Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1.C(=O)(O)[O-].[Na+].[N+:18]([C:21]1[CH:27]=[C:26]([N+:28]([O-:30])=[O:29])[C:25](F)=[CH:24][C:22]=1[NH2:23])([O-:20])=[O:19]>O.C(O)C>[N+:28]([C:26]1[CH:27]=[C:21]([N+:18]([O-:20])=[O:19])[C:22]([NH2:23])=[CH:24][C:25]=1[NH:1][CH2:2][CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1)([O-:30])=[O:29]
Reactant: Nc1cc(F)c([N+](=O)[O-])cc1[N+](=O)[O-]
Reactant: NCCc1c[nH]c2ccccc12
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: Nc1cc(NCCc2c[nH]c3ccccc23)c([N+](=O)[O-])cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 2 h
Yield: 90 %

Procedure:
1 mMole of tryptamine was dissolved in 100 ml of water and the pH was adjusted to pH 8.3 with 2.5 moles of sodium bicarbonate (NaHCO3), A 1.5% solution of 2,4-dinitro-5-fluoroaniline in 200 ml ethanol was added and the mixture was stirred during 2 hours at room temperature. The desired product precipitates out, it is washed and dried. The product is obtained in 90% yield, and TLC (chloroform, silica-gel plates, reveals one yellow spot (Rf=0.57) which is well resolved from the starting materials under the same conditions
Reaction SMILES: [SH:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[CH:4][N:3]=1.[CH3:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][C:22]([S:25]([NH:28][CH:29]([CH2:34][CH:35]3[O:37][CH2:36]3)[C:30]([O:32]C)=[O:31])(=[O:27])=[O:26])=[CH:21][CH:20]=2)=[CH:15][CH:14]=1>>[CH3:11][O:12][C:13]1[CH:14]=[CH:15][C:16]([C:19]2[CH:20]=[CH:21][C:22]([S:25]([NH:28][CH:29]([CH2:34][CH:35]([OH:37])[CH2:36][S:1][C:2]3[N:10]=[C:9]4[C:5]([NH:6][CH:7]=[N:8]4)=[CH:4][N:3]=3)[C:30]([OH:32])=[O:31])(=[O:26])=[O:27])=[CH:23][CH:24]=2)=[CH:17][CH:18]=1
Reactant: COC(=O)C(CC1CO1)NS(=O)(=O)c1ccc(-c2ccc(OC)cc2)cc1
Reactant: Sc1ncc2[nH]cnc2n1
Product: COc1ccc(-c2ccc(S(=O)(=O)NC(CC(O)CSc3ncc4[nH]cnc4n3)C(=O)O)cc2)cc1

Procedure:
Example 48 is prepared from 2-mercaptopurine and 1d using the procedure described for compound 20.
Reaction SMILES: Cl.[S:2]1[C:10]2[CH2:9][CH2:8][NH:7][CH2:6][C:5]=2[CH:4]=[CH:3]1.Br[CH:12]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[Cl:22])[C:13]([OH:15])=[O:14].[OH-].[K+].Cl>O.CO>[Cl:22][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[CH:12]([N:7]1[CH2:8][CH2:9][C:10]2[S:2][CH:3]=[CH:4][C:5]=2[CH2:6]1)[C:13]([OH:15])=[O:14]
Reactant: O=C(O)C(Br)c1ccccc1Cl
Reactant: c1cc2c(s1)CCNC2
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: O=C(O)C(c1ccccc1Cl)N1CCc2sccc2C1
Temperature: 40 °C
Yield: 93.3 %

