Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]([CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])=[CH:3][CH2:4][CH2:5][CH2:6][C:7]([OH:9])=[O:8].S(=O)(=O)(O)O.O.[C:25](=O)(O)[O-].[K+]>CO>[CH3:1][C:2]([CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])=[CH:3][CH2:4][CH2:5][CH2:6][C:7]([O:9][CH3:25])=[O:8]
Reactant: CCCCCCCCCC(C)=CCCCC(=O)O
Reactant: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: [K+]
Solvent: CO
Solvent: O
Product: CCCCCCCCCC(C)=CCCCC(=O)OC
Yield: 85 %

Procedure:
98 g of crude 6-methylpentadec-5-enoic acid acid (from the proceeding Example) were dissolved in 305 ml of methanol, treated with 2 ml of sulphuric acid and heated to reflux temperature 2 hours. Then, the mixture was poured into water, made basic with saturated potassium bicarbonate solution, extracted twice with t-butyl methyl ether, concentrated and distilled in a high vacuum (0.1 Torr, 162-170° C.). 75 g (85%) of methyl 6-methylpentadec-5-enoate were obtained having the following characteristics: Z/E=56/46;
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:14]=[CH:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=1)=[O:4].[ClH:15].[N+:16]([C:19]1[CH:20]=[C:21]([CH:29]=[CH:30][CH:31]=1)[O:22][CH:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1)([O-:18])=[O:17].C(N(CC)CC)C.Cl>C(O)C>[ClH:15].[N+:16]([C:19]1[CH:20]=[C:21]([CH:29]=[CH:30][CH:31]=1)[O:22][CH:23]1[CH2:24][CH2:25][N:26]([CH2:2][C:3]([C:5]2[CH:14]=[CH:13][C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[CH:6]=2)=[O:4])[CH2:27][CH2:28]1)([O-:18])=[O:17]
Reactant: O=[N+]([O-])c1cccc(OC2CCNCC2)c1
Reactant: O=C(CBr)c1ccc2ccccc2c1
Agent: Cl
Solvent: CCO
Solvent: CCN(CC)CC
Product: O=C(CN1CCC(Oc2cccc([N+](=O)[O-])c2)CC1)c1ccc2ccccc2c1

Procedure:
0.63 g of 2-bromo-2'-acetonaphthone, 0.65 g of 4-(m-nitrophenoxy)piperidine hydrochloride, and 1 g of triethylamine were added to 100 ml of ethanol. The mixture was refluxed for 30 min. The solvent was distilled off, and dichloromethane was added to the residue. The mixture was washed with water and dried. The dichloromethane was distilled off, and the residue was purified by column chromatography (silica gel) to prepare an oleaginous intended compound. The compound was converted into a hydrochloride by an ordinary method and then recrystallized to prepare 0.15 g of an intended hydrochloride.
Reaction SMILES: C[N:2]1CCOCC1.ClC(OCC(C)C)=O.[C:16]([O:20][C:21]([N:23]1[CH2:27][CH2:26][CH2:25][C@@H:24]1[C:28]([OH:30])=O)=[O:22])([CH3:19])([CH3:18])[CH3:17].[OH-].[NH4+]>C1COCC1>[C:16]([O:20][C:21]([N:23]1[CH2:27][CH2:26][CH2:25][C@@H:24]1[C:28](=[O:30])[NH2:2])=[O:22])([CH3:19])([CH3:18])[CH3:17]
Reactant: CC(C)(C)OC(=O)N1CCC[C@@H]1C(=O)O
Reactant: CN1CCOCC1
Agent: CC(C)COC(=O)Cl
Agent: [NH4+]
Agent: [OH-]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC[C@@H]1C(N)=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 54.3 %

