Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[C:3]2[C:10](I)=[CH:9][N:8]([C@H:12]3[CH2:15][C@H:14]([CH2:16][OH:17])[CH2:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[C:18]1([C:24]2[CH:33]=[CH:32][C:31]3[C:26](=[CH:27][C:28](B4OC(C)(C)C(C)(C)C4)=[CH:29][CH:30]=3)[N:25]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C([O-])([O-])=O.[Na+].[Na+].O>CN(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>[NH2:1][C:2]1[C:3]2[C:10]([C:28]3[CH:27]=[C:26]4[C:31]([CH:32]=[CH:33][C:24]([C:18]5[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=5)=[N:25]4)=[CH:30][CH:29]=3)=[CH:9][N:8]([C@H:12]3[CH2:15][C@H:14]([CH2:16][OH:17])[CH2:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: Nc1ncnc2c1c(I)cn2[C@H]1C[C@H](CO)C1
Reactant: CC1(C)CB(c2ccc3ccc(-c4ccccc4)nc3c2)OC1(C)C
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: CN(C)C=O
Solvent: O
Product: Nc1ncnc2c1c(-c1ccc3ccc(-c4ccccc4)nc3c1)cn2[C@H]1C[C@H](CO)C1

Procedure:
Following the general procedure for the Suzuki coupling, trans-[3-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-cyclobutyl]-methanol (139.2 mg, 0.4045 mmol) was reacted with 2-phenyl-7-(4,4,5,5-tetramethyl-[2,3,2]dioxaborolan-2-yl)-quinoline (141 mg, 0.426 mmol), Na2CO3 (107 mg, 1.01 mmol) and Pd(PPh3)4 (30 mg, 0.026 mmol) in DMF (10 mL)/water (2 mL). The crude material was purified by column chromatography on silica gel [Jones Flashmaster, 10 g/70 mL cartridge, eluting with CH2Cl2 (1-7)→2% MeOH in CH2Cl2 (8-22)→5% MeOH in CH2Cl2 (23-41)→7% MeOH in CH2Cl2 (42-51)], yielding the title compound. 1H NMR (CDCl3, 400 MHz) δ 2.42-2.60 (m, 3H), 2.60-2.73 (m, 3H), 3.88 (d, J=6.4 Hz, 2H), 5.19 (brs, 2H), 5.44-5.53 (mc, 1H), 7.39 (s, 1H), 7.46-7.52 (m, 1H), 7.52-7.58 (m, 2H), 7.71 (dd, J=1.7, 8.3 Hz, 1H), 7.92 (d, J=8.5 Hz, 1H), 7.94 (d, J=7.7 Hz, 1H), 8.17-8.22 (m, 2H), 8.27 (d, J=8.5 Hz, 1H), 8.29-8.32 (m, 1H), 8.36 (s, 1H). 13C NMR (CDCl3, 100.6 MHz, DEPT135) δ 30.62 (+), 32.16 (2C, −), 46.70 (+), 65.12 (−), 101.04 (Cquart), 116.13 (Cquart), 118.88 (+), 120.64 (+), 125.82 (Cquart), 127.27 (+), 127.45 (2C, +), 128.17 (+), 128.21 (+), 128.71 (2C, +), 129.40 (+), 136.23 (Cquart), 136.49 (+), 139.23 (Cquart), 148.28 (Cquart), 150.47 (Cquart), 151.57 (+), 157.09 (Cquart) 157.97 (Cquart). MS (ES+): m/z 422.1 (51) [MH+], 338.2 (39) [MH+-cyclobutene-CH2OH]. HPLC: tR=2.4 min (OpenLynx, polar—5 min).
Reaction SMILES: Cl.[CH2:2]([NH:4][C:5]([N:7]1[CH2:11][C:10]([CH3:13])([CH3:12])[CH:9]=[N:8]1)=[NH:6])[CH3:3].CCN(C(C)C)C(C)C.[Cl:23][C:24]1[CH:25]=[C:26]([S:30](Cl)(=[O:32])=[O:31])[CH:27]=[CH:28][CH:29]=1>C(Cl)Cl>[Cl:23][C:24]1[CH:25]=[C:26]([S:30]([N:6]=[C:5]([N:7]2[CH2:11][C:10]([CH3:12])([CH3:13])[CH:9]=[N:8]2)[NH:4][CH2:2][CH3:3])(=[O:32])=[O:31])[CH:27]=[CH:28][CH:29]=1
Reactant: CCNC(=N)N1CC(C)(C)C=N1
Reactant: O=S(=O)(Cl)c1cccc(Cl)c1
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CCNC(=NS(=O)(=O)c1cccc(Cl)c1)N1CC(C)(C)C=N1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
6.39 g N-Ethyl-4,4-dimethyl-4,5-dihydro-pyrazole-1-carboxamidine hydrochloride was suspended in 65 mL DCM. 12.0 mL DiPEA and 3.96 mL 3-chloro-benzenesulfonyl chloride were added and the suspension was stirred for 20 h. at room temperature, resulting in a dark brown turbid solution. The mixture was extracted with 2M NaOH (2×125 mL) and 1M HCl (2×125 mL), washed with water (100 mL), and the organic layer was dried over Na2SO4 followed by evaporation under reduced pressure to yield 7.70 g of a brown oil. The oil (1.0 g) was dissolved in MTBE (3 mL) under reflux, and the solution was slowly cooled to room temperature, initializing crystallization The suspension was stirred for 10 min at room temperature, hexane (6 mL) was added over a period of 1 minute. The resulting suspension was stirred for 20 min. at room temperature and 50 min. at 0° C., and product was collected by filtration and washed with hexane (1 mL). Drying under reduced pressure at 40° C. yielded 0.85 g of a light-brown solid, m.p. 62-67° C.
Reaction SMILES: [N:1]([CH:4]1[C:16]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:10]2[C:5]1=[CH:6][CH:7]=[CH:8][CH:9]=2)=[N+:2]=[N-].P>C1(C)C=CC=CC=1>[N+:1](=[C:4]1[C:16]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:10]2[C:5]1=[CH:6][CH:7]=[CH:8][CH:9]=2)=[N-:2]
Reactant: [N-]=[N+]=NC1c2ccccc2-c2ccccc21
Agent: P
Solvent: Cc1ccccc1
Product: [N-]=[N+]=C1c2ccccc2-c2ccccc21
Yield: 85 %

