Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O=[CH:15][CH2:16][NH:17]C(=O)OC(C)(C)C.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Cl:43]CCCl>>[ClH:43].[ClH:43].[ClH:43].[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([CH2:15][CH2:16][NH2:17])[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: c1ccc(CN2CCNCC2)cc1
Reactant: ClCCCl
Reactant: CC(C)(C)OC(=O)NCC=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Product: Cl
Product: NCCN1CCN(Cc2ccccc2)CC1
Yield: 61 %

Procedure:
To a solution of 1-benzylpiperazine (4.4 g), tert-butyl N-(2-oxoethyl)carbamate (3.8 g) and acetic acid (1.7 ml) in 1,2-dichloroethane (50 ml) was added sodium triacetoxyborohydride (8.1 g) under ice-cooling. The reaction mixture was mixed at room temperature for 2 days. Then, the reaction solution washed with an aqueous potassium carbonate solution and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was dissolved in methanol (50 ml). A 4 N solution of hydrogen chloride in ethanol (40 ml) was added thereto, and mixed at room temperature for 5 hours. The precipitate was collected by filtration and washed with diethyl ether and hexane to obtain the title compound (5.0 g, 61%).
Reaction SMILES: [O:1]=[S:2]1(=[O:26])[CH2:7][CH:6]=[C:5]([C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:18][C@H:17]([CH2:19][NH:20][C:21](=[O:23])[CH3:22])[O:16][C:15]3=[O:24])=[CH:10][C:9]=2[F:25])[CH2:4][CH2:3]1.CS(N)(=O)=[O:29].S([O-])([O-])=O.[Na+].[Na+]>C(O)(C)(C)C.O>[OH:29][C:5]1([C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:18][C@H:17]([CH2:19][NH:20][C:21](=[O:23])[CH3:22])[O:16][C:15]3=[O:24])=[CH:10][C:9]=2[F:25])[CH:4]=[CH:3][S:2](=[O:1])(=[O:26])[CH2:7][CH2:6]1
Reactant: CC(=O)NC[C@H]1CN(c2ccc(C3=CCS(=O)(=O)CC3)c(F)c2)C(=O)O1
Reactant: CS(N)(=O)=O
Agent: O=S([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CC(C)(C)O
Product: CC(=O)NC[C@H]1CN(c2ccc(C3(O)C=CS(=O)(=O)CC3)c(F)c2)C(=O)O1
Temperature: 0 °C
Reaction time: 120 h

Procedure:
A solution of (S)-N-[[3-[4-(3,6-dihydro-1,1-dioxido-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide (0.415 g, 1.08 mmol; prepared as described in U.S. Pat. No. 5,968,962) in 1:1 t-butanol-water (4 mL) is added to a solution of the standard reagent AD mix-β (1.51 g; available from Aldrich Co.) and methanesulfonamide (0.103 g, 1.08 mmol) in 1:1 t-butanol-water (10 mL) cooled at 0° C. The reaction mixture is stirred 5 days at 4° C. and then treated with sodium sulfite (1.5 g) and stirred 30 minutes. The solution is then extracted with four 10 mL portions of ethyl acetate and the combined organic phases dried (MgSO4), filtered and concentrated. Purification by column chromatography (0-5% MeOH-DCM) provided the title compound as a mixture of diastereomers. Yield 0.29 g (64%). 1H NMR.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:8]2[O:9][C:10]([CH3:17])=[C:11]([CH2:13][C:14](O)=[O:15])[N:12]=2)[CH:5]=[CH:6][CH:7]=1>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([C:8]2[O:9][C:10]([CH3:17])=[C:11]([CH2:13][CH2:14][OH:15])[N:12]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: Cc1oc(-c2cccc(Br)c2)nc1CC(=O)O
Solvent: C1CCOC1
Product: Cc1oc(-c2cccc(Br)c2)nc1CCO
Temperature: 25 °C
Reaction time: 2 h
Yield: 73.3 %

