Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[NH:16][CH:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1)=[CH:13][CH:12]=[CH:11][C:10]=2[O:22][CH3:23])=O)C.[N:24]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[C:33]([F:36])([F:35])[F:34])=[C:25]=[O:26]>>[CH:17]1([N:16]2[C:15]3[C:14]4[CH:13]=[CH:12][CH:11]=[C:10]([O:22][CH3:23])[C:9]=4[N:8]=[CH:7][C:6]=3[C:4](=[O:3])[N:24]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[C:33]([F:34])([F:35])[F:36])[C:25]2=[O:26])[CH2:18][CH2:19][CH2:20][CH2:21]1
Reactant: CCOC(=O)c1cnc2c(OC)cccc2c1NC1CCCC1
Reactant: O=C=Nc1ccccc1C(F)(F)F
Product: COc1cccc2c1ncc1c(=O)n(-c3ccccc3C(F)(F)F)c(=O)n(C3CCCC3)c12
Yield: 46.1 %

Procedure:
1-Cyclopentyl-7-methoxy-3-(2-trifluoromethyl-phenyl)-1H-pyrimido[5,4-c]quinoline-2,4-dione (21 mg) was prepared from 4-cyclopentylamino-8-methoxy-quinoline-3-carboxylic acid ethyl ester (0.1 mmol) and 1-isocyanato-2-trifluoromethyl-benzene (0.5 mmol) following general procedure C. LCMS: m/z 456 [M+1]+.
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([C:8]([C:13]#[N:14])=[CH:9][NH:10]2)=[CH:6][CH:5]=1)([O-])=O>CCO.[Pd]>[NH2:1][C:4]1[CH:12]=[C:11]2[C:7]([C:8]([C:13]#[N:14])=[CH:9][NH:10]2)=[CH:6][CH:5]=1
Reactant: N#Cc1c[nH]c2cc([N+](=O)[O-])ccc12
Agent: [Pd]
Solvent: CCO
Product: N#Cc1c[nH]c2cc(N)ccc12
Yield: 25.4 %

Procedure:
A suspention of 6-nitro-1H-indole-3-carbonitrile (4.6 g, 25 mmol) and 10% Pd—C (0.46 g) in EtOH (50 mL) was stirred under H2 (1 atm) at room temperature overnight. After filtration, the filtrate was concentrated and the residue was purified by column chromatography on silica gel (petroleum ether/ethyl acetate=3/1) to give 6-amino-1H-indole-3-carbonitrile (1.0 g, 98%) as a pink solid. 1H NMR (DMSO-d6) δ 11.51 (s, 1 H), 7.84 (d, J=2.4 Hz, 1 H), 7.22 (d, J=8.4 Hz, 1 H), 6.62 (s, 1H), 6.56 (d, J=8.4 Hz, 1 H), 5.0 (s, 2H); MS (ESI) (M+H+) 157.1.
Reaction SMILES: [CH:1]12[NH:18][CH:14]([CH2:15][CH2:16][CH2:17]1)[CH2:13][NH:12][CH2:11][CH2:10][NH:9][CH2:8][CH2:7][NH:6][CH2:5][CH2:4][NH:3][CH2:2]2.CO.[Cl-:21].[Mn+2:22].[Cl-:23]>CCO>[Cl:21][CH:13]1[NH:12][CH2:11][CH2:10][NH:9][CH2:8][CH2:7][NH:6][CH2:5][CH2:4][NH:3][CH2:2][CH:1]2[NH:18][C:14]1([Cl:23])[CH2:15][CH2:16][CH2:17]2.[Mn+2:22]
Reactant: [Cl-]
Reactant: C1CC2CNCCNCCNCCNCC(C1)N2
Agent: [Mn+2]
Solvent: CCO
Solvent: CO
Product: ClC1NCCNCCNCCNCC2CCCC1(Cl)N2
Temperature: 25 °C
Reaction time: 8 h
Yield: 72 %