Procedure:
50.0 g of 4,5,6,7-tetrahydrothieno[3,2-c]pyridine hydrochloride and 74.6 g of α-bromo-(2-chlorophenyl)acetic acid were successively added to a mixture of 275 ml of water and 75 ml of methanol, and the resulting solution was cooled to below 10° C. while stirring. 63.9 g of 85.0% KOH dissolved in 142 ml of water was slowly added to the above solution while maintaining the temperature at below 15° C. The resulting transparent solution was heated to 40° C. and stirred at that temperature for 3 hrs. The pH of the reaction solution was adjusted to 3.5 with 6N—HCl, cooled to room temperature and stirred for 2 hrs. Then, the reaction mixture was further cooled to below 5° C. and stirred for 2 hrs. The precipitated crystals were filtered, washed sequentially with 150 ml of water and 100 ml of n-hexane, and dried at 40° C. to obtain 81.7 g of the title compound (yield: 88%) as a white-yellow monohydrate.
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]([C:7]([O:9][CH3:10])=[O:8])=[CH:5][N:6]=1.[CH3:11][CH:12]([C:18]([CH3:20])=O)[C:13](OCC)=[O:14]>>[CH3:11][C:12]1[C:13](=[O:14])[N:6]2[CH:5]=[C:4]([C:7]([O:9][CH3:10])=[O:8])[S:3][C:2]2=[N:1][C:18]=1[CH3:20]
Reactant: CCOC(=O)C(C)C(C)=O
Reactant: COC(=O)c1cnc(N)s1
Product: COC(=O)c1cn2c(=O)c(C)c(C)nc2s1
Temperature: 100 °C
Reaction time: 3 h

Procedure:
2-amino-thiazole-5-carboxylic acid, methyl ester (5 g) was reacted with ethyl 2-methyl-acetoacetate (9.11 g) in polyphosphoric acid (25 g: 13.3 g of H3PO4 and 11.7 g of P2O5) under stirring at 100° C. for three hours. After cooling, dilution with ice water and neutralization with 20% NaOH, the precipitate was filtered, washed with water and crystallized from CH2Cl2 -hexane to give 6,7-dimethyl-5-oxo-5H-thiazolo[3,2-a]pyrimidine-2-carboxylic acid, methyl ester, m.p. 158°-159° C. (5.46 g), which was reacted with benzaldehyde (3.52 g) in methanol (120 ml) in the presence of sodium methylate (2.7 g) under stirring at reflux temperature for 120 hours. After cooling and concentration in vacuo, the precipitate was filtered and dissolved in a mixture of dimethylformamide and formic acid. The solution was diluted with ice water and the precipitate was filtered, washed with water until neutral and crystallized from isopropyl alcohol to give 2.8 g of 6-methyl-7-trans-(2-phenylethenyl)-5-oxo-5H-thiazolo[3,2-a]pyrimidine-2-carboxylic acid, m.p. 257°-259° C., N.M.R. (CF3COOD) δp.p.m.: 2.50 (s) (3H, --CH3), 7.36 (d) (1H, β-ethenyl proton), 7.40-7.90 (m) (5H, phenyl protons), 7.73 (d) (1H, α-ethenyl proton), 9.07 (s) (1H, C-3 proton), JHαHβ =16 Hz.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([N+:18]([O-:20])=[O:19])[CH:5]=[C:6]([CH3:17])[C:7]=1[O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=1.[Br:21]N1C(=O)CCC1=O.FC(F)(F)C(O)=O>C(Cl)(Cl)Cl>[Br:21][C:13]1[CH:14]=[C:9]([CH:10]=[CH:11][C:12]=1[O:15][CH3:16])[O:8][C:7]1[C:6]([CH3:17])=[CH:5][C:4]([N+:18]([O-:20])=[O:19])=[CH:3][C:2]=1[CH3:1]
Reactant: COc1ccc(Oc2c(C)cc([N+](=O)[O-])cc2C)cc1
Reactant: O=C1CCC(=O)N1Br
Solvent: ClC(Cl)Cl
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc(Oc2c(C)cc([N+](=O)[O-])cc2C)cc1Br
Yield: 97.2 %