Procedure:
A solution of 2-(3-bromophenyl)-5-methyl-4-oxazoleacetic acid (39.1 g, 0.13 mol) in dry THF (175 mL) was treated dropwise with borane-THF complex (227 mL of a 1.0 M solution in THF, 1.3 mol) over 2 h (reaction temperature to 35° C.). After stirring 2 h at room temperature under N2, the reaction was quenched with slow addition of methanol (60 mL) and stirred overnight at room temperature. The reaction was diluted with 1 N NaOH (50 mL) and extracted with CH2Cl2 (2×200 mL). The organic layer was washed with H2O (3×100 mL), dried (MgSO4), and the solvent removed in vacuo to give 38.7 g of crude product that was recrystallized from toluene (200 mL, wash solid with cold hexanes) to give 26.9 g (72%) of 2-(3-bromophenyl)-5-methyl-4-oxazoleethanol as a white powder. Mp 92-93° C.; 1H NMR (300 MHz, d6-DMSO) δ7.99 (s, 1H), 7.88 (d, J=7.7 Hz, 1H), 7.64 (d, J=7.7 Hz, 1H), 7.44 (t, J=7.7 Hz, 1H), 4.61 (t, J=5.5 Hz, OH), 3.63 (q, J=5.5 Hz, 2H), 2.60 (t, J=6.6 Hz, 2H), 2.32 (s, 3H).
Reaction SMILES: CC(OC([NH:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[S:16][CH:17]=[CH:18][CH:19]=2)=[CH:11][C:10]=1[NH:20][C:21]([C:23]1[CH:28]=[CH:27][C:26]([C:29](=[O:38])[CH2:30][CH2:31][P:32]([CH3:37])(=[O:36])[O:33][CH2:34][CH3:35])=[CH:25][CH:24]=1)=[O:22])=O)(C)C.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[NH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[S:16][CH:17]=[CH:18][CH:19]=2)=[CH:11][C:10]=1[NH:20][C:21]([C:23]1[CH:28]=[CH:27][C:26]([C:29](=[O:38])[CH2:30][CH2:31][P:32]([CH3:37])(=[O:36])[O:33][CH2:34][CH3:35])=[CH:25][CH:24]=1)=[O:22]
Reactant: CCOP(C)(=O)CCC(=O)c1ccc(C(=O)Nc2cc(-c3cccs3)ccc2NC(=O)OC(C)(C)C)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCOP(C)(=O)CCC(=O)c1ccc(C(=O)Nc2cc(-c3cccs3)ccc2N)cc1
Reaction time: 3 h

Procedure:
Ethyl {3-[4-({[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]-3-oxopropyl}methylphosphinate (125 mg, 0.225 mmol) was taken up in DCM (5 mL)/TFA (2 mL). After 3 hours, saturated NaHCO3 was added and the products extracted into EtOAc (×2). The combined organic extracts were washed with brine, dried over MgSO4 and concentrated in vacuo to give ethyl {3-[4-({[2-amino-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]-3-oxopropyl}methylphosphinate as an orange solid.
Reaction SMILES: [ClH:1].[N:2]1([CH2:7][C:8]2[CH:9]=[C:10]([CH:14]=[CH:15][CH:16]=2)[C:11]([NH2:13])=[NH:12])[CH2:6][CH2:5][CH2:4][CH2:3]1.CC[O-].[Na+].[CH3:21][S:22][C:23]1[CH:32]=[CH:31][C:26]([C:27]([NH:29]N)=O)=[CH:25][CH:24]=1.Cl.CCOCC>C(O)C>[ClH:1].[CH3:21][S:22][C:23]1[CH:32]=[CH:31][C:26]([C:27]2[NH:29][N:13]=[C:11]([C:10]3[CH:14]=[CH:15][CH:16]=[C:8]([CH2:7][N:2]4[CH2:6][CH2:5][CH2:4][CH2:3]4)[CH:9]=3)[N:12]=2)=[CH:25][CH:24]=1
Reactant: CSc1ccc(C(=O)NN)cc1
Reactant: N=C(N)c1cccc(CN2CCCC2)c1
Agent: CC[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCOCC
Solvent: CCO
Product: CSc1ccc(-c2nc(-c3cccc(CN4CCCC4)c3)n[nH]2)cc1
Reaction time: 0.5 h
Yield: 51.7 %

