Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[C:5]([F:10])=[CH:4][N:3]=1.[CH3:11][C:12]1[CH:13]=[C:14]([CH:16]=[C:17]([B:19]2[O:23][C:22]([CH3:25])([CH3:24])[C:21]([CH3:27])([CH3:26])[O:20]2)[CH:18]=1)[NH2:15].O1CCOCC1.CS(O)(=O)=O>C(OCC)(=O)C>[F:10][C:5]1[C:6]([O:8][CH3:9])=[N:7][C:2]([NH:15][C:14]2[CH:16]=[C:17]([B:19]3[O:23][C:22]([CH3:24])([CH3:25])[C:21]([CH3:27])([CH3:26])[O:20]3)[CH:18]=[C:12]([CH3:11])[CH:13]=2)=[N:3][CH:4]=1
Reactant: COc1nc(Cl)ncc1F
Reactant: Cc1cc(N)cc(B2OC(C)(C)C(C)(C)O2)c1
Agent: CS(=O)(=O)O
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: COc1nc(Nc2cc(C)cc(B3OC(C)(C)C(C)(C)O3)c2)ncc1F
Temperature: 100 °C

Procedure:
To a flask containing 2-chloro-5-fluoro-4-methoxypyrimidine (0.32 g, 1.97 mmol) and 3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (0.40 g, 1.72 mmol) were added dioxane (17 mL) and methanesulfonic acid (0.13 mL, 1.97 mmol). The reaction was heated at 100° C. overnight. The reaction was then cooled to room temperature, diluted with ethyl acetate, washed with water, dried over magnesium sulfate, filtered and concentrated. Flash chromatography was used for purification to yield 5-fluoro-4-methoxy-N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrimidin-2-amine. MS ESI calc'd for C18H24BFN3O3 [M+H]+ 360. found 360. 1H NMR (500 MHz, DMSO-d6) δ 9.51 (s, 1H), 8.27 (d, J=3.2, 1H), 8.00 (s, 1H), 7.57 (s, 1H), 7.07 (s, 1H), 4.01 (s, 3H), 2.25 (s, 3H), 1.26 (s, 12H).
Reaction SMILES: [CH3:1][C:2]1[N:12]=[CH:11][CH:10]=[CH:9][C:3]=1[C:4]([O:6]CC)=[O:5].[CH:13](=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(OC(=O)C)(=O)C>>[OH:20][CH:13]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH2:1][C:2]1[N:12]=[CH:11][CH:10]=[CH:9][C:3]=1[C:4]([OH:6])=[O:5]
Reactant: O=Cc1ccccc1
Reactant: CCOC(=O)c1cccnc1C
Solvent: CC(=O)OC(C)=O
Product: O=C(O)c1cccnc1CC(O)c1ccccc1

Procedure:
In carrying out the reaction, an appropriate ethyl 2-methylnicotinate and benzaldehyde compound and acetic anhydride are refluxed together under nitrogen for about 24 hours. Thereafter, the excess anhydride is removed in vacuo and the residue poured into water and extracted with ether. The ether solution extracted with dilute acid, the acid solution then made basic with ammonia to obtain a lactone of 2-(2-hydroxy-2-phenylethyl)nicotinic acid. The lactone is reduced to 2-phenylethylnicotinic acid adding the lactone to a freshly prepared mixture of phosphorus and iodine and the resulting mixture heated at reflux temperature for 3 to 10 hours with stirring. The acid is recovered from the reaction mixture by filtering to remove the phosphorus and cooling to recover the hydroiodic acid salt which is collected, dissolved in water and the solution neutralized with ammonia to obtain the 2-phenethylnicotinic acid.
Reaction SMILES: [F:1][C:2]([F:23])([F:22])[C:3]([N:5]([CH2:16][CH2:17][S:18]([CH3:21])(=[O:20])=[O:19])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([N+:13]([O-])=O)[CH:8]=1)=[O:4].[H][H]>CC(O)C.[Pd]>[NH2:13][C:9]1[CH:8]=[C:7]([CH2:6][N:5]([CH2:16][CH2:17][S:18]([CH3:21])(=[O:20])=[O:19])[C:3](=[O:4])[C:2]([F:23])([F:1])[F:22])[CH:12]=[CH:11][CH:10]=1
Reactant: CS(=O)(=O)CCN(Cc1cccc([N+](=O)[O-])c1)C(=O)C(F)(F)F
Reactant: [H][H]
Agent: [Pd]
Solvent: CC(C)O
Product: CS(=O)(=O)CCN(Cc1cccc(N)c1)C(=O)C(F)(F)F
Temperature: 25 °C
Reaction time: 64 h
Yield: 93 %

