Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=2)[CH:3]=1.[F:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[C:21]([O:28][CH3:29])[CH:20]=1.ClC1C=C(C2C=CC(F)=CC=2OC)C=CN=1>>[F:18][C:19]1[CH:24]=[CH:23][C:22]([C:2]2[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]3[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=3)[CH:3]=2)=[C:21]([O:28][CH3:29])[CH:20]=1
Reactant: COc1cc(F)ccc1B(O)O
Reactant: O=[N+]([O-])c1cccc(Nc2cc(I)ccn2)c1
Agent: COc1cc(F)ccc1-c1ccnc(Cl)c1
Product: COc1cc(F)ccc1-c1ccnc(Nc2cccc([N+](=O)[O-])c2)c1
Yield: 80.2 %

Procedure:
The title compound C2 was prepared from A5 (122 mg, 0.36 mmol) and (4-fluoro-2-methoxyphenyl)boronic acid (112 mg, 0.66 mmol) following the procedure reported for the intermediate A2. The residue was purified by flash chromatography on silica gel (cHex/EtOAc 100:0 to 50:50) to yield the desired product C2 as an orange solid (98 mg, 80%). MS (ES) C18H14FN3O3 requires: 339. found: 340 (M+H)+.
Reaction SMILES: NC1C=C(C=CC=1)O[C:6]1[CH:11]=[CH:10][N:9]=[C:8]([C:12]([NH2:14])=O)[CH:7]=1.[NH2:18][C:19]1[CH:24]=[CH:23][C:22]([OH:25])=[C:21]([F:26])[CH:20]=1.ClC1C=CN=C(C#N)C=1>>[NH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][C:6]2[CH:11]=[CH:10][N:9]=[C:8]([C:12]#[N:14])[CH:7]=2)=[C:21]([F:26])[CH:20]=1
Reactant: Nc1ccc(O)c(F)c1
Reactant: NC(=O)c1cc(Oc2cccc(N)c2)ccn1
Agent: N#Cc1cc(Cl)ccn1
Product: N#Cc1cc(Oc2ccc(N)cc2F)ccn1

Procedure:
4-(4-Amino-2-fluorophenoxy) pyridine-2-carbonitrile (2H) was prepared by a method analogous to that described for 4-(3-aminophenoxy) pyridine-2-carboxamide (2C), starting from 4-amino-2-fluorophenol and 4-chloro-2-cyanopyridine, MS ES: 230 (M+H)+, calcd 230, RT=2.18 min.
Reaction SMILES: Cl[C:2]1[C:3](=[O:22])[C:4](=[O:21])[C:5]=1[C:6]1[CH:7]=[C:8]([CH3:20])[C:9]2[C:15]=1[C:14]([CH3:16])=[CH:13][CH:12]=[C:11]([CH:17]([CH3:19])[CH3:18])[CH:10]=2.[OH2:23].Cl>O1CCOCC1>[OH:23][C:2]1[C:3](=[O:22])[C:4](=[O:21])[C:5]=1[C:6]1[CH:7]=[C:8]([CH3:20])[C:9]2[C:15]=1[C:14]([CH3:16])=[CH:13][CH:12]=[C:11]([CH:17]([CH3:19])[CH3:18])[CH:10]=2
Reactant: Cc1cc(-c2c(Cl)c(=O)c2=O)c2c(C)ccc(C(C)C)cc1-2
Reactant: O
Agent: Cl
Solvent: C1COCCO1
Product: Cc1cc(-c2c(O)c(=O)c2=O)c2c(C)ccc(C(C)C)cc1-2
Yield: 62 %