Procedure:
To a stirred ethanolic suspension of 3-pyrrolidin-1-ylmethyl-benzamidine hydrochloride salt (1:2) (414 mg, 1.5 mmol, 1.5 eq.) in 15 ml ethanol was added over 3 minutes 1.2N NaOEt in ethanol (3.4 ml, 4 eq.) and stirring was continued for 30 min. at r.t. 4-Methylsulfanyl-benzoic acid hydrazide (182 mg, 1 mmol) in ethanol at 20° C. was then added and the mixture heated to reflux for 50 hrs. Upon cooling the product mixture was filtered, solvent evaporated and residue chromatographed over 20 g SiO2 (Merck 230-400 mesh) with CH2Cl2-MeOH (2M NH3) 96:4, affording a foam after solvent evaporation. This material was dissolved in ethanol at r.t. and an excess 2N HCl/ether solution (1.0 ml, 2 mmol) was added. After 30 min. the solvent was evaporated and the residue was dried overnight under high vacuum at 30° C. affording the title compound (200 mg, 52% yield) as a yellow foam. MS: m/e=351.5 (M+H+).
Reaction SMILES: [Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[CH2:13]([C:20]1[C:25](=[O:26])[N:24]([CH2:27][C:28]2[CH:33]=[CH:32][C:31]([C:34]3[C:35]([C:40]#[N:41])=[CH:36][CH:37]=[CH:38][CH:39]=3)=[CH:30][CH:29]=2)[C:23]([CH2:42][CH2:43][CH3:44])=[N:22][C:21]=1[CH3:45])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>O.C(OCC)(=O)C>[CH2:13]([C:20]1[C:25](=[O:26])[N:24]([CH2:27][C:28]2[CH:33]=[CH:32][C:31]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[C:40]3[NH:3][C:4](=[O:7])[O:5][N:41]=3)=[CH:30][CH:29]=2)[C:23]([CH2:42][CH2:43][CH3:44])=[N:22][C:21]=1[CH3:45])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: CCCc1nc(C)c(Cc2ccccc2)c(=O)n1Cc1ccc(-c2ccccc2C#N)cc1
Reactant: [NH3+]O
Reactant: O=C([O-])O
Agent: [Cl-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Solvent: CCOC(C)=O
Product: CCCc1nc(C)c(Cc2ccccc2)c(=O)n1Cc1ccc(-c2ccccc2-c2noc(=O)[nH]2)cc1
Temperature: 40 °C
Reaction time: 0.5 h
Yield: 55.8 %

Procedure:
A mixture of hydroxylammonium chloride (1.20 g), sodium hydrogen carbonate (1.80 g) and dimethyl sulfoxide (10 mL) was stirred at 40° C. for 30 min, 4′-[(5-benzyl-4-methyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl]biphenyl-2-carbonitrile (0.93 g) was added, and the mixture was stirred at 90° C. for 18 hr. The reaction mixture was allowed to cool to room temperature, ethyl acetate and water were added to the reaction mixture, and the aqueous layer was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was dissolved in tetrahydrofuran (10 mL). N,N′-carbonyldiimidazole (0.38 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.36 mL) were added, and the mixture was stirred at room temperature for 3 hr. The reaction mixture was diluted with ethyl acetate, washed with 1 M hydrochloric acid and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give the title compound as a colorless solid (0.59 g, 56%).
Reaction SMILES: [H-].[Na+].[Cl-].[C:4]([CH2:6][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)#[N:5].[CH:26]([C:29]1[CH:34]=[C:33]([CH:35]=O)[CH:32]=[CH:31][N:30]=1)([CH3:28])[CH3:27].CO>O1CCCC1.CN(C)C=O>[CH:26]([C:29]1[CH:34]=[C:33]([CH:35]=[CH:6][C:4]#[N:5])[CH:32]=[CH:31][N:30]=1)([CH3:28])[CH3:27]
Reactant: N#CC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CC(C)c1cc(C=O)ccn1
Agent: [Cl-]
Agent: [H-]
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: CC(C)c1cc(C=CC#N)ccn1
Reaction time: 1 h
Yield: 11.5 %

