Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [SH:1][CH2:2][C:3]([OH:5])=[O:4].CC1(C)C2(CS(O)(=O)=O)C(CC1CC2)=O.[CH3:21][C:22]1[C:23]([CH:31](O)[CH3:32])=[CH:24][C:25]2[O:29][CH2:28][O:27][C:26]=2[CH:30]=1>C1C=CC=CC=1>[CH3:21][C:22]1[C:23]([CH:31]([S:1][CH2:2][C:3]([OH:5])=[O:4])[CH3:32])=[CH:24][C:25]2[O:29][CH2:28][O:27][C:26]=2[CH:30]=1
Reactant: O=C(O)CS
Reactant: Cc1cc2c(cc1C(C)O)OCO2
Agent: CC1(C)C2CCC1(CS(=O)(=O)O)C(=O)C2
Solvent: c1ccccc1
Product: Cc1cc2c(cc1C(C)SCC(=O)O)OCO2
Yield: 93 %

Procedure:
3.7 g of mercaptoacetic acid and a catalytic amount of D-10-camphorsulfonic acid were added to 3.2 g of 1-(6-methyl-1,3-benzodioxol-5-yl)ethanol and the mixture was heated under reflux in 100 ml of benzene for 1 h. The reaction mixture was washed with water and then extracted with a 1 1Nsodium hydroxide solution. The aqueous layer was washed with ethyl acetate, acidified with 1Nhydrochloric acid and extracted with chloroform. The organic layer was dried over magnesium sulfate and the solvent was distilled off to obtain a crystalline residue. After recrystallization from diisopropyl ether, 4.2 g of the intended compound was obtained in the form of white crystals.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:22]=[CH:21][C:6]([O:7][CH2:8][C:9]2[N:10]=[C:11]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[O:12][C:13]=2[CH3:14])=[CH:5][CH:4]=1.[SH:23][C:24]1[CH:29]=[CH:28][C:27]([CH2:30][CH2:31][C:32]([OH:34])=[O:33])=[CH:26][CH:25]=1.C(N(CC)CC)C.Cl>O.CN(C)C=O>[CH3:14][C:13]1[O:12][C:11]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[N:10][C:9]=1[CH2:8][O:7][C:6]1[CH:21]=[CH:22][C:3]([CH2:2][S:23][C:24]2[CH:25]=[CH:26][C:27]([CH2:30][CH2:31][C:32]([OH:34])=[O:33])=[CH:28][CH:29]=2)=[CH:4][CH:5]=1
Reactant: Cc1oc(-c2ccccc2)nc1COc1ccc(CCl)cc1
Reactant: O=C(O)CCc1ccc(S)cc1
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: O
Product: Cc1oc(-c2ccccc2)nc1COc1ccc(CSc2ccc(CCC(=O)O)cc2)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A mixture of 4-(4-chloromethylphenoxymethyl)-5-methyl-2-phenyloxazole (1.73 g), 3-(4-mercaptophenyl)propionic acid (1.00 g), triethylamine (1.22 g) and N,N-dimethylformamide (20 mL) was stirred at room temperature for 2 hrs. The reaction mixture was poured into water, acidified with 2N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated to give crystals of 3-[4-[[4-[(5-methyl-2-phenyl-4-oxazolyl)methoxy]benzyl]sulfanyl]phenyl]propionic acid. Recrystallization from ethyl acetate gave colorless prism crystals (1.85 g, 73%). melting point: 157-158° C.
Reaction SMILES: [Cl:1][C:2]1[CH:13]=[C:12]([F:14])[C:11]([NH:15][C:16]([NH2:18])=[O:17])=[CH:10][C:3]=1[C:4]([O:6][CH:7]([CH3:9])[CH3:8])=[O:5].[CH3:19][CH2:20][C:21]([CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])=O>>[Cl:1][C:2]1[CH:13]=[C:12]([F:14])[C:11]([NH:15][C:16]([NH:18][C:21]([CH2:20][CH3:19])=[CH:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])=[O:17])=[CH:10][C:3]=1[C:4]([O:6][CH:7]([CH3:9])[CH3:8])=[O:5]
Reactant: CCOC(=O)CC(=O)CC
Reactant: CC(C)OC(=O)c1cc(NC(N)=O)c(F)cc1Cl
Product: CCOC(=O)C=C(CC)NC(=O)Nc1cc(C(=O)OC(C)C)c(Cl)cc1F