Procedure:
62.4 g (0.2 mol) of 3-chloro-4-(7-isopropyl-1,4-dimethyl-3-azulenyl)cyclobut-3-ene-1,2-dione were refluxed in 200 ml of dioxane, 40 ml of water and 2 ml of concentrated hydrochloric acid for 8 hours. The solvent was removed under reduced pressure, and the remaining oily residue was crystallized by adding dichloromethane. 36.5 g (62%) of 3-hydroxy-4-(7-isopropyl-1,4-dimethyl-3-azulenyl)cyclobut-3-ene-1,2-dione were obtained as dark brown crystals of melting point 120°-123° C. The substance was used without further purification for synthesizing dyes.
Reaction SMILES: Br[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[C:8]([O:12][C:13](=[O:19])[NH:14][CH2:15][CH2:16][NH:17][CH3:18])([CH3:11])([CH3:10])[CH3:9].C(N(CC)CC)C>C1COCC1>[C:8]([O:12][C:13]([NH:14][CH2:15][CH2:16][N:17]([CH3:18])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4])=[O:19])([CH3:11])([CH3:10])[CH3:9]
Reactant: CCOC(=O)CBr
Reactant: CNCCNC(=O)OC(C)(C)C
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CCOC(=O)CN(C)CCNC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 24 h

Procedure:
Ethyl bromoacetate (1.27 ml, 11.48 mmol) was added to a mixture of tert-butyl(2-(methylamino)ethyl)carbamate (2.0 g, 11.48 mmol), triethylamine (4.81 ml) and THF (24 ml) at 0° C. After stirring 24 h at room temperature the reaction mixture was partitioned between saturated aqueous NaHCO3 and DCM, extracted 2× with DCM, the organic layers dried over Na2SO4 and evaporated to give the title compound as a clear pale-yellow oil. 1H NMR (400 MHz, CDCl3) δ 5.20 (s, br, 1H), 4.18 (q, 2H), 3.24 (s, 2H), 3.22-3.16 (m, 2H), 2.65-2.61 (m, 2H), 2.38 (s, 3H), 1.42 (s, 9H), 1.24 (t, 3H).
Reaction SMILES: [Br:1][C:2]1[CH:15]=[CH:14][C:13]2[C:12]3[C:7](=[CH:8][C:9](Br)=[CH:10][CH:11]=3)[CH:6]=[CH:5][C:4]=2[CH:3]=1.B(OC(C)C)(OC(C)C)[O:18]C(C)C.C([Li])CCC.Cl>C1COCC1.CCCCCC>[Br:1][C:2]1[CH:15]=[CH:14][C:13]2[C:12]3[C:7](=[CH:8][C:9]([OH:18])=[CH:10][CH:11]=3)[CH:6]=[CH:5][C:4]=2[CH:3]=1
Reactant: Brc1ccc2c(ccc3cc(Br)ccc32)c1
Reactant: CC(C)OB(OC(C)C)OC(C)C
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: Oc1ccc2c(ccc3cc(Br)ccc32)c1
Reaction time: 1 h

Procedure:
25.0 g (74.4 mmol) of 2,7-dibromophenanthrene (CAS No. 62325-30-8) and 24.0 ml (104 mmol) of triisopropyl borate are initially introduced in 750 ml of THF, and 61 ml (97 mmol) of a 15 percent solution of n-butyllithium in hexane are added dropwise at −70° C. When the addition is complete, the batch is left to stir for a further 1 h, hydrolysed using 2 N hydrochloric acid, and the cooling is removed. After addition of MTB ether, the aqueous phase is removed and extracted with MTB ether. The combined org. phases are dried over sodium sulfate, evaporated, and the residue is recrystallised from heptane. 30 ml of 30 percent hydrogen peroxide are added to the resultant boronic acid in 350 ml of toluene and 150 ml of 2 N sodium hydroxide solution with vigorous stirring at such a rate that the temp. does not exceed 45° C. When the addition is complete, the batch is left to stir for a further 30 min, added to 200 ml of water and acidified using 2 N hydrochloric acid. The aqueous phase is separated off and extracted three times with ethyl acetate. The combined org. phases are washed with dil. ammonium iron(II) sulfate solution and water and dried over sodium sulfate. The solvent is removed in vacuo, and the residue is filtered through silica gel with dichloromethane and recrystallised from toluene, giving 2-bromo-7-hydroxyphenanthrene as colourless crystals.
Reaction SMILES: [CH2:1]([N:3]1[C:7]([C:8]([OH:10])=O)=[CH:6][C:5]([CH3:11])=[N:4]1)[CH3:2].S(Cl)(Cl)=O.[NH2:16][C:17]1[CH:34]=[CH:33][C:20]([C:21]([C:23]2[CH:24]=[C:25]3[C:29](=[CH:30][CH:31]=2)[NH:28][C:27](=[O:32])[CH2:26]3)=[O:22])=[CH:19][CH:18]=1>C1COCC1>[O:32]=[C:27]1[CH2:26][C:25]2[C:29](=[CH:30][CH:31]=[C:23]([C:21]([C:20]3[CH:33]=[CH:34][C:17]([NH:16][C:8]([C:7]4[N:3]([CH2:1][CH3:2])[N:4]=[C:5]([CH3:11])[CH:6]=4)=[O:10])=[CH:18][CH:19]=3)=[O:22])[CH:24]=2)[NH:28]1
Reactant: CCn1nc(C)cc1C(=O)O
Reactant: Nc1ccc(C(=O)c2ccc3c(c2)CC(=O)N3)cc1
Solvent: C1CCOC1
Solvent: O=S(Cl)Cl
Product: CCn1nc(C)cc1C(=O)Nc1ccc(C(=O)c2ccc3c(c2)CC(=O)N3)cc1
Temperature: 79 °C
Reaction time: 2 h
Yield: 72.1 %