Procedure:
To a suspension of 6.55 g (0.15 mol) sodiumhydride in 220 ml tetrahydrofurane and 220 ml dimethylformamide were added 50.7 g (0.15 mol) (cyanomethyl)triphenylphosphonium chloride. After sirring for 1 hour at room temperature a solution of 22.4 g (0.15 mol) 2-isopropyl-4-pyridinecarboxaldehyde in 50 ml tetrahydrofuran were added and stirring was continued for 15 hours. Then 10 ml methanol were added, the solvents were evaporated and the residue chromatographed on aluminiumoxide with dichloromethane to yield 2.96 g 3-(2-isopropyl-pyridin-4-yl)-acrylonitrile as coorless oil. MS m/e (%): 172 (M+, 100).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1)[CH:9]([CH3:11])[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:18][O:19][C:20]1[CH:25]=[CH:24][N:23]=[CH:22][C:21]=1[C:26]([O-])=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClC(Cl)C>[C:1]([O:5][C:6]([N:8]([CH:12]1[CH2:13][CH2:14][N:15]([CH2:26][C:21]2[CH:22]=[N:23][CH:24]=[CH:25][C:20]=2[O:19][CH3:18])[CH2:16][CH2:17]1)[CH:9]([CH3:11])[CH3:10])=[O:7])([CH3:3])([CH3:4])[CH3:2]
Reactant: CC(C)N(C(=O)OC(C)(C)C)C1CCNCC1
Reactant: COc1ccncc1C(=O)[O-]
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CC(Cl)Cl
Product: COc1ccncc1CN1CCC(N(C(=O)OC(C)(C)C)C(C)C)CC1
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 105.9 %

Procedure:
A solution of 4-(N-tert-butoxycarbonyl-N-isopropylamino)piperidine (118 g, 0.49 mol) in dichloroethane (600 mL) was stirred at room temperature for 1 hour, and then 4-methoxypyridine-3-carboxylate (63.5 g, 0.46 mol) was added. The resulting solution was stirred at room temperature for 2.5 hours and then cooled to 5° C. in an ice/water bath. Sodium triacetoxyborohydride (124 g, 0.58 mol) in dichloroethane (600 mL) was added and the reaction mixture was stirred at 5° C. for 15 minutes. The ice bath was then removed and reaction mixture was stirred for 4 hours at room temperature. Acetic acid (30 mL) was then added to the reaction mixture and the resulting mixture was stirred for 0.5 hours, and then concentrated to half its original volume. This solution was cooled in a dry ice/acetone bath and 10 N aqueous sodium hydroxide (350 mL) was added. This mixture was stirred for 0.5 hours and then the organic layer was separated and washed with 1 N aqueous sodium hydroxide (400 mL). The aqueous layer was then washed three times with dichloromethane (400 mL) and the combined organic layers were dried over sodium sulfate (40 g). The sodium sulfate was filtered off and washed with dichloromethane (100 mL) and the combined organic layers were concentrated in vacuo to give 177 g of the title intermediate as a yellow oil (>99% yield; 74% purity by GC).
Reaction SMILES: Br[CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH3:10][C:11]1[CH:16]=[CH:15][C:14]([NH:17][C:18]2([C:24]([NH2:26])=[O:25])[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]2)=[CH:13][CH:12]=1.C(N(CC)CC)C>CN(C)C(=O)C>[CH3:10][C:11]1[CH:16]=[CH:15][C:14]([NH:17][C:18]2([C:24]([NH2:26])=[O:25])[CH2:19][CH2:20][N:21]([CH2:2][CH2:3][C:4]3[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=3)[CH2:22][CH2:23]2)=[CH:13][CH:12]=1
Reactant: Cc1ccc(NC2(C(N)=O)CCNCC2)cc1
Reactant: BrCCc1ccccc1
Solvent: CCN(CC)CC
Solvent: CC(=O)N(C)C
Product: Cc1ccc(NC2(C(N)=O)CCN(CCc3ccccc3)CC2)cc1
Reaction time: 4 h

