Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CN(C)C1CC2C(=CC=CC=2)C1.[CH3:13][S:14](Cl)(=[O:16])=[O:15].[CH2:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:20][CH:19]1[OH:27].CCN(C(C)C)C(C)C>C(Cl)Cl>[CH3:13][S:14]([O:27][CH:19]1[CH2:20][C:21]2[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:18]1)(=[O:16])=[O:15]
Reactant: CS(=O)(=O)Cl
Reactant: OC1Cc2ccccc2C1
Agent: CN(C)C1Cc2ccccc2C1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CS(=O)(=O)OC1Cc2ccccc2C1
Temperature: 20 °C
Reaction time: 16 h
Yield: 98.5 %

Procedure:
N,N-Dimethyl-2-indanamine (107). Methanesulfonyl chloride (11.5 mL, 149 mmol) was added dropwise to a stirred solution of 2-indanol (106) (20 g, 149 mmol) and iPr2NEt (28.6 mL, 164 mmol) in DCM (300 mL) at 0° C., and the solution stirred at 20° C. for 16 h. The solution was washed with 1 M HCl (80 mL), aqueous saturated NaHCO3 solution (80 mL) and brine (100 mL), dried and the solvent evaporated. The residue was recrystallised from EtOH to give 2,3-dihydro-1H-inden-2-yl methanesulfonate (31.14 g, 98%) as a white solid. Aqueous HNMe2 (40%, 180 mL, 1.42 mol) was added slowly to a stirred solution of mesylate (30.25 g, 143 mmol) in DMF (200 mL) and the solution stirred at 20° C. for 16 h. The solution was partitioned between EtOAc (400 mL) and water (800 mL) and the organic fraction washed with water (3×80 mL), brine (100 mL), dried and the solvent evaporated. The residue was suspended in 1 M HCl (400 mL) and washed with DCM (3×80 mL). The pH of the aqueous fraction was adjusted to 14 with NaOH, the mixture chilled at 5° C. for 8 h and the precipitate filtered. The precipitate was washed with water (50 mL) and dried to give amine 107 (21.54 g, 93%) as a light gray solid: 1H NMR δ 7.10-7.17 (m, 4H, Harom), 3.01-3.08 (m, 3H, H-2, CH2), 2.82-2.91 (m, 2H, CH2), 2.31 [s, 6H, N(CH3)2].
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10]([NH:13][C:14](=[O:44])[CH:15]([C:35]2[CH:40]=[CH:39][C:38]3[O:41][CH2:42][O:43][C:37]=3[CH:36]=2)[O:16][C:17]2[CH:22]=[CH:21][C:20]([CH2:23][O:24][Si](C(C)(C)C)(C)C)=[CH:19][C:18]=2[CH2:32][CH2:33][CH3:34])(=[O:12])=[O:11])=[CH:6][CH:5]=1)([CH3:3])[CH3:2].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([S:10]([NH:13][C:14](=[O:44])[CH:15]([C:35]2[CH:40]=[CH:39][C:38]3[O:41][CH2:42][O:43][C:37]=3[CH:36]=2)[O:16][C:17]2[CH:22]=[CH:21][C:20]([CH2:23][OH:24])=[CH:19][C:18]=2[CH2:32][CH2:33][CH3:34])(=[O:11])=[O:12])=[CH:8][CH:9]=1)([CH3:2])[CH3:3]
Reactant: CCCc1cc(CO[Si](C)(C)C(C)(C)C)ccc1OC(C(=O)NS(=O)(=O)c1ccc(C(C)C)cc1)c1ccc2c(c1)OCO2
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: CCCc1cc(CO)ccc1OC(C(=O)NS(=O)(=O)c1ccc(C(C)C)cc1)c1ccc2c(c1)OCO2
Temperature: 25 °C
Yield: 26.2 %

