Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[N:7]2[N:8]=[C:9]([S:11][CH2:12][C:13]3[NH:14][CH:15]=[C:16]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[N:17]=3)[N:10]=[C:6]2[CH:5]=[C:4]([CH3:24])[CH:3]=1.[CH2:25](Br)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH2:25]([SH:11]([CH2:12][C:13]1[NH:14][CH:15]=[C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[N:17]=1)[C:9]1[N:10]=[C:6]2[CH:5]=[C:4]([CH3:24])[CH:3]=[C:2]([CH3:1])[N:7]2[N:8]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: BrCc1ccccc1
Reactant: Cc1cc(C)n2nc(SCc3nc(-c4ccccc4)c[nH]3)nc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1cc(C)n2nc([SH](Cc3ccccc3)Cc3nc(-c4ccccc4)c[nH]3)nc2c1
Temperature: 75 °C
Reaction time: 8 h

Procedure:
To a solution of 5,7-dimethyl-2-(4-phenyl-1H-imidazol-2-ylmethylsulfanyl)-[1,2,4]triazolo[1,5-a]pyridine (15 mg, 0.045 mmol) in DMF (0.5 mL) was added benzyl bromide (5.4 μL, 0.045 mmol) and potassium carbonate (9.3 mg, 0.067 mmol) and the resulting mixture was stirred overnight at 75° C. Volatiles were evaporated and the residue was purified by preparative LC-MS to yield the title compound. LC-MS: m/z 426.3 (MH+), tR=1.06 min, method A.
Reaction SMILES: C([O:8][CH2:9][C:10]12[CH2:18][CH:14]3[CH2:15][CH:16]([CH2:17]1)[C:12]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])([CH2:13]3)[CH2:11]2)C1C=CC=CC=1>CO.[Pd]>[OH:8][CH2:9][C:10]12[CH2:18][CH:14]3[CH2:15][CH:16]([CH2:17]1)[C:12]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:24])([CH3:23])[CH3:25])([CH2:13]3)[CH2:11]2
Reactant: CC(C)(C)OC(=O)NC12CC3CC1CC(COCc1ccccc1)(C3)C2
Agent: [Pd]
Solvent: CO
Product: CC(C)(C)OC(=O)NC12CC3CC1CC(CO)(C3)C2
Reaction time: 2 h
Yield: 93.5 %

