Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([SH:8])=[CH:4][CH:3]=1.Br[CH2:10][CH2:11][CH2:12][OH:13].[OH-].[Na+]>O1CCCC1.C(OCC)(=O)C.CCCCCC>[F:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:10][CH2:11][CH2:12][OH:13])=[CH:4][CH:3]=1
Reactant: OCCCBr
Reactant: Fc1ccc(S)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: C1CCOC1
Product: OCCCSc1ccc(F)cc1
Temperature: 80 °C
Yield: 51.7 %

Procedure:
4-Fluorobenzenethiol (788 mg, 6.15 mmol) and 3-bromopropanol (0.535 ml, 6.16 mmol) was dissolved in tetrahydrofuran (20 ml). The solution was added with 1N aqueous solution of sodium hydroxide (6.2 ml, 6.2 mmol) and heated at 80° C. for 3 hours with stirring. The reaction mixture was diluted with a mixed solvent of ethyl acetate-hexane and washed with diluted aqueous solution of sodium hydroxide, water, and then with saturated brine, and dried over magnesium sulfate. Insoluble solids were moved by filtration and the filtrate was concentrated under reduced pressure. The resulting oil was purified by silica gel column chromatography (ethyl acetate-hexane) to obtain the title compound as colorless oil (592 mg, yield: 52%).
Reaction SMILES: [F:1][C:2]1[CH:21]=[CH:20][CH:19]=[CH:18][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][C:11]([CH3:14])=[N:12][CH:13]=[C:8]2[C:7]([C:15](=[NH:17])[NH2:16])=[N:6]1.C([N:24](CC)CC)C.O.NN>C(O)C>[F:1][C:2]1[CH:21]=[CH:20][CH:19]=[CH:18][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][C:11]([CH3:14])=[N:12][CH:13]=[C:8]2[C:7]([C:15](=[NH:16])[NH:17][NH2:24])=[N:6]1
Reactant: Cc1ncc2c(C(=N)N)nn(Cc3ccccc3F)c2n1
Reactant: CCN(CC)CC
Agent: NN
Solvent: CCO
Solvent: O
Product: Cc1ncc2c(C(=N)NN)nn(Cc3ccccc3F)c2n1
Temperature: 0 °C
Reaction time: 18 h

Procedure:
688 mg (approx. 2.20 mmol, purity 92%) of 1-(2-fluorobenzyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidine-3-carboximidamide were initially charged in 10 ml of ethanol and cooled to 0° C. 891 mg (8.80 mmol) of triethylamine and 138 mg (2.20 mmol) of 80% hydrazine hydrate were added, and the mixture was stirred at room temperature for 18 h. The mixture was concentrated on a rotary evaporator, taken up in ethyl acetate and washed three times with saturated aqueous sodium chloride solution. The organic phase was dried over sodium sulphate, concentrated on a rotary evaporator and dried under high vacuum. 654 mg (purity 93%, 92% of theory) of the target compound were obtained.
Reaction SMILES: [OH:1][NH:2]C(=O)C(CCOC1C=CC=CC=1)C(S(C1C=CC(OC)=CC=1)(=O)=O)CCCCC1C=CC=CC=1.[CH3:37][O:38][C:39]1[CH:44]=[CH:43][C:42]([S:45]([CH:48]([CH2:62][CH2:63][CH2:64][CH2:65][C:66]2[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=2)[CH:49]([CH2:53][CH2:54][S:55][C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=2)[C:50]([OH:52])=[O:51])(=[O:47])=[O:46])=[CH:41][CH:40]=1>>[OH:1][NH:2][C:50](=[O:51])[C@@H:49]([CH2:53][CH2:54][S:55][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1)[C@H:48]([S:45]([C:42]1[CH:43]=[CH:44][C:39]([O:38][CH3:37])=[CH:40][CH:41]=1)(=[O:47])=[O:46])[CH2:62][CH2:63][CH2:64][CH2:65][C:66]1[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=1.[CH3:37][O:38][C:39]1[CH:40]=[CH:41][C:42]([S:45]([CH:48]([CH2:62][CH2:63][CH2:64][CH2:65][C:66]2[CH:67]=[CH:68][CH:69]=[CH:70][CH:71]=2)[CH:49]([CH2:53][CH2:54][S:55][C:56]2[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=2)[C:50]([OH:52])=[O:51])(=[O:47])=[O:46])=[CH:43][CH:44]=1.[OH:1][NH:2][C:50](=[O:51])[CH:49]([CH2:53][CH2:54][S:55][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1)[CH:48]([S:45]([C:42]1[CH:43]=[CH:44][C:39]([O:38][CH3:37])=[CH:40][CH:41]=1)(=[O:47])=[O:46])[CH2:62][CH2:63][CH2:64][CH2:65][C:66]1[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=1
Reactant: COc1ccc(S(=O)(=O)C(CCCCc2ccccc2)C(CCOc2ccccc2)C(=O)NO)cc1
Agent: COc1ccc(S(=O)(=O)C(CCCCc2ccccc2)C(CCSc2ccccc2)C(=O)O)cc1
Product: COc1ccc(S(=O)(=O)C(CCCCc2ccccc2)C(CCSc2ccccc2)C(=O)NO)cc1
Product: COc1ccc(S(=O)(=O)[C@H](CCCCc2ccccc2)[C@H](CCSc2ccccc2)C(=O)NO)cc1
Yield: 79 %

