Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][CH:2]([C:28]1[CH:33]=[CH:32][C:31]([N+:34]([O-])=O)=[CH:30][CH:29]=1)[CH2:3][NH:4][C:5]([NH:10][CH2:11][CH2:12][CH2:13][O:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([CH2:21][N:22]2[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)[CH:16]=1)=[CH:6][N+:7]([O-:9])=[O:8].[H][H]>C(O)C>[NH2:34][C:31]1[CH:30]=[CH:29][C:28]([CH:2]([OH:1])[CH2:3][NH:4][C:5]([NH:10][CH2:11][CH2:12][CH2:13][O:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH2:21][N:22]3[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]3)[CH:16]=2)=[CH:6][N+:7]([O-:9])=[O:8])=[CH:33][CH:32]=1
Reactant: [H][H]
Reactant: O=[N+]([O-])C=C(NCCCOc1cccc(CN2CCCCC2)c1)NCC(O)c1ccc([N+](=O)[O-])cc1
Solvent: CCO
Product: Nc1ccc(C(O)CNC(=C[N+](=O)[O-])NCCCOc2cccc(CN3CCCCC3)c2)cc1
Yield: 39.9 %

Procedure:
With 15 ml of ethanol was mixed 0.8 g of N-[2-hydroxy-2-(4-nitrophenyl)ethyl]-2-nitro-N'-[3-(3-piperidinomethylphenoxy)propyl]-1,1-ethenediamine, and hydrogen gas was introduced thereinto in the presence of 0.1 g of 5% (by weight) palladium carbon at ordinary temperature and under atmospheric pressure for 7 hours until the absorption of hydrogen gas ceased. Subsequently, the catalyst was removed by filtration and the solvent was removed by distillation under reduced pressure. The resulting residue was purified by a column chromotography (Wako Silica Gel C-200, eluent; chloroform:methanol=5:1 by volume) to obtain 0.3 g (yield 40%) of amorphous N-[2-(4-aminophenyl)-2-hydroxyethyl]-2-nitro-N'-[3-(3-piperidinomethylphenoxy)propyl] -1,1-ethenediamine.
Reaction SMILES: [CH:1]1[C:14]2[CH2:13][C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[C:15]([C:17]1[C:22](=[O:23])[C:21]([C:24]#[N:25])=[C:20]([C:26]#[N:27])[C:19](=[O:28])[C:18]=1[C:29]#[N:30])#[N:16]>C(#N)C>[CH:4]1[C:5]2[C:14](=[CH:13][C:12]3[C:7]([CH:6]=2)=[CH:8][CH:9]=[CH:10][CH:11]=3)[CH:1]=[CH:2][CH:3]=1.[C:29]([C:18]1[C:19](=[O:28])[C:20]([C:26]#[N:27])=[C:21]([C:24]#[N:25])[C:22](=[O:23])[C:17]=1[C:15]#[N:16])#[N:30]
Reactant: c1ccc2c(c1)Cc1ccccc1C2
Agent: N#CC1=C(C#N)C(=O)C(C#N)=C(C#N)C1=O
Solvent: CC#N
Product: c1ccc2cc3ccccc3cc2c1
Temperature: -20 °C

Procedure:
A solution of 9,10-dihydroanthracene (35 mg; 0.192 mmol) dissolved in 1 mL dry acetonitrile was reacted with tetracyano-1,4-benzoquinone (40 mg; 0.192 mmol) also dissolved in 1 mL dry acetonitrile. After reducing the volume in half and cooling to -20° C. crystals precipitated and were collected. The infrared spectra of the precipitate was identical to that obtained from a mixture of authentic anthracene and tetracyano-1,4-hydroquinone (υ(C≡N)=2239 and 2263 cm-1) verifying that tetracyano-1,4-benzoquinone dehydrogenates 9,10-dihydroanthracene.
Reaction SMILES: [C:1]([O:4][C:5]1[C:6](=[O:16])[O:7][C:8]([CH2:11][O:12][C:13](=[O:15])[CH3:14])=[CH:9][CH:10]=1)(=[O:3])[CH3:2].C(Cl)(Cl)Cl>C(OCC)(=O)C.[Pd]>[C:1]([O:4][CH:5]1[C:6](=[O:16])[O:7][CH:8]([CH2:11][O:12][C:13](=[O:15])[CH3:14])[CH2:9][CH2:10]1)(=[O:3])[CH3:2]
Reactant: CC(=O)OCc1ccc(OC(C)=O)c(=O)o1
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: ClC(Cl)Cl
Product: CC(=O)OCC1CCC(OC(C)=O)C(=O)O1
Temperature: 75 °C