Procedure:
N-Methylmorpholine (9.85 g, 97.5 mmol) and isobutyl chloroformate (13.33 g, 97.5 mmol) was added to (R)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (20.0 g, 92.9 mmol) in THF (200 mL) at −78° C. and stirred for 1 h. Ammonium hydroxide (58 mL) was added slowly as the reaction warmed up to RT and stirred for a further 2 h. The reaction mixture was partitioned between DCM and water. The organic extracts were washed with 1 M HCl, dried over sodium sulphate, filtered and concentrated to afford the title product (10.8 g, 54%) as a colourless semisolid.
Reaction SMILES: [CH:1]([N:4](C(C)C)[CH2:5]C)(C)C.[NH2:10][C:11]1[CH:12]=[CH:13][C:14]([Br:20])=[C:15]([CH:19]=1)[C:16](O)=[O:17].CNC.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C.O>[NH2:10][C:11]1[CH:12]=[CH:13][C:14]([Br:20])=[C:15]([CH:19]=1)[C:16]([N:4]([CH3:5])[CH3:1])=[O:17]
Reactant: CCN(C(C)C)C(C)C
Reactant: Nc1ccc(Br)c(C(=O)O)c1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: CNC
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: O
Product: CN(C)C(=O)c1cc(N)ccc1Br
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Diisopropyl ethylamine (21 ml, 121 mmol) was dissolved in a solution of 5-amino-2-bromo benzoic acid (5 g, 23 mmol), dimethylamine (5 g, 115 mmol) and BOP (51 g, 121 mmol) in 100 ml DMF. And the reaction mixture was stirred at room temperature 30 minutes. Three times of water was added into the reaction solution. The reaction mixture was extracted by ethyl acetate. The organic layer was evaporated to give a crude product, which was purified using column chromatography to give the product. (3.1 g, 54%)
Reaction SMILES: [N+:1]([C:4]1[CH:20]=[CH:19][C:7]2[NH:8][C:9]3[C:10](=[CH:12][NH:13][C:14](=[O:18])[C:15]=3[C:16]#[N:17])[S:11][C:6]=2[CH:5]=1)([O-])=O.Cl>C(O)(=O)C>[NH2:1][C:4]1[CH:20]=[CH:19][C:7]2[NH:8][C:9]3[C:10](=[CH:12][NH:13][C:14](=[O:18])[C:15]=3[C:16]#[N:17])[S:11][C:6]=2[CH:5]=1
Reactant: N#Cc1c2c(c[nH]c1=O)Sc1cc([N+](=O)[O-])ccc1N2
Agent: Cl
Solvent: CC(=O)O
Product: N#Cc1c2c(c[nH]c1=O)Sc1cc(N)ccc1N2
Reaction time: 2 h

Procedure:
To a suspension of 25 parts of a 1:1 solvate of 2,3-dihydro-8-nitro-3-oxo-5H-pyrido[3,4-b][1,4]benzothiazine-4-carbonitrile in 1000 parts of glacial acetic acid is added a solution of 75 parts of stannous chloride dihydrate in 230 parts of 28% hydrochloric acid. The resultant mixture is heated at the boiling point under reflux with stirring for 2 hours, then chilled. Insoluble solids are filtered out and dissolved in a mixture of 1100 parts of sulfinylbis[methane] with 200 parts of water. This solution is basified with concentrated ammonium hydroxide and thereupon diluted with 1 volume of water. The precipitate which forms is filtered off and consecutively recrystallized from (1) a mixture of sulfinylbis[methane] and methanol and (2) a mixture of sulfinylbis[methane], N,N-dimethylformamide, and water to give 8-amino-2,3-dihydro-3-oxo-5H-pyrido[3,4-b][1,4]benzothiazine-4-carbonitrile melting above 305°.
Reaction SMILES: [C:1]([O:5][C:6](=[O:14])[NH:7][C@H:8]1[CH2:12][CH2:11][NH:10][C:9]1=[O:13])([CH3:4])([CH3:3])[CH3:2].Br[CH2:16][C:17]1[CH:26]=[CH:25][CH:24]=[C:23]2[C:18]=1[CH:19]=[CH:20][C:21]([Cl:27])=[N:22]2.BrCC1C=C2C(C=CC(Cl)=N2)=CC=1.BrCC1C=C2C(C=CN=C2Cl)=CC=1>>[C:1]([O:5][C:6](=[O:14])[NH:7][C@H:8]1[CH2:12][CH2:11][N:10]([CH2:16][C:17]2[CH:26]=[CH:25][CH:24]=[C:23]3[C:18]=2[CH:19]=[CH:20][C:21]([Cl:27])=[N:22]3)[C:9]1=[O:13])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N[C@H]1CCNC1=O
Reactant: Clc1ccc2c(CBr)cccc2n1
Agent: Clc1ccc2ccc(CBr)cc2n1
Agent: Clc1nccc2ccc(CBr)cc12
Product: CC(C)(C)OC(=O)N[C@H]1CCN(Cc2cccc3nc(Cl)ccc23)C1=O