Procedure:
3,6,9,12,18-Pentaazabicyclo[12.3.1]octadecane prepared as in Example 38C (0.405 g, 1.59 mmol) was added to a refluxing solution of anhydrous MeOH (50 ml) containing anhydrous manganese(II) chloride (0.200 g, 1.59 mmo) under a dry nitrogen atmosphere. After refluxing for 2 h, the solution was stirred overnight at room temperature. The solution was taken to dryness. The solid was dissolved in EtOH (10 ml) and the solution was filtered through celite. Ethyl ether was added to the filtrate which induced crystallization of a white solid. The solid was collected by filtration, washed with ethyl ether and dried in vacuo to give 0.43 g (72% yield) of a white solid as product: FAB mass spectrum (NBA) m/z (relative intensity) 380 (M+, 3), 345/347 [(M-Cl)+, 100/2]; Anal. calcd for C14H31N5MnCl2 : C, 40.96; H, 7.67; N, 18.37. Found: C,40.85; H, 7.72; N, 18.32.
Reaction SMILES: Cl.Cl.[N:3]12[CH2:10][CH2:9][CH:6]([CH2:7][CH2:8]1)[C@@H:5]([NH2:11])[CH2:4]2.[Br:12][C:13]1[O:17][C:16]([C:18](O)=[O:19])=[CH:15][CH:14]=1.O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[N:3]12[CH2:10][CH2:9][CH:6]([CH2:7][CH2:8]1)[C@@H:5]([NH:11][C:18]([C:16]1[O:17][C:13]([Br:12])=[CH:14][CH:15]=1)=[O:19])[CH2:4]2
Reactant: O=C(O)c1ccc(Br)o1
Reactant: N[C@H]1CN2CCC1CC2
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(N[C@H]1CN2CCC1CC2)c1ccc(Br)o1
Reaction time: 8 h
Yield: 54.7 %

Procedure:
A mixture of (R)-1-azabicyclo[2.2.2]oct-3-ylamine dihydrochloride (655 mg), 5-bromofuran-2-carboxylic acid (681 mg), 1-hydroxybenzotriazole hydrate (457 mg), O-benzotriazol-1-yl-N,N,N′-tetramethyluronium tetrafluoroborate (1.069 g), and N,N-diisopropylethylamine (2.5 mL) in N,N-dimethylformamide (10 mL) was agitated until a homogenous solution was obtained, and was then allowed to stand at room temperature overnight. The solution was evaporated, and the residue was partitioned between aqueous sodium hydroxide and chloroform. The chloroform layer was dried over magnesium sulfate, filtered, and evaporated and the residue was purified by chromatography on silica gel in a solid phase extraction cartridge using ammoniated methanol/chloroform mixtures as the eluent. The compound was then dissolved in tetrahydrofuran (20 mL), excess hydrogen chloride (5 mL; 1M solution in diethyl ether) was added, and the solution was evaporated and then recrystallised from methanol/diethyl ether to give the hydrochloride salt of the title compound as a colourless solid (538 mg); MS (ES+) 299, 301 (MH+).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][N:3]=1.[F:14][C:15]1[CH:16]=[C:17]([NH2:26])[CH:18]=[CH:19][C:20]=1[N:21]1[CH:25]=[CH:24][N:23]=[CH:22]1.CCN(C(C)C)C(C)C.O>CC#N.CCOC(C)=O>[Cl:1][C:2]1[N:7]=[C:6]([NH:26][C:17]2[CH:18]=[CH:19][C:20]([N:21]3[CH:25]=[CH:24][N:23]=[CH:22]3)=[C:15]([F:14])[CH:16]=2)[C:5]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][N:3]=1
Reactant: Nc1ccc(-n2ccnc2)c(F)c1
Reactant: CCOC(=O)c1cnc(Cl)nc1Cl
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Product: CCOC(=O)c1cnc(Cl)nc1Nc1ccc(-n2ccnc2)c(F)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 83.4 %

