Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[C:8]([O:10][C:11](=[O:25])[C:12]2[CH:17]=[CH:16][C:15]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])=[CH:14][CH:13]=2)[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].CC(C)=[O:28].OS(O)(=O)=O.O=[Cr](=O)=O>CC(C)=O>[Cl:1][C:2]1[CH:9]=[C:8]([O:10][C:11](=[O:25])[C:12]2[CH:13]=[CH:14][C:15]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])=[CH:16][CH:17]=2)[CH:7]=[CH:6][C:3]=1[C:4]([OH:28])=[O:5]
Reactant: CC(C)=O
Reactant: CCCCCCCc1ccc(C(=O)Oc2ccc(C=O)c(Cl)c2)cc1
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Product: CCCCCCCc1ccc(C(=O)Oc2ccc(C(=O)O)c(Cl)c2)cc1
Reaction time: 1 h

Procedure:
The resulting, crude 2-chloro-4-[(p-heptylbenzoyl)oxy]benzaldehyde is dissolved in 350 ml of acetone. Within 40 minutes there are added dropwise thereto 30 ml of Jones' reagent, the mixture warming slightly. The mixture is stirred for a further 1 hour, precipitated inorganic material is then filtered off under suction, the filtrate is diluted with 300 ml of water (the product precipitating), concentrated on a rotary evaporator to about 300 ml and the suspension obtained is suction filtered. The suction filter material is washed three times with 50 ml of 10% aqueous acetone, dried and recrystallized from about 60 ml of benzene. There are obtained 13.8 g of 2-chloro-4-[(p-heptylbenzoyl)oxy]benzoic acid, m.p. 108° C. (nematic).
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.CC(C)([O-])C.[K+].[CH:12]([Si:15](Cl)([CH:19]([CH3:21])[CH3:20])[CH:16]([CH3:18])[CH3:17])([CH3:14])[CH3:13]>CCOCC.C1OCCOCCOCCOCCOCCOC1>[CH:12]([Si:15]([CH:19]([CH3:21])[CH3:20])([CH:16]([CH3:18])[CH3:17])[N:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1)([CH3:14])[CH3:13]
Reactant: c1cc[nH]c1
Reactant: CC(C)[Si](Cl)(C(C)C)C(C)C
Agent: C1COCCOCCOCCOCCOCCO1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CCOCC
Product: CC(C)[Si](C(C)C)(C(C)C)n1cccc1
Reaction time: 16 h
Yield: 85.3 %

Procedure:
Pyrrole (2.9 ml, 42 mmol) was added dropwise with stirring at room temperature to a suspension of potassium tert-butoxide (4.66 g, 42 mmol) and 18-crown-6 (0.2 g, 0.76 mmol) in ether (300 ml). After 1 hour tri-isopropylsilyl chloride (8.Og, 42 mmol) was added dropwise, and then the reaction mixture was stirred for 16 hours, and filtered. The residue was washed with ether and the combined filtrate and washings were washed with brine, then dried and concentrated to give N-tri-isopropylsilylpyrrole (8.0 g, 86% yield) as a clear oil, 1H nmr : delta 1.04 (18H, d), 1.38 (3H, m), 6.22 (2H, m), 6.72 (2H, m) ppm.
Reaction SMILES: [CH:1]([NH:4][CH:5]([CH3:7])[CH3:6])([CH3:3])C.[Li]CCCC.C[C:14]1[CH2:18][CH2:17][CH2:16][N:15]=1.CSC1CCCN=1>C1COCC1>[NH:15]1[CH2:16][CH2:17][CH2:18][C:14]1=[CH:7][C:5]1[CH2:6][CH2:3][CH2:1][N:4]=1
Reactant: CC1=NCCC1
Reactant: CC(C)NC(C)C
Agent: CSC1=NCCC1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: C(=C1CCCN1)C1=NCCC1
Reaction time: 0.5 h