Procedure:
To a suspension of 2,2,2-trifluoro-N-[2-(methylsulfonyl)ethyl]-N-[(3-nitrophenyl)methyl]acetamide (0.88 g, 2.5 mmol) in i-PrOH was added 10% Pd/C (80 mg, 0.08 mmol). A balloon filled with hydrogen gas was installed, and the reaction was stirred vigorously at rt. After 64 h, the reaction mixture was filtered through celite, adsorbed onto silica gel, and purified by column chromatography to generate the title compound in 93% yield. 1H NMR (400 MHz, CDCl3) δ 7.17 (t, J=7.5 Hz, 1H), 6.60-6.67 (m, 2H), 6.53 (s, 1H), 4.62 (s, 2H), 3.73 (t, J=6.9 Hz, 2H), 3.18 (t, J=6.8 Hz, 2H), 2.92 (s, 3H). ES-LC/MS m/z=324 [M+H]+.
Reaction SMILES: C(NC(C)C)(C)C.[Li]CCCC.[C:13]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])(=[O:15])[CH3:14].[C:21](OCC)(=[O:29])[C:22]1[C:23](=[CH:25][CH:26]=[CH:27][CH:28]=1)[OH:24]>C1COCC1>[OH:24][C:23]1[CH:25]=[CH:26][CH:27]=[CH:28][C:22]=1[C:21](=[O:29])[CH2:14][C:13]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15]
Reactant: CCOC(=O)c1ccccc1O
Reactant: CC(=O)OC(C)(C)C
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Product: CC(C)(C)OC(=O)CC(=O)c1ccccc1O
Temperature: -78 °C
Reaction time: 1.5 h
Yield: 74.8 %

Procedure:
To a N2 purged 250 mL RBF is added 30 mL of THF and diisopropylamine (12.0 mL, 86 mmol). The solution is cooled to −78° C. and nBuLi (50 mL, 1.6 M) is added and the solution is warmed to 0° C. for 45 min. The solution is cooled to −78° C. and t-butyl acetate (7.1 mL, 53 mmol) in 12 mL THF is added dropwise over 10 minutes. After 90 min., ethyl salicylate (2.2 mL, 15 mmol) in 15 mL of THF is added. The solution is allowed to warm to RT overnight and quenched with 90 mL of aq. NH4Cl (sat.), extracted with EtOAc (2×25 mL), washed brine (40 mL), dried Na2SO4, filtered, concentrated in vacuo. Purified via column chromatography (silica gel, 10% EtOAc/hex) to give 2.65 g of pale yellow oil (75% yield). IR (film) 2980.2; 2934.9; 1733.6; 1643.7; 1146.6; 757.0 cm−1; 1H NMR (500 MHz, CDCl3) δ 11.93 (s, 1H); 7.68 (d, J=7.9 Hz, 1H); 7.51 (t, J=7.3, 1H); 7.01 (d, J=8.2 Hz, 1H); 6.93 (t, J=7.3 Hz, 1H); 3.93 (s, 2H); 1.47 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 198.7, 165.8, 162.3, 136.6, 130.3, 118.8, 118.7, 118.3, 82.1, 46.9, 27.6; LRMS (electrospray): Mass calculated for C13H16O4, [M]+, 236.10. Found, [M+23]+259.5.
Reaction SMILES: [CH3:1][C:2]1[N:29]=[C:5]2[NH:6][C:7](=[O:28])[C:8]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([C:20]4[C:21]([C:26]#[N:27])=[CH:22][CH:23]=[CH:24][CH:25]=4)=[CH:16][CH:15]=3)=[C:9]([CH2:10][CH2:11][CH3:12])[N:4]2[N:3]=1.[H-].[Na+].CN(C)C=O.Br[CH:38]1[CH2:43][CH2:42][CH2:41][CH:40]=[CH:39]1>C(OCC)(=O)C>[CH:43]1([N:6]2[C:7](=[O:28])[C:8]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([C:20]4[C:21]([C:26]#[N:27])=[CH:22][CH:23]=[CH:24][CH:25]=4)=[CH:16][CH:15]=3)=[C:9]([CH2:10][CH2:11][CH3:12])[N:4]3[N:3]=[C:2]([CH3:1])[N:29]=[C:5]23)[CH2:42][CH2:41][CH2:40][CH:39]=[CH:38]1
Reactant: BrC1C=CCCC1
Reactant: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)[nH]c2nc(C)nn12
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n(C2C=CCCC2)c2nc(C)nn12
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 17 %