Procedure:
To a solution of 3,5-dimethyl-4-(4′-methoxyphenoxy)nitrobenzene (4.0 g) (J. Med. Chem., 38: 703 (1995)) in chloroform (150 ml) were added N-bromosuccinimide (2.6 g) and trifluoroacetic acid (1.1 ml), and the resulting mixture was heated under reflux for 90 min. Additional portions of N-bromosuccinimide (2.6 g) and trifluoroacetic acid (1.1 ml) were added, followed by further heating for 18 h. The reaction was washed with sodium bicarbonate, dried (Na2SO4) and concentrated to afford the title compound of Step A as an orange solid (5.0 g). MS (APCl+) Calc: 351; Found: 352 (M+1).
Reaction SMILES: C1(C)C=CC=CC=1.S(Cl)([Cl:10])=O.[CH:12]1([CH2:15][O:16][C:17]2[CH:18]=[C:19]([CH:23]=[CH:24][C:25]=2[O:26][CH:27]([F:29])[F:28])[C:20](O)=[O:21])[CH2:14][CH2:13]1>CN(C=O)C>[CH:12]1([CH2:15][O:16][C:17]2[CH:18]=[C:19]([CH:23]=[CH:24][C:25]=2[O:26][CH:27]([F:29])[F:28])[C:20]([Cl:10])=[O:21])[CH2:14][CH2:13]1
Reactant: O=C(O)c1ccc(OC(F)F)c(OCC2CC2)c1
Reactant: O=S(Cl)Cl
Solvent: CN(C)C=O
Solvent: Cc1ccccc1
Product: O=C(Cl)c1ccc(OC(F)F)c(OCC2CC2)c1

Procedure:
A reaction vessel is charged with toluene, a catalytic amount of DMF (1-5% by weight of the amount of thionyl chloride employed) and 1 equivalent of 3-cyclopropylmethoxy-4-difluoromethoxybenzoic acid. While stirring, 1 to 4 equivalents of thionyl chloride are slowly added at 70 to 90° C.
Reaction SMILES: [O:1]=[S:2]1(=[O:29])[CH2:7][CH2:6][N:5]([C:8]([C:10]2[N:11]([CH:26]([CH3:28])[CH3:27])[C:12]3[C:17]([CH:18]=2)=[CH:16][C:15]([O:19][CH:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)=[CH:14][CH:13]=3)=[O:9])[CH2:4][CH2:3]1.C(O)(=O)C.[CH2:34]1[CH2:37][CH2:36][CH2:35]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O1CCCC1>[CH:34]1([N:23]2[CH2:24][CH2:25][CH:20]([O:19][C:15]3[CH:16]=[C:17]4[C:12](=[CH:13][CH:14]=3)[N:11]([CH:26]([CH3:27])[CH3:28])[C:10]([C:8]([N:5]3[CH2:6][CH2:7][S:2](=[O:1])(=[O:29])[CH2:3][CH2:4]3)=[O:9])=[CH:18]4)[CH2:21][CH2:22]2)[CH2:37][CH2:36][CH2:35]1
Reactant: C1CCC1
Reactant: CC(C)n1c(C(=O)N2CCS(=O)(=O)CC2)cc2cc(OC3CCNCC3)ccc21
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: CC(C)n1c(C(=O)N2CCS(=O)(=O)CC2)cc2cc(OC3CCN(C4CCC4)CC3)ccc21
Temperature: 55 °C
Reaction time: 2 h
Yield: 32.1 %

Procedure:
To a mixture of (1,1-dioxo-1λ6-thiomorpholin-4-yl)-[1-isopropyl-5-(piperidin-4-yloxy)-1H-indol-2-yl]-methanone (268 mg, 1.0 eq.) in acetic acid (115 mg, 3.0 eq.) was added a solution of cyclobutane (90 mg, 2.0 eq.) in tetrahydrofuran (8 mL). The mixture was stirred for 2 h at 55° C. Then the mixture was cooled to room temperature and sodium triacetoxyborohydride (279 mg, 2.0 eq.) was added. The reaction mixture was stirred overnight at 65° C. The residue was partitioned between water and ethyl acetate. The organic layer was washed with a sodium hydrogenocarbonate aqueous solution, dried over sodium sulfate, filtered and dried in vacuo. Then the residue was purified on silica eluting with a gradient of dichloromethane/methanol to yield 97 mg (32%) of the desired product as off-white oil. MS (m/e): 474.5 (MH+, 100%).
Reaction SMILES: CN(C)[CH:3]=[C:4]([N:9]=[CH:10]N(C)C)[C:5]([O:7][CH3:8])=[O:6].[CH3:15][N:16]1[CH:20]=[CH:19][CH:18]=[CH:17]1>C(O)(=O)C.C(O)(C(F)(F)F)=O>[CH3:15][N:16]1[C:20]2[CH:3]=[C:4]([C:5]([O:7][CH3:8])=[O:6])[N:9]=[CH:10][C:19]=2[CH:18]=[CH:17]1
Reactant: COC(=O)C(=CN(C)C)N=CN(C)C
Reactant: Cn1cccc1
Solvent: CC(=O)O
Solvent: O=C(O)C(F)(F)F
Product: COC(=O)c1cc2c(ccn2C)cn1
Temperature: 110 °C
Reaction time: 4 h
Yield: 37.6 %

