Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[NH2:2][CH2:3][CH2:4][C:5]([NH:7][CH2:8][CH:9]1[O:23][C:12]2=[C:13]3[C:18](=[C:19]([CH3:21])[CH:20]=[C:11]2[CH2:10]1)[NH:17][C:16](=[O:22])[CH:15]=[CH:14]3)=[O:6].[H][H].CO>O.[Pd]>[NH2:2][CH2:3][CH2:4][C:5]([NH:7][CH2:8][CH:9]1[O:23][C:12]2=[C:13]3[C:18](=[C:19]([CH3:21])[CH:20]=[C:11]2[CH2:10]1)[NH:17][C:16](=[O:22])[CH2:15][CH2:14]3)=[O:6]
Reactant: Cc1cc2c(c3ccc(=O)[nH]c13)OC(CNC(=O)CCN)C2
Reactant: [H][H]
Agent: [Pd]
Agent: Cl
Solvent: O
Solvent: CO
Product: Cc1cc2c(c3c1NC(=O)CC3)OC(CNC(=O)CCN)C2
Yield: 73.5 %

Procedure:
A hydrochloric acid salt of 2-(β-Alanylaminomethyl)-5-methyl-2,3,6,7-tetrahydrofuro-[2,3-f]quinoline-7-one (1.10 g, 3.26 mmol) was dissolved in water (50 ml). To the obtained solution, 10% palladium-on-carbon (1.10 g) was added, followed by stirring at 80° C. for 3 hours in the atmosphere of hydrogen. The reaction mixture was filtered, and the filtrate was condensed under reduced pressure. The resultant residue was submitted to a recrystallizing procedure using methanol to obtain 727 mg of the title compound as colorless powdery crystals (66.1%).
Reaction SMILES: Br[C:2]1[C:3]([Cl:29])=[CH:4][C:5]([N+:26]([O-:28])=[O:27])=[C:6]([NH:8][CH2:9][CH:10]2[CH2:25][CH2:24][CH2:23][C:12]3([O:16][C:15](=[O:17])[N:14]([CH2:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:13]3)[CH2:11]2)[CH:7]=1.[Cu][C:31]#[N:32]>CN(C=O)C.[Cl-].[Na+].O>[Cl:29][C:3]1[CH:4]=[C:5]([N+:26]([O-:28])=[O:27])[C:6]([NH:8][CH2:9][CH:10]2[CH2:25][CH2:24][CH2:23][C:12]3([O:16][C:15](=[O:17])[N:14]([CH2:18][C:19]([CH3:20])([CH3:21])[CH3:22])[CH2:13]3)[CH2:11]2)=[CH:7][C:2]=1[C:31]#[N:32]
Reactant: CC(C)(C)CN1CC2(CCCC(CNc3cc(Br)c(Cl)cc3[N+](=O)[O-])C2)OC1=O
Reactant: N#C[Cu]
Agent: [Cl-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)CN1CC2(CCCC(CNc3cc(C#N)c(Cl)cc3[N+](=O)[O-])C2)OC1=O
Temperature: 180 °C
Reaction time: 0.33 h

Procedure:
A suspension containing 7-(((5-bromo-4-chloro-2-nitrophenyl)amino)methyl)-3-neopentyl-1-oxa-3-azaspiro[4.5]decan-2-one (0.260 g, 0.532 mmol) and copper (I) cyanide (0.333 g, 3.72 mmol) in DMF (2 mL) was subject to microwave heating at 180° C. for 1.5 h. The reaction was cooled to rt, diluted with brine solution, and stirred for 20 min. The mixture was filtered through a pad of celite, and the celite was washed with EtOAc. The combined filtrates were washed with EtOAc. The combined organics were washed with water, dried over magnesium sulfate, filtered, and concentrated. The crude product was purified on a 24 g silica gel column (0-75% EtOAc/hexanes, 15 min gradient; 75% EtOAc/hexanes, 10 min; 35 mL/min elution; 254 nm detection) to afford the title compound as an orange solid. MS (m/z) 435.2 (M+H+).
Reaction SMILES: [CH3:1][CH:2]([CH3:17])[CH2:3][N:4]1[C:16]2[C:15]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[N:9]=[CH:8][C:7]=2[N:6]=[CH:5]1.C([Li])CCC.[CH:23](=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>O1CCCC1>[CH3:1][CH:2]([CH3:17])[CH2:3][N:4]1[C:16]2[C:15]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[N:9]=[CH:8][C:7]=2[N:6]=[C:5]1[CH:23]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[OH:30]
Reactant: CC(C)Cn1cnc2cnc3ccccc3c21
Reactant: O=Cc1ccccc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CC(C)Cn1c(C(O)c2ccccc2)nc2cnc3ccccc3c21
Temperature: -78 °C