Procedure:
3-Acetoxy-6-acetoxymethyl-pyran-2-one (2.2) (4.80 g, 21.2 mmol) was dissolved in ethyl acetate (50 mL) and added to the Parr reactor, followed by Pd/C (5%, 0.2 g). The mixture was stirred under hydrogen (5×106 Pa) and heated to 75° C. for 4 hours. The product was filtered through celite and the solvent removed under vacuum. A colourless syrup was obtained (4.83 g, 21.0 mmol, 99%). 1H NMR (400 MHz, CDCl3) δ 5.45 (1H, dd, 3JH—H=17.08 Hz, 3JH—H=8.55 Hz, H-2), 4.65 (1H, m, H-5), 4.26 (1 H, dd, 2JH—H=12.13 Hz, 3JH—H=3.54 Hz, H-6), 4.18 (1 H, dd, 2JH—H=12.16, 3JH—H=6.32 Hz, H-6′), 2.36 (1H, m, H-3), 2.19 (3H, s, COCH3), 2.11 (3H, s, COCH3), 2.07-1.88 (3H, m, H-3′, H-4, H-4′) ppm. 13C{1H} NMR (125 MHz, CDCl3) δ 170.6, 169.8, 168.6 (2×COCH3, C-1), 74.9 (C-5), 65.9 (C-2), 64.9 (C-6), 22.7, 22.4 (C-3, C-4), 20.7 (2×COCH3) ppm. CI (NH4+): 248 (100%), 306 (30%), 478 (20%). m/z (CI-ammonia gas): 248 [M+NH4+]. [α]D=0° (CHCl3, 10 mg/mL). Anal. Calcd for C10H14O6: C, 52.17; H, 6.13. Found: C, 52.11; H, 6.17.
Reaction SMILES: [CH2:1]([NH2:5])[CH:2]([CH3:4])[CH3:3].[Cl:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[S:13](Cl)(=[O:15])=[O:14].C(N(CC)C(C)C)(C)C>ClCCl>[Cl:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[S:13]([NH:5][CH2:1][CH:2]([CH3:4])[CH3:3])(=[O:15])=[O:14]
Reactant: O=S(=O)(Cl)c1ccccc1Cl
Reactant: CC(C)CN
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(C)CNS(=O)(=O)c1ccccc1Cl

Procedure:
In analogy to example 1, step 1, isobutylamine was reacted with 2-chlorobenzenesulfonyl chloride and N,N-diisopropyl ethyl amine in dichloromethane to give 2-chloro-N-isobutyl-benzenesulfonamide as a colorless solid. MS: 248.1 ([M+H]+)
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)([O-:3])=[O:2].Cl[CH2:11][S:12]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)(=[O:14])=[O:13].CC([O-])(C)C.[K+].C1COCC1.C(O)(=O)C>C1COCC1.O>[C:15]1([S:12]([CH2:11][C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N+:1]([O-:3])=[O:2])(=[O:14])=[O:13])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: O=[N+]([O-])c1ccccc1
Reactant: O=S(=O)(CCl)c1ccccc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Solvent: CC(=O)O
Product: O=[N+]([O-])c1ccccc1CS(=O)(=O)c1ccccc1
Temperature: -30 °C
Yield: 81 %