Procedure:
To a solution of 3.20 g (5.01 mmol) of the product of Step D dissolved in 5.0 mL of anhydrous THF was added 5.06 mL (5.06 mmol) of a 1.0 M solution of tetrabutylammonium fluoride in THF and the reaction mixture was stirred at room temperature under a nitrogen atmosphere. After 2.5 hours 1.0 mL additional tetrabutylammonium fluoride in THF was added and the reaction mixture was stirred for an additional 14 hours. The reaction mixture was then concentrated in vacuo and applied to a silica gel flash chromatography column and eluted with 60% EtOAc-hexane. Combination of the purified fractions and drying in vacuo afforded 0.691 g (26%) of the title compound as an amorphous powder.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.[C:9]([O:13][CH2:14][CH3:15])(=[O:12])[CH:10]=[CH2:11]>CO>[Br:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[O:8][CH2:11][CH2:10][C:9]([O:13][CH2:14][CH3:15])=[O:12]
Reactant: Oc1cccc(Br)c1
Reactant: C=CC(=O)OCC
Solvent: CO
Product: CCOC(=O)CCOc1cccc(Br)c1
Yield: 52.9 %

Procedure:
A mixture of 20 g of 3-bromophenol, 92 g of ethyl acrylate and 1.8 ml of Triton B (35% in methanol) was boiled at reflux overnight. After distilling off the excess acrylate at normal pressure, the residue was distilled in a high vacuum. There were obtained 16.7 g of ethyl 3-(m-bromophenoxy)propionate as a colorless oil, boiling point 107°-110° C./67 Pa.
Reaction SMILES: Cl.[F:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]=1[O:11][CH2:10][CH2:9][C@H:8]2[NH2:13].C(=O)([O-])[O-].[K+].[K+].[F:20][C:21]1[CH:26]=[CH:25][C:24]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[C:23]([NH:35][C:36]2[N:41]=[C:40](SC#N)[C:39]([N+:45]([O-:47])=[O:46])=[CH:38][N:37]=2)[CH:22]=1>CS(C)=O.C(#N)C>[F:20][C:21]1[CH:26]=[CH:25][C:24]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[C:23]([NH:35][C:36]2[N:37]=[C:38]([NH:13][C@H:8]3[C:7]4[C:12](=[C:3]([F:2])[CH:4]=[CH:5][CH:6]=4)[O:11][CH2:10][CH2:9]3)[C:39]([N+:45]([O-:47])=[O:46])=[CH:40][N:41]=2)[CH:22]=1
Reactant: CC(C)(C)OC(=O)Nc1ccc(F)cc1Nc1ncc([N+](=O)[O-])c(SC#N)n1
Reactant: N[C@@H]1CCOc2c(F)cccc21
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: CC#N
Product: CC(C)(C)OC(=O)Nc1ccc(F)cc1Nc1ncc([N+](=O)[O-])c(N[C@@H]2CCOc3c(F)cccc32)n1
Temperature: 25 °C
Reaction time: 15 h
Yield: 83 %

Procedure:
A solution of the (R)-8-fluorochroman-4-amine hydrochloride (104 mg) in DMSO (2 mL) and potassium carbonate (141 mg) were added to a stirred solution of tert-butyl 4-fluoro-2-(5-nitro-4-thiocyanatopyrimidin-2-ylamino)phenylcarbamate (140 mg) in ACN (10 mL). The mixture was stirred for 15 hr at room temperature then partitioned between brine and EtOAc and separated. The aq. layer was washed with additional EtOAc, the combined organics were evaporated and purified via column chromatography, elution with 20-30% EtOAc/H gave the titled product in 83% yield. 1H-NMR (300 MHz, CDCl3) δ 9.1 (s, 1H), 8.7 (m, 1H), 8.2 (br s, 1H), 7.7 (m, 1H), 7.3 (m, 1H), 7.3-6.8 (m, 4H), 6.5 (s, 1H), 5.5 (br s, 1H), 4.4 (m 2H), 2.4 (m, 1H), 2.2 (m, 1H), 1.5 (s, 9H); MH+=515, 459 (-tBu).
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[C:3]1[CH:8]=[CH:7][C:6]([NH:9][NH2:10])=[CH:5][CH:4]=1.Cl.[C:14]([OH:18])(=[O:17])[CH:15]=O.C(OCC)(=O)C>O>[F:1][C:2]([F:11])([F:12])[C:3]1[CH:4]=[CH:5][C:6]([NH:9][N:10]=[CH:15][C:14]([OH:18])=[O:17])=[CH:7][CH:8]=1
Reactant: O=CC(=O)O
Reactant: NNc1ccc(C(F)(F)F)cc1
Agent: Cl
Solvent: CCOC(C)=O
Solvent: O
Product: O=C(O)C=NNc1ccc(C(F)(F)F)cc1
Temperature: 25 °C
Reaction time: 5 h
Yield: 88 %