Procedure:
1-(2-Methylpropyl)-1H-imidazo[4,5-c]quinoline (4 g; 0.017 mol) was dissolved in tetrahydrofuran (50 mL) then cooled to −78° C. A 7.75 mL portion of n-butyl lithium (2.5 M in hexanes) was added dropwise to the cooled solution. At 15 minutes post addition, benzaldehyde (2.7 mL; 0.027 mol) was added and the reaction mixture was allowed to warm slightly. The reaction was quenched with water then diluted with ethyl ether. The ether was separated, dried with magnesium sulfate then concentrated under vacuum. The resulting residue was purified by silica gel chromatography using 5% methanol in methylene chloride as the eluent to give an oily yellow solid. This material was recrystallized from methylene chloride/hexane to provide a white crystalline solid, m.p. 160-166° C. Analysis: Calculated: C, 76.1; H, 6.4; N, 12.7; Found: C, 75.9; H, 6.3; N, 12.7.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH:9]([OH:13])[CH2:10][CH:11]=[CH2:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:14]([Si:17]([CH3:20])([CH3:19])[CH3:18])C=C.CCCCCC.CCOCC>C(Cl)Cl.CC1C=C(C)C(N2C(=[Ru](Cl)(Cl)=CC3C=CC=CC=3OC(C)C)N(C3C(C)=CC(C)=CC=3C)CC2)=C(C)C=1>[C:1]1([CH2:7][CH2:8][CH:9]([OH:13])[CH2:10][CH:11]=[CH:12][CH2:14][Si:17]([CH3:20])([CH3:19])[CH3:18])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: C=CCC(O)CCc1ccccc1
Reactant: C=CC[Si](C)(C)C
Agent: Cc1cc(C)c(N2CCN(c3c(C)cc(C)cc3C)C2=[Ru](Cl)(Cl)=Cc2ccccc2OC(C)C)c(C)c1
Solvent: ClCCl
Solvent: CCCCCC
Solvent: CCOCC
Product: C[Si](C)(C)CC=CCC(O)CCc1ccccc1
Temperature: 25 °C
Yield: 60.6 %