Procedure:
A solution of nitrobenzene (3.08 g, 25.0 mmol) and chloromethylphenylsulfone (4.76 g, 25.0 mmol) in dry THF is cooled to −50° C. and treated with 1.0M KOtBu/THF (55.0 mL, 55.0 mmol). The reaction is allowed to warm to −30° C. over 1 h, treated with glacial acetic acid (3.6 mL), warmed to 20° C., treated with water and extracted with CH2Cl2. The combined extracts are dried over MgSO4 and concentrated in vacuo. Chromatography (1:1 ethyl acetate:hexanes) of the resultant residue give the title product as a white solid, 5.62 g, (81% yield), mp 106-108° C., identified by mass spectral and HNMR analyses.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:21][CH:20]2[CH2:22][CH:10]([C:11]3[CH:12]=[C:13]4[C:17](=[CH:18][C:19]=32)[N:16]=[C:15]([CH3:23])[NH:14]4)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CS(C)=O.I[CH2:29][CH2:30][CH3:31].O>[OH-].[Na+]>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH:10]2[CH2:22][CH:20]([C:19]3[CH:18]=[C:17]4[C:13](=[CH:12][C:11]=32)[N:14]=[C:15]([CH3:23])[N:16]4[CH2:29][CH2:30][CH3:31])[CH2:21]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CCCI
Reactant: Cc1nc2cc3c(cc2[nH]1)C1CC3CN(C(=O)OC(C)(C)C)C1
Agent: [Na+]
Agent: [OH-]
Solvent: CS(C)=O
Solvent: O
Product: CCCn1c(C)nc2cc3c(cc21)C1CC3CN(C(=O)OC(C)(C)C)C1
Temperature: 40 °C

Procedure:
6-Methyl-5,7,13-triazatetracyclo[9.3.1.02,10.04,8]pentadeca-2(10),3,5,8-tetraene-13-carboxylic acid tert-butyl ester (80 mg, 0.267 mmol) was stirred in 50% aqueous NaOH solution (3 mL) and DMSO (1 mL) then treated with 1-iodopropane (0.03 mL, 0.321 mmol). This mixture was warmed to 40° C. for 2 hours then cooled, treated with H2O and extracted with EtOAc. The organic layer was washed with H2O (3×) then dried (Na2SO4), filtered and concentrated to an oil (90 mg,.0.253 mmol). (TLC 5% MeOH/CH2Cl2 (NH3) Rf 0.15).
Reaction SMILES: C([S:4][CH2:5][CH:6]([CH2:10][CH2:11][CH2:12][NH2:13])[C:7]([OH:9])=[O:8])(=O)C>O.N>[NH2:13][CH2:12][CH2:11][CH2:10][CH:6]([CH2:5][SH:4])[C:7]([OH:9])=[O:8]
Reactant: CC(=O)SCC(CCCN)C(=O)O
Agent: N
Solvent: O
Product: NCCCC(CS)C(=O)O

Procedure:
2-Acetylthiomethyl-5-aminopentanoic acid (1 g.) is dissolved in a mixture of water (12 ml.) and concentrated ammonia (12 ml.) under a blanket of argon. The solution is stored for twenty minutes at room temperature and concentrated to dryness in vacuo. The residue is applied to a column of Dowex 50 in the hydrogen cycle, the column is washed with water and 5-amino-2-mercaptomethylpentanoic acid is eluted with 2M pyridine-acetate buffer pH 6.5.
Reaction SMILES: OCCCN1C=C(C2C=CC(NC3C(C(F)(F)F)=CN=C(NC4C=CC(CP(=O)(OCC)OCC)=CC=4OC)N=3)=C3C=2CN(C)C3=O)C=N1.[NH2:50][C:51]1[C:52]([C:58]([NH:60][CH3:61])=[O:59])=[N:53][C:54]([Br:57])=[CH:55][CH:56]=1.C(OP1(=O)CC2C=CC(=CC=2)NC2=NC(=C(C(F)(F)F)C=N2)NC2C=CC(=NC=2C(NC)=O)C2=CN(N=C2)CCCCO1)C.[Cl:106][C:107]1[CH:108]=[C:109]([CH:119]=[CH:120][C:121]=1[NH:122][C:123]1[N:128]=[C:127](Cl)[C:126]([C:130]([F:133])([F:132])[F:131])=[CH:125][N:124]=1)[CH2:110][P:111](=[O:118])([O:115][CH2:116][CH3:117])[O:112][CH2:113][CH3:114]>>[Br:57][C:54]1[N:53]=[C:52]([C:58](=[O:59])[NH:60][CH3:61])[C:51]([NH:50][C:127]2[C:126]([C:130]([F:131])([F:132])[F:133])=[CH:125][N:124]=[C:123]([NH:122][C:121]3[CH:120]=[CH:119][C:109]([CH2:110][P:111](=[O:118])([O:115][CH2:116][CH3:117])[O:112][CH2:113][CH3:114])=[CH:108][C:107]=3[Cl:106])[N:128]=2)=[CH:56][CH:55]=1
Reactant: CNC(=O)c1nc(Br)ccc1N
Reactant: CCOP(=O)(Cc1ccc(Nc2ncc(C(F)(F)F)c(Cl)n2)c(Cl)c1)OCC
Agent: CCOP(=O)(Cc1ccc(Nc2ncc(C(F)(F)F)c(Nc3ccc(-c4cnn(CCCO)c4)c4c3C(=O)N(C)C4)n2)c(OC)c1)OCC
Agent: CCOP1(=O)Cc2ccc(cc2)Nc2ncc(C(F)(F)F)c(n2)Nc2ccc(nc2C(=O)NC)-c2cnn(c2)CCCCO1
Product: CCOP(=O)(Cc1ccc(Nc2ncc(C(F)(F)F)c(Nc3ccc(Br)nc3C(=O)NC)n2)c(Cl)c1)OCC