Procedure:
4-Trifluoromethylphenyl hydrazine (4.1 g, 23 mmol) was gradually added to a solution of concentrated hydrochloric acid (5 ml) in water (120 ml). 40% aqueous solution (4.3 g, 23 mmol) of glyoxylic acid was gradually added, and stirred at room temperature for 5 hours. After leaving it overnight, the mixture was extracted with ethyl acetate. The organic phase was washed with a saturated brine, and dried on anhydrous sodium sulfate. The solvent was distilled off, and the resulting crystals were washed with hexane and a little amount of ethyl acetate to obtain (4-trifluoromethylphenyl hydrazono) acetic acid (4.7 g, 20 mmol, 88%).
Reaction SMILES: [F:1][C:2]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][C:3]=1[NH2:4].[CH3:10][C:11]1[CH:16]=[CH:15][C:14]([S:17](Cl)(=[O:19])=[O:18])=[CH:13][CH:12]=1>N1C=CC=CC=1>[CH3:10][C:11]1[CH:16]=[CH:15][C:14]([S:17]([NH:4][C:3]2[CH:5]=[C:6]([F:9])[CH:7]=[CH:8][C:2]=2[F:1])(=[O:19])=[O:18])=[CH:13][CH:12]=1
Reactant: Nc1cc(F)ccc1F
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)Nc2cc(F)ccc2F)cc1

Procedure:
Following Intermediate Method 1, a substituted aniline, for example 2,5-difluoroaniline, may be reacted with 4-methylphenylsulfonyl chloride in pyridine to form N-(4-methylphenylsulfonyl)-2,5-difluoroaniline, (V). Nitration of (V) with sodium nitrite in nitric acid, acetic acid and water produces N-(4-methylphenylsulfonyl)-2,5-difluoro-4-nitroaniline, (VI). The reaction of (VI) with aqueous sulfuric acid yields 2,5-difluoro-4-nitroaniline, (VII). Subsequent reaction of (VII) with acetic anhydride and a small amount of dimethylaminopyridine (DMAP) in methylene chloride produces N-(2,5-difluoro-4-nitrophenyl)-acetamide (VIII). Treatment of (VIII) with a borane/dimethyl sulfide complex in tetrahydrofuran yields N-ethyl-2,5-difluoro-4-nitroaniline, (IX). Repeating the previous two steps, the reaction of (IX) first with acetic anhydride (to produce N-(2,5-difluoro-4-nitrophenyl)-acetamide, (X)) followed by treatment with a borane/dimethyl sulfide complex yields N,N-diethyl-2,5-difluoro-4-nitroaniline, (XI). Hydrogenation of (XI) with platinum oxide in ethanol produces the desired 2,5-difluoro-4-diethylaminoaniline, (XII). ##STR28##
Reaction SMILES: [C:1](=[O:3])=O.Cl.[CH3:5][O:6][C:7](=[O:17])[C@H:8]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[NH2:9].C(N(CC)CC)C.P(Cl)(Cl)(Cl)=O>ClCCl.C(OCC)C>[N-:9]=[C:1]=[O:3].[CH3:5][O:6][C:7](=[O:17])[C@H:8]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[NH2:9]
Reactant: O=C=O
Agent: COC(=O)[C@@H](N)Cc1ccccc1
Agent: Cl
Solvent: ClCCl
Solvent: O=P(Cl)(Cl)Cl
Solvent: CCN(CC)CC
Product: [N-]=C=O

