure:
A mixture of 3,6-dichloropyridazine (25 g), 1,3-propanediamine (62 g) and sodium carbonate (18 g) in ethanol (500 mL) was stirred and refluxed overnight. The reaction mixture was filtered over dicalite and the filtrate was evaporated. The residue was crystallized from acetonitrile. The crystals were filtered off and dried, yielding 20.7 g of N-(6-chloro-3-pyridazinyl)-1,3-propanediamine; mp. 124.9° C. (intermediate 2).
Reaction SMILES: [N:1]([C:4](=[CH:9][C:10]1[CH:15]=[CH:14][C:13]([CH:16]([P:18]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[OH:17])=[CH:12][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6])=[N+]=[N-].[H][H].C(Cl)(Cl)Cl.CO>CO.[Pd]>[C:26]([O:25][P:18]([CH:16]([OH:17])[C:13]1[CH:14]=[CH:15][C:10]([CH2:9][CH:4]([C:5]([O:7][CH3:8])=[O:6])[NH2:1])=[CH:11][CH:12]=1)([O:20][C:21]([CH3:23])([CH3:22])[CH3:24])=[O:19])([CH3:27])([CH3:28])[CH3:29]
Reactant: [H][H]
Reactant: COC(=O)C(=Cc1ccc(C(O)P(=O)(OC(C)(C)C)OC(C)(C)C)cc1)N=[N+]=[N-]
Agent: [Pd]
Solvent: ClC(Cl)Cl
Solvent: CO
Product: COC(=O)C(N)Cc1ccc(C(O)P(=O)(OC(C)(C)C)OC(C)(C)C)cc1
Yield: 92 %

Procedure:
A solution of 7 (1.25 g, 2.85 mmol) in MeOH (50 mL) was hydrogenated in a Parr apparatus over 10% Pd.C (200 mg) under 40 psi H2. The hydrogen was replenished after 10 minutes. The reaction was terminated after 3 hours, and catalyst removed by filtration. Evaporation of solvent yielded 8 as a clear, colorless syrup, 1.17 g (100% crude yield). Silica gel chromatography [CHCl3 :MeOH(25:1)] provided pure 8 (92%).
Reaction SMILES: [C:1]([C:4]1(C)[CH2:8][C:7]([CH3:9])=[C:6]([OH:10])[C:5]1=[O:11])(O)=O.S(=O)(=O)(O)O.[OH-].[Na+]>>[CH3:1][C:4]1[CH2:8][CH:7]([CH3:9])[C:6](=[O:10])[C:5]=1[OH:11]
Reactant: CC1=C(O)C(=O)C(C)(C(=O)O)C1
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Product: CC1=C(O)C(=O)C(C)C1
Yield: 91 %

Procedure:
85.1 g (0.5 mol) of the acid obtained according to paragraph (c), namely 2-carboxy-2,4-dimethylcyclopent-4-en-5-olone, are treated with 851 of 10% sulphuric acid and the mixture is refluxed for 45 minutes. For the working-up, the mixture is adjusted to pH 7 with 2 N sodium hydroxide solution and then extracted three times with methylene chloride. The combined organic phases are dried over sodium sulphate and dried in a high vacuum for 1 hour. There are obtained 57.4 g (91%) of crystalline 3,5-dimethylcyclopent-2-en-2-olone of melting point 93°-94° C. The product is identical with the product obtained according to paragraph (c) of Example 4.
Reaction SMILES: [Br:1][C:2]1[N:3]=[CH:4][NH:5][CH:6]=1.[F:7][C:8]1[CH:13]=[CH:12][C:11](B(O)O)=[CH:10][CH:9]=1.N1C=CC=CC=1>ClCCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Br:1][C:2]1[N:3]=[CH:4][N:5]([C:11]2[CH:12]=[CH:13][C:8]([F:7])=[CH:9][CH:10]=2)[CH:6]=1
Reactant: Brc1c[nH]cn1
Reactant: OB(O)c1ccc(F)cc1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: ClCCCl
Solvent: c1ccncc1
Product: Fc1ccc(-n2cnc(Br)c2)cc1
Temperature: 25 °C
Reaction time: 44 h
Yield: 36.8 %