Procedure:
This material was prepared analogously to Compound 1B replacing Compound 1C with Compound 6D and Compound 1 E with Compound 24C. MS (ES+): m/z 651.22/653.22 (MH+). UPLC: tR=1.48 min (UPLC-SQD: analytical—2 min).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][N:4]1[C:8](=[O:9])/[C:7](=[CH:10]/[C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[N:16]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:22]=2[C:28]([F:31])([F:30])[F:29])[N:15]=[CH:14]3)/[S:6][C:5]1=[O:32].[C:33](OC(=O)C)(=[O:35])[CH3:34]>>[Cl:27][C:24]1[CH:25]=[CH:26][C:21]([CH2:20][N:16]2[C:17]3[C:13](=[CH:12][C:11](/[CH:10]=[C:7]4/[C:8](=[O:9])[N:4]([CH2:3][CH2:2][NH:1][C:33](=[O:35])[CH3:34])[C:5](=[O:32])[S:6]/4)=[CH:19][CH:18]=3)[CH:14]=[N:15]2)=[C:22]([C:28]([F:30])([F:29])[F:31])[CH:23]=1
Reactant: NCCN1C(=O)S/C(=C\c2ccc3c(cnn3Cc3ccc(Cl)cc3C(F)(F)F)c2)C1=O
Reactant: CC(=O)OC(C)=O
Product: CC(=O)NCCN1C(=O)S/C(=C\c2ccc3c(cnn3Cc3ccc(Cl)cc3C(F)(F)F)c2)C1=O

Procedure:
N-{2-[(5Z)-5-({1-[4-Chloro-2-(trifluoromethyl)benzyl]-1H-indazol-5-yl}methylidene)-2,4-dioxo-1,3-thiazolidin-3-yl]ethyl}acetamide was prepared from 3-(2-aminoethyl)-(5Z)-5-({1-[4-chloro-2-(trifluoromethyl)benzyl]-1H-indazol-5-yl}methylidene)-1,3-thiazolidine-2,4-dione (from Example 49) and acetic anhydride following General Procedure U.
Reaction SMILES: [CH:1]1([NH:4][C:5]2[N:10]3[N:11]=[C:12]([CH3:16])[C:13]([CH:14]=O)=[C:9]3[N:8]=[C:7]([CH3:17])[CH:6]=2)[CH2:3][CH2:2]1.[S:18]1[CH2:22][C:21](=[O:23])[NH:20][C:19]1=[O:24].N1CCCCC1>CN(C=O)C>[CH:1]1([NH:4][C:5]2[N:10]3[N:11]=[C:12]([CH3:16])[C:13]([CH:14]=[C:22]4[S:18][C:19](=[O:24])[NH:20][C:21]4=[O:23])=[C:9]3[N:8]=[C:7]([CH3:17])[CH:6]=2)[CH2:3][CH2:2]1
Reactant: Cc1cc(NC2CC2)n2nc(C)c(C=O)c2n1
Reactant: O=C1CSC(=O)N1
Solvent: C1CCNCC1
Solvent: CN(C)C=O
Product: Cc1cc(NC2CC2)n2nc(C)c(C=C3SC(=O)NC3=O)c2n1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To 7-(cyclopropylamino)-2,5-dimethylpyrazolo[1,5-a]pyrimidine-3-carbaldehyde (0.25 mmol) in DMF was added thiazolidine-2,4-dione (88 mg, 0.75 mmol) and piperidine (25 μl, 0.25 mmol). The mixture was stirred at room temperature overnight. Mixture was prepared by HPLC to yield 5-((7-(cyclopropylamino)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)methylene)thiazolidine-2,4-dione. LCMS (M+1=330)
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:25])[C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:19]3[C:14](=[CH:15][C:16]([C:20](O)=[O:21])=[CH:17][CH:18]=3)[C:13]([C:23]#[N:24])=[CH:12]2)=[CH:7][CH:6]=1)[CH3:2].Cl.[CH3:27][NH:28][CH3:29].C(N(CC)CC)C.Cl>CN(C)C1C=CN=CC=1.ClCCl>[CH2:1]([O:3][C:4](=[O:25])[C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:19]3[C:14](=[CH:15][C:16]([C:20]([N:28]([CH3:29])[CH3:27])=[O:21])=[CH:17][CH:18]=3)[C:13]([C:23]#[N:24])=[CH:12]2)=[CH:7][CH:6]=1)[CH3:2]
Reactant: CCOC(=O)c1ccc(-n2cc(C#N)c3cc(C(=O)O)ccc32)cc1
Reactant: CNC
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCOC(=O)c1ccc(-n2cc(C#N)c3cc(C(=O)N(C)C)ccc32)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 22 %

