Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[C:7]([CH:8]=[O:9])=[CH:6][C:5]([O:10][CH3:11])=[N:4][CH:3]=1.Cl.Cl[CH2:14][C:15]1[C:16]([C:21]2[N:25]([CH:26]([CH3:28])[CH3:27])[N:24]=[CH:23][CH:22]=2)=[N:17][CH:18]=[CH:19][CH:20]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH:26]([N:25]1[C:21]([C:16]2[C:15]([CH2:14][O:1][C:2]3[C:7]([CH:8]=[O:9])=[CH:6][C:5]([O:10][CH3:11])=[N:4][CH:3]=3)=[CH:20][CH:19]=[CH:18][N:17]=2)=[CH:22][CH:23]=[N:24]1)([CH3:28])[CH3:27]
Reactant: COc1cc(C=O)c(O)cn1
Reactant: CC(C)n1nccc1-c1ncccc1CCl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1cc(C=O)c(OCc2cccnc2-c2ccnn2C(C)C)cn1
Temperature: 70 °C
Yield: 64.9 %

Procedure:
A mixture of 5-hydroxy-2-methoxyisonicotinaldehyde (395 mg, 2.58 mmol, 1 eq.), 3-(chloromethyl)-2-(1-isopropyl-1H-pyrazol-5-yl)pyridine hydrochloride (700 mg, 2.58 mmol, 1 eq.), and K2CO3 (1.4 g, 10.32 mmol, 4 eq.) in DMF (10.0 mL) was heated at 70° C. for 2 h. The mixture was cooled, filtered, concentrated, and purified on silica gel using a mixture of EtOAc and hexanes as eluent to give 5-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)-2-methoxyisonicotinaldehyde (590 mg, 65%) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ 10.41 (s, 1H), 8.76 (dd, J=4.7, 1.6 Hz, 1H), 8.04 (dd, J=7.9, 1.6 Hz, 1H), 7.90 (s, 1H), 7.61 (d, J=1.8 Hz, 1H), 7.44 (dd, J=7.9, 4.8 Hz, 1H), 7.10 (s, 1H), 6.37 (d, J=1.8 Hz, 1H), 5.14 (s, 2H), 4.65 (sep, J=6.6 Hz, 1H), 3.91 (s, 3H), 1.49 (d, J=6.6 Hz, 6H); MS (ESI) m/z 353.1 [M+H]+.
Reaction SMILES: [CH2:1]([N:19]=[C:20]=[O:21])[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:22]([CH2:47][CH2:48][OH:49])([C:25]([C:28]([C:31]([C:34]([C:37]([C:40]([C:43]([F:46])([F:45])[F:44])([F:42])[F:41])([F:39])[F:38])([F:36])[F:35])([F:33])[F:32])([F:30])[F:29])([F:27])[F:26])([F:24])[F:23]>>[CH2:1]([NH:19][C:20]([O:49][CH2:48][CH2:47][C:22]([C:25]([C:28]([C:31]([C:34]([C:37]([C:40]([C:43]([F:44])([F:45])[F:46])([F:41])[F:42])([F:38])[F:39])([F:35])[F:36])([F:33])[F:32])([F:30])[F:29])([F:27])[F:26])([F:24])[F:23])=[O:21])[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]
Reactant: CCCCCCCCCCCCCCCCCCN=C=O
Reactant: OCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Product: CCCCCCCCCCCCCCCCCCNC(=O)OCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Temperature: 90 °C
Reaction time: 8 h

