Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]([C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[C:10]([CH2:15][CH2:16][CH3:17])[CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Br:18][CH2:19][CH2:20][CH2:21]Br.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[C:2]1([O:1][C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:21][CH2:20][CH2:19][Br:18])=[C:10]([CH2:15][CH2:16][CH3:17])[CH:9]=2)[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: BrCCCBr
Reactant: CCCc1cc(Oc2ccccc2)ccc1O
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CCCc1cc(Oc2ccccc2)ccc1OCCCBr

Procedure:
A solution of 4-phenoxy-2-propylphenol (12.0 g, 52.60 mmol), 1,3-dibromopropane ( 31.86 g, 157.81 mmol) and cesium carbonate (18.0 g, 55.23 mmol) in dry DMF ( 110 mL) was stirred at room temperature overnight. The reaction mixture was partitioned between ethyl acetate and 0.2N HCl. The organic was washed twice with water, then dried over sodium sulfate. The organic was filtered and evaporated to an oil which was chromatographed over silica gel with methylene chloride/hexane (1:1) to afford the title compound.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)[NH:8][N:7]=1)=[O:5])[CH3:2].[CH3:18]I.[OH-].[K+]>>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH3:18])[N:8]=[C:9]([C:11]2[CH:12]=[CH:13][C:14]([Cl:17])=[CH:15][CH:16]=2)[CH:10]=1)=[O:5])[CH3:2].[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([C:11]2[CH:12]=[CH:13][C:14]([Cl:17])=[CH:15][CH:16]=2)[N:8]([CH3:18])[N:7]=1)=[O:5])[CH3:2]
Reactant: CI
Reactant: CCOC(=O)c1cc(-c2ccc(Cl)cc2)[nH]n1
Agent: [K+]
Agent: [OH-]
Product: CCOC(=O)c1cc(-c2ccc(Cl)cc2)n(C)n1
Product: CCOC(=O)c1cc(-c2ccc(Cl)cc2)nn1C

Procedure:
In analogy to the procedure described for example 2 a], 5-(4-chloro-phenyl)-1H-pyrazole-3-carboxylic acid ethyl ester (T. van Herk et al., J. Med. Chem. 2003, 46, 3945-3951) was reacted with methyl iodide in the presence of potassium hydroxide to to give 5-(4-chloro-phenyl)-2-methyl-2H-pyrazole-3-carboxylic acid ethyl ester as colorless crystals and 5-(4-chloro-phenyl)-1-methyl-1H-pyrazole-3-carboxylic acid ethyl ester as colorless oil.
Reaction SMILES: C(O[C:4]([N:6]1[CH2:11][CH2:10][C:9](=O)[CH2:8][CH2:7]1)=O)C.[CH2:13]([NH2:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[Cl:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([CH:28]=[CH:29][N+]([O-])=O)[CH:23]=1.N>CO.CCOC(C)=O>[CH2:13]([N:20]1[C:9]2[CH2:8][CH2:7][N:6]([CH3:4])[CH2:11][C:10]=2[C:28]([C:24]2[CH:25]=[CH:26][CH:27]=[C:22]([Cl:21])[CH:23]=2)=[CH:29]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: CCOC(=O)N1CCC(=O)CC1
Reactant: NCc1ccccc1
Reactant: O=[N+]([O-])C=Cc1cccc(Cl)c1
Agent: N
Solvent: CCOC(C)=O
Solvent: CO
Product: CN1CCc2c(c(-c3cccc(Cl)c3)cn2Cc2ccccc2)C1

Procedure:
The title compound (0.34 g) was prepared from 3.0 g of 4-oxo-piperidine-1-carboxylic acid ethyl ester, 1.91 mL of benzylamine, and 1.2 g of 1-chloro-3-(2-nitro-vinyl)-benzene as in Example 38. TLC (SiO2, 2% NH3 in MeOH/EtOAc): Rf=0.25. MS (ESI): exact mass calculated for C21H21ClN2, 336.14. found, m/z 337.2 [M+H]+, 339.2 [M+H]+. 1H NMR (500 MHz, CD3OD): 7.36-7.32 (m, 4H), 7.30-7.25 (m, 2H), 7.21-7.16 (m, 4H), 5.15 (s, 2H), 4.41 (s, 2H), 3.53 (t, J=6.3 Hz, 2H), 2.98 (s, 3H), 2.91 (t, J=6.3 Hz, 2H), 2.82-2.70 (m, 4H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[C:5]#[N:6].[S].[CH2:13](N)[CH2:14][NH2:15]>>[Br:1][C:2]1[CH:3]=[C:4]([C:5]2[NH:15][CH2:14][CH2:13][N:6]=2)[CH:7]=[CH:8][C:9]=1[O:10][CH3:11]
Reactant: NCCN
Reactant: COc1ccc(C#N)cc1Br
Agent: [S]
Product: COc1ccc(C2=NCCN2)cc1Br
Temperature: 110 °C

Procedure:
To a solution of 3-bromo-4-methoxybenzonitrile (1 g, 4.72 mmol) in 10 mL of ethane-1,2-diamine was added sulfur (0.121 g, 3.77 mmol) and the mixture was heated at 110° C. overnight. The mixture was cooled, quenched with water and extracted with ethyl acetate. The organic layer was washed with water and brine (25 mL each), dried over sodium sulfate, filtered, and concentrated to afford the title compound. LCMS: 257 (M+2)+.
Reaction SMILES: [CH:1]([N:4]1[C:10](=[O:11])[CH2:9][CH2:8][CH2:7][C:6]2[CH:12]=[C:13]([N+:16]([O-])=O)[CH:14]=[CH:15][C:5]1=2)([CH3:3])[CH3:2].Cl[C:20]1[N:25]=[C:24]([NH:26][C@@H:27]2[CH2:32][CH2:31][CH2:30][CH2:29][C@H:28]2[NH:33][S:34]([CH3:37])(=[O:36])=[O:35])[C:23]([Cl:38])=[CH:22][N:21]=1>>[Cl:38][C:23]1[C:24]([NH:26][C@@H:27]2[CH2:32][CH2:31][CH2:30][CH2:29][C@H:28]2[NH:33][S:34]([CH3:37])(=[O:36])=[O:35])=[N:25][C:20]([NH:16][C:13]2[CH:14]=[CH:15][C:5]3[N:4]([CH:1]([CH3:3])[CH3:2])[C:10](=[O:11])[CH2:9][CH2:8][CH2:7][C:6]=3[CH:12]=2)=[N:21][CH:22]=1
Reactant: CS(=O)(=O)N[C@@H]1CCCC[C@H]1Nc1nc(Cl)ncc1Cl
Reactant: CC(C)N1C(=O)CCCc2cc([N