Procedure:
To a round-bottomed flask containing 1-phenyl-hex-5-en-3-ol (495 mg, 2.8 mmol, 1 eq) in DCM (12 mL) was added allyltrimethylsilane (1.79 mL, 11.2 mmol, 4 eq). Hoveyda-Grubbs' Catalyst (44 mg, 0.07 mmol, 0.025 eq) was subsequently added as a solid and left to stir at room temperature under an atmosphere of argon. After 72 hours a further equivalent of allyltrimethylsilane was added (0.445 mL, 2.78 mmol). After 7 days the reaction mixture was concentrated under reduced pressure to a dark brown oil. Column chromatography (hexane:ether, 100:0, 9:1, 85:15) gave 1-phenyl-7-(trimethylsilyl)-hept-5-en-3-ol as a colourless oil (445 mg, 61% yield). For major isomer E: 1H NMR (400 MHz, CDCl3) δ 0.006 (s, 9H, SiMe3), 1.47-1.49 (d, 2H, CH2SiMe3, J=8 Hz), 1.74-1.84 (mn, 2H, CH2CH2CHOH), 2.06-2.14 (m, 1H, CHOHCH2CH), 2.20-2.31 (m, 1H, CHOHCH2CH), 2.66-2.74 (m, 1H, PhCH2), 2.79-2.86 (m, 1H, PhCH2), 3.57-3.63 (m, 1H, CHOH), 5.21-5.28 (dt, 1H, CH2CHCH, J=15.2 Hz, 8 Hz), 5.50-5.58 (dt, 1H, CH2CHCH, J=15.2 Hz, 8 Hz), 7.18-7.24 (m, 3H, Ph), 7.27-7.31 (m, 2H, Ph); 13C NMR (100 MHz, CDCl3) δ −2.0 (SiMe3), 23.0 (CH2SiMe3), 32.1 (PhCH2), 38.3 (PhCH2CH2), 41.0 (CHOHCH2), 70.2 (CHOH), 123.8 (CHCH), 125.7 (Ph), 128.4 (Ph), 130.9 (CHCH), 142.2 (Ph). For minor isomer Z: 1H NMR (400 MHz, CDCl3) δ 0.012 (s, 9H, SiMe3), 1.47-1.49 (d, 2H, CH2SiMe3, J=8 Hz), 1.74-1.84 (m, 2H, CH2CH2CHOH), 2.06-2.14 (m, 1H, CHOHCH2CH), 2.20-2.31 (m, 1H, CHOHCH2CH), 2.66-2.74 (m, 1H, PhCH2), 2.79-2.86 (m, 1H, PhCH2), 3.64-3.69 (m, 1H, CHOH), 5.30-5.35 (dt, 1H, CH2CHCH, J=10.4 Hz, 8 Hz), 5.61-5.66 (dt, 1H, CH2CHCH, J=10.4 Hz, 8 Hz), 7.18-7.24 (m, 3H, Ph), 7.27-7.31 (m, 2H, Ph); 13C NMR (100 MHz, CDCl3) δ −1.82 (SiMe3), 18.7 (CH2SiMe3), 32.1 (PhCH2), 31.5 (CHOHCH2), 38.4 (PhCH2CH2), 70.8 (CHOH), 122.4 (CHCH), 125.7 (Ph), 128.3 (Ph), 129.3 (CHCH), 142.1 (Ph); IR (v, cm−1) 3383 (OH), 3063 (ArH), 1667 (C═C), 1604 (Ar), 1496 (Ar), 850 (Si—C). MS (GCT, CI+) m/z 280.2101 [M+NH4]+ HRMS required for C16H26OSiNH4: 280.2097, found 280.2101.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11]2[C:23](=[O:24])[N:22]([CH3:25])[C:14]3[N:15]=[C:16](S(C)=O)[N:17]=[CH:18][C:13]=3[CH:12]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[NH2:26][C:27]1[CH:35]=[C:34]2[C:30]([CH:31]=[CH:32][NH:33]2)=[CH:29][CH:28]=1.Cl[C:37]1C=CC(N)=C[CH:38]=1>>[NH:33]1[C:34]2[C:30](=[CH:29][CH:28]=[C:27]([NH:26][C:16]3[N:17]=[CH:18][C:13]4[CH:12]=[C:11]([S:8]([C:5]5[CH:6]=[CH:7][CH:2]=[CH:3][CH:4]=5)(=[O:10])=[O:9])[C:23](=[O:24])[N:22]([CH2:25][CH2:37][CH3:38])[C:14]=4[N:15]=3)[CH:35]=2)[CH:31]=[CH:32]1
Reactant: Nc1ccc2cc[nH]c2c1
Reactant: Nc1ccc(Cl)cc1
Reactant: Cn1c(=O)c(S(=O)(=O)c2ccc(Cl)cc2)cc2cnc(S(C)=O)nc21
Product: CCCn1c(=O)c(S(=O)(=O)c2ccccc2)cc2cnc(Nc3ccc4cc[nH]c4c3)nc21

Procedure:
The title compound was prepared according to the procedure of Example 3, substituting 2-(methylsulfinyl)-6-(phenylsulfonyl)-8-propylpyrido[2,3-d]pyrimidin-7(8H)-one for 6-(4-chlorophenylsulfonyl)-8-methyl-2-(methylsulfinyl)pyrido[2,3-d]pyrimidin-7(8H)-one, and 6-aminoindole for 4-chloroaniline.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[C:7]([CH2:10][CH2:11][O:12][CH2:13][C:14](N3CCCCC3)=[O:15])[CH:8]=[CH:9][C:2]1=2.[OH-:22].[Na+]>C(O)C.O>[S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[C:7]([CH2:10][CH2:11][O:12][CH2:13][C:14]([OH:15])=[O:22])[CH:8]=[CH:9][C:2]1=2
Reactant: O=C(COCCc1ccc2sccc2c1)N1CCCCC1
Reactant: [OH-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: O=C(O)COCCc1ccc2sccc2c1
Yield: 74.6 %