Procedure:
To probe the scope of the reaction even further, we investigated the synthesis of semi-stabilized diazo-compounds. Treatment of 9-azido-fluorene 2j with phosphine 1e under anhydrous conditions at low temperature (toluene, 0° C.), followed by loading the red solution directly on basic alumina (Grade 5) and eluting with 10% CH2Cl2/hexanes, 9-diazo-fluorene 5j was isolated in 85% yield and excellent purity (96%). Apparently, thermal fragmentation of the putative triazenophosphonium salt, which more than likely exists in its neutral λ5-phosphorane form[16] is suppressed sufficiently for this substrate under the reaction conditions. The low temperature and low polarity of the solvent probably contribute to that greater stability. Under the standard conditions (THF/H2O), incomplete conversion of the azide 2j and contamination of the diazo-compound 5j with substantial amounts of other products, probably arising from alternative triazene decomposition and dimerization of the diazo-compound, were apparent. Finally, a vinylogous diazo-carbonyl compound 5k (96% purity) was prepared in good yield from anthraquinone-based azide 2k using the standard conditions.
Reaction SMILES: [F:1][C:2]1[C:7]([O:8][C:9]([F:12])([F:11])[F:10])=[CH:6][CH:5]=[CH:4][C:3]=1[C:13]1[CH2:14][CH2:15][NH:16][CH2:17][CH:18]=1.Cl>[Pd].CO>[F:1][C:2]1[C:7]([O:8][C:9]([F:10])([F:11])[F:12])=[CH:6][CH:5]=[CH:4][C:3]=1[CH:13]1[CH2:14][CH2:15][NH:16][CH2:17][CH2:18]1
Reactant: Fc1c(OC(F)(F)F)cccc1C1=CCNCC1
Agent: [Pd]
Agent: Cl
Solvent: CO
Product: Fc1c(OC(F)(F)F)cccc1C1CCNCC1

