Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(O)C.[C:4]([C:6]1[CH:7]=[C:8]([NH:26][C:27]([C:29]2[CH:30]=[N:31][N:32]([C:35]3[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=3)[C:33]=2[CH3:34])=[O:28])[CH:9]=[CH:10][C:11]=1[N:12]1[CH2:17][CH2:16][N:15]([C:18]([C:20]2[CH:21]=[N:22][O:23][C:24]=2[CH3:25])=[O:19])[CH2:14][CH2:13]1)#[N:5].[OH-].[Na+]>O>[C:4]([C:6]1[CH:7]=[C:8]([NH:26][C:27]([C:29]2[CH:30]=[N:31][N:32]([C:35]3[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=3)[C:33]=2[CH3:34])=[O:28])[CH:9]=[CH:10][C:11]=1[N:12]1[CH2:17][CH2:16][N:15]([C:18](=[O:19])/[C:20](/[C:21]#[N:22])=[C:24](\[OH:23])/[CH3:25])[CH2:14][CH2:13]1)#[N:5]
Reactant: Cc1oncc1C(=O)N1CCN(c2ccc(NC(=O)c3cnn(-c4ccc(F)cc4)c3C)cc2C#N)CC1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: C/C(O)=C(\C#N)C(=O)N1CCN(c2ccc(NC(=O)c3cnn(-c4ccc(F)cc4)c3C)cc2C#N)CC1
Reaction time: 2 h
Yield: 47.4 %

Procedure:
A mixed solvent of ethanol (10 ml) and water (10 ml) containing N-{3-cyano-4-[4-(5-methylisoxazol-4-ylcarbonyl) piperazin-1-yl]phenyl}-1-(4-fluorophenyl)-5-methylpyrazole-4-carboxamide (0.95 g) and sodium hydroxide (0.1 g) was stirred at a refluxing temperature for 2 h. The solvent was evaporated under reduced pressure. Dilute hydrochloric acid was added to the residue to allow crystallization. The crystals were recrystallized from hydrous dimethylformamide to give the title compound (0.45 g), melting point: 210° C.
Reaction SMILES: [CH3:1][CH:2]([CH3:6])[C:3]([OH:5])=O.CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[NH2:43][CH:44]1[CH2:49][CH2:48][CH:47]([C:50]2[O:54][N:53]=[C:52]([C:55]3[N:60]=[C:59]([N:61]([CH3:68])[C:62]4[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=4)[N:58]=[C:57]([NH2:69])[N:56]=3)[N:51]=2)[CH2:46][CH2:45]1>CN(C=O)C>[NH2:69][C:57]1[N:58]=[C:59]([N:61]([CH3:68])[C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)[N:60]=[C:55]([C:52]2[N:51]=[C:50]([CH:47]3[CH2:48][CH2:49][CH:44]([NH:43][C:3](=[O:5])[CH:2]([CH3:6])[CH3:1])[CH2:45][CH2:46]3)[O:54][N:53]=2)[N:56]=1
Reactant: CN(c1ccccc1)c1nc(N)nc(-c2noc(C3CCC(N)CC3)n2)n1
Reactant: CC(C)C(=O)O
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)C(=O)NC1CCC(c2nc(-c3nc(N)nc(N(C)c4ccccc4)n3)no2)CC1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 21.4 %