Procedure:
In a mixture of 58 mL of ethanol and 6 mL of water is dissolved 6.40 g of 2-(2-benzo[b]thiophen-5-ylethoxy)-1-piperidino-1-ethanone, to which is added 1.27 g of sodium hydroxide. The mixture is heated under reflux for 4 hours. After cooling the mixture, the deposited matter is collected by filtration. The deposited matter is added to a mixture of ethyl acetate and water, pH is adjusted to 1.5 with 2 mol/L hydrochloric acid, and the organic layer is separated. The organic layer is washed with water and saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and the solvent is distilled off under reduced pressure to obtain 3.72 g of 2-(2-benzo[b]thiophen-5-ylethoxy)-acetic acid as a colorless crystalline product.
Reaction SMILES: [H-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][N:8]=[C:7]2[CH:13]=[O:14].[CH3:15][Si:16]([CH2:19][CH2:20][O:21][CH2:22]Cl)([CH3:18])[CH3:17]>CN(C=O)C>[Br:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH2:22][O:21][CH2:20][CH2:19][Si:16]([CH3:18])([CH3:17])[CH3:15])[N:8]=[C:7]2[CH:13]=[O:14]
Reactant: O=Cc1n[nH]c2ccc(Br)cc12
Reactant: C[Si](C)(C)CCOCCl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: C[Si](C)(C)CCOCn1nc(C=O)c2cc(Br)ccc21
Temperature: 25 °C
Reaction time: 2 h
Yield: 100 %

Procedure:
To a suspension of NaH (6.6 g, 166 mmol, 1.10 eq) in DMF (500 mL) was added a solution of 5-bromo-1H-indazole-3-carbaldehyde (X) (34.0 g, 151 mmol, 1.00 eq) in DMF (50 mL) dropwise at 0° C. over a period of 30 min. The mixture was stirred at room temperature for 2 h, then SEM-Cl (26.4 g, 159 mmol, 1.08 eq) was added dropwise and the mixture was stirred at room temperature for another 3 h. Then the mixture was poured into an ice-water mixture (1000 mL) and extracted with EtOAc (300 mL×3), the organic phases were combined, dried over Na2SO4, filtered and concentrated in vacuo, the resultant residue was purified by flash chromatography on silica gel (PE:EtOAc=20:1→10:1) to afford 5-bromo-1-((2-(trimethylsilyl) ethoxy)methyl)-1H-indazole-3-carb aldehyde (XIX) as a mixture of regioisomers (53.0 g, 151 mmol, 100% yield) as a yellow oil. ESIMS found for C14H19BrN2O2Si m/z 355 (M+H).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([CH3:8])[CH:5]=[CH:4][N:3]=1.[N+:9]([C:12]1[CH:19]=[CH:18][C:15]([CH:16]=O)=[CH:14][CH:13]=1)([O-:11])=[O:10].[C:20](OC(=O)C)(=[O:22])[CH3:21]>>[C:20]([NH:1][C:2]1[N:7]=[C:6]([CH:8]=[CH:16][C:15]2[CH:18]=[CH:19][C:12]([N+:9]([O-:11])=[O:10])=[CH:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1)(=[O:22])[CH3:21]
Reactant: CC(=O)OC(C)=O
Reactant: O=Cc1ccc([N+](=O)[O-])cc1
Reactant: Cc1ccnc(N)n1
Product: CC(=O)Nc1nccc(C=Cc2ccc([N+](=O)[O-])cc2)n1