Procedure:
The titled compound is prepared according to the method used in the preparation of (±)-(2R*, R*)-3-(4-methoxybenzenesulfonyl)-7-phenyl-2-(2-phenoxyethyl)heptanoic acid hydroxyamide, except using (±)-(2R*, 3R*)-3-(4-methoxybenzenesulfonyl)-7-phenyl-2-(2-phenylsulfanyl-ethyl)heptanoic acid as the starting material. From (±)-(2R*, 3R*)-3-(4-methoxybenzenesulfonyl)-7-phenyl-2-(2-phenylsulfanylethyl)heptanoic acid (0.64 g, 1.2 mmol) provides (±)-(2R*, 3R*)-3-(4-methoxybenzenesulfonyl)-7-phenyl-2-(2-phenylsulfanylethyl)heptanoic acid hydroxyamide (0.5 g, 79%): 1H NMR (300 MHz, CDCl3) δ 9.44 (bs, 1H), 7.75 (d, J=8.9 Hz, 2H), 7.28-7.14 (m, 8H), 7.05 (d, J=7.2 Hz, 2H), 6.99 (d, J=9.0 Hz, 2H), 3.88 (s, 3H), 3.28-3.25 (m, 1H), 3.00-2.93 (m, 2H), 2.75-2.66 (m, 1H), 2.46 (t, J=7.3 Hz, 2H), 2.43-2.30 (m, 1H) 1.83-1.17 (m, 8H); MS (FAB) m/e 528 (M+H)+ ; Anal. (C28H33O5NS2.0.3 H2O) C, H, N.
Reaction SMILES: [F:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:5]([F:9])[C:3]=1[NH2:4].C(=O)(O)[O-].[Na+].Br[CH2:16][C:17]([O:19][CH3:20])=[O:18]>ClCC(OC)=O>[CH3:20][O:19][C:17](=[O:18])[CH2:16][NH:4][C:3]1[C:2]([F:1])=[CH:8][CH:7]=[CH:6][C:5]=1[F:9]
Reactant: COC(=O)CBr
Reactant: Nc1c(F)cccc1F
Agent: COC(=O)CCl
Agent: O=C([O-])O
Agent: [Na+]
Product: COC(=O)CNc1c(F)cccc1F
Reaction time: 16 h