Procedure:
To a solution of diisopropylamine (11.1 g, 109.7 mmol) in THF (200 mL) was dropwise added n-BuLi (2.89 M, 37.97 mL, 109.7 mmol) at −78° C. under nitrogen. Once all the n-BuLi was added, the temperature was adjusted to −5° C., and the reaction mixture was stirred for 30 min. Then a solution of 2-methyl-1-pyrroline (5.65 g, 67.9 mmol) in THF (15 mL) was added dropwise to the reaction mixture at −5° C., and then stirred. After 30 min, 2-methylthio-1-pyrroline (6.02 g, 52.3 mmol) was added dropwise over 30 min at −78° C. The reaction mixture was stirred as the temperature was allowed to gradually rise to room temperature, and was continuously stirred at room temperature overnight. THF solvent was removed under reduced pressure, then 50 mL of methanol was added dropwise to the residue. After removing all of the volatile solvent, pentane (2×100 mL) was added to the residue, and the mixture was filtered. Concentration of the filtrate under reduced pressure, followed by vacuum distillation (65° C. at 110 mTorr), delivered 6.29 of product (79%). 1H NMR (CD2Cl2, 500 MHz): δ 7.89 (s, br, 1H), 4.65 (s, 1H), 3.64 (t, 2H, J=7.2 Hz), 2.51 (t, 2H, J=8.0 Hz), 1.85 (m, 2H). 13C NMR (CD2Cl2, 125 MHz): δ 167.0, 81.7, 53.7, 34.8, 23.2.
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:12]=[CH:11][C:8]([CH:9]=[O:10])=[CH:7][CH:6]=1)=O.[NH2:13][C:14]1[S:15][CH:16]=[CH:17][N:18]=1>CN(C=O)C>[S:15]1[CH:16]=[CH:17][N:18]2[CH:2]=[C:3]([C:5]3[CH:12]=[CH:11][C:8]([CH:9]=[O:10])=[CH:7][CH:6]=3)[N:13]=[C:14]12
Reactant: O=Cc1ccc(C(=O)CBr)cc1
Reactant: Nc1nccs1
Solvent: CN(C)C=O
Product: O=Cc1ccc(-c2cn3ccsc3n2)cc1

Procedure:
0.7 g (2.1 mM) 4-(2-Bromo-acetyl)-benzaldehyde and 2-aminothiazole (2 eq) are stirred in 15 ml DMF at 90° C. for 6 h. The DMF is evaporated and the residue suspended in ethyl acetate over night. The desired product is collected by filtration.
Reaction SMILES: [CH:1]([C:5]1[CH:11]=[CH:10][CH:9]=[C:8](Br)[C:6]=1[NH2:7])([CH2:3][CH3:4])[CH3:2].[C:13](B1OC(C)(C)C(C)(C)O1)([CH3:15])=[CH2:14].CC#N.C([O-])([O-])=O.[K+].[K+]>O.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>[CH:1]([C:5]1[CH:11]=[CH:10][CH:9]=[C:8]([CH:13]([CH3:15])[CH3:14])[C:6]=1[NH2:7])([CH2:3][CH3:4])[CH3:2]
Reactant: C=C(C)B1OC(C)(C)C(C)(C)O1
Reactant: CCC(C)c1cccc(Br)c1N
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: [K+]
Solvent: CC#N
Solvent: O
Product: CCC(C)c1cccc(C(C)C)c1N

Procedure:
(−)-2-Sec-butyl-6-bromoaniline (2) (0.684 g, 3 mmol), isopropenylboronic acid pinacol ester (1 g, 6 mmol), tetrakis(triphenylphosphine)palladium(0) (0.035 g, 0.03 mmol), MeCN 10 ml and K2CO3 (5 ml, 1M solution) were heated in a microwave at 160° C. for 400 sec. The reaction mixture was diluted with water (75 ml). Products were extracted with ethyl acetate (50 ml). The organic layer was washed with 5% NaHCO3, brine and dried over anhydrous MgSO4. The solvent was removed under reduced pressure, and the compound purified by silica gel chromatography (CombiFlash, 30 g column, hexane-ethyl acetate). The reduction was then performed in MeOH (40 ml) over 5% Pd/C (˜0.3 g), hydrogen pressure 60 psi overnight (0.48 g, 72%).
Reaction SMILES: [Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[O:9][CH3:10].CCN(C(C)C)C(C)C.Cl[C:21]([O:23][CH2:24][CH2:25]Cl)=[O:22]>C(#N)C>[Br:1][C:2]1[CH:8]=[CH:7][C:5]([N:6]2[CH2:25][CH2:24][O:23][C:21]2=[O:22])=[CH:4][C:3]=1[O:9][CH3:10]
Reactant: O=C(Cl)OCCCl
Reactant: COc1cc(N)ccc1Br
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: COc1cc(N2CCOC2=O)ccc1Br
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 17.1 %