Procedure:
A dry 25 mL flask was charged with 2-Ethyl-5-methyl-2H-pyrazole-3-carboxylic acid (0.608 mg, 3.53 mmol) and thionyl chloride (10 mL) and allowed to stir at 79° C. for 2 h. The thionyl chloride was then removed by distillation. The crude acid chloride was cooled to room temperature, and then dissolved in THF (5 mL). 5-(4-Amino-benzoyl)-1,3-dihydro-indol-2-one (0.685 g, 2.72 mmol) was added to the THF solution of the acid chloride, and the mixture was allowed to reflux for 2 h. The reaction mixture was then allowed to cool to room temperature. The room temperature reaction mixture was concentrated in vacuo, and the crude residue was dissolved in EtOH (5 mL). The ethanolic solution was treated with 1M NaOH(aq) (2 mL) and stirred for 30 min. The basic solution was acidified to a pH of 1 with 1M HCl(aq) yielding a tan precipitate. The tan solids were filtered to afford pure 2-Ethyl-5-methyl-2H-pyrazole-3-carboxylic acid [4-(2-oxo-2,3-dihydro-1H-indole-5-carbonyl)-phenyl]-amide (0.760 g, 1.96 mmol, 72%).
Reaction SMILES: [CH2:1]([OH:3])[CH3:2].C([O:7][CH2:8][CH2:9][CH:10]([CH3:17])[CH2:11][CH2:12][CH:13]=[C:14]([CH3:16])[CH3:15])(=O)C.[OH-].[K+].[BH4-].[Na+]>O>[CH2:1]([O:3][C:14]([CH3:16])([CH3:15])[CH2:13][CH2:12][CH2:11][CH:10]([CH3:17])[CH2:9][CH2:8][OH:7])[CH3:2]
Reactant: CCO
Reactant: CC(=O)OCCC(C)CCC=C(C)C
Agent: [BH4-]
Agent: [K+]
Agent: [Na+]
Solvent: O
Product: CCOC(C)(C)CCCC(C)CCO
Reaction time: 8 h

Procedure:
150 Grams of mercuric acetate in 400 ml. of dry ethanol is added to 100 g. of 1-acetoxy-3,7-dimethyloct-6-ene (citronellol acetate) in 200 ml. of dry ethanol cooled in an ice bath. The temperature is allowed to come to room temperature by standing overnight. Then the mixture is cooled to 0°, 100 g. of potassium hydroxide in 1.5 l. of ethanol is added followed by addition of 10 g. of sodium borohydride in small portions. After about 30 minutes at 0°, water (100 ml.) is added and mixture left at room temperature for two hours. The mixture is filtered, filtrate concentrated and extracted with ether. The ethereal extract is washed, dried and evaporated to yield 7-ethoxy-3,7-dimethyloctan-1-ol which is purified by distillation or chromatography.
Reaction SMILES: [F:1][C:2]1[CH2:7][CH2:6][C:5]([OH:18])([C:8]([O:10]CC2C=CC=CC=2)=[O:9])[CH2:4][CH:3]=1.O.[OH-].[Na+].Cl>C1COCC1>[F:1][C:2]1[CH2:7][CH2:6][C:5]([OH:18])([C:8]([OH:10])=[O:9])[CH2:4][CH:3]=1
Reactant: O=C(OCc1ccccc1)C1(O)CC=C(F)CC1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)C1(O)CC=C(F)CC1
Reaction time: 1.5 h