Procedure:
Preparation according to preparation 18: 4-[2-fluoro-3-(trifluoromethoxy)phenyl]-1,2,3,6-tetrahydropyridine (3.33 g, 12.7 mmol), palladium on carbon (0.35 g), hydrochloric acid (0.5 ml), methanol (30 ml). Yield: 2.68 g. MS m/z (relative intensity, 70 eV) 263 (M+, 39), 262 (27), 206 (8), 178 (7) 56 (bp).
Reaction SMILES: [F:1][C:2]([F:21])([F:20])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[NH:15][C:14](=O)[CH2:13][CH2:12]3)=[CH:5][CH:4]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>O1CCCC1>[F:21][C:2]([F:1])([F:20])[C:3]1[CH:4]=[CH:5][C:6]([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[NH:15][CH2:14][CH2:13][CH2:12]3)=[CH:7][CH:8]=1
Reactant: O=C1CCc2cc(-c3ccc(C(F)(F)F)cc3)ccc2N1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: FC(F)(F)c1ccc(-c2ccc3c(c2)CCCN3)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 80.9 %

Procedure:
630 mg 6-(4-Trifluoromethyl-phenyl)-3,4-dihydro-1H-quinolin-2-one were dissolved in 10 ml tetrahydrofuran. 4.76 ml lithium aluminiumhydride 1M solution in tetrahydrofuran were added and the reaction mixture stirred for one hour at room temperature. Then 100 μl water and 100 μl 15% sodium hydroxide solution were added to the ice cooled reaction mixture. Then the reaction mixture was filtered off insoluble salts, and the filtrate evaporated under reduced pressure to obtain 485 mg 6-(4-Trifluoromethyl-phenyl)-1,2,3,4-tetrahydro-quinoline.
Reaction SMILES: C1CCCCC1.C([Li])(CC)C.[F:12][C:13]1[CH:14]=[C:15]([CH2:19][CH2:20][C:21]2[CH:30]=[CH:29][C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:22]=2)[CH:16]=[CH:17][CH:18]=1.[I:31]I>O.C1COCC1>[F:12][C:13]1[CH:14]=[C:15]([CH2:19][CH2:20][C:21]2[CH:30]=[CH:29][C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:22]=2)[CH:16]=[CH:17][C:18]=1[I:31]
Reactant: II
Reactant: Fc1cccc(CCc2ccc3ccccc3c2)c1
Agent: [Li]C(C)CC
Solvent: O
Solvent: C1CCCCC1
Solvent: C1CCOC1
Product: Fc1cc(CCc2ccc3ccccc3c2)ccc1I
Temperature: 25 °C
Reaction time: 1 h
Yield: 83.7 %

Procedure:
A 53.35 ml cyclohexane solution of sec-butyl lithium in a concentration of 1.01M was dropped into a 200 ml THF solution of 8.43 g (33.68 mmol) of the above 2-[2-(3-fluorophenyl)ethyl]naphthalene at −70° C. After the dropping was finished, the reaction solution was stirred at the same temperature for 1 hour, added with a 200 ml THF solution of 13.68 g (=53.90 mmol) of iodine through dropping and then slowly heated to room temperature. After being stirred for 18 hours, the reaction solution was added in iced water dissolved with Na2S2O3.5H2O, and then the reaction mixture was extracted twice with toluene. The extract was washed thrice with water, and was then dried with anhydrous MgSO4. After the solvent was evaporated under a reduced pressure, the obtained orange solid of 13.05 g was purified with silica gel chromatography using heptane/toluene in a ratio of 5:1 as the eluent to obtain a yellowish solid of 11.66 g, which was recrystallized with a mixed solvent of Solumix/heptane in a ratio of 5:1 to obtain 10.60 g of 2-[2-(3-fluoro-4-iodophenyl)ethyl]naphthalene as yellowish crystals.
Reaction SMILES: [CH3:1][N:2]([CH3:14])[C:3](=[S:13])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][CH:6]=1.C([Mg]Br)(C)C.[C:20]1(=[O:26])[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1.Cl>C1(C)C=CC=CC=1.C(OC)(C)(C)C>[CH3:14][N:2]([CH3:1])[C:3](=[S:13])[CH:4]([C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][CH:6]=1)[C:20]1([OH:26])[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1
Reactant: COc1ccc(CC(=S)N(C)C)cc1
Reactant: O=C1CCCCC1
Agent: CC(C)[Mg]Br
Agent: Cl
Solvent: Cc1ccccc1
Solvent: COC(C)(C)C
Product: COc1ccc(C(C(=S)N(C)C)C2(O)CCCCC2)cc1
Yield: 62.9 %