Procedure:
A mixture of 4-bromo-1H-imidazole (223 mg, 1.52 mmol), 4-fluorophenylboronic acid (425 mg, 3.03 mmol), copper(II) acetate (413 mg, 2.28 mmol), pyridine (0.25 mL) and powdered 4 Å molecular sieves (1 g) in 1,2-dichloroethane (7 mL) was stirred at room temperature under a slow stream of air for 44 hours. The reaction mixture was filtered through Celite®, washing with ethyl acetate. The filtrate was concentrated and the residue purified by flash column chromatography on silica eluting with 10 to 20% ethyl acetate/isohexane to give the product as a white solid (135 mg, 37%).
Reaction SMILES: [Br:1][C:2]1[CH:20]=[CH:19][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:21])[CH:3]=1.C=O.[OH-].[K+].[O:26]1[CH2:30][CH2:29][CH2:28][CH2:27]1>O.C(O)=O>[Br:1][C:2]1[CH:20]=[CH:19][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:26][CH2:30][CH:29]4[CH2:4][CH2:5][N:6]([CH3:7])[CH2:27][CH2:28]4)=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:21])[CH:3]=1
Reactant: C1CCOC1
Reactant: COc1ccc2ncnc(Nc3ccc(Br)cc3F)c2c1
Agent: C=O
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: O=CO
Product: COc1cc2c(Nc3ccc(Br)cc3F)ncnc2cc1OCC1CCN(C)CC1
Temperature: 81 °C
Reaction time: 5 h

Procedure:
7-(1-tert-butoxycarbonyl)piperidine-4-ylmethoxy)-4-(4-bromo-2-fluoroanilino)-6-methoxyquinazoline (40 g), water (16 ml), formic acid (43 ml) and aqueous formaldehyde (37% w/w, 33 ml) were added to a vessel equipped with overhead stirrer, reflux condenser and thermometer. The reaction mixture was heated to 81° C. and stirred at this temperature for 5 hours. The reaction mixture was cooled to 60° C. and tetrahydrofuran (178 ml) was added. The temperature of the reaction mixture was adjusted to 40° C. and potassium hydroxide (49% w/w, 84 ml) was added, followed by water (22 ml). The aqueous phase was separated and discarded. The organic phase was adjusted to 60° C. and water (107 ml) and butyl acetate (107 ml) were added. The aqueous phase was separated and discarded. The organic phase was filtered, following through with tetrahydrofuran (18 ml) wash. The temperature of the filtrates was adjusted to 60° C. and butyl acetate (107 ml) was added. The reaction mixture was set for distillation at ambient pressure. The distillation was stopped when the contents temperature reached 106° C. The slurry was cooled to 65° C. and tetrahydrofuran (107 ml) was added. The slurry was cooled to 0-5° C. and held for 1 hour before isolating the product by filtration. The product was washed with ethyl acetate (72 ml) and dried at 50° C. Yield: 24.82 g, 80.3%.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:16]=[C:17]([OH:20])[C:18]=1[OH:19])[C:5]([C:7]1[C:12]([OH:13])=[C:11]([OH:14])[C:10]([OH:15])=[CH:9][CH:8]=1)=[O:6].[C:21](Cl)(=[O:26])[C:22]([CH3:25])([CH3:24])[CH3:23]>N1C=CC=CC=1>[C:21]([O:1][C:2]1[CH:3]=[C:4]([CH:16]=[C:17]([O:20][C:21](=[O:26])[C:22]([CH3:25])([CH3:24])[CH3:23])[C:18]=1[O:19][C:21](=[O:26])[C:22]([CH3:25])([CH3:24])[CH3:23])[C:5]([C:7]1[C:12]([O:13][C:21](=[O:26])[C:22]([CH3:25])([CH3:24])[CH3:23])=[C:11]([O:14][C:21](=[O:26])[C:22]([CH3:25])([CH3:24])[CH3:23])[C:10]([O:15][C:21](=[O:26])[C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:9][CH:8]=1)=[O:6])(=[O:26])[C:22]([CH3:25])([CH3:24])[CH3:23]
Reactant: CC(C)(C)C(=O)Cl
Reactant: O=C(c1cc(O)c(O)c(O)c1)c1ccc(O)c(O)c1O
Solvent: c1ccncc1
Product: CC(C)(C)C(=O)Oc1cc(C(=O)c2ccc(OC(=O)C(C)(C)C)c(OC(=O)C(C)(C)C)c2OC(=O)C(C)(C)C)cc(OC(=O)C(C)(C)C)c1OC(=O)C(C)(C)C

