Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]>C1(C)C=CC=CC=1>[CH2:1]=[CH:2][CH3:3].[CH2:1]=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: CCCCCCCCCC
Solvent: Cc1ccccc1
Product: C=CC
Product: C=CCCCCCCCC
Temperature: 55 °C
Reaction time: 1.5 h
Yield: 1942.7 %

Procedure:
A 1000 ml autoclave was charged with 6.0 mg of lnd2ZrCl2, 100 ml of toluene and 2.45 ml of a solution of MAO in toluene (d=0.860 g/ml, 5.9 wt. % Al, Al/Zr ratio of about 300), and 3.88 g of anhydrous decane (internal standard). The autoclave was sealed and removed from the dry box. The reactor was warmed to 55° C. and charged with 22.2 g of dry 1-decene, and then 100 g of dry polymer grade propylene at 136 psi. Stirring at 55° C. was continued for 1.5 hours. Work-up as described above gave 48.3 g of a propylene/1-decene copolymer containing approximately 21.5% 1-decene based on GC analysis of the crude reaction mixture. This clear, viscous copolymer was determined to have a Mn of 1,704 and a DI of 1.67. Using Proton NMR, a terminal vinylidine content of better than 80% was calculated for this product.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)[C:12]2[S:16]N=[CH:14][N:13]=2)(=[O:10])=[O:9])=[CH:4][C:3]=1[O:26][CH2:27][C:28](=[O:35])[C:29]1C=CC=CC=1.Cl[CH2:37]C(=O)C>>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH2:17][C:18]2[CH:19]=[CH:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=2)[C:12]2[S:16][CH:37]=[CH:14][N:13]=2)(=[O:10])=[O:9])=[CH:4][C:3]=1[O:26][CH2:27][C:28](=[O:35])[CH3:29]
Reactant: CC(=O)CCl
Reactant: COc1ccc(CN(c2ncns2)S(=O)(=O)c2ccc(N)c(OCC(=O)c3ccccc3)c2)cc1
Product: COc1ccc(CN(c2nccs2)S(=O)(=O)c2ccc(N)c(OCC(C)=O)c2)cc1

Procedure:
4-Amino-N-(4-methoxybenzyl)-3-(2-oxopropoxy)-1N-(thiazol-2-yl)benzenesulfonamide was prepared from INTERMEDIATE AD in the same manner as described for INTERMEDIATE Q, using 1-chloropropan-2-one instead of 2-bromo-1-phenylethanone.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]2[C:13]3[N:14]([C:18]([C:21]#[C:22][Si](C)(C)C)=[CH:19][N:20]=3)[CH:15]=[CH:16][CH:17]=2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.CO.C(Cl)Cl>C1COCC1>[C:21]([C:18]1[N:14]2[CH:15]=[CH:16][CH:17]=[C:12]([NH:11][C:8]3[CH:9]=[CH:10][C:5]([S:2]([CH3:1])(=[O:4])=[O:3])=[CH:6][CH:7]=3)[C:13]2=[N:20][CH:19]=1)#[CH:22]
Reactant: C[Si](C)(C)C#Cc1cnc2c(Nc3ccc(S(C)(=O)=O)cc3)cccn12
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: CO
Solvent: C1CCOC1
Solvent: ClCCl
Product: C#Cc1cnc2c(Nc3ccc(S(C)(=O)=O)cc3)cccn12
Reaction time: 0.25 h
Yield: 100.6 %