Procedure:
The title compound is prepared from (2-oxopyrrolidin-3-(S)-yl)-carbamic acid tert-butyl ester as described in EXAMPLE 1, Part H using a 2:1 mixture of 5-bromomethyl-2-chloro-quinoline to 7-bromomethyl-2-chloro-quinoline, as prepared in EXAMPLE 15, Part C, in place of 7-bromomethyl-1-chloro-isoquinoline. The crude product mixture is purified by column chromatography eluting with 1% MeOH in 25% EtOAc/CH2Cl2 to afford as the major product the title compound as a beige solid.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][N:8]2[CH:11]=[N:12][CH:13]=[C:7]2[C:6]=1[NH:14][C:15]1[CH:20]=[CH:19][C:18](Br)=[CH:17][C:16]=1[F:22])=[O:4].[I-:23].[Na+].CN[C@@H]1CCCC[C@H]1NC.C(OCC)(=O)C>O1CCOCC1.CO.ClCCl.[Cu]I>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][N:8]2[CH:11]=[N:12][CH:13]=[C:7]2[C:6]=1[NH:14][C:15]1[CH:20]=[CH:19][C:18]([I:23])=[CH:17][C:16]=1[F:22])=[O:4]
Reactant: [I-]
Reactant: COC(=O)c1ccn2cncc2c1Nc1ccc(Br)cc1F
Agent: [Cu]I
Agent: CN[C@@H]1CCCC[C@H]1NC
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Solvent: ClCCl
Product: COC(=O)c1ccn2cncc2c1Nc1ccc(I)cc1F
Temperature: 110 °C
Yield: 68.1 %

Procedure:
A mixture of 8-(4-bromo-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester (235 mg, 0.65 mmol), copper (I) iodide (6 mg, 0.03 mmol), sodium iodide (195 mg, 1.3 mmol) and trans-N,N′-dimethyl-1,2-cyclohexane diamine (0.01 mL, 0.06 mmol) in 1,4-dioxane (1.0 mL) was heated at 110° C. for 26 hours under an argon atmosphere. The reaction mixture was cooled to room temperature, diluted with methanol and loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was then washed with methanol and the desired product was subsequently eluted using 2M NH3 in MeOH. The eluent was collected and concentrated to give a residue. The residue was subjected to flash chromatography (Si-PPC, gradient 0% to 20%, ethyl acetate in dichloromethane) to afford the title compound as a pale yellow solid (182 mg, 67%). LCMS (method B): RT=3.45 min, [M+H]+=412.
Reaction SMILES: [H-].[Na+].[F:3][CH:4]1[N:10]=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:8]2[CH:17]=[C:18]([N+:21]([O-:23])=[O:22])[CH:19]=[CH:20][C:7]=2[NH:6][C:5]1=[O:24].[CH3:25]I>O1CCCC1>[F:3][CH:4]1[N:10]=[C:9]([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:8]2[CH:17]=[C:18]([N+:21]([O-:23])=[O:22])[CH:19]=[CH:20][C:7]=2[N:6]([CH3:25])[C:5]1=[O:24]
Reactant: O=C1Nc2ccc([N+](=O)[O-])cc2C(c2ccccc2)=NC1F
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CN1C(=O)C(F)N=C(c2ccccc2)c2cc([N+](=O)[O-])ccc21
Temperature: 0 °C
Reaction time: 3 h
Yield: 60 %