Procedure:
Octadecyl isocyanate (29.5 g, 0.1 moles) and C8F17CH2CH2OH (46.4 g, 0.1 moles) were mixed under nitrogen and heated with stirring to 90° C. for 8 hours. An infrared spectrum showed no --NCO absorption, indicating completion of the reaction. The product is a white wax melting at 72°-75° C. NMR showed proton resonances at 4.7 ppm (1 proton NH), 4.4 ppm (2 proton CH2OCO--), 3.2 ppm (2 protons CH2CH2NH), 2.5 ppm (2 protons C8F17CH2), 1.3 pm (32 protons CH3 (CH2)16) and 0.8 ppm (3 protons CH3 (CH2)16).
Reaction SMILES: [Cl:1][C:2]1[N:11]=[C:10](Cl)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[CH3:13][O:14][C:15]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][C:16]=1[NH2:17]>>[Cl:1][C:2]1[N:11]=[C:10]([NH:17][C:16]2[CH:18]=[C:19]([O:22][CH3:23])[CH:20]=[CH:21][C:15]=2[O:14][CH3:13])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1
Reactant: Clc1nc(Cl)c2ccccc2n1
Reactant: COc1ccc(OC)c(N)c1
Product: COc1ccc(OC)c(Nc2nc(Cl)nc3ccccc23)c1

Procedure:
The title compound was prepared from 2,4-dichloroquinazoline and 2,5-dimethoxyaniline by a procedure similar to Example 28 (98% yield). 1H NMR (CDCl3): 8.59 (d, J=3.0 Hz, 1H), 8.53 (s, broad, 1H), 7.78-7.87 (m, 3H), 7.57 (ddd, J=8.4, 6.6 and 1.8 Hz, 1H), 6.88 (d, J=9.0 Hz, 1H), 6.60 (dd, J=8.7 and 3.0 Hz, 1H), 3.97 (s, 3H), 3.87 (s, 3H).
Reaction SMILES: [OH-].[Na+].C([O:5][C:6]([C:8]1[N:23]=[CH:22][C:11]2[N:12]([CH:19]([CH3:21])[CH3:20])[C:13]3[C:18]([C:10]=2[CH:9]=1)=[CH:17][CH:16]=[CH:15][CH:14]=3)=[O:7])C>CO.O>[C:6]([C:8]1[N:23]=[CH:22][C:11]2[N:12]([CH:19]([CH3:20])[CH3:21])[C:13]3[C:18]([C:10]=2[CH:9]=1)=[CH:17][CH:16]=[CH:15][CH:14]=3)([OH:7])=[O:5]
Reactant: CCOC(=O)c1cc2c3ccccc3n(C(C)C)c2cn1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: CC(C)n1c2ccccc2c2cc(C(=O)O)ncc21
Temperature: 25 °C
Reaction time: 20 h
Yield: 82.1 %

Procedure:
A solution (1 mol dm−3) of sodium hydroxide (21 ml, 21 mmol) was added over 10 minutes to a stirred solution of 3-ethoxycarbonyl-9-isopropyl-9H-pyrido[3,4-b]indole (Method 1; 2.9 g, 10.3 mmol) in a MeOH/water mix (100 ml 2:1 v/v), and the mixture was allowed to stir for 20 hours at room temperature. MeOH was removed in vacuo and the mixture acidified by the addition of HCl (1 mol dm−3). The precipitate was filtered, washed with water and dried under vacuum at 65° C. for 2 hours to give a light yellow solid (2.15 g). NMR (300 MHz) 9.19 (s, 1H), 8.91 (s, 1H), 8.41 (d, 1H), 7.85 (d, 1H), 7.62 (t, 1H), 7.31 (t, 1H), 5.26 (m, 1H), 1.66 (d 6H); m/z 255.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:19]=[CH:18][C:12]([C:13](OCC)=[O:14])=[CH:11][C:10]=1[Cl:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:21][NH2:22]>CO>[CH2:1]([O:8][C:9]1[CH:19]=[CH:18][C:12]([C:13]([NH:21][NH2:22])=[O:14])=[CH:11][C:10]=1[Cl:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NN
Reactant: CCOC(=O)c1ccc(OCc2ccccc2)c(Cl)c1
Solvent: CO
Product: NNC(=O)c1ccc(OCc2ccccc2)c(Cl)c1
Temperature: 25 °C
Yield: 96.7 %

