Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.C(N1C=CN=C1)(N1C=CN=C1)=O.[F:33][C:34]([F:43])([F:42])[C:35]1[CH:36]=[C:37]([CH:39]=[CH:40][CH:41]=1)[NH2:38]>O1CCCC1.ClCCl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]([NH:38][C:37]2[CH:39]=[CH:40][CH:41]=[C:35]([C:34]([F:33])([F:42])[F:43])[CH:36]=2)=[O:11])=[CH:6][CH:7]=1
Reactant: O=C(O)Cc1ccc(Br)cc1
Reactant: Nc1cccc(C(F)(F)F)c1
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: O=C(Cc1ccc(Br)cc1)Nc1cccc(C(F)(F)F)c1
Reaction time: 1 h
Yield: 78.1 %

Procedure:
Dissolve 4-bromophenylacetic acid (10.00 g, 46.50 mmol), diisopropylethylamine (12.02 g, 16.20 mL, 93.00 mmol) and 1,1′-carbonyldiimidazole (8.29 g, 51.15 mmol) in tetrahydrofuran (200 mL) at room temperature. Stir the contents under nitrogen for one hour. Add m-trifluoromethylaniline (15.00 g, 93.00 mmol) and stir the reaction overnight at room temperature. Concentrate the reaction to near dryness, dissolve in dichloromethane (250 mL) and extract with 2 N NaOH (200 mL), water (100 mL) and 1 N HCl (2×200 mL). Wash the organic layer with saturated aqueous saturated sodium chloride (100 mL), dry over MgSO4, filter and concentrate. Dry load the material onto silica (100 g) and chromatograph on silica using dichloromethane as eluent to yield the product (13.00 g, 78.1%). MS(ES), m/z 356/358 (M+1).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:28])[CH:9]([NH:20]C(=O)OC(C)(C)C)[CH2:10][C:11]2[S:15][C:14]([C:16]([F:19])([F:18])[F:17])=[N:13][CH:12]=2)=[CH:4][CH:3]=1.Cl.C(=O)([O-])[O-].[K+].[K+]>CO.O>[NH2:20][CH:9]([CH2:10][C:11]1[S:15][C:14]([C:16]([F:19])([F:18])[F:17])=[N:13][CH:12]=1)[CH:8]([C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)[OH:28]
Reactant: CC(C)(C)OC(=O)NC(Cc1cnc(C(F)(F)F)s1)C(O)c1ccc(F)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CO
Product: NC(Cc1cnc(C(F)(F)F)s1)C(O)c1ccc(F)cc1

Procedure:
A solution of tert-butyl N-[(1RS,2SR)-2-(4-fluorophenyl)-2-hydroxy-1-[[2-(trifluoromethyl)-1,3-thiazol-5-yl]methyl]ethyl]carbamate (0.711 g, 1.691 mmol) and conc. hydrochloric acid (0.5 ml) in methanol (5 ml) was heated under reflux for 10 min. The reaction solution was diluted with water, alkalified with potassium carbonate and extracted twice with ethyl acetate. The collected organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The residue was purified by silica gel (APS type) column chromatography (ethyl acetate) to give the objective substance.
Reaction SMILES: Cl[C:2]1[C:6]2[CH:7]=[C:8]([CH:20]=[O:21])[C:9]([N:12]3[CH2:17][C@H:16]([CH3:18])[O:15][C@H:14]([CH3:19])[CH2:13]3)=[C:10]([F:11])[C:5]=2[O:4][N:3]=1.C1CCN2C(=NCCC2)CC1.[NH:33]1[CH:37]=[N:36][CH:35]=[N:34]1>C(#N)C>[CH3:19][C@H:14]1[O:15][C@@H:16]([CH3:18])[CH2:17][N:12]([C:9]2[C:8]([CH:20]=[O:21])=[CH:7][C:6]3[C:2]([N:33]4[CH:37]=[N:36][CH:35]=[N:34]4)=[N:3][O:4][C:5]=3[C:10]=2[F:11])[CH2:13]1
Reactant: C[C@@H]1CN(c2c(C=O)cc3c(Cl)noc3c2F)C[C@H](C)O1
Reactant: c1nc[nH]n1
Solvent: C1CCC2=NCCCN2CC1
Solvent: CC#N
Product: C[C@@H]1CN(c2c(C=O)cc3c(-n4cncn4)noc3c2F)C[C@H](C)O1
Temperature: 100 °C
Reaction time: 12 h