Procedure:
A solution of 2-amino-4-methylpyrimidine (32.74 g) in acetic anhydride (150 ml) was refluxed for one hour under stirring. To the above solution was added 4-nitrobenzaldehyde (49.8 g) and the resultant mixture was refluxed for 7 hours under stirring. The reaction mixture was cooled and the precipitate was collected by filtlation. The residue was washed with diethyl ether to give 2-acetamido-4-[2-(4-nitrophenyl)vinyl]pyrimidine (72.7 g).
Reaction SMILES: CS[C:3]1[N:8]2[CH:9]=[CH:10][N:11]=[C:7]2[CH:6]=[N:5][N:4]=1.[CH2:12]([NH2:18])[C:13]1[O:17][CH:16]=[CH:15][CH:14]=1>>[CH2:12]([NH:18][C:3]1[N:8]2[CH:9]=[CH:10][N:11]=[C:7]2[CH:6]=[N:5][N:4]=1)[C:13]1[O:17][CH:16]=[CH:15][CH:14]=1
Reactant: CSc1nncc2nccn12
Reactant: NCc1ccco1
Product: c1coc(CNc2nncc3nccn23)c1
Reaction time: 8 h

Procedure:
A 5.0 gm. portion of 5-(methylthio)-imidazo[1,2-d]-as-triazine is combined with 45 ml. of furfurylamine and refluxed for 2 hours. The mixture is allowed to stand at room temperature overnight. The gummy solid is collected and crystallized from 60 ml. of hot methanol, giving 2.75 gm. of the desired product as crystals, m.p. 212°-214° C.
Reaction SMILES: [O:1]([C:8]1[CH:27]=[CH:26][C:11]([O:12][C:13]2[CH:18]=[CH:17][N:16]=[CH:15][C:14]=2[C:19]2[CH:25]=[CH:24][C:22]([NH2:23])=[CH:21][CH:20]=2)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.CN1C[CH2:38][CH2:37][C:36]1=[O:40]>ClCCl>[O:1]([C:8]1[CH:9]=[CH:10][C:11]([O:12][C:13]2[CH:18]=[CH:17][N:16]=[CH:15][C:14]=2[C:19]2[CH:20]=[CH:21][C:22]([NH:23][C:36](=[O:40])[CH2:37][CH3:38])=[CH:24][CH:25]=2)=[CH:26][CH:27]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CN1CCCC1=O
Reactant: Nc1ccc(-c2cnccc2Oc2ccc(Oc3ccccc3)cc2)cc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: CCC(=O)Nc1ccc(-c2cnccc2Oc2ccc(Oc3ccccc3)cc2)cc1
Yield: 77 %

Procedure:
N-(4-(4-(4-phenoxyphenoxy)pyridin-3-yl)phenyl)propionamide was prepared from 4-(4-(4-phenoxyphenoxy)pyridin-3-yl)aniline and pyridine instead of N,N-diethylethanamine, 1-methylpyrrolidin-2-one, dichloromethane using Method G (77% yield). HPLC: 98%, RT=4.157 min. MS: m/z=411 [M+H]+, RT=3.39 min.
Reaction SMILES: C(O)(=O)C.[CH3:5][S:6]([C:9]1[CH:14]=[C:13]([CH:15]2[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)[CH:12]=[CH:11][C:10]=1[NH2:21])(=[O:8])=[O:7].[C:22]([O:26][C:27](=O)[O:28]C(C)(C)C)([CH3:25])([CH3:24])[CH3:23].C(=O)([O-])[O-].[Na+].[Na+]>ClCCl>[C:22]([O:26][C:27]([N:18]1[CH2:17][CH2:16][CH:15]([C:13]2[CH:12]=[CH:11][C:10]([NH2:21])=[C:9]([S:6]([CH3:5])(=[O:8])=[O:7])[CH:14]=2)[CH2:20][CH2:19]1)=[O:28])([CH3:25])([CH3:24])[CH3:23]
Reactant: CC(C)(C)OC(=O)OC(C)(C)C
Reactant: CS(=O)(=O)c1cc(C2CCNCC2)ccc1N
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CC(=O)O
Product: CC(C)(C)OC(=O)N1CCC(c2ccc(N)c(S(C)(=O)=O)c2)CC1
Temperature: 25 °C
Reaction time: 3 h
Yield: 37.8 %