Procedure:
To a solution of 2-methylpropanoic acid (0.03 g, 0.327 mmol) in DMF (5 mL) was added DIPEA (0.122 mL, 0.682 mmol) followed by (1H-benzotriazol-1-yloxy)[tris(dimethylamino)]phosphonium hexafluorophosphate (0.13 g, 0.3 mmol). The reaction mixture was stirred at room temperature for 5 min and 6-[5-(4-aminocyclohexyl)-1,2,4-oxadiazol-3-yl]-2-N-methyl-2-N-phenyl-1,3,5-triazine-2,4-diamine (batch 1 from Example 422, 0.1 g, 0.273 mmol) was added. The reaction mixture was stirred at room temperature for 16 h and then concentrated, extracted with EtOAc, washed with water, dried over sodium sulfate and concentrated. The residue was purified by FCC, eluting with 0-10% MeOH in DCM. The crude product was dissolved in EtOAc, washed with saturated aq. sodium bicarbonate, dried over sodium sulfate and concentrated under vacuum to afford the title compound (0.0255 g, 21%).
Reaction SMILES: [C:1]12([O:11][C:12]3[CH:18]=[C:17]([CH3:19])[C:15]([NH2:16])=[C:14]([CH2:20]SC)[CH:13]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2>[Ni]>[C:1]12([O:11][C:12]3[CH:13]=[C:14]([CH3:20])[C:15]([NH2:16])=[C:17]([CH3:19])[CH:18]=3)[CH2:2][CH:3]3[CH2:9][CH:7]([CH2:6][CH:5]([CH2:4]3)[CH2:10]1)[CH2:8]2
Reactant: CSCc1cc(OC23CC4CC(CC(C4)C2)C3)cc(C)c1N
Agent: [Ni]
Product: Cc1cc(OC23CC4CC(CC(C4)C2)C3)cc(C)c1N
Yield: 29.6 %

Procedure:
9.6 g (33.6 mmoles) of 4-(1-adamantyloxy)-2-(methylthiomethyl)-6-methylaniline is disulfurized as in Example 89 using six rounded teaspoonfuls of Raney nickel sludge (approximately 48 g of Raney nickel). The product is chromatographed by HPLC on a 5.1 cm×109 cm column at 30 psi, eluting with CH2Cl2 followed by 0.5% acetone in CH2Cl2, 5 l., 0.75% acetone in CH2Cl2, 3 l., and 1% acetone in CH2Cl2, 5 l., affording 2.7 g of red solid. Center fractions (0.9 g) give product of m.p. 132.6-139.0.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][S:12]([OH:15])(=[O:14])=O)=[CH:6][CH:5]=1)([O-:3])=[O:2].S(Cl)(Cl)=O.[NH:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1>O.C([O-])(O)=O.[Na+]>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([CH2:10][CH2:11][S:12]([N:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)(=[O:14])=[O:15])=[CH:8][CH:9]=1)([O-:3])=[O:2]
Reactant: C1COCCN1
Reactant: O=[N+]([O-])c1ccc(CCS(=O)(=O)O)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: O=S(Cl)Cl
Product: O=[N+]([O-])c1ccc(CCS(=O)(=O)N2CCOCC2)cc1
Temperature: 80 °C
Reaction time: 16 h
Yield: 52 %

Procedure:
A flask was charged with 491 mg (2.12 mmol) of solid 2-(4-nitro-phenyl)-ethanesulfonic acid (as prepared in the previous step), which was treated with 3.10 mL (42.4 mmol) of thionyl chloride and heated to 80° C. for 7 h. The volatile components were removed in vacuo, the residue was taken up in THF (20 mL), and 927 μL (10.6 mmol) of morpholine was added. The mixture was stirred at RT for 16 h, diluted with water (15 mL) and saturated aqueous NaHCO3 (15 mL) and extracted with EtOAc (2×70 mL). The organic layer was dried (MgSO4) and concentrated in vacuo to afford 370 mg (52%) of the title compound as a pale yellow solid: 1H-NMR (CDCl3; 400 MHz): δ 8.20 (d, 2H, J=8.8 Hz), 7.40 (d, 2H, J=8.8 Hz), 3.79-3.73 (m, 4H), 3.31-3.23 (m, 6H), 3.21-3.14 (m, 2H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.[C:9]([Si:13](Cl)([CH3:15])[CH3:14])([CH3:12])([CH3:11])[CH3:10].N1C=CN=C1.O>CN(C)C=O>[Si:13]([O:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Br:1])[CH:3]=1)([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:15])[CH3:14]
Reactant: Oc1cccc(Br)c1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)[Si](C)(C)Oc1cccc(Br)c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 133.1 %