Procedure:
A suspension of 2,6-difluoroaniline (15.0 g) and sodium bicarbonate (19.5 g) in methyl chloroacetate (15.2 ml) was stirred at 90°-100° under nitrogen for 16 h. Methyl bromoacetate (11.0 ml) and sodium bicarbonate (9.75 g) were added, and the suspension was stirred at 90°-100° for a further 5 h. Work up according to the method of Intermediate 11 gave an oil (14.7 g) which was purified by FCC eluting with system A (1:8) to give the title compound (8.27 g) as an oil, t.l.c. (System A, 1:8) Rf 0.3.
Reaction SMILES: [CH2:1]([N:7]=[C:8]=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[NH2:10][CH2:11][CH2:12][CH2:13][N:14]1[CH2:19][CH2:18][N:17]([CH2:20][CH2:21][C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=2)[CH2:16][CH2:15]1>C(Cl)Cl>[ClH:28].[ClH:28].[Cl:28][C:25]1[CH:24]=[CH:23][C:22]([CH2:21][CH2:20][N:17]2[CH2:16][CH2:15][N:14]([CH2:13][CH2:12][CH2:11][NH:10][C:8]([NH:7][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])=[O:9])[CH2:19][CH2:18]2)=[CH:27][CH:26]=1
Reactant: CCCCCCN=C=O
Reactant: NCCCN1CCN(CCc2ccc(Cl)cc2)CC1
Solvent: ClCCl
Product: CCCCCCNC(=O)NCCCN1CCN(CCc2ccc(Cl)cc2)CC1
Product: Cl
Yield: 56.6 %

Procedure:
A solution of n-hexyl isocyanate (1.27 g; 10 mmole) in methylene chloride (25 ml) was added to a solution of 1-(3-aminopropyl)-4-(4-chlorophenethyl)piperazine (2.82 g; 10 mmole) in methylene chloride (50 ml). The resulting mixture was refluxed for 6 hours and concentrated in vacuo to give a yellow oil which was chromatographed on silica gel (methylene chloride/methanol/ammonium hydroxide; 45/5/1). Precipitation as the dihydrochloride and recrystallization from ethanol provided the title compound (0.91 g; 19% yield) as colorless crystals, m.p. 230°-233° C.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH:4]([OH:11])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.N([C:16]1[NH:17][CH2:18][CH2:19][CH2:20][N:21]=1)[N+]([O-])=O.C1(C)C(C)=CC=CC=1>O>[NH:21]1[CH2:20][CH2:19][CH2:18][N:17]=[C:16]1[NH:1][CH2:2][CH2:3][CH:4]([OH:11])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: O=[N+]([O-])NC1=NCCCN1
Reactant: NCCC(O)c1ccccc1
Solvent: O
Solvent: Cc1ccccc1C
Product: OC(CCNC1=NCCCN1)c1ccccc1

Procedure:
A mixture of 8 parts of α-(2-aminoethyl)benzylalcohol, 7.2 parts of 2-(nitramino)-1,4,5,6-tetrahydropyrimidine and 40 parts of xylene is stirred and refluxed for 48 hours with water-separator. Upon cooling the reaction mixture, the product is separated as an oil. The xylene is decanted and the oily product is triturated in diisopropylether. The solid product is filtered off and crystallized from acetone, yielding α-[2-(1,4,5,6-tetrahydro-2-pyrimidinylamino)ethyl]benzylalcohol; m.p. 130°-135°C.
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=O.C([N:13]([CH:17]([CH3:19])[CH3:18])C(C)C)C.C1(N)CC1>S(Cl)(Cl)=O.O1CCOCC1.C(OCC)(=O)C>[CH:17]1([NH:13][C:5](=[O:7])[C:4]2[CH:8]=[CH:9][CH:10]=[C:2]([I:1])[CH:3]=2)[CH2:19][CH2:18]1
Reactant: O=C(O)c1cccc(I)c1
Reactant: CCN(C(C)C)C(C)C
Agent: NC1CC1
Solvent: C1COCCO1
Solvent: O=S(Cl)Cl
Solvent: CCOC(C)=O
Product: O=C(NC1CC1)c1cccc(I)c1
Temperature: 70 °C
Reaction time: 1 h