Procedure:
To a solution of ethyl 2,4-dichloropyrimidine-5-carboxylate (280 mg, 1.27 mmol) and 3-fluoro-4-(1H-imidazol-1-yl)benzenamine (230 mg, 1.30 mmol) in CH3CN (8 mL) at room temperature, DIEA (0.442 mL, 2.54 mmol) was added. The mixture was stirred at room temperature overnight. Water and EtOAc were added. The organic phase was separated, dried over Na2SO4, concentrated in vacuo to give ethyl 2-chloro-4-(3-fluoro-4-(1H-imidazol-1-yl)phenylamino)pyrimidine-5-carboxylate as a solid (383 mg). MS 362.4 and 364.3 (M+H, Cl pattern)
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[CH:12][C:7]([O:8][CH2:9][CH2:10][OH:11])=[CH:6][CH:5]=1)([O-:3])=[O:2].N1C=CN=C1.[CH3:19][C:20]([Si:23](Cl)([CH3:25])[CH3:24])([CH3:22])[CH3:21].CCCCCC.C(OCC)(=O)C>CN(C=O)C.O>[C:20]([Si:23]([CH3:25])([CH3:24])[O:11][CH2:10][CH2:9][O:8][C:7]1[CH:12]=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=1)([CH3:22])([CH3:21])[CH3:19]
Reactant: O=[N+]([O-])c1ccc(OCCO)cc1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Solvent: O
Product: CC(C)(C)[Si](C)(C)OCCOc1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of 2-(4-nitrophenoxy)ethanol (6.40 g) in DMF were added imidazole (4.75 g) and TBDMSCl (6.84 g) and reaction mixture was stirred at room temperature for 1 hr. The reaction was monitored on TLC using hexane:ethyl acetate (7:3) as mobile phase. After completion of the reaction, water was added and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and the solvent removed under reduced pressure. The crude material was purified by column chromatography eluted with 6% ethyl acetate in hexane to give, after concentration, 10 g of tert-butyldimethyl(2-(4-nitrophenoxy)ethoxy)silane.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[C:11]([Cl:17])[CH:10]=2)[N:5]=[C:4]([NH:18][CH:19]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[CH:3]=1.[OH:26][CH:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1.C(N(CC)CC)C>C(O)CCC>[Cl:17][C:11]1[CH:10]=[C:9]([NH:8][C:6]2[N:7]=[C:2]([N:30]3[CH2:31][CH2:32][CH:27]([OH:26])[CH2:28][CH2:29]3)[CH:3]=[C:4]([NH:18][CH:19]3[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)[N:5]=2)[CH:14]=[CH:13][C:12]=1[O:15][CH3:16]
Reactant: OC1CCNCC1
Reactant: COc1ccc(Nc2nc(Cl)cc(NC3CCCCCC3)n2)cc1Cl
Solvent: CCN(CC)CC
Solvent: CCCCO
Product: COc1ccc(Nc2nc(NC3CCCCCC3)cc(N3CCC(O)CC3)n2)cc1Cl
Yield: 23 %

Procedure:
To a solution of compound 6-chloro-N2-(3-chloro-4-methoxy-phenyl)-N4-cycloheptyl-pyrimidine-2,4-diamine (0.15 g, 0.39 mmol) in 1-butanol (5 mL) was added 4-hydroxypiperidine (0.12 g, 1.18 mmol) at 25° C. with stirring. To this triethylamine (0.43 mL, 3.15 mmol) was added dropwise and the mixture was stirred at 25° C. for 30 minutes. This was heated and refluxed for 12 hours under nitrogen atmosphere. The mixture was concentrated under vacuum, diluted with cold water (30 mL) and extracted with ethyl acetate (2×30 mL). The organic layers were collected, combined, washed with brine (30 mL), dried over anhydrous sodium sulphate, and concentrated under vacuum to give the desired compound. Yield: 23%.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)=[CH:10][C:11]([N:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)=O)=[CH:5][CH:4]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:36])=CC=1.O>C1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)=[CH:10][C:11]([N:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)=[S:36])=[CH:5][CH:4]=1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: COc1ccc(C(=CC(=O)N2CCNCC2)c2ccc(OC)cc2)cc1
Solvent: O
Solvent: c1ccccc1
Product: COc1ccc(C(=CC(=S)N2CCNCC2)c2ccc(OC)cc2)cc1
Temperature: 25 °C
Yield: 97.5 %

