Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([Si]([C:11]#[C:12][C:13]1[CH:14]=[CH:15][C:16]2[N:17]([CH2:38][CH:39]([OH:50])[CH2:40][NH:41][C:42]3[CH:47]=[CH:46][CH:45]=[C:44]([O:48][CH3:49])[CH:43]=3)[C:18]3[C:23]([C:24]=2[CH:25]=1)=[CH:22][C:21]([C:26]#[C:27][Si](C(C)C)(C(C)C)C(C)C)=[CH:20][CH:19]=3)(C(C)C)C(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C(O)(=O)C>C1COCC1.CCOC(C)=O>[C:26]([C:21]1[CH:20]=[CH:19][C:18]2[N:17]([CH2:38][CH:39]([OH:50])[CH2:40][NH:41][C:42]3[CH:47]=[CH:46][CH:45]=[C:44]([O:48][CH3:49])[CH:43]=3)[C:16]3[C:24]([C:23]=2[CH:22]=1)=[CH:25][C:13]([C:12]#[CH:11])=[CH:14][CH:15]=3)#[CH:27]
Reactant: COc1cccc(NCC(O)Cn2c3ccc(C#C[Si](C(C)C)(C(C)C)C(C)C)cc3c3cc(C#C[Si](C(C)C)(C(C)C)C(C)C)ccc32)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: C#Cc1ccc2c(c1)c1cc(C#C)ccc1n2CC(O)CNc1cccc(OC)c1
Temperature: 25 °C
Reaction time: 27 h
Yield: 71.9 %

Procedure:
The title compound of Example 100 was prepared as follows. To a solution of 1-(3,6-bis((triisopropylsilyl)ethynyl)-9H-carbazol-9-yl)-3-(3-methoxyphenylamino)propan-2-ol (0.0152 g, 0.0215 mmol) in 200 μL anhydrous THF, a solution of TBAF in THF (1 M, 64.5 μL, 0.0645 mmol) and acetic acid (2.5 μL, 0.0430 mmol) were added. The mixture was sealed and stirred under N2 atmosphere at rt for 27 h until TLC showed the complete disappearance of starting material. The crude was diluted with 10 mL EtOAc and washed with saturated NaHCO3 (3×10) mL. The organic layer was dried over anhydrous Na2SO4 and evaporated to afford the crude product, which was subjected to silica gel chromatography using Hexanes/EtOAc to afford white solid as product (0.0061 g, yield 71.9%).
Reaction SMILES: [CH2:1]([O:3][NH2:4])[CH3:2].Cl.[Br:6][C:7]1[N:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[NH:13][C:12](=[O:17])[CH:11]=[C:10]2O.O.C(OCC)(=O)C>N1C=CC=CC=1>[Br:6][C:7]1[N:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[NH:13][C:12](=[O:17])[CH:11]=[C:10]2[NH:4][O:3][CH2:1][CH3:2]
Reactant: CCON
Reactant: O=c1cc(O)c2nc(Br)ccc2[nH]1
Agent: Cl
Solvent: O
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Product: CCONc1cc(=O)[nH]c2ccc(Br)nc12
Temperature: 25 °C
Reaction time: 17 h