Procedure:
To a solution of 3-chloro-6-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-7-fluoro-1,2-benzoxazole-5-carbaldehyde (Intermediate 534, 0.2 g, 0.68 mmol) in acetonitrile was added DBU (0.19 mL, 1.28 mmol) followed by 1,2,4-triazole (0.053 g, 0.76 mmol), and the mixture was stirred at 100° C. for 12 hours. The reaction mixture was concentrated, the residue was purified by silica gel column chromatography using EtOAc in pet. ether to give title product.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([S:10](Cl)(=[O:12])=[O:11])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].[CH3:14][NH2:15]>C1COCC1.[Cl-].[Na+].C(OCC)(=O)C>[CH3:14][NH:15][S:10]([C:6]1[CH:7]=[CH:8][CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=1)(=[O:12])=[O:11]
Reactant: CN
Reactant: O=[N+]([O-])c1cccc(S(=O)(=O)Cl)c1
Agent: [Cl-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CNS(=O)(=O)c1cccc([N+](=O)[O-])c1

Procedure:
To a solution of 4.42 g (20.0 mmol) of 3-nitrobenzenesulfonyl chloride in 150 mL of dry THF was added 25.0 mL (50.0 mmol) of methylamine as a 2 M solution in THF under ice cooling and stirring. The resulting cloudy solution was stirred overnight at ambient temperature. After this time period, the reaction mixture was diluted with 150 mL of saturated sodium chloride solution and 50 mL of ethyl acetate, then transferred to a 500 mL separatory funnel, mixed thoroughly, and the organic phase was separated. The aqueous phase was extracted twice with 50 mL of ethyl acetate. The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting residue was purified by recrytallization from EtOH. The yield of the title compound was 97% (4.20 g, 19.48 mmol).
Reaction SMILES: [C:1]([O:5][C:6](=[O:18])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][C:10]=1[C:16]#[CH:17])([CH3:4])([CH3:3])[CH3:2].Br[C:20]1[CH:21]=[C:22]([S:27]([N:30]([CH2:32][CH2:33][O:34][CH3:35])[CH3:31])(=[O:29])=[O:28])[CH:23]=[CH:24][C:25]=1[CH3:26]>>[C:1]([O:5][C:6](=[O:18])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][C:10]=1[C:16]#[C:17][C:20]1[CH:21]=[C:22]([S:27]([N:30]([CH2:32][CH2:33][O:34][CH3:35])[CH3:31])(=[O:29])=[O:28])[CH:23]=[CH:24][C:25]=1[CH3:26])([CH3:4])([CH3:3])[CH3:2]
Reactant: C#Cc1cc(Cl)ccc1OCC(=O)OC(C)(C)C
Reactant: COCCN(C)S(=O)(=O)c1ccc(C)c(Br)c1
Product: COCCN(C)S(=O)(=O)c1ccc(C)c(C#Cc2cc(Cl)ccc2OCC(=O)OC(C)(C)C)c1

