Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br-:1].[Br-].[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C([N+](CCCC)(CCCC)CCCC)CCC.C([N+](CCCC)(CCCC)CCCC)CCC.[CH3:55][O:56][C:57]1[CH:65]=[C:64]2[C:60]([CH2:61][CH2:62][C:63]2=[O:66])=[CH:59][CH:58]=1>CO.ClCCl>[Br:1][CH:62]1[CH2:61][C:60]2[C:64](=[CH:65][C:57]([O:56][CH3:55])=[CH:58][CH:59]=2)[C:63]1=[O:66]
Reactant: [Br-]
Reactant: COc1ccc2c(c1)C(=O)CC2
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Solvent: CO
Solvent: ClCCl
Product: COc1ccc2c(c1)C(=O)C(Br)C2

Procedure:
49.2 g (102 mmol) of tetra-n-butylammonium tribromide are added in fractions over the course of 15 minutes, at room temperature, to 16.2 g (100 mmol) of 6-methoxy-indan-1-one dissolved in 400 ml of methanol and 1 litre of dichloromethane, and the mixture is then stirred overnight at room temperature. After evaporation, the residue is taken up in 500 ml of dichloromethane and washed twice with 250 ml of N hydrochloric acid. Drying over magnesium sulphate and concentration, and then rapid filtration over 500 g of silica (eluant:dichloromethane) yield 23.4 g of the desired product.
Reaction SMILES: Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([CH3:10])[CH:3]=1.[C:11]1(B(O)O)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>>[CH3:10][C:4]1[CH:3]=[C:2]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:9]=[CH:8][C:5]=1[C:6]#[N:7]
Reactant: OB(O)c1ccccc1
Reactant: Cc1cc(Br)ccc1C#N
Product: Cc1cc(-c2ccccc2)ccc1C#N

Procedure:
The title compound was prepared in a similar manner to that described in Reference Example 2 using 4-bromo-2-methylbenzonitrile instead of tert-butyl N-(4-bromobenzyl) carbamate and phenylboronic acid instead of 3-benzyloxyphenylboronic acid.
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:8]([F:11])([F:10])[F:9])=[N:4][NH:5][C:6]=1[CH3:7].Br[CH2:13][C:14]([O:16]CC)=[O:15].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[Cl:1][C:2]1[C:3]([C:8]([F:9])([F:11])[F:10])=[N:4][N:5]([CH2:13][C:14]([OH:16])=[O:15])[C:6]=1[CH3:7]
Reactant: CCOC(=O)CBr
Reactant: Cc1[nH]nc(C(F)(F)F)c1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1c(Cl)c(C(F)(F)F)nn1CC(=O)O
Temperature: 55 °C
Yield: 84.1 %

Procedure:
To a solution of 4-chloro-5-methyl-3-(trifluoromethyl)pyrazole (15 g, 81.3 mmol) in DMF (82 mL) was added ethyl 2-bromoacetate (13.6 g, 81.3 mmol) and potassium carbonate (12.4 g, 89.4 mmol). The mixture was heated at 55° C. for 10 hours with stirring. After cooling to room temperature, the reaction mixture was diluted with water (100 mL) and extracted with ethyl acetate (3×150 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. The crude residue was purified by flash chromatography (SiO2, 0-30% ethyl acetate in hexanes) to afford the desired product (18.5 g, 68.4 mmol, 84%).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[N:9]1[N:13]=[C:12]2[CH:14]=[CH:15][CH:16]=[CH:17][C:11]2=[N:10]1.Br[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[O:27][C:28]3[CH:34]=[CH:33][CH:32]=[CH:31][C:29]=3[N:30]=2)=[CH:22][CH:21]=1>CC(=O)CC.C(=O)([O-])[O-].[K+].[K+]>[OH:1][C:2]1[CH:7]=[C:6]([O:8][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]3[O:27][C:28]4[CH:34]=[CH:33][CH:32]=[CH:31][C:29]=4[N:30]=3)=[CH:22][CH:21]=2)[CH:5]=[CH:4][C:3]=1[N:9]1[N:13]=[C:12]2[CH:14]=[CH:15][CH:16]=[CH:17][C:11]2=[N:10]1
Reactant: Oc1ccc(-n2nc3ccccc3n2)c(O)c1
Reactant: BrCc1ccc(-c2nc3ccccc3o2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCC(C)=O
Product: Oc1cc(OCc2ccc(-c3nc4ccccc4o3)cc2)ccc1-n1nc2ccccc2n1
Temperature: 0 °C