Procedure:
In a 500 ml round bottom flask, methyl 3-(dimethylamino)-2-((dimethylamino)methyleneamino)acrylate (1A, 24 g, 120 mmol) was dissolved in acetic acid (60 ml) and TFA (20 ml). 1-Methyl-1H-pyrrole (10.56 ml, 119 mmol) was added. The mixture was stirred at room temperature for an hour and at 110° C. for 4 hours until completion of the reaction. Volatiles were then evaporated from the reaction mixture, the residue was cooled in an ice bath. Ice cold saturated K2CO3 solution (200 ml) was slowly added to it. The mixture was extracted with EtOAc (3×250 ml). Combined organic layers were then washed with brine, dried over sodium sulfate, filtered and evaporated. The crude product was purified on silica column using hexane-EtOAc (0-100%). Desired product methyl 1-methyl-1H-pyrrolo[3,2-c]pyridine-6-carboxylate (1B, 8.5 g, 38%) was obtained as a thick brown oil.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:5]([CH2:6][CH2:7][OH:8])=[CH:4][CH:3]=1.Br[CH:12]([CH3:21])[C:13]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:14]>CN(C=O)C>[OH:8][CH2:7][CH2:6][C:5]1[CH:9]=[CH:10][C:2]([NH:1][CH:12]([CH3:21])[C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:14])=[CH:3][CH:4]=1
Reactant: CC(Br)C(=O)c1ccccc1
Reactant: Nc1ccc(CCO)cc1
Solvent: CN(C)C=O
Product: CC(Nc1ccc(CCO)cc1)C(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
A mixture of 4-aminophenethyl alcohol (690 mg, 5.0 mmol), 2-bromopropiophenone (2.1 g, 10 mmol) potassium carbonate (690 mg, 5.0 mmol) in DMF (50 mL) was stirred at ambient temperature for 3 days. The mixture was partitioned between ethyl acetate and water. The combined organic phase was dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel eluting with hexane/ethyl acetate (2:1) to afford the title compound quantitatively as yellow oil: 1H-NMR (CDCl3) δ 1.49 (2H, d, J=6.9 Hz), 2.74 (2H, t, J=6.4 Hz), 3.79 (2H, t, J=6.4 Hz), 4.65 (1H, br), 5.11 (1H, m), 6.65 (2H, d, J=8.4 Hz), 7.05 (2H, d, J=8.6 Hz), 7.48-7.65 (3H, m), 8.03 (2H, d, J=7.2 Hz).
Reaction SMILES: [C:1]([O:4][C:5]1[CH:13]=[CH:12][CH:11]=[CH:10][C:6]=1[C:7]([OH:9])=O)(=[O:3])[CH3:2].[CH3:14][C:15]1[N:16]=[C:17]([NH2:26])[S:18][C:19]=1[CH2:20][CH2:21][O:22][N+:23]([O-:25])=[O:24]>>[CH3:14][C:15]1[N:16]=[C:17]([NH:26][C:7]([C:6]2[CH:10]=[CH:11][CH:12]=[CH:13][C:5]=2[O:4][C:1](=[O:3])[CH3:2])=[O:9])[S:18][C:19]=1[CH2:20][CH2:21][O:22][N+:23]([O-:25])=[O:24]
Reactant: Cc1nc(N)sc1CCO[N+](=O)[O-]
Reactant: CC(=O)Oc1ccccc1C(=O)O
Product: CC(=O)Oc1ccccc1C(=O)Nc1nc(C)c(CCO[N+](=O)[O-])s1
Yield: 25 %