Procedure:
To a suspension of EtONH2.HCl (1.05 g, 10.8 mmol) in pyridine (5 ml) was added 6-bromo-4-hydroxy-1H-1,5-naphthyridin-2-one (324 mg, 1.34 mmol) and stirring was continued for 17 h at 100° C. The mixture was allowed to cool to ambient temperature then water and ethyl acetate were added followed by separation of phases. The aqueous phase was extracted with ethyl acetate and the combined organic phases were dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash chromatography eluting with ethyl acetate/MeOH, gradient, afforded 6-bromo-4-(ethoxyamino)-1H-1,5-naphthyridin-2-one.
Reaction SMILES: [F:1][C:2]1([F:27])[CH2:7][CH2:6][CH:5]([CH2:8][NH:9][C:10]([C:12]2[C:13]3[CH:14]=[CH:15][C:16]([C:23]#[C:24][CH2:25][OH:26])=[N:17][C:18]=3[CH:19]=[CH:20][C:21]=2[Cl:22])=[O:11])[CH2:4][CH2:3]1.C[SiH](C)C>CO.[Pd]>[F:27][C:2]1([F:1])[CH2:7][CH2:6][CH:5]([CH2:8][NH:9][C:10]([C:12]2[C:13]3[CH:14]=[CH:15][C:16]([CH2:23][CH2:24][CH2:25][OH:26])=[N:17][C:18]=3[CH:19]=[CH:20][C:21]=2[Cl:22])=[O:11])[CH2:4][CH2:3]1
Reactant: O=C(NCC1CCC(F)(F)CC1)c1c(Cl)ccc2nc(C#CCO)ccc12
Agent: [Pd]
Agent: C[SiH](C)C
Solvent: CO
Product: O=C(NCC1CCC(F)(F)CC1)c1c(Cl)ccc2nc(CCCO)ccc12
Reaction time: 0.5 h
Yield: 29 %

Procedure:
To a solution of 6-chloro-2-(3-hydroxy-prop-1-ynyl)-quinoline-5-carboxylic acid (4,4-difluoro-cyclohexylmethyl)-amide (0.25 g, 0.62 mmol, 1.00 eq) in methanol (5 mL, 20 V) were added trimethylsilane (0.65 mL, 6.23 mmol, 10 eq) and followed by palladium on carbon (10% w/w) (0.07 g, 0.06 mmol, 0.10 eq) at 0 OC. The reaction mixture was stirred for 0.5 h. After the completion of the reaction as evidenced by TLC, the reaction mixture was concentrated under vacuum. The reaction mixture was diluted with ethyl acetate (20 mL) and extracted with water (20 mL) and brine solution (20 mL). The organic layer was separated and dried over Na2SO4 and concentrated under vacuum. The crude product was further purified by column chromatography to afford the title compound (0.08 g, 0.18 mmol, 29.0%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 8.82 (t, J=5.83 Hz, 1H), 7.96-8.01 (m, 2H), 7.76 (d, J=9.01 Hz, 1H), 7.55 (d, J=8.72 Hz, 1H), 4.58 (t, J=6.22 Hz, 1H), 3.46 (t, J=6.41 Hz, 2H), 3.27 (t, J=6.22 Hz, 2H), 2.95 (t, J=7.62 Hz, 2H), 2.02-2.04 (m, 2H), 1.74-1.93 (m, 7H), 1.29-1.33 (m, 2H). m/z: 397.2 [M+H]+
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]2[N:12]=[C:11]([C:13]3[CH:18]=[CH:17][C:16]([C:19]([CH3:22])([CH3:21])[CH3:20])=[CH:15][CH:14]=3)[O:10][C:9](=[O:23])[C:8]=2[CH:24]=1)([O-:3])=[O:2].[CH3:25][O:26][C:27]1[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=1>CN(C)C=O>[C:19]([C:16]1[CH:17]=[CH:18][C:13]([C:11]([NH:12][C:7]2[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:24][C:8]=2[C:9]([NH:33][C:30]2[CH:31]=[CH:32][C:27]([O:26][CH3:25])=[CH:28][CH:29]=2)=[O:23])=[O:10])=[CH:14][CH:15]=1)([CH3:20])([CH3:22])[CH3:21]
Reactant: COc1ccc(N)cc1
Reactant: CC(C)(C)c1ccc(-c2nc3ccc([N+](=O)[O-])cc3c(=O)o2)cc1
Solvent: CN(C)C=O
Product: COc1ccc(NC(=O)c2cc([N+](=O)[O-])ccc2NC(=O)c2ccc(C(C)(C)C)cc2)cc1
Temperature: 80 °C
Yield: 14.5 %