Procedure:
using isopropyl 2-chloro-4-fluoro-5-ureidobenzoate and ethyl 3-oxo-n-valerate and finely powdered Amberlyst®-15 (an organic polymeric resin featuring free sulphone groups) as catalyst there is obtained isopropyl 2-chloro-4-fluoro-5-{3-[2-(ethoxycarbonyl)-1-ethylvinyl]ureido}-benzoate, m.p. 123°-126° C.,
Reaction SMILES: [Na].[CH2:2]([OH:4])[CH3:3].CS[C:7]1[N:8]=[N:9][CH:10]=[CH:11][N:12]=1.C(=O)=O>C1C=CC=CC=1.O>[CH2:2]([O:4][C:7]1[N:8]=[N:9][CH:10]=[CH:11][N:12]=1)[CH3:3]
Reactant: CCO
Reactant: CSc1nccnn1
Agent: O=C=O
Agent: [Na]
Solvent: O
Solvent: c1ccccc1
Product: CCOc1nccnn1
Temperature: 0 °C
Reaction time: 0.57 h

Procedure:
Sodium (30.8g - 1.34g.atm) is reacted with 6 pints of absolute ethyl alcohol below 43° C. 3- Methylthio-1,2,4-triazine (159 g. - 1.25 m) is added, and the black mixture stirred under nitrogen at 40° to 44° C. for 34 minutes. The heating bath is replaced by ice water and carbon dioxide gas bubbled in, giving a red-orange mixture at pH 9 within 23/4 hours. Water (1.25 m) is added and carbon dioxide addition continued for 35 minutes without visible or pH change. Air is introduced for another half hour, giving a brown mixture. One liter of benzene is added and the contents filtered with suction at 19° C. The solids are slurried in a liter of water and extracted with CHCl3 several times. The combined filtrate and extracts are vacuum distilled, giving 3-ethoxy-1,2,4-triazine, b.p. 113°-115° C. at 16 mm. The pot residue is recrystallized from methanol to give 16 g. of golden brown platelets, m.p. 95°-99° C. Recrystallizing again from methanol, and finally from ethyl alcohol, yields 7.7 g. of 3,3'-diethoxy-5,5'-bis-1,2,4-triazinyl.
Reaction SMILES: [N+:1]([O-:4])(O)=[O:2].[Br:5][C:6]1[CH:13]=[CH:12][CH:11]=[CH:10][C:7]=1[CH:8]=[O:9]>OS(O)(=O)=O>[Br:5][C:6]1[CH:13]=[CH:12][C:11]([N+:1]([O-:4])=[O:2])=[CH:10][C:7]=1[CH:8]=[O:9]
Reactant: O=Cc1ccccc1Br
Reactant: O=[N+]([O-])O
Agent: O=S(=O)(O)O
Product: O=Cc1cc([N+](=O)[O-])ccc1Br
Temperature: 0 °C
Reaction time: 0.75 h