Procedure:
2-(p-Tolyl)benzoxazole was reacted with N-bromosuccinimide in the presence of benzoyl peroxide by the standard procedure to produce the known compound, 2-(4-bromomethylphenyl)benzoxazole (A). 2-(2,4-Dihydroxyphenyl)benzotriazole (B) (0.1 mole) and 2-(4-bromomethylphenyl)benzoxazole (A) (0.1 mole) was stirred in a mixture of 2-butanone (300 ml.) and potassium carbonate (100 g.). After refluxing 16 hr., the mixture was poured onto 1000 g. ice/water. Filtration, washing with water and recrystallization from methyl cellosolve/isopropyl alcohol gave the tan, crystalline product I.
Reaction SMILES: [C:1]1([C:7]2[CH2:8][O:9][C:10]3[C:15]([C:16]=2[C:17]2[CH:22]=[CH:21][C:20]([CH:23]=[CH:24][C:25]([OH:27])=O)=[CH:19][CH:18]=2)=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:28][S:29]([NH2:32])(=[O:31])=[O:30]>>[C:1]1([C:7]2[CH2:8][O:9][C:10]3[C:15]([C:16]=2[C:17]2[CH:22]=[CH:21][C:20]([CH:23]=[CH:24][C:25]([NH:32][S:29]([CH3:28])(=[O:31])=[O:30])=[O:27])=[CH:19][CH:18]=2)=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C(O)C=Cc1ccc(C2=C(c3ccccc3)COc3ccccc32)cc1
Reactant: CS(N)(=O)=O
Product: CS(=O)(=O)NC(=O)C=Cc1ccc(C2=C(c3ccccc3)COc3ccccc32)cc1

Procedure:
Prepared by coupling 3d and methylsulfonamide in accordance with Procedure 1, Method A described hereinabove. Yield (35%); ESI m/z: 430 (M−H−, 100%).
Reaction SMILES: [Br:1][C:2]1[N:7]=[C:6]([O:8][CH3:9])[C:5](I)=[CH:4][CH:3]=1.C([Li])CCC.CN(C)[CH:18]=[O:19].O>C(OCC)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH:18]=[O:19])=[C:6]([O:8][CH3:9])[N:7]=1
Reactant: CN(C)C=O
Reactant: COc1nc(Br)ccc1I
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: O
Product: COc1nc(Br)ccc1C=O
Reaction time: 1 h
Yield: 90 %

Procedure:
A solution of 6-bromo-3-iodo-2-methoxypyridine (1.0 g) in diethyl ether (38 mL) was cooled to −80° C. in a nitrogen atmosphere, and n-butyllithium (2.6 M, 0.735 mL) were added dropwise. After stirring at the same temperature for one hour, N,N-dimethylformamide (0.62 mL) was added dropwise. The mixture was stirred at the same temperature for one hour and water was added to the reaction system, followed by extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and filtered, after which the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=94:6→9:1) to give 6-bromo-2-methoxynicotinaldehyde as a colorless powder (618 mg, 90%).
Reaction SMILES: CCN(CC)CC.Br[C:9]1[CH:14]=[CH:13][C:12]([CH:15]=[CH:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[CH:19][CH:18]=2)=[CH:11][CH:10]=1.[C:30]([O:34][C:35](=[O:44])[C:36]1[CH:41]=[CH:40][C:39]([C:42]#[CH:43])=[CH:38][CH:37]=1)([CH3:33])([CH3:32])[CH3:31]>C(#N)C.[Cu]I>[C:35]([C:36]1[CH:41]=[CH:40][C:39]([C:42]#[C:43][C:9]2[CH:14]=[CH:13][C:12](/[CH:15]=[CH:16]/[C:17]3[CH:22]=[CH:21][C:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[CH:19][CH:18]=3)=[CH:11][CH:10]=2)=[CH:38][CH:37]=1)([O:34][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:44]
Reactant: CC(C)(C)OC(=O)c1ccc(C=Cc2ccc(Br)cc2)cc1
Reactant: C#Cc1ccc(C(=O)OC(C)(C)C)cc1
Agent: [Cu]I
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)c1ccc(C#Cc2ccc(/C=C/c3ccc(C(=O)OC(C)(C)C)cc3)cc2)cc1
Reaction time: 0.33 h