Procedure:
A slurry of 0.20 g (0.08 mole) of sodium hydride in 10 ml of tetrahydrofuran was added to a solution of 1.74 g (0.0058 mole) of 3-fluoro-1,3-dihydro-7-nitro-5-phenyl-2H-1,4-benzodiazepin-2-one and 10 ml methyl iodide in 100 ml of tetrahydrofuran at 25°. The reaction mixture was stirred for 3 hr at 25°, and then poured into 300 ml of ice water. The aqueous mixture was extracted with methylene chloride, and the extracts were dried (MgSO4) and then evaporated to dryness under reduced pressure. The residue was dissolved in hot benzene and then fractionally precipitated by the addition of hexane. The first dark fractions of solid were discarded. The remaining fractions were collected on a filter and dried in vacuum to give 1.10 g (60%) of 3-fluoro-1,3-dihydro-1-methyl-7-nitro-5-phenyl-2H-1,4-benzodiazepin-2-one as a light tan amorphous solid with no distinct melting point: 1H nmr (CDCl3) δ 3.53 ppm (s, 3H), 5.59 ppm (d, J = 57 Hz, 1H), 7.2-7.9 ppm (m, 6H) and 8.2-8.9 ppm (m, 2H); 19F nmr (CDCl3) δ -161.7 ppm (d, J = 57 Hz).
Reaction SMILES: Cl.[NH:2]1[CH2:7][CH2:6][CH2:5][C@@H:4]([NH:8][C:9]([C:11]2[C:15]3[N:16]=[CH:17][N:18]=[C:19]([C:20]4[C:28]5[O:27][CH2:26][O:25][C:24]=5[CH:23]=[CH:22][C:21]=4[O:29][CH2:30][CH:31]4[CH2:33][CH2:32]4)[C:14]=3[NH:13][CH:12]=2)=[O:10])[CH2:3]1.[C:34](Cl)(=[O:37])[CH2:35][CH3:36]>>[C:34]([N:2]1[CH2:7][CH2:6][CH2:5][C@@H:4]([NH:8][C:9]([C:11]2[C:15]3[N:16]=[CH:17][N:18]=[C:19]([C:20]4[C:28]5[O:27][CH2:26][O:25][C:24]=5[CH:23]=[CH:22][C:21]=4[O:29][CH2:30][CH:31]4[CH2:32][CH2:33]4)[C:14]=3[NH:13][CH:12]=2)=[O:10])[CH2:3]1)(=[O:37])[CH2:35][CH3:36]
Reactant: O=C(N[C@@H]1CCCNC1)c1c[nH]c2c(-c3c(OCC4CC4)ccc4c3OCO4)ncnc12
Reactant: CCC(=O)Cl
Agent: Cl
Product: CCC(=O)N1CCC[C@@H](NC(=O)c2c[nH]c3c(-c4c(OCC5CC5)ccc5c4OCO5)ncnc23)C1

Procedure:
Starting from 4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid (R)-piperidin-3-ylamide hydrochloride (example A149) and propionyl chloride the title compound is obtained as colorless solid.
Reaction SMILES: Cl[C:2]1[C:7](=[O:8])[CH:6]=[CH:5][N:4]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)[CH:3]=1.[C:19]1([N:25]2[C:29](B3OC(C)(C)C(C)(C)O3)=[CH:28][CH:27]=[N:26]2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.O.C(=O)([O-])O.[Na+].CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[C:19]1([N:25]2[C:29]([C:2]3[C:7](=[O:8])[CH:6]=[CH:5][N:4]([C:9]4[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=4)[CH:3]=3)=[CH:28][CH:27]=[N:26]2)[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1
Reactant: CC1(C)OB(c2ccnn2-c2ccccc2)OC1(C)C
Reactant: O=c1ccn(-c2cccc(C(F)(F)F)c2)cc1Cl
Agent: Cl[Pd]Cl
Agent: CN(C)c1ccc(P(C(C)(C)C)C(C)(C)C)cc1
Agent: O=C([O-])O
Solvent: Cc1ccccc1
Solvent: O
Product: O=c1ccn(-c2cccc(C(F)(F)F)c2)cc1-c1ccnn1-c1ccccc1
Temperature: 25 °C
Yield: 3.5 %