Procedure:
N,N-Dimethyl-p-methoxyphenylthioacetamide (20.9 g) in toluene was added to a solution of 1.45M isopropyl magnesium bromide in methyl t-butyl ether (80 ml) and toluene (400 ml) under an inert atmosphere of nitrogen whilst the internal temperature was maintained below 10° C. After 2 hours a solution of cyclohexanone (9.82 g) in toluene (50 ml) was added to the reaction mixture under nitrogen. After a further 15 minutes the mixture was blown over onto 1N hydrochloric acid (150 ml). The organic phase was washed, dried and evaporated. Recrystallisation of the residue from di-isopropyl ether gave the title compound (19.3 g, 64% yield), melting point 132° to 3° C.
Reaction SMILES: C[O:2][CH2:3][C:4]1[N:9]=[C:8]([NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[N:7]=[C:6]([N:17]2[CH2:26][CH2:25][C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH:18]2[CH3:27])[C:5]=1[CH3:28].B(Br)(Br)Br.C(OCC)C.[ClH:38]>ClCCl.C(O)C>[ClH:38].[OH:2][CH2:3][C:4]1[N:9]=[C:8]([NH:10][C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:7]=[C:6]([N:17]2[CH2:26][CH2:25][C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH:18]2[CH3:27])[C:5]=1[CH3:28]
Reactant: COCc1nc(Nc2ccccc2)nc(N2CCc3ccccc3C2C)c1C
Agent: BrB(Br)Br
Agent: Cl
Solvent: CCO
Solvent: CCOCC
Solvent: ClCCl
Product: Cc1c(CO)nc(Nc2ccccc2)nc1N1CCc2ccccc2C1C
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 59.5 %

Procedure:
A solution of 6-methoxymethyl-5-methyl-2-phenylamino-4-(1-methyl-1,2,3,4-tetrahydroisoquinolin-2-yl)pyrimidine(4.0 g, 9.7 mmol) in dichloromethane (50 ml) was cooled under 0° C. Boron tribromide (1M-dichloromethane solution, 38.8 ml, 38.8 mmol) was added dropwise to the solution. The reaction mixture was stirred for 30 minutes at 0° C. and poured into ice water. The separated dichloromethane layer was washed with aqueous sodium bicarbonate solution, dried over anhydrous sodium sulfate, concentrated under a reduced pressure. Ethyl ether was added to the resulting residue to give a solid, which was then dissolved in ethanol and treated with ethyl ether saturated with hydrochloric acid to give 2.3 g of the titled compound.
Reaction SMILES: C([Li])(C)(C)C.[C:6]([Si:10]([O:13][CH:14]([C:19]1([CH2:23][CH2:24][CH3:25])[CH2:22][CH2:21][CH2:20]1)[CH2:15][CH:16]=[CH:17]I)([CH3:12])[CH3:11])([CH3:9])([CH3:8])[CH3:7].[CH2:26]=[O:27]>CCCCC.C1COCC1>[Si:10]([O:13][CH:14]([C:19]1([CH2:23][CH2:24][CH3:25])[CH2:22][CH2:21][CH2:20]1)[CH2:15][CH:16]=[CH:17][CH2:26][OH:27])([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:12])[CH3:11]
Reactant: C=O
Reactant: CCCC1(C(CC=CI)O[Si](C)(C)C(C)(C)C)CCC1
Agent: [Li]C(C)(C)C
Solvent: C1CCOC1
Solvent: CCCCC
Product: CCCC1(C(CC=CCO)O[Si](C)(C)C(C)(C)C)CCC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 26.4 %