Procedure:
To a solution of 4-(5-carboxy-3-cyanoindol-1yl)benzoic acid ethyl ester (0.084 g), dimethylamine hydrochloride (0.061 g), triethylamine (0.13 g) and 4-dimethylaminopyridine (0.006 g) in dichloromethane (2.5 mL) was added N-ethyl-N′-3-dimethylaminopropylcarbodiimide (0.058 g) at room temperature, and this mixture was stirred at room temperature overnight. This reaction mixture was poured into 1 mol/L hydrochloric acid, and this mixture was extracted with ethyl acetate. This organic layer was washed with a saturated aqueous sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: ethyl acetate/n-hexane=1/2) to give the title compound (0.020 g).
Reaction SMILES: [CH2:1]([C:7]1[CH:19]=[CH:18][CH:17]=[CH:16][C:8]=1[O:9]C1CCCCO1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].C([Li])CCC.C([O:28][B:29](OC(C)C)[O:30]C(C)C)(C)C.Cl>C1COCC1.CCOCC>[CH2:1]([C:7]1[C:8]([OH:9])=[C:16]([B:29]([OH:30])[OH:28])[CH:17]=[CH:18][CH:19]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: CCCCCCc1ccccc1OC1CCCCO1
Reactant: CC(C)OB(OC(C)C)OC(C)C
Agent: Cl
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: C1CCOC1
Product: CCCCCCc1cccc(B(O)O)c1O
Reaction time: 0.17 h
Yield: 26.4 %

Procedure:
2-(2-Hexylphenoxy)tetrahydropyran (1.162 g, 4.43 mmol) was dissolved in dry THF (20 ml) and the solution cooled to 0° C. n-Butyl lithium (1.6M in hexanes, 4.15 ml, 6.64 mmol) was added dropwise with stirring over 10 minutes. The ice-bath was removed and the reaction stirred at room temperature overnight. Triisopropoxy borane (1.43 ml, 6.2 mmol) was added and stirring continued for 24 hours. The reaction was quenched with water, acidified to pH 1 with 2N hydrochloric acid and extracted with ether (20 ml). The combined organic extracts were washed with 2N hydrochloric acid (50 ml), dried with sodium sulphate and concentrated under vacuum. The oily solid produced was dissolved in ether (30 ml) and stirred with 2N hydrochloric acid (15 ml) for 1 hour. The organic phase was separated, dried with sodium sulphate and concentrated under vacuum. The residue was triturated with cyclohexane and the solid filtered off to give the title compound (260 mg, 26%); MS 221 (M−H)−.
Reaction SMILES: [O:1]=[CH:2][C:3]1[CH:11]=[CH:10][C:8]([OH:9])=[C:5]([O:6][CH3:7])[CH:4]=1.[Cl:12][C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][C:20]=1F)[C:16]#[N:17]>>[Cl:12][C:13]1[CH:14]=[C:15]([C:16]#[N:17])[CH:18]=[CH:19][C:20]=1[O:9][C:8]1[CH:10]=[CH:11][C:3]([CH:2]=[O:1])=[CH:4][C:5]=1[O:6][CH3:7]
Reactant: COc1cc(C=O)ccc1O
Reactant: N#Cc1ccc(F)c(Cl)c1
Product: COc1cc(C=O)ccc1Oc1ccc(C#N)cc1Cl