Procedure:
Benzyl 4-fluoro-1-hydroxycyclohex-3-ene-1-carboxylate (0.554 g, 2.21 mmol) was dissolved in 27.5 mL of a 4:1 solution of THF:deionized water. A solution of 1 N NaOH was added to the reaction mixture. After stirring for 1.5 hours, the reaction mixture was acidified with 6 N HCl and extracted with EtOAc three times. The organic extracts were combined, washed with water, dried over sodium sulfate, filtered and concentrated to give 4-fluoro-1-hydroxycyclohex-3-ene-1-carboxylic acid as an oil.
Reaction SMILES: [C:1]1([C:7]2[O:11][CH:10]=[N:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li]CCCC.[Cl:17]C(Cl)(Cl)C(Cl)(Cl)Cl>C1COCC1>[Cl:17][C:10]1[O:11][C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[CH:8][N:9]=1
Reactant: c1ccc(-c2cnco2)cc1
Reactant: ClC(Cl)(Cl)C(Cl)(Cl)Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: Clc1ncc(-c2ccccc2)o1
Temperature: -78 °C
Reaction time: 0.25 h
Yield: 48.5 %

Procedure:
To a round bottom flask was added 5-phenyloxazole (1.0 gm, 6.89 mmol) and THF (10 mL). The reaction was cooled to −78° C. Then 2.5 M nBuLi (3.03 mL, 7.58 mmol) was added to the reaction at −78° C. The reaction turned to deep red color. After 15 min, hexachloroethane (1.170 mL, 10.33 mmol) was added at −78° C. The reaction was slowly warmed to rt over 2 hrs and then was poured onto ice. The resulting solution was extracted with EtOAc (2×30 ml). The combined EtOAc layers were washed with saturated aqueous NaCl, dried over MgSO4, filtered and concentrated. The resulting residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-100% EtOAc/Hex to give the product, 2-chloro-5-phenyloxazole, (600 mg, 3.34 mmol, 49% yield) as a light pale liquid. Anal. Calcd. for C9H6ClNO m/z 179.1, found: 180.1 (M+H)+; 1H NMR (500 MHz, CDCl3) δ ppm 7.60 (d, J=7.15 Hz, 2H), 7.43 (t, J=7.42 Hz, 2H), 7.38-7.33 (m, 1H), 7.29 (s, 1H); 13C NMR (126 MHz, CDCl3) δ ppm 153.78, 146.16, 129.01, 126.93, 124.03, 123.31.
Reaction SMILES: [H-].[Na+].[C:3]1([S:9]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=2[Cl:20])(=[O:11])=[O:10])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:21]([O:28][C@@H:29]1[CH2:34][C@@H:33]([CH2:35]I)[O:32][C@@H:31]([O:37][CH3:38])[CH2:30]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>CN(C=O)C>[C:3]1([S:9]([CH:12]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=2[Cl:20])[CH2:35][C@H:33]2[O:32][C@@H:31]([O:37][CH3:38])[CH2:30][C@H:29]([O:28][CH2:21][C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH2:34]2)(=[O:11])=[O:10])[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1
Reactant: CO[C@H]1C[C@H](OCc2ccccc2)C[C@@H](CI)O1
Reactant: O=S(=O)(Cc1ccc(Cl)cc1Cl)c1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CO[C@H]1C[C@H](OCc2ccccc2)C[C@@H](CC(c2ccc(Cl)cc2Cl)S(=O)(=O)c2ccccc2)O1
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 68.5 %