Procedure:
Ethyl 4-benzyloxy-3-chlorobenzoate [c.f., Jones & Robinson, J. Chem. Soc. 3845 (1955)] (32.0 g., 0.11 mole), 25 ml. methanol and 20 ml. 95% hydrazine are stirred under reflux for 8 hours and cooled to room temperature. The mixture is filtered and the resulting solid dried in vacuo to give 29.4 g. 4-benzyloxy-3-chlorobenzoic acid hydrazide (96.7% yield), m.p. 168°-171° C.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][S:9]([C:12]2[CH:17]=[CH:16][C:15](Cl)=[C:14]([N+:19]([O-:21])=[O:20])[CH:13]=2)(=[O:11])=[O:10])=[CH:4][CH:3]=1.[NH2:22][C:23]1[CH:28]=[CH:27][C:26]([SH:29])=[CH:25][CH:24]=1.C([O-])(=O)C.[Na+]>C(O)C>[NH2:22][C:23]1[CH:28]=[CH:27][C:26]([S:29][C:15]2[CH:16]=[CH:17][C:12]([S:9]([NH:8][C:5]3[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][CH:4]=3)(=[O:11])=[O:10])=[CH:13][C:14]=2[N+:19]([O-:21])=[O:20])=[CH:25][CH:24]=1
Reactant: Nc1ccc(S)cc1
Reactant: O=[N+]([O-])c1cc(S(=O)(=O)Nc2ccc(Br)cc2)ccc1Cl
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CCO
Product: Nc1ccc(Sc2ccc(S(=O)(=O)Nc3ccc(Br)cc3)cc2[N+](=O)[O-])cc1
Temperature: 25 °C
Yield: 99.9 %

Procedure:
A mixture of the product of Example 149A (500 mg, 1.277 mmol), 4-aminothiophenol (240 mg, 1.915 mmol) and anhydrous sodium acetate (524 mg, 6.384 mmol) in anhydrous ethanol (9 mL) was heated at reflux under a nitrogen atmosphere for 1 hour. The reaction was cooled to room temperature and the ethanol removed by rotary evaporation under vacuum. The residue was taken up in ethyl acetate (100 mL) and washed with water (2×50 mL) and brine (50 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum, co-evaporating the oil with methylene chloride/hexanes to obtain the title compound as an orange foam (613 mg, 100%).
Reaction SMILES: F[C:2]1[C:11]([N+:12]([O-:14])=[O:13])=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].C(=O)([O-])[O-].[K+].[K+].[CH3:21][NH2:22]>C(Cl)Cl.O>[CH3:21][NH:22][C:2]1[C:11]([N+:12]([O-:14])=[O:13])=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]
Reactant: COC(=O)c1cccc([N+](=O)[O-])c1F
Reactant: CN
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: ClCCl
Product: CNc1c(C(=O)OC)cccc1[N+](=O)[O-]
Temperature: 25 °C

Procedure:
Methyl 2-fluoro-3-nitrobenzoate (25 g, 0.126 mol) was dissolved in DCM (400 ml) and to this was added Potassium carbonate (34.7 g, 0.25 mol) followed by Methylamine (20.63 ml, 0.5 mol). Reaction was stirred at room temperature under argon. Upon completion reaction was diluted with water and extracted with DCM (3×) then dried over magnesium sulfate. Solvents were removed under reduced pressure to afford methyl 2-(methylamino)-3-nitrobenzoate as a yellow solid.
Reaction SMILES: C(OC([N:8]([S:13]([O:16][N:17]1[C:21](=[O:22])[CH2:20][CH2:19][C:18]1=[O:23])(=[O:15])=[O:14])[CH2:9][CH2:10][O:11][CH3:12])=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[CH3:12][O:11][CH2:10][CH2:9][NH:8][S:13]([O:16][N:17]1[C:18](=[O:23])[CH2:19][CH2:20][C:21]1=[O:22])(=[O:15])=[O:14]
Reactant: COCCN(C(=O)OC(C)(C)C)S(=O)(=O)ON1C(=O)CCC1=O
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COCCNS(=O)(=O)ON1C(=O)CCC1=O
Temperature: 0 °C
Reaction time: 2 h
Yield: 104.1 %