Procedure:
A nitrating acid prepared at -10° C. by adding 55 ml of concentrated H2SO4 to 20 ml of 98 percent HNO3 was added dropwise, in the course of 60 minutes, to a solution of 63.4 g (0.34 mole) of 2-bromobenzaldehyde in 110 ml of concentrated H2SO4 at -5° C. Stirring was continued for a further 45 minutes, after which the reaction mixture was poured onto 550 g of ice, and the precipitated solid was filtered off under suction, washed with water, then with 10 percent strength Na2CO3 solution and again with water. Drying under reduced pressure at 50° C. gave 72 g (92% of theory) of product as a yellow solid of melting point 86°-88° C.
Reaction SMILES: [Br:1][C:2]1[CH:24]=[C:5]2[N:6]=[C:7]([CH3:23])[C:8]([CH2:18][C:19]([O:21][CH3:22])=[O:20])=[C:9]([N:10]3[CH2:15][CH2:14][C:13]([CH3:17])([CH3:16])[CH2:12][CH2:11]3)[N:4]2[N:3]=1.CC([OH:28])C.C(=O)=O.C[Si]([N-][Si](C)(C)C)(C)C.[K+].C1(C2ON2S(C2C=CC=CC=2)(=O)=O)C=CC=CC=1>C1COCC1>[Br:1][C:2]1[CH:24]=[C:5]2[N:6]=[C:7]([CH3:23])[C:8]([CH:18]([OH:28])[C:19]([O:21][CH3:22])=[O:20])=[C:9]([N:10]3[CH2:15][CH2:14][C:13]([CH3:17])([CH3:16])[CH2:12][CH2:11]3)[N:4]2[N:3]=1
Reactant: CC(C)O
Reactant: COC(=O)Cc1c(C)nc2cc(Br)nn2c1N1CCC(C)(C)CC1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: O=C=O
Agent: O=S(=O)(c1ccccc1)N1OC1c1ccccc1
Solvent: C1CCOC1
Product: COC(=O)C(O)c1c(C)nc2cc(Br)nn2c1N1CCC(C)(C)CC1
Reaction time: 0.25 h
Yield: 82 %

Procedure:
To a solution of methyl 2-(2-bromo-7-(4,4-dimethylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (1.49 g, 3.79 mmol, 1 equiv) in THF (38 mL) at −78° C. (IPA/CO2) was added KHMDS (6.8 mL of a 0.91M solution in THF, 6.07 mmol, 1.6 equiv). The reaction turned a deep orange color. After 15 min, 3-phenyl-2-(phenylsulfonyl)-1,2-oxaziridine (1.49 g, 5.69 mmol, 1.5 equiv) was added in a single portion. The reaction solution significantly darkened and was then allowed to stir for 30 min. The reaction was then removed from the cooling bath and quenched with saturated aqueous solution of NaHCO3, added to water, and extracted with EtOAc (×3). The combined EtOAc extracts were dried over Na2SO4 and concentrated in vacuo. The crude product was purified by silica gel flash chromatography (0-100% EtOAc/hexane) to provide methyl 2-(2-bromo-7-(4,4-dimethylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate as a waxy yellow solid (1.28 g, 82%). 1H NMR (400 MHz, CDCl3) δ 6.57 (s, 1H), 5.53 (d, J=5.3 Hz, 1H), 4.78 (br. s., 1H), 4.52 (d, J=5.3 Hz, 1H), 3.80 (s, 3H), 2.60 (s, 3H), 1.57-1.53 (m, J=3.8 Hz, 4H), 1.10 (s, 6H); LCMS (ESI, M+1): 411.2.
Reaction SMILES: [CH3:1][C:2]1([CH3:14])[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH:12]=O)[CH:8]=2)[O:3]1.[NH:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:17][C:16]1=[O:24]>>[CH3:1][C:2]1([CH3:14])[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH:12]=[C:17]3[C:18]4[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=4)[NH:15][C:16]3=[O:24])[CH:8]=2)[O:3]1
Reactant: CC1(C)CCc2cc(C=O)ccc2O1
Reactant: O=C1Cc2ccccc2N1
Product: CC1(C)CCc2cc(C=C3C(=O)Nc4ccccc43)ccc2O1