Procedure:
3-Chloro-1-[3-(trifluoromethyl)phenyl]pyridin-4(1H)-one (0.0247 g), 1-phenyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.0365 g), potassium carbonate (0.0249 g) and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (0.0032 g) were suspended in toluene (1 mL) and water (0.1 mL), and the suspension was heated under reflux for 22 hr under an argon atmosphere. To the reaction mixture were added 1-phenyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.0365 g) and potassium carbonate (0.0249 g) at room temperature, and the mixture was heated under reflux for 1 day under an argon atmosphere. The reaction mixture was cooled to room temperature, diluted with aqueous sodium hydrogen carbonate solution, extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by NH silica gel column chromatography (ethyl acetate/hexane) to give the title compound (1.2 mg).
Reaction SMILES: [CH3:1][N:2]1[C:6]2[N:7]=[C:8]3[S:14][CH2:13][CH2:12][N:9]3[C:10](=O)[C:5]=2[CH:4]=[N:3]1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:24])=CC=1>C1(C)C=CC=CC=1>[CH3:1][N:2]1[C:6]2[N:7]=[C:8]3[S:14][CH2:13][CH2:12][N:9]3[C:10](=[S:24])[C:5]=2[CH:4]=[N:3]1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: Cn1ncc2c(=O)n3c(nc21)SCC3
Solvent: Cc1ccccc1
Product: Cn1ncc2c(=S)n3c(nc21)SCC3
Yield: 84.7 %

Procedure:
In 50 ml of toluene was dissolved 2.08 g (10.0 mmol) of Compound 2 prepared in Example 2, and 4.45 g (11.0 mmol) of Lawesson's reagent was added to the solution, followed by heating under reflux for 30 minutes. After cooling, the precipitated crystals were collected by filtration, and then washed with toluene. The crystals were subjected to silica gel column chromatography and eluted with chloroform to give 1.90 g (85%) of Compound 39. The compound was recrystallized from chloroform/ethanol for purification.
Reaction SMILES: [Li+].[I-].[CH:3](=[O:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Br[CH:12]([CH3:23])[C:13](=[O:22])[C:14]([CH3:21])([CH3:20])[CH:15]([O:18][CH3:19])[O:16][CH3:17]>C1COCC1>[OH:10][CH:3]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH:12]([CH3:23])[C:13](=[O:22])[C:14]([CH3:20])([CH3:21])[CH:15]([O:16][CH3:17])[O:18][CH3:19]
Reactant: COC(OC)C(C)(C)C(=O)C(C)Br
Reactant: O=Cc1ccccc1
Agent: [I-]
Agent: [Li+]
Solvent: C1CCOC1