Procedure:
100 mg of 3,4,5,4',5',6'-hexahydroxy benzophenone (0.00036 mole) and 450 MG (0.004 mole) of pivaloyl chloride were warmed to 50° C. in 20 mls of pyridine for 4 hrs. Solvent removed via N2 stream. Water added and extraction of product was done via CH2Cl2. The organic layer was washed with K2CO3 (5%) and dried over MgSo4. Solvent removal left an oil. 250 mg. (88%) yield.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[CH:36]=[CH:35][C:34]([F:37])=[CH:33][C:10]=2[CH2:11][N:12]2[C:16]([CH3:18])([CH3:17])[C:15](=[O:19])[N:14]([C:20]3[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[C:22]([C:28]([F:31])([F:30])[F:29])[CH:21]=3)[C:13]2=[O:32])=[CH:4][CH:3]=1.[F:38]C1C=CC(NC2C=CC=CC=2)=C(C=1)CN1C(C)(C)C(=O)N(C2C=CC(C#N)=C(C(F)(F)F)C=2)C1=O>>[F:37][C:34]1[CH:35]=[CH:36][C:9]([NH:8][C:5]2[CH:6]=[CH:7][C:2]([F:38])=[CH:3][CH:4]=2)=[C:10]([CH:33]=1)[CH2:11][N:12]1[C:16]([CH3:18])([CH3:17])[C:15](=[O:19])[N:14]([C:20]2[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[C:22]([C:28]([F:31])([F:30])[F:29])[CH:21]=2)[C:13]1=[O:32]
Reactant: CC1(C)C(=O)N(c2ccc(C#N)c(C(F)(F)F)c2)C(=O)N1Cc1cc(F)ccc1Nc1ccc(Cl)cc1
Reactant: CC1(C)C(=O)N(c2ccc(C#N)c(C(F)(F)F)c2)C(=O)N1Cc1cc(F)ccc1Nc1ccccc1
Product: CC1(C)C(=O)N(c2ccc(C#N)c(C(F)(F)F)c2)C(=O)N1Cc1cc(F)ccc1Nc1ccc(F)cc1

Procedure:
The compounds of example 16, 4-{3-[2-(4-chlorophenylamino)-5-fluorobenzyl]-4,4-dimethyl-2,5-dioxoimidazolidin-1-yl}-2-trifluoromethylbenzonitrile (molecular weight 530.11 (C26H19ClF4N4O2); retention time Rt=2.38 min. [B]; MS (ESI): 531.21 (MH+), and of example 18, 4-[3-(5-fluoro-2-phenylaminobenzyl)-4,4-dimethyl-2,5-dioxoimidazolidin-1-yl]-2-trifluoromethylbenzonitrile (molecular weight 496.15 (C26H20F4N4O2); retention time Rt=2.28 min. [B]; MS (ESI): 497.20 (MH+)
Reaction SMILES: [NH2:1][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([C:19]#[N:20])[C:3]=1[C:21]1[S:22][CH:23]=[CH:24][CH:25]=1.[F:26][C:27]([F:31])([F:30])[S:28]Cl.O>ClCCl>[NH2:1][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:16])([F:15])[F:17])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([C:19]#[N:20])[C:3]=1[C:21]1[S:22][C:23]([S:28][C:27]([F:31])([F:30])[F:26])=[CH:24][CH:25]=1
Reactant: N#Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c(N)c1-c1cccs1
Reactant: FC(F)(F)SCl
Solvent: O
Solvent: ClCCl
Product: N#Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c(N)c1-c1ccc(SC(F)(F)F)s1
Reaction time: 48 h

Procedure:
To a stirred solution of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(thien-2-yl)pyrazole (0.806 g) in dry dichloromethane (25 ml) at room temperature was added a solution of stannic chloride (500 μl) in dry dichloromethane (5 ml). To this was added 7.2 ml of a 50 mg/ml solution of trifluoromethylsulphenyl chloride in dichloromethane and the mixture was stirred for 48 hours after which it was poured onto a mixture of ice, water and dichloromethane. The aqueous layer was separated and washed with dichloromethane. The combined organic layers were washed with saturated aqueous sodium hydrogen carbonate solution, dried and evaporated. The residue was purified by column chromatography on silica gel (40 g) eluted with dichloromethane:hexane (1:1). Combination and evaporation of suitable fractions gave the title compound as a white solid, m.p. 162-3° C.