Procedure:
A mixture of 4′-[(2-methyl-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)methyl]biphenyl-2-carbonitrile (5 g), sodium hydride (0.62 g) and N,N-dimethylformamide (50 mL) was stirred at room temperature for 10 min, 3-bromocyclohexene (1.8 mL) was added, and the mixture was stirred at the same temperature for 16 hr. The reaction mixture was diluted with ethyl acetate, washed with 5% aqueous potassium hydrogensulfate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound as a colorless solid (1 g, 17%).
Reaction SMILES: [NH:1]1[CH2:4][CH:3]([CH2:5][C:6]2[S:7][C:8]3[N:9]=[C:10]([N:21]4[C:25]5[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=5[N:23]=[C:22]4[CH2:30][CH3:31])[N:11]=[C:12]([N:15]4[CH2:20][CH2:19][O:18][CH2:17][CH2:16]4)[C:13]=3[N:14]=2)[CH2:2]1.[OH:32][C:33]([CH3:38])([CH3:37])[C:34](O)=[O:35].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH2:30]([C:22]1[N:21]([C:10]2[N:11]=[C:12]([N:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)[C:13]3[N:14]=[C:6]([CH2:5][CH:3]4[CH2:2][N:1]([C:34](=[O:35])[C:33]([OH:32])([CH3:38])[CH3:37])[CH2:4]4)[S:7][C:8]=3[N:9]=2)[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[N:23]=1)[CH3:31]
Reactant: CC(C)(O)C(=O)O
Reactant: CCc1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(CC3CNC3)sc2n1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCc1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(CC3CN(C(=O)C(C)(C)O)C3)sc2n1
Temperature: 25 °C
Reaction time: 2 h
Yield: 35.5 %