Procedure:
Pet-159 was prepared according to the general procedure described hereinabove and the procedure described above for the preparation of Pet-154, using 2-acetoxy-benzoic acid (Aspirin) and 4-methyl-5-(2-nitrooxy-ethyl)-thiazol-2-ylamine (Pet-10) as the starting materials, in an overall yield of 25%.
Reaction SMILES: [CH3:1][C:2]1([CH3:34])[CH2:11][CH2:10][C:9]([CH3:13])([CH3:12])[C:8]2[CH:7]=[C:6]([CH2:14][C:15]([O:17][C:18]3[CH:33]=[CH:32][C:21]([C:22]([O:24]CC4C=CC=CC=4)=[O:23])=[CH:20][CH:19]=3)=[O:16])[CH:5]=[CH:4][C:3]1=2.O1CCOCC1>[Pd].C(OCC)C>[CH3:1][C:2]1([CH3:34])[CH2:11][CH2:10][C:9]([CH3:12])([CH3:13])[C:8]2[CH:7]=[C:6]([CH2:14][C:15]([O:17][C:18]3[CH:19]=[CH:20][C:21]([C:22]([OH:24])=[O:23])=[CH:32][CH:33]=3)=[O:16])[CH:5]=[CH:4][C:3]1=2
Reactant: CC1(C)CCC(C)(C)c2cc(CC(=O)Oc3ccc(C(=O)OCc4ccccc4)cc3)ccc21
Agent: [Pd]
Solvent: C1COCCO1
Solvent: CCOCC
Product: CC1(C)CCC(C)(C)c2cc(CC(=O)Oc3ccc(C(=O)O)cc3)ccc21
Reaction time: 3 h
Yield: 70.8 %

Procedure:
2.4 g (5.2 mmol) of benzyl 4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylacetoxy)benzoate, 1 g of palladium on charcoal (5%) and 100 ml of dioxane are introduced into a reactor. The mixture is hydrogenated at room temperature and under a pressure of 7 bars for three hours, the catalyst is filtered off and washed with twice 50 ml of THF and the filtrates are evaporated. The residue obtained is ground in the minimum amount of ethyl ether, filtered off and dried. 1.35 g (70%) of 4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylacetoxy)benzoic acid, melting point 142°-143° C., are obtained.
Reaction SMILES: O[C:2]1[C:3]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:4][C:5]2[CH:10]=[N:9][C:8]([C:11]#[N:12])=[N:7][C:6]=2[N:13]=1.O=P(Cl)(Cl)[Cl:22]>CC#N>[Cl:22][C:2]1[C:3]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:4][C:5]2[CH:10]=[N:9][C:8]([C:11]#[N:12])=[N:7][C:6]=2[N:13]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: N#Cc1ncc2cc(-c3ccccc3)c(O)nc2n1
Solvent: CC#N
Product: N#Cc1ncc2cc(-c3ccccc3)c(Cl)nc2n1

Procedure:
The solution of 7-hydroxy-6-phenylpyrido[2,3-d]pyrimidine-2-carbonitrile (2-3; 0.300 g, 1.21 mmol) in CH3CN and POCl3 (2 mL) was heated to 100° C. for 4 h. The mixture was concentrated and the residue was basified with saturated NaHCO3 at 0° C. Extracted with CH2Cl2 and the combined organic layer was dried, filtered and concentrated. The residue was purified by silica gel chromatography (10-20% EtOAc in hexane) to give the title compound (2-4). LRMS m/z (M+H) Calcd: 267.7, found: 267.2.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([O:19][CH3:20])=[C:6]([C:8]([CH3:18])([CH3:17])[CH2:9][C:10]2([C:13]([F:16])([F:15])[F:14])[CH2:12][O:11]2)[CH:7]=1.[NH:21]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[NH:24][CH2:23][CH2:22]1>CN(C=O)C.C(OCC)C>[N:21]1([CH2:12][C:10]([OH:11])([CH2:9][C:8]([C:6]2[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=2[O:19][CH3:20])([CH3:18])[CH3:17])[C:13]([F:16])([F:15])[F:14])[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[NH:24][CH2:23][CH2:22]1
Reactant: COc1ccc(F)cc1C(C)(C)CC1(C(F)(F)F)CO1
Reactant: c1ccc2c(c1)NCCN2
Solvent: CCOCC
Solvent: CN(C)C=O
Product: COc1ccc(F)cc1C(C)(C)CC(O)(CN1CCNc2ccccc21)C(F)(F)F
Yield: 39.3 %