Procedure:
A mixture of 6-nitro-2-(4-tert-butylphenyl)-4H-3,1-benzoxazin-4-one (1.21 g, 3.73 mmol) and p-anisidine (551 mg, 4.47 mmol) in N,N-dimethylformamide (5 mL) was heated at 80° C. for 2.5 h. After cooling to room temperature, the reaction mixture was poured into an ice/water mixture and extracted twice with methylene chloride. The combined organic layers were washed with water, dried (sodium sulfate), and filtered. From the resulting solution crystallized 706 mg (42%) of the title product as a light brown solid. The mother liquor was chromatographed (silica gel, 20% diethyl ether/80% hexanes to 40% diethyl ether/60% hexanes) to give 242 mg (14%) of additional product; mp 210-11° C.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][C:13](=O)[CH2:12][CH2:11]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH3:17][C@H:18]1[O:23][C@@H:22]([CH3:24])[CH2:21][NH:20][CH2:19]1.C([BH3-])#N.[Na+]>C(O)(=O)C>[CH3:24][CH:22]1[O:23][CH:18]([CH3:17])[CH2:19][N:20]([CH:13]2[CH2:14][CH2:15][N:10]([C:7]3[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=3)[CH2:11][CH2:12]2)[CH2:21]1
Reactant: C[C@@H]1CNC[C@H](C)O1
Reactant: O=C1CCN(c2ccc([N+](=O)[O-])cc2)CC1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Product: CC1CN(C2CCN(c3ccc([N+](=O)[O-])cc3)CC2)CC(C)O1
Temperature: 0 °C
Yield: 87 %

Procedure:
To an ice-cooled solution of 1-(4-nitro-phenyl)-piperidin-4-one (400 mg, 1.8 mmol) in acetic acid was added cis-2,6-dimethyl-morpholine (0.32 mL, 2.68 mmol) and sodium cyanoborohydride (220 mg, 3.50 mmol). The mixture was heated at reflux overnight then allowed to cool and concentrated to dryness under reduced pressure. The residue was partitioned between 5% sodium hydroxide solution and ethyl acetate. The organic phase was washed with water, brine, dried and concentrated to afford 2,6-dimethyl-4-[1-(4-nitrophenyl)-piperidin-4-yl]-morpholine (500 mg, 86%) as a yellow solid.
Reaction SMILES: [F:1][C:2]([F:25])([F:24])[C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][NH:13][CH2:12][CH:11]([NH:15][C:16](=[O:23])[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:10]2)=[CH:5][CH:4]=1.[N:26]1([C:32](Cl)=[O:33])[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1.C(N(CC)CC)C.O>ClCCl>[N:26]1([C:32]([N:13]2[CH2:14][CH:9]([C:6]3[CH:5]=[CH:4][C:3]([C:2]([F:24])([F:1])[F:25])=[CH:8][CH:7]=3)[CH2:10][CH:11]([NH:15][C:16]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)=[O:23])[CH2:12]2)=[O:33])[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1
Reactant: O=C(NC1CNCC(c2ccc(C(F)(F)F)cc2)C1)c1ccccc1
Reactant: O=C(Cl)N1CCOCC1
Solvent: O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(NC1CC(c2ccc(C(F)(F)F)cc2)CN(C(=O)N2CCOCC2)C1)c1ccccc1
Temperature: 25 °C

Procedure:
At 0° C., 705 mg (2.02 mmol) of N-{5-[4-(trifluoromethyl)phenyl]piperidin-3-yl}benzamide were initially charged in 70 ml of dichloromethane, and 321 mg (2.02 mmol) of morpholine-4-carbonyl chloride and 564 μl (4.04 mmol) of triethylamine were added. The mixture was slowly warmed to RT overnight. Water was added, and the reaction mixture was extracted. The organic phase was dried over magnesium sulphate and concentrated under reduced pressure. The residue was then purified by preparative HPLC (Reprosil C18, water/acetonitrile gradient). Yield: 960 mg (100% of theory)
Reaction SMILES: [CH2:1]=[C:2]1[O:6][C:4](=[O:5])[CH2:3]1.[NH2:7][CH:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]([O:15][CH2:16][CH3:17])=[O:14]>C1C=CC=CC=1>[C:13]([CH:9]1[CH2:10][CH2:11][CH2:12][CH:8]1[NH:7][C:4](=[O:5])[CH2:3][C:2](=[O:6])[CH3:1])([O:15][CH2:16][CH3:17])=[O:14]
Reactant: CCOC(=O)C1CCCC1N
Reactant: C=C1CC(=O)O1
Solvent: c1ccccc1
Product: CCOC(=O)C1CCCC1NC(=O)CC(C)=O
Temperature: 20 °C
Reaction time: 72 h
Yield: 55.9 %