Procedure:
Following the general method as outlined in Intermediate 20, starting from (4-chloro-2-ethynyl-phenoxy)-acetic acid tert-butyl ester (Intermediate 3) and 3-bromo-N-(2-methoxy-ethyl)-4,N-dimethyl-benzenesulfonamide (Intermediate 141), the title compound was obtained as a yellow sticky solid after purification by flash column chromatography (silica), eluting with cyclohexane containing increasing amounts of EtOAc.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[N:14]([CH:15]([CH3:19])[C:16]([OH:18])=O)[C:13](=[O:20])[N:12]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=3)[C:11]3[CH2:31][CH2:32][C:33](=[O:34])[C:10]2=3)=[CH:5][CH:4]=1)#[N:2].C(N(CC)CC)C.F[B-](F)(F)F.C[N+](C)=C(N(C)C)ON1C2C=CC=CC=2N=N1.[CH2:64]([CH2:66][NH2:67])[OH:65]>CN(C)C=O>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[N:14]([CH:15]([CH3:19])[C:16]([NH:67][CH2:66][CH2:64][OH:65])=[O:18])[C:13](=[O:20])[N:12]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:28])([F:30])[F:29])[CH:22]=3)[C:11]3[CH2:31][CH2:32][C:33](=[O:34])[C:10]2=3)=[CH:5][CH:4]=1)#[N:2]
Reactant: NCCO
Reactant: CC(C(=O)O)N1C(=O)N(c2cccc(C(F)(F)F)c2)C2=C(C(=O)CC2)C1c1ccc(C#N)cc1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CC(C(=O)NCCO)N1C(=O)N(c2cccc(C(F)(F)F)c2)C2=C(C(=O)CC2)C1c1ccc(C#N)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of 2-(4-(4-cyanophenyl)-2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-6,7-dihydro-1H-cyclopenta[d]pyrimidin-3(2H,4H,5H)-yl)propanoic acid (intermediate 28, 40 mg, 85 μmol) and triethylamine (45 μL, 0.32 mmol) in N,N-dimethylformamide (1.5 mL) is treated with N,N,N′,N′-tetramethyl-O-(benzotriazol-1-yl)uronium tetrafluoroborate (27 mg, 85 μmol) and stirred at room temperature for 15 min Ethanolamine (12 μL, 0.21 mmol) is added and the mixture is stirred at room temperature for 1 h. The mixture is diluted with N,N-dimethylformamide and purified by reversed phase HPLC (Waters SunFire™-C18, gradient of acetonitrile in water, 0.1% TFA). Yield: 37 mg; ESI mass spectrum [M+H]+=513; Retention time HPLC: 0.81 min (Z018_S04).
Reaction SMILES: [NH2:1]/[C:2](/[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[C:3]1\[C:4](=[O:12])[C:5]2[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=2[S:7]\1.BrN1C(=[O:25])CCC1=O>CO.O>[NH2:1]/[C:2](/[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[C:3]1\[C:4](=[O:12])[C:5]2[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=2[S:7]\1=[O:25]
Reactant: O=C1CCC(=O)N1Br
Reactant: N/C(=C1/Sc2ccccc2C1=O)c1ccccc1
Solvent: O
Solvent: CO
Product: N/C(=C1\C(=O)c2ccccc2S1=O)c1ccccc1
Temperature: 25 °C
Reaction time: 15 h

Procedure:
1.18 gm (4.66 mmols) of (E)-2-[(amino)phenylmethylene]-benzo[b]thiophen-3(2H)-one were dissolved in 50 ml of methanol and mixed with 0.9 gm (4.94 mmols) of N-bromo-succinimide. The mixture was stirred at room temperature for 15 hours, diluted with 500 ml of hot water (60° C.), and decanted off the residue which crystallized. After recrystallization from ethanol, 0.83 gm (66% of theory) of pale yellow crystals were obtained, m.p. 245°-247° C. (decomposition).
Reaction SMILES: [CH3:1][NH:2][C:3]1[CH:8]=[CH:7][N:6]=[CH:5][C:4]=1[S:9]([NH2:12])(=[O:11])=[O:10].[CH:13](=O)[CH2:14][CH3:15].Cl>C(O)(C)C.C(OCC)(=O)C>[CH2:14]([CH:13]1[N:2]([CH3:1])[C:3]2[CH:8]=[CH:7][N:6]=[CH:5][C:4]=2[S:9](=[O:11])(=[O:10])[NH:12]1)[CH3:15]
Reactant: CNc1ccncc1S(N)(=O)=O
Reactant: CCC=O
Agent: Cl
Solvent: CC(C)O
Solvent: CCOC(C)=O
Product: CCC1NS(=O)(=O)c2cnccc2N1C
Temperature: 50 °C