Procedure:
A mixture of 300.0 g (1.7 mol) of 3-bromophenol, 392.1 g (2.6 mol) of tert-butylchlorodimethylsilane and 295.1 g (4.3 mol) of imidazole in 1 L of N,N-dimethylformamide was stirred at room temperature under nitrogen for 18 hours. The reaction mixture was poured into cold water and extracted with diethyl ether. The ether extracts were washed with water and brine, dried over sodium sulfate, and the solvent was evaporated under vacuum to give 650 g of crude 3-bromophenyl tert-butyldimethylsilyl ether as an orange oil. NMR (CDCl3, 200 MHz) δ: 0.2 (s, 6H); 0.95 (s, 9H); 6.8 (m, 1H); 7.0-7.1 (m, 3H).
Reaction SMILES: [C:1]1([S:7](Cl)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+].[NH:13]1[C:23]2[C:24]3[C:15]([CH2:16][NH:17][C:18](=[O:25])[C:19]=3[CH:20]=[CH:21][CH:22]=2)=[CH:14]1>C(Cl)Cl>[C:1]1([S:7]([N:13]2[C:23]3[C:24]4[C:15]([CH2:16][NH:17][C:18](=[O:25])[C:19]=4[CH:20]=[CH:21][CH:22]=3)=[CH:14]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C1NCc2c[nH]c3cccc1c23
Reactant: O=S(=O)(Cl)c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Product: O=C1NCc2cn(S(=O)(=O)c3ccccc3)c3cccc1c23
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Benzenesulfonyl chloride (140 mg, 0.79 mmol), NBu4HSO4 (24 mg, 0.07 mmol) and 4M aq. NaOH (2 mL) were, in that order, added to 3,4-Dihydropyrrolo[4,3,2-de]isoquinolin-5(1H)-one, Intermediate 1 (124 mg, 0.72 mmol) in DCM (10 mL). The reaction was stirred at room temperature for 2 h and then extracted with water and DCM (×2). The product seems to be only partially soluble in DCM and some solid material in the water layer was filtered off and added to the DCM layer, which was concentrated and dried to give 227 mg of the title compound, as a light brown solid. MS m/z 313 [M+H]+.
Reaction SMILES: [OH:1][CH:2]([CH2:9]/[CH:10]=[CH:11]\[CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[C:3]#[C:4][Si](C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[OH:1][CH:2]([CH2:9]/[CH:10]=[CH:11]\[CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[C:3]#[CH:4]
Reactant: CCCCC/C=C\CC(O)C#C[Si](C)(C)C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: C#CC(O)C/C=C\CCCCC
Temperature: 0 °C
Reaction time: 1 h
Yield: 89.5 %

Procedure:
3-Hydroxy-1-trimethylsilyl-undec-5Z-ene-1-yne (6.3 g, 26 mmole) is dissolved in 100 ml dry THF in a flame dried 250 ml one-neck round bottom flask under nitrogen. The solution is cooled to 0° C. and treated slowly dropwise with tetrabutylammonium fluoride (1.0M/THF; 32 ml, 32 mmole). The reaction is stirred one hour at 0° C., quenched with 50 ml 90% saturated sodium chloride, and the THF removed in vacuo. The aqueous residue is extracted with 4×20 ml diethyl ether. The organics are combined, washed with 1×50 ml saturated sodium chloride, and dried over magnesium sulfate. The organics are concentrated in vacuo to a dark amber oil. The crude oil is chromatographed over 100 g silica gel (230-400 mesh), eluting with 8% ethyl acetate/hexane and collecting 20 ml fractions. Fractions 16-39 are combined and concentrated to provide 3.87 g of the title compound as a yellow oil.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][N:3]=1.[CH2:9]([N:11]=[C:12]=[O:13])[CH3:10]>C1COCC1>[Cl:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:1][C:12]([NH:11][CH2:9][CH3:10])=[O:13])[CH:7]=1
Reactant: Nc1cc(Cl)ccn1
Reactant: CCN=C=O
Solvent: C1CCOC1
Product: CCNC(=O)Nc1cc(Cl)ccn1
Temperature: 55 °C
Yield: 50.1 %