Procedure:
tert-Butyllithium (1.32 mL of a 1.7M solution in pentane, 2.25 mmol) was added to a solution of the vinyl iodide 6 (460 mg, 1.25 mmol) in THF (2.2 mL) at −78° C. After 0.5 h paraformaldehyde (50 mg, 1.67 mmol) was added. The reaction was warmed to room temperature and stirred for 16 h. The reaction was quenched with saturated aqueous NH4Cl and extracted with EtOAc. The organic portion was dried (MgSO4), filtered and concentrated in vacuo. FCC (silica gel, 4:1 hex/EtOAc) yielded 103 mg (33%) of the alcohol 7 as a clear, colorless oil.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]=[CH:8][C:9]([OH:11])=O)[CH:2]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[OH:24][C:25]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH2:26][CH2:27][CH2:28][CH2:29][NH2:30]>C1COCC1>[OH:24][C:25]([C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1)([C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)[CH2:26][CH2:27][CH2:28][CH2:29][NH:30][C:9](=[O:11])[CH:8]=[CH:7][C:3]1[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=1
Reactant: NCCCCC(O)(c1ccccc1)c1ccccc1
Reactant: O=C(O)C=Cc1cccnc1
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Product: O=C(C=Cc1cccnc1)NCCCCC(O)(c1ccccc1)c1ccccc1

Procedure:
Batch size: 1.7 g (11.3 mmol) 3-(3-pyridyl)-acrylic acid, 1.7 g (10 mmol) CDI and 2.4 g (9.4 mmol) 5-hydroxy-5,5-diphenyl-pentylamine in 40 ml abs. THF.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[S:11]([O-:14])(=[O:13])=[O:12].[Na+:15].[Na].[H-].[Na+].[CH3:19][CH2:20][O:21][CH2:22][CH2:23][OH:24]>>[CH2:20]([O:21][CH2:22][CH2:23][O:24][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[S:11]([O-:14])(=[O:13])=[O:12])[CH3:19].[Na+:15]
Reactant: CCOCCO
Reactant: O=[N+]([O-])c1ccc(Cl)c(S(=O)(=O)[O-])c1
Agent: [H-]
Agent: [Na+]
Agent: [Na]
Product: CCOCCOc1ccc([N+](=O)[O-])cc1S(=O)(=O)[O-]
Reaction time: 0.5 h

Procedure:
55 g of sodium 2-chloro-5-nitrobenzenesulfonate was added to a sodium 2-ethoxyethylate solution prepared by adding 7.3 g of sodium hydride (14.6 g in the form of a 50% liquid paraffin suspension) to 300 ml of ethyl cellosolve. This reaction mixture was stirred for 30 minutes while maintaining the temperature at 80° to 85° C. After completion of the reaction, insolubles were filtered off, and 150 ml of ethyl cellosolve was distilled out of the filtrate. 300 ml of isopropyl alcohol was added to the concentrate and cooled with ice. Crystals thus formed were collected by filtration, washed with 100 ml of isopropyl alcohol, and air-dried. Yield: 33 g; m.p. above 250° C.
Reaction SMILES: [CH3:1][O:2][N:3]=[C:4]([CH3:17])[CH2:5][N:6]1C(=O)C2=CC=CC=C2C1=O.O.NN.Cl[C:22]1[N:30]=[CH:29][N:28]=[C:27]2[C:23]=1[NH:24][CH:25]=[N:26]2.C(N(C(C)C)C(C)C)C>CO.O.CCOCC>[CH3:1][O:2][N:3]=[C:4]([CH3:17])[CH2:5][NH:6][C:22]1[N:30]=[CH:29][N:28]=[C:27]2[C:23]=1[NH:24][CH:25]=[N:26]2
Reactant: Clc1ncnc2nc[nH]c12
Reactant: CON=C(C)CN1C(=O)c2ccccc2C1=O
Agent: NN
Solvent: CO
Solvent: O
Solvent: CCOCC
Product: CON=C(C)CNc1ncnc2nc[nH]c12
Temperature: 25 °C
Reaction time: 1 h
Yield: 21.4 %