Procedure:
To a stirred suspension of sodium hydride (0.030 g of 50% NaH in mineral oil) in dry DMF (0.5 ml) under nitrogen is added 2,4-dichlorobenzyl phenyl sulfone (0.18 g; 0.6 mmole) as the crystalline solid all at once. The reaction mixture is stirred at room temperature under nitrogen under hydrogen evolution ceases (50 min.) A solution of (2R,4R,6S)-4-benzyloxy-6-iodomethyl-2-methoxy-3,4,5,6-tetrahydro-2H-pyran (0.109 g; 0.3 mmole) in dry DMF (0.4 ml) is added by syringe through a septum. The reaction is stirred for 2.5 hours at room temperature and then partitioned between ether (100 ml) and water (20 ml). The ether layer is extracted with water (4×20 ml), dried (MgSO4), filtered, and the solvent evaporated in vacuo to leave 0.24 g of crude product. Flash chromatography of this product on silica gel with a 30 mm×130 mm column, eluting with 2% (by volume) acetone in methylene chloride, gives 40 mg of the major diastereoisomer and 10 mg of the minor diastereoisomer and 60 mg of a mixture of the two with a total of 110 mg of 1-(2,4-dichlorophenyl)-2-(4(R)-benzyloxy-2(R)-methoxy-3,4,5,6-tetra-hydro-2H-pyran-6(S)-yl)ethyl phenyl sulfone.
Reaction SMILES: N1CCCCC1.[O:7]1[C:11]2[CH:12]=[CH:13][C:14]([C:16]3[CH2:17][C@H:18]4[CH:24]=[N:23][C:22]5[CH:25]=[C:26]([O:31][CH2:32][CH2:33][CH2:34][O:35][C:36]6[C:37]([O:84][CH3:85])=[CH:38][C:39]7[C:45](=[O:46])[N:44]8[CH:47]=[C:48]([C:50]#[C:51][CH2:52][NH:53][C:54](=[O:82])[C@@H:55]([NH:57][C:58](=[O:81])[C@H:59]([NH:63]C(=O)OCC9C%10C=CC=CC=%10C%10C9=CC=CC=%10)[CH:60]([CH3:62])[CH3:61])[CH3:56])[CH2:49][C@H:43]8[CH:42]=[N:41][C:40]=7[CH:83]=6)[C:27]([O:29][CH3:30])=[CH:28][C:21]=5[C:20](=[O:86])[N:19]4[CH:87]=3)=[CH:15][C:10]=2[O:9][CH2:8]1>CN(C=O)C.C(Cl)Cl>[NH2:63][C@@H:59]([CH:60]([CH3:62])[CH3:61])[C:58]([NH:57][C@@H:55]([CH3:56])[C:54]([NH:53][CH2:52][C:51]#[C:50][C:48]1[CH2:49][C@H:43]2[CH:42]=[N:41][C:40]3[CH:83]=[C:36]([O:35][CH2:34][CH2:33][CH2:32][O:31][C:26]4[C:27]([O:29][CH3:30])=[CH:28][C:21]5[C:20](=[O:86])[N:19]6[CH:87]=[C:16]([C:14]7[CH:13]=[CH:12][C:11]8[O:7][CH2:8][O:9][C:10]=8[CH:15]=7)[CH2:17][C@H:18]6[CH:24]=[N:23][C:22]=5[CH:25]=4)[C:37]([O:84][CH3:85])=[CH:38][C:39]=3[C:45](=[O:46])[N:44]2[CH:47]=1)=[O:82])=[O:81]
Reactant: COc1cc2c(cc1OCCCOc1cc3c(cc1OC)C(=O)N1C=C(c4ccc5c(c4)OCO5)C[C@H]1C=N3)N=C[C@@H]1CC(C#CCNC(=O)[C@H](C)NC(=O)[C@H](NC(=O)OCC3c4ccccc4-c4ccccc43)C(C)C)=CN1C2=O
Solvent: C1CCNCC1
Solvent: CN(C)C=O
Solvent: ClCCl
Product: COc1cc2c(cc1OCCCOc1cc3c(cc1OC)C(=O)N1C=C(c4ccc5c(c4)OCO5)C[C@H]1C=N3)N=C[C@@H]1CC(C#CCNC(=O)[C@H](C)NC(=O)[C@@H](N)C(C)C)=CN1C2=O
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
Excess piperidine was added (0.01 mL, 0.1 mmol) to a solution of SEM-dilactam 11d (1 mg, 0.0009 mmol) in DMF (0.1 mL). The mixture was allowed to stir at room temperature for 20 min, at which point the reaction had gone to completion (monitored by LC/MS). The reaction mixture was diluted with CH2Cl2 (1 mL) and the organic phase was washed with H2O (3×1 mL) until complete piperidine removal. The organic phase was dried over MgSO4, filtered and excess solvent removed by rotary evaporation under reduced pressure to afford crude material 12d. LC/MS (1.917 min (ES+)). m/z: 872.2 [M+H]+
Reaction SMILES: [CH3:1][C:2]1[N:7]=[C:6]2[S:8][C:9]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:5]2=[C:4]([C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)[C:3]=1[CH2:21][C:22]([O:24][CH3:25])=[O:23].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH2:36]1[CH2:40]OC[CH2:37]1.ICCC>CN(C=O)C>[CH3:1][C:2]1[N:7]=[C:6]2[S:8][C:9]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:5]2=[C:4]([C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)[C:3]=1[CH:21]([CH2:37][CH2:36][CH3:40])[C:22]([O:24][CH3:25])=[O:23]
Reactant: COC(=O)Cc1c(C)nc2sc3c(c2c1-c1cccnc1)CCCC3
Reactant: C1CCOC1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: CCCI
Solvent: CN(C)C=O
Product: CCCC(C(=O)OC)c1c(C)nc2sc3c(c2c1-c1cccnc1)CCCC3
Yield: 184.9 %