Procedure:
To a solution of N-(4-(methylsulfonyl)phenyl)-3-((trimethylsilyl)ethynyl)imidazo[1,2-a]pyridin-8-amine (0.058 g, 0.15 mmol) in 1.5 mL of THF was added 0.23 mL (0.23 mmol) of tetrabutylammonium fluoride (1.0M in THF) at ambient temperature. The solution was stirred for 15 min, concentrated, and the crude product purified by silica gel flash chromatography (triethylamine-treated silica gel; eluted with 100% DCM then 5% MeOH/DCM) to provide a quantitative yield (0.047 g) of product: 312 m/z (M+H).
Reaction SMILES: [C:1]([CH2:3][C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5])#[N:2].[Cl:11][C:12]1[CH:13]=[C:14]([CH:17]=[CH:18][C:19]=1[Cl:20])[CH:15]=O.N1CCCCC1>CCO>[C:1](/[C:3](=[CH:15]\[C:14]1[CH:17]=[CH:18][C:19]([Cl:20])=[C:12]([Cl:11])[CH:13]=1)/[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5])#[N:2]
Reactant: CC(C)(C)OC(=O)CC#N
Reactant: O=Cc1ccc(Cl)c(Cl)c1
Solvent: CCO
Solvent: C1CCNCC1
Product: CC(C)(C)OC(=O)/C(C#N)=C/c1ccc(Cl)c(Cl)c1
Temperature: 80 °C
Reaction time: 15 h
Yield: 81.7 %

Procedure:
A solution of tert-butyl cyanoacetate (2.52 ml, 17.63 mmol), 3,4-dichlorobenzaldehyde (2.57 g, 14.69 mmol) and piperidine (0.145 ml, 1.469 mmol) in EtOH (50 ml) was allowed to stir at 80° C. for 15 hours, and then cooled to ambient temperature. A half volume of the solvent was evaporated, and 400 ml of water was added to the resulting mixture. The precipitated solid was collected and washed with 5% iPrOH/H2O (200 ml). The solid was dried under reduced pressure to give (E)-tert-butyl 2-cyano-3-(3,4-dichlorophenyl)acrylate (3.577 g); Retention time=1.61 minutes (condition A); MS (ES+)=315.1 (m+18).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:3][CH2:2]1.[Cl:15][C:16]1[CH:17]=[C:18]([CH:23]=[C:24](Cl)[N:25]=1)[C:19]([O:21][CH3:22])=[O:20].O.[Na+].[Cl-]>CN1C(=O)CCC1.CCOC(C)=O>[C:10]([O:9][C:8]([NH:7][CH:4]1[CH2:3][CH2:2][N:1]([C:24]2[CH:23]=[C:18]([CH:17]=[C:16]([Cl:15])[N:25]=2)[C:19]([O:21][CH3:22])=[O:20])[CH2:6][CH2:5]1)=[O:14])([CH3:11])([CH3:13])[CH3:12]
Reactant: COC(=O)c1cc(Cl)nc(Cl)c1
Reactant: CC(C)(C)OC(=O)NC1CCNCC1
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CN1CCCC1=O
Product: COC(=O)c1cc(Cl)nc(N2CCC(NC(=O)OC(C)(C)C)CC2)c1
Temperature: 150 °C