Procedure:
To 2-amino-4-chloropyridine (1.02 g, 7.9 mmol) in THF (20 mL) was added ethyl isocyanate (0.69 ml, 8.69 mmol) and the reaction heated at 55° C. for 18 hours. The reaction was concentrated in vacuo. The resulting white solid was suspended in EtOAc and filtered to give the product as a white solid (0.79 g).
Reaction SMILES: [OH:1][CH2:2][CH:3]1[CH2:7][O:6][C:5]([O:14][CH3:15])([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[O:4]1.C(N(CC)CC)C.[C:23](Cl)(=[O:26])[CH:24]=[CH2:25]>C(Cl)Cl>[C:23]([O:1][CH2:2][CH:3]1[CH2:7][O:6][C:5]([O:14][CH3:15])([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[O:4]1)(=[O:26])[CH:24]=[CH2:25]
Reactant: C=CC(=O)Cl
Reactant: COC1(c2ccccc2)OCC(CO)O1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C=CC(=O)OCC1COC(OC)(c2ccccc2)O1

Procedure:
The procedure of Example 1 was repeated, employing 21 grams (100 mmol.) of 4-hydroxymethyl-2-methoxy-2-phenyl-1,3-dioxolane, 25.3 grams (250 mmol.) of triethylamine, 9.5 grams (105 mmol.) of acryloyl chloride and 150 ml. of methylene chloride. The crude product was purified by column chromatography over basic alumina, using 15% (by volume) ethyl acetate in hexane as an eluant, to yield the desired 4-acryloyloxymethyl-2-methoxy-2-phenyl-1,3-dioxolane.
Reaction SMILES: [Br:1][C:2]1[N:6]=[CH:5][N:4]([C:7]2[CH:12]=[CH:11][C:10](OC(C)C)=[CH:9][CH:8]=2)[N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].IC1C=CC([C:30]([F:33])([F:32])[F:31])=CC=1>[Cu]I.CS(C)=O>[Br:1][C:2]1[N:6]=[CH:5][N:4]([C:7]2[CH:8]=[CH:9][C:10]([C:30]([F:33])([F:32])[F:31])=[CH:11][CH:12]=2)[N:3]=1
Reactant: CC(C)Oc1ccc(-n2cnc(Br)n2)cc1
Reactant: FC(F)(F)c1ccc(I)cc1
Agent: [Cu]I
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CS(C)=O
Product: FC(F)(F)c1ccc(-n2cnc(Br)n2)cc1
Temperature: 100 °C
Reaction time: 0.5 h
Yield: 63.3 %

Procedure:
3-Bromo-1-(4-isopropoxyphenyl)-1H-1,2,4-triazole (7.15 g, 48.3 mmol), copper(I) iodide (1.25 g, 6.56 mmol), cesium carbonate (18.9 g, 58.0 mmol), and 1-iodo-4-(trifluoromethyl)benzene (8.29 g, 30.5 mmol) were added to dimethylsulfoxide (50 mL) and the solution was degassed with nitrogen for 10 minutes. The solution was heated at 100° C. for 20 hours. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate and filtered through Celite®. The resulting filter cake was rinsed with additional ethyl acetate (100 mL). Saturated aqueous ammonium chloride was added to the filtrate which was then stirred for 30 minutes. The layers were separated and the aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organic extracts were dried over anhydrous magnesium sulfate and concentrated onto Celite®. Purification by silica gel chromatography using 0-100% ethyl acetate/hexanes as eluent provided the title compound as a white solid (5.64 g, 64%): mp 87-89° C.; 1H NMR (400 MHz, CDCl3) δ 8.53 (s, 1H), 7.85-7.77 (m, 4H); ESIMS m/z 292.0 ([M+H]+).
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:13]=[C:12]2[C:7]([C:8](=O)[CH2:9][CH:10]=[N:11]2)=[CH:6][CH:5]=1.[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][NH:25][CH:24]([CH3:28])[CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]>CN(C=O)C>[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][N:25]([C:8]2[C:7]3[C:12](=[CH:13][C:4]([Cl:3])=[CH:5][CH:6]=3)[N:11]=[CH:10][CH:9]=2)[CH:24]([CH3:28])[CH2:23]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]
Reactant: O=C1CC=Nc2cc(Cl)ccc21
Reactant: CC1CN(C(=O)OC(C)(C)C)CCN1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC1CN(C(=O)OC(C)(C)C)CCN1c1ccnc2cc(Cl)ccc12
Temperature: 80 °C
Reaction time: 1 h