Procedure:
A mixture of 2-azetidin-3-ylmethyl-5-(2-ethylbenzoimidazol-1-yl)-7-morpholin-4-ylthiazolo[5,4-d]pyrimidine (209 mg, 0.48 mmol), 2-hydroxyisobutyric acid (56 mg, 0.54 mmol), HATU (200 mg, 0.53 mmol) and DIPEA (94 μL, 0.54 mmol) in DCM (5 mL) was allowed to stir at r.t. for 2 h. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The resulting residue was purified by column chromatography (Si-PCC, MeOH:EtOAc, 0-2%) followed by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 20 mM triethylamine in water on a gradient of acetonitrile 5-98%) affording 814 as a white solid (89 mg, 35%). LCMS (method I): RT 3.39 min, [M+H]+ 522.2. 1H NMR (CDCl3, 400 MHz): δ 8.00-7.99 (1 H, m), 7.75-7.74 (1 H, m), 7.28-7.28 (2 H, m), 4.62-4.12 (7 H, m), 4.05-3.92 (1 H, m), 3.88 (4 H, t, J=4.76 Hz), 3.45 (1 H, s), 3.43-3.38 (2 H, m), 3.33 (2 H, q, J=7.47 Hz), 3.27-3.21 (1 H, m), 1.43-1.42 (9 H, m)
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][Cl:18])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:19][C:20]1[CH:28]=[C:27]([C:29]#[C:30][CH2:31][O:32][CH3:33])[C:23]2[O:24][CH2:25][O:26][C:22]=2[C:21]=1[NH2:34].C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>CN(C=O)C>[Cl:19][C:20]1[CH:28]=[C:27]([C:29]#[C:30][CH2:31][O:32][CH3:33])[C:23]2[O:24][CH2:25][O:26][C:22]=2[C:21]=1[NH:34][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][Cl:18])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1
Reactant: COc1cc2c(Cl)ncnc2cc1OCCCCl
Reactant: COCC#Cc1cc(Cl)c(N)c2c1OCO2
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: CN(C)C=O
Product: COCC#Cc1cc(Cl)c(Nc2ncnc3cc(OCCCCl)c(OC)cc23)c2c1OCO2
Yield: 66.6 %

Procedure:
This was prepared using the method described in example 4 using 4-chloro-7-(3-chloropropoxy)-6-methoxyquinazoline (400 mg, 1.39 mmol), 5-chloro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-amine (367 mg, 1.53 mmol) and sodium bis(trimethylsilyl)amide (1.0M in THF, 2.90 ml) in DMF (3 ml). The crude product was purified by column chromatography on silica using ethyl acetate as eluent. There was thus obtained the title compound (454 mg, 66%) as a pale yellow solid; NMR Spectrum:(CDCl3) 2.39 (quintet, 2H), 3.46 (s, 3H), 3.79 (t, 2H), 3.98 (s, 3H), 4.33 (t, 2H), 4.35 (s, 2H), 6.07 (s, 2H), 6.94 (s, 1H), 7.07 (s, 1H), 7.10 (s, 1H), 7.29 (s, 1H), 8.63 (s, 1H); Mass Spectrum: M+H+ 490.
Reaction SMILES: [N+](C[C:5](=[O:14])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])([O-])=O.[CH3:15][N:16]([CH2:18][CH2:19][OH:20])[CH3:17]>C1C=CC=CC=1>[C:5]([O:20][CH2:19][CH2:18][N:16]([CH3:17])[CH3:15])(=[O:14])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13]
Reactant: CN(C)CCO
Reactant: CCCCCCCCC(=O)C[N+](=O)[O-]
Solvent: c1ccccc1
Product: CCCCCCCCC(=O)OCCN(C)C
Yield: 72 %