Procedure:
To a solution of 2-methanesulfonyl-4-piperidin-4-yl-phenylamine; compound with acetic acid (1.5 g) in dichloromethane (30 ml) was added di-tert-butylcarbonate (1.15 g) and saturated aqueous sodium carbonate solution (10 ml). The reaction mixture was stirred at rt for 3 h and extracted with dichloromethane. The organic phases were dried and concentrated, and the residue was chromatographed on silica gel using heptane/ethyl acetate as eluent to obtain the desired compound (0.64 g) as an off-white solid. MS (ISP): 355.1 (M+H)+
Reaction SMILES: [CH3:1][N:2]([CH2:4][C:5]1[CH:10]=[CH:9][C:8]([CH:11]2[CH:20]([C:21]3[CH:26]=[CH:25][C:24]([CH2:27][N:28]([CH3:30])[CH3:29])=[CH:23][CH:22]=3)[C:19](=O)[C:18]3[C:17]([C:32](OCC)=[O:33])=[CH:16][C:15]([F:37])=[CH:14][C:13]=3[NH:12]2)=[CH:7][CH:6]=1)[CH3:3].O.[NH2:39][NH2:40]>CO>[CH3:1][N:2]([CH2:4][C:5]1[CH:10]=[CH:9][C:8]([CH:11]2[NH:12][C:13]3[C:18]4[C:19](=[N:39][NH:40][C:32](=[O:33])[C:17]=4[CH:16]=[C:15]([F:37])[CH:14]=3)[CH:20]2[C:21]2[CH:26]=[CH:25][C:24]([CH2:27][N:28]([CH3:30])[CH3:29])=[CH:23][CH:22]=2)=[CH:7][CH:6]=1)[CH3:3]
Reactant: NN
Reactant: CCOC(=O)c1cc(F)cc2c1C(=O)C(c1ccc(CN(C)C)cc1)C(c1ccc(CN(C)C)cc1)N2
Solvent: O
Solvent: CO
Product: CN(C)Cc1ccc(C2Nc3cc(F)cc4c(=O)[nH]nc(c34)C2c2ccc(CN(C)C)cc2)cc1
Temperature: 23 °C
Reaction time: 8 h
Yield: 20 %

Procedure:
A mixture of ethyl 2,3-bis(4-((dimethylamino)methyl)phenyl)-7-fluoro-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate (520 mg) in 85% hydrazine monohydrate (10 mL) and methanol (50 mL) was stirred at 23° C. for overnight. Methanol was removed under reduced pressure. The mixture was filtered and washed with water to give the title compound (11 mg, yield 20%). LC-MS (ESI) m/z: 472 (M+1)+. 1H-NMR (400 MHz, CD3OD) δ (ppm): 2.09 (s, 12H), 3.31 (s, 4H), 4.22 (d, J=8.0 Hz, 1H), 4.67 (d, J=8.0 Hz, 1H), 6.80 (dd, 1H), 6.97-6.99 (m, 2H), 7.06-7.11 (m, 5H), 7.14-7.16 (m, 2H); 19F-NMR (400 MHz, CD3OD) δ (ppm): −105.58 (s).
Reaction SMILES: [N:1]1[CH2:2][CH2:3][CH2:4][CH2:5][CH:6]=1.[P:7]([O-:22])([O:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.N1CCCCC1P(=O)(O)O>>[NH:1]1[CH2:2][CH2:3][CH2:4][CH2:5][CH:6]1[P:7]([O:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)(=[O:22])[O:8][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1
Reactant: [O-]P(Oc1ccccc1)Oc1ccccc1
Reactant: C1=NCCCC1
Agent: O=P(O)(O)C1CCCCN1
Product: O=P(Oc1ccccc1)(Oc1ccccc1)C1CCCCN1
Temperature: 100 °C
Yield: 41 %

Procedure:
This compound was prepared from the trimer of 2,3,4,5-tetrahydropyridine and diphenyl phosphite using the procedure previously described for the synthesis of the diethyl ester (Solodenko, V. A., Kukhar, V. P., Synthesis of DL-(2-Piperidyl) Phosphonic Acid, Zh. Obsh. Khim. 1987, 57, 2392). A mixture of the trimer (10 mmol, 2.5 g) and diphenyl phosphite (30 mmol, 7.0 g) was heated for 1.5 h at 100° C. under argon. The resulted crude diphenyl piperidine-2-phosphonate was dissolved in 100 mL of dry ether, undisolved material was removed by filtration, and the solution was saturated with gaseous HCl. The precipitated hydrochloride 2 was collected by filtration, washed with ether, dried and recrystallized from acetone to give a white solid in 41% yield: top. 172°-174° C.; 1H-NMR (D2O), δ (ppm) 1.5-2.4 (m, 6H), 3.05 (m, 1H), 3.45 (m, 1H), 4.10 (m, 1H), 6.9-7.4 (m, 10H); MS (FAB) m/e 318 (M-Cl)+. Anal. (C17H21NO3PCl): C, H, N, Cl.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:16][Si:17]([C:20]#[CH:21])([CH3:19])[CH3:18]>C1COCC1.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:21]#[C:20][Si:17]([CH3:19])([CH3:18])[CH3:16])=[CH:4][CH:3]=1
Reactant: C#C[Si](C)(C)C
Reactant: Fc1ccc(I)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: C[Si](C)(C)C#Cc1ccc(F)cc1
Temperature: 23 °C
Reaction time: 18 h