Procedure:
3-Iodobenzoic acid (4.79 g, 19.3 mmol) was suspended in thionyl chloride (19.3 mL) and stirred for 1 h at 70° C. before it was conc. and azeotropically dried with toluene. The reaction mixture was dissolved in dioxane (19.3 mL) before N-ethyl-N-isopropylpropan-2-amine (13.5 mL, 77.3 mmol) and cyclopropylamine (6.77 mL, 96.6 mmol) were added and stirred for 16 h at ambient temperature. The reaction mixture was diluted with 75 mL of ethyl acetate, added to a separation funnel, partitioned with sodium bicarbonate (saturated, aqueous), washed 2× with 50 mL of 3 N HCl (aqueous), separated, dried over sodium sulfate, and concentrated in vacuo to give the title compound. MS (ES+): 288 (M+H)+.
Reaction SMILES: C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH2:12][C@H:13]1[C@H:17]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=2)[CH2:16][N:15]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:14]1.C(N(CC)CC)C.[Cl:40][C:41]1[CH:49]=[CH:48][C:44]([C:45](Cl)=[O:46])=[CH:43][CH:42]=1.O>C(#N)C>[Cl:40][C:41]1[CH:49]=[CH:48][C:44]([C:45]([NH:12][C@H:13]2[C@H:17]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=3)[CH2:16][N:15]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:14]2)=[O:46])=[CH:43][CH:42]=1
Reactant: CC(C)(C)OC(=O)N1C[C@@H](N)[C@H](c2ccc(Cl)c(Cl)c2)C1
Reactant: O=C(Cl)c1ccc(Cl)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CC#N
Solvent: O
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1C[C@@H](NC(=O)c2ccc(Cl)cc2)[C@H](c2ccc(Cl)c(Cl)c2)C1
Temperature: 25 °C
Reaction time: 14 h
Yield: 78 %

Procedure:
To a solution of the compound (1.1 g) obtained in step 6 and triethylamine (664 μL) in acetonitrile (10 mL) was added 4-chlorobenzoyl chloride (308 μL) at 0° C., and the mixture was stirred at room temperature for 14 hr. The reaction mixture was poured into water, and the resultant product was extracted with ethyl acetate. The organic layer was washed with aqueous sodium hydrogen carbonate solution and brine and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 10→40% ethyl acetate/hexane) to give the title compound (0.80 g, 78%) as a white powder.
Reaction SMILES: Br[C:2]1[CH:20]=[CH:19][C:5]2[N:6]=[C:7]([C@H:9]3[CH2:12][C@H:11]([N:13]4[CH2:17][CH2:16][CH2:15][C@H:14]4C)[CH2:10]3)[S:8][C:4]=2[CH:3]=1.[CH3:21][C:22]1[CH:23]=[CH:24][C:25](=[O:28])[NH:26][CH:27]=1.N1NC(=O)C=CC=1>>[CH3:21][C:22]1[CH:23]=[CH:24][C:25](=[O:28])[N:26]([C:2]2[CH:20]=[CH:19][C:5]3[N:6]=[C:7]([C@H:9]4[CH2:10][C@H:11]([N:13]5[CH2:14][CH2:15][CH2:16][CH2:17]5)[CH2:12]4)[S:8][C:4]=3[CH:3]=2)[CH:27]=1
Reactant: Cc1ccc(=O)[nH]c1
Reactant: C[C@@H]1CCCN1[C@H]1C[C@H](c2nc3ccc(Br)cc3s2)C1
Agent: O=c1cccn[nH]1
Product: Cc1ccc(=O)n(-c2ccc3nc([C@H]4C[C@H](N5CCCC5)C4)sc3c2)c1