Procedure:
A solution of 0.5 g of 4-methylaminopyridine-3- sulfonamide (Preparation 12) and 0.9 cm3 of propionaldehyde in 5 cm3 of isopropanol, to which 3 drops of a saturated solution of hydrochloric acid in ethyl acetate have been added, is heated for 3 hours at 50° C. The solvent is then removed under partial vacuum and the residue obtained is recrystallized several times from a chloroform/petroleum ether (1/3) mixture.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([Cl:12])[C:3]=1[N:13]1[C:17]([NH:18][C:19](=[O:21])[CH3:20])=[C:16]2[CH2:22][S:23][CH2:24][C:15]2=[N:14]1.C1C=C(Cl)C=C(C(OO)=[O:33])C=1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:10])([F:11])[F:9])[CH:5]=[C:4]([Cl:12])[C:3]=1[N:13]1[C:17]([NH:18][C:19](=[O:21])[CH3:20])=[C:16]2[CH2:22][S:23](=[O:33])[CH2:24][C:15]2=[N:14]1
Reactant: CC(=O)Nc1c2c(nn1-c1c(Cl)cc(C(F)(F)F)cc1Cl)CSC2
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CC(=O)Nc1c2c(nn1-c1c(Cl)cc(C(F)(F)F)cc1Cl)CS(=O)C2
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of acetamide (2) (145 mg, 0.37 mmol) in CH2Cl2 (5 mL), m-CPBA (500 mg) was added. The reaction mixture was stirred at room temperature for 30 min. and aq. NaHCO3 (10 mL) was added and the organic layer separated and washed with water (2×10 mL), dried (Na2SO4) and concentrated to obtain the title compound as a white solid. (35%); 1H NMR (CDCl3) δ 7.8 (2H, m), 4.33 and 4.46 (2H each, m), 2.12 (3H, s); MS (M+) 428.
Reaction SMILES: [Cl-].C([Al+]CC)C.[F:7][C:8]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:9]=1[NH2:10].[C:16]1(=[O:20])[O:19][CH2:18][CH2:17]1.Cl>ClCCl>[F:7][C:8]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:9]=1[NH:10][C:18](=[O:19])[CH2:17][CH2:16][OH:20]
Reactant: O=C1CCO1
Reactant: Nc1cc(F)ccc1F
Agent: CC[Al+]CC
Agent: Cl
Agent: [Cl-]
Solvent: ClCCl
Product: O=C(CCO)Nc1cc(F)ccc1F
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
4 ml of a solution of diethylaluminum chloride (1M in hexane) is added dropwise at 0° C. to a solution of 0.519 g of 2,5-difluoroaniline in 10 ml of anhydrous dichloromethane. The reaction solution is stirred at room temperature for a further 20 minutes and subsequently cooled back to 0° C. A solution of 0.147 g of propiolactone in 8 ml of dichloromethane is added dropwise and the reaction mixture is stirred at room temperature over a further 2 hours. The reaction mixture is subsequently hydrolysed at 0° C. with 30 ml of 0.2M HCl and the phases are separated. The aqueous phase is re-extracted with 2×50 ml of dichloromethane and the combined organic phases are washed with 50 ml of water, dried over sodium sulphate and concentrated by evaporation. The title compound is obtained as a beige solid from the residue by means of flash chromatography (SiO2 60F). Rf=0.15 (1:1 EtOAc-heptane); Rt=2.62.
Reaction SMILES: [N:1]1[C:2]([C:12](OCC)=[O:13])=[CH:3][N:4]2[CH2:9][CH2:8][CH2:7][S:6](=[O:11])(=[O:10])[C:5]=12.[H-].C([Al+]CC(C)C)C(C)C.O>ClCCl>[N:1]1[C:2]([CH:12]=[O:13])=[CH:3][N:4]2[CH2:9][CH2:8][CH2:7][S:6](=[O:10])(=[O:11])[C:5]=12
Reactant: CCOC(=O)c1cn2c(n1)S(=O)(=O)CCC2
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: O
Solvent: ClCCl
Product: O=Cc1cn2c(n1)S(=O)(=O)CCC2
Temperature: -70 °C