Procedure:
This compound was prepared according to the procedure C from methyl [2-methyl-4-(pyridin-3-yl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetate (0.096 g; 0.27 mmol), LHMDS 1N in THF (0.3 mL; 0.3 mmol), 1-iodopropane (0.039 mL; 0.4 mmol) in DMF (1.1 mL) for 18 h. Purification by flash chromatography on silica gel using a gradient of ethyl acetate (3-30%) in heptane furnished 0.197 g (77%) of the title compound as a yellow oil.
Reaction SMILES: P(Cl)(Cl)(Cl)(Cl)Cl.[CH2:7]([N:10]1[S:15](=[O:17])(=[O:16])[NH:14][C:13]([O:18][CH3:19])=[N:12][C:11]1=O)[CH2:8][CH3:9].P(Cl)(Cl)([Cl:23])=O>>[Cl:23][C:11]1[N:10]([CH2:7][CH2:8][CH3:9])[S:15](=[O:17])(=[O:16])[N:14]=[C:13]([O:18][CH3:19])[N:12]=1
Reactant: CCCN1C(=O)N=C(OC)NS1(=O)=O
Reactant: O=P(Cl)(Cl)Cl
Agent: ClP(Cl)(Cl)(Cl)Cl
Product: CCCN1C(Cl)=NC(OC)=NS1(=O)=O
Temperature: 110 °C
Reaction time: 7 h

Procedure:
50 parts of phosphorus pentachloride were added to a stirred mixture of 44 parts of 6-n-propyl-3-methoxy-6H-1,2,4,6-thiatriazin-5-one-1,1-dioxide and 268 parts of phosphorus oxychloride at 22° C., and the batch was heated to 110° C. in the course of 20 minutes. After 7 hours' stirring under reflux, it was evaporated down under reduced pressure, giving 45 parts of oily 5-chloro-6-n-propyl-3-methoxy-6H-1,2,4,6-thiatriazine-1,1-dioxide; NMR (CDCl3): N-CH2 4.0-4.28.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([NH2:16])[CH:12]=[CH:13][C:14]=1[Br:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:17]([O:23][CH2:24][CH3:25])(=[O:22])[CH2:18][C:19]([CH3:21])=O>C1CCCCC1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH2:24]([O:23][C:17](=[O:22])[CH:18]=[C:19]([NH:16][C:11]1[CH:12]=[CH:13][C:14]([Br:15])=[C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH:10]=1)[CH3:21])[CH3:25]
Reactant: CCOC(=O)CC(C)=O
Reactant: Nc1ccc(Br)c(OCc2ccccc2)c1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: C1CCCCC1
Product: CCOC(=O)C=C(C)Nc1ccc(Br)c(OCc2ccccc2)c1
Yield: 106.2 %