Procedure:
300 ml of NEt3 and 20.46 g of Pφ3 are added under nitrogen to 234 g of 4-bromo-4'-carbo-tert.-butoxystilbene in 1 l of absolute acetonitrile. Nitrogen is passed through the stirred suspension for 20 minutes and 9.12 g of (Pφ3)2PdCl2 and 2.5 g of copper(I)iodide are then added. 144 g of 4-Ethinyl benzoic acid tert.-butyl ester dissolved in 1 l of absolute acetonitrile are then added dropwise under reflux over a period of 6 hours and the reaction mixture is boiled under reflux overnight. The hot product obtained after suction filtration is dissolved in CH2Cl2, washed several times with H2O and dried and the solvent is removed.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([C:8]2[C:9]3[C:10]4[CH:24]=[CH:23][S:22][C:11]=4[C:12](=[O:21])[NH:13][C:14]=3[C:15]([CH3:20])=[CH:16][C:17]=2[O:18][CH3:19])[CH:5]=[CH:4][C:3]=1[C@@H:25]([CH3:35])[CH2:26][NH:27]C(=O)OC(C)(C)C.[ClH:36]>CCOCC>[ClH:36].[NH2:27][CH2:26][C@@H:25]([C:3]1[CH:4]=[CH:5][C:6]([C:8]2[C:9]3[C:10]4[CH:24]=[CH:23][S:22][C:11]=4[C:12](=[O:21])[NH:13][C:14]=3[C:15]([CH3:20])=[CH:16][C:17]=2[O:18][CH3:19])=[CH:7][C:2]=1[F:1])[CH3:35]
Reactant: COc1cc(C)c2[nH]c(=O)c3sccc3c2c1-c1ccc([C@@H](C)CNC(=O)OC(C)(C)C)c(F)c1
Agent: Cl
Solvent: CCOCC
Product: COc1cc(C)c2[nH]c(=O)c3sccc3c2c1-c1ccc([C@@H](C)CN)c(F)c1
Yield: 81 %

Procedure:
Following General Procedure D1, (R)-tert-butyl 2-(2-fluoro-4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (150 mg, 0.30 mmol) was reacted with HCl in ether (15 mL) to afford the desired product (105 mg, 81%) as an off-white solid: 1H NMR (500 MHz, MeOD) δ 7.63 (dd, J=5.4, 2.4 Hz, 1H), 7.52 (dt, J=24.8, 7.8 Hz, 1H), 7.30 (s, 1H), 7.09 (m, 2H), 6.11 (dd, J=26.4, 5.4 Hz, 1H), 3.76 (s, 3H), 3.63-3.43 (m, 1H), 3.42-3.16 (m, 2H), 2.64 (s, 3H), 1.51 (d, J=7.0 Hz, 3H). ESI MS m/z 397 [C22H21FN2O2S+H]+; HPLC >99% (AUC), tR=11.57 min.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([O:8][CH:9]([CH2:13][CH3:14])[C:10]([OH:12])=O)[CH:5]=[N:6][CH:7]=1.[NH2:15][C:16]([CH3:29])([CH3:28])[C:17]#[C:18][CH:19]([O:24][SiH:25]([CH3:27])[CH3:26])[C:20]([CH3:23])([CH3:22])[CH3:21].Cl.CN(CCCN=C=NCC)C>CN(C)C1C=CN=CC=1.ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([O:8][CH:9]([CH2:13][CH3:14])[C:10]([NH:15][C:16]([CH3:29])([CH3:28])[C:17]#[C:18][CH:19]([O:24][SiH:25]([CH3:27])[CH3:26])[C:20]([CH3:22])([CH3:23])[CH3:21])=[O:12])[CH:5]=[N:6][CH:7]=1
Reactant: C[SiH](C)OC(C#CC(C)(C)N)C(C)(C)C
Reactant: CCC(Oc1cncc(Cl)c1)C(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Product: CCC(Oc1cncc(Cl)c1)C(=O)NC(C)(C)C#CC(O[SiH](C)C)C(C)(C)C
Temperature: 25 °C
Reaction time: 3 h