Procedure:
Ethyl 6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazine-2-carboxylate-8,8-dioxide (200 mg, 0.82 mmol) was dissolved in dry dichloromethane (minimum volume) under argon and cooled to -70° C. Diisobutylaluminium hydride (1.5M in toluene, 1 ml, 1.5 mmol) was added at <-70° C. and the mixture stirred at -70° C. until thin layer chromatography and infra-red spectroscopy showed little or no starting material remaining. Water (5 ml) was added carefully, cooling removed and the mixture stirred at ambient temperature for 1 h. Celite was added to the mixture and the resulting mixture filtered through a Celite pad. The Celite pad was washed with dichloromethane and water and the filtrate and washings combined and evaporated to dryness under reduced pressure. The residue was re-evaporated with ethanol (2×), triturated under diethyl ether and the product collected by filtration, washed with diethyl ether and dried in air (274 mg, 30%) (Found: M+ 200.0256. C7H8N2O3S requires M 200.0253); nmax (Nujol) 1678, 1316, 1161 and 1191 cm-1 ; dH [250 MHz; (CD3)2SO] 2.50-2.57 (2H, m), 3.81-3.85 (2H, m), 4.31 (2H, t, J 6 Hz), 8.27 (1H, s), 9.80 (1H, s).
Reaction SMILES: N#N.[CH3:3][C:4]1([C:9]2[N:10]=[C:11]([CH2:14][N:15]3[CH:19]=[CH:18][C:17]([N+:20]([O-])=O)=[N:16]3)[S:12][CH:13]=2)[O:8][CH2:7][CH2:6][O:5]1.[NH4+].[Cl-]>CCO.O.[Fe]>[CH3:3][C:4]1([C:9]2[N:10]=[C:11]([CH2:14][N:15]3[CH:19]=[CH:18][C:17]([NH2:20])=[N:16]3)[S:12][CH:13]=2)[O:8][CH2:7][CH2:6][O:5]1
Reactant: CC1(c2csc(Cn3ccc([N+](=O)[O-])n3)n2)OCCO1
Agent: [Fe]
Agent: N#N
Agent: [Cl-]
Solvent: CCO
Solvent: O
Product: CC1(c2csc(Cn3ccc(N)n3)n2)OCCO1
Temperature: 75 °C
Reaction time: 1 h

Procedure:
In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a 0.1M solution of 4-(2-methyl-[1,3]dioxolan-2-yl)-2-(3-nitro-pyrazol-1-ylmethyl)-thiazole (320 mg, 1.08 mmol), iron powder (183 mg, 3.24 mmol) and NH4Cl (292 mg, 5.40 mmol) in a mixture of EtOH (2.0 mL) and water (1.0 mL) was stirred at 75° C. for 60 min. The reaction mixture was filtered while hot and concentrated under reduced pressure. CH2Cl2 (10 mL) was added followed by 1N NaOH (10 mL). The aq. layer was extracted with CH2Cl2 (2×10 mL) and the combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure to give the title compound as a brown oil. LC-MS-conditions 01: tR=0.54 min; [M+H]+=266.97.
Reaction SMILES: C[CH2:2][N:3]([C:6]([S:8][S:9][C:10]([N:12]([CH2:15]C)[CH2:13]C)=[S:11])=[S:7])[CH2:4]C.C1C=C2N=C(SSC3SC4C(=CC=CC=4)N=3)SC2=CC=1>>[CH3:15][N:12]([C:10]([S:9][S:8][C:6]([N:3]([CH3:4])[CH3:2])=[S:7])=[S:11])[CH3:13]
Reactant: CCN(CC)C(=S)SSC(=S)N(CC)CC
Agent: c1ccc2sc(SSc3nc4ccccc4s3)nc2c1
Product: CN(C)C(=S)SSC(=S)N(C)C