Procedure:
To a stirred mixture of tert-butyl [1-(benzyloxymethyl)tricyclo[3.3.1.03,7]non-3-yl]carbamate (1.0 g, 2.8 mmol) obtained in step V in MeOH (11 mL), Pd/C (10%, 0.2 g) was added. The H2 pressure was then applied with the balloon for 2 h. The reaction mixture was filtered through a pad of celite and the filtrate was concentrated under reduced pressure to obtain tert-butyl [1-(hydroxymethyl)tricyclo[3.3.1.03,7]non-3-yl]carbamate as a viscous liquid (0.7 g) in 95% yield. m/z (M+1) 268; 1H NMR (CDCl3) 300 MHz δ 4.74 (s (br), 1H), 3.45 (s, 2H), 2.50-2.40 (m, 1H), 2.40-2.33 (m, 1H), 2.05-1.87 (m, 4H), 1.80 (dd, J=2.4, 10.3 Hz, 1H), 1.65 (dd, J=3.0, 10.0 Hz, 1H), 1.54-1.40 (m, 3H), 1.45 (s, 9H), 1.37 (dd, J=3.1, 10.0 Hz, 1H).
Reaction SMILES: [Si:1]([O:18][CH2:19][C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][C:28]=1[S:29]([CH3:32])(=[O:31])=[O:30])[N:25](S(C)(=O)=O)[C:24]([C:37](=[O:41])[CH:38]([CH3:40])[CH3:39])=[CH:23]2)([C:14]([CH3:17])([CH3:16])[CH3:15])([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.C([O-])([O-])=O.[Cs+].[Cs+]>C1COCC1.CO>[Si:1]([O:18][CH2:19][C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][C:28]=1[S:29]([CH3:32])(=[O:30])=[O:31])[NH:25][C:24]([C:37](=[O:41])[CH:38]([CH3:39])[CH3:40])=[CH:23]2)([C:14]([CH3:17])([CH3:16])[CH3:15])([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
Reactant: CC(C)C(=O)c1cc2cc(CO[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)c(S(C)(=O)=O)cc2n1S(C)(=O)=O
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: C1CCOC1
Solvent: CO
Product: CC(C)C(=O)c1cc2cc(CO[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)c(S(C)(=O)=O)cc2[nH]1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a stirred solution of 1-(5-(((tert-butyldiphenylsilyl)oxy)methyl)-1,6-bis(methylsulfonyl)-1H-indol-2-yl)-2-methylpropan-1-one (780 mg, 1.27 mmol) in THF/methanol (15 mL/15 mL) was added Cs2CO3 (1.25 g, 3.83 mmol) in one portion. The mixture was allowed to stir at rt for 4 h and concentrated in vacuo to afford the crude product 1-(5-(((tert-butyldiphenylsilyl)oxy)methyl)-6-(methylsulfonyl)-1H-indol-2-yl)-2-methylpropan-1-one. It was used for the next step reaction without further purification. To a solution of crude 1-(5-(((tert-butyldiphenylsilyl)oxy)methyl)-6-(methylsulfonyl)-1H-indol-2-yl)-2-methylpropan-1-one, 2-(Boc-amino)ethyl bromide (2.8 g, 12 mmol), tetrabutylammonium iodide (235 mg, 0.63 mmol) in CH2Cl2/toluene (2 mL/4 mL) was added 40% NaOH aqueous solution (20 mL). The mixture was allowed to stir at rt for 20 h. The reaction mixture was diluted with CH2Cl2 (40 mL) and washed with H2O (50 mL). The organic layer was separated, and the aqueous layer was extracted with CH2Cl2 (4×50 mL). The combined organic solution was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography over silica gel eluting with CH2Cl2/Methanol (95/5) to provide tert-butyl(2-(5-(((tert-butyldiphenylsilyl)oxy)methyl)-2-isobutyryl-6-(methylsulfonyl)-1H-indol-1-yl)ethyl)carbamate (300 mg, 35% yield for two steps).
Reaction SMILES: [CH2:1]([NH:5][C:6]1[CH:7]=[CH:8][C:9]2[N:10]([C:12]([C:15]3[CH:23]=[CH:22][C:18]([C:19](O)=[O:20])=[CH:17][CH:16]=3)=[CH:13][N:14]=2)[N:11]=1)[CH2:2][CH2:3][CH3:4].[NH:24]1[CH2:29][CH2:28][CH:27]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:26][CH2:25]1.C(N=C=NCCCN(C)C)C>ClCCl>[C:33]([O:32][C:31](=[O:37])[NH:30][CH:27]1[CH2:26][CH2:25][N:24]([C:19](=[O:20])[C:18]2[CH:17]=[CH:16][C:15]([C:12]3[N:10]4[N:11]=[C:6]([NH:5][CH2:1][CH2:2][CH2:3][CH3:4])[CH:7]=[CH:8][C:9]4=[N:14][CH:13]=3)=[CH:23][CH:22]=2)[CH2:29][CH2:28]1)([CH3:34])([CH3:36])[CH3:35]
Reactant: CCCCNc1ccc2ncc(-c3ccc(C(=O)O)cc3)n2n1
Reactant: CC(C)(C)OC(=O)NC1CCNCC1
Agent: CCN=C=NCCCN(C)C
Solvent: ClCCl
Product: CCCCNc1ccc2ncc(-c3ccc(C(=O)N4CCC(NC(=O)OC(C)(C)C)CC4)cc3)n2n1
Temperature: 25 °C
Yield: 51.4 %