Procedure:
0.232 g (1.00 mmol) of N-[2-(N-methoxyimino)propyl]phthalimide was dissolved in 6 ml of methanol and to the solution was added 60 μl (1.2 mmol) of hydrazine hydrate, followed by being refluxed for 5 hours. The reaction mixture was cooled to room temperature and then, 20 ml of ether was added thereto and the mixture was left to stand at 0° C. for 1 hour to sufficiently precipitate solids. The solids were removed by suction filtration and the filtrate was dried over sodium sulfate and concentrated to 1 ml by an evaporator. This concentrated filtrate was dissolved in 5 ml of isopropanol and to the solution were added 105 mg (0.680 mmol) of 6-chloropurine and 101 μl of ethyldiisopropylamine, followed by being refluxed with heating on an oil bath for 5 hours. The reaction mixture was poured into 20 ml of water and extracted with chloroform (15 ml×5). The extract was dried over magnesium sulfate and the solvent was distilled off. The residue was purified by a thin layer chromatography (silica gel, developing agent: 15% ethanol-chloroform) to give 32.0 mg (yield 15%) of the titled compound as white solids.
Reaction SMILES: [NH:1]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C@H:2]([C:11]([NH:13][C@@H:14]([C:19]([NH:21][CH2:22][C:23]([OH:25])=[O:24])=[O:20])[CH2:15][CH2:16][S:17][CH3:18])=[O:12])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.OO.CN(C=[O:39])C>CO.C(O)(=O)C.[Pd]>[NH:1]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C@H:2]([C:11]([NH:13][C@@H:14]([C:19]([NH:21][CH2:22][C:23]([OH:25])=[O:24])=[O:20])[CH2:15][CH2:16][S:17]([CH3:18])=[O:39])=[O:12])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1
Reactant: CN(C)C=O
Reactant: CSCC[C@@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)OC(C)(C)C)C(=O)NCC(=O)O
Agent: [Pd]
Agent: OO
Solvent: CO
Solvent: CC(=O)O
Product: CS(=O)CC[C@@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)OC(C)(C)C)C(=O)NCC(=O)O
Reaction time: 5 h

Procedure:
In a mixed solvent comprising 10 ml of MeOH and 5 ml of acetic acid is dissolved 2.2 g of BOC-Tyr-(D)-Met-Gly-OH, followed by adding 0.6 ml of 30% aqueous hydrogen peroxide solution, and the mixture is stirred at roomtemperature for 5 hours. Following the addition of a small amount of palladium black, the mixture is stirred. The catalyst is filtered out, andthe solvent is distilled off, whereby the precipitated crystals are collected by filtration. Thus obtained is 2.1 g of the desired product, m.p. 185° C. (decomposed), Rf1 =0.20, [α]D21 +1.8° (c=0.5, DMF)
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[CH:4][C:3]=1[OH:11].Cl.Cl[CH2:14][C:15]1[N:16]=[CH:17][S:18][CH:19]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>C(#N)C.C(Cl)Cl.O>[ClH:1].[Cl:1][C:2]1[CH:7]=[C:6]([NH2:8])[CH:5]=[CH:4][C:3]=1[O:11][CH2:14][C:15]1[N:16]=[CH:17][S:18][CH:19]=1
Reactant: ClCc1cscn1
Reactant: O=[N+]([O-])c1ccc(O)c(Cl)c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [I-]
Solvent: O
Solvent: CC#N
Solvent: ClCCl
Product: Nc1ccc(OCc2cscn2)c(Cl)c1
Reaction time: 8 h
Yield: 0.2 %

Procedure:
To a solution of 2-chloro-4-nitrophenol (1.00 g, 5.76 mmol) in acetonitrile (125 mL) were added 4-chloromethylthiazole hydrochloride (1.08 g, 6.34 mmol), Potassium carbonate (2.39 g, 17.29 mmol) and sodium iodide (1.73 g, 11.52 mmol). The reaction mixture was stirred at 60 C overnight. Water (60 mL) and DCM (10 mL) were added. After all solid material dissolved, layers formed were separated. The organic layer was washed with water and brine, dried over Na2SO4 and concentrated down to give the required material as a light yellow solid (1.29 mg, 83%). 1H-NMR (CD2Cl2) δ 8.87 (d, 1H), 8.32 (d, 1H), 8.16 (dd, 1H), 7.54-7.56 (m, 1H), 7.22 (d, 1H), 5.33-5.34 (m, 2H); LCMS RT=3.01 min; [M+H]+=271.0.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.Cl[CH2:11][CH2:12][CH2:13][CH2:14][O:15]C(=O)C.C(=O)([O-])[O-].[K+].[K+].[OH-].[K+]>CO.O>[OH:15][CH2:14][CH2:13][CH2:12][CH2:11][O:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1
Reactant: O=Cc1ccc(O)cc1
Reactant: CC(=O)OCCCCCl
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: O=Cc1ccc(OCCCCO)cc1
Temperature: 120 °C
Reaction time: 3 h
Yield: 908.7 %