Procedure:
To a solution of N-(N-t-butoxycarbonyl-N-(2-methoxyethyl)aminosulfonyloxy)succinimide (200 mg) in dichloromethane (2 ml) was added trifluoroacetic acid (2 ml) under ice-water cooling and the mixture was stirred at 0° C. for 2 hours. The solution was evaporated in vacuo to give N-(2-methoxyethylaminosulfonyloxy)succinimide as a colorless amorphous powder (149 mg).
Reaction SMILES: [F:1][C@H:2]([CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10])[CH2:3][OH:4].N1C=CC=CC=1.[S:17](Cl)([C:20]1[CH:26]=[CH:25][C:23]([CH3:24])=[CH:22][CH:21]=1)(=[O:19])=[O:18]>O>[S:17]([C:20]1[CH:26]=[CH:25][C:23]([CH3:24])=[CH:22][CH:21]=1)([O:4][CH2:3][C@H:2]([F:1])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10])(=[O:19])=[O:18]
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: CCCCCC[C@@H](F)CO
Solvent: c1ccncc1
Solvent: O
Product: CCCCCC[C@@H](F)COS(=O)(=O)c1ccc(C)cc1
Reaction time: 6 h
Yield: 93.1 %

Procedure:
A reaction vessel was charged with 10.0 g of (2R)-2fluorooctanol and 25 ml of pyridine, and 13.0 g of tosyl chloride was added with stirring at 0°-5° C. After the reaction was effected for 6 hours, the mixture was poured into water and extracted with 100 ml of benzene. The resultant solution in benzene was washed sequentially with water, an aqueous solution of NaHCO3 and water in that order, and dried over Glauber's salt. The solvent was distilled off to obtain 19.0 g (yield 92.6%) of crude (2R)-2-fluorooctyl tosylate as the residue.
Reaction SMILES: [Na+].[CH3:2][C:3]1[NH:7][CH:6]=[N:5][C:4]=1[C:8]([O-])=[O:9].C=O.O1CCOCC1.[ClH:19]>C(O)C>[ClH:19].[OH:9][CH2:8][C:4]1[N:5]=[CH:6][NH:7][C:3]=1[CH3:2]
Reactant: Cc1[nH]cnc1C(=O)[O-]
Agent: C=O
Agent: Cl
Agent: [Na+]
Solvent: CCO
Solvent: C1COCCO1
Product: Cc1[nH]cnc1CO
Yield: 63 %

Procedure:
A mixture of 1.48 g (0.01 mol) of 5-methylimidazole-4-carboxylic acid sodium salt, 2 ml of ~37% formaldehyde solution and 3 ml of 1,4-dioxane was heated at 75°-85° C. for 3 hours. After completion of the reaction, the solvent was stripped off, and the remaining residue was extracted with isopropanol. The isopropanol extract was concentrated to give a viscous oil. This viscous oil was dissolved in absolute ethanol and dry hydrogen chloride gas was passed through the resulting solution to afford 0.93 g of 4-hydroxymethyl-5-methylimidazole hydrochloride, m.p. 241°-244° C. Yield 63%.
Reaction SMILES: [C:1]([O:5][C:6](=[O:29])[N:7]([C:14]1[N:19]=[CH:18][C:17]([CH2:20][O:21][Si](C(C)(C)C)(C)C)=[CH:16][N:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([CH3:4])([CH3:3])[CH3:2].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C1COCC1>C1COCC1.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:29])[N:7]([C:14]1[N:19]=[CH:18][C:17]([CH2:20][OH:21])=[CH:16][N:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N(c1ccccc1)c1ncc(CO[Si](C)(C)C(C)(C)C)cn1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N(c1ccccc1)c1ncc(CO)cn1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 83.2 %