Procedure:
4-Fluoroiodobenzene (112 mL, 0.97 mol) and triethylamine (176 mL, 1.26 mol) are dissolved in dry THF (1.2 L) and nitrogen gas was bubbled through the solution for about 20 min. Copper (I) iodide (1.08 g, 5.7 mmol) and bis(triphenyphosphine)palladium dichloride (2.15 g, 3 mmol) are added and then trimethylsilylacetylene (178 mL, 1.3 mol) was added dropwise over about 40 min with the temperature being maintained at about 23° C. A large amount of precipitate forms (presumably Et3NHCl) which necessitates mechanical stirring. Following complete addition of the trimethylsilylacetylene the mixture was allowed to stir at room temperature for about 18 h. The mixture was filtered and the solid washed with cyclohexane. The combined filtrates are concentrated under reduce pressure to give a brown oil. Application of this oil to a pad of silica gel followed by elution with cyclohexane gave a yellow solution. Removal of the solvent gave the title compound as a yellow oil; 182.8 g (95%).
Reaction SMILES: [C:1]([OH:8])(=O)[CH2:2][CH2:3][C:4]([CH3:6])=[O:5].C(N(CC)CC)C.ClC(OCC)=O.[CH2:22]([NH:26][CH2:27][CH2:28][CH2:29][CH3:30])[CH2:23][CH2:24][CH3:25]>CC(C)=O>[CH2:22]([N:26]([CH2:27][CH2:28][CH2:29][CH3:30])[C:1](=[O:8])[CH2:2][CH2:3][C:4](=[O:5])[CH3:6])[CH2:23][CH2:24][CH3:25]
Reactant: CCCCNCCCC
Reactant: CC(=O)CCC(=O)O
Agent: CCOC(=O)Cl
Solvent: CC(C)=O
Solvent: CCN(CC)CC
Product: CCCCN(CCCC)C(=O)CCC(C)=O
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 57.5 %

Procedure:
A! A solution of 100 g (0.86 mole) of levulinic acid in 1 l of acetone was added with 118 ml (0.86 mole) of triethylamine, and stirred for 15 minutes at room temperature. The mixture was cooled to 5° C. and added with a solution of ethyl chloroformate (83.3 ml, 0.86 mole) in 500 ml of acetone, then stirred for 15 minutes. The solid was filtered off and the mother liquor was added to a solution of dibutylamine (180 ml, 1 mole) in 1 l of acetone, then stirred overnight at room temperature, evaporated to dryness under vacuum, and the residue was dissolved in 1 l of ethyl ether, washed with 400 ml of 0.5N HCl, then with 400 ml of 0.5N sodium hydroxide. The ether phase was anhydrified over sodium sulfate and evaporated to dryness thus providing 175.5 g of a crude which by distillation under vacuum gave 112.5 g (yield: 57%) of N,N-dibutyl-4-oxo-pentanamide (b.p. 135°-138° C./1 mmHg).
Reaction SMILES: Cl[C:2](=[O:8])[C:3]([O:5][CH2:6][CH3:7])=[O:4].[Cl:9][C:10]1[CH:18]=[C:17]2[C:13]([CH:14]=[C:15]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[N:16]2[CH3:19])=[CH:12][CH:11]=1.ClCCl.O>ClCCCl.[Ti](Cl)(Cl)(Cl)Cl>[Cl:9][C:10]1[CH:18]=[C:17]2[C:13]([C:14]([C:2](=[O:8])[C:3]([O:5][CH2:6][CH3:7])=[O:4])=[C:15]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[N:16]2[CH3:19])=[CH:12][CH:11]=1
Reactant: CCOC(=O)c1cc2ccc(Cl)cc2n1C
Reactant: CCOC(=O)C(=O)Cl
Agent: Cl[Ti](Cl)(Cl)Cl
Solvent: ClCCCl
Solvent: ClCCl
Solvent: O
Product: CCOC(=O)C(=O)c1c(C(=O)OCC)n(C)c2cc(Cl)ccc12
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 84.5 %