Procedure:
To a stirred solution of 4-Bromo-3-methoxy-aniline (10.0 g) in acetonitrile (176 mL) was added Hünig Base (25 mL) and 2-chloroethyl chloroformate (10.6 g). The mixture was stirred at room temperature for 0.5 h. The solvent was removed in vacuum. The residue was dissolved in tetrahydrofurane (250 mL), and potassium tert-butoxide (16.2 g) was added. The mixture was stirred at room temperature for 2 h. The solvent was removed in vacuum. The residue was dissolved in ethyl acetate and the mixture was washed with water and with saturated sodium chloride solution, dried (sodium sulfate) and the solvent was removed in vacuum. Silica gel chromatography gave a compound that was crystallized from ethanol. Yield: 7.7 g of the title compound. The mother liquor was concentrated in vacuum and aminophase-silica-gel chromatography gave a solid that was recrystallized from ethanol to give further 2.3 g of the title compound.
Reaction SMILES: [CH2:1]([C:3]1[C:8](=[O:9])[NH:7][C:6]([CH3:10])=[C:5]([C:11]2[CH:12]=[N:13][CH:14]=[C:15]([C:17]([OH:19])=O)[CH:16]=2)[CH:4]=1)[CH3:2].[OH:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25][NH2:26])=[CH:23][C:22]=1[O:29][CH3:30]>>[OH:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25][NH:26][C:17]([C:15]2[CH:16]=[C:11]([C:5]3[CH:4]=[C:3]([CH2:1][CH3:2])[C:8](=[O:9])[NH:7][C:6]=3[CH3:10])[CH:12]=[N:13][CH:14]=2)=[O:19])=[CH:23][C:22]=1[O:29][CH3:30]
Reactant: CCc1cc(-c2cncc(C(=O)O)c2)c(C)[nH]c1=O
Reactant: COc1cc(CN)ccc1O
Product: CCc1cc(-c2cncc(C(=O)NCc3ccc(O)c(OC)c3)c2)c(C)[nH]c1=O

Procedure:
Method 1, Example 205 is substantially repeated except for utilizing 5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid and 4-hydroxy-3-methoxy-benzylamine to afford the title compound. MS: m/e=394 (M+H).
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][C:5](C=O)=[C:4]([O:10][CH3:11])[CH:3]=1.CO[CH:14]([O:17][CH3:18])[O:15][CH3:16].C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+]>CO>[CH3:18][O:17][CH:14]([O:15][CH3:16])[C:5]1[CH:8]=[CH:9][C:2]([Br:1])=[CH:3][C:4]=1[O:10][CH3:11]
Reactant: COc1cc(Br)ccc1C=O
Reactant: COC(OC)OC
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: COc1cc(Br)ccc1C(OC)OC