Procedure:
2,2-Dimethyl-6-formylchromane (commercially available) was condensed with 2-oxindole to give 0.3 g of 3-(2,2-dimethylchroman-6-ylmethylene)-1,3-dihydroindol-2-one as a yellow-orange solid.
Reaction SMILES: [CH3:1][N:2]([C@@H:4]1[CH2:9][CH2:8][CH2:7][CH2:6][C@H:5]1[NH:10][C:11](=O)[CH3:12])[CH3:3].CCOCC.[H-].[H-].[H-].[H-].[Li+].[Al+3].[OH-].[Na+]>O>[CH3:1][N:2]([CH3:3])[CH:4]1[CH2:9][CH2:8][CH2:7][CH2:6][CH:5]1[NH:10][CH2:11][CH3:12]
Reactant: CC(=O)N[C@@H]1CCCC[C@H]1N(C)C
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Solvent: O
Product: CCNC1CCCCC1N(C)C
Reaction time: 1 h
Yield: 76 %

Procedure:
A Solution of the trans-N-[2-(N,N-dimethylamino)-cyclohexyl]acetamide (acetyl compound) (5.03 g.; 0.027 mole) in 100 ml. of ether was added during 10 minutes to a solution of LAH (5.03 g.) in 300 ml. of ether and the mixture was refluxed 24 hours. It was cooled, decomposed in succession with 5 ml. of H2O, 5 ml. of 15% NaOH, and 15 ml. of H2O. The suspension was stirred 1 hour at room temperture, filtered and the cake washed with ether. The solvent was evaporated through a 9" Vigreux and the product distilled at 91°(13 mm), 3.5 g. (76% yield). ir NH3680w, 3,300; CH 2960, 2920, 2850, 2820; N-alkyl 2780, CH/CN 1455, 1265, 1140, 1060, 1045, 1025, 1025. NMR in CDCl3 (100 MHz) was in accord. Mass spectrum M+ 170.
Reaction SMILES: C([O:5][C:6](=[O:42])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][C:17]([N:19]2[CH2:40][CH2:39][C:22]3([NH:26]/[C:25](=[N:27]/[C:28]([C:30]4[C:35]([NH2:36])=[N:34][C:33]([NH2:37])=[C:32]([Cl:38])[N:31]=4)=[O:29])/[NH:24][CH2:23]3)[CH2:21][CH2:20]2)=[O:18])=[CH:11][C:10]=1[Cl:41])(C)(C)C.Cl>O1CCOCC1>[Cl:41][C:10]1[CH:11]=[C:12]([CH2:15][CH2:16][C:17]([N:19]2[CH2:20][CH2:21][C:22]3([NH:26]/[C:25](=[N:27]/[C:28]([C:30]4[C:35]([NH2:36])=[N:34][C:33]([NH2:37])=[C:32]([Cl:38])[N:31]=4)=[O:29])/[NH:24][CH2:23]3)[CH2:39][CH2:40]2)=[O:18])[CH:13]=[CH:14][C:9]=1[O:8][CH2:7][C:6]([OH:42])=[O:5]
Reactant: CC(C)(C)OC(=O)COc1ccc(CCC(=O)N2CCC3(CC2)CN/C(=N\C(=O)c2nc(Cl)c(N)nc2N)N3)cc1Cl
Agent: Cl
Solvent: C1COCCO1
Product: Nc1nc(N)c(C(=O)/N=C2\NCC3(CCN(C(=O)CCc4ccc(OCC(=O)O)c(Cl)c4)CC3)N2)nc1Cl
Temperature: 25 °C
Reaction time: 24 h

Procedure:
[2-Chloro-4-(3-{2-[(E)-3,5-diamino-6-chloro-pyrazine-2-carbonylimino]-1,3,8-triaza-spiro[4.5]dec-8-yl}-3-oxo-propyl)-phenoxy]-acetic acid tert-butyl ester (step 1) (5.3 g, 8.53 mmol) was suspended in 1,4-dioxane (25 ml) and treated with 4N HCl in dioxane (30 ml). The reaction mixture was stirred at RT for 24 h and filtered. The solid was washed with iso-hexane (300 ml) to afford the title compound as a hydrochloride salt;
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:19])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([S:14][CH3:15])[C:9]=1[C:16](=[O:18])[NH2:17])=[O:6])[CH3:2].ClC1C=C(C=CC=1)C(OO)=[O:25].C(Cl)Cl.C(=O)(O)[O-].[Na+]>O>[CH2:1]([O:3][C:4](=[O:19])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([S:14]([CH3:15])=[O:25])[C:9]=1[C:16]([NH2:17])=[O:18])=[O:6])[CH3:2]
Reactant: CCOC(=O)C(=O)Nc1cccc(SC)c1C(N)=O
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Product: CCOC(=O)C(=O)Nc1cccc(S(C)=O)c1C(N)=O