Procedure:
4 ml (36.4 mmol) of titanium(IV) chloride are added to a solution of 4 ml (36 mmol) of ethyl chlorooxoacetate in 100 ml of 1,2-dichloroethane. The reaction mixture is stirred for 30 min at room temperature, 7.8 g (32.8 mmol) of ethyl 6-chloro-1-methyl-1H-indole-2-carboxylate are then added and the reaction mixture is stirred for 4 hours at room temperature. The mixture is cooled and 200 ml of dichloromethane and 100 ml of water are added. The organic phase is separated by settling, washed with water, dried over sodium sulphate, filtered and concentrated under reduced pressure and the residue is purified by chromatography on a column of silica gel. 9.4 g (27.7 mmol) of product are isolated.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[C:14](=[O:15])[N:13]=[N:12][NH:11]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[C:16]1([S:22][CH2:23][CH2:24]O)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([N:10]2[C:14](=[O:15])[N:13]([CH2:24][CH2:23][S:22][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[N:12]=[N:11]2)=[CH:8][CH:9]=1)([O-:3])=[O:2]
Reactant: O=c1nn[nH]n1-c1ccc([N+](=O)[O-])cc1
Reactant: OCCSc1ccccc1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: O=c1n(CCSc2ccccc2)nnn1-c1ccc([N+](=O)[O-])cc1
Yield: 90.5 %

Procedure:
1-(4-Nitrophenyl)-5-tetrazolone (Example 8) (153 mg, 0.74 mmol), 2-hydroxyethyl phenyl sulfide (0.1 mL, 0.74 mmol), and triphenylphosphine (194 mg, 0.74 mmol) were suspended in tetrahydrofuran (2.5 mL). Diethyl azodicarboxylate (0.12 mL, 0.74 mmol) was added dropwise. After 12 hours the mixture was concentrated in vacuo to an oil. Silica gel chromatography (9:1 hexane/ethyl acetate) afforded a solid (230 mg, 90%). 1H NMR (CDCl3, 300 MHz) δ 8.30 (d, 9.2 Hz, 2 H), 8.13 (d, 9.2 Hz, 2 H), 7.37 (d, 7.0 Hz, 2 H), 7.20 (d, 7.0 Hz, 2 H), 7.12 (m, 1 H), 4.19 (t, 6.6 Hz, 2 H), 3.32 (t, 6.6 Hz, 2 H); MS (CI) m/z 344 (MH+).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12]C)[CH:8]([CH3:14])[CH:7](C)[CH2:6][CH2:5]2.B(Br)(Br)Br.Cl[CH2:21]Cl>>[Br:1][C:2]1[C:11]([OH:12])=[CH:10][C:9]2[C:8]([CH3:14])([CH3:21])[CH2:7][CH2:6][CH2:5][C:4]=2[CH:3]=1
Reactant: ClCCl
Reactant: COc1cc2c(cc1Br)CCC(C)C2C
Agent: BrB(Br)Br
Product: CC1(C)CCCc2cc(Br)c(O)cc21
Temperature: 0 °C

Procedure:
To 6-bromo-7-methoxy-1,2-dimethyl-1,2,3,4-tetrahydro-naphthalene (Compound A-1 ([U.S. Pat. No. 6,613,917, incorporated herein by reference), 6.34 g, 23.56 mmol) in dichloromethane (10 mL) at −30° C. was added a solution of boron tribromide (1.0 M in dichloromethane, 47 mL, 47 mmol). After warming to 0° C. over 1 h, the reaction mixture was quenched carefully with ice water and extracted with ether. The organic layer was washed successively with water, brine, dried over Na2SO4, and concentrated in vacuo. Purification by flash column chromatography (silica gel, 5% ethyl acetate/hexane) yielded the title compound as a white solid.