Procedure:
1.155 g of the 1-[3,3-bis(4-methoxyphenyl)acryloyl]piperazine [prepared as described in step (a) above] were dissolved in 12 ml of benzene, and the resulting solution was heated under reflux for 2 hours with 1.326 g of Lawesson's Reagent. At the end of this time, the reaction mixture was cooled to room temperature, after which it was poured into water and extracted twice with ethyl acetate. The combined extracts were washed with water, dried over anhydrous sodium sulfate, and concentrated by evaporation under reduced pressure. The residue was purified by column chromatography through 30 g of silica gel eluted with a 19:1 by volume mixture of methylene chloride and methanol, to give 1.177 g of 1-[3,3-bis(4-methoxyphenyl)thioacryloyl]piperazine as a powder.
Reaction SMILES: [CH2:1]1[O:3][CH:2]1[CH2:4][OH:5].N1C=CC=CC=1.[CH3:12][O:13][C:14]([CH2:16][C:17]1[CH:25]=[CH:24][C:20]([C:21](Cl)=[O:22])=[CH:19][CH:18]=1)=[O:15]>CCOCC>[CH3:12][O:13][C:14]([CH2:16][C:17]1[CH:25]=[CH:24][C:20]([C:21]([O:5][CH2:4][CH:2]2[O:3][CH2:1]2)=[O:22])=[CH:19][CH:18]=1)=[O:15]
Reactant: OCC1CO1
Reactant: COC(=O)Cc1ccc(C(=O)Cl)cc1
Solvent: CCOCC
Solvent: c1ccncc1
Product: COC(=O)Cc1ccc(C(=O)OCC2CO2)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A mixture containing 14.8 g (0.2 mole) of glycidol, 150 ml of anhydrous ether, 16 g (0.4 mole of pyridine and 43 g (0.2 mole) of 4-[(methoxycarbonyl)methyl]benzoyl chloride is stirred at room temperature for two hours. The mixture is filtered and the ether evaporated to leave an oil. This oil is distilled to give a colorless oil.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:18]=[CH:17][C:16]([CH:19]2[CH2:23][CH2:22][CH2:21][N:20]2[S:24]([CH3:27])(=[O:26])=[O:25])=[CH:15][CH:14]=1.CC(=CC)C.Cl([O-])=[O:34].[Na+].P([O-])([O-])([O-])=O.[Na+].[Na+].[Na+].S([O-])([O-])=O.[Na+].[Na+]>C(#N)C.C(O)(C)(C)C.O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:34])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:18]=[CH:17][C:16]([CH:19]2[CH2:23][CH2:22][CH2:21][N:20]2[S:24]([CH3:27])(=[O:26])=[O:25])=[CH:15][CH:14]=1
Reactant: CS(=O)(=O)N1CCCC1c1ccc(-c2cc3c(C=O)c[nH]c3cc2Cl)cc1
Reactant: [O-][Cl+][O-]
Agent: CC=C(C)C
Agent: O=P([O-])([O-])[O-]
Agent: O=S([O-])[O-]
Solvent: O
Solvent: CC(C)(C)O
Solvent: CC#N
Product: CS(=O)(=O)N1CCCC1c1ccc(-c2cc3c(C(=O)O)c[nH]c3cc2Cl)cc1
Temperature: 0 °C
Reaction time: 8 h
Yield: 50.4 %

Procedure:
To a mixture of 6-chloro-5-{4-[1-(methylsulfonyl)pyrrolidin-2-yl]phenyl}-1H-indole-3-carbaldehyde (75 mg, 0.19 mmol) in acetonitrile/t-butanol (4.5 mL/4.5 mL) was added 2-methyl-2-butene (3.00 mL, 28.2 mmol). The reaction mixture was cooled to 0° C. followed by the addition of an aqueous solution of sodium chlorite (377 mg, 5.58 mmol) and sodium phosphate (monobasic and monohydrate, 770 mg, 5.58 mmol) in water (9 mL) dropwise via additional funnel. The ice bath was removed and the reaction was stirred at room temperature overnight. The following morning, 2-methyl-2-butene (1.50 mL, 14.1 mmol) and an aqueous solution of sodium chlorite (125 mg, 1.86 mmol) and sodium phosphate (monobasic and monohydrate, 257 mg, 1.86 mmol) in water (3 mL) was added in a dropwise manner. The reaction was allowed to stir overnight at room temperature. The reaction was quenched with sodium sulfite (940 mg, 7.44 mmol) in water (3 mL). The reaction mixture was concentrated under reduced pressure to remove the volatile organics. The aqueous layer was extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by reverse phase HPLC to give the desired product (40.1 mg, 51.2% yield). MS (ES+) 441.0 (M+Na)+. 1H NMR (400 MHz, DMSO-d6) δ 11.95 (s, 1H), 8.07 (s, 1H), 7.95 (s, 1H), 7.64 (s, 1H), 7.40 (m, 4H), 4.94-4.91 (m, 1H), 3.51-3.49 (s, 2H), 2.95 (s, 3H), 2.40-2.30 (m, 1H), 1.91-1.86 (m, 3H).
Reaction SMILES: Br[C:2]1[S:3][C:4]([CH3:7])=[CH:5][CH:6]=1.[CH2:8]([C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:21]=[CH:20][C:19](B(O)O)=[C:18]([F:25])[CH:17]=2)=[CH:12][CH:11]=1)[CH3:9].C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.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>[CH2:8]([C:10]1[CH:11]=[CH:12][C:13]([C:16]2[CH:21]=[CH:20][C:19]([C:2]3[S:3][C:4]([CH3:7])=[CH:5][CH:6]=3)=[C:18]([F:25])[CH:17]=2)=[CH:14][CH:15]=1)[CH3:9]
Reactant: CCc1ccc(-c2ccc(B(O)O)c(F)c2)cc1
Reactant: Cc1ccc(Br)s1
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: Cc1ccccc1
Product: CCc1ccc(-c2ccc(-c3ccc(C)s3)c(F)c2)cc1