Procedure:
A mixture of 2.0 g. of [2-carbamyl-3-(methylthio)phenyl] oxamic acid ethyl ester and 1.44 g. of m-chloroperoxybenzoic acid in 200 ml. of methylene chloride is stirred for 2 hours. 0.6 g. of sodium bicarbonate in 20 ml. of water is added, the methylene chloride layer is separated, dried and evaporated. The residue is recrystallized from ethanol-diethyl ether, m.p. 164°-166° C.
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].[NH2:14][C:15]1[CH:16]=[C:17]([CH:21]([NH:28][S:29]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)(=[O:31])=[O:30])[CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH:18]=[CH:19][CH:20]=1>N1C=CC=CC=1>[C:32]1([S:29]([NH:28][CH:21]([C:17]2[CH:18]=[CH:19][CH:20]=[C:15]([NH:14][S:10]([C:6]3[CH:7]=[CH:8][CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)(=[O:12])=[O:11])[CH:16]=2)[CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])(=[O:30])=[O:31])[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1
Reactant: CCOC(=O)CC(NS(=O)(=O)c1ccccc1)c1cccc(N)c1
Reactant: O=[N+]([O-])c1cccc(S(=O)(=O)Cl)c1
Solvent: c1ccncc1
Product: CCOC(=O)CC(NS(=O)(=O)c1ccccc1)c1cccc(NS(=O)(=O)c2cccc([N+](=O)[O-])c2)c1
Yield: 84.8 %

Procedure:
382 mg of 3-nitrobenzenesulphonyl chloride were added at 0° C. to a solution of 500 mg of (1d) in 4 ml of pyridine. After a reaction time of 1 h at 0° C. and 2 h at room temperature, the mixture was concentrated, treated with 1 N HCl and extracted with dichloromethane. After drying over MgSO4, the solvent was removed and 649 mg of a solid were obtained.
Reaction SMILES: I[C:2]1[CH:18]=[CH:17][C:5]([O:6][CH2:7][C:8]2[CH:9]=[C:10]([C:14]([OH:16])=[O:15])[O:11][C:12]=2[CH3:13])=[CH:4][CH:3]=1.[F:19][C:20]([F:32])([F:31])[O:21][C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1>>[CH3:13][C:12]1[O:11][C:10]([C:14]([OH:16])=[O:15])=[CH:9][C:8]=1[CH2:7][O:6][C:5]1[CH:17]=[CH:18][C:2]([C:25]2[CH:24]=[CH:23][C:22]([O:21][C:20]([F:19])([F:31])[F:32])=[CH:27][CH:26]=2)=[CH:3][CH:4]=1
Reactant: Cc1oc(C(=O)O)cc1COc1ccc(I)cc1
Reactant: OB(O)c1ccc(OC(F)(F)F)cc1
Product: Cc1oc(C(=O)O)cc1COc1ccc(-c2ccc(OC(F)(F)F)cc2)cc1

Procedure:
Compound (114) was prepared from compound (26) and (4-trifluoromethoxy-phenyl)-boronic acid by adapting the procedure of Example 27B. LC/MS System C; Rt=11.01 mins, m/z (ES−)=391 (M−H for C20H15F3O5).
Reaction SMILES: [CH3:1][C:2]1[N:6]=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([N+:13]([O-])=O)=[CH:9][CH:8]=2)[S:4][N:3]=1.C(=O)([O-])O.[Na+]>C(O)C>[CH3:1][C:2]1[N:6]=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([NH2:13])=[CH:9][CH:8]=2)[S:4][N:3]=1
Reactant: Cc1nsc(-c2ccc([N+](=O)[O-])cc2)n1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Product: Cc1nsc(-c2ccc(N)cc2)n1
Temperature: 70 °C
Reaction time: 0.5 h
Yield: 97.7 %