Procedure:
A solution of 2-[2-(5-fluoro-2-methoxyphenyl)-2-methylpropyl]-2-trifluoromethyloxirane (see Example 1) (54.4 mg) and tetrahydroquinoxaline (124.8 mg) in DMF (0.6 mL) was heated at 100° C. for 6 hours. The resulting mixture was diluted with diethyl ether, washed with water and brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by preparative TLC (eluted with 25% diethyl ether-benzene) to give the title compound as a clear oil (31.2 mg).
Reaction SMILES: [CH3:1][C:2]([CH:9]=[CH:10][CH:11]=[C:12]([CH3:24])[CH:13]=[CH:14][C:15]1[C:20]([CH3:22])([CH3:21])[CH2:19][CH2:18][CH2:17][C:16]=1[CH3:23])=[CH:3][CH:4]=[CH:5][C:6]([OH:8])=[O:7].[C:25]([NH:28][C:29]1[CH:34]=[CH:33][C:32](O)=[CH:31][CH:30]=1)(=[O:27])[CH3:26].FC(F)(F)C([O-])=O>O1CCCC1>[CH3:1][C:2]([CH:9]=[CH:10][CH:11]=[C:12]([CH3:24])[CH:13]=[CH:14][C:15]1[C:20]([CH3:22])([CH3:21])[CH2:19][CH2:18][CH2:17][C:16]=1[CH3:23])=[CH:3][CH:4]=[CH:5][C:6]([O:8][C:32]1[CH:33]=[CH:34][C:29]([NH:28][C:25](=[O:27])[CH3:26])=[CH:30][CH:31]=1)=[O:7]
Reactant: CC(C=CC=C(C)C=CC1=C(C)CCCC1(C)C)=CC=CC(=O)O
Reactant: CC(=O)Nc1ccc(O)cc1
Agent: O=C([O-])C(F)(F)F
Solvent: C1CCOC1
Product: CC(=O)Nc1ccc(OC(=O)C=CC=C(C)C=CC=C(C)C=CC2=C(C)CCCC2(C)C)cc1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
A solution of 5,9-dimethyl-11-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8,10-undecapentaenoic acid (0.5 g. 1.5 mmol) and 4-acetamidophenol (1.2 g, 8 mmol) in 40 ml of tetrahydrofuran (THF) was stirred in an ice bath under nitrogen and a solution of trifluroacetate (1.4 ml) in 5 ml of THF was added dropwise. The mixture was stirred at room temperature for 24 hours and concentrated in vacuo. The residue was diluted with methylene chloride and washed with aqueous NaHCO3 solution and brine. After drying with Na2SO4, the organic solution was concentrated in vacuo to give orange powders. Crystallization from ethyl acetate afforded 0.55 g. of the title compound as orange colored crystals. mp 219°-222° C., MS (EI): 459 (m+), 309, 291, 109; UV(MeOH) λmax. 394 nm, 245 nm.
Reaction SMILES: [C:1]12([C:11]3[CH:12]=[C:13]([SH:19])[CH:14]=[CH:15][C:16]=3[O:17][CH3:18])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.Br[CH2:21][C:22]1[S:23][CH:24]=[C:25]([C:27]([O:29][CH3:30])=[O:28])[CH:26]=1>>[C:1]12([C:11]3[CH:12]=[C:13]([S:19][CH2:21][C:22]4[S:23][CH:24]=[C:25]([C:27]([O:29][CH3:30])=[O:28])[CH:26]=4)[CH:14]=[CH:15][C:16]=3[O:17][CH3:18])[CH2:2][CH:3]3[CH2:9][CH:7]([CH2:6][CH:5]([CH2:4]3)[CH2:10]1)[CH2:8]2
Reactant: COC(=O)c1csc(CBr)c1
Reactant: COc1ccc(S)cc1C12CC3CC(CC(C3)C1)C2
Product: COC(=O)c1csc(CSc2ccc(OC)c(C34CC5CC(CC(C5)C3)C4)c2)c1