Procedure:
To a solution of 4-bromo-2-methoxybenzaldehyde (5.2 g, 24.2 mmol) in methanol (20 ml) and trimethylorthoformate (14 ml, 5.5 eq.) was added p-toluenesulfonic acid (46 mg, 0.01 eq.) and the mixture was refluxed for 3 hr. Potassium carbonate (125 mg, 0.03 eq.) and silicagel was added, the solvent was removed under reduced pressure and the solid residue packed into a loading column and purified by MPLC (hexanes-ethylacetate 40-80% gradient). MS (EI+): 262, 260 (1/1, M+, 10%); 231, 229 (1/1, 90%); 215, 213 (1/1, 10%); 199, 170, 150, 118, 92, 75, 45 (100%).
Reaction SMILES: [NH2:1][C:2]1[CH:17]=[CH:16][C:5]([O:6][C:7]2[CH:8]=[CH:9][C:10]3[S:14][N:13]=[CH:12][C:11]=3[CH:15]=2)=[CH:4][CH:3]=1.C1(C)C=CC=CC=1.[CH3:25][N:26]=[C:27]=[O:28]>C(N(CC)CC)C>[CH3:25][NH:26][C:27]([NH:1][C:2]1[CH:17]=[CH:16][C:5]([O:6][C:7]2[CH:8]=[CH:9][C:10]3[S:14][N:13]=[CH:12][C:11]=3[CH:15]=2)=[CH:4][CH:3]=1)=[O:28]
Reactant: Nc1ccc(Oc2ccc3sncc3c2)cc1
Reactant: CN=C=O
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: CNC(=O)Nc1ccc(Oc2ccc3sncc3c2)cc1
Yield: 85 %

Procedure:
24.2 parts of 5-(4'-aminophenoxy)-benzisothiazole, 400 parts of toluene, 1 part of triethylamine and 11.4 parts of methyl isocyanate were heated at 80° C. for 12 hours, and the reaction mixture was then evaporated down under reduced pressure. 25 parts (85% of theory) of 5-(4'-methylaminocarbonylaminophenoxy)-benzisothiazole of melting point 178° C. were obtained.
Reaction SMILES: I[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([NH2:11])[N:10]=2)[N:7]=1.[C:12]([C:14]1[CH:19]=[CH:18][C:17]([NH:20][C:21]([NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[CH:25]=2)=[O:22])=[CH:16][CH:15]=1)#[CH:13].C(N(CC)CC)C>CN(C=O)C.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.[Cu]I>[NH2:11][C:9]1[N:10]=[C:5]2[CH:4]=[CH:3][C:2]([C:13]#[C:12][C:14]3[CH:15]=[CH:16][C:17]([NH:20][C:21]([NH:23][C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[CH:25]=4)=[O:22])=[CH:18][CH:19]=3)=[N:7][N:6]2[CH:8]=1
Reactant: C#Cc1ccc(NC(=O)Nc2cccc(C)c2)cc1
Reactant: Nc1cn2nc(I)ccc2n1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: Cc1cccc(NC(=O)Nc2ccc(C#Cc3ccc4nc(N)cn4n3)cc2)c1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
To a nitrogen bubbled solution of 6-iodo-imidazo[1,2-b]pyridazin-2-ylamine (260 mg, 1 mmol, 1 eq) and 1-(4-ethynylphenyl)-3-(3-methylphenyl)urea (375 mg, 1.5 eq) in DMF (5 mL) was added triethylamine (0.56 mL, 4 eq), bis(triphenylphosphine)palladium(II) dichloride (70.2 mg, 0.1 eq), and copper(I) iodide (38.1 mg, 0.2 eq). The reaction mixture was stirred at room temperature for 10 minutes and then partitioned between saturated aq NaHCO3 and i-PrOH—CHCl3 (1:4). The aqueous layer was extracted once more with i-PrOH—CHCl3 (1:4). The two organic layers were combined, washed with brine, and dried with anhydrous Na2SO4. The upper clear liquid was decanted, concentrated with silica gel, and the solid mixture was chromatographed (eluted from DCM to MeOH-DCM 1:15). The product fractions were collected and concentrated. The solid residue was triturated with EtOAc-Hex (1:1) and gave 1-{4-[(2-aminoimidazo[1,2-b]pyridazin-6-yl)ethynyl]phenyl}-3-(3-methylphenyl)urea as a brown solid upon filtration in amount of 133 mg.
Reaction SMILES: Cl.[NH2:2][C@H:3]([C:6]([NH2:8])=[O:7])[CH2:4][OH:5].[C:9]([O:24][C@H:25]([CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[CH2:26][C:27](O)=[O:28])(=[O:23])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].C(N(CC)CC)C.CCOC1N(C(OCC)=O)C2C(=CC=CC=2)C=C1>C(Cl)Cl>[C:9]([O:24][C@H:25]([CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[CH2:26][C:27]([NH:8][C:6](=[O:7])[C@H:3]([CH2:4][OH:5])[NH2:2])=[O:28])(=[O:23])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]
Reactant: CCCCCCCCCCCCCC(=O)O[C@H](CCCCCCCCCCC)CC(=O)O
Reactant: NC(=O)[C@@H](N)CO
Agent: CCOC(=O)N1c2ccccc2C=CC1OCC
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCCCCCCCCCCCC(=O)O[C@H](CCCCCCCCCCC)CC(=O)NC(=O)[C@@H](N)CO
Reaction time: 0.5 h
Yield: 71.3 %