Procedure:
Carbon dioxide was added subsurface to a dichloromethane (20 mL) solution containing phenylalanine methylester hydrochloride salt (0.005 mol, 1.07 g), N-cyclohexyl-N',N',N",N"-tetraethylguanidine (0.005 mol, 1.3 g) and triethylamine (0.02 mol, 2.0 g) at -10° C. (ice and salt bath) for 30 min at a pressure of 0 psig. The reaction mixture was transferred rapidly via cannula under carbon dioxide to a pre-cooled solution of phosphorus oxychloride (0.005 mol, 0.8 g) in 20 mL dichloromethane. After stirring for 20 min at -10° C. diethylether (40 mL) was added to the reaction mixture. A white ppt. formed and was filtered off. The filtrate was concentrated in vacuo and the residue was extracted with 3×20 mL diethylether. The ether layers were concentrated and the residue distilled under vacuum (ca. 0.1-0.3 torr) collecting product, phenylalanine methyl ester isocyanate, at 91°-93° C. (0.426 g, 41.6%) of 93% purity as judged by GC. IR (neat) 2253, 1745 cm-1. 1H NMR (CDCl3) δ 7.35-7.17 (m, 5H), 4.26 (dd, 1H, Jgem =7.7, Jvic =4.7), 3.79 (s, 3H), 3.15 (dd, 2H, Jgem =13.8, Jvic =4.7), 3.01 (dd, 1H, Jgem =13.8, Jvic =7.8) ppm.
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[C:6]([O:11][CH3:12])[CH:5]=1)=[O:3].[CH2:13](Br)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH2:13]([O:10][C:7]1[CH:8]=[CH:9][C:4]([C:2](=[O:3])[CH3:1])=[CH:5][C:6]=1[O:11][CH3:12])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: COc1cc(C(C)=O)ccc1O
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1cc(C(C)=O)ccc1OCc1ccccc1
Temperature: 25 °C
Yield: 99.2 %

Procedure:
A solution of 4-hydroxy-3-methoxyacetophenone (40 g, 240 mmol), benzyl bromide (31.4 mL, 260 mmol) and potassium carbonate (99.6 g, 360 mmol) in DMF (800 mL) was heated to 40° C. overnight. The solution was cooled to room temperature, poured over ice and the resultant solid was filtered. This material was washed with water and dried to give 1-(4-benzyloxy-3-methoxyphenyl)ethanone (61 g, 99%).
Reaction SMILES: S(Cl)([Cl:3])=O.CN(C)C=O.[Cl:10][C:11]1[C:12]([N+:26]([O-:28])=[O:27])=[C:13](OC)[C:14]([N+:21]([O-:23])=[O:22])=[C:15]([Cl:20])[C:16]=1[N+:17]([O-:19])=[O:18]>C1(C)C=CC=CC=1>[Cl:10][C:11]1[C:12]([N+:26]([O-:28])=[O:27])=[C:13]([Cl:3])[C:14]([N+:21]([O-:23])=[O:22])=[C:15]([Cl:20])[C:16]=1[N+:17]([O-:19])=[O:18]
Reactant: O=S(Cl)Cl
Reactant: COc1c([N+](=O)[O-])c(Cl)c([N+](=O)[O-])c(Cl)c1[N+](=O)[O-]
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1c(Cl)c([N+](=O)[O-])c(Cl)c([N+](=O)[O-])c1Cl
Temperature: 95 °C
Yield: 9.5 %