Procedure:
2-(5-Chloro-3-pyridyloxy)butyric acid (2.26 g), 4-amino-1-tert.-butyldimethylsilyloxy-4-methylpent-2-yne (2.27 g) and 4-dimethylaminopyridine (0.010 g) in dry dichloromethane (50 ml) were stirred at ambient temperature and N-dimethylaminopropyl-N′-ethylcarbodiimide hydrochloride (2.11 g) was added. The mixture was stirred at ambient temperature for 3 hours, stored for 18 hours, diluted with dichloromethane and washed with saturated aqueous sodium hydrogen carbonate (twice) then water (twice). The organic phase was dried over magnesium sulphate and evaporated under reduced pressure to give a dark yellow oil, 4.4 g, containing the required product.
Reaction SMILES: [OH:1][C:2]1[N:6]([C:7]2[CH:12]=[C:11]([C:13]#[N:14])[CH:10]=[CH:9][N:8]=2)[N:5]=[CH:4][CH:3]=1.[Cl:15][C:16]1[CH:17]=[C:18]([CH2:23]O)[CH:19]=[CH:20][C:21]=1[CH3:22]>>[Cl:15][C:16]1[CH:17]=[C:18]([CH2:23][O:1][C:2]2[N:6]([C:7]3[CH:12]=[C:11]([C:13]#[N:14])[CH:10]=[CH:9][N:8]=3)[N:5]=[CH:4][CH:3]=2)[CH:19]=[CH:20][C:21]=1[CH3:22]
Reactant: Cc1ccc(CO)cc1Cl
Reactant: N#Cc1ccnc(-n2nccc2O)c1
Product: Cc1ccc(COc2ccnn2-c2cc(C#N)ccn2)cc1Cl

Procedure:
The title compound was prepared from 2-(5-hydroxy-1H-pyrazol-1-yl)pyridine-4-carbonitrile and (3-chloro-4-methylphenyl)methanol according to the procedure for the preparation of Example 39, part C. 1H NMR (400 MHz, CDCl3): δ 2.38 (3H, s), 5.18 (2H, s), 5.73 (1H, d, J=1.6 Hz), 7.19-7.25 (2H, m), 7.41 (1H, dd, J=1.2, 4.8 Hz), 7.44 (1H, s), 7.57 (1H, d, J=1.6 Hz), 8.03 (1H, s), 8.71 (1H, d, J=5.2 Hz). [M+H] Calc'd for C17H13ClN4O, 325. Found, 325.
Reaction SMILES: I[C:2]1[CH:3]=[C:4]([O:12][CH3:13])[C:5]([O:10][CH3:11])=[C:6]([O:8][CH3:9])[CH:7]=1.[Li]C(C)(C)C.CCCCC.[N+:24]([C:27]1[C:32]([CH:33]=[O:34])=[CH:31][C:30]([O:35][CH3:36])=[C:29]([O:37][CH3:38])[CH:28]=1)([O-:26])=[O:25]>C1COCC1>[CH3:38][O:37][C:29]1[C:30]([O:35][CH3:36])=[CH:31][C:32]([CH:33]([C:2]2[CH:3]=[C:4]([O:12][CH3:13])[C:5]([O:10][CH3:11])=[C:6]([O:8][CH3:9])[CH:7]=2)[OH:34])=[C:27]([N+:24]([O-:26])=[O:25])[CH:28]=1
Reactant: COc1cc(C=O)c([N+](=O)[O-])cc1OC
Reactant: COc1cc(I)cc(OC)c1OC
Agent: [Li]C(C)(C)C
Solvent: CCCCC
Solvent: C1CCOC1
Product: COc1cc(C(O)c2cc(OC)c(OC)c(OC)c2)c([N+](=O)[O-])cc1OC
Temperature: -78 °C
Reaction time: 1 h
Yield: 40.2 %