Procedure:
[5-(tert-Butyldimethylsiloxymethyl)pyrimidin-2-yl]phenylcarbamic acid tert-butyl ester (560 mg, 1.34 mmol) obtained in Step 5 was dissolved in THF (10 mL), and a 1.0 mol/L tetrabutylammonium fluoride-THF solution (4.02 mL, 4.02 mmol) was added to the solution, followed by stirring at room temperature for 1.5 hours. The reaction mixture was diluted with ethyl acetate and washed with water and saturated brine. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=3:1) to obtain (5-hydroxymethylpyrimidin-2-yl)phenylcarbamic acid tert-butyl ester (336 mg, 83%).
Reaction SMILES: [C:1]1([CH2:7][C:8]([OH:10])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[CH3:42][O:43][C:44]1[C:45]2[N:58]=[C:57]([NH2:59])[S:56][C:46]=2[C:47]([N:50]2[CH2:55][CH2:54][O:53][CH2:52][CH2:51]2)=[N:48][CH:49]=1>C1COCC1>[CH3:42][O:43][C:44]1[C:45]2[N:58]=[C:57]([NH:59][C:8](=[O:10])[CH2:7][C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[S:56][C:46]=2[C:47]([N:50]2[CH2:51][CH2:52][O:53][CH2:54][CH2:55]2)=[N:48][CH:49]=1
Reactant: O=C(O)Cc1ccccc1
Reactant: COc1cnc(N2CCOCC2)c2sc(N)nc12
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN1CCOCC1
Solvent: C1CCOC1
Product: COc1cnc(N2CCOCC2)c2sc(NC(=O)Cc3ccccc3)nc12

Procedure:
From phenylacetic acid, HATU and N-methylmorpholine in THF, then treatment with 7-methoxy-4-morpholin-4-yl-thiazolo[5,4-c]pyridin-2-ylamine. ES-MS m/e (%): 385 (M+H+, 100).
Reaction SMILES: [Br-].[CH3:2][O:3][C:4]1[CH:5]=[C:6]([CH2:12][P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:7]=[CH:8][C:9]=1[O:10][CH3:11].[Li]CCCC.[CH:37]([C:40]1[CH:41]=[C:42]([CH:46]([CH3:50])[CH2:47][CH:48]=O)[CH:43]=[CH:44][CH:45]=1)([CH3:39])[CH3:38].O>C1COCC1>[CH:37]([C:40]1[CH:41]=[C:42]([CH:46]([CH3:50])[CH2:47][CH:48]=[CH:12][C:6]2[CH:7]=[CH:8][C:9]([O:10][CH3:11])=[C:4]([O:3][CH3:2])[CH:5]=2)[CH:43]=[CH:44][CH:45]=1)([CH3:39])[CH3:38]
Reactant: COc1ccc(C[P+](c2ccccc2)(c2ccccc2)c2ccccc2)cc1OC
Reactant: CC(C)c1cccc(C(C)CC=O)c1
Agent: [Br-]
Agent: [Li]CCCC
Solvent: O
Solvent: C1CCOC1
Product: COc1ccc(C=CCC(C)c2cccc(C(C)C)c2)cc1OC
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 82.3 %

Procedure:
A solution of (3,4-dimethoxyphenyl)methyltriphenylphosphonium bromide (4.93 g, 10.0 mmol, 1.0 equiv.) in THF (10 mL), was cooled to 0° C. After adding n-BuLi (1.6 M in hexanes, 6.3 mL, 10.0 mmol, 1.0 equiv.) at 0° C., the red suspension was stirred at 0° C. for 20 min. 3-(3-Isopropylphenyl)butanal (2.09 g, 11.0 mmol, 1.1 equiv.) in THF (11 mL) was added, and the mixture was stirred at 0° C.→25° C. for 16 h. After addition of H2O at 25° C., the aqueous layer was extracted with hexanes (2×), the combined organic phases were dried (MgSO4), filtered and the filtrate was concentrated. The residue was purified by flash chromatography on SiO2 (hexanes/EtOAc 99:1→4:1) to yield 2.67 g (82%) of the title compound as a colorless oil.
Reaction SMILES: Br[C:2]1[CH2:7][C:6]([CH3:9])([CH3:8])[CH2:5][C:4](=[O:10])[CH:3]=1.[NH:11]1[C:19]2[C:14](=[CH:15][C:16](B3OC(C)(C)C(C)(C)O3)=[CH:17][CH:18]=2)[CH:13]=[CH:12]1>>[NH:11]1[C:19]2[C:14](=[CH:15][C:16]([C:2]3[CH2:7][C:6]([CH3:9])([CH3:8])[CH2:5][C:4](=[O:10])[CH:3]=3)=[CH:17][CH:18]=2)[CH:13]=[CH:12]1
Reactant: CC1(C)OB(c2ccc3[nH]ccc3c2)OC1(C)C
Reactant: CC1(C)CC(=O)C=C(Br)C1
Product: CC1(C)CC(=O)C=C(c2ccc3[nH]ccc3c2)C1
Yield: 95 %