Procedure:
tert-Butyl piperidin-4-ylcarbamate (972 mg, 4.85 mmol), was dissolved in anhydrous NMP (5 ml). Methyl 2,6-dichloroisonicotinate (Intermediate 24, 1 g, 4.85 mmol) was added followed by TEA (675 μl, 4.85 mmol). The mixture was heated under microwave conditions at 150° C. for 10 minutes. Water (50 ml) and EtOAc (100 ml) were added, the aqueous phase was treated with solid NaCl and extracted with EtOAc (4×100 ml). The EtOAc layer was dried, concentrated in vacuo and purified by flash chromatography eluting with hexane:EtOAc (4:1) to give the title product as an off-white solid. (1.4 g).
Reaction SMILES: CCN(C(C)C)C(C)C.[N:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[N:16]1[CH:20]=[C:19]([C:21]([OH:23])=O)[N:18]=[N:17]1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[NH2:46][CH2:47][C:48]([N:50]1[CH2:55][CH2:54][N:53]([C:56](=[O:68])[C:57]2[CH:62]=[C:61]([F:63])[CH:60]=[CH:59][C:58]=2[C:64]([F:67])([F:66])[F:65])[CH2:52][CH2:51]1)=[O:49]>CN(C=O)C.O>[F:63][C:61]1[CH:60]=[CH:59][C:58]([C:64]([F:66])([F:65])[F:67])=[C:57]([CH:62]=1)[C:56]([N:53]1[CH2:54][CH2:55][N:50]([C:48](=[O:49])[CH2:47][NH:46][C:21]([C:19]2[N:18]=[N:17][N:16]([C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][N:10]=3)[CH:20]=2)=[O:23])[CH2:51][CH2:52]1)=[O:68]
Reactant: O=C(O)c1cn(-c2ccccn2)nn1
Reactant: NCC(=O)N1CCN(C(=O)c2cc(F)ccc2C(F)(F)F)CC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: O=C(NCC(=O)N1CCN(C(=O)c2cc(F)ccc2C(F)(F)F)CC1)c1cn(-c2ccccn2)nn1
Temperature: 25 °C
Reaction time: 0.03 h
Yield: 83.1 %

Procedure:
DIPEA (166 mg, 0.23 mL, 1.28 mmol) was added to a stirred solution of 1-Pyridin-2-yl-1H-[1,2,3]triazole-4-carboxylic acid (61 mg, 0.25 mmol)(prepared by the method as described above) in DMF (4 mL). HOBT (38 mg, 0.28 mmol) and EDCI (123 mg, 0.64 mmol) were then added at room temperature. After 2 minutes, 2-amino-1-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone hydrochloride salt (104 mg, 0.28 mmol) was added and the resulting mixture was stirred at room temperature overnight. Cold water was then added and filtered the solid precipitated out to afford 105 mg (80.7% yield) of 1-pyridin-2-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amide. LCMS Purity: 95.70%. 1H NMR (DMSO-d6): δ 9.2 (s, 1H), 8.7 (m, 2H), 8.22 (d, 2H), 8.0 (t, 1H), 7.66-7.5 (m, 3H), 4.3-4.16 (dd, 2H), 3.84 (bs, 1H), 3.66-3.4 (m, 5H), 3.26 (d, 2H).
Reaction SMILES: [CH:1]1C=CC=CC=1.C[CH:8]([OH:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C1(CCO)C=CC=CC=1>C1(C)C=CC=CC=1>[C:14]1([CH3:1])[C:9]([CH:8]=[O:15])=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: CC(O)c1ccccc1
Reactant: c1ccccc1
Solvent: OCCc1ccccc1
Solvent: Cc1ccccc1
Product: Cc1ccccc1C=O
Yield: 385 %

Procedure:
The experimental procedure was substantially the same as in Example excepting replacement of the benzene as the starting hydrocarbon compound with the same volume of toluene. The reaction mixture after completion of the reaction contained position isomers of methylbenzyl alcohol in a total molar yield of 6332% based on the amount of the rhodium complex used as the catalyst including o-, m- and p-methylbenzyl alcohols in a proportion of 3:60:37. 2-phenylethyl alcohol was not detected in the reaction mixture. Tolualdehyde was produced in a molar yield of 385% as a total value for the o-, m and p-isomers relative to the rhodium complex used as the catalyst.
Reaction SMILES: [CH3:1][N:2]1[CH2:19][CH2:18][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([O:13][C:14]([F:17])([F:16])[F:15])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.[H-].[Na+].[O:22]1[CH2:24][CH:23]1[C:25]1[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=1>CN(C=O)C>[CH3:1][N:2]1[CH2:19][CH2:18][C:5]2[N:6]([CH2:24][CH:23]([C:25]3[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=3)[OH:22])[C:7]3[CH:8]=[CH:9][C:10]([O:13][C:14]([F:17])([F:15])[F:16])=[CH:11][C:12]=3[C:4]=2[CH2:3]1
Reactant: CN1CCc2[nH]c3ccc(OC(F)(F)F)cc3c2C1
Reactant: c1cc(C2CO2)ccn1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CN1CCc2c(c3cc(OC(F)(F)F)ccc3n2CC(O)c2ccncc2)C1
Reaction time: 0.17 h