Procedure:
A flame-dried round-bottomed flask under N2 atmosphere was charged with 5-iodo-1,2,3-trimethoxybenzene (2.92 g, 9.93 mmol) and THF (31 mL) was added. The solution was cooled down to −78° C. and 1.5 M solution of t-BuLi in pentane (13.6 mL, 20.57 mmol) was added dropwise. The mixture was stirred for 1 h and transferred via canula to a precooled (−78° C.) solution of 6-nitroveratraldehyde (2.02 g, 9.57 mmol) in THF (12 mL) under N2 atmosphere. The resulting mixture was stirred for 2 h and slowly warmed up to 0° C., quenched with saturated aqueous solution of NH4Cl and allowed to warm-up to rt. Solvent was removed in vacuo and the residue was partitioned between water and DCM. Organic layer was collected and washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash chromatography using EtOAc/DCM (9:91) affording the title compound 241 (1.46 g, 40% yield) 1H NMR (CDCl3) δ (ppm): 7.61 (s, 1H), 7.16 (s, 1H), 6.58 (s, 2H), 6.45 (s, 1H), 6.09 (s, 1H), 3.97 (s, 3H), 3.93 (s, 3H), 3.84 (s, 3H), 3.83 (s, 6H). m/z: 402.4 (MH+).
Reaction SMILES: C([O:8][C:9](=[O:19])[C@@H:10]1[CH2:14][CH2:13][CH2:12][N:11]1[CH2:15][CH:16]1[O:18][CH2:17]1)C1C=CC=CC=1.[Li+].[OH-].O>CO>[CH2:15]([N:11]1[CH2:12][CH2:13][CH2:14][C@H:10]1[C:9]([OH:19])=[O:8])[CH:16]1[O:18][CH2:17]1
Reactant: O=C(OCc1ccccc1)[C@@H]1CCCN1CC1CO1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: O=C(O)[C@@H]1CCCN1CC1CO1

Procedure:
N-Glycidyl-L-proline is prepared from compound 120 by hydrolyzing the benzyl ester with LiOH/H2O in methanol.
Reaction SMILES: [H-].[Na+].[OH:3][C:4]1[CH:13]=[C:12]([C:14]2[CH:27]=[CH:26][C:25]3[C:16](=[CH:17][C:18]4[C:19]([CH3:31])([CH3:30])[CH2:20][CH2:21][C:22]([CH3:29])([CH3:28])[C:23]=4[CH:24]=3)[CH:15]=2)[CH:11]=[CH:10][C:5]=1[C:6]([O:8][CH3:9])=[O:7].I[CH3:33].O>CN(C=O)C>[CH3:33][O:3][C:4]1[CH:13]=[C:12]([C:14]2[CH:27]=[CH:26][C:25]3[C:16](=[CH:17][C:18]4[C:19]([CH3:31])([CH3:30])[CH2:20][CH2:21][C:22]([CH3:29])([CH3:28])[C:23]=4[CH:24]=3)[CH:15]=2)[CH:11]=[CH:10][C:5]=1[C:6]([O:8][CH3:9])=[O:7]
Reactant: CI
Reactant: COC(=O)c1ccc(-c2ccc3cc4c(cc3c2)C(C)(C)CCC4(C)C)cc1O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)c1ccc(-c2ccc3cc4c(cc3c2)C(C)(C)CCC4(C)C)cc1OC