Product: COC(OC)C(C)(C)C(=O)C(C)C(O)c1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of 298 mg (2.42 mmol) CrCl2 and 20 mg (0.15 mmol) LiI in 6.0 mL abs. THF were added 117 μl (1.1 mmol) benzaldehyde and 253 mg (1.0 mmol) 4-bromo-1,1-dimethoxy-2,2-dimethyl-pentan-3-one (225). After stirring at ambient temperature for 30 minutes the brown solution was quenched with 5.0 mL brine. The aqueous phase was extracted three times with 5.0 mL diethylether. The organic layers were combined, washed with conc. NH4C, solution (2×5.0 mL), dried over MgSO4, filtrated and concentrated in vacuo. The remaining green oil (196 mg) was purified via flash chromatography (column dimensions: 3.5×20.0 cm, ethyl acetate/petroleum ether=1:6).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH2:9][S:10][CH3:11])[CH:6]=[CH:5][C:4]=1[C:12]1[NH:13][C:14]2[C:15]([N:20]=1)=[N:16][CH:17]=[CH:18][CH:19]=2.[OH:21]O.N>C(O)(=O)C.O>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH2:9][S:10]([CH3:11])=[O:21])[CH:6]=[CH:5][C:4]=1[C:12]1[NH:13][C:14]2[C:15]([N:20]=1)=[N:16][CH:17]=[CH:18][CH:19]=2
Reactant: COc1cc(CSC)ccc1-c1nc2ncccc2[nH]1
Reactant: OO
Agent: N
Solvent: CC(=O)O
Solvent: O
Product: COc1cc(CS(C)=O)ccc1-c1nc2ncccc2[nH]1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A quantity of 1.4 gm (4.9 mmol) of 2-(2'-methoxy-4'-methylthiomethyl-phenyl)-imidazo[4,5-b]pyridine was dissolved in 30 ml of glacial acetic acid and mixed with 3 ml of 30% hydrogen peroxide. After stirring for two hours at ambient temperature, the solution was diluted with 200 ml of water, made alkaline with concentrated ammonia solution, saturated with sodium chloride, and extracted three times with 30 ml of methylene chloride. The organic extracts were concentrated by evaporation, and the solid residue was purified by column chromatography (200 gm of silica gel; eluant: methylene chloride with 2 to 10% of ethanol).
Reaction SMILES: [NH2:1][N:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=O.[C:13]1([C:19]2[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=2)[C:22]#[N:23])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>C(OCC)(=O)C>[C:19]1([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:26]=[CH:25][CH:24]=[C:21]([C:22]2[N:23]=[C:3]3[C:4]4[C:9]([CH:10]=[CH:11][N:2]3[N:1]=2)=[CH:8][CH:7]=[CH:6][CH:5]=4)[CH:20]=1
Reactant: Nn1ccc2ccccc2c1=O
Reactant: N#Cc1cccc(-c2ccccc2)c1
Solvent: CCOC(C)=O
Product: c1ccc(-c2cccc(-c3nc4c5ccccc5ccn4n3)c2)cc1
Yield: 49 %