Procedure:
Thionyl chloride (0.20 ml, 0.027 mol) and dimethylformamide (0.15 ml, 0.022 mol) were added to a solution of 5 (0.624 g, 0.020 mol) in toluene (2 ml) at 50° C. The mixture was stirred and heated to 95° C. over a period of 15 min. and maintained at that temperature for another hour. The pale yellow solution was washed with water, dried over magnesium sulfate, treated with activated carbon, filtered, and evaporated to give a cream-colored solid (0.600 g, 95% yield). The melting point of the material so obtained was 194-195° C. (195-196° C. after recrystallization from acetic acid).
Reaction SMILES: [C:1]1(=[O:11])[NH:5][C:4](=[O:6])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.[K].[Br:13][CH2:14][CH2:15][CH2:16]Br>CN(C)C=O>[Br:13][CH2:14][CH2:15][CH2:16][N:5]1[C:1](=[O:11])[C:2]2=[CH:10][CH:9]=[CH:8][CH:7]=[C:3]2[C:4]1=[O:6]
Reactant: O=C1NC(=O)c2ccccc21
Reactant: BrCCCBr
Agent: [K]
Solvent: CN(C)C=O
Product: O=C1c2ccccc2C(=O)N1CCCBr
Temperature: 120 °C
Reaction time: 6 h
Yield: 51.8 %

Procedure:
In 100 ml of dimethylformamide were suspended 18.52 g of potassium phthalimide and 200 g of 1,3-dibromopropane, and then this suspension was heated with stirring at 120° C. for 6 hours so as to perform reaction. Next, insoluble matters were removed from the resulting reaction mixture by filtration, and the filtrate was then concentrated to dryness under reduced pressure. The residue was washed with hexane and then recrystallized from ethanol/water, and the resulting crystals were collected by filtration, washed, and dried to obtain 13.8 g of N-(3-bromopropyl)phthalimide.
Reaction SMILES: Cl.Cl.[CH3:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)=[CH:7][CH:6]=1.Cl[C:18]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][N:19]=1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O>[CH3:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([N:11]2[CH2:16][CH2:15][N:14]([C:18]3[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][N:19]=3)[CH2:13][CH2:12]2)=[CH:9][CH:10]=1
Reactant: COc1ccc(N2CCNCC2)cc1
Reactant: O=[N+]([O-])c1ccc(Cl)nc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: COc1ccc(N2CCN(c3ccc([N+](=O)[O-])cn3)CC2)cc1
Temperature: 140 °C
Reaction time: 8 h
Yield: 57.4 %

Procedure:
A mixture of 36 g of 1-(4-methoxyphenyl)piperazine dihydrochloride, 22 g of 2-chloro-5-nitropyridine, 58 g of potassium carbonate and 227 ml of dimethyl sulfoxide was stirred overnight at 140° C. The reaction mixture was cooled and poured onto water. The precipitated product was filtered off, washed with water and dissolved in dichloromethane. The solution was treated with activated charcoal. The latter is filtered off and the filtrate was evaporated. The residue was triturated in 2-propanol. The product was filtered off and crystallized from 1-butanol, yielding 24.5 g of 1-(4-methoxyphenyl)-4-(5-nitro-2-pyridinyl)piperazine; mp. 170° C. (interm. 21).
Reaction SMILES: [CH:1](=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.COC(OC)OC.[NH2:16][CH2:17][CH2:18][CH2:19][OH:20].[BH4-].[Na+]>CO>[CH2:1]([NH:16][CH2:17][CH2:18][CH2:19][OH:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=Cc1ccccc1
Reactant: NCCCO
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: COC(OC)OC
Product: OCCCNCc1ccccc1
Temperature: 25 °C
Reaction time: 5 h
Yield: 92.6 %