Procedure:
To a solution of 2-methyl-8-trifluoromethoxy-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (1.0 g, 3.70 mmol) in DMF (10 mL) was added sodium hydride (445 mg, 11.12 mmol) under nitrogen at 0° C. After stirring for 10 min, 4-(oxiran-2-yl)pyridine (806 g, 6.66 mmol) was added dropwise under nitrogen and the reaction mixture was stirred at RT for 12 h. The progress of reaction was monitored by TLC and LCMS. The reaction mixture was poured into ice-cold water and extracted with EtOAc (2×100 mL). The combined organic layer was washed with water (5×50 mL) and dried over anhydrous sodium sulfate, concentrated and re-crystallized in diethyl ether to yield 2-(2-methyl-8-trifluoromethoxy-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-1-pyridin-4-yl-ethanol. 1H NMR (CDCl3, freebase) δ (ppm): 8.58 (d, 2H), 7.17-7.21 (m, 4H), 7.0 (d, 1H), 4.6 (m, 1H), 4.0 (m, 2H), 3.38 (dd, 2H), 2.8 (m, 1H), 2.7 (m, 2H), 2.6 (m, 1H), 2.18 (s, 3H). Separation by chiral HPLC provides enantiomers II-67a-b.
Reaction SMILES: [CH2:1]([C:3]1([CH2:7][O:8][C:9](=[O:22])/[CH:10]=[CH:11]/[C:12]([O:14][CH2:15][C:16]2([CH2:20][CH3:21])[CH2:19][O:18][CH2:17]2)=[O:13])[CH2:6][O:5][CH2:4]1)[CH3:2].[SH:23][CH2:24][CH2:25][CH2:26][Si:27]([O:34][CH2:35][CH3:36])([O:31][CH2:32][CH3:33])[O:28][CH2:29][CH3:30]>C1(C)C=CC=CC=1.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>[CH2:20]([C:16]1([CH2:15][O:14][C:12](=[O:13])[CH:11]([S:23][CH2:24][CH2:25][CH2:26][Si:27]([O:34][CH2:35][CH3:36])([O:28][CH2:29][CH3:30])[O:31][CH2:32][CH3:33])[CH2:10][C:9]([O:8][CH2:7][C:3]2([CH2:1][CH3:2])[CH2:6][O:5][CH2:4]2)=[O:22])[CH2:17][O:18][CH2:19]1)[CH3:21]
Reactant: CCO[Si](CCCS)(OCC)OCC
Reactant: CCC1(COC(=O)/C=C/C(=O)OCC2(CC)COC2)COC1
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: Cc1ccccc1
Product: CCO[Si](CCCSC(CC(=O)OCC1(CC)COC1)C(=O)OCC1(CC)COC1)(OCC)OCC
Yield: 68.8 %