Procedure:
4.8 g of diketene were added to a mixture of 9 g of 1-amino-2-carbethoxy-cyclopentane and 90 ml of benzene and after stirring for 72 hours at 20° C., the mixture was evaporated to dryness under reduced pressure. The residue was chromatographed over silica gel and was eluted with an 8-2 methylene chloride-acetone mixture to obtain 7.7 g of N-(2-carbethoxycyclopentyl)-acetylacetamide with a refractive index of ND22 =1.487. 6.3 g of the latter product and 0.25 g of p-toluene sulfonic acid were added to a mixture of 4.2 g of methyl orthoformate and 60 ml of methanol and after stirring the mixture at 20° C. for 16 hours, the mixture was evaporated to dryness under reduced pressure. The residue was added to toluene and 0.5 ml of quinoline and the mixture was heated at 145° C. for 1 hour while distilling a toluene-methanol azeotrope. The mixture was evaporated to dryness under reduced pressure and the residue was chromatographed over silica gel. Elution with a 9-1 methylene chloride-acetone mixture gave 1.8 g of N-(2'-carbethoxycyclopentyl)-3-methoxy-crotonamide melting at 74° C. The RMN spectra showed it to be the E isomer.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]([N:13]3[CH2:17][CH2:16][C:15]4([C:25]5[CH:24]=[CH:23][N:22]=[CH:21][C:20]=5[C:19](=[O:26])[O:18]4)[CH2:14]3)=[O:12])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[NH:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH:29]=[N:28]1.C1(C)C=CC=CC=1.CN[C@H]1CCCC[C@@H]1NC.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[Cu]I>[N:27]1[N:28]([C:2]2[CH:7]=[CH:6][C:5]([C:8]3([C:11]([N:13]4[CH2:17][CH2:16][C@@:15]5([C:25]6[CH:24]=[CH:23][N:22]=[CH:21][C:20]=6[C:19](=[O:26])[O:18]5)[CH2:14]4)=[O:12])[CH2:10][CH2:9]3)=[CH:4][CH:3]=2)[CH:29]=[C:30]2[C:35]=1[CH:34]=[CH:33][CH:32]=[CH:31]2
Reactant: c1ccc2[nH]ncc2c1
Reactant: O=C1OC2(CCN(C(=O)C3(c4ccc(Br)cc4)CC3)C2)c2ccncc21
Agent: [Cu]I
Agent: CN[C@H]1CCCC[C@@H]1NC
Agent: O=P([O-])([O-])[O-]
Solvent: Cc1ccccc1
Product: O=C1O[C@]2(CCN(C(=O)C3(c4ccc(-n5cc6ccccc6n5)cc4)CC3)C2)c2ccncc21
Temperature: 25 °C