Procedure:
Synthesized from 3-Bromo-5,5-dimethyl-cyclohex-2-enone and indole-5-boronic acid pinacol ester according to the general procedure described for the Suzuki coupling. Purification by automated flash chromatography using gradient elution (0 to 80% ethyl acetate/hexanes) yielded the product (177 mg, 95%) as an off-white solid. 1H NMR (300 MHz, CDCl3): δ 8.97 (bs, 1H), 7.84 (s, 1H), 7.39 (d, J=1.2 Hz, 2H), 7.22 (dd, J=3.0, 2.1 Hz, 1H), 6.56 (dd, J=3.0, 2.1 Hz, 1H), 6.49 (t, J=1.5 Hz, 1H), 2.74 (d, J=1.2 Hz, 2H), 2.35 (s, 2H), 1.25 (s, 3H), 1.14 (s, 3H). 13C (75 MHz, CDCl3): 200.4, 159.5, 136.8, 130.2, 127.9, 125.5, 122.4, 120.1, 119.1, 111.3, 103.1, 50.9, 42.6, 33.8, 28.4, 24.9. HRMS (LCT Electrospray): mass calcd for (C16H17NO+Na) m/z 262.1208; measured [M+Na]+: m/z 262.1204.
Reaction SMILES: [S-:1][C:2]#[N:3].[K+].Cl[CH2:6][CH2:7][CH2:8][Si:9]([O:20][CH2:21][CH2:22][CH2:23][CH3:24])([O:15][CH2:16][CH2:17][CH2:18][CH3:19])[O:10][CH2:11][CH2:12][CH2:13][CH3:14].[Cl-].[K+]>C(O)CCC>[S:1]([CH2:6][CH2:7][CH2:8][Si:9]([O:20][CH2:21][CH2:22][CH2:23][CH3:24])([O:10][CH2:11][CH2:12][CH2:13][CH3:14])[O:15][CH2:16][CH2:17][CH2:18][CH3:19])[C:2]#[N:3]
Reactant: CCCCO[Si](CCCCl)(OCCCC)OCCCC
Reactant: N#C[S-]
Agent: [Cl-]
Agent: [K+]
Solvent: CCCCO
Product: CCCCO[Si](CCCSC#N)(OCCCC)OCCCC
Reaction time: 20 h
Yield: 85 %

Procedure:
24.3 grams of potassium thiocyanate were dissolved in 900 ml. of n-butanol and the solution heated to boiling. Then there were added dropwise in about 30 minutes 81.3 grams of 3-chloropropyl tri-n-butoxy silane. After a further 20 hours of boiling at reflux temperature the precipitated potassium chloride was separated off with a Seitz filter. The solvent was distilled off from the filtrate and the 3-thiocyanatopropyl tri-n-butoxy silane distilled in vacuo. B.P. 0.1 128°-129° C., yield 85% based on the weight of the 3-chloropropyl tri-n-butoxy silane.
Reaction SMILES: Cl.[CH3:2][O:3][C:4](=[O:7])[CH2:5][NH2:6].CO.[C:10]1([CH2:16][CH:17]=O)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C>[CH2:17]([NH:6][CH2:5][C:4]([O:3][CH3:2])=[O:7])[CH2:16][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: O=CCc1ccccc1
Reactant: COC(=O)CN
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: COC(=O)CNCCc1ccccc1
Temperature: 0 °C
Yield: 33.4 %