Procedure:
8.4 g (26.9 mmol) of fumaric acid-bis-[(3-ethyloxetan-3-yl)methyl]ester, 5.3 g (26.9 mmol) of 3-mercaptopropyltriethoxysilane and 0.33 g (1.3 mmol) of dibenzoyl peroxide were stirred for 5 hours in 20 ml of toluene at 100° C. When the solvent was distilled off, a white deposit precipitated which produced 10.2 g (70% yield) of (10) after filtering off and drying.
Reaction SMILES: [C:1]([N:4]1[C:12]2[C:7](=[C:8]([CH3:14])[CH:9]=[C:10]([CH3:13])[CH:11]=2)[CH:6]([CH2:15][CH2:16][O:17][C:18](=[O:20])[CH3:19])[CH2:5]1)(=[O:3])[CH3:2].[Br:21]Br.[N+:23]([O-:26])(O)=[O:24].Cl>CC(O)=O>[C:1]([N:4]1[C:12]2[C:7](=[C:8]([CH3:14])[C:9]([Br:21])=[C:10]([CH3:13])[C:11]=2[N+:23]([O-:26])=[O:24])[CH:6]([CH2:15][CH2:16][O:17][C:18](=[O:20])[CH3:19])[CH2:5]1)(=[O:3])[CH3:2]
Reactant: CC(=O)OCCC1CN(C(C)=O)c2cc(C)cc(C)c21
Reactant: BrBr
Reactant: O=[N+]([O-])O
Agent: Cl
Solvent: CC(=O)O
Product: CC(=O)OCCC1CN(C(C)=O)c2c1c(C)c(Br)c(C)c2[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
1-Acetyl-3-(2-acetoxyethyl)-4,6-dimethylindoline (2.0 g) was dissolved in AcOH (40 ml) and Br2 (1.9 g) was added, which was followed by stirring at room temperature for 30 min. The reaction mixture was poured into ice water and precipitate was collected by filtration. The precipitate was dissolved in CHCl3, and the mixture was washed with water and dried over anhydrous sodium sulfate. CHCl3 was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: CHCl3 /MeOH=50/1-10/1) to give 2.7 g of crude crystals of 1-acetyl-3-(2-acetoxyethyl)-5-bromo-4,6-dimethylindoline. The crude crystals were added by portions to a mixture of nitric acid (0.47 ml), AcOH (10 ml) and conc. hydrochloric acid (10 ml) under ice-cooling, and the mixture was stirred at the same temperature for 4 hr. The reaction mixture was poured into ice water and precipitate was collected by filtration. The precipitate was dissolved in CHCl3. After washing with water, the mixture was dried over anhydrous sodium sulfate and CHCl3 was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: CHCl3 /MeOH=50/1-10/1) to give 1.4 g of 1-acetyl-3-(2-acetoxyethyl)-5-bromo-4,6-dimethyl-7-nitroindoline.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([C:20]([OH:22])=[O:21])[CH2:10][C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[NH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[Cl:30][CH2:31]I>CN(C)C=O>[Cl:30][CH2:31][O:21][C:20](=[O:22])[C@H:9]([CH2:10][C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[NH:13][CH:12]=1)[NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7]
Reactant: ClCI
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)O
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)OCCl

Procedure:
The compound was prepared by the method of Example 7A from N-tert.butoxycarbonyl-tryptophan, triethylamine, and chloroiodomethane in dimethylformamide; reaction time 4 hours. M.p. 155°-157°C.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([C:10]2[CH2:11][CH2:12][N:13](C(OC(C)(C)C)=O)[CH2:14][CH:15]=2)[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].Cl>O1CCOCC1>[N+:1]([C:4]1[CH:5]=[C:6]([C:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH:11]=2)[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2]
Reactant: CC(C)(C)OC(=O)N1CC=C(c2cccc([N+](=O)[O-])c2)CC1
Agent: Cl
Solvent: C1COCCO1
Product: O=[N+]([O-])c1cccc(C2=CCNCC2)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 87.2 %