Procedure:
To a solution of 1′-{[1-(4-bromophenyl)cyclopropyl]carbonyl}-3H-spiro[furo[3,4-c]pyridine-1,3′-pyrrolidin]-3-one (30 mg, 0.00007 mol), 1H-Indazole (10.3 mg, 0.0000871 mol) in toluene (1 mL, 0.01 mol) were added (1S,2S)—N,N′-dimethylcyclohexane-1,2-diamine (2.1 mg, 0.000014 mol), copper(I) iodide (1 mg, 0.000007 mol), and potassium phosphate (32.4 mg, 0.000152 mol) in a sealed vial. The mixture was microwaved at 150 Celsius for 60 minutes. Then the mixture was cooled down to r.t. and filtered. The filtrate was diluted with methanol, and the desired compound was obtained by revised phase prep-HPLC. MS (ESI): 451.1 (M+H+). The enantiomers were separated by chiral HPLC.
Reaction SMILES: [Li]CCCC.Br[C:7]1[CH:12]=[CH:11][C:10]([C:13]#[C:14][Si:15]([CH3:18])([CH3:17])[CH3:16])=[CH:9][CH:8]=1.C1COCC1.[CH3:24][Si:25]([C:28]#[C:29][C:30]1[CH:49]=[CH:48][C:33]([C:34]([C:36]2[CH:41]=[CH:40][C:39]([C:42]#[C:43][Si:44]([CH3:47])([CH3:46])[CH3:45])=[CH:38][CH:37]=2)=[O:35])=[CH:32][CH:31]=1)([CH3:27])[CH3:26]>CCOCC.O>[CH3:16][Si:15]([C:14]#[C:13][C:10]1[CH:11]=[CH:12][C:7]([C:34]([C:33]2[CH:32]=[CH:31][C:30]([C:29]#[C:28][Si:25]([CH3:24])([CH3:26])[CH3:27])=[CH:49][CH:48]=2)([C:36]2[CH:37]=[CH:38][C:39]([C:42]#[C:43][Si:44]([CH3:47])([CH3:46])[CH3:45])=[CH:40][CH:41]=2)[OH:35])=[CH:8][CH:9]=1)([CH3:18])[CH3:17]
Reactant: C[Si](C)(C)C#Cc1ccc(C(=O)c2ccc(C#C[Si](C)(C)C)cc2)cc1
Reactant: C[Si](C)(C)C#Cc1ccc(Br)cc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCOCC
Solvent: O
Product: C[Si](C)(C)C#Cc1ccc(C(O)(c2ccc(C#C[Si](C)(C)C)cc2)c2ccc(C#C[Si](C)(C)C)cc2)cc1
Temperature: -30 °C
Reaction time: 0.25 h
Yield: 77 %

Procedure:
A solution of n-BuLi (2.1 mL, 3.36 mmol, 1.6 M in hexane) was added to a solution of (4-bromophenylethynyl)trimethylsilane (0.69 mg, 2.74 mmol) in 50 mL of Et2O prechilled to -78° C. The solution was then stirred at -30° C. for 15 minutes. The solution was warmed to room temperature, stirred for 1 hour, and cooled to -30° C. A THF solution (20 mL) of 4,4'-bis(trimethylsilylethynyl)benzophenone (0.83 g, 2.19 nmol) prechilled to -30° C. was added slowly and the resulting mixture was stirred for 15 minutes. The solution was warmed to 0° C. and stirred for 2 hours. After addition of 1 mL of H2O the solution was pumped dry. The residue was chromatographed using CH2Cl2 /hexane (1:5 to 2:1) as eluent to afford tri(4-(trimethylsilylethynyl)phenyl)methanol as a colorless powder in 77% yield (0.92 q). 1H NMR (300 MHz, CDCL3, 25° C., TMS): 0.22 (s, 27 H, CH3), 2.72 (s, 1 h, OH), 7.13 (d, J=8.4 Hz, 6 H, C6H4), 7.38 (d, 6 H, C6H4). To a mixture of tri (4-(trimethylsilylethynyl)phenyl)methanol (0.92 g, 1.68 mmol) and KOH (0.28 g, 5.0 mmol) was added 50 mL of MeOH and the solution was stirred at room temperature for 3 hours. The solution was then extracted with Et2O solution was pumped dry and the residue was chromatographed using EtOAc/hexane (1:50 to 1:5) as eluent to afford tri(4-ethynylphenyl)methanol as a colorless powder in 84% yield (0.47 g). Anal. Calcd for C34H40Si3O: C 74.39, H 7.34. Found: C 74.03, H 7.28. 1H NMR (300 MHz, CDCl3, 25° C., TMS) : 2.73 (s, 1 H, OH), 3.06 (s, 3 H, ≡CH), 7.19 (d, J=8.2 Hz, 6 H, C6H4), 7.43 (d, 6 H, C6H4) ; IR (KBr, cm-1): 1018 (m, C--O), 2107 (w, C≡C); 3554 (m, O--H).
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1.[C:11](Cl)(=[O:21])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20].CN(C1C=CC=CN=1)C.Cl>C(Cl)Cl.O.C(N(CC)CC)C>[CH2:12]([C:11]([O:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1)=[O:21])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]
Reactant: CCCCCCCCCC(=O)Cl
Reactant: O=C(O)c1ccc(O)cc1
Agent: CN(C)c1ccccn1
Agent: Cl
Solvent: O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCCCCCCCC(=O)Oc1ccc(C(=O)O)cc1
Yield: 42.5 %