Procedure:
In a 1 L three neck distillation flask, p-hydroxybenzaldehyde (24.4 g, 20 mmol), 4-chlorobutylacetate (36.1 g, 240 mmol), potassium carbonate (33.2 g, 240 mmol) and dimethylformamido (150 ml) were placed and stirred for 3 hours at 120° C. After the reaction mixture was cooled, water was added and the resulting mixture was extracted with ethyl acetate. The solvent was removed to obtain an oily product. The product was dissolved in methanol (100 ml), and potassium hydroxide (22.4 g, 0.4 mmol) dissolved in water (50 ml) was dropwise added to the solution. The mixture was refluxed for 2 hours, and then cooled. Water was added and the resulting mixture was extracted with ethyl acetate. The solvent was removed to obtain an oily product. The product was purified through column chromatography to prepare the titled compound (35.3 g, yield: 91%).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[N:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]1)([O-])=O>CCO.[Pd]>[NH2:1][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[N:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]1
Reactant: CC(C)(C)OC(=O)N1CCN(c2ccccc2[N+](=O)[O-])CC1
Agent: [Pd]
Solvent: CCO
Product: CC(C)(C)OC(=O)N1CCN(c2ccccc2N)CC1
Yield: 99.1 %

Procedure:
Into a 500 mL round bottomed flask equipped with magnetic stirring was added tert-butyl 4-(2-nitrophenyl)piperazinecarboxylate (5.0 g, 16 mmol) in 95% EtOH (250 mL), and 10% Pd/C (2.0 g, 1.9 mmol) (Aldrich). The flask was equipped with a balloon filled with H2, and the reaction was stirred for 18 h. After filtering through a pad of Celite®, the crude material was concentrated in vacuo to afford the desired compound (4.4 g). MS (ESI, pos. ion) m/z: 278 (M+H), (ESI, neg. ion) m/z: 276 (M−H). Calc'd for C15H23N3O2: 277.18.
Reaction SMILES: [S:1](Cl)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].[OH:12][CH:13]([CH2:17][C:18]#[CH:19])[C:14](=[O:16])[CH3:15].C(N(CC)CC)C>C(Cl)Cl>[S:1]([O:12][CH:13]([CH2:17][C:18]#[CH:19])[C:14](=[O:16])[CH3:15])([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2]
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: C#CCC(O)C(C)=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C#CCC(OS(=O)(=O)c1ccc(C)cc1)C(C)=O
Reaction time: 2.5 h
Yield: 55.3 %

Procedure:
Tosyl chloride (3.81 g) was added to a solution of 3-hydroxy-5-hexyn-2-one (2.24 g) and triethylamine (2.424 g) in methylene chloride (20 ml) under ice-cooling. After being stirred for 2.5 hours, the mixture was washed with water, dried over magnesium sulfate and evaporated in vacuo. The oily residue was purified by column chromatography on silica gel (60 g) using methylene chloride as an eluent to give an oil of 3-tosyloxy-5-hexyn-2-one (2.94 g).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[C:6]([OH:12])[CH:5]=1.[CH2:14](Br)[CH:15]=[CH:16][CH3:17]>>[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[C:6]([O:12][CH2:14][CH:15]=[CH:16][CH3:17])[CH:5]=1
Reactant: CC=CCBr
Reactant: COC(=O)c1cc(O)cc(OC)c1
Product: CC=CCOc1cc(OC)cc(C(=O)OC)c1

Procedure:
3,5-Dimethoxy-4-(1-methyl) propyl-benzoyl chloride. Starting from 3-hydroxy-5-methoxy-benzoic acid methyl ester by reaction with 2-butenylbromide, 3-(2-butenyloxy)-5-methoxy-benzoic acid methyl ester is obtained. B.p. 156°-58°C/0.4 mmHg. By operating as described under C) the 3,5-dimethoxy-4-(3-methylpropen-3-yl)-benzoic acid is obtained. M.p. 140°-41°C (from diethyl ether/light petroleum). This compound is hydrogenated as under D) to give 3,5-dimethoxy-4-(1-methyl)propyl-benzoic acid, m.p. 125°-26°C (from diethyl ether/light petroleum). This compound is allowed to react with thionyl chloride, thus obtaining the title compound. M.p. 47°-48°C (from diethyl ether upon cooling).