Procedure:
This compound was prepared according to the procedure of the foregoing Example, starting from 2-amino-isoquinoline-1(2H)-one and 3-phenyl-benzonitrile. Yield 49%. M.p. 167°-69° C. (from ethyl acetate).
Reaction SMILES: [C:1]([O:5][C:6]([O:8]N=C(C(OCC)=O)C(OCC)=O)=O)([CH3:4])([CH3:3])[CH3:2].[NH2:21][C@H:22]([C:27]([OH:29])=[O:28])[C@H:23]([CH2:25][CH3:26])[CH3:24].[OH-].[Na+]>C(O)(C)(C)C>[C:1]([O:5][C:6]([NH:21][C@H:22]([C:27]([OH:29])=[O:28])[C@H:23]([CH2:25][CH3:26])[CH3:24])=[O:8])([CH3:2])([CH3:3])[CH3:4]
Reactant: CC[C@H](C)[C@H](N)C(=O)O
Reactant: CCOC(=O)C(=NOC(=O)OC(C)(C)C)C(=O)OCC
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)(C)O
Product: CC[C@H](C)[C@H](NC(=O)OC(C)(C)C)C(=O)O
Temperature: 25 °C
Reaction time: 3 h
Yield: 103.7 %

Procedure:
A solution of diethyl 2-tert-butoxycarbonyloxyiminomalonate (1.9 g.) in tert-butyl alcohol (5 ml.) was added to a solution of L-isoleucine (656 mg.) in a 1N sodium hydroxide aqueous solution (5.0 ml.). The mixture was stirred for 3 hours at room temperature. The tert-Butyl alcohol was removed from the reaction mixture under reduced pressure and water was added to the residue. The mixture was washed with ether, adjusted to pH 3 with a 5% citric acid aqueous solution and extracted with ethyl acetate. The extract was washed with water, dried and concentrated to give N-tert-butoxycarbonyl-L-isoleucine (1.2 g.), oil.
Reaction SMILES: [CH3:1][S:2][CH2:3][C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[NH:11][CH:10]=[CH:9]2.[CH:13]1([C:16]([C:19]2[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=2)(O)[CH3:17])[CH2:15][CH2:14]1.ClC1C=CC(C(C2C3C(=C(CSC)C=CC=3)NC=2)(C2CC2)C)=CC=1>>[CH:13]1([C:16]([C:9]2[C:8]3[C:12](=[C:4]([CH2:3][S:2][CH3:1])[CH:5]=[CH:6][CH:7]=3)[NH:11][CH:10]=2)([C:19]2[CH:20]=[CH:21][C:22]([C:25]([F:26])([F:27])[F:28])=[CH:23][CH:24]=2)[CH3:17])[CH2:15][CH2:14]1
Reactant: CC(O)(c1ccc(C(F)(F)F)cc1)C1CC1
Reactant: CSCc1cccc2cc[nH]c12
Agent: CSCc1cccc2c(C(C)(c3ccc(Cl)cc3)C3CC3)c[nH]c12
Product: CSCc1cccc2c(C(C)(c3ccc(C(F)(F)F)cc3)C3CC3)c[nH]c12

Procedure:
The title compound was prepared starting from 462 mg (2.61 mmol) of the compound from Example 8A and 600 mg (2.61 mmol) of the compound from Example 139A in analogy to the synthesis of the compound from Example 184. 273 mg (27% of theory) of the target compound were obtained.
Reaction SMILES: [C:1]([NH:4][C:5]1[C:14](=[O:15])[C:13]2[N:12]=[C:11]([CH:16]=O)[CH:10]=[CH:9][C:8]=2[C:7](=[O:18])[CH:6]=1)(=[O:3])[CH3:2].CN(C[CH2:23][O:24][C:25](=[O:39])[C@H:26]([CH2:29][C:30]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[NH:32][CH:31]=1)[NH:27]C)C>C1(OC)C=CC=CC=1>[CH3:2][C:1]([NH:4][C:5]1[C:14](=[O:15])[C:13]2[N:12]=[C:11]([C:16]3[N:27]=[C:26]([C:25]([O:24][CH3:23])=[O:39])[CH:29]=[C:30]4[C:38]5[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=5[NH:32][C:31]=34)[CH:10]=[CH:9][C:8]=2[C:7](=[O:18])[CH:6]=1)=[O:3]
Reactant: CN[C@@H](Cc1c[nH]c2ccccc12)C(=O)OCCN(C)C
Reactant: CC(=O)NC1=CC(=O)c2ccc(C=O)nc2C1=O
Solvent: COc1ccccc1
Product: COC(=O)c1cc2c([nH]c3ccccc32)c(-c2ccc3c(n2)C(=O)C(NC(C)=O)=CC3=O)n1
Temperature: 100 °C