Procedure:
A solution of 4-hydroxybenzoic acid (3 g), decanoic acid chloride (4.3 g), triethylamine (2.4 g) and dimethylaminopyridine (0.2 g) in methylene chloride (50 ml) was stirred at room temperature for 24 hours, and then poured in water. The solution was neutralized with dilute aqueous hydrochloric acid solution and extracted with dimethyl ether. The extracted product was dried over anhydrous magnesium sulfate and distilled to remove the solvent. The residue was washed enough with hexane to obtain the titled compound (2.7 g).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:36]=[CH:37][CH:38]=1)[CH2:5][NH:6][C:7]([C:9]1[N:10]([CH2:30][CH:31](OC)OC)[CH:11]=[C:12]([CH:24]([OH:29])[C:25]([CH3:28])([CH3:27])[CH3:26])[C:13](=[O:23])[C:14]=1[O:15]CC1C=CC=CC=1)=[O:8].Cl>O1CCOCC1>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([CH:36]=[CH:37][CH:38]=1)[CH2:5][N:6]1[CH:31]=[CH:30][N:10]2[CH:11]=[C:12]([CH:24]([OH:29])[C:25]([CH3:27])([CH3:28])[CH3:26])[C:13](=[O:23])[C:14]([OH:15])=[C:9]2[C:7]1=[O:8]
Reactant: COC(Cn1cc(C(O)C(C)(C)C)c(=O)c(OCc2ccccc2)c1C(=O)NCc1cccc(Cl)c1)OC
Agent: Cl
Solvent: C1COCCO1
Product: CC(C)(C)C(O)c1cn2ccn(Cc3cccc(Cl)c3)c(=O)c2c(O)c1=O
Temperature: 90 °C
Reaction time: 2 h
Yield: 187.3 %

Procedure:
To a solution of 3-benzyloxy-1-(2,2-dimethoxyethyl)-5-(1-hydroxy-2,2-dimethylpropyl)-4-oxo-1,4-dihydropyridine-2-carboxylic acid 3-chlorobenzylamide (60 mg) in dioxane (0.55 ml) was added conc. hydrochloric acid (0.55 ml) and the mixture was stirred at 90° C. for 2 hr. The solvent was evaporated, toluene was added, and the mixture was concentrated, which operations were performed twice. Crystallization from ethyl acetate-diisopropyl ether gave 2-(3-chlorobenzyl)-9-hydroxy-7-(1-hydroxy-2,2-dimethylpropyl)-2H-pyrido[1,2-a]pyrazine-1,8-dione hydrochloride (44 mg).
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=O)[CH2:15][CH2:16][CH:17]=[CH2:18])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:20][C:21]([S@:24]([NH2:26])=[O:25])([CH3:23])[CH3:22]>C1COCC1.[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11](/[C:14](=[N:26]\[S@@:24]([C:21]([CH3:23])([CH3:22])[CH3:20])=[O:25])/[CH2:15][CH2:16][CH:17]=[CH2:18])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)[S@](N)=O
Reactant: C=CCCC(=O)C1CCN(Cc2ccccc2)CC1
Agent: [Ti+4]
Agent: CC[O-]
Solvent: C1CCOC1
Product: C=CCC/C(=N/[S@](=O)C(C)(C)C)C1CCN(Cc2ccccc2)CC1
Temperature: 70 °C
Yield: 42.2 %