Procedure:
In accordance with practice of the process of this invention, ten parts of 1-nitro-2-decanone, 5.0 parts of dimethylaminoethanol, and 110 parts of dry benzene are admitted to a reaction vessel wherein they are refluxed for four hours. At the end of this time, there are distilled off from the reaction mixture 44 parts by weight of benzene solvent and 2.0 parts by weight of nitromethane. The remaining benzene is then distilled at atmospheric pressure and 80°C. Thereafter the residual dark oil is distilled at 106°-110°C, at 2mm Hg to yield 8.2 parts by weight of N,N-dimethylaminoethyl nonanoate, a pale yellow liquid having a boiling point of 106°-110°C/2mm and a refractive index ND24 1.4355. (Yield 72%)
Reaction SMILES: F[C:2](F)(F)[C:3]([O:5][C:6](=[O:11])[C:7]([F:10])([F:9])[F:8])=O.N1C=CC=CC=1.O[C@@H]1[CH2:40][CH2:39][C@@:38]2([CH3:41])[C@@H:23]([CH2:24][CH2:25][C@@H:26]3[C@@H:37]2[C:36](=[O:42])[CH2:35][C@@:34]2([CH3:43])[C@H:27]3[CH2:28][CH2:29][C@@H:30]2[C:31](=[O:33])[CH3:32])C1>C(Cl)Cl>[F:8][C:7]([F:10])([F:9])[C:6]([O:5][C@@H:3]1[CH2:40][CH2:39][C@@:38]2([CH3:41])[C@@H:23]([CH2:24][CH2:25][C@@H:26]3[C@@H:37]2[C:36](=[O:42])[CH2:35][C@@:34]2([CH3:43])[C@H:27]3[CH2:28][CH2:29][C@@H:30]2[C:31](=[O:33])[CH3:32])[CH2:2]1)=[O:11]
Reactant: CC(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@H](O)CC[C@]4(C)[C@H]3C(=O)C[C@]12C
Reactant: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@H](OC(=O)C(F)(F)F)CC[C@]4(C)[C@H]3C(=O)C[C@]12C
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A solution of trifluoroacetic anhydride (0.34 ml.) and pyridine (0.24 ml.) in methylene dichloride (10 ml.) was added to a cooled (-80°) and stirred solution of 3α-hydroxy-5α-pregnane-11,20-dione (0.50 g.) in methylene dichloride (20 ml.) and the mixture was allowed to warm up to room temperature. After 11/2 hours more trifluoroacetic anhydride (0.34 ml.) was added and the reaction was complete after 1/2 hour more. The solution was washed successively with water, sodium bicarbonate solution and water. The dried and concentrated solution afforded a crystalline residue that was triturated with petroleum to give the title compound as needles (0.44 g.) m.p. 107°-108°, [α]D + 96°.
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[C:5]([N:11]2[N:15]=[C:14]3[CH:16]=[CH:17][C:18]([O:20][CH3:21])=[CH:19][C:13]3=[N:12]2)[C:4]=1[OH:22].C(N(CC)CC)C.[C:30](Cl)(=[O:34])[C:31]([CH3:33])=[CH2:32]>C1COCC1>[C:30]([O:1][CH2:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[C:5]([N:11]2[N:15]=[C:14]3[CH:16]=[CH:17][C:18]([O:20][CH3:21])=[CH:19][C:13]3=[N:12]2)[C:4]=1[OH:22])(=[O:34])[C:31]([CH3:33])=[CH2:32]
Reactant: COc1cc(CO)c(O)c(-n2nc3ccc(OC)cc3n2)c1
Reactant: C=C(C)C(=O)Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: C=C(C)C(=O)OCc1cc(OC)cc(-n2nc3ccc(OC)cc3n2)c1O
Temperature: -5 °C
Reaction time: 2 h