Procedure:
The reaction of the 4-(6-(butylamino)imidazo[1,2-b]pyridazin-3-yl)benzoic acid (93 mg, 0.3 mmol), tert-butyl piperidin-4-ylcarbamate (66 mg, 0.33 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (63 mg, 0.33 mmol) and dichloromethane (3 mL) was maintained at room temperature overnight. The resulting solution was purified by preparative HPLC (neutral) to afford tert-butyl(1-(4-(6-(butylamino)imidazo[1,2-b]pyridazin-3-yl)benzoyl)piperidin-4-yl)carbamate (76 mg, 52% yield) as a yellow solid: 1H NMR (METHANOL-d4) δ: 8.23-8.43 (m, J=8.3 Hz, 2H), 7.85 (s, 1H), 7.63 (d, J=9.9 Hz, 1H), 7.45-7.56 (m, 2H), 6.68-6.87 (m, 1H), 4.55 (d, J=12.1 Hz, 1H), 3.82 (br. s., 1H), 3.59-3.72 (m, 1H), 3.35-3.48 (m, 4H), 3.19 (d, J=15.2 Hz, 2H), 1.92-2.17 (m, 1H), 1.90 (br. s., 1H), 1.72 (m, 2H), 1.35-1.59 (m, 13H), 1.01 (t, J=7.3 Hz, 3H); LRMS (ESI) m/e 493.3 [(M+H)+, calcd for C27H37N6O3 493.3].
Reaction SMILES: [CH3:1][N:2]1[CH2:15][CH2:14][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].N1CCC[C@H]1C(O)=O.Br[CH:33]=[C:34]([CH:36]1[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1)[CH3:35]>CN(C=O)C.[Cu]I>[CH:36]1(/[C:34](/[CH3:35])=[CH:33]/[N:6]2[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]3[CH2:3][N:2]([CH3:1])[CH2:15][CH2:14][C:5]2=3)[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1
Reactant: CC(=CBr)C1CCCCC1
Reactant: Cc1ccc2[nH]c3c(c2c1)CN(C)CC3
Agent: [Cu]I
Agent: O=C(O)[C@@H]1CCCN1
Agent: O=P([O-])([O-])[O-]
Solvent: CN(C)C=O
Product: C/C(=C\n1c2c(c3cc(C)ccc31)CN(C)CC2)C1CCCCC1
Temperature: 85 °C

Procedure:
2,3,4,5-tetrahydro-2,8-dimethyl-1H-pyrido[4,3-b]indole (100 mg, 0.5 mmol) was dissolved in DMF (3 mL) and potassium phosphate (212.4 mg, 1 mmol), copper(I) iodide (9.5 mg, 0.05 mmol) and L-proline (11.51 mg, 0.1 mmol) was added in to it. (1-bromoprop-1-en-2-yl)cyclohexane (121.8 mg, 0.6 mmol) was dissolved in DMF (2 mL) and added dropwise. Nitrogen was purged for 2 min. and the reaction mixture was heated at 85° C. overnight (prolonged heating was required in some cases). DMF was evaporated and water was added. The precipitate obtained was filtered and purified by silica gel chromatography (100-200 mesh) using 0-3% MeOH:DCM as eluent. The compound was further purified through reverse phase purification. Yield: 11 mg. 1H NMR (CD3OD, TFA salt) δ (ppm): 7.24 (s, 1H), 7.06 (d, 1H), 7.0 (d, 1H), 6.25 (s, 1H), 4.70 (m, 1H), 4.35 (m, 1H), 3.82 (m, 1H), 3.48 (m, 1H), 3.10 (s, 3H), 3.04 (m, 2H), 2.42 (s, 3H), 2.10 (m, 1H), 1.90 (s, 3H), 1.65 (m, 2H), 1.60-1.40 (m, 5H), 1.20-1.0 (m, 3H).
Reaction SMILES: CN(C=O)C.C(=O)([O-])[O-].[K+].[K+].[CH3:12][C:13]1[CH:20]=[CH:19][C:16]([CH2:17]Cl)=[CH:15][CH:14]=1.[CH3:21][O:22][N:23]=[C:24]([N:32]1[CH:36]=[CH:35][N:34]=[CH:33]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[OH:31]>CCOCC>[CH3:21][O:22][N:23]=[C:24]([N:32]1[CH:36]=[CH:35][N:34]=[CH:33]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[O:31][CH2:17][C:16]1[CH:19]=[CH:20][C:13]([CH3:12])=[CH:14][CH:15]=1
Reactant: Cc1ccc(CCl)cc1
Reactant: CON=C(c1ccccc1O)n1ccnc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOCC
Solvent: CN(C)C=O
Product: CON=C(c1ccccc1OCc1ccc(C)cc1)n1ccnc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 57.2 %