Procedure:
A mixture of 33.35 parts of (2-bromoethyl)benzene, 35 parts of 4-[N-(4-methylphenyl)amino]-4-piperidinecarboxamide, 20 parts of N,N-diethylethanamine and 225 parts of N,N-dimethylacetamide is stirred for 4 hours at 70°-80° C. The reaction mixture is poured onto water and the product is extracted with trichloromethane. The extract is washed with water, dried, filtered and evaporated. The oily residue is poured onto water, whereupon the product is precipitated. It is filtered off and suspended twice in water. The product is filtered off again, washed with 2,2'-oxybispropane and dried, yielding 4-[N-(4-methylphenyl)amino]-1-(2-phenylethyl)-4-piperidinecarboxamide; mp. 163.1° C.
Reaction SMILES: [C:1]([O:4][C@H:5]1[C@@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@H:8]([N:14]2[CH:22]=[N:21][C:20]3[C:15]2=[N:16][C:17]([C:24]#[N:25])=[N:18][C:19]=3Cl)[O:7][C@@H:6]1[CH2:26][O:27][C:28](=[O:30])[CH3:29])(=[O:3])[CH3:2].C(N(CC)CC)C.[CH2:38]([NH2:46])[CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>C(#N)C>[C:1]([O:4][C@H:5]1[C@@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@H:8]([N:14]2[CH:22]=[N:21][C:20]3[C:15]2=[N:16][C:17]([C:24]#[N:25])=[N:18][C:19]=3[NH:46][CH2:38][CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[O:7][C@@H:6]1[CH2:26][O:27][C:28](=[O:30])[CH3:29])(=[O:3])[CH3:2]
Reactant: NCCc1ccccc1
Reactant: CC(=O)OC[C@H]1O[C@@H](n2cnc3c(Cl)nc(C#N)nc32)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CC(=O)OC[C@H]1O[C@@H](n2cnc3c(NCCc4ccccc4)nc(C#N)nc32)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 87.6 %

Procedure:
A solution of (2R,3R,4R,5R)-4-(acetyloxy)-2-[(acetyloxy)methyl]-5-(6-chloro-2-cyano-9H-purin-9-yl)tetrahydro-3-furanyl acetate (1.96 g, 4.48 mmol) (Preparation 10) and triethylamine (1.8 g, 17.8 mmol) in acetonitrile (20 ml) was treated with phenethylamine (0.60 g, 4.96 mmol) and the mixture was stirred at room temperature under a nitrogen atmosphere for 2 hours. The solvent was removed under reduced pressure and the residue was partitioned between dichloromethane (75 ml) and water (20 ml). The organic phase was separated and the solvent was removed under reduced pressure. The foam was purified by column chromatography on silica gel eluting with dichloromethane:ethyl acetate (4:1 by volume) to give a product which was then azeotroped with diethyl ether to afford the title compound as a foam (2.05 g).
Reaction SMILES: [CH:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]3[O:16][CH2:15][O:14][C:11]=3[CH:12]=2)[CH:7]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[NH:6][C:5]1=[O:23])([CH3:3])[CH3:2].O1CCOCC1.[Mn]([O-])(=O)(=O)=O.[K+].C=O>O>[CH:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]3[O:16][CH2:15][O:14][C:11]=3[CH:12]=2)[C:7]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[N:6][C:5]1=[O:23])([CH3:3])[CH3:2]
Reactant: CC(C)N1C(=O)NC(c2ccccc2)c2cc3c(cc21)OCO3
Agent: O=[Mn](=O)(=O)[O-]
Agent: C=O
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Product: CC(C)n1c(=O)nc(-c2ccccc2)c2cc3c(cc21)OCO3