Procedure:
In a 100 ml round bottom 3-neck flask equipped with a magnetic stirrer and nitrogen inlet was dissolved 3.24 g (10.8 mmol) 2-(hydroxymethyl)-4-methoxy-6-(5-methoxy-2H-benzo[d][1,2,3]-triazol-2-yl)phenol in 60 ml anhydrous THF. Triethylamine (1.2 ml) was added and the mixture was cooled to −10-0° C. Methacryloyl chloride (1.40 g, 13.4 mmol) was added dropwise and the mixture was stirred for 2 hr at 0° C. followed by 20 hours at ambient temperature. The salts were filtered off and the filtrate was poured into 100 ml diethyl ether and washed with 0.5 N HCl and water. The organic layer was dried with magnesium sulfate, filtered, and concentrated via rotary evaporation to give the desired product as a dark yellow oil which was recrystallized in ethanol to give a light yellow solid. 1H NMR (CDCl3) delta: 11.20 (s, 1H, phenol OH), 7.80 (m, 1H, Ar—H benzotriazole), 7.77 (s, 1H, Ar—H phenol), 7.17 (m, 1H, Ar—H benzotriazole), 7.14 (s, 1H, Ar—H phenol), 7.10 (m, 1H, Ar—H benzotriazole), 6.21 (s, 1H, C═C—H trans), 5.61 (s, 1H, C═C—H cis), 5.38 (s, 2H, Ar—C1-12), 3.92 (s, 3H, Ar—OCH3, phenol), 3.88 (s, 3H, Ar—OCH3, benzotriazole), 2.01 (s, 3H, C═C—CH3).
Reaction SMILES: [NH2:1][C:2]1[C:3]([N+:22]([O-:24])=[O:23])=[CH:4][C:5]([Cl:21])=[C:6]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)[CH:7]=1.[CH3:25][N:26]([C:28]1[CH:36]=[CH:35][C:31]([C:32](Cl)=[O:33])=[CH:30][CH:29]=1)[CH3:27].CCN(P1(N(C)CCCN1C)=NC(C)(C)C)CC>CN(C1C=CN=CC=1)C.ClCCCl.N1CCCCC1>[Cl:21][C:5]1[CH:4]=[C:3]([N+:22]([O-:24])=[O:23])[C:2]([NH:1][C:32](=[O:33])[C:31]2[CH:30]=[CH:29][C:28]([N:26]([CH3:25])[CH3:27])=[CH:36][CH:35]=2)=[CH:7][C:6]=1[N:8]1[CH2:9][CH2:10][N:11]([C:14]([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15])[CH2:12][CH2:13]1
Reactant: CN(C)c1ccc(C(=O)Cl)cc1
Reactant: CC(C)(C)OC(=O)N1CCN(c2cc(N)c([N+](=O)[O-])cc2Cl)CC1
Agent: CCN(CC)P1(=NC(C)(C)C)N(C)CCCN1C
Agent: CN(C)c1ccncc1
Solvent: C1CCNCC1
Solvent: ClCCCl
Product: CN(C)c1ccc(C(=O)Nc2cc(N3CCN(C(=O)OC(C)(C)C)CC3)c(Cl)cc2[N+](=O)[O-])cc1
Temperature: 85 °C
Yield: 70.9 %

Procedure:
A mixture of tert-butyl 4-(5-amino-2-chloro-4-nitrophenyl)piperazine-1-carboxylate (1.2 g, 3.36 mmol), 4-(N,N-dimethylamino)benzoyl chloride (803 mg, 4.37 mmol), BEMP (1846 mg, 6.73 mmol), and DMAP (411 mg, 3.36 mmol) in DCE (Volume: 15 ml) was heated at 85° C. foe 4 h. Cooled down and treated with a few drops of piperidine for 1 h. After the solvent was removed and mixture was diluted with MeOH, a orange precipitate formed. Filtration and washing with MeOH gave tert-butyl 4-(2-chloro-5-(4-(dimethylamino)benzamido)-4-nitrophenyl)piperazine-1-carboxylate (1.2 g, 2.381 mmol, 70.8% yield). 1H-NMR (CDCl3, 500 MHz): δ11.53 (1H, s), 8.82 (1H, s), 8.31 (1H, s), 7.89 (2H, d, J=8.85 Hz), 6.74 (1H, d, J=8.85 Hz), 3.64 (4H, m), 3.27 (4H, m), 3.09 (6H, s), 1.50 (9H, s).
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][OH:16]>>[C:1]1([O:7][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][OH:16])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: Oc1ccccc1
Reactant: OCCCCCCCBr
Product: OCCCCCCCOc1ccccc1

Procedure:
alkylating a phenol with 7-bromo-1-heptanol to provide 7-(phenyloxy)-1-heptanol;
Reaction SMILES: [Cl:1][C:2]1[CH:6]=[CH:5][S:4][C:3]=1[C:7]1[N:8]=[C:9]([NH2:12])[S:10][CH:11]=1.[Cl:13][C:14]1[CH:19]=[C:18]([Cl:20])[CH:17]=[C:16]([Cl:21])[C:15]=1[S:22](Cl)(=[O:24])=[O:23]>>[Cl:13][C:14]1[CH:19]=[C:18]([Cl:20])[CH:17]=[C:16]([Cl:21])[C:15]=1[S:22]([NH:12][C:9]1[S:10][CH:11]=[C:7]([C:3]2[S:4][CH:5]=[CH:6][C:2]=2[Cl:1])[N:8]=1)(=[O:24])=[O:23]
Reactant: O=S(=O)(Cl)c1c(Cl)cc(Cl)cc1Cl
Reactant: Nc1nc(-c2sccc2Cl)cs1
Product: O=S(=O)(Nc1nc(-c2sccc2Cl)cs1)c1c(Cl)cc(Cl)cc1Cl