Procedure:
DMF (3 ml), potassium carbonate (0.22 g) and 4-methylbenzyl chloride (0.20 g) were added to 2-hydroxy-α-(1-imidazolyl)benzaldehyde O-methyloxime (0.26 g), and the mixture was stirred at room temperature overnight. After completion of the reaction, ether (100 ml) was added, and the mixture was washed with brine (80 ml) twice, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting crude product was purified by silica gel chromatography and recrystallized from ethyl acetate/n-hexane to give α-(1-imidazolyl)-2-(4-methylbenzyloxy)benzaldehyde O-methyloxime (0.22 g) as colorless crystals. mp. 70.5°-72.0° C.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:15])[NH:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([Cl:12])=[C:8]([CH2:13][OH:14])[CH:7]=1>CC#N.O=[Mn]=O>[CH3:1][O:2][C:3](=[O:15])[NH:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([Cl:12])=[C:8]([CH:13]=[O:14])[CH:7]=1
Reactant: COC(=O)NCc1ccc(Cl)c(CO)c1
Agent: O=[Mn]=O
Solvent: CC#N
Product: COC(=O)NCc1ccc(Cl)c(C=O)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 91.8 %

Procedure:
MnO2 (6.68 g, 76.9 mmol) was added to a sol. of (4-chloro-3-hydroxymethyl-benzyl)-carbamic acid methyl ester (3.53 g, 15.4 mmol) in CH3CN (300 mL). The mixture was stirred at rt for 3 h, and MnO2 (2.67 g, 30.7 mmol) was added again. The mixture was stirred for 1 h, and MnO2 (1.34 g, 15.4 mmol) was added again. The mixture was stirred for 2 h, and was filtered through celite. The precipitate was washed with CH2Cl2, and the filtrate was evaporated under reduced pressure. Drying the residue under high vacuum yielded the crude title compound (3.22 g, 92%) that was used further without purification.
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([CH2:11][C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])[CH:7]=[CH:8][C:9]=1[Cl:10].Cl[CH2:23][C:24]([O-:26])=[O:25].[Na+].Cl>CCCCCCC.C1(C)C=CC=CC=1.C(OCC)(=O)C.CS(C)=O>[Cl:3][C:4]1[CH:5]=[C:6]([CH:11]([C:12]([O:14][CH2:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)=[O:13])[CH2:23][C:24]([OH:26])=[O:25])[CH:7]=[CH:8][C:9]=1[Cl:10]
Reactant: O=C([O-])CCl
Reactant: O=C(Cc1ccc(Cl)c(Cl)c1)OCc1ccccc1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CCCCCCC
Solvent: CS(C)=O
Solvent: Cc1ccccc1
Product: O=C(O)CC(C(=O)OCc1ccccc1)c1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 74.7 %

Procedure:
To a DMSO (50 ml) suspension of 3.63 g (0.100 mol) of sodium hydride, a DMSO solution (30 ml) of 31.57 g (0.100 mol) of benzyl 3,4-dichlorophenylacetate was added at a temperature of 30° C. or below over a period of 45 minutes, and then the solution was further stirred at an internal temperature of 25° C. for 45 minutes. Then 11.65 g (0.100 mol) of sodium chloroacetate was added over a period of 10 minutes and the suspension was stirred at an internal temperature of 25° C. for 18.5 hours. The reaction solution was added dropwise into 50 ml of 2N hydrochloric acid and 250 ml of ice water while maintaining the internal temperature at 20° C. or below, and then 250 ml of ethyl acetate was added to the mixed solution. After separating the liquid, the organic layer was washed with 250 ml of water and then further washed with 250 ml of a 5% saline solution. It was then concentrated under reduced pressure, again concentrated under reduced pressure by adding 50 ml of toluene and further concentrated under reduced pressure by additionally adding 50 ml of toluene to obtain a crude product. Then 100 ml of toluene was added and the solution was heated to an internal temperature of 90° C. and stirred for one hour, after which 100 ml of heptane was added at an internal temperature of 80° C. and the solution was cooled slowly until the internal temperature dropped to 25° C. The precipitated crystals were filtered out and washed twice with 25 ml of heptane to obtain 26.40 g (74.7% yield) of the title compound.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]2[CH:15]=[CH:16][C:17]3[NH:22][C:21](=[O:23])[O:20][CH2:19][C:18]=3[CH:24]=2)=[CH:4][CH:3]=1.[OH:25]O>>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]2[CH:15]=[CH:16][C:17]3[NH:22][C:21](=[O:23])[O:20][CH2:19][C:18]=3[CH:24]=2)=[O:25])=[CH:6][CH:7]=1
Reactant: Cc1ccc(SCCCCOc2ccc3c(c2)COC(=O)N3)cc1
Reactant: OO
Product: Cc1ccc(S(=O)CCCCOc2ccc3c(c2)COC(=O)N3)cc1