Procedure:
To a suspension of 3-methyl-5-(4-nitro-phenyl)-[1,2,4]thiadiazole (422 mg, 1.9 mmol, CAS 800408-77-9, Wilkins, D. J.; Bradley, P. A. Science of Synthesis (2004), 13, 277-295.) in ethanol (19 mL) was added under stirring tin(II)chloride (1.86 g, 9.54 mmol) and heated to 70° C. for 4 hours. The mixture was poured on cold aqueous saturated sodium hydrogen carbonate solution. The suspension was stirred for 30 minutes and the solid was filtered off, washed with water. The residue was heated two to three times with tetrahydrofurane and filtered. The aqueous layer was extracted twice with ethyl acetate. The combined organic layers were dried over sodium sulfate and the solvent was evaporated under reduced pressure. The residue was stirred with diethyl ether and the solid was filtered off and washed with diethyl ether/heptane to yield the title compound as a yellow solid (355 mg, 97%). MS ISP (m/e): 192.2 (100) [(M+H)+]. 1H NMR (DMSO-D6, 300 MHz): δ (ppm)=7.64 (d, 2H), 6.63 (d, 3H), 6.01 (BR s, 2H, NH2), 2.54 (s, 3H).
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4](=[O:13])[CH:5]=[C:6]([C:8](OCC)=[O:9])[N:7]=1.[NH3:14]>CO>[CH3:1][C:2]1[NH:3][C:4](=[O:13])[CH:5]=[C:6]([C:8]([NH2:14])=[O:9])[N:7]=1
Reactant: N
Reactant: CCOC(=O)c1cc(=O)[nH]c(C)n1
Solvent: CO
Product: Cc1nc(C(N)=O)cc(=O)[nH]1
Temperature: 25 °C
Reaction time: 17 h
Yield: 93.4 %

Procedure:
Dissolve ethyl 2-methyl-6-oxo-1H-pyrimidine-4-carboxylate (7.26 g, 39.9 mmol) in a solution of ammonia in MeOH (70 mL, 7 N) and stir the mixture for 17 hours at ambient temperature. Remove the solvents under reduced pressure to provide the title compound as a black solid (5.7 g, 93.4%). MS (m/z): 154 (M+1).
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH2:11]([N:18]1[CH2:23][CH:22]=[C:21]([C:24]([CH3:28])([CH3:27])[CH2:25][OH:26])[CH2:20][CH2:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C>ClCCl.O>[CH2:11]([N:18]1[CH2:19][CH:20]=[C:21]([C:24]([CH3:28])([CH3:27])[CH:25]=[O:26])[CH2:22][CH2:23]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: CC(C)(CO)C1=CCN(Cc2ccccc2)CC1
Agent: O=C(Cl)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: O
Product: CC(C)(C=O)C1=CCN(Cc2ccccc2)CC1
Temperature: -78 °C
Reaction time: 0.08 h
Yield: 89.9 %