Procedure:
130 mg (4.2 mmol) of sodium hydride (80% in oil) and 20 ml of DMF were introduced into a three-necked flask, a solution of 1.6 g (4.2 mmol) of methyl 2-hydroxy-4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-anthryl)benzoate in 50 ml of DMF was added dropwise and the mixture was stirred until gaseous emission ceased. 340 μl (5.5 mmol) of iodomethane were then added and the mixture was stirred at room temperature for two hours. The reaction medium was poured into water, extracted with ethyl ether, the organic phase decanted, dried over magnesium sulfate and evaporated. 1.6 g (96%) of the expected compound was recovered in the form of a colorless oil.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]([CH2:20]Cl)=[CH:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[NH:22]1[CH2:28][CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1>>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]([CH2:20][N:22]3[CH2:28][CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)=[CH:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1
Reactant: Cc1ccc(S(=O)(=O)n2cc(CCl)c3ccccc32)cc1
Reactant: C1CNCCNC1
Product: Cc1ccc(S(=O)(=O)n2cc(CN3CCCNCC3)c3ccccc32)cc1

Procedure:
Using essentially the same procedure as described in example 127, 1-(4-methylbenzenesulfonyl)-3-chloromethyl-1H-indole was reacted with homopiperazine to obtain the above derivative.
Reaction SMILES: [H-].[Na+].[CH2:3]([O:10][CH2:11][CH2:12][O:13][CH2:14][CH2:15][O:16][CH2:17][CH2:18][O:19][CH2:20][CH2:21][O:22][CH2:23][CH2:24][O:25][C:26]1[CH:47]=[CH:46][C:29]([O:30][CH2:31][CH2:32][O:33][CH2:34][CH2:35][O:36][CH2:37][CH2:38][O:39][CH2:40][CH2:41][O:42][CH2:43][CH2:44][OH:45])=[CH:28][CH:27]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[C:48]([O:52][C:53](=[O:56])[CH2:54]Br)([CH3:51])([CH3:50])[CH3:49]>C1COCC1.CN(C=O)C.C1COCC1>[C:48]([O:52][C:53](=[O:56])[CH2:54][O:45][CH2:44][CH2:43][O:42][CH2:41][CH2:40][O:39][CH2:38][CH2:37][O:36][CH2:35][CH2:34][O:33][CH2:32][CH2:31][O:30][C:29]1[CH:28]=[CH:27][C:26]([O:25][CH2:24][CH2:23][O:22][CH2:21][CH2:20][O:19][CH2:18][CH2:17][O:16][CH2:15][CH2:14][O:13][CH2:12][CH2:11][O:10][CH2:3][C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=2)=[CH:47][CH:46]=1)([CH3:51])([CH3:50])[CH3:49]
Reactant: CC(C)(C)OC(=O)CBr
Reactant: OCCOCCOCCOCCOCCOc1ccc(OCCOCCOCCOCCOCCOCc2ccccc2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)COCCOCCOCCOCCOCCOc1ccc(OCCOCCOCCOCCOCCOCc2ccccc2)cc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 67.8 %

Procedure:
To an ice-cooled suspension of sodium hydride (180 mg, 4.5 mmol; 60% in mineral oil) in THF/DMF (5/1 mixed solution 7 ml), a solution of Compound 24 (817 mg, 1.28 mmol) in THF (6 ml) was gradually added; this was followed by stirring for 30 minutes. A solution of bromoacetic acid tert-butyl ester (1.0 g, 5.1 mmol) in THF (7 ml) was added thereto. After the ice bath was removed, stirring was further conducted at room temperature for 2 hours. Water was carefully added to stop the reaction, this was followed by extraction from ethyl acetate, and the combined organic phases were washed with saturated brine and dried with anhydrous sodium sulfate. After filtration and concentration under reduced pressure, the residue obtained was purified by silica gel column chromatography (Yamazen YFLC Gel, eluent (ethyl acetate-ethyl acetate solution containing 5% methanol)) to yield Compound 25 (light-yellow oil 655 mg, 68%).
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[CH3:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[N:21]=[C:22]([S:33][C:34]3[CH:39]=[CH:38][C:37]([C:40]([F:43])([F:42])[F:41])=[CH:36][CH:35]=3)[NH:23][C:24]=2[C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)=[CH:16][CH:15]=1>ClCCl>[CH3:12][O:13][C:14]1[CH:15]=[CH:16][C:17]([C:20]2[N:21]=[C:22]([S:33]([C:34]3[CH:39]=[CH:38][C:37]([C:40]([F:42])([F:43])[F:41])=[CH:36][CH:35]=3)=[O:9])[NH:23][C:24]=2[C:25]2[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=2)=[CH:18][CH:19]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: COc1ccc(-c2nc(Sc3ccc(C(F)(F)F)cc3)[nH]c2-c2ccc(OC)cc2)cc1
Solvent: ClCCl
Product: COc1ccc(-c2nc(S(=O)c3ccc(C(F)(F)F)cc3)[nH]c2-c2ccc(OC)cc2)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 79.9 %