Procedure:
Prepared analogously to Example 2 from 6-[4-(4-methyl-phenylmercapto)-butoxy]-4H-3,1-benzoxazin-2-one and hydrogen peroxide.
Reaction SMILES: [F:1]/[C:2](=[CH:5]\[CH2:6][CH3:7])/[CH:3]=[O:4].[Br-].[Mg+2].[CH:10]#[CH:11].[Br-].Cl>O1CCCC1>[OH:4][CH:3](/[C:2](/[F:1])=[CH:5]/[CH2:6][CH3:7])[C:10]#[CH:11]
Reactant: CC/C=C(\F)C=O
Reactant: C#C
Agent: Cl
Agent: [Br-]
Agent: [Mg+2]
Solvent: C1CCOC1
Product: C#CC(O)/C(F)=C/CC
Reaction time: 0.5 h

Procedure:
After 13.0 g of (Z)-2-fluoro-2-pentenal was dissolved in 30 ml of dry tetrahydrofurane, a tetrahydrofurane solution of acetylene magnesium bromide (the molar amount of acetylene magnesium bromide was 1.5 times that of the said aldehyde) was added to the solution dropwise while it was cooled with ice and maintained at a temperature of 10° C. or below. The mixture was stirred for 30 minutes while being cooled with ice and then stirred at 20° C. for one hour. The reaction solution was poured into ice-cooled 5% dilute hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. After the solvent was distilled off, the residue was distilled under reduced pressure, thereby obtaining 9.5 g of the desired substance as a pale yellow oil.
Reaction SMILES: [CH3:1][C:2]1([CH3:16])[CH2:7][C:6]([CH3:9])([CH3:8])[CH2:5][CH:4]([CH2:10][C:11](OCC)=[O:12])[CH2:3]1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>CCOCC>[CH3:8][C:6]1([CH3:9])[CH2:7][C:2]([CH3:1])([CH3:16])[CH2:3][CH:4]([CH2:10][CH2:11][OH:12])[CH2:5]1
Reactant: CCOC(=O)CC1CC(C)(C)CC(C)(C)C1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Product: CC1(C)CC(CCO)CC(C)(C)C1
Yield: 81.4 %

Procedure:
A solution of ethyl 3,3,5,5-tetramethylcyclohexylacetate 8 (1.8 g, 8.0 mmol) in ether (30 ml) was added dropwise to a stirred suspension of lithium aluminum hydride (0.9 g, 24.0 mmol) in ether (30 ml), which was cooled in an ice bath. The reaction mixture was refluxed for 3 h, cooled and residual lithium aluminum hydnde was destroyed with water. The aqueous layer was separated and twice extracted with ether. The combined ether phases were washed with saline, dried over MgSO4, filtered and evaporated. The crude product was purified by flash chromatography on silica gel, eluting with hexane--ethyl acetate mixture (4:1) to give 1.2 g (79%) of 11 as an oil. 1H NMR (CDCl3, TMS) δ: 0.89 and 1.00 (total 12H, both s, cyclohexane 3,5-CH3); 1.44 (2H, q, J=7 Hz, 2-CH2); 0.55-1.95 (8H, m, ring protons and OH) and 3.70 ppm (2H, t, J=7 Hz, CH2O).
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].[CH3:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[CH:8][CH:7]=1.[Cl:14][C:15]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][C:16]=1[C:17](Cl)=[O:18].Cl>C(Cl)Cl>[Cl:14][C:15]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][C:16]=1[C:17](=[O:18])[C:8]1[CH:7]=[C:6]([CH3:5])[CH:11]=[CH:10][C:9]=1[O:12][CH3:13]
Reactant: COc1ccc(C)cc1
Reactant: O=C(Cl)c1cc([N+](=O)[O-])ccc1Cl
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: COc1ccc(C)cc1C(=O)c1cc([N+](=O)[O-])ccc1Cl
Temperature: 5 °C
Reaction time: 1 h