Procedure:
In a manner analogous to that of Example 17(a), 800 mg (2.9 mmol) of 3-(1-adamantyl)-4-methoxythiophenol were reacted with 690 mg (2.9 mmol) of methyl 2-bromomethyl-4-thiophenecarboxylate and 700 mg (56%) of the expected methyl ester were recovered in the form of a colorless oil.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[C:12]([CH3:14])[CH:11]=[C:10]([CH3:15])[CH:9]=2)[N:5]=[C:4]([NH2:16])[N:3]=1.C1C(=O)N([I:24])C(=O)C1>C(Cl)Cl.CO>[I:24][C:7]1[C:2]([CH3:1])=[N:3][C:4]([NH2:16])=[N:5][C:6]=1[C:8]1[CH:13]=[C:12]([CH3:14])[CH:11]=[C:10]([CH3:15])[CH:9]=1
Reactant: O=C1CCC(=O)N1I
Reactant: Cc1cc(C)cc(-c2cc(C)nc(N)n2)c1
Solvent: ClCCl
Solvent: CO
Product: Cc1cc(C)cc(-c2nc(N)nc(C)c2I)c1

Procedure:
The title compound is synthesized according to general procedure GP1 starting from 3.2 g (11 mmol) 4-methyl-6-(3,5-dimethyl-phenyl)-pyrimidin-2-ylamine and 2.5 g (11 mmol) NIS. Yield after chromatography on silica gel with DCM/MeOH: 1.1 g (31%).
Reaction SMILES: [F:1][CH2:2][C@@H:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[CH3:4].[Cl:11][S:12](O)(=[O:14])=[O:13].P(Cl)(Cl)(Cl)(Cl)Cl>ClCCl>[F:1][CH2:2][C@@H:3]([C:5]1[CH:10]=[CH:9][C:8]([S:12]([Cl:11])(=[O:14])=[O:13])=[CH:7][CH:6]=1)[CH3:4]
Reactant: C[C@@H](CF)c1ccccc1
Reactant: O=S(=O)(O)Cl
Agent: ClP(Cl)(Cl)(Cl)Cl
Solvent: ClCCl
Product: C[C@@H](CF)c1ccc(S(=O)(=O)Cl)cc1
Temperature: 2.5 °C
Reaction time: 0.33 h
Yield: 11.7 %

Procedure:
1.3 g of ((R)-2-fluoro-1-methyl-ethyl)-benzene (9.4 mmol) were dissolved in 50 ml of dichloromethane. At 0-5° C., 1.1 g of chlorosulfonic acid (9.4 mmol), dissolved in 10 ml of dichloromethane were added dropwise. The reaction mixture was stirred for 20 min at 0-5° C. and then added to a solution of 2.15 g of phosphorous pentachloride dissolved in 40 ml of dichloromethane. The reaction mixture was stirred for 30 min at 0-5° C. and 1 h at room temperature. The solvent was evaporated, 100 ml of diethyl ether were added, the mixture was washed once with 150 ml of water, and the organic layer was dried over magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure. The crude product was purified via silica gel chromatography with n-heptane-dichloromethane (1:1) as eluent to give 0.261 g of the title compound.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([O:9][C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=2)=[CH:7][CH:6]=[CH:5][C:4]=1CC#N.Cl.[C:21]([OH:24])(=[O:23])[CH3:22]>>[CH3:1][O:2][C:3]1[C:8]([O:9][C:10]2[CH:11]=[CH:12][C:13]([Cl:16])=[CH:14][CH:15]=2)=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:22][C:21]([OH:24])=[O:23]
Reactant: COc1c(CC#N)cccc1Oc1ccc(Cl)cc1
Reactant: CC(=O)O
Agent: Cl
Product: COc1c(CC(=O)O)cccc1Oc1ccc(Cl)cc1