Procedure:
To a solution of 8.5 gm. of 1-isopropyl-4-phenyl-6,7-methylenedioxy-3,4-dihydro-2(1H)-quinazolinone in 225 ml. of p-dioxane, cooled to 10°-13°C., is added dropwise a solution of 4.3 gm. of potassium permanganate in 185 ml. of water. When the addition is complete, 2 ml. of formalin solution are added. Precipitated solids are removed by filtration and the solvents stripped from the filtrate at reduced pressure. The residue is decolorized with activated charcoal in ethyl acetate and recrystallized from ethyl acetate to obtain 1-isopropyl-4-phenyl-6,7-methylenedioxy-2(1H)-quinazolinone, m.p. 187°-191°C.
Reaction SMILES: [C:1]1(C)C=CC=CC=1.N1CCCCC1.[C:14]([C:18]1[CH:19]=[C:20]([C:26]2[CH:27]=[C:28]3[C:33](=[CH:34][CH:35]=2)[CH:32]=[C:31](C=O)[CH:30]=[CH:29]3)[CH:21]=[CH:22][C:23]=1[O:24][CH3:25])([CH3:17])([CH3:16])[CH3:15].[S:38]=[C:39]1[NH:43][C:42](=[O:44])[CH2:41][S:40]1>C(O)(=O)C>[C:14]([C:18]1[CH:19]=[C:20]([C:26]2[CH:27]=[C:28]3[C:33](=[CH:34][CH:35]=2)[CH:32]=[C:31]([N:43]2[C:42](=[O:44])[C:41](=[CH2:1])[S:40][C:39]2=[S:38])[CH:30]=[CH:29]3)[CH:21]=[CH:22][C:23]=1[O:24][CH3:25])([CH3:17])([CH3:15])[CH3:16]
Reactant: O=C1CSC(=S)N1
Reactant: Cc1ccccc1
Reactant: COc1ccc(-c2ccc3cc(C=O)ccc3c2)cc1C(C)(C)C
Solvent: CC(=O)O
Solvent: C1CCNCC1
Product: C=C1SC(=S)N(c2ccc3cc(-c4ccc(OC)c(C(C)(C)C)c4)ccc3c2)C1=O
Yield: 56 %

Procedure:
A solution of toluene (2.5 mL), piperidine (0.003 mL), acetic acid (0.003 mL), 6-[3-(t-butyl)-4-methoxyphenyl]-2-naphthaldehyde (0.100 g, 0.31 mmol) and 2-thioxo-4-thiazolidinone (0.041 mg, 0.31 mmol) was heated at reflux for 16.5 hours under an argon atmosphere. The resulting suspension was filtered and the solid was washed with EtOH and H2O. The solid was dried under high vacuum to afford 0.076 g (56%) of 6-[3-(t-butyl)-4-methoxyphenyl]-naphthalen-2-yl-methylene-2-thioxo-4-thiazolidinone, mp 281–284° C. 1H NMR (300 MHz, DMSO-d6): δ 1.40 (s, 9H), 3.86 (s, 3H), 7.11 (d, J=8.4 Hz, 1H), 7.61–7.70 (m, 3H), 7.77 (s, 1H), 7.89 (d, J=8.4 Hz, 1H), 8.09 (dd, J1=8.4 Hz, J2=3.0 Hz, 2H), 8.10 (s, 2H), 13.9 (brs, 1H).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[NH2:9].C(N(CC)CC)C.[CH:17]1([C:20](Cl)=[O:21])[CH2:19][CH2:18]1>C(Cl)(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[NH:9][C:20]([CH:17]1[CH2:19][CH2:18]1)=[O:21]
Reactant: O=C(Cl)C1CC1
Reactant: Cc1ccc(Br)c(N)c1
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: Cc1ccc(Br)c(NC(=O)C2CC2)c1