Procedure:
Sodium hydride (72 mg, 3 mmol) is added to a solution of 7-chloro-4-quinolone (359 mg, 2 mmol) in DMF. After 1 h at 40° C. N-phenyl(trifluoromethylsulfon)imide (1.0 g, 2.8 mmol) and, 1 h later, 1-tert-butoxycarbonyl-3-methylpiperazine (1.8 g, 8 mmol) is added. The reaction mixture is stirred at 80° C. for 2 days, concentrated, diluted with EtOAc, washed with water and brine, dried (Na2SO4), and concentrated. The residue is purified by reversed phase HPLC with water-MeCN-TFA to give the title product.
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[CH:10][C:5]2[O:6][CH2:7][CH2:8][O:9][C:4]=2[C:3]=1[CH3:12].[C:13](Cl)(Cl)=[S:14].[OH-].[Na+]>O.Cl>[N:1]([C:2]1[CH:11]=[CH:10][C:5]2[O:6][CH2:7][CH2:8][O:9][C:4]=2[C:3]=1[CH3:12])=[C:13]=[S:14]
Reactant: Cc1c(N)ccc2c1OCCO2
Reactant: S=C(Cl)Cl
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: Cc1c(N=C=S)ccc2c1OCCO2

Procedure:
1.90 g of 6-amino-5-methyl-benzodioxan is dissolved in 50 mL of water containing 11.8 mL of 1.0N hydrochloric acid. 1.10 mL of thiophosgene is added dropwise while stirring vigorously. After 4 hours of stirring at room temperature, the mixture is made basic with 50% sodium hydroxide solution, and then extracted with methylene chloride. The extracts are dried over sodium sulfate and concentrated. The residue is found to be 2.0 g of 6-isothiocyanato-5-methylbenzodioxan.
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[CH:11]=[CH:10][C:9]([N+:12]([O-])=O)=[CH:8][CH:7]=2)[CH2:3][CH2:2]1.O.O.[Sn](Cl)Cl>C(O)C>[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[CH:8][C:9]([NH2:12])=[CH:10][CH:11]=2)[CH2:2][CH2:3]1
Reactant: O=[N+]([O-])c1ccc(OCC2CC2)cc1
Agent: Cl[Sn]Cl
Solvent: O
Solvent: CCO
Product: Nc1ccc(OCC2CC2)cc1
Yield: 56.8 %