Procedure:
To a solution of benzaldehyde (10 g, 94.23 mmol) and trimethylorthoformate (15.5 mL, 141 mmol) in MeOH (300 mL) was added dropwise 3-amino-1-propanol (7.21 mL, 94.23 mmol) at room temperature. The reaction was allowed to stir at room temperature for 5 hours followed by cooling to 0° C. in an ice bath. Sodium borohydride (3.56 g, 94.23 mmol) was added in two portions and when the bubbling stopped the solvent was evaporated. The resulting residue was partitioned between ethyl acetate (75 mL) and water (75 mL). The aqueous layer was extracted twice with ethyl acetate (75 mL). The ethyl acetate extracts were collected and washed twice with Brine (50 mL), dried over MgSO4, filtered, and concentrated. Drying afforded 14.42 g (93%) of the compound which was used in the next step of synthesis without further purification.
Reaction SMILES: [CH3:1][C:2]1[C:7]([CH3:8])=[C:6]([N+]([O-])=O)[C:5]([CH3:12])=[CH:4][N+:3]=1[O-:13].[ClH:14].C(=O)([O-])[O-].[K+].[K+]>C(OC(C)C)(C)C.CCCCCC.O.CN(C)C=O>[Cl:14][C:6]1[C:5]([CH3:12])=[CH:4][N+:3]([O-:13])=[C:2]([CH3:1])[C:7]=1[CH3:8]
Reactant: Cc1c[n+]([O-])c(C)c(C)c1[N+](=O)[O-]
Reactant: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)OC(C)C
Solvent: CCCCCC
Solvent: O
Product: Cc1c[n+]([O-])c(C)c(C)c1Cl
Temperature: 70 °C
Yield: 83.1 %

Procedure:
To 2,3,5-trimethyl-4-nitropyridine 1-oxide (850 g, 4.67 mol), water (400 g) and 36% concentrated hydrochloric acid (1.69 kg) was added and the mixture was heated to 70° C. To the mixture, N,N-dimethylformamide (115 mL) was added and then the resultant mixture was heated to 100° C. After completion of the reaction, the reaction mixture was cooled to 20° C. and poured into a mixture of potassium carbonate (1.40 kg) and water (7 L). The mixture was extracted with chloroform (1.0 L×3), the organic layer dried over sodium sulfate and concentrated. The obtained crude product was stirred for 2 hours in a mixture of diisopropyl ether (500 mL) and n-hexane (1.0 L), and thereafter, sucking filtration was performed. The obtained wet product was dried under vacuum overnight to obtain a desired product (666.4 g).
Reaction SMILES: Br[C:2]1[CH:10]=[C:9]([C:11]([OH:13])=[O:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].COCCOC.[NH2:20][C:21]1[N:25]([CH2:26][CH3:27])[N:24]=[CH:23][CH:22]=1.C([O-])([O-])=O.[K+].[K+]>CC([O-])=O.CC([O-])=O.[Cu+2].C(O)(=O)C.O>[CH2:26]([N:25]1[C:21]([NH:20][C:2]2[C:3](=[CH:7][CH:8]=[C:9]([C:11]([OH:13])=[O:12])[CH:10]=2)[C:4]([OH:6])=[O:5])=[CH:22][CH:23]=[N:24]1)[CH3:27]
Reactant: O=C(O)c1ccc(C(=O)O)c(Br)c1
Reactant: CCn1nccc1N
Agent: [Cu+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: CC(=O)O
Solvent: COCCOC
Solvent: O
Product: CCn1nccc1Nc1cc(C(=O)O)ccc1C(=O)O
Temperature: 135 °C
Yield: 45.4 %