Procedure:
The solution of 13.95 g of 2-bromo-5-methylphenylamine in 250 ml of chloroform is cooled to 0° C. with stirring and admixed with 12.6 ml of triethylamine. 7.56 ml of cyclopropanecarbonyl chloride are slowly added dropwise. The mixture is stirred for 1 hour each at 0° C. and at room temperature. The reaction mixture is poured onto water (400 ml) and extracted with dichloromethane (1×250 ml). The organic phases are washed with brine (350 ml), dried over sodium sulphate and concentrated by evaporation. The title compound is obtained as a white solid from the residue by means of crystallization from ethyl acetate. Rf=0.37 (1:4 EtOAc-heptane); Rt=4.19.
Reaction SMILES: [CH2:1]([N:5]([CH2:21][CH2:22][CH2:23][CH3:24])[C:6]1[CH:11]=[CH:10][C:9]([CH:12]=[CH:13][C:14]2[S:18][C:17]([CH:19]=O)=[CH:16][CH:15]=2)=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH3:4].[C:25]([C:27]1[C:28](=[C:35]([C:38]#[N:39])[C:36]#[N:37])[O:29][C:30]([CH3:34])([CH3:33])[C:31]=1[CH3:32])#[N:26].C([O-])(=O)C.[NH4+]>C(O)C.O1CCCC1>[CH2:1]([N:5]([CH2:21][CH2:22][CH2:23][CH3:24])[C:6]1[CH:11]=[CH:10][C:9]([CH:12]=[CH:13][C:14]2[S:18][C:17]([CH:19]=[CH:32][C:31]3[C:30]([CH3:33])([CH3:34])[O:29][C:28](=[C:35]([C:36]#[N:37])[C:38]#[N:39])[C:27]=3[C:25]#[N:26])=[CH:16][CH:15]=2)=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCN(CCCC)c1ccc(C=Cc2ccc(C=O)s2)cc1
Reactant: CC1=C(C#N)C(=C(C#N)C#N)OC1(C)C
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCO
Product: CCCCN(CCCC)c1ccc(C=Cc2ccc(C=CC3=C(C#N)C(=C(C#N)C#N)OC3(C)C)s2)cc1
Temperature: 25 °C
Yield: 75.8 %

Procedure:
In an ethanol/tetrahydrofuran mixed solvent were dissolved 170 mg (0.50 mmol) of 5-[2-[4-(dibutylamino)phenyl]vinyl]thiophene-2-carboaldehyde and 110 mg (0.55 mmol) of 2-(3-cyano-4,5,5-trimethyl-2(5H)-furanylidene) propanedinitrile. To this mixture, 42 mg of ammonium acetate was added, and the mixture was stirred at room temperature. The solvent was evaporated off. The residue was purified by silica gel column chromatography and washed with ethanol to give 198 mg of a black crystal having amp of 208-209° C. (yield: 76.1%).
Reaction SMILES: S(Cl)([Cl:4])(=O)=O.[CH:6]([S:9]([CH2:12][C:13](=[O:15])[CH3:14])(=[O:11])=[O:10])([CH3:8])[CH3:7]>CC(O)=O.C(Cl)Cl>[Cl:4][CH:12]([S:9]([CH:6]([CH3:8])[CH3:7])(=[O:11])=[O:10])[C:13](=[O:15])[CH3:14]
Reactant: O=S(=O)(Cl)Cl
Reactant: CC(=O)CS(=O)(=O)C(C)C
Solvent: CC(=O)O
Solvent: ClCCl
Product: CC(=O)C(Cl)S(=O)(=O)C(C)C
Temperature: 25 °C
Reaction time: 4 h
Yield: 157.9 %