Procedure:
A mixture of 5.0 g (28.2 mmol) of 2-bromo-5-methylthiophene, 7.70 g (28.3 mmol) of 4′-ethyl-3-fluoro-4-biphenylboronic acid, 1.70 g (1.47 mmol) of tetrakis(triphenylphosphine)palladium(0) and 30 ml of 2 N sodium carbonate solution in 90 ml of toluene/ethanol (1:2) is refluxed for 3 h. After cooling, the organic phase is separated off, and the aqueous phase is extracted a number of times with toluene. The combined organic phases are washed with water and sat. sodium chloride solution. The solution is dried using sodium sulfate and evaporated to dryness. The residue is purified by column chromatography (SiO2, n-heptane:toluene=97:3). The further purification is carried out by recrystallisation from ethanol and n-heptane, giving 2-(4′-ethyl-3-fluorobiphenyl-4-yl)-5-methylthiophene as a colourless solid (m.p. 102° C.).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:15]2[C:23]3[C:18](=[C:19]([CH2:24][S:25][CH3:26])[CH:20]=[CH:21][CH:22]=3)[NH:17][CH:16]=2)[CH2:9][C:10](OCC)=[O:11])=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].Cl>C1COCC1>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([C:15]2[C:23]3[C:18](=[C:19]([CH2:24][S:25][CH3:26])[CH:20]=[CH:21][CH:22]=3)[NH:17][CH:16]=2)[CH2:9][CH2:10][OH:11])=[CH:6][CH:7]=1
Reactant: CCOC(=O)CC(c1ccc(C)cc1)c1c[nH]c2c(CSC)cccc12
Agent: Cl
Agent: [Al+3]
Agent: [H-]
Solvent: C1CCOC1
Product: CSCc1cccc2c(C(CCO)c3ccc(C)cc3)c[nH]c12

Procedure:
A solution of 2.41 g (6.57 mmol) of the compound from Example 100A in 20 ml of THF was added dropwise to 23 ml (23.0 mmol) of a 1N lithium aluminum hydride solution in THF under argon in 80 ml of THF at RT. 1N hydrochloric acid was then added, the mixture was extracted with dichloromethane, and the organic phase was dried over magnesium sulfate, filtered and concentrated. The crude product was purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% formic acid) to result in 1.77 g (83% of theory) of the title compound.
Reaction SMILES: [OH-].[Na+].[CH:3]1[CH2:7][CH:6]=[CH:5][CH:4]=1.[CH3:8][CH2:9][CH:10](Br)[CH2:11][CH3:12]>CCCCCCCC[N+](CCCCCCCC)(CCCCCCCC)C.[Cl-].O>[CH3:8][CH2:9][CH:10]([C:4]1[C:3]([CH:3]([CH2:7][CH3:6])[CH2:4][CH3:5])=[C:7]([CH:10]([CH2:11][CH3:12])[CH2:9][CH3:8])[CH2:6][CH:5]=1)[CH2:11][CH3:12]
Reactant: CCC(Br)CC
Reactant: C1=CCC=C1
Agent: CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Product: CCC(CC)C1=CCC(C(CC)CC)=C1C(CC)CC
Temperature: 70 °C
Reaction time: 3 h