Procedure:
A mixture of aluminum chloride (33.3 g, 25.0 mmol) in methylene chloride is cooled to about 5° C., treated over one hour with p-methylanisole (31.6 g, 25.0 mmol) while maintaining the reaction mixture temperature below 10° C., treated over 20 minutes with a solution of 2-chloro-5-nitrobenzoyl chloride (50.0 g, 22.7 mmol) in methylene chloride while maintaining the reaction mixture temperature below 10° C., warmed to and stirred at room temperature for 60 minutes, and poured onto ice. The resultant aqueous mixture is treated with concentrated hydrochloric acid (50 mL) and extracted with methylene chloride. The organic extract is dried over anhydrous magnesium sulfate and concentrated in vacuo to give a yellow solid. After placing the solid in a Kugelrohr apparatus at 40° C. to remove residual p-methylanisole, the title product is obtained as a beige solid (68.8 g, 99.1%) which is identified by NMR spectral analyses.
Reaction SMILES: [C:1]1([CH3:10])[CH:6]=[CH:5][C:4](B(O)O)=[CH:3][CH:2]=1.Br[C:12]1[O:13][CH:14]=[CH:15][CH:16]=1.C(COC)OC.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.C(O)C>[C:1]1([CH3:10])[CH:6]=[CH:5][C:4]([C:12]2[O:13][CH:14]=[CH:15][CH:16]=2)=[CH:3][CH:2]=1
Reactant: Cc1ccc(B(O)O)cc1
Reactant: Brc1ccco1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: COCCOC
Solvent: O
Product: Cc1ccc(-c2ccco2)cc1

Procedure:
4-tolylboronic acid (500 mg), 2-bromofuran, and tetrakis(triphenylphosphine)palladium (177 mg) were added to the mixture of 24 ml of dimethoxyethane and 15 ml of ethanol under nitrogen atmosphere. Additionally 1N sodium carbonate (12 ml) was added to the mixture and the resulting mixture was heated at reflux for 2 h. Water was added to the mixture and the mitture was extracted with diethyl ether. The organic layer was dried and the solvent was removed under reduced pressure. The residue was purified by the use of silica gel column chromatography to give 438 mg of 2-(4-tolyl)furan.
Reaction SMILES: [NH2:1][C:2]1[N:24]=[C:5]2[C:6]([C:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH:12]=3)=[CH:7][C:8]([CH3:10])=[CH:9][N:4]2[N:3]=1.[CH3:25][C:26]1[N:31]=[CH:30][N:29]=[C:28]([N:32]2[CH2:37][CH2:36][C:35](=O)[CH2:34][CH2:33]2)[CH:27]=1.C(Cl)Cl>C(Cl)Cl.CO>[CH3:10][C:8]1[CH:7]=[C:6]([C:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:21])([CH3:23])[CH3:22])=[O:18])[CH2:13][CH:12]=2)[C:5]2[N:4]([N:3]=[C:2]([NH:1][CH:35]3[CH2:36][CH2:37][N:32]([C:28]4[CH:27]=[C:26]([CH3:25])[N:31]=[CH:30][N:29]=4)[CH2:33][CH2:34]3)[N:24]=2)[CH:9]=1
Reactant: Cc1cc(N2CCC(=O)CC2)ncn1
Reactant: Cc1cc(C2=CCN(C(=O)OC(C)(C)C)CC2)c2nc(N)nn2c1
Solvent: ClCCl
Solvent: CO
Product: Cc1cc(C2=CCN(C(=O)OC(C)(C)C)CC2)c2nc(NC3CCN(c4cc(C)ncn4)CC3)nn2c1