Procedure:
Into a stirred solution of 5.00 g (16.0 mmol) of tert-butyl 1,2,3,6-tetrahydro-4-(3-nitrophenyl)pyridine-1-carboxylate in 100 ml of 1,4-dioxane at 0° C. was bubbled HCl gas for 10 minutes. The reaction mixture was allowed to warm to room temperature and the bubbling of the HCl gas was continued for an additional 1 hour. The solvent was removed in vacuo, the residue was dissolved in 50 mL of water and was neutralized by the addition of KOH pellets. The aqueous solution was extracted with 3×80 mL of dichloromethane and the combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (silica, 9:1, dichloromethane methanol+1% isopropyl amine) to afford 2.85 g (87.5% yield) of the desired product: 1H NMR (400 MHz, CDCl3) δ 8.24 (s, 1H), 8.09 (d, 1H, J=8.4 Hz), 7.71 (d, 1H, J=8.0 Hz), 7.49 (t, 1H, J=8.0 Hz), 6.35-6.25 (m, 1H), 3.58 (apparent q, 2H, J=3.0 Hz), 3.14 (t, 2H, J=5.6 Hz), 2.54-2.46 (m, 2H)
Reaction SMILES: Cl[C:2]([O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:3].[Br:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][NH:21][CH3:22])=[CH:15][CH:14]=1.C(N(CC)CC)C>C(Cl)Cl>[Br:12][C:13]1[CH:14]=[CH:15][C:16]([CH2:19][CH2:20][N:21]([CH3:22])[C:2](=[O:3])[O:4][CH2:5][C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)=[CH:17][CH:18]=1
Reactant: CNCCc1ccc(Br)cc1
Reactant: O=C(Cl)OCc1ccccc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CN(CCc1ccc(Br)cc1)C(=O)OCc1ccccc1
Yield: 64.8 %

Procedure:
Benzyl chloroformate (0.97 mL, 6.7 mmol) was added dropwise to a solution of 23B (1.1 g, 5.1 mmol)in CH2Cl2 (26 mL) and triethylamine (1 mL, 7.5 mmol). The reaction mixture washed with brine, dried over Na2SO4 and concentrated in vacuo. Purification by flash chromatography (0% to 50% EtOAc in hexanes) afforded 28C (1.15 g, 65%) as a clear oil. 1H NMR (400 MHz, CDCl3) δ ppm 2.70-2.94 (m, 5 H) 3.47 (m, 2 H) 5.08 (m, 2 H) 6.90-7.12 (m, 2 H) 7.26-7.44 (m, 7 H).
Reaction SMILES: [CH:1]1([C:7]2[CH:8]=[CH:9][C:10]3[O:14][C:13](B(O)O)=[CH:12][C:11]=3[CH:18]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Br[C:20]1[CH:27]=[CH:26][C:23]([CH:24]=[O:25])=[CH:22][CH:21]=1.C(N(CC)CC)C>C(O)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[CH:1]1([C:7]2[CH:8]=[CH:9][C:10]3[O:14][C:13]([C:20]4[CH:27]=[CH:26][C:23]([CH:24]=[O:25])=[CH:22][CH:21]=4)=[CH:12][C:11]=3[CH:18]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: OB(O)c1cc2cc(C3CCCCC3)ccc2o1
Reactant: O=Cc1ccc(Br)cc1
Agent: Cl[Pd]Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: CCO
Product: O=Cc1ccc(-c2cc3cc(C4CCCCC4)ccc3o2)cc1
Yield: 50.2 %

Procedure:
A mixture of 5-cyclohexylbenzofuran-2-ylboronic acid (75 mg, 0.37 mmol), 4-bromobenzaldehyde (62 mg, 0.34 mmol), triethylamine (1.1 mL, 7.5 mmol) and bis(triphenylphosphine)palladium(II)chloride (13 mg, 0.05 mmol) in ethanol (11 mL) was irradiated in a microwave instrument at 100° C. for 20 min. The reaction mixture was cooled, and the solvent was removed. The residue was purification by silica gel chromatography on ISCO system gave the title compound (52 mg, 46% yield): >95% purity by LCMS, ESI-MS: 305.2 M+H+). 1H NMR (400 MHz, CDCl3) δ 10.03 (s, 1H), 8.00 (d, 2H), 7.95 (d, 2H), 7.46 (d, 2H), 7.19 (d, 1H), 7.16 (s, 1H), 2.63-2.58 (m, 1H), 1.94-1.76 (m, 4H), 1.53-1.42 (m, 4H), 1.38-1.25 (m, 2H). MS (ESI) m/z: Calculated: 304.38; Observed: 305.2 (M++1).
Reaction SMILES: [C:1]([N:4]1[CH2:9][C:8](=[O:10])[N:7]([C:11](=[O:20])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[CH2:6][C:5]1=[O:21])(=[O:3])[CH3:2].[C:22](Cl)(=O)[CH2:23]CCCCCCCC=C>>[C:1]([N:4]1[CH2:9][C:8](=[O:10])[N:7]([C:11](=[O:20])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH:22]=[CH2:23])[CH2:6][C:5]1=[O:21])(=[O:3])[CH3:2]
Reactant: CCCCCCCCC(=O)N1CC(=O)N(C(C)=O)CC1=O
Reactant: C=CCCCCCCCCC(=O)Cl
Product: C=CCCCCCCCCC(=O)N1CC(=O)N(C(C)=O)CC1=O