Procedure:
The title compound was prepared from 4-(3-chloro-2-thienyl)-1,3-thiazol-2-amine and 2,4,6-trichlorobenzenesulfonyl chloride as described in the synthetic METHOD B to give a white solid (5.0 mg) with purity >90%. MS (pos) m/z 459.1, 461.1, 463.1.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[CH:9](C#N)[CH2:10][CH2:11][C:12]([CH3:20])([CH3:19])[CH2:13][C:14]([O:16]CC)=O.Cl.C(O)(=[O:26])C.O>C(OCC)C>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[C:10](=[O:26])[CH2:11][C:12]([CH3:19])([CH3:20])[CH2:13][C:14]1=[O:16]
Reactant: CC(=O)O
Reactant: CCOC(=O)CC(C)(C)CCC(C#N)c1ccc(C)cc1C
Agent: Cl
Solvent: O
Solvent: CCOCC
Product: Cc1ccc(C2C(=O)CC(C)(C)CC2=O)c(C)c1
Reaction time: 12 h
Yield: 32 %

Procedure:
A one-neck round bottom flask was charged with 52.50 g (0.17 mol) of ethyl 6-(2',4'-dimethylphenyl)-6-cyano-3,3-dimethylhexanoate, 250 ml of concentrated hydrochloric acid, 250 ml of glacial acetic acid, and 100 ml of water. The reaction mixture was stirred and refluxed for 48 hours. After 12 hours and 24 hrs. of refluxing, an additional 100 ml of conc. HCl and 100 ml glacial HOAC were added. After 48 hours, the mixture was stripped to dryness under reduced pressure. To the residue were added 150 ml of water and 150 ml of ethyl ether, and the mixture shaken vigorously. A white, crystalline precipitate formed, and this was removed by suction filtration to give 13.20 g (32%) of 2-(2',4'-Dimethylphenyl)-5,5-dimethyl-1,3-cyclohexanedione as a white, crystalline solid, m.p. 167°-168.5° C.
Reaction SMILES: [N:1]1[CH:2]=[C:3]2[N:12]3[C:7](=[CH:8][CH:9]=[CH:10][C:11]=13)[S:6][C:5]([C:13]([OH:15])=O)=[CH:4]2.ON1C(=O)CCC1=O.Cl.C(N=C=NCCCN(C)C)C.Cl.Cl.[NH2:38][CH2:39][CH2:40][CH2:41][N:42]1[CH2:47][CH2:46][CH:45]([CH2:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[CH2:44][CH2:43]1>C(#N)C.C(N(CC)CC)C>[CH2:48]([CH:45]1[CH2:44][CH2:43][N:42]([CH2:41][CH2:40][CH2:39][NH:38][C:13]([C:5]2[S:6][C:7]3[N:12]4[C:3](=[CH:2][N:1]=[C:11]4[CH:10]=[CH:9][CH:8]=3)[CH:4]=2)=[O:15])[CH2:47][CH2:46]1)[C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1
Reactant: O=C(O)C1=Cc2cnc3cccc(n23)S1
Reactant: NCCCN1CCC(Cc2ccccc2)CC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: O=C1CCC(=O)N1O
Solvent: CC#N
Solvent: CCN(CC)CC
Product: O=C(NCCCN1CCC(Cc2ccccc2)CC1)C1=Cc2cnc3cccc(n23)S1
Reaction time: 2 h