Procedure:
4-(2-Chloro-4-cyanophenoxy)-3-methoxybenzaldehyde was prepared from vanillin and 3-Chloro-4-fluorobenzonitrile following General Procedure A. 1H NMR (400 Hz, CDCl3) δ 9.95 (s, 1H), 7.76 (d, 1H), 7.56 (br s, 1H), 7.50 (d, 1H), 7.45 (brd, 1H), 7.15 (d, 1H), 6.78 (d, 1H), 3.90 (s, 3H).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:29])[CH:4]([N:9]1[C:15](=[O:16])[CH2:14][CH2:13][N:12]([C:17](=[O:28])/[CH:18]=[CH:19]/[C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=2)[CH2:11][CH2:10]1)[CH2:5][C:6](O)=[O:7].[NH:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.OS([O-])(=O)=O.[K+]>ClCCl>[CH3:1][O:2][C:3](=[O:29])[CH:4]([N:9]1[C:15](=[O:16])[CH2:14][CH2:13][N:12]([C:17](=[O:28])/[CH:18]=[CH:19]/[C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=2)[CH2:11][CH2:10]1)[CH2:5][C:6](=[O:7])[N:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1
Reactant: COC(=O)C(CC(=O)O)N1CCN(C(=O)/C=C/c2ccc(Cl)c(Cl)c2)CCC1=O
Reactant: C1CCNCC1
Agent: CCN=C=NCCCN(C)C
Agent: O=S(=O)([O-])O
Agent: On1nnc2ccccc21
Solvent: ClCCl
Product: COC(=O)C(CC(=O)N1CCCCC1)N1CCN(C(=O)/C=C/c2ccc(Cl)c(Cl)c2)CCC1=O
Temperature: 25 °C

Procedure:
A solution of 0.286 g (0.65 mmol) of 2-{4-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-7-oxo-[1,4]diazepan-1-yl}-succinic acid 1-methyl ester (intermediate 7) in 15 ml of dichloromethane was treated with 0.070 ml (0.71 mmol) of piperidine and at 0° C. with 0.148 g (0.77 mmol) of EDCI and 0.009 g (0.06 mmol) of HOBT. Over night, the suspension was naturally warmed to RT, poured on aqueous 10% KHSO4 solution and extracted with EtOAc (3×). The organic phases were washed with aqueous saturated NaHCO3 and aqueous 10% NaCl, dried (Na2SO4) and evaporated to give 0.332 g (quant.) of the titled compound as white foam. MS: 510.1 (MH+, 2Cl).
Reaction SMILES: Cl[CH2:2][C:3]([O:5][CH:6]1[CH2:11][C:10]([CH3:13])([CH3:12])[N:9]([O:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])[C:8]([CH3:24])([CH3:23])[CH2:7]1)=[O:4].[CH3:25][C:26]1[CH:31]=[C:30]([CH3:32])[CH:29]=[CH:28][C:27]=1[C:33]1[N:38]=[C:37]([C:39]2[CH:44]=[CH:43][C:42]([CH3:45])=[CH:41][C:40]=2[CH3:46])[N:36]=[C:35]([C:47]2[CH:52]=[CH:51][C:50]([OH:53])=[CH:49][C:48]=2[OH:54])[N:34]=1.[OH-].[Na+]>CN(C)C=O>[CH3:25][C:26]1[CH:31]=[C:30]([CH3:32])[CH:29]=[CH:28][C:27]=1[C:33]1[N:38]=[C:37]([C:39]2[CH:44]=[CH:43][C:42]([CH3:45])=[CH:41][C:40]=2[CH3:46])[N:36]=[C:35]([C:47]2[CH:52]=[CH:51][C:50]([O:53][CH2:2][C:3]([O:5][CH:6]3[CH2:11][C:10]([CH3:13])([CH3:12])[N:9]([O:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])[C:8]([CH3:24])([CH3:23])[CH2:7]3)=[O:4])=[CH:49][C:48]=2[OH:54])[N:34]=1
Reactant: Cc1ccc(-c2nc(-c3ccc(C)cc3C)nc(-c3ccc(O)cc3O)n2)c(C)c1
Reactant: CCCCCCCCON1C(C)(C)CC(OC(=O)CCl)CC1(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: CN(C)C=O
Product: CCCCCCCCON1C(C)(C)CC(OC(=O)COc2ccc(-c3nc(-c4ccc(C)cc4C)nc(-c4ccc(C)cc4C)n3)c(O)c2)CC1(C)C
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 48.4 %