Procedure:
A suspension of L-serinamide hydrochloride (0.157 g, 1.18 mmol) and (R)-3-tetradecanoyloxytetradecanoic acid (0.61 g, 1.34 mmol) in CH2Cl2 (6 mL) was treated with triethylamine (0.18 mL, 1.3 mmol) and the resulting solution was stirred with 4 Å molecular sieves for 30 min. EEDQ (0.437 g, 1.77 mmol) was then added and the mixture was stirred for 16 h at room temperature. The product that precipitated was collected and washed with CH2Cl2 (2×25 mL) to give 0.455 g (71%) of N-[(R)-3-tetradecanoyloxytetradecanoyl]-L-serinamide as a colorless powder: mp 126-130° C.; 1H NMR (CDCl3) δ 0.88 (t, 6H, J=˜7 Hz), 1.15-1.7 (m, 42H), 2.31 (t, 2H, J=7.5 Hz), 2.51 (d, 2H, J=6.3 Hz), 3.56 (br s, 1H), 3.65 (dd, 1H, J=11.2, 5.5 Hz), 3.86 (dd, 1H, J=11.2, 4.5 Hz), 4.21 (s, 2H), 4.40 (m, 1H), 5.22 (m, 1H).
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C:12]1[CH:13]=[CH:14][C:15]([O:18][C:19]2[CH:24]=[CH:23][C:22]([CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:21][CH:20]=2)=[N:16][CH:17]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:35][CH2:36][O:37][CH3:38].O>CN(C=O)C>[CH2:1]([O:8][C:9]([N:11]([CH2:35][CH2:36][O:37][CH3:38])[C:12]1[CH:13]=[CH:14][C:15]([O:18][C:19]2[CH:20]=[CH:21][C:22]([CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:23][CH:24]=2)=[N:16][CH:17]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COCCBr
Reactant: CCOC(=O)CCc1ccc(Oc2ccc(NC(=O)OCc3ccccc3)cn2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)CCc1ccc(Oc2ccc(N(CCOC)C(=O)OCc3ccccc3)cn2)cc1
Reaction time: 0.58 h

Procedure:
Under a nitrogen atmosphere, to a solution of ethyl 3-[4-(5-benzyloxycarbonylaminopyridin-2-yloxy)phenyl]propionate (1.7 g, 4.0 mmol) in DMF (50 mL) was added 60% sodium hydride (0.19 g, 4.9 mmol) under ice cooling, and the resulting solution was stirred for 35 minutes at the same temperature. 2-Bromoethylmethyl ether (0.4 mL, 4.2 mmol) was added dropwise to the solution. The reaction solution was stirred for 2 hours under ice cooling, and then stirred for 2 days at room temperature. To the reaction solution was added water, and extracted with ethyl acetate. The ethyl acetate layer was washed with water, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=4:1), to thereby yield 1.6 g of the title compound.
Reaction SMILES: [CH:1]1([C:6]2[C:15]([C:16]([C:18]3[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=3)=[O:17])=[C:14]([C:28]3[CH:33]=[CH:32][C:31]([F:34])=[C:30]([F:35])[CH:29]=3)[C:13]3[CH:12]([OH:36])[CH2:11][C:10]([CH3:38])([CH3:37])[CH2:9][C:8]=3[N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.N1C(C)=CC=CC=1C.FC(F)(F)S(O[Si:53]([C:56]([CH3:59])([CH3:58])[CH3:57])([CH3:55])[CH3:54])(=O)=O>C1(C)C=CC=CC=1>[Si:53]([O:36][CH:12]1[CH2:11][C:10]([CH3:38])([CH3:37])[CH2:9][C:8]2[N:7]=[C:6]([CH:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)[C:15]([C:16]([C:18]3[CH:23]=[CH:22][C:21]([C:24]([F:26])([F:27])[F:25])=[CH:20][CH:19]=3)=[O:17])=[C:14]([C:28]3[CH:33]=[CH:32][C:31]([F:34])=[C:30]([F:35])[CH:29]=3)[C:13]1=2)([C:56]([CH3:59])([CH3:58])[CH3:57])([CH3:55])[CH3:54]
Reactant: CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F
Reactant: CC1(C)Cc2nc(C3CCCC3)c(C(=O)c3ccc(C(F)(F)F)cc3)c(-c3ccc(F)c(F)c3)c2C(O)C1
Solvent: Cc1cccc(C)n1
Solvent: Cc1ccccc1
Product: CC1(C)Cc2nc(C3CCCC3)c(C(=O)c3ccc(C(F)(F)F)cc3)c(-c3ccc(F)c(F)c3)c2C(O[Si](C)(C)C(C)(C)C)C1
Temperature: 20 °C
Reaction time: 3 h