Procedure:
2-[2-Methoxy-3-(4-chlorophenoxy)phenyl]acetonitrile (11.8 g), glacial acetic acid (50 ml) and conc. hydrochloric acid (25 ml) were treated in a similar manner to that of Example 5-(4) to give oily 2-[2-methoxy-3-(4-chlorophenoxy)phenyl]acetic acid (6.7 g).
Reaction SMILES: [C:1]([C:3]([CH3:13])([CH3:12])[CH2:4][CH2:5][Si:6]([CH3:11])([O:9][CH3:10])[O:7][CH3:8])#[N:2].N.[H][H]>[Ni]>[NH2:2][CH2:1][C:3]([CH3:13])([CH3:12])[CH2:4][CH2:5][Si:6]([CH3:11])([O:9][CH3:10])[O:7][CH3:8]
Reactant: [H][H]
Reactant: CO[Si](C)(CCC(C)(C)C#N)OC
Agent: [Ni]
Agent: N
Product: CO[Si](C)(CCC(C)(C)CN)OC
Yield: 95.8 %

Procedure:
To a 1-liter, high-pressure, stirred autoclave was added a mixture of 3-cyano-3-methylbutylmethyldimethoxysilane (631 grams, 3.13 moles) containing 12.0 grams of dissolved ammonia and 8.5 grams of nickel (5%) on kieselguhr. The autoclave was sealed, pressurized to 800 psi with hydrogen and heated for 10 hours. The contents were cooled and the product was collected, filtered, and distilled. The yield was 615.9 grams (95.9% yield after distillation) of 4-amino-3,3-dimethylbutylmethyldimethoxysilane, as characterized by 1H and 13C NMR spectroscopy.
Reaction SMILES: [CH2:1]([OH:4])[CH2:2][CH3:3].[H-].[Na+].Cl[C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[CH:10][C:9]=1[C:17]1[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=1>CN(C)C=O.O>[N+:14]([C:11]1[CH:12]=[CH:13][C:8]([O:4][CH2:1][CH2:2][CH3:3])=[C:9]([C:17]2[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=2)[CH:10]=1)([O-:16])=[O:15]
Reactant: CCCO
Reactant: O=[N+]([O-])c1ccc(Cl)c(-c2ccc(OC(F)(F)F)cc2)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCCOc1ccc([N+](=O)[O-])cc1-c1ccc(OC(F)(F)F)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 54.5 %

Procedure:
1-Propanol (284 mg, 4.72 mmol) was added dropwise at a slow speed to a suspension of sodium hydride (206 mg, 4.72 mmol) in dimethylformamide (4 ml) at 0° under argon atmosphere, then the mixture was stirred at room temperature for 30 minutes. A solution of 2-chloro-5-nitro-4′-(trifluoromethoxy)biphenyl (1.00 g, 3.15 mmol) in dimethylformamide (2 ml) was added dropwise at a slow speed to this mixture at OD, and then stirred at room temperature for 2 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The residue obtained by evaporation of the solvent under reduced pressure was purified by column chromatography on silica gel (n-hexane:ethyl acetate=6:1) to give the title compound (586g, 54.5%) as a pale yellow solid.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.[OH:11][CH2:12][CH2:13][N:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1.[H-].[Na+].O>CN(C=O)C>[N+:8]([C:5]1[CH:6]=[CH:7][C:2]([O:11][CH2:12][CH2:13][N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)=[CH:3][CH:4]=1)([O-:10])=[O:9]
Reactant: O=[N+]([O-])c1ccc(Cl)cc1
Reactant: OCCN1CCOCC1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1ccc(OCCN2CCOCC2)cc1
Temperature: 25 °C

Procedure:
To the solution of 8.0 g (51 mMol) of 1-chloro-4-nitrobenzene and 6.7 g (6.3 mL; 51 mMol) of N-hydroxyethyl-morpholine in 50 mL of DMF at 0° C. is added 2.7 g of NaH portionwise over 2.5 h. After stirring another hour at rt, the reaction mixture is poured onto 200 mL of water and stirred. The precipitated crystals are filtered and dried at 60° C. under vacuum to obtain 4-[2-(4-nitro-phenoxy)-ethyl]-morpholine. Title compound: ES-MS: 253 [M+H]+; single peak at tR=4.8 min (System 2).