Procedure:
##STR27## Synthesized as for 1-Acetyl4-nonanoyl-2,5-piperazinedione in EXAMPLE I using 10-undecenoyl chloride in place of nonanoyl chloride.
Reaction SMILES: [H-].[Na+].[F:3][C:4]1[C:9]([F:10])=[CH:8][CH:7]=[CH:6][C:5]=1[C@H:11]1[CH2:17][NH:16][C:15](=[O:18])[C@H:14]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH2:13][CH2:12]1.I[CH2:28][CH2:29][S:30][CH3:31]>CN(C)C=O>[F:3][C:4]1[C:9]([F:10])=[CH:8][CH:7]=[CH:6][C:5]=1[C@H:11]1[CH2:17][N:16]([CH2:28][CH2:29][S:30][CH3:31])[C:15](=[O:18])[C@H:14]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:23])([CH3:25])[CH3:24])[CH2:13][CH2:12]1
Reactant: CC(C)(C)OC(=O)N[C@@H]1CC[C@@H](c2cccc(F)c2F)CNC1=O
Reactant: CSCCI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CSCCN1C[C@H](c2cccc(F)c2F)CC[C@@H](NC(=O)OC(C)(C)C)C1=O
Temperature: -30 °C
Reaction time: 3 h
Yield: 37.2 %

Procedure:
Sodium hydride (60% dispersion in mineral oil; 40 mg, 0.600 mmol) was added to a solution of tert-butyl (3R,6S)-6-(2,3-difluorophenyl)-2-oxoazepan-3-ylcarbamate (170 mg, 0.500 mmol) in N,N-dimethylformamide (4 mL) at 0° C. After 5 min the mixture was cooled to −30° C. and 1-iodo-2-(methylthio)ethane [prepared according to known procedures: J. Org. Chem., 1987, 52, 2299-2301 (158 mg, 0.782 mmol)] was added. Additional sodium hydride (33 mg, 0.50 mmol) was added and after 4 h excess sodium hydride (33 mg, 0.50 mmol) and 1-iodo-2-(methylthio)ethane (75.6 mg, 0.374 mmol) were added. After 3 h, the final portions of sodium hydride (33 mg, 0.50 mmol) and 1-iodo-2-(methylthio)ethane (75.6 mg, 0.374 mmol) were added and the mixture stirred at −20° C. overnight. The reaction was quenched with water and the mixture was extracted with ethyl acetate. The organic layer was washed with water (3×), saturated brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (0% ethyl acetate/hexanes→50% ethyl acetate/hexanes) gave the title compound (77 mg). MS 415 (M+1).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]3[N:12]([CH3:16])[CH:13]=[N:14][CH:15]=3)[S:10][C:3]=12.[NH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[CH3:16][N:12]1[C:11]([C:9]2[S:10][C:3]3[C:4](=[N:5][CH:6]=[CH:7][C:2]=3[NH:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH:8]=2)=[CH:15][N:14]=[CH:13]1
Reactant: Nc1ccccc1
Reactant: Cn1cncc1-c1cc2nccc(Cl)c2s1
Product: Cn1cncc1-c1cc2nccc(Nc3ccccc3)c2s1