Procedure:
Step D To a solution of oxalyl chloride (2.46 mL, 28 mmol) (Aldrich) in dichloromethane (150 mL) at −78° C. was added the solution of dimethyl sulfoxide (4 mL, 56 mmol) in dichloromethane (25 mL) dropwise. After 5 mins, the solution of 2-(1-benzyl-1,2,3,6-tetrahydro-pyridin-4-yl)-2-methyl-propan-1-ol (6.3 g, 25.6 mmol) in dichloromethane (25 mL) was added dropwise. The reaction mixture was stirred at −78° C. for 15 min. Triethylamine (12.8 mL, 92 mmol) was added and the reaction mixture was slowly warmed up to room temperature and stirred at room temperature for 45 min. Then water was added. The organic layers were separated, and the aqueous layer was extracted with dichloromethane. The organic layers were combined, washed with 10% of HCl, saturated NaHCO3, brine, dried over MgSO4, and concentrated to give 2-(1-benzyl-1,2,3,6-tetrahydro-pyridin-4-yl)-2-methyl-propionaldehyde as a brown oil (Yield: 5.6 g, 89%).
Reaction SMILES: [NH2:1][C@@H:2]([CH3:12])[C@@H:3]([C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1)[OH:4].Br[CH2:14][CH2:15][C:16]1[CH:28]=[CH:27][C:19]([O:20][CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:18][C:17]=1[Cl:29].C(N(CC)C(C)C)(C)C.O>CN(C)C=O>[Cl:29][C:17]1[CH:18]=[C:19]([CH:27]=[CH:28][C:16]=1[CH2:15][CH2:14][NH:1][C@@H:2]([CH3:12])[C@H:3]([OH:4])[C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1)[O:20][CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23]
Reactant: CCOC(=O)COc1ccc(CCBr)c(Cl)c1
Reactant: C[C@H](N)[C@H](O)c1ccc(O)cc1
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CCOC(=O)COc1ccc(CCN[C@@H](C)[C@H](O)c2ccc(O)cc2)c(Cl)c1
Yield: 31.7 %

Procedure:
A solution of (1R,2S)-2-amino-1-(4-hydroxyphenyl)propan-1-ol (97 mg), ethyl 2-[4-(2-bromoethyl)-3-chlorophenoxy]acetate (187 mg) and N,N-diisopropylethylamine (203 μl) in N,N-dimethylformamide (3 ml) was stirred for 10 hours at 60° C. After cooling, water was added to the reaction mixture and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate. After the solvent was removed in vacuo, purification of the residue by medium pressure liquid column chromatography on aminopropyl silica gel (eluent: ethyl acetate/ethanol=30/1) gave ethyl 2-[3-chloro-4-[2-[[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methyl-ethyl]amino]ethyl]phenoxy]acetate (75 mg).
Reaction SMILES: [CH3:1][S:2][C:3]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH:17]=[O:18])=[C:9]2[C:4]=1[CH:5]=[CH:6][CH:7]=[CH:8]2.C1C=C(Cl)C=C(C(OO)=[O:27])C=1>C(Cl)Cl>[CH3:1][S:2]([C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[C:10]([CH:17]=[O:18])=[C:11]2[C:16]=1[CH:15]=[CH:14][CH:13]=[CH:12]2)=[O:27]
Reactant: CSc1c2ccccc2c(C=O)c2ccccc12
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: CS(=O)c1c2ccccc2c(C=O)c2ccccc12
Temperature: 25 °C
Yield: 94 %