Procedure:
To a suspension of 1.0 g (4.58 mM) of 5-thia-1,8b-diazaacenaphthylene-4-carboxylic acid and 1.05 g (9.12 mM) of N-hydroxysuccinimide in acetonitrile (10 ml) was added 1.76 g (9.18 mM) of N-ethyl-N′-3-(N,N-dimethylamino)propylcarbodiimide hydrochloride at room temperature and the mixture was stirred at the prevailing temperature for 2 hours. To this mixture was added a suspension of 2.09 g (6.85 mM) of 1-(3-aminopropan-1-yl)-4-benzylpiperidine dihydrochloride and 3.87 ml (27.8 mM) of triethylamine in acetonitrile (5 ml) and the mixture was further stirred for 30 minutes. The solvent was then distilled off under reduced pressure and the residue was diluted with water and extracted with chloroform. The organic layer was washed with saturated aqueous solution of sodium chloride, dried over MgSO4, and purified by column chromatography (methanol/ethyl acetate 20-40-60%) to provide the title compound as red-purple amorphous substance.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([SH:8])=[CH:4][CH:3]=1.CO[CH:11](OC)[CH2:12]Br>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]2[S:8][CH:11]=[CH:12][C:4]=2[CH:3]=1
Reactant: COC(CBr)OC
Reactant: Sc1ccc(Br)cc1
Product: Brc1ccc2sccc2c1

Procedure:
5-Bromobenzo[b]thiophene was prepared in quantitative yield for two steps from 4-bromobenzenethiol and bromoacetaldehyde dimethyl acetal as described in the preparation of 4- and 6-methoxybenzo[b]thiophene (see Example 92, Part A): mp 40-43.5° C.; FDMS 212.1 (M−1); Anal. Calcd for C8H5BrS·0.10C7H8OS: C, 46.01; H, 2.57; S, 15.53. Found: C, 46.19; H, 2.49; S, 15.79.
Reaction SMILES: F[C:2]1[CH:3]=[C:4]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.[NH2:11][CH2:12][CH2:13][CH2:14][N:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1.O>CS(C)=O>[N:15]1([CH2:14][CH2:13][CH2:12][NH:11][C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([N+:8]([O-:10])=[O:9])[CH:3]=2)[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1
Reactant: NCCCN1CCOCC1
Reactant: O=[N+]([O-])c1cccc(F)c1
Solvent: O
Solvent: CS(C)=O
Product: O=[N+]([O-])c1cccc(NCCCN2CCOCC2)c1
Temperature: 100 °C
Reaction time: 60 h

Procedure:
28.2 g 3-fluoronitrobenzene and 158.4 g 4-(3-aminopropyl)morpholine were dissolved in 300 ml dimethyl sulfoxide, and the batch was stirred for 60 h at 100° C. After cooling, the batch was poured into 1 l water. The mixture was extracted several times with methyl tert-butyl ether, and the combined organic phases were reduced to dryness on a rotary evaporator. The product obtained was an orange-brown oil.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]2[CH:18]=[C:17]([CH2:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[S:16][C:10]=2[NH:11][C:12](=O)[CH2:13][N:14]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:36])=CC=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]2[CH:18]=[C:17]([CH2:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[S:16][C:10]=2[NH:11][C:12](=[S:36])[CH2:13][N:14]=1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: O=C1CN=C(c2ccccc2Cl)c2cc(CCc3ccccc3)sc2N1
Solvent: Cc1ccccc1
Product: S=C1CN=C(c2ccccc2Cl)c2cc(CCc3ccccc3)sc2N1
Yield: 208 %

Procedure:
A suspension of 7.5 g of 5-(2-chlorophenyl)-7-(2-phenylethyl)-1,3-dihydro-2H-thieno[2,3-e]-1,4-diazepin-2-one, melting at 175°-176° C. and 4.8 g of Lawesson reagent in 150 ml of toluene is stirred at 40°-45° C. for an hour. The resultant solution is concentrated under reduced pressure, and the residue is subjected to chromatography on silica gel and then eluted with chloroform-methanol (100:1 to 100:2). The objective fraction is concentrated under reduced pressure to give 9.8 g of 5-(2-chlorophenyl)-7-(2-phenylethyl)-1,3-dihydro-2H-thieno[2,3-e]-1,4-diazepine-2-thione.