Procedure:
A solution of 2.164 g of 3-chloroperbenzoic acid (80%) in 150 ml of dichloromethane is added dropwise to a solution of 4.57 g of 4,5-bis(4-methoxyphenyl)-2-(4-trifluoromethylphenylthio)imidazole in 100 ml of dichloromethane. The mixture is agitated for 3 hours at room temperature, the solution is washed with sodium bicarbonate solution, dried over sodium sulfate, and concentrated to dryness under vacuum. The residue is chromatographed on 150 g of silica gel with acetone/hexane, thus producing 3.78 g of 4,5-bis-(4-methoxyphenyl)-2-(4-trifluoromethylphenylsulfinyl)imidazole as an amorphous foam.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:11]([O:12][CH3:13])=[C:10]([O:14][CH3:15])[CH:9]=[C:5]([C:6]([OH:8])=O)[C:4]=1[NH2:16].[NH2:17][C:18](N)=[O:19]>O>[CH3:15][O:14][C:10]1[CH:9]=[C:5]2[C:4](=[C:3]([O:2][CH3:1])[C:11]=1[O:12][CH3:13])[NH:16][C:18](=[O:19])[NH:17][C:6]2=[O:8]
Reactant: COc1cc(C(=O)O)c(N)c(OC)c1OC
Reactant: NC(N)=O
Solvent: O
Product: COc1cc2c(=O)[nH]c(=O)[nH]c2c(OC)c1OC
Temperature: 145 °C
Yield: 45.1 %

Procedure:
A mixture of 4.94 g (21.7 mmols) of 3,4,5-trimethoxyanthranilic acid and 15.15 g (249.8 mmols) of urea was heated at 145° C for an hour with stirring. After cooling, water was added and the mixture was heated at the boiling point with stirring. The solid was taken out by filtration and dried to afford 2.47 g (yield: 45%) of 6,7,8-trimethoxyquinazoline-2,4-dione.
Reaction SMILES: [N:1]1([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[NH:13][C:14]([C:16]2[O:17][C:18]([C:21]#[N:22])=[CH:19][CH:20]=2)=[O:15])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1>C1C=CC=CC=1.C(O)C>[O:15]=[C:14]1[C:16]2[O:17][C:18]([C:21]#[N:22])=[CH:19][C:20]=2[C:9]2[CH:10]=[CH:11][CH:12]=[C:7]([N:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)[C:8]=2[NH:13]1
Reactant: N#Cc1ccc(C(=O)Nc2ccccc2N2CCCCC2)o1
Solvent: CCO
Solvent: c1ccccc1
Product: N#Cc1cc2c(o1)c(=O)[nH]c1c(N3CCCCC3)cccc12

Procedure:
5-Cyano-furan-2-carboxylic acid (2-piperidin-1-yl-phenyl)-amide (200 mg) is dissolved in a mixture of benzene (180 mL) and ethanol (20 mL). The solution is irradiated with a 100 W high pressure Hg Lamp at room temperature for 10 h, according to the method described by Kanoka and Itoh [Synthesis, 36 (1972)]. The solvent is removed in vacuo and the residue is purified by preparative thin layer chromatography (“TLC”) (silica gel) to yield the pure product.
Reaction SMILES: [CH:1]1[C:11]2[CH2:10][CH2:9][C:8]3[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=3[C:6](=[CH:16][C:17]3[CH:18]=[C:19]([NH2:23])[CH:20]=[CH:21][CH:22]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[CH:24]([S:27](Cl)(=[O:29])=[O:28])([CH3:26])[CH3:25]>>[CH:1]1[C:11]2[CH2:10][CH2:9][C:8]3[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=3[C:6](=[CH:16][C:17]3[CH:18]=[C:19]([NH:23][S:27]([CH:24]([CH3:26])[CH3:25])(=[O:29])=[O:28])[CH:20]=[CH:21][CH:22]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1
Reactant: CC(C)S(=O)(=O)Cl
Reactant: Nc1cccc(C=C2c3ccccc3CCc3ccccc32)c1
Product: CC(C)S(=O)(=O)Nc1cccc(C=C2c3ccccc3CCc3ccccc32)c1
Yield: 22 %