Procedure:
The title compound was prepared according to the procedure described in Example 22, substituting the product of Example 62A for the product of Example 1E and substituting 5-methyl-2(1H)-pyridone for 3(2H)-pyridazinone. 1H NMR (300 MHz, CDCl3) δ ppm 8.03 (d, J=9.15 Hz, 1H) 7.87-7.90 (m, 1H) 7.44 (td, J=9.00, 2.03 Hz, 1H) 7.29 (dt, J=9.00, 2.37 Hz, 2H) 7.15 (s, 1H) 6.63 (d, J=9.15 Hz, 1H) 3.61-3.73 (m, 1H) 3.03-3.16 (m, 1H) 2.43-2.78 (m, 6H) 2.12 (s, 3H) 1.81-1.91 (m, 4H) 1.51-1.61 (m, 2H). MS: (M+H)+=366.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:12]=[CH:11][C:9]([NH2:10])=[CH:8][CH:7]=1.N1C=CC=CC=1.Cl[C:20]([O:22][C:23]1[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[CH:25][CH:24]=1)=[O:21]>C(Cl)Cl>[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:12]=[CH:11][C:9]([NH:10][C:20](=[O:21])[O:22][C:23]2[CH:24]=[CH:25][C:26]([N+:29]([O-:31])=[O:30])=[CH:27][CH:28]=2)=[CH:8][CH:7]=1
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Reactant: COCCOc1ccc(N)cc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: COCCOc1ccc(NC(=O)Oc2ccc([N+](=O)[O-])cc2)cc1
Temperature: 25 °C
Reaction time: 5 h
Yield: 72.4 %

Procedure:
A solution of 4-(2-methoxyethoxy)aniline (0.397 g, 2.37 mmol) and pyridine (1 mL, 12.4 mmol) in DCM (3 mL) in was treated with 4-nitrophenyl chloroformate (Aldrich) (0.505 g, 2.51 mmol) added in portions (exothermic!). The pale yellow solution was stirred at RT for 5 h. The reaction mixture was partitioned between 0.5 N HCl (20 mL) and DCM (30 mL). The organic phase was washed with 0.5 N HCl (30 mL), saturated aqueous sodium bicarbonate (30 mL), water (30 mL) and saturated aqueous sodium chloride (30 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (50 g, eluent: EtOAc in hexanes 10%-50%) to give 4-nitrophenyl 4-(2-methoxyethoxy)phenylcarbamate (0.57 g, 72% yield) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ 8.25-8.32 (m, 2H); 7.32-7.43 (m, 4H); 6.87-6.97 (m, 3H); 4.09-4.15 (m, 2H); 3.72-3.79 (m, 2H); 3.46 (s, 3H). m/z (ESI, +ve ion) 333.0 (M+H)+.
Reaction SMILES: [H-].[Na+].[Br:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]([O:13]CC)=O)=[CH:6][CH:5]=1.[H][H].Cl>C1(C)C=CC=CC=1.O>[Br:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11](=[O:13])[CH2:10][C:7]2[CH:6]=[CH:5][C:4]([Br:3])=[CH:9][CH:8]=2)=[CH:6][CH:5]=1
Reactant: CCOC(=O)Cc1ccc(Br)cc1
Reactant: [H][H]
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O
Product: O=C(Cc1ccc(Br)cc1)Cc1ccc(Br)cc1
Temperature: 50 °C
Yield: 80.7 %