Procedure:
The title compound was prepared from 7-Chloro-2-(3-methyl-3H-imidazol-4-yl)-thieno[3,2-b]pyridine and aniline by the procedure analogous to example 148(c) above. 1H NMR (400 MHz, CD3OD) δ8.18 (d, 1H), 7.77 (s, 1H), 7.39 (s, 1H), 7.37 (m, 3H), 7.28 (m, 2H), 7.18 (t, 1H), 6.80 (d, 1H), 3.86 (s, 3H); RP18-HPLC RT: 3.93 minutes; API MS: 307 (M+1).
Reaction SMILES: Cl[C:2]1[CH:11]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[NH2:18][C:19]1[CH:24]=[CH:23][C:22]([SH:25])=[CH:21][CH:20]=1.C1COCC1>CN(C1C=CN=CC=1)C.C(O)C>[NH2:18][C:19]1[CH:24]=[CH:23][C:22]([S:25][C:2]2[CH:11]=[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[N:3]=2)=[CH:21][CH:20]=1
Reactant: Clc1cc(-c2ccccc2)c2ccccc2n1
Reactant: Nc1ccc(S)cc1
Agent: CN(C)c1ccncc1
Solvent: CCO
Solvent: C1CCOC1
Product: Nc1ccc(Sc2cc(-c3ccccc3)c3ccccc3n2)cc1
Yield: 451.6 %

Procedure:
2-Chloro-4-phenylquinoline (4.18 mmoles, 10.0 g), 4-aminothiophenol (41.8 mmoles, 5.2 g) and DMAP (41.8 mmoles, 5.0 g) were stirred in 200 ml ethanol and 50 ml THF for 3 days. The solution was concentrated, ethyl acetate added, washed with water, dried over sodium sulfate and the solvent removed. The product was purified by HPLC over silica gel eluted with 30% ethyl acetate in hexane to yield 2-(4-aminophenylthio)-4-phenylquinoline 6.2 g, 45%. Mass Spec (FD) 328. Calculated for C21H16N2S: C, 76.80; H, 4.91 N, 8.53. Found: C, 77.04; H, 5.00; N, 8.55.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=3[Cl:20])[N:11]=[C:10]([C:21](=O)[CH2:22][C:23](=O)[C:24]([CH3:27])([CH3:26])[CH3:25])[C:9]=2[CH3:30])=[CH:4][CH:3]=1.O.[NH2:32][NH2:33].C1COCC1>CCO>[C:24]([C:23]1[NH:33][N:32]=[C:21]([C:10]2[C:9]([CH3:30])=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)[N:12]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=3[Cl:20])[N:11]=2)[CH:22]=1)([CH3:27])([CH3:26])[CH3:25]
Reactant: Cc1c(C(=O)CC(=O)C(C)(C)C)nn(-c2ccc(Cl)cc2Cl)c1-c1ccc(Cl)cc1
Reactant: NN
Solvent: O
Solvent: C1CCOC1
Solvent: CCO
Product: Cc1c(-c2cc(C(C)(C)C)[nH]n2)nn(-c2ccc(Cl)cc2Cl)c1-c1ccc(Cl)cc1
Temperature: 90 °C
Yield: 63.4 %

Procedure:
To a suspension of 1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)-4,4-dimethylpentane-1,3-dione (555 mg, 1.20 mmol) (B) in EtOH (5.5 mL) was added hydrazine monohydrate (0.12 g, 2.4 mmol). The reaction mixture was refluxed at 90° C. for 6 hours. After cooled down to room temperature, the resulting suspension was dissolved by addition of THF (15 mL) and further purified by prep HPLC to provide 350 mg (0.761 mmol, 63%) of the title compound.