Procedure:
A double-walled reactor having a volume of 1 L, provided with baffles, condenser, top stirrer, thermometer and dropping funnel, was charged with 430 g (5.4 mol) of clear 50% strength NaOH. Then 23 g of Aliquat 336 (57 mmol) and 27 g (0.41 mol) of freshly cracked cyclopentadiene were added. The reaction mixture was stirred vigorously for a few minutes, then 150 g of 3-pentyl bromide (1.0 mol) were added over a period of one hour, while the reaction mixture was cooled with circulating water at 10° C. After one hour of stirring at room temperature, the reaction mixture was heated to 70° C., followed by a further three hours of stirring. Stirring was stopped and phase separation was performed. The aqueous layer was drawn off and 540 g (6.70 mol) of fresh 50% strength NaOH were added, followed by a further 4 hours of stirring at 70° C. GC was used to show that the mixture consisted of di- and tri(3-pentyl)cyclopentadiene in a ratio of approximately 3:2, respectively. The products were distilled at 0.2 mbar, 51° C. and 0.2 mbar, 77-80° C., respectively. After distillation, 32 g of di- and 18 g of tri(3-pentyl)cyclopentadiene were obtained, which were characterized with GC, GC-MS, 13C- and 1H-NMR.
Reaction SMILES: [Cl:1][C:2]1[C:7]2[NH:8][CH:9]=[CH:10][C:6]=2[C:5]([C:11]([OH:13])=O)=[CH:4][N:3]=1.C(N1CCOCC1)C.[O:22]1[CH2:27][CH2:26][CH:25]([CH2:28][NH2:29])[CH2:24][CH2:23]1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C)C=O>[O:22]1[CH2:27][CH2:26][CH:25]([CH2:28][NH:29][C:11]([C:5]2[C:6]3[CH:10]=[CH:9][NH:8][C:7]=3[C:2]([Cl:1])=[N:3][CH:4]=2)=[O:13])[CH2:24][CH2:23]1
Reactant: O=C(O)c1cnc(Cl)c2[nH]ccc12
Reactant: NCC1CCOCC1
Agent: CCN1CCOCC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CN(C)C=O
Solvent: O
Product: O=C(NCC1CCOCC1)c1cnc(Cl)c2[nH]ccc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 56.6 %

Procedure:
To a solution of 7-chloro-1H-pyrrolo[2,3-c]pyridine-4-carboxylic acid (110 mg) in dimethylformamide (4 ml) was added 4-ethylmorpholine (187 μl), tetrahydro-pyran-4-ylmethylamine (97 mg), 1-hydroxybenzotriazole hydrate (118 mg) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (129 mg) and the solution stirred at room temperature overnight. The dimethylformamide was evaporated and the residue dissolved in ethyl acetate (10 ml). The organic layer was then washed with 5% sodium hydrogen carbonate solution (4 ml) and brine (4 ml). The organic layer was dried (MgSO4) and evaporated to give a pale orange solid. The solid was triturated with diethyl ether and then filtered off, sucked dry then dried at 40° C. under vacuum to afford the title compound (93 mg).
Reaction SMILES: [CH2:1]([C:19]([OH:58])([CH:38]([OH:57])[CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46]/[CH:47]=[CH:48]\[CH2:49]/[CH:50]=[CH:51]\[CH2:52][CH2:53][CH2:54][CH2:55][CH3:56])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]/[CH:28]=[CH:29]\[CH2:30]/[CH:31]=[CH:32]\[CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11]/[CH:12]=[CH:13]\[CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[CH3:59][N:60]([CH3:68])[CH2:61][CH2:62][CH2:63][CH2:64][C:65](O)=[O:66].CCN=C=NCCCN(C)C.Cl.CCN(C(C)C)C(C)C>CN(C1C=CN=CC=1)C.ClCCl>[CH3:59][N:60]([CH3:68])[CH2:61][CH2:62][CH2:63][CH2:64][C:65]([O:57][CH:38]([C:19]([OH:58])([CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]/[CH:28]=[CH:29]\[CH2:30]/[CH:31]=[CH:32]\[CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])[CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11]/[CH:12]=[CH:13]\[CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46]/[CH:47]=[CH:48]\[CH2:49]/[CH:50]=[CH:51]\[CH2:52][CH2:53][CH2:54][CH2:55][CH3:56])=[O:66]
Reactant: CN(C)CCCCC(=O)O
Reactant: CCCCC/C=C\C/C=C\CCCCCCCCC(O)C(O)(CCCCCCCC/C=C\C/C=C\CCCCC)CCCCCCCC/C=C\C/C=C\CCCCC
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CCCCC/C=C\C/C=C\CCCCCCCCC(OC(=O)CCCCN(C)C)C(O)(CCCCCCCC/C=C\C/C=C\CCCCC)CCCCCCCC/C=C\C/C=C\CCCCC
Temperature: 25 °C
Reaction time: 16 h
Yield: 61.1 %