Procedure:
A solution of 14.5 g (40.0 mmol) of 1-octyloxy-2,2,6,6-tetramethylpiperidin-4-yl chloroacetate in 25 ml of N,N-dimethylformamide is rapidly added to a mixture of 20.0 g (50.2 mmol) of 2,4-bis(2,4-dimethylphenyl)-6-(2,4-dihydroxyphenyl)-1,3,5-triazine (Example 8A), 125 ml of N,N-dimethylformamide, and 4.0 g of 50% sodium hydroxide solution that has been stirred at ambient temperature for 30 minutes. The reaction mixture is then heated at 70° C. for 1 hour and stirred at ambient temperature for 17 hours. The reaction mixture is partitioned between ethyl acetate (300 ml) and a mixture of water (1000 ml) and 1N hydrochloric acid (10 ml). The aqueous layer is extracted with diethyl (2×500 ml) and saturated sodium chloride solution (500 ml), dried over magnesium sulfate, and concentrated to an oil. Purification by flash chromatography on silica gel (5:1 heptane: ethyl acetate) affords 14.0 g (48% yield) of the title compound, a yellow solid, mp 86°-90° C.
Reaction SMILES: Br[C:2]1[C:15]2[C:16]3=[C:17]4[C:12](=[CH:13][CH:14]=2)[CH:11]=[CH:10][CH:9]=[C:8]4[CH:7]=[CH:6][C:5]3=[CH:4][CH:3]=1.[C:18]1(B(O)O)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.O1CCCC1.C(=O)([O-])[O-].[K+].[K+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[C:18]1([C:9]2[C:8]3[C:17]4=[C:16]5[C:5](=[CH:6][CH:7]=3)[CH:4]=[CH:3][CH:2]=[C:15]5[CH:14]=[CH:13][C:12]4=[CH:11][CH:10]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: Brc1ccc2ccc3cccc4ccc1c2c34
Reactant: OB(O)c1ccccc1
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Product: c1ccc(-c2ccc3ccc4cccc5ccc2c3c45)cc1
Temperature: 100 °C

Procedure:
1-bromopyrene (2 g, 7.11 mmol) and phenylboronic acid (1.40 g, 14.30 mmol) were put into a 2-neck round bottom flask filled with 80 ml of anhydrous tetrahydrofuran and stirred. Tetrakis(triphenylphosphine) palladium (0.41 g, 5 mol %), 20 g of potassium carbonate and 80 ml of distilled water were added into the same flask, which was then subjected to reflux at a temperature of 100° C. for 24 hours. After completion of the reaction, the tetrahydrofuran was removed and thusly generated solid was filtered. The filtered solid was recrystallized by dichloromethane and ethanol, thereby synthesizing 1-phenylpyrene (1.84 g, 93%).
Reaction SMILES: [CH:1]([C:3]1[CH:7]=[CH:6][S:5][C:4]=1[C:8]([OH:10])=[O:9])=[O:2].I[CH2:12][CH3:13].C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[CH2:12]([O:9][C:8]([C:4]1[S:5][CH:6]=[CH:7][C:3]=1[CH:1]=[O:2])=[O:10])[CH3:13]
Reactant: CCI
Reactant: O=Cc1ccsc1C(=O)O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)c1sccc1C=O
Temperature: 25 °C
Reaction time: 15 h