Procedure:
Nocceler DM: dibenzothiazyl disulfide (vulcanization accelerator) manufactured by Ohuchi Shinko Kagaku Kogyo Co., Ltd.
Reaction SMILES: C(O)(=O)C.Cl.[CH3:6][O:7][C:8]([N:10]1[CH2:15][CH2:14][CH2:13][CH:12]([NH:16]C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH2:11]1)=[O:9]>C(#N)C>[CH3:6][O:7][C:8]([N:10]1[CH2:15][CH2:14][CH2:13][CH:12]([NH2:16])[CH2:11]1)=[O:9]
Reactant: COC(=O)N1CCCC(NC(c2ccccc2)(c2ccccc2)c2ccccc2)C1
Agent: Cl
Solvent: CC#N
Solvent: CC(=O)O
Product: COC(=O)N1CCCC(N)C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 95.6 %

Procedure:
Add acetic acid saturated with HCl(g) (100 mL, ˜3N in HCl) to 3-(trityl-amino)-piperidine-1-carboxylic acid methyl ester (6.51 g, 16.2 mmol). Stir the solution vigorously at room temperature for 2 hours. Concentrate the reaction, follow this by addition of acetonitrile and concentration to assist in the removal of acetic acid (×2). Partition the resulting material between 1N HCl and ethyl acetate, separate the layers, extract the organic layer with 1N HCl. Basify the combined aqueous layers with 5N sodium hydroxide, extract with 20% isopropanol/chloroform (×3). Dry the combined organic layers over magnesium sulfate and concentrate to give 2.45 g of the title compound as a white solid, 95% yield. 1H NMR: consistent with structure. MS (ion spray) 158 (M+).
Reaction SMILES: [CH2:1]=[C:2]1[O:6][C:4](=[O:5])[CH2:3]1.[Br:7][C:8]1[CH:14]=[CH:13][C:11]([NH2:12])=[C:10]([N+:15]([O-:17])=[O:16])[CH:9]=1.C(N(CC)CC)C>C1(C)C=CC=CC=1>[Br:7][C:8]1[CH:14]=[CH:13][C:11]([NH:12][C:4](=[O:5])[CH2:3][C:2](=[O:6])[CH3:1])=[C:10]([N+:15]([O-:17])=[O:16])[CH:9]=1
Reactant: Nc1ccc(Br)cc1[N+](=O)[O-]
Reactant: C=C1CC(=O)O1
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: CC(=O)CC(=O)Nc1ccc(Br)cc1[N+](=O)[O-]
Reaction time: 0.5 h
Yield: 73.6 %

Procedure:
A solution of diketene (0.32 ml, 4.15 mmol) in toluene (2 ml) was added to an 80° C. solution of 4-bromo-2-nitroaniline (900 mg, 4.15 mmol) in toluene (7 ml) and the solution was heated at reflux for 5 h. Triethylamine (0.58 ml, 4.15 mmol) in toluene (2 ml) was added and refluxing was continued for 30 min. The cooled solution was concentrated in vacuo and the crude product purified by column chromatography on silica gel eluting with 2:1 hexane/EtOAc to give the title compound as a yellow solid (920 mg, 74%).
Reaction SMILES: Br[CH:2]([CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[CH:8][CH:7]=1)[CH:3]=O.[NH2:14][C:15]([NH2:17])=[S:16]>CCO>[CH3:13][O:12][C:9]1[CH:10]=[CH:11][C:6]([CH2:5][C:2]2[S:16][C:15]([NH2:17])=[N:14][CH:3]=2)=[CH:7][CH:8]=1
Reactant: COc1ccc(CC(Br)C=O)cc1
Reactant: NC(N)=S
Solvent: CCO
Product: COc1ccc(Cc2cnc(N)s2)cc1
Yield: 75.2 %