Procedure:
0.529 g (1 mmol) of [2-cyclopentyl-4-(3,4-difluorophenyl)-5-hydroxy-7,7-dimethyl-5,6,7,8-tetrahydro-quinolin-3-yl]-(4-trifluoromethylphenyl)-methanone are dissolved in 6 ml of abs. toluene and admixed with 0.465 ml of lutidine at −5° C. At from −5° C. to −10° C., 0.459 ml (2 mmol) of tert-butyldimethylsilyl trifluoromethanesulphonate is added. The mixture is stirred at 20° C. for 3 hours. The mixture is diluted with toluene, the reaction is quenched with 10% strength aqueous ammonium chloride solution and the organic phase is washed with 0.1 N hydrochloric acid and saturated aqueous sodium bicarbonate solution and dried. The solvent is distilled off under reduced pressure and the residue is then purified using a column. This gives 620 mg of colourless crystals of melting point: 128° C.-129° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([NH2:21])=[CH:5][C:6]2[CH2:12][CH2:11][N:10]([CH:13]([CH2:17][O:18][CH3:19])[CH2:14][O:15][CH3:16])[CH2:9][CH2:8][C:7]=2[CH:20]=1.Cl[C:23]1[N:28]=[C:27]([NH:29][C:30]2([CH2:36][C:37]([NH2:39])=[O:38])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]2)[C:26]([Cl:40])=[CH:25][N:24]=1>>[Cl:40][C:26]1[C:27]([NH:29][C:30]2([CH2:36][C:37]([NH2:39])=[O:38])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]2)=[N:28][C:23]([NH:21][C:4]2[C:3]([O:2][CH3:1])=[CH:20][C:7]3[CH2:8][CH2:9][N:10]([CH:13]([CH2:14][O:15][CH3:16])[CH2:17][O:18][CH3:19])[CH2:11][CH2:12][C:6]=3[CH:5]=2)=[N:24][CH:25]=1
Reactant: COCC(COC)N1CCc2cc(N)c(OC)cc2CC1
Reactant: NC(=O)CC1(Nc2nc(Cl)ncc2Cl)CCCCC1
Product: COCC(COC)N1CCc2cc(Nc3ncc(Cl)c(NC4(CC(N)=O)CCCCC4)n3)c(OC)cc2CC1