Procedure:
3-Formyl-2-thiophenecarboxylic acid (3.12 g) was dissolved in N,N-dimethylformamide (30 ml), and iodoethane (1.76 ml) and potassium carbonate (2.76 g) were added. The mixture was stirred at room temperature for 15 hours and poured into water. The mixture was extracted with ethyl acetate, washed with 5% aqueous potassium hydrogen sulfate, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, and the desired fractions were concentrated under reduced pressure to give 3-formyl-2-thiophenecarboxylic acid ethyl ester (2.91 g). 3-Formyl-2-thiphenecarboxylic acid ethyl ester (1.84 g) in methylene chloride (10 ml) was slowly added dropwise to diethylaminosulfur trifluoride (DAST) (1.45 ml) in methylene chloride (10 ml) at room temperature. The mixture was stirred at room temperature for 3 hours, and saturated aqueous sodium bicarbonate was added. The organic layer was collected, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give 3-difluoromethyl-2-thiophenecarboxylic acid ethyl ester (1.58 g). 3-Difluoromethyl-2-thiophenecarboxylic acid ethyl ester was dissolved in a mixture of ethanol (10 ml) and tetrahydrofuran (10 ml), and 1N aqueous sodium hydroxide (11 ml) was added. The mixture was stirred at room temperature for 2 hours and washed with diethyl ether. The aqueous layer was acidified with 1N hydrochloric acid and extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced ppressure to give 3-difluoromethyl-2-thiophenecarboxylic acid (1.12 g) as crystals.
Reaction SMILES: [C:1]([C:3]1[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[CH:8][C:4]=1[C:5]([OH:7])=O)#[N:2].[CH3:14][CH2:15][CH2:16][CH:17]([NH2:21])[CH2:18][CH2:19][CH3:20]>>[C:1]([C:3]1[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[CH:8][C:4]=1[C:5]([NH:21][CH:17]([CH2:18][CH2:19][CH3:20])[CH2:16][CH2:15][CH3:14])=[O:7])#[N:2]
Reactant: CCCC(N)CCC
Reactant: COc1ccc(C(=O)O)c(C#N)c1
Product: CCCC(CCC)NC(=O)c1ccc(OC)cc1C#N
Yield: 73 %

Procedure:
Prepared in a similar manner to example 4 using 2-cyano-4-methoxybenzoic acid and 4-Heptylamine. Yield: 73%. 1H NMR (CD3OD): 0.94 (t, 6H, J=7.3 Hz), 1.38 (m, 4H), 1.53 (m, 4H), 4.02 (s, 3H), 4.12 (m, 1H), 7.27 (d, 1H, J=9.40 Hz), 8.11 (d, 2H, J=2.21 Hz). MS (M+H, 275).
Reaction SMILES: Cl.[CH:2]1([CH2:5][O:6][C:7]2[CH:12]=[C:11]([O:13][CH3:14])[C:10]([F:15])=[CH:9][C:8]=2[C:16]2[C:17]3[NH:24][C:23]([CH3:25])=[C:22]([C:26]([NH:28][CH:29]4[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]4)=[O:27])[C:18]=3[N:19]=[CH:20][N:21]=2)[CH2:4][CH2:3]1.[C:35](Cl)(=[O:38])[CH2:36][CH3:37]>>[CH:2]1([CH2:5][O:6][C:7]2[CH:12]=[C:11]([O:13][CH3:14])[C:10]([F:15])=[CH:9][C:8]=2[C:16]2[C:17]3[NH:24][C:23]([CH3:25])=[C:22]([C:26]([NH:28][CH:29]4[CH2:30][CH2:31][N:32]([C:35](=[O:38])[CH2:36][CH3:37])[CH2:33][CH2:34]4)=[O:27])[C:18]=3[N:19]=[CH:20][N:21]=2)[CH2:4][CH2:3]1
Reactant: COc1cc(OCC2CC2)c(-c2ncnc3c(C(=O)NC4CCNCC4)c(C)[nH]c23)cc1F
Reactant: CCC(=O)Cl
Agent: Cl
Product: CCC(=O)N1CCC(NC(=O)c2c(C)[nH]c3c(-c4cc(F)c(OC)cc4OCC4CC4)ncnc23)CC1

Procedure:
Starting from 4-[2-(cyclopropylmethoxy)-5-fluoro-4-methoxyphenyl]-6-methyl-N-piperidin-4-yl-5H-pyrrolo[3,2-d]pyrimidine-7-carboxamide hydrochloride (example D.f44) and commercially available propionyl chloride the title compound is obtained as colorless solid.