Procedure:
A mixture of 2-bromo-3-(4-methoxy-phenyl)-propionaldehyde (9c) and thiourea (0.84 g, 11.0 mmol) in 95% EtOH (20.0 mL) was heated at reflux for 60 minutes. The solution was concentrated under reduced pressure and the residue was re-dissolved in ethyl acetate. The solution was washed with saturated aqueous NaHCO3, dried over MgSO4(s), and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel to give 5-(4-methoxy-benzyl)-thiazol-2-ylamine (9d, 1.01 g, 4.54 mmol) as yellow solids in 75.2% yield.
Reaction SMILES: [NH2:1][C:2]1[C:15]2[C:16]3=[C:17]4[C:12](=[CH:13][CH:14]=2)[CH:11]=[CH:10][CH:9]=[C:8]4[CH:7]=[CH:6][C:5]3=[CH:4][CH:3]=1.[Cl:18][S:19]([OH:22])(=O)=[O:20]>>[NH2:1][C:2]1[CH:3]=[C:4]([S:19]([Cl:18])(=[O:22])=[O:20])[C:5]2[CH:6]=[CH:7][C:8]3[C:17]4[C:16]=2[C:15]=1[CH:14]=[CH:13][C:12]=4[C:11]([S:19]([Cl:18])(=[O:22])=[O:20])=[CH:10][C:9]=3[S:19]([Cl:18])(=[O:22])=[O:20]
Reactant: Nc1ccc2ccc3cccc4ccc1c2c34
Reactant: O=S(=O)(O)Cl
Product: Nc1cc(S(=O)(=O)Cl)c2ccc3c(S(=O)(=O)Cl)cc(S(=O)(=O)Cl)c4ccc1c2c43
Temperature: 0 °C
Yield: 69 %

Procedure:
Dyes 2a, 2d and 3 were obtained from Eastman, and the following dyes were prepared as described previously: 2c (8); 2g (9). The syntheses of 2e, 2f, 2h, 2I and 2j were modeled after the sulfonation procedures described in (10). Thus, for 2f, a solution of finely powdered 1-aminopyrene (869 mg, 4 mmol) in 10 ml chlorosulfonic acid was stirred under argon atmosphere for 10 hours at room temperature. The solution was poured on 30 g of crushed ice and the crude product was collected by filtration, washed with 20 mL cold water and dried under argon to give 1.4 g of 8-amino-1,3,6-pyrenetrisulfonylchloride (69%). Hydrolysis of this chloride in basic water (NaOH, pH 8) gave a solution of 2f (8-amino-1,3,6-pyrenetrisulfonate). Analogous procedures were used to prepare 2g-2j, except replacing the 1-aminopyrene with the appropriate substituted pyrene starting material.
Reaction SMILES: O1CCOCC1.[CH2:7]([S:9]([N:12](S(CC)(=O)=O)[C:13]1[C:14]([Cl:33])=[CH:15][C:16]([Cl:32])=[C:17]([N:19]2[C:24](=[O:25])[CH:23]=[C:22]([C:26]([F:29])([F:28])[F:27])[N:21]([CH3:30])[C:20]2=[O:31])[CH:18]=1)(=[O:11])=[O:10])[CH3:8].[OH-].[Na+].Cl>O>[Cl:32][C:16]1[CH:15]=[C:14]([Cl:33])[C:13]([NH:12][S:9]([CH2:7][CH3:8])(=[O:10])=[O:11])=[CH:18][C:17]=1[N:19]1[C:24](=[O:25])[CH:23]=[C:22]([C:26]([F:28])([F:27])[F:29])[N:21]([CH3:30])[C:20]1=[O:31]
Reactant: CCS(=O)(=O)N(c1cc(-n2c(=O)cc(C(F)(F)F)n(C)c2=O)c(Cl)cc1Cl)S(=O)(=O)CC
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: CCS(=O)(=O)Nc1cc(-n2c(=O)cc(C(F)(F)F)n(C)c2=O)c(Cl)cc1Cl
Reaction time: 4 h
Yield: 69.4 %