Procedure:
The above 4-nitrobenzene (2.0 g, 9.5 mmol) was dissolved in ethanol (50 mL) and tin(II) chloride dihydrate (10.7 g, 48 mmol) was added and the mixture was refluxed for 24 hours. After cooling, the mixture was concentrated in vacuo. The residue was dissolved in ethyl acetate (40 mL) and 1N aqueous sodium hydroxide (180 mL). This mixture was filtered through celite. The aqueous phase was extracted with ethyl acetate (2×50 mL) and the combined organic extracts were dried (MgSO4) and concentrated in vacuo to afford 0.88 g (52%) of 4-cyclopropylmethoxyaniline.
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:14]3[CH:15]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[CH2:16][NH:17][CH2:18][CH2:19][C:13]=3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:26](O)=O.C=O>CN(C)C=O>[C:1]1([S:7]([N:10]2[C:14]3[CH:15]([C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=4)[CH2:16][N:17]([CH3:26])[CH2:18][CH2:19][C:13]=3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=CO
Reactant: O=S(=O)(c1ccccc1)n1ccc2c1C(c1ccccc1)CNCC2
Agent: C=O
Solvent: CN(C)C=O
Product: CN1CCc2ccn(S(=O)(=O)c3ccccc3)c2C(c2ccccc2)C1

Procedure:
A mixture of 1-phenylsulphonyl-1,4,5,6,7,8-hexahydro-8-phenylpyrrolo[2,3-d]azepine (1.24 g), formic acid (0.86 gm), 40% formaldehyde (1.3 ml), and dimethylformamide (30 ml) were refluxed for 1 hour. After evaporating to dryness, 5M hydrochloric acid was added to the residue and the solution was washed with ether three times. The aqueous solution was basified with 5M sodium hydroxide and the product was extracted into dichloromethane. The extracts were washed with water, dried and evaporated to give a solid, m.p. 115°-116° C. (ethanol).
Reaction SMILES: [CH2:1]([OH:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[C:20]([C:24]1[CH:25]=[C:26]([CH:33]=[C:34]([C:37]([CH3:40])([CH3:39])[CH3:38])[C:35]=1[OH:36])[CH2:27][CH2:28][C:29](OC)=[O:30])([CH3:23])([CH3:22])[CH3:21]>>[C:37]([C:34]1[CH:33]=[C:26]([CH:25]=[C:24]([C:20]([CH3:23])([CH3:22])[CH3:21])[C:35]=1[OH:36])[CH2:27][CH2:28][C:29]([O:19][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])=[O:30])([CH3:39])([CH3:40])[CH3:38]
Reactant: COC(=O)CCc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1
Reactant: CCCCCCCCCCCCCCCCCCO
Product: CCCCCCCCCCCCCCCCCCOC(=O)CCc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1
Reaction time: 2.5 h

Procedure:
The general procedure of Example 1 is repeated, but using 337.0 g (1.246 mole) of octadecyl alcohol and 391.9 g (1.340 mole) of methyl 3,5-di-tert-butyl-4-hydroxyhydrocinnamate and a reflux temperature of between 189 and 201° C. After 2.5 hours, analysis of the contents of the reaction flask using Gas shows a mixture of 32.1 wt % of the title compound, 32.0 wt % of methyl 3,5-di-tert-butyl-4-hydroxyhydrocinnamate and 29.6 wt % octadecyl alcohol.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][C@@:6]12[CH2:17][CH2:16][CH2:15][C:13]3[C:14]1=[C:9]([CH:10]=[CH:11][CH:12]=3)[NH:8][C:7]2=[O:18].[CH2:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:22][CH2:21][NH:20]1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CN(C)C=O>[CH2:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:22][CH2:21][N:20]1[CH2:2][CH2:3][CH2:4][CH2:5][C@@:6]12[CH2:17][CH2:16][CH2:15][C:13]3[C:14]1=[C:9]([CH:10]=[CH:11][CH:12]=3)[NH:8][C:7]2=[O:18]
Reactant: c1ccc2c(c1)CCNC2
Reactant: O=C1Nc2cccc3c2[C@@]1(CCCCBr)CCC3
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: O=C1Nc2cccc3c2[C@@]1(CCCCN1CCc2ccccc2C1)CCC3
Yield: 100 %