Procedure:
To a slurry of sodium hydride (9.17 grams, 0.23 mole) in 50 milliliters of toluene was added dropwise, a solution of ethyl 4-bromophenylacetate (50 grams, 0.21 mole) in toluene (50 milliliters) at 30-32° C. After addition was completed, the reaction mixture was slowly warmed to 50° C. where the reaction began to rapidly exotherm with evolution of hydrogen gas. The reaction mixture was further heated to 78° C. for 2 hours, cooled to room temperature and then HCl (45 grams) in water (22.5 grams) was slowly added dropwise to neutralize the solution. The layers were separated and the aqueous phase was extracted with diethylether. The combined organic extracts were dried and the solvent was removed to leave a yellow oil. This oil was refluxed for 24 hours in a mixture of glacial acid (60 milliliters) and concentrated HCl (30 milliliters). After cooling, the layers were separated, and the organic layer solidified to provide a yellow solid. This crude product was recrystallized from n-heptane to give a pure product as a white solid (31.2 grams, 82% isolated yield).
Reaction SMILES: [C:1]([OH:13])(=[O:12])[CH2:2][C:3]([CH2:8][C:9]([OH:11])=[O:10])([C:5]([OH:7])=[O:6])[OH:4].C(=O)([O-])[O-].[Ca+2:18]>O>[C:1]([O-:13])(=[O:12])[CH2:2][C:3]([CH2:8][C:9]([O-:11])=[O:10])([C:5]([O-:7])=[O:6])[OH:4].[Ca+2:18].[C:1]([O-:13])(=[O:12])[CH2:2][C:3]([CH2:8][C:9]([O-:11])=[O:10])([C:5]([O-:7])=[O:6])[OH:4].[Ca+2:18].[Ca+2:18]
Reactant: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: O=C([O-])[O-]
Agent: [Ca+2]
Solvent: O
Product: O=C([O-])CC(O)(CC(=O)[O-])C(=O)[O-]

Procedure:
Six powder mixes of potassium calcium citrate were prepared; their compositions are presented in Table 3. Calcium was provided as calcium carbonate. By adding equivalent amount of citric acid, calcium carbonate was allowed to dissolve in water or gastric juice by reacting with citric acid to form soluble calcium citrate. Potassium was provided as potassium citrate. When the premix of calcium carbonate, citric acid and potassium citrate was dissolved in water, the resulting aqueous preparations delivered the same single doses of calcium and potassium, as provided by the usual single doses of commercial calcium citrate and potassium citrate; that is, 20 mEq (400 mg) of calcium and 20 mEq of potassium, respectively. Preparation A contained just the amount of total citrate (40 mEq) to neutralize total amount of calcium and potassium cations (40 mEq). Thus, the molar ratio of Preparation A was 2:1:1.33, since each dose in 250 cc yielded 20 mmol potassium, 10 mmol calcium, and 1.33 mmol citrate (40 mEq divided by a valence of 3). The chemical composition of Preparation A was identical to a single dose of combined calcium citrate and potassium citrate treatment described in Examples 1 and 2.
Reaction SMILES: [OH:1][CH:2]([CH:8]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[O:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[N+:16]([O-:18])=[O:17])[C:3]([O:5][CH2:6][CH3:7])=[O:4].[CH3:25]I.[H-].[Na+].O>CN(C)C=O>[CH3:25][O:1][CH:2]([CH:8]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[O:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[N+:16]([O-:18])=[O:17])[C:3]([O:5][CH2:6][CH3:7])=[O:4]
Reactant: CCOC(=O)C(O)C(Oc1ccccc1[N+](=O)[O-])c1ccccc1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)C(OC)C(Oc1ccccc1[N+](=O)[O-])c1ccccc1
Temperature: 3 °C
Reaction time: 1 h
Yield: 96 %