Procedure:
A cold solution (0° C.) of glycine methyl ester hydrochloride (1.0 g, 8 mmol), methanol (25 mL), glacial acetic acid (0.8 mmol, and phenylacetaldehyde (0.481 g, 4 mmol) was treated with sodium triacetoxyborohydride (1.7 g, 8 mmol) in two portions. The reaction mixture was maintained at 0° C. for 1.5 hr, and then quenched with saturated sodium bicarbonate (15 mL). The solution was extracted with ethyl acetate. The organic phase was collected, dried over anhydrous sodium sulfate, and adsorbed onto silica gel (100 mg) and applied to a column prepacked with silica gel. The column was eluted with CH2Cl2 /MeOH (97:3, v:v) to afford titled compound (258 mg).
Reaction SMILES: [CH:1]([O:14][CH2:15][CH2:16][N:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:23][O:24][C:25]1[CH:26]=[C:27]([CH:40]=[CH:41][CH:42]=[CH:43][C:44](N2CCSC2)=[O:45])[CH:28]=[C:29]([O:38][CH3:39])[C:30]=1[O:31][CH2:32][O:33][CH2:34][CH2:35][O:36][CH3:37]>CN(C)C=O>[CH3:39][O:38][C:29]1[CH:28]=[C:27]([CH:40]=[CH:41][CH:42]=[CH:43][C:44]([N:20]2[CH2:19][CH2:18][N:17]([CH2:16][CH2:15][O:14][CH:1]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[CH2:22][CH2:21]2)=[O:45])[CH:26]=[C:25]([O:24][CH3:23])[C:30]=1[O:31][CH2:32][O:33][CH2:34][CH2:35][O:36][CH3:37]
Reactant: COCCOCOc1c(OC)cc(C=CC=CC(=O)N2CCSC2)cc1OC
Reactant: c1ccc(C(OCCN2CCNCC2)c2ccccc2)cc1
Solvent: CN(C)C=O
Product: COCCOCOc1c(OC)cc(C=CC=CC(=O)N2CCN(CCOC(c3ccccc3)c3ccccc3)CC2)cc1OC
Yield: 25.7 %

Procedure:
To a solution of 794 mg (2.68 mmol) of N-(2-benzhydroxyethyl)piperazine in dry dimethylformamide (4 ml) was added, under argon atmosphere, a solution of 1.15 g (2.61 mmol) of N[5-[3,5-dimethoxy-4-(β-methoxyethoxymethoxy)phenyl]-2,4-pentadienoyl)thiazolidine in dry dimethylformamide (4 ml), and the mixture was allowed to react at room temperature for 17 hours. At the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure and the residue was subjected to silica gel column chromatography, eluted with chloroform-methanol (100:1), to give 413 mg (0.670 mmol) of N-[5-[3,5-dimethoxy-4-(β-methoxyethoxymethoxy)phenyl]-2,4-pentadienoyl]-N'-(2-benzhydroxyethyl)piperazine.
Reaction SMILES: [C:1]([NH:5][CH2:6][C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]=1[C:17]1[N:22]=[C:21]([CH:23]=O)[CH:20]=[CH:19][CH:18]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:25][C:26]1[CH:32]=[C:31]([CH3:33])[CH:30]=[C:29]([CH3:34])[C:27]=1[NH2:28]>C(O)C>[C:1]([NH:5][CH2:6][C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]=1[C:17]1[N:22]=[C:21]([CH:23]=[N:28][C:27]2[C:29]([CH3:34])=[CH:30][C:31]([CH3:33])=[CH:32][C:26]=2[CH3:25])[CH:20]=[CH:19][CH:18]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: Cc1cc(C)c(N)c(C)c1
Reactant: CC(C)(C)NCc1ccc2ccccc2c1-c1cccc(C=O)n1
Solvent: CCO
Product: Cc1cc(C)c(N=Cc2cccc(-c3c(CNC(C)(C)C)ccc4ccccc34)n2)c(C)c1