Procedure:
(S)-2a-(4-bromobutyl)-2a,3,4,5-tetrahydro-1H-benz[cd]indol-2-one (120 mg, 0.40 mmol), 1,2,3,4-tetrahydroisoquinoline (59 mg, 0.44 mmol), and potassium carbonate (83 mg, 0.60 mmol) in anhydrous N,N-dimethylformamide (1 ml) were stirred at room temperature for 2 days. To the reaction mixture obtained was added ethyl acetate (80 ml), which was then washed with water and saturated saline solution. After drying with anhydrous sodium sulfate, the solvent was evaporated under reduced pressure to obtain a product. The product obtained was separated and purified by means of silica gel column chromatography, whereby 150 mg (0.40 mmol, yield 100%) of the above-described object compound could be obtained.
Reaction SMILES: [OH:1][C:2]1[N:6]([CH3:7])[N:5]=[C:4]([C:8]([F:11])([F:10])[F:9])[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].F[C:19]1[CH:20]=[C:21]([CH3:28])[CH:22]=[CH:23][C:24]=1[N+:25]([O-:27])=[O:26]>CS(C)=O>[CH3:28][C:21]1[CH:20]=[CH:19][C:24]([N+:25]([O-:27])=[O:26])=[C:23]([O:1][C:2]2[N:6]([CH3:7])[N:5]=[C:4]([C:8]([F:11])([F:10])[F:9])[CH:3]=2)[CH:22]=1
Reactant: Cc1ccc([N+](=O)[O-])c(F)c1
Reactant: Cn1nc(C(F)(F)F)cc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: Cc1ccc([N+](=O)[O-])c(Oc2cc(C(F)(F)F)nn2C)c1
Temperature: 70 °C
Yield: 41.2 %

Procedure:
5-Hydroxy-1-methyl-3-trifluoromethylpyrazole (8.30 g, 50 mmol) and powdered potassium carbonate (8.29 g, 60 mmol) were stirred together in dimethylsulfoxide (40 ml) for 30 minutes. 3-Fluoro-4-nitrotoluene (7.76 g, 50 mmol) was added and the mixture heated at 70° C. for 17 h, then cooled to room temperature. The mixture was partitioned between diethyl ether and water, the ethereal extract washed with water and brine, dried over magnesium sulfate, filtered and the filtrate evaporated. The residue was further purified by flash column chromatography over silica gel, and the desired fraction collected and triturated with hexane to give the desired product as a pale yellow solid (6.20 g), m.p. 88°-90° C.
Reaction SMILES: [Cl:1][C:2]1[N:11]=[C:10](Cl)[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([N+]([O-])=O)[CH:8]=2)[N:3]=1.[CH3:16][N:17]([CH3:26])[C:18]1[CH:23]=[CH:22][C:21]([NH:24][CH3:25])=[CH:20][CH:19]=1>>[Cl:1][C:2]1[N:11]=[C:10]([N:24]([C:21]2[CH:22]=[CH:23][C:18]([N:17]([CH3:16])[CH3:26])=[CH:19][CH:20]=2)[CH3:25])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1
Reactant: O=[N+]([O-])c1ccc2nc(Cl)nc(Cl)c2c1
Reactant: CNc1ccc(N(C)C)cc1
Product: CN(C)c1ccc(N(C)c2nc(Cl)nc3ccccc23)cc1

Procedure:
The title compound was prepared from 2,4-dichloro-6-nitro-quinazoline and N1,N1,N4-trimethylbenzene-1,4-diamine by a procedure similar to example 10. 1H NMR (CDCl3): 7.71 (m, 1H), 7.51-7.56 (m, 1H), 7.07 (m, 2H), 6.99 (m, 2H), 6.71 (m, 2H), 3.59 (s, 3H), 3.01 (s, 6H).
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]([C:21]([O:23][CH2:24][CH3:25])=[O:22])N=N[C:14]=2[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:5][CH:4]=1)[CH3:2].[CH:26](N1CCCC1)=[CH2:27]>C(Cl)(Cl)Cl>[CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:27]=[CH:26][C:14]=2[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:5][CH:4]=1)[CH3:2]
Reactant: C=CN1CCCC1
Reactant: CCOC(=O)c1nnc(-c2ccccc2)c(-c2ccc(CC)cc2)n1
Solvent: ClC(Cl)Cl
Product: CCOC(=O)c1ccc(-c2ccccc2)c(-c2ccc(CC)cc2)n1