Procedure:
To a mixture of 3-benzyloxy-4-bromo-phenylamine (55.7 g, 0.168 mol) and ethyl acetoacetate (23.4 mL, 0.185 mol) in cyclohexane was added toluene-4-sulfonic acid monohydrate (0.320 g, 1.68 mmol) The reaction mixture was refluxed during 6 h and the water was azeotropically removed. The reaction mixture was then partitioned between ethyl acetate and an aqueous solution of sodium hydrogenocarbonate. The organic layer was washed with brine, dried over sodium sulfate, filtered and the solvents were evaporated under vacuum. 69.6 g of the title compound were obtained. Black oil, ISP-MS: m/e=392.2 ([M+H]+).
Reaction SMILES: [C:1]1([CH3:15])[CH:6]=[CH:5][C:4]([S:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2Br)=[CH:3][CH:2]=1.C([Li])CCC.[C:21]([N:26]1[CH2:31][CH2:30][C:29](=[O:32])[CH2:28][CH2:27]1)([O:23][CH2:24][CH3:25])=[O:22]>O1CCCC1>[C:21]([N:26]1[CH2:27][CH2:28][C:29]([OH:32])([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[S:7][C:4]2[CH:5]=[CH:6][C:1]([CH3:15])=[CH:2][CH:3]=2)[CH2:30][CH2:31]1)([O:23][CH2:24][CH3:25])=[O:22]
Reactant: CCOC(=O)N1CCC(=O)CC1
Reactant: Cc1ccc(Sc2ccccc2Br)cc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CCOC(=O)N1CCC(O)(c2ccccc2Sc2ccc(C)cc2)CC1
Temperature: -15 °C

Procedure:
2-(4-tolylsulfanyl)-phenyl bromide (6.98 g, 25 mmol) was dissolved in heptanes (40 mL) and dry tetrahydrofuran (4.1 mL) and after 1.5 hrs the reaction mixture was cooled down to 0° C. under an atmosphere of nitrogen. n-Butyllithium in heptanes 2.7 M (9.8 mL, 26.5 mmol) was added at 0° C. and after 45 min the reaction mixture was cooled to −15° C. A solution of N-carbethoxy-4-piperidone (3.8 mL, 25 mmol) in tetrahydrofuran (15 mL) was added maintaining the temperature below −15° C. Once the addition was complete the reaction was allowed to warm to room temperature. The reaction was quenched with a dilute hydrogen chloride solution. A sample from the organic phase shows a ratio of 1-carbethoxy-4-hydroxy-4-[2-(4-methylphenylsulfanyl)phenyl]piperidine to 1-methyl-4-phenylsulfanyl-benzene of 28:58.
Reaction SMILES: [NH:1]1[C:9]2[CH:8]=[CH:7][CH:6]=[C:5]([CH:10]=[O:11])[C:4]=2[CH:3]=[CH:2]1.CS(O[CH2:17][CH:18]1[O:23][C:22]2[CH:24]=[CH:25][CH:26]=[CH:27][C:21]=2[O:20][CH2:19]1)(=O)=O>>[O:23]1[C:22]2[CH:24]=[CH:25][CH:26]=[CH:27][C:21]=2[O:20][CH2:19][CH:18]1[CH2:17][N:1]1[C:9]2[CH:8]=[CH:7][CH:6]=[C:5]([CH:10]=[O:11])[C:4]=2[CH:3]=[CH:2]1
Reactant: O=Cc1cccc2[nH]ccc12
Reactant: CS(=O)(=O)OCC1COc2ccccc2O1
Product: O=Cc1cccc2c1ccn2CC1COc2ccccc2O1

Procedure:
The same procedures used in Example 1 were repeated except for using 870 mg of indole-4-carbaldehyde and 2-benzodioxanylmethyl methanesulfonate instead of the benzyl bromide used in Example 1 to give 699 mg of 1-(2-benzodioxanylmethyl)indole-4-carbaldehyde as a pale yellow oily substance. The yield thereof was found to be 40%.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=[O:6].[F:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[N:17]=[C:18]=[O:19].S([O-])(O)(=O)=O.[K+]>ClCCCl>[F:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[NH:17][C:18]([NH:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:4]([CH:5]=[O:6])[CH:3]=1)=[O:19]
Reactant: Nc1cccc(C=O)c1
Reactant: O=C=Nc1ccccc1F
Agent: O=S(=O)([O-])O
Agent: [K+]
Solvent: ClCCCl
Product: O=Cc1cccc(NC(=O)Nc2ccccc2F)c1
Yield: 83.7 %