Procedure:
To a solution of (6Z,9Z,29Z,32Z)-19-((9Z,12Z)-octadeca-9,12-dienyl)octatriaconta-6,9,29,32-tetraene-19,20-diol (0.75 g, 0.98 mmol), 5-(dimethylamino)pentanoic acid (285 mg, 2.0 mmol), EDC hydrochloride (378 mg, 2.0 mmol), and 4-(N,N-dimethylamino)pyridine (5 mg) in anhydrous dichloromethane (10 mL) was added DIPEA (0.68 mL, 3.9 mmol). The reaction was stirred for 16 hours at room temperature under nitrogen. TLC (1:1 hexanes/ethyl acetate) indicated that the reaction had stalled, so additional 5-(dimethylamino)pentanoic acid (70 mg, 0.5 mmol) and fresh EDC hydrochloride (300 mg, 1.6 mmol) were added. The reaction was stirred for an additional 24 hours under nitrogen at room temperature. The solution was diluted with dichloromethane (100 mL) and washed with saturated sodium bicarbonate (50 mL), water (50 mL), and brine (50 mL). The combined aqueous layers were back extracted once with dichloromethane (50 mL). The combined dichloromethane extracts were dried on magnesium sulfate, filtered, and concentrated in vacuo to dryness. The resulting orange oil was purified by column chromatography on silica gel 60 (eluted with a gradient of 25%→50% ethyl acetate in hexanes) to afford (6Z,9Z,29Z,32Z)-20-hydroxy-20-((9Z,12Z)-octadeca-9,12-dienyl)octatriaconta-6,9,29,32-tetraen-19-yl 5-(dimethylamino)pentanoate as a pale yellow oil (560 mg, 64%). 1H NMR (400 MHz, CDCl3) δ 5.43-5.29 (m, 12H), 4.95 (dd, 1H, J=10.1, 2.7 Hz), 2.78 (t, 6H, J=6.5 Hz), 2.38 (t, 2H, J=7.5 Hz), 2.28 (t, 2H, J=7.5 Hz), 2.22 (s, 6H), 2.09-2.02 (m, 12H), 1.72-1.42 (m, 13H), 1.41-1.19 (m, 56H), 0.90 (t, 9H, J=6.7 Hz).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([N:7]2[CH2:11][CH2:10][NH:9][C:8]2=[O:12])[CH:2]=1.Br[C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][CH:23]=1)[N:20]([CH2:24][CH3:25])[C:19](=[O:26])[CH2:18][CH2:17]2.N[C@@H]1CCCC[C@H]1N.C(=O)([O-])[O-].[K+].[K+]>[Cu](I)I.O1CCOCC1>[CH2:24]([N:20]1[C:21]2[C:16](=[CH:15][C:14]([N:9]3[CH2:10][CH2:11][N:7]([C:3]4[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=4)[C:8]3=[O:12])=[CH:23][CH:22]=2)[CH2:17][CH2:18][C:19]1=[O:26])[CH3:25]
Reactant: CCN1C(=O)CCc2cc(Br)ccc21
Reactant: O=C1NCCN1c1cccnc1
Agent: I[Cu]I
Agent: N[C@@H]1CCCC[C@H]1N
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Product: CCN1C(=O)CCc2cc(N3CCN(c4cccnc4)C3=O)ccc21
Yield: 47.5 %

Procedure:
Using the same reaction conditions as in Example 1, 1-pyridin-3-yl-imidazolidin-2-one (I-1b: 95 mg, 0.5882 mmol) was reacted with 6-bromo-1-ethyl-3,4-dihydro-1H-quinolin-2-one (150 mg, 0.5882 mmol), 1,4-dioxane (5 mL), copper iodide (11 mg, 0.05882 mmol), trans-1,2-diamino cyclohexane (10 mg, 0.08823 mmol) and potassium carbonate (162 mg, 1.1764 mmol) to afford the crude product. Purification by column chromatography on silica gel (1% MeOH in chloroform), afforded 94 mg of the product (47.71% yield).