Procedure:
7-N-ACETYLLAVENDAMYCIN N,N-DIMETHYLAMINOETHYL ESTER (Compound 19, Table I): 7-Acetamido-2-formylquinoline-5,8-dione (23) (prepared as described in Example 23) (317 mg, 0.13 mmol) was dissolved in 16 ml of dry anisole and heated to 80° C. b -methyltryptophan N,N-dimethylaminoethyl ester (41) (prepared as described in Example 41) (37.5 mg, 0.13 mmol) was added with stirring, and the stirred mixture was heated at 100° C. for 5.5 hr. The reaction mixture was allowed to cool to room temperature and the solid was filtered. The filtrate was distilled under vacuum to dryness. Ethyl acetate (3 ml) was added, and the mixture was stirred. Upon filtration 24.5 mg (a yield of 36%) of an orange solid was obtained.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([F:11])[CH:10]=1)[NH:7][C:6]([CH2:12][CH2:13][C:14]([OH:16])=[O:15])=[CH:5]2.S(Cl)(Cl)=O.[CH2:21](O)[CH3:22]>>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([F:11])[CH:10]=1)[NH:7][C:6]([CH2:12][CH2:13][C:14]([O:16][CH2:21][CH3:22])=[O:15])=[CH:5]2
Reactant: CCO
Reactant: O=C(O)CCc1cc2cc(Br)cc(F)c2[nH]1
Solvent: O=S(Cl)Cl
Product: CCOC(=O)CCc1cc2cc(Br)cc(F)c2[nH]1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a suspension of 3-(5-bromo-7-fluoro-1H-indol-2-yl)propanoic acid (D160) (1 g) in ethanol (15 mL) was added thionyl dichloride (0.083 g). The reaction mixture was stirred at room temperature overnight. The solvent was removed in vacuo. The residue was diluted with EtOAc (30 mL). The organic phase was washed with 2 M sodium carbonate solution (25 mL) and water (50 mL), dried over sodium sulphate and evaporated in vacuo to give the crude product ethyl 3-(5-bromo-7-fluoro-1H-indol-2-yl)propanoate (D161) (1.1 g) as a yellow solid. δH (CDCl3, 400 MHz): 1.23 (3H, t), 2.73 (2H, t), 3.06 (2H, t), 4.16 (2H, m), 6.20 (1H, s), 7.05 (1H, d), 7.41 (1H, s), 8.85 (1H, s).
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([C:12]2[CH2:17][CH2:16][CH:15]([C:18]3[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=3)[CH2:14][CH:13]=2)[CH:8]=[CH:9][C:10]=1[OH:11])([CH3:4])([CH3:3])[CH3:2]>[Ni].C(O)(C)C>[OH:24][C:21]1[CH:22]=[CH:23][C:18]([CH:15]2[CH2:14][CH2:13][CH:12]([C:7]3[CH:8]=[CH:9][C:10]([OH:11])=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[CH:6]=3)[CH2:17][CH2:16]2)=[CH:19][CH:20]=1
Reactant: CC(C)(C)c1cc(C2=CCC(c3ccc(O)cc3)CC2)ccc1O
Agent: [Ni]
Solvent: CC(C)O
Product: CC(C)(C)c1cc(C2CCC(c3ccc(O)cc3)CC2)ccc1O
Yield: 101.2 %

Procedure:
26.6 g (0.081 mol) of 1-(3-t-butyl-4-hydroxyphenyl)-4-(4-hydroxyphenyl)-1-cyclohexene obtained in Example 4 of Example A, 266 g of isopropyl alcohol and 5.5 g of Raney nickel catalyst were placed in a reaction vessel (1L capacity autoclave), and then in the same manner as in Example 3, 26.6 g of 4-(4′-(4″-hydroxyphenyl)-cyclohexyl)-2-t-butyl-1-hydroxybenzene was obtained as white crystals having a purity of 97.9% (high performance liquid chromatography). The yield was found to be 99.2 mol % based on the 1-(3-t-butyl-4-hydroxyphenyl)-4-(4-hydroxyphenyl)-1-cyclohexene. The selectivity of trans-/cis-isomers of 4-(4′-(4″-hydroxyphenyl)cyclohexyl)-2-t-butyl-1-hydroxybenzene was found to be 64/36 (high performance liquid chromatography).
Reaction SMILES: [CH2:1]([CH:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:18])[C:15]([OH:17])=O)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:19][C:20]1[CH:29]=[CH:28][C:23]2[NH:24][C:25](=[O:27])[O:26][C:22]=2[CH:21]=1>C(OCC)C>[CH2:1]([CH:8]1[CH2:9][CH2:10][N:11]([C:14](=[O:18])[C:15]([NH:19][C:20]2[CH:29]=[CH:28][C:23]3[NH:24][C:25](=[O:27])[O:26][C:22]=3[CH:21]=2)=[O:17])[CH2:12][CH2:13]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)C(=O)N1CCC(Cc2ccccc2)CC1
Reactant: Nc1ccc2[nH]c(=O)oc2c1
Solvent: CCOCC
Product: O=C(Nc1ccc2[nH]c(=O)oc2c1)C(=O)N1CCC(Cc2ccccc2)CC1

Procedure:
The title compound is prepared from (4-benzyl-piperidin-1-yl)-oxo-acetic acid (Example 5b) and 6-amino-3H-benzoxazol-2-one according to the method described in Example 1c. Melting Point: 190-193° C. (diethylether)