Procedure:
To 2 g of ethyl 2-hydroxy-3-phenyl-3-(2-nitro-phenoxy)-propionate dissolved in 30 ml of anhydrous dimethylformamide, CH3I (0.78 ml) was added at 3° C., then in two additions at the same temperature, NaH 50% (0.3 g) was added too. The whole was stirred at 3° C. for one hour and at room temperature for one hour, after which it was poured into 300 ml of water, extracted with ethyl ether which, after washing with NaCl saturated water and dehydration with sodium sulphate, was evaporated to dryness under reduced pressure. There was obtained 2 g (96%) of ethyl 2-methoxy-3-phenyl-3-(2-nitro-phenoxy)-propionate as an oil.
Reaction SMILES: [NH2:1][CH2:2][CH:3]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH2:4][OH:5].C(N(C(C)C)CC)(C)C.Cl[C:22](Cl)([O:24]C(=O)OC(Cl)(Cl)Cl)Cl>C(Cl)Cl>[C:6]1([CH:3]2[CH2:4][O:5][C:22](=[O:24])[NH:1][CH2:2]2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: NCC(CO)c1ccccc1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: O=C1NCC(c2ccccc2)CO1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
A cooled (0° C.) solution of 3-amino-2-phenylpropan-1-ol (245 mg, 1.62 mmol) in CH2Cl2 (10 mL) was treated with diisopropylethylamine (1.65 mL, 9.72 mmol) and triphosgene (241 mg, 0.81 mmol), under an atmosphere of nitrogen. The reaction was stirred at 0° C. for an additional 2 h. The reaction was quenched with sat. NaHCO3 (2 mL) and then extracted with EtOAc (3×40 mL). The combined organic extracts were washed with brine (30 mL), dried (MgSO4), filtered and concentrated to afford the title compound as a colorless oil. LCMS=178.2 (M+1)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11](=NNS(C2C=CC(C)=CC=2)(=O)=O)[CH2:12][C:13]2[CH:18]=CC3OCOC=3[CH:14]=2)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.C[C:35]([CH3:38])([O-:37])[CH3:36].[K+].[C:40]1(C)[CH:45]=CC=C[CH:41]=1>O>[CH3:10][O:9][C:7]1[CH:6]=[C:5](/[CH:11]=[CH:12]/[C:13]2[CH:18]=[CH:38][C:35]([O:37][CH:40]([CH3:45])[CH3:41])=[CH:36][CH:14]=2)[CH:4]=[C:3]([O:2][CH3:1])[CH:8]=1
Reactant: Cc1ccccc1
Reactant: COc1cc(OC)cc(C(Cc2ccc3c(c2)OCO3)=NNS(=O)(=O)c2ccc(C)cc2)c1
Reactant: CC(C)(C)[O-]
Agent: [K+]
Solvent: O
Product: COc1cc(/C=C/c2ccc(OC(C)C)cc2)cc(OC)c1
Temperature: 90 °C
Yield: 55.6 %

Procedure:
19 g of N-[1-(3,5-dimethoxyphenyl)-2-(3,4-methylenedioxyphenyl)ethylidene]-N′-tosylhydrazine (0.39 mol) prepared as in Example 29. 9.3 g of potassium ter-butoxide (0.83 mol) and 1.9 g of Triton X100® are introduced into a three-necked round-bottomed flask comprising 100 ml of toluene. The mixture is brought to reflux for 3 h, cooled to approximately 90° C. and 70 ml of water are introduced. Separation by settling is carried out and the aqueous phase is re-extracted with 50 ml of toluene. The toluene phases are washed with 50 ml of water and concentrated to result in 12.3 g of a viscous product with a yellow color, which is taken up in 10 ml of methanol and maintained for 3 h under agitation. The precipitate is filtered off, washed on the filter with methanol and dried. 6.5 g of (E)-3,5-dimethoxy-4′-isopropyloxy-stilbene is recovered in the form of a white solid, which exhibits a melting point of 61° C., i.e. a yield of 55.6% with respect to the starting hydrazone.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]2[C:8]([CH:11]3[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]3)=[CH:9][NH:10][C:5]2=[CH:4][CH:3]=1.[CH3:18][C:19]1[CH:23]=[CH:22][S:21][C:20]=1[C:24](Cl)=[O:25]>>[CH3:18][C:19]1[CH:23]=[CH:22][S:21][C:20]=1[C:24]([NH:1][C:2]1[N:7]=[C:6]2[C:8]([CH:11]3[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]3)=[CH:9][NH:10][C:5]2=[CH:4][CH:3]=1)=[O:25]
Reactant: CN1CCC(c2c[nH]c3ccc(N)nc23)CC1
Reactant: Cc1ccsc1C(=O)Cl
Product: Cc1ccsc1C(=O)Nc1ccc2[nH]cc(C3CCN(C)CC3)c2n1
Yield: 82.7 %