Procedure:
The product was prepared as described in Example 2, starting with 484 mg of 3-amino-benzaldehyde (4 mmol) (polymerized form) and 548 mg of 2-fluorophenyl isocyanate in 4 ml of DCE. After cooling, the mixture is poured into 100 ml of saturated potassium hydrogen sulfate solution and extracted with twice 50 ml of ethyl acetate. The combined organic phases are washed with water, dried over sodium sulfate and evaporated. 864 mg of the expected aldehyde are isolated in the form of a gum, in an LC/MS purity of 77%. A crystallized fraction is obtained after trituration from ethyl ether. 165 mg of solid are isolated ([M+H]+): 259. RT=4.28 min (acetonitrile/water gradient from 5% to 85%—Method B).
Reaction SMILES: C([Li])CCC.[C:6](#[N:8])[CH3:7].CO[C:11]([C:13]1[C:22]([N:23]=[CH:24]N(C)C)=[CH:21][C:20]2[C:15](=[CH:16][C:17]([O:30][CH3:31])=[C:18]([O:28][CH3:29])[CH:19]=2)[CH:14]=1)=[O:12].C(O)(=O)C>C1COCC1.O>[CH3:31][O:30][C:17]1[C:18]([O:28][CH3:29])=[CH:19][C:20]2[CH:21]=[C:22]3[C:13]([C:11](=[O:12])[C:7]([C:6]#[N:8])=[CH:24][NH:23]3)=[CH:14][C:15]=2[CH:16]=1
Reactant: COC(=O)c1cc2cc(OC)c(OC)cc2cc1N=CN(C)C
Reactant: CC#N
Agent: [Li]CCCC
Solvent: CC(=O)O
Solvent: O
Solvent: C1CCOC1
Product: COc1cc2cc3[nH]cc(C#N)c(=O)c3cc2cc1OC
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a solution of 2.6 mL (6.3 mmol) of n-butyllithium (2.5M in hexane) in 2.0 ml of THF is added dropwise a solution of 0.36 mL (6.9 mmol) of acetonitrile in 6 mL of THF at −78° C. After completion of addition, the suspension is stirred for 15 minutes. To this is added 496.7 mg (1.57 mmol) of 3-(dimethylaminomethyleneamino)-6,7-dimethoxy-naphthalene-2-carboxylic acid methyl ester in 15 mL of THF dropwise. The resulting reaction mixture is stirred at −78° C. for 1.5 hours. Then 942.8 mg (15.7 mmol) of acetic acid is added dropwise. The reaction mixture is warmed to room temperature and is diluted with water. The precipitate is collected by filtration and washed with water and methanol. After drying in vacuo, this yields 406.0 mg (92.3%) of the product as a light brown solid, mp>265° C.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:11]2[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=2)([CH3:10])[CH3:9])=[CH:4][CH:3]=1.[C:18]([O:21]C(=O)C)(=[O:20])[CH3:19]>>[C:18]([OH:21])(=[O:20])[CH3:19].[C:18]([OH:21])(=[O:20])[CH3:19].[OH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([C:11]2[CH:12]=[CH:13][C:14]([OH:17])=[CH:15][CH:16]=2)([CH3:10])[CH3:9])=[CH:6][CH:7]=1
Reactant: CC(=O)OC(C)=O
Agent: CC(C)(c1ccc(O)cc1)c1ccc(O)cc1
Product: CC(=O)O
Temperature: 140 °C

Procedure:
22.8 g of bisphenol A and 25.5 g of acetic anhydride were introduced into a 150 ml three-necked flask provided with a reflux condenser and a stirrer, and stirred under heating at 140° C. for 7 hours. Then, the obtained reaction product was transferred to a 150 ml flask, and the acetic acid and acetic anhydride therein were removed by heating the mixture to 100° C. under reduced pressure of 10 Torr to obtain 31.1 g of bisphenol A diacetate.