Procedure:
A mixture of 4.80 g (15.0 mmol) of 6-{2-[(tert-butylamino)methyl]-1-naphthyl}pyridine-2-carbaldehyde and 2.00 g (15.0 mmol) of 2,4,6-trimethylaniline in 50 ml of dry ethanol was refluxed overnight. The resulting mixture was evaporated to dryness. The product was isolated by flash chromatography on silica gel 60 (40-63 um; eluent: dichloromethane-methanol-triethylamine=100:10:1, vol.). Yield 5.80 g (88%) of orange oil. Anal. calc. for C30H33N3: C, 82.72; H, 7.64; N, 9.65. Found: C, 82.89; H, 7.73; N, 9.54. 1H NMR (CDCl3): 8.40-8.42 (m, 2H, CH═N and 3-H in Py), 7.99 (m, 1H, 4-H in Py), 7.91 (d, J=8.4 Hz, 1H, 4-H in naphthyl), 7.87 (m, 1H, 8-H in naphthyl), 7.66 (d, J=8.4 Hz, 1H, 3-H in naphthyl), 7.55 (m, 1H, 5-H in Py), 7.36-7.47 (m, 3H, 5,6,7-H in naphthyl), 6.90 (s, 2H, 3,5-H in mesityl), 3.60 (d, J=10.9 Hz, 1H, CHH′N), 3.53 (d, J=10.9 Hz, CHH′N), 3.40 (s, 1H, NH), 2.29 (s, 3H, 4-Me in mesityl), 2.17 (s, 6H, 2,6-Me in mesityl), 0.96 (s, 9H, tBu).
Reaction SMILES: [CH2:1]([N:5]([S:15]([C:18]1[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=1)(=[O:17])=[O:16])[C@H:6]([C:12]([OH:14])=[O:13])[CH2:7][CH2:8][CH2:9][CH2:10][NH2:11])[CH:2]([CH3:4])[CH3:3].[C:25]([O:29][C:30]([N:32]([CH3:44])[C@H:33]([C:41](O)=[O:42])[CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:31])([CH3:28])([CH3:27])[CH3:26]>>[CH3:24][C:21]1[CH:22]=[CH:23][C:18]([S:15]([N:5]([C@H:6]([C:12]([OH:14])=[O:13])[CH2:7][CH2:8][CH2:9][CH2:10][NH:11][C:41]([C@@H:33]([N:32]([C:30]([O:29][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:31])[CH3:44])[CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[O:42])[CH2:1][CH:2]([CH3:3])[CH3:4])(=[O:17])=[O:16])=[CH:19][CH:20]=1
Reactant: Cc1ccc(S(=O)(=O)N(CC(C)C)[C@@H](CCCCN)C(=O)O)cc1
Reactant: CN(C(=O)OC(C)(C)C)[C@@H](Cc1ccccc1)C(=O)O
Product: Cc1ccc(S(=O)(=O)N(CC(C)C)[C@@H](CCCCNC(=O)[C@H](Cc2ccccc2)N(C)C(=O)OC(C)(C)C)C(=O)O)cc1

Procedure:
The title compound was prepared from Nα-isobutyl-Nα-(4-methylbenzenesulfonyl)-L-lysine (100 mg, 0.29 mmol, example 1, step E) as described in general procedure Bc using commercially available Nα-tert-butoxycarbonyl-Nα-methyl-L-phenylalanine (83 mg, 0.3 mmol). The final product was triturated with ether to yield 176 mg (90%) of the desired material.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([CH3:11])[C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:7]2.[H-].[Na+].Cl[CH2:19][C:20]([NH2:22])=[O:21]>CN(C)C=O>[C:20]([CH2:19][O:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([CH3:11])[C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:7]2)(=[O:21])[NH2:22]
Reactant: COC(=O)c1cc2cccc(O)c2n1C
Reactant: NC(=O)CCl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)c1cc2cccc(OCC(N)=O)c2n1C
Temperature: 25 °C
Yield: 84.4 %

Procedure:
After 0.50 g (2.44 mmol) of methyl 7-hydroxy-1-methyl-2-indolecarboxylate was added to a suspension of 0.01 g (2.44 mmol) of 60% sodium hydride in 25 ml of dimethyl-formamide, the mixture was stirred at room temperature until the mixture became a transparent solution. Then 0.25 g (2.68 mmols) of 2-chloroacetamide was added dropwise to the transparent solution at room temperature followed by stirring at 50° C. for an hour. The reaction mixture was poured onto ice water. The resulting mixture was then extracted three times with ethyl acetate. The combined extracts were washed with water. After drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography to give 0.54 g (84.4%) of methyl 7-carbamoylmethoxy-1-methyl-2-indolecarboxylate.