Procedure:
Prepared in analogy to example 1h, starting from tert-butyl 4-(2-amino-6-methyl-[1,2,4]triazolo[1,5-a]pyridin-8-yl)-5,6-dihydropyridine-1(2H)-carboxylate and 1-(6-methylpyrimidin-4-yl)piperidin-4-one (see example 93b). The title compound was obtained as a light yellow solid (yield: 32%) after column chromatography on silica gel using a gradient from methylene chloride to methylene chloride/methanol 19:1 (v/v) as eluent.
Reaction SMILES: [CH:1]([C:4]1[CH:5]=[C:6]([CH:9]=[C:10]([CH:13]([CH3:15])[CH3:14])[C:11]=1[OH:12])[CH:7]=O)([CH3:3])[CH3:2].[N+:16]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[CH2:25]C(O)=O)([O-:18])=[O:17].N1CCCCC1>C1(C)C(C)=CC=CC=1>[CH:1]([C:4]1[CH:5]=[C:6]([CH:7]=[CH:25][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[N+:16]([O-:18])=[O:17])[CH:9]=[C:10]([CH:13]([CH3:15])[CH3:14])[C:11]=1[OH:12])([CH3:3])[CH3:2]
Reactant: CC(C)c1cc(C=O)cc(C(C)C)c1O
Reactant: O=C(O)Cc1ccccc1[N+](=O)[O-]
Solvent: C1CCNCC1
Solvent: Cc1ccccc1C
Product: CC(C)c1cc(C=Cc2ccccc2[N+](=O)[O-])cc(C(C)C)c1O
Yield: 86.8 %

Procedure:
To a solution of 3,5-diisopropyl-4-hydroxybenzaldehyde (0.95 g, 4.6 mmol) and 2-nitrophenyl acetic acid (1.1 g, 6.2 mmol) in xylene (10 ml) was added piperidine (0.05 ml) and the mixture was heated under reflux for 8 hrs while removing water producing with the progress of reaction. After distilling off the solvent followed by purification of the residue by a silica gel column chromatography, recrystallization from hexane gave 2,6-diisopropyl-4-(2-nitrostyryl)phenol (1.3 g, 87%) as crystals.
Reaction SMILES: [CH:1]1([O:6][C:7]2[CH:8]=[C:9](/[CH:15]=[CH:16]/[C:17](OC)=[O:18])[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].C([Al+]CC(C)C)C(C)C.[Cl-].[NH4+].C(OCC)(=O)C>C(Cl)Cl.C1(C)C=CC=CC=1.CCCCCC>[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH2:15][CH:16]=[CH:17][OH:18])[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: COC(=O)/C=C/c1ccc(OC)c(OC2CCCC2)c1
Agent: CC(C)C[Al+]CC(C)C
Agent: [Cl-]
Agent: [H-]
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: COc1ccc(CC=CO)cc1OC1CCCC1
Reaction time: 0.5 h

Procedure:
To a stirred solution of 0.50 g (1.81 mmol) of methyl 3-(3-cyclopentoxy-4-methoxyphenyl)-E-propenoate in 70 mL of dry methylene chloride under a nitrogen atmosphere was added dropwise 3.0 mL (3.0 mmol) of a 1.0M solution of diisobutylaluminum hydride in toluene over a 10 minute period at room temperature. The mixture was stirred for 30 minutes at the end of which time the solution was slowly poured over a stirring solution of 30 mL of saturated ammonium chloride. The resulting solution was stirred for 30 minutes during which time a gelatinous solid formed. Absorption of the solid on excess Celite 545 followed by filtration over a pad of Celite 545 and elution with three, 30 mL portions of chloroform provided a yellow suspension. Separation of the layers followed by washing the organic fraction with 30 mL of saturated sodium chloride, drying over magnesium sulfate and concentration gave a crude yellow product. Liquid chromatography over 100 g of silica gel eluting with 30% ethyl acetate in hexane provided the desired, analytically pure product after drying in vacuo.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.[S:9]1[CH2:14][CH2:13][CH2:12][CH:11]([OH:15])[CH2:10]1>>[S:9]1[CH2:14][CH2:13][CH2:12][CH:11]([O:15][C:2]2[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=2)[CH2:10]1
Reactant: OC1CCCSC1
Reactant: Brc1ccc(Br)nc1
Product: Brc1ccc(OC2CCCSC2)nc1

Procedure:
Prepared from 2,5-dibromopyridine and tetrahydrothiopyran-3-ol by the method of Example 10 (b).