Procedure:
Following General Procedure D, ethyl 5-(4-ethylphenyl)-6-phenyl-1,2,4-triazine-3-carboxylate (Compound 18, 245 mg, 0.74 mmol) and crude 1-vinylpyrrolidine (Compound 38, 572 mg) in CHCl3 (10 ml) were reacted to produce the title compound as a yellow oil.
Reaction SMILES: [CH3:1]O.[CH3:3][O:4][C:5]1[CH:6]=[C:7]([CH:18]=[C:19]([O:23][CH3:24])[C:20]=1[O:21][CH3:22])[CH2:8][N:9]1[CH2:14][CH2:13][N:12]([C:15]([S-:17])=[S:16])[CH2:11][CH2:10]1.[Na+].CI>O>[CH3:24][O:23][C:19]1[CH:18]=[C:7]([CH:6]=[C:5]([O:4][CH3:3])[C:20]=1[O:21][CH3:22])[CH2:8][N:9]1[CH2:10][CH2:11][N:12]([C:15]([S:17][CH3:1])=[S:16])[CH2:13][CH2:14]1
Reactant: CO
Reactant: COc1cc(CN2CCN(C(=S)[S-])CC2)cc(OC)c1OC
Agent: [Na+]
Solvent: CI
Solvent: O
Product: COc1cc(CN2CCN(C(=S)SC)CC2)cc(OC)c1OC
Temperature: 0 °C
Reaction time: 3 h

Procedure:
To 70 ml of methanol containing 6.67 g of sodium 4-(3,4,5-trimethoxybenzyl)piperazinecarbodithioate was dropwise added under chilling with ice 20 ml of methanol solution containing 2.6 g of methyl iodide for 20 min. The resulting mixture was further stirred for 3 hours under chilling with ice. The reaction solution was placed under reduced pressure to distill off the solvent, leaving a residue. The residue was dissolved in water, and then extracted with chloroform. The chloroform portion was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and placed under reduced pressure to distill off the solvent. Thus obtained crude product was purified by silica gel chromatography to give 3.7 g of the desired compound as a pale yellow crystalline product.
Reaction SMILES: F[B-](F)(F)F.[Br:6][C:7]1[CH:12]=[C:11]([CH2:13][CH3:14])[C:10]([N+]#N)=[C:9]([CH2:17][CH3:18])[CH:8]=1.[CH3:19][OH:20]>[Cl-].[Zn+2].[Cl-]>[Br:6][C:7]1[CH:12]=[C:11]([CH2:13][CH3:14])[C:10]([O:20][CH3:19])=[C:9]([CH2:17][CH3:18])[CH:8]=1
Reactant: CO
Reactant: CCc1cc(Br)cc(CC)c1[N+]#N
Agent: F[B-](F)(F)F
Agent: [Cl-]
Agent: [Zn+2]
Product: CCc1cc(Br)cc(CC)c1OC
Temperature: 25 °C

Procedure:
A stirred solution containing 4-bromo-2,6-diethylbenzenediazonium tetrafluoroborate (17.25 g, 52.77 mmol) and freshly ground anhydrous zinc chloride (7.2 g, 52.9 mmol) in methanol (1.06 L) was refluxed for 6 h. The reaction was cooled to ambient temperature, quenched with H2O (1.2 L), saturated with solid sodium chloride and extracted with hexane. The combined organic extracts were sequentially washed with sat. aq. NaHCO3 (1×100 mL), with H2O (1×100 mL), with brine (1×100 mL), dried (Na2SO4) and concentrated to give 12.0 g (94%) of tide compound. 1H NMR: consistent. mass spectrum (EI), m/z 242 (M+).