Procedure:
A mixture of 2-bromoterephthalic acid (4.8 g, 0.02 mol), DME (50 ml), Cu(OAc)2 (0.2 g), 5-amino-1-ethylpyrazole (2.22 g, 0.02 mol) and K2CO3 (2.71 g, 0.02 mol) is heated at 135° C. overnight, then at reflux overnight. The reaction mixture is poured into water, acidified with acetic acid and the precipitate which forms is collected by filtration and dried to afford 2.5 g of N-(1-ethylpyrazol-5-yl)-4-carboxyanthranilic acid.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[CH:7]1([N:10]2[C:19]3[C:14](=[CH:15][C:16]([F:23])=[C:17](F)[C:18]=3[O:20][CH3:21])[C:13](=[O:24])[C:12]([C:25]([OH:27])=[O:26])=[CH:11]2)[CH2:9][CH2:8]1>CS(C)=O>[CH:7]1([N:10]2[C:19]3[C:14](=[CH:15][C:16]([F:23])=[C:17]([N:1]4[CH2:6][CH2:5][O:4][CH2:3][CH2:2]4)[C:18]=3[O:20][CH3:21])[C:13](=[O:24])[C:12]([C:25]([OH:27])=[O:26])=[CH:11]2)[CH2:8][CH2:9]1
Reactant: COc1c(F)c(F)cc2c(=O)c(C(=O)O)cn(C3CC3)c12
Reactant: C1COCCN1
Solvent: CS(C)=O
Product: COc1c(N2CCOCC2)c(F)cc2c(=O)c(C(=O)O)cn(C3CC3)c12
Temperature: 70 °C
Reaction time: 6 h
Yield: 59.8 %

Procedure:
1.2 g (0.012 mole) of morpholine was added to a solution of 0.9 g (0.003 mole) of 1-cyclopropyl-6,7-difluoro-8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (IIc) (prepared as described in Preparation 6) in 5 ml of dimethyl sulfoxide, and the mixture was stirred at 70° C. for 6 hours. At the end of this time, the solvent and the excess morpholine were removed at the same temperature by evaporation under reduced pressure. The residue was washed with ethyl acetate and then subjected to silica gel column chromatography eluted with methanol, to afford 0.65 g of 1-cyclopropyl-6-fluoro-8-methoxy-7-morpholino-1,4-dihydro-4-oxoquinoline-3-carboxylic acid as a pale brown powder melting at 235°-237° C.
Reaction SMILES: COC1C=CC=C2C=1N=C(N)N=C2.[CH3:14][O:15][C:16]1[C:17]([N+:24]([O-])=O)=[C:18]([CH:21]=[CH:22][CH:23]=1)[CH:19]=[O:20].[NH4+].[Cl-]>CO.[Fe]>[NH2:24][C:17]1[C:16]([O:15][CH3:14])=[CH:23][CH:22]=[CH:21][C:18]=1[CH:19]=[O:20]
Reactant: COc1cccc(C=O)c1[N+](=O)[O-]
Agent: [Fe]
Agent: COc1cccc2cnc(N)nc12
Agent: [Cl-]
Solvent: CO
Product: COc1cccc(C=O)c1N
Temperature: 60 °C
Reaction time: 2 h
Yield: 31.4 %

Procedure:
8-Methoxy-quinazolin-2-ylamine. To a solution of 3-methoxy-2-nitro-benzaldehyde (14.8 g, 81 mmol, Aldrich) and NH4Cl (4.4 g, 82 mmol, Aldrich) in 80% aq. MeOH (250 mL) was added iron dust (20.5 g, 367 mmol, Aldrich) and the reaction mixture was heated at 60° C. with stirring for 2 h. The reaction mixture was allowed to cool to room temperature and filtered through a pad of Celite®. The filter cake was washed with MeOH and the solution was concentrated in vacuum. The concentrated aq. solution was extracted with CH2Cl2 and the combined organic layers were washed with brine and dried over Na2SO4. Purification with EtOAc/Hexanes (0:1→1:4) as eluant gave 3.84 g (31%) of 2-amino-3-methoxy-benzaldehyde as a yellow oil. This oil was heated at 190° C. for 2.5 h in the presence of guanidine hydrochloride (4.9 g, 51 mmol, Aldrich), Na2CO3 (5.4 g, 51 mmol) and decalin (55 mL). The reaction was decanted while hot and the solution was allowed to cool to room temperature. The resultant precipitate was stirred with hexanes, filtered, washed with hexanes, and dried in vacuum to give the title compound as a yellow amorphous solid. MS (ESI, pos ion.) m/z: 176 (M+1).
Reaction SMILES: O[C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5](O)=[CH:4][C:3]=1O.S(=O)(=O)(O)O.C(NC(=O)C=C)O>>[CH:9]1[C:8]2[C:7](=[O:17])[C:6]3[C:15](=[CH:2][CH:3]=[CH:4][CH:5]=3)[C:14](=[O:16])[C:13]=2[CH:12]=[CH:11][CH:10]=1
Reactant: O=C1c2ccccc2C(=O)c2c(O)c(O)cc(O)c21
Agent: C=CC(=O)NCO
Agent: O=S(=O)(O)O
Product: O=C1c2ccccc2C(=O)c2ccccc21
Temperature: 25 °C
Reaction time: 24 h