Procedure:
The title compound was prepared from 8-Methoxy-3-(2-methoxy-1-methoxymethyl-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine and 2-[1-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclohexyl]-acetamide in an analogous manner to Example 61e. Product isolated as a pale yellow foam (0.064 g, 49%). MP: 71-83° C. 1H NMR (400 MHz, CDCl3, δ, ppm): 7.92 (s, 1H), 7.84 (s, 1H), 7.14 (s, 1H), 6.64 (s, 1H), 5.40 (br s, 1H), 5.24 (s, 1H), 5.05 (br s, 1H), 3.85 (s, 3H), 3.57-3.51 (m, 2H), 3.47-3.41 (m, 2H), 3.32 (s, 6H), 3.06-2.98 (m, 1H), 2.90 (s, 2H), 2.87-2.77 (m, 8H), 2.37-2.29 (m, 2H), 1.71-1.29 (m, 8H). MS: 561.29 (MH)+.
Reaction SMILES: [N+:1]([CH:4]=[C:5](SC)[NH:6][CH2:7][CH2:8][S:9][CH2:10][C:11]1[NH:15][CH:14]=[N:13][C:12]=1[CH3:16])([O-:3])=[O:2].[NH2:19][CH2:20][CH2:21][S:22][CH2:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=1>>[N+:1]([CH:4]=[C:5]([NH:19][CH2:20][CH2:21][S:22][CH2:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=1)[NH:6][CH2:7][CH2:8][S:9][CH2:10][C:11]1[NH:15][CH:14]=[N:13][C:12]=1[CH3:16])([O-:3])=[O:2]
Reactant: NCCSCCc1ccccn1
Reactant: CSC(=C[N+](=O)[O-])NCCSCc1[nH]cnc1C
Product: Cc1nc[nH]c1CSCCNC(=C[N+](=O)[O-])NCCSCCc1ccccn1

Procedure:
Reaction of 1-nitro-2-methylthio-2-[2-((4-methyl-5-imidazolyl)-methylthio)ethylamino]ethylene with 2-[2-(2-aminoethyl)thioethyl] pyridine according to the procedure of Example 1 (a) (ii) yields the title compound.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][O:9][C:10]2[CH:17]=[CH:16][C:13]([CH:14]=O)=[CH:12][CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:18][C:19](=[O:24])[CH2:20][C:21](=[O:23])[CH3:22].FC(F)(F)C(O)=O.S(Cl)(Cl)=O>>[C:1]1([CH2:7][CH2:8][O:9][C:10]2[CH:17]=[CH:16][C:13]([CH:14]=[CH:18][C:19](=[O:24])[CH2:20][C:21](=[O:23])[CH3:22])=[CH:12][CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(=O)CC(C)=O
Reactant: O=Cc1ccc(OCCc2ccccc2)cc1
Solvent: O=S(Cl)Cl
Solvent: O=C(O)C(F)(F)F
Product: CC(=O)CC(=O)C=Cc1ccc(OCCc2ccccc2)cc1

Procedure:
The procedure described in example 8 was repeated by using 5.9 g of 4-(2-phenylethoxy)benzaldehyde, 3.9 ml of 2,4-pentanedione, 26 ml of trifluoroacetic acid and 2.1 ml of thionyl chloride. Yield 4.7 91 an viscous oil.
Reaction SMILES: [Mn]([O-])(=O)(=O)=[O:2].[K+].[CH:7]([C:9]1[CH:10]=[CH:11][C:12]2[O:16][CH:15]=[C:14]([CH2:17][CH2:18][NH:19][C:20](=[O:22])[CH3:21])[C:13]=2[CH:23]=1)=[O:8]>CC(C)=O.O.CC(C)=O>[C:20]([NH:19][CH2:18][CH2:17][C:14]1[C:13]2[CH:23]=[C:9]([C:7]([OH:2])=[O:8])[CH:10]=[CH:11][C:12]=2[O:16][CH:15]=1)(=[O:22])[CH3:21]
Reactant: CC(=O)NCCc1coc2ccc(C=O)cc12
Reactant: O=[Mn](=O)(=O)[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: O
Product: CC(=O)NCCc1coc2ccc(C(=O)O)cc12
Temperature: 25 °C
Reaction time: 2 h