Procedure:
Sulfuryl chloride (0.248 mL, 3.05 mmol) was added dropwise to a solution of 1-(isopropylsulfonyl)propan-2-one (418 mg, 2.55 mmol) in 1:1 AcOH/DCM (16 ml) at 0° C. The reaction was stirred at rt for 4 h. The solvent was removed in vacuo, then diluted with dichloromethane. The organic layer was washed (2×) with saturated NaHCO3 solution, dried over Na2SO4, filtered, and concentrated to leave 800 mg of a colorless oil. The material was used without further purification.
Reaction SMILES: [OH:1][NH:2][C:3]([NH2:5])=[O:4].[C:6]([CH2:9][C:10](=O)[CH3:11])(=O)[CH3:7].[ClH:13]>>[ClH:13].[CH3:7][C:6]1[N:5]=[C:3]([OH:4])[N+:2]([O-:1])=[C:10]([CH3:11])[CH:9]=1
Reactant: CC(=O)CC(C)=O
Reactant: NC(=O)NO
Agent: Cl
Product: Cc1cc(C)[n+]([O-])c(O)n1
Temperature: 2 °C

Procedure:
0.40 mol (30.6 g) hydroxy urea was dissolved in 600 ml of 1 M HCl and 0.50 mol (50.06 g) acetyl acetone were added dropwise under ice cooling, maintaining the internal temperature at 1-3° C. The solution was thawed to room temperature in an ice bath and stirred over night, then filtered off and evaporated to dryness. The residue was suspended with 400 ml of acetone, the mixture was cooled to −18° C., the solid filtered off and washed with a little ice-cold acetone. After drying, 45.5 g of crude product were obtained. The crude product was recrystallized with 4.0 l ethanol from the boiling heat, cooled to −18° C., filtered off and washed with little ethanol and dried (fraction 1). The mother liquor was concentrated on a rotary evaporator until product started to precipitate again, cool stored and a second fraction isolated. After drying 26.0 g (1. fraction, purity>98%) and 11.0 g (2. fraction, contained 32% NH4Cl as by-product) of the title compound was obtained.
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([OH:17])[CH:15]=2)[C:10]([C:18]([NH:20][CH2:21][C:22]2[CH:27]=[CH:26][C:25]([F:28])=[C:24]([F:29])[CH:23]=2)=[O:19])=[C:9]1[CH:30]([CH3:32])[CH3:31])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:33]([O-])([O-])=O.[K+].[K+].I[CH:40]([CH2:42][CH3:43])C>CN(C=O)C>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:17][CH2:33][CH:42]([CH3:40])[CH3:43])[CH:15]=2)[C:10]([C:18]([NH:20][CH2:21][C:22]2[CH:27]=[CH:26][C:25]([F:28])=[C:24]([F:29])[CH:23]=2)=[O:19])=[C:9]1[CH:30]([CH3:32])[CH3:31])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCC(C)I
Reactant: CC(C)c1c(C(=O)NCc2ccc(F)c(F)c2)c2ccc(O)cc2n1Cc1ccccc1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)COc1ccc2c(C(=O)NCc3ccc(F)c(F)c3)c(C(C)C)n(Cc3ccccc3)c2c1

Procedure:
Following General Procedure A, 1-benzyl-N-(3,4-difluorobenzyl)-6-hydroxy-2-isopropyl-1H-indole-3-carboxamide (Compound 8, 10.7 mg, 0.025 mmol) in DMF (1.0 ml) was reacted with K2CO3 (10.0 mg, 0.074 mmol) and 2-iodobutane (14.0 μl, 0.12 mmol) to yield the title compound as a white solid.