Procedure:
A 1 L round bottom flask fitted with addition funnel and stirring bar was charged with 10-methylthio-9-anthracenecarbaldehyde (example 6A, 12.0 g, 48 mmol) and 450 mL of CH2Cl2. The resulting solution was cooled to 5° with an ice bath. A solution of MCPBA (Aldrich (85%), 9.64 g, 48 mmol) in 350 mL of CH2Cl2 was then added dropwise to the flask over 1 h. The reaction mixture was allowed to warm to RT over 1 h and then was washed with 5% NaHCO3 solution (2×500 mL), dried (Na2SO4), filtered, concentrated to 500 mL, and passed through SiO2 (250 g) using PhCH3 (5 L) eluting solvent. The desired material was then eluted from the SiO2 using EtOAc (2 L) as the eluting solvent. The solvent volume was reduced to 100 mL and then diluted to 700 mL with hexane. The resulting yellow solid was filtered and dried at 50° to give 11.98 g (94% of 10-methylsulfinyl-9-anthracenecarbaldehyde mp 182°-184°, (C, H, S).
Reaction SMILES: [Si:1]([O:8][C@H:9]([C:23]#[N:24])[C@@H:10]([NH:12][C:13](=[O:22])[O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH3:11])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C([S:27]P([O-])(OCC)=S)C>O>[NH2:24][C:23](=[S:27])[C@@H:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2])[C@@H:10]([NH:12][C:13](=[O:22])[O:14][CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[CH3:11]
Reactant: CCOP([O-])(=S)SCC
Reactant: C[C@H](NC(=O)OCc1ccccc1)[C@@H](C#N)O[Si](C)(C)C(C)(C)C
Solvent: O
Product: C[C@H](NC(=O)OCc1ccccc1)[C@H](O[Si](C)(C)C(C)(C)C)C(N)=S
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of benzyl ((1S,2S)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-cyano-1-methylethyl)carbamate (115.6 mg, 0.287 mmol), diethyldithiophosphate (1 mL) and water (3 drops) was stirred overnight at room temperature. The reaction mixture was partitioned between saturated NaHCO3 (40 mL) and EtOAc (40 mL). The aqueous layer was separated and extracted with EtOAc (2×40 mL). The combined extracts were dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 12×160 mm, 0-40% EtOAc in hexanes gradient) to afford benzyl ((1S,2S)-3-amino-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methyl-3-thioxopropyl)carbamate as a colorless oil. Rf=0.30 (20% EtOAc in hexanes). LCMS calc.=383.2; found=383.1 (M+1)+. 1H NMR (500 MHz, CDCl3) δ 8.36 (s, 1H), 7.87 (s, 1H), 7.37-7.29 (m, 5H), 5.13 (m, 2H), 4.85 (d, J=8.2 Hz, 1H), 4.72 (s, 1H), 4.47 (m, 1H), 1.05 (d, J=6.7 Hz, 3H), 0.96 (s, 9H), 0.08 (s, 3H), 0.07 (s, 3H).
Reaction SMILES: [CH:1]1([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[OH:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[C:15]([Cl:23])(=[O:22])[C:16]1[CH:21]=[CH:20][CH:19]=[N:18][CH:17]=1>N1C=CC=CC=1>[ClH:23].[C:15]([O:13][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=1[CH:1]1[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1)(=[O:22])[C:16]1[CH:21]=[CH:20][CH:19]=[N:18][CH:17]=1
Reactant: Oc1ccccc1C1CCCCC1
Reactant: O=C(Cl)c1cccnc1
Agent: Cl
Solvent: c1ccncc1
Product: O=C(Oc1ccccc1C1CCCCC1)c1cccnc1
Temperature: 30 °C
Reaction time: 24 h

Procedure:
15 g (85 mmol) of o-cyclohexylphenol and 16.5 g (93 mmol) of nicotinic acid chloride hydrochloride was mixed with 200 ml of dry pyridine and stirred for 24 hours at 30° C. After cooling precipitated pyridine hydrochloride was sucked off and 300 ml of water added. The precipitated raw product was washed with two 200 ml portions of water, dissolved in alcohol and reduced by means of a rotary evaporator. The remaining viscous oil was dissolved in 500 ml of dry ether and hydrochlorinated with HCl gas. Subsequently, the mixture was filtered, washed with ether and dried.
Reaction SMILES: [O:1]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH2:14][C:15]([OH:17])=[O:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(=O)(=O)(O)O.O.[CH3:24]O>>[O:1]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH2:14][C:15]([O:17][CH3:24])=[O:16])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CO
Reactant: O=C(O)Cc1ccccc1Oc1ccccc1
Agent: O=S(=O)(O)O
Solvent: O
Product: COC(=O)Cc1ccccc1Oc1ccccc1
Yield: 91 %

Procedure:
A solution of 2-phenoxyphenylacetic acid (2.75 g) in dry methanol (30 ml) containing concentrated sulphuric acid (0.3 ml) was heated under reflux for 2 hours then allowed to cool, poured into water and extracted with ether. The extracts were washed with water, dried and concentrated under reduced pressure to give methyl 2-phenoxyphenylacetate (2.65 g, 91%) as a pale yellow oil.