Procedure:
Following procedures essentially as described in Example 90, 3-(10,11-dihydro-dibenzo[a,d]cyclohepten-5-ylidenemethyl)-phenylamine and isopropylsulfonyl chloride gives the title compound in 22% yield as a white solid, mp 187.7° C. 1H NMR (CDCl3) δ 1.28 (d, 6H), 2.80-3.60 (br m, 5H), 6.47 (s, 1H), 6.75-7.50 (m, 13H); MS (ES) 426 (M+Na), 402 (M−H). HPLC shows 94% purity.
Reaction SMILES: [NH2:1][C:2]1([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[Cl:33])[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([Cl:11])[CH:9]=2)[N:4]([S:12]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=2[N+:23]([O-])=O)(=[O:14])=[O:13])[C:3]1=[O:26].CO>[Ni].C1COCC1>[NH2:1][C:2]1([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[Cl:33])[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([Cl:11])[CH:9]=2)[N:4]([S:12]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=2[NH2:23])(=[O:14])=[O:13])[C:3]1=[O:26]
Reactant: COc1ccc(S(=O)(=O)N2C(=O)C(N)(c3ccccc3Cl)c3cc(Cl)ccc32)c([N+](=O)[O-])c1
Agent: [Ni]
Solvent: CO
Solvent: C1CCOC1
Product: COc1ccc(S(=O)(=O)N2C(=O)C(N)(c3ccccc3Cl)c3cc(Cl)ccc32)c(N)c1
Reaction time: 1 h
Yield: 14 %

Procedure:
A mixture of 2.4 g of the compound obtained in EXAMPLE 105, 1 g of Raney® nickel, 50 ml of MeOH and 50 ml of THF is hydrogenated at atmospheric pressure for 1 hour at RT. The catalyst is filtered off on Celite® and the filtrate is evaporated under vacuum. The residue is chromatographed on silica using DCM and then a DCM/AcOEt mixture (95/5; v/v) as the eluent to give 0.316 g of the expected product after crystallization from a DCM/iso ether mixture. M.p.=160°-166° C.
Reaction SMILES: Br[C:2]1[C:3]2[C:4]3[CH:17]=[CH:16][S:15][C:5]=3[C:6](=[O:14])[NH:7][C:8]=2[CH:9]=[CH:10][C:11]=1[O:12][CH3:13].CC1(C)C(C)(C)OB([C:26]2[CH:31]=[CH:30][C:29]([CH:32]([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[CH3:33])=[CH:28][CH:27]=2)O1>>[CH3:13][O:12][C:11]1[CH:10]=[CH:9][C:8]2[NH:7][C:6](=[O:14])[C:5]3[S:15][CH:16]=[CH:17][C:4]=3[C:3]=2[C:2]=1[C:26]1[CH:27]=[CH:28][C:29]([CH:32]([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[CH3:33])=[CH:30][CH:31]=1
Reactant: COc1ccc2[nH]c(=O)c3sccc3c2c1Br
Reactant: CC(NC(=O)OC(C)(C)C)c1ccc(B2OC(C)(C)C(C)(C)O2)cc1
Product: COc1ccc2[nH]c(=O)c3sccc3c2c1-c1ccc(C(C)NC(=O)OC(C)(C)C)cc1
Yield: 39.7 %

Procedure:
Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (600 mg, 1.9 mmol) was reacted with tert-butyl 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethylcarbamate (1.34 g, 3.87 mmol) to afford the desired product (340 mg, 39%) as a brown solid: ESI MS m/z 451 [C25H26N2O4S+H]+.