Procedure:
To 8 ml of dioxane, 0.80 g of the obtained 3-[5-bis (ethanesulfonyl)amino-2,4-dichlorophenyl]-1-methyl-6-trifluoromethyl-2,4 (1H,3H)-pyrimidinedione was dissolved and 0.12 g of sodium hydroxide (93%) and 2 ml of water were added to the obtained solution. After the mixed solution was stirred for 4 hours, a dilute hydrochloric acid was added thereto in order to acidify the resultant solution. The reaction mixture was extracted with ethyl acetate. The obtained extract of the ethyl acetate layer was washed with water and a saturated sodium chloride aqueous solution, and dried over anhydrous sodium sulfate. Then ethyl acetate was distilled off to obtain a crude product. The obtained product was purified by preparative thin-layer chromatography (developing solvent: hexane/ethyl acetate=3/2) to obtain 0.46 g of the objective product as white crystals.
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:19]=[C:18]([CH2:20]Cl)[C:17]([C:22](OCC)=[O:23])=[CH:16][N:15]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:27]1([NH2:33])[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>C(O)CC(C)C>[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:15]=[CH:16][C:17]3[C:22](=[O:23])[N:33]([CH:27]4[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]4)[CH2:20][C:18]=3[N:19]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NC1CCCCC1
Reactant: CCOC(=O)c1cnc(N2CCN(Cc3ccccc3)CC2)nc1CCl
Solvent: CC(C)CCO
Product: O=C1c2cnc(N3CCN(Cc4ccccc4)CC3)nc2CN1C1CCCCC1
Yield: 63.1 %

Procedure:
Dissolved in 40 ml of isoamyl alcohol was 2.0 g (5.34 mmol) of ethyl 2(4-benzylpiperazino)-4-chloromethylpyrimidine-5-carboxylate, followed by an addition of 10.5 g (107 mmol) of cyclohexylamine. The resultant mixture was refluxed for 6 hours. After completion of the reaction, the solvent was distilled off and the residue was washed with ether to obtain 1.32 g of the above-identified compound as crystals (yield: 63%).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[C:7]([O:12][CH:13]([CH3:15])[CH3:14])[CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([CH3:16])[N:3]=1.[C:17]1(B(O)O)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C([O-])([O-])=O.[Na+].[Na+].CCO>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC=CC=1>[CH:13]([O:12][C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:6]=1[N:5]=[C:4]([CH3:16])[N:3]=[C:2]2[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)([CH3:15])[CH3:14]
Reactant: OB(O)c1ccccc1
Reactant: Cc1nc(Cl)c2cccc(OC(C)C)c2n1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: c1ccccc1
Solvent: CCO
Product: Cc1nc(-c2ccccc2)c2cccc(OC(C)C)c2n1

Procedure:
To a stirred mixture of 4-chloro-8-isopropoxy-2-methyl-quinazoline (35) (0.58 mmol), phenylboronic acid (0.62 mmol), 2 N Na2CO3 (7.2 mL), EtOH (1.2 mL) and benzene (6 mL) was added, under a blanket of argon, Pd(PPh3)4 (20 mg). The mixture was stirred under reflux for 16 h, cooled, and concentrated. Subsequent column chromatography (ethyl acetate/hexane) provided 8-isopropoxy-2-methyl-4-phenyl-quinazoline (36) as a solid.