Procedure:
A solution of 1-(1-benzylpiperidin-4-yl)pent-4-en-1-one (6.11 g, 21.3 mmol) and (R)-2-methylpropane-2-sulfinamide (3.62 g, 27.6 mmol) in THF (71 mL, 0.3 M) was treated with titanium (IV) ethoxide (12.6 g, 55.3 mmol) and heated to 70° C. overnight. Because the reaction was incomplete, additional portions of (R)-2-methylpropane-2-sulfinamide (1.81 g, 13.8 mmol) and titanium (IV) ethoxide (6.3 g, 27.7 mmol) were added and the mixture was heated to 75° C. for 6 more hours. The reaction was quenched by pouring it slowly into rapidly stirred saturated aqueous sodium chloride (100 mL) and filtering through Celite. The Celite pad was washed with ethyl acetate (3×) and the combined organics were washed with saturated aqueous sodium chloride, dried over MgSO4, and concentrated in vacuo. The residue was chromatographed on silica gel (60% ethyl acetate in heptane) to afford the desired product (3.24 g, 42%). Rf 0.44 (EtOAc). 1H NMR (CDCl3, 300 MHz) δ 7.34-7.19 (m, 5H), 5.88-5.75 (m, 1H), 5.09-4.94 (m, 2H), 3.50 (d, J=5.5 Hz, 2H), 2.97-2.83 (m, 2H), 2.74-2.70 (m, 1H), 2.55-2.23 (m, 4H), 2.00 (t, J=8.8 Hz, 2H), 1.77-1.63 (m, 4H), 1.23 (s, 9H). ESI MS found for C21H32N2OS m/z [361.4 (M+1)].
Reaction SMILES: C1C=CC=CC=1.[C:7]1([CH3:15])[CH:12]=[C:11]([CH3:13])[CH:10]=[C:9]([CH3:14])[CH:8]=1.O=O.C1(C2C=CC=CC=2)C=CC=CC=1.CC1C=C(C)C=C(C)C=1C1C=CC=CC=1.CC1C=C(C)C=C(C)C=1CC1C=C(C)C=C(C)C=1.C1([OH:69])C=CC=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(O)(=O)C>[CH3:15][C:7]1[CH:12]=[C:11]([CH3:13])[CH:10]=[C:9]([CH3:14])[C:8]=1[OH:69]
Reactant: Oc1ccccc1
Reactant: Cc1cc(C)cc(C)c1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1cc(C)c(-c2ccccc2)c(C)c1
Solvent: c1ccccc1
Solvent: CC(=O)O
Solvent: c1ccc(-c2ccccc2)cc1
Product: Cc1cc(C)c(O)c(C)c1
Yield: 50 %

Procedure:
In a flask, 1.17 g (15 mmol) of benzene, 1.38 g (11 mmol) of mesitylene, 4.5 mg (0.02 mmol) of palladium(II) acetate, 323 mg (about 0.14 mmol) of H4PMo11V1O40-nH2O, and 10 ml of acetic acid were placed and were stirred at a constant temperature of 90° C. in an atmosphere of oxygen gas at 1 atm (0.1 MPa) for 15 hours. The resulting reaction mixture was analyzed by gas chromatography to find that 0.59 g (3.8 mmol) of biphenyl, 0.82 g (4.2 mmol) of 1,3,5-trimethyl-2-phenylbenzene, 0.85 g (3.6 mmol) of 1,3,5-trimethyl-2-(3′,5′-dimethylbenzyl)benzene, 0.13 g (1.4 mmol) of phenol, and 0.10 g (0.7 mmol) of 2,4,6-trimethylphenol were produced.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[N+:8]([O-:10])=[O:9].[F:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][NH2:19])=[CH:14][CH:13]=1.C(=O)([O-])[O-].[Na+].[Na+]>O>[F:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][NH:19][C:2]2[CH:7]=[CH:6][N:5]=[CH:4][C:3]=2[N+:8]([O-:10])=[O:9])=[CH:14][CH:13]=1
Reactant: NCc1ccc(F)cc1
Reactant: O=[N+]([O-])c1cnccc1Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Product: O=[N+]([O-])c1cnccc1NCc1ccc(F)cc1
Temperature: 50 °C
Reaction time: 1 h
Yield: 75 %