Procedure:
Twenty-five parts of 1,2,4-trihydroxy-anthraquinone was added to 45 parts of concentrated sulfuric acid. The obtained mixture was cooled with ice in a nitrogen atmosphere. Then, 15 parts of N-methylolacrylamide was added to the resulting mixture in portions. After the completion of the addition, the obtained mixture was stirred at room temperature for 24 hours and poured over a large amount of ice. The precipitate thus formed was recrystallized from ethanol to give a reddish-brown polymerizable anthraquinone dye F. The anthraquinone dye F is represented by the below chemical formula (VII). ##STR7##
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.N1C=CN=C1.[CH:14]([Si:17](Cl)([CH:21]([CH3:23])[CH3:22])[CH:18]([CH3:20])[CH3:19])([CH3:16])[CH3:15]>CN(C=O)C.O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][Si:17]([CH:21]([CH3:23])[CH3:22])([CH:18]([CH3:20])[CH3:19])[CH:14]([CH3:16])[CH3:15])=[CH:4][CH:3]=1
Reactant: Oc1ccc(Br)cc1
Reactant: CC(C)[Si](Cl)(C(C)C)C(C)C
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)[Si](Oc1ccc(Br)cc1)(C(C)C)C(C)C
Yield: 97.9 %

Procedure:
To a solution of 4-bromophenol (17.3 g, 100 mmole) in dry DMF (100 mL) at RT was added imidazole (13.62 g, 200 mmole), followed by triisopropylsilyl chloride (22.5 mL, 105 mmole). After 4 hr the mixture was diluted with H2O (50 mL) and extracted with hexanes (3×75 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated to give the title compound (32.23 g, 100%) as a clear oil which was used without purification: 1H NMR (300 MHz, CDCl3) δ 7.29 (d, J=6 Hz, 2 H), 6.71 (d, J=6 Hz, 2 H), 1.22 (m, 3 H), 1.09 (m, 18 H).
Reaction SMILES: CCOCC.[OH:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[C:13]([O:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH2:26][N:27]3[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]3)=[CH:20][CH:19]=1)=[C:12]([C:33]1[C:34]([C:38]#[N:39])=[CH:35][S:36][CH:37]=1)[CH:11]=[CH:10]2.[Cl:40]CCl>>[ClH:40].[OH:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[C:13]([O:17][C:18]1[CH:19]=[CH:20][C:21]([O:24][CH2:25][CH2:26][N:27]3[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]3)=[CH:22][CH:23]=1)=[C:12]([C:33]1[C:34]([C:38]#[N:39])=[CH:35][S:36][CH:37]=1)[CH:11]=[CH:10]2
Reactant: ClCCl
Agent: N#Cc1cscc1-c1ccc2cc(O)ccc2c1Oc1ccc(OCCN2CCCCC2)cc1
Solvent: CCOCC
Product: Cl

Procedure:
Add a solution of hydrogen dichloride in ether (1 M, 122 μL, 122.0 μmol) to a solution of 4-(6-hydroxy-1-(4-(2-(piperidin-1-yl)ethoxy)phenoxy)naphthalen-2-yl)thiophene-3-carbonitrile (52 mg, 110.5 μmol) and dichloromethane (4 mL). Sonicate the mixture 5 minutes and then concentrate to obtain the title compound (57 mg, 110.5 μmol). MS (m/z): 471 (M+1-HCl).