Procedure:
2.7 g of potassium permanganate in 50 ml of an acetone/water mixture (50/50) are added at ambient temperature to a solution of 6.88 mmol of the product obtained in Step D in 30 ml of acetone. The solution is stirred for 2 hours at ambient temperature and then filtered. The filtrate is concentrated under reduced pressure and chromatographed on silica gel to yield the title product.
Reaction SMILES: [NH2:1][C@H:2]([C:12]([NH:14][C@H:15]([C:19]([NH:21][C@H:22]([C:27]([OH:29])=[O:28])[CH2:23][CH:24]([CH3:26])[CH3:25])=[O:20])[CH:16]([CH3:18])[CH3:17])=[O:13])[CH2:3][S:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[NH:30]([C:79]([O:81][C:82]([CH3:85])([CH3:84])[CH3:83])=[O:80])[C@H:31]([C:41]([NH:43][C@H:44]([C:47]([NH:49][C@H:50]([C:55]([NH:57][C@H:58]([C:63]([NH:65][C@H:66]([C:69]([NH:71][C@H:72]([C:76](O)=[O:77])[C@@H:73]([CH3:75])[OH:74])=[O:70])[CH2:67][OH:68])=[O:64])[CH2:59][CH:60]([CH3:62])[CH3:61])=[O:56])[CH2:51][C:52](=[O:54])[NH2:53])=[O:48])[CH2:45][OH:46])=[O:42])[CH2:32][S:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.ON1C(=O)CCC1=O.C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C=O.C(N(CC)CC)C>[NH:30]([C:79]([O:81][C:82]([CH3:85])([CH3:84])[CH3:83])=[O:80])[C@H:31]([C:41]([NH:43][C@H:44]([C:47]([NH:49][C@H:50]([C:55]([NH:57][C@H:58]([C:63]([NH:65][C@H:66]([C:69]([NH:71][C@H:72]([C:76]([NH:1][C@H:2]([C:12]([NH:14][C@H:15]([C:19]([NH:21][C@H:22]([C:27]([OH:29])=[O:28])[CH2:23][CH:24]([CH3:25])[CH3:26])=[O:20])[CH:16]([CH3:18])[CH3:17])=[O:13])[CH2:3][S:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:77])[C@@H:73]([CH3:75])[OH:74])=[O:70])[CH2:67][OH:68])=[O:64])[CH2:59][CH:60]([CH3:62])[CH3:61])=[O:56])[CH2:51][C:52](=[O:54])[NH2:53])=[O:48])[CH2:45][OH:46])=[O:42])[CH2:32][S:33][CH2:34][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1
Reactant: CC(C)C[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CSCc1ccccc1)C(C)C)C(=O)O
Reactant: CC(C)C[C@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CSCc1ccccc1)NC(=O)OC(C)(C)C)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)O)[C@@H](C)O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: O=C1CCC(=O)N1O
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CC(C)C[C@H](NC(=O)[C@@H](NC(=O)[C@H](CSCc1ccccc1)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CSCc1ccccc1)NC(=O)OC(C)(C)C)[C@@H](C)O)C(C)C)C(=O)O
Temperature: 25 °C
Reaction time: 72 h

Procedure:
3.90 g (6 mmols) of H-Cys(Bzl)-Val-Leu-OH, 1.15TFA are dissolved in freshly distilled dimethylformamide, treated with 4.48 g (5.5 mmols) of BOC-Cys(Bzl)-Ser-Asn-Leu-Ser-Thr-OH and stirred at room temperature until all is dissolved. The solution is then cooled to 0°C, 1.26 g (11 mmols) of N-hydroxysuccinimide and 0.98 ml of triethylamine in 45 ml of dimethylformamide are added, followed by cooling to -22°C and the addition of 1.13 g (5.5 mmols) of dicyclohexylcarbodimide in 10 ml of dimethylformamide. The batch is stirred for 1 hour at -22°C, then at room temperature for 3 days, filtered to remove precipitated dicyclohexylurea, and evaporated to dryness. The residue is stirred twice with a mixture of 200 ml of ethyl acetate and 20 ml of 5% citric acid solution, then once with a mixture of 200 ml of ethyl acetate and 20 ml of 5% sodium bicabonate solution. The resulting product is filtered off and dried at 40°C in a high vacuum. Melting point: 218°-221°C; [α]D20 -28.5° (c = 2 in dimethylformamide); Rf8 = 0.43.