Procedure:
A mixture of 90 parts of 4-chloro-3-nitropyridine, 71 parts of 4-fluorobenzenemethanamine, 63 parts of sodium carbonate and 900 parts of N,N-diamethylacetamide was stirred for 1 hour at 50° C. Water was added and the product was extracted with 4-methyl-2-pentanone. The extract was dried, filtered and evaporated. The residue was crystallized from acetonitrile. The product was filtered off and dried, yielding 106 parts (75%) of N-[(4-fluorophenyl)methyl]-3-nitro-4-pyridinamine; mp. 136.8° C. (intermediate 1).
Reaction SMILES: [C:1]1([P:7]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:8][CH2:9][NH2:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:17]1([CH:23]=O)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1>C(O)C>[CH:17]1([CH:23]=[N:10][CH2:9][CH2:8][P:7]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1
Reactant: O=CC1CCCCC1
Reactant: NCCP(c1ccccc1)c1ccccc1
Solvent: CCO
Product: C(=NCCP(c1ccccc1)c1ccccc1)C1CCCCC1
Yield: 98 %

Procedure:
Under argon, a solution of 2-diphenylphosphino-ethylamine (619.0 mg, 2.7 mmol) and cyclohexane carbaldehyde (306.2 mg, 2.73 mmol) in ethanol (15 mL) was heated at 65° C. (oil bath) for 4 h. Then, the solvent was removed in-vacuo to give the desired product (>98% by 1H-NMR) as a colourless liquid (880.5 mg, 2.7 mmol, quantitative).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][C:5]([S:8](Cl)(=[O:10])=[O:9])=[CH:4][CH:3]=1.S([O-])([O-])=O.[Na+].[Na+].S(Cl)(Cl)(=O)=O.[OH-].[Na+].[Cl-].[Na+]>O>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([S:8]([OH:10])=[O:9])=[CH:4][CH:3]=1
Reactant: O=S(=O)(Cl)c1ccc(Cl)nc1
Agent: O=S([O-])[O-]
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: O=S(=O)(Cl)Cl
Product: O=S(O)c1ccc(Cl)nc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Finely powdered 6-chloro-3-pyridinesulfonyl chloride (1), (20 g, 94.31 mMole) was gradually added over a 30 minute period, to a solution of sodium sulfite (12 g, 94.31 mMole) in water (200 mL), with good stirring. During the addition of the sulfonyl chloride the temperature of the solution was maintained at approximately 20° C. with the aid of ice/water and the pH kept at approximately 7 with the addition of 3N-sodium hydroxide (50-60 mL). After all of the sulfonyl chloride had been added the resulting solution was stirred at room temperature for an additional 60 minutes. To the solution was then added solid sodium chloride to get a near saturated solution which was then stored at 4° C. overnight. The solid product was then filtered off and air dried. Yield 18.1 g.
Reaction SMILES: [I-:1].[N:2]1([C:6]2[CH:15]=[CH:14][C:13]3[N+:12]4[CH:16]=[C:17]5[CH:26]=[CH:25][C:24]6[CH:23]=[C:22]([CH2:27][CH3:28])[CH:21]=[CH:20][C:19]=6[N:18]5[C:11]=4[CH:10]=[CH:9][C:8]=3[CH:7]=2)[CH2:5][CH2:4][CH2:3]1.[CH3:29]O>>[I-:1].[N:2]1([C:6]2[CH:15]=[CH:14][C:13]3[N+:12]4[CH:16]=[C:17]5[CH:26]=[CH:25][C:24]6[CH:23]=[C:22]([CH2:27][CH2:28][CH3:29])[CH:21]=[CH:20][C:19]=6[N:18]5[C:11]=4[CH:10]=[CH:9][C:8]=3[CH:7]=2)[CH2:5][CH2:4][CH2:3]1
Reactant: CCc1ccc2c(ccc3c[n+]4c5ccc(N6CCC6)cc5ccc4n32)c1
Reactant: CO
Agent: [I-]
Product: CCCc1ccc2c(ccc3c[n+]4c5ccc(N6CCC6)cc5ccc4n32)c1

Procedure:
3-(1-Azetidinyl)-10-ethylimidazo[1,2-a:3,4-a']diquinolin-15-ium Iodide; m.p. 246°-256° C., from methanol.