Procedure:
Beginning with 0.40 gm (1.74 mMol) 5-amino-3-(1-methylpiperidin-4-yl)pyrrolo[3,2-b]pyridine and 0.34 gm (2.08 mMol) 3-methyl-2-thiophenecarbonyl chloride, 0.51 gm (83%) of the title compound were prepared as a light brown foam essentially by the procedure described in Example 4. A sample was crystallized from ethanol/water for analysis.
Reaction SMILES: [CH3:1][C:2]1([CH3:19])[CH2:11][C:10](=[O:12])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:13]#[C:14][Si](C)(C)C)[CH:8]=2)[S:3]1.C([O-])([O-])=O.[K+].[K+]>CO.O>[C:13]([C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[S:3][C:2]([CH3:1])([CH3:19])[CH2:11][C:10]2=[O:12])#[CH:14]
Reactant: CC1(C)CC(=O)c2cc(C#C[Si](C)(C)C)ccc2S1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Product: C#Cc1ccc2c(c1)C(=O)CC(C)(C)S2
Yield: 98.5 %

Procedure:
A solution of 2,2-dimethyl-6-trimethylsilanylethynyl-thiochroman-4-one (110.0 mg, 0.38 mmol) and K2CO3 (40.0 mg, 0.29 mmol) in 10.0 mL MeOH was stirred overnight at room temperature. The solution was diluted with H2O and extracted with Et2O. The combined organic layers were washed with H2O and saturated aqueous NaCl and dried over MgSO4. Removal of the solvent under reduced pressure afforded 81 mg (99%) of the 6-ethynyl-2,2-dimethylthiochroman-4-one as an orange oil. 1H NMR (300 MHz, CDCl3) δ:8.20 (1H, d, J=1.9Hz), 7.46(1H, dd, J=1.9, 8.1 Hz), 7.18 (1H, d, J=8.1 Hz), 3.08 (1H, s), 2.86 (2H, s), 1.46 (6H, s).
Reaction SMILES: [OH-].[K+].[C:3]([OH:11])(=[S:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[NH2:12]OS(O)(=O)=O.C1(N=C=O)C=CC=CC=1>O>[C:3]([S:10][NH2:12])(=[O:11])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: NOS(=O)(=O)O
Reactant: OC(=S)c1ccccc1
Agent: [K+]
Agent: [OH-]
Solvent: O=C=Nc1ccccc1
Solvent: O
Product: NSC(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 60 %

Procedure:
To a stirred solution of KOH (560 mg, 10 mmol) in water (15 mL) was added thiobenzoic acid (690 mg, 5 mmol) and hydroxylamine-O-sulfonic acid (565 mg, 5 mmol). The solution was stirred for 20 min at room temperature. The white solid (S-benzoylthiohydroxylamine) was collected by filtration and then dissolved in CH2Cl2 (10 mL). To this mixture was added phenyl isocyanate (1.19 g, 10 mmol). The resulting solution was allowed to stir overnight at room temperature. The crude product was collected by the filtration and recrystallized in CH2Cl2/hexane. Pure compound 14 was obtained as a white solid (overall yield 60%). m.p. 184-186° C.; 1H NMR (300 MHz, DMSO-d6) δ 9.11 (s, 1H), 7.99 (s, 1H), 7.88 (d, 7.5 Hz, 2H), 7.74 (t, J=8.1 Hz, 1H), 7.59 (t, J=7.5 Hz, 2H), 7.45 (d, J=7.5 Hz, 2H), 7.24 (t, J=7.8 Hz, 2H), 6.98 (t, J=7.2 Hz, 1H); 13C NMR (75 MHz, DMSO-d6) δ 193.4, 155.0, 140.1, 135.2, 134.6, 130.1, 129.4, 127.2, 123.1, 119.3; IR (thin film) cm−1 3286, 3240, 1697, 1638, 1541, 1474, 1459, 1207; MS m/z 273.1 [M+H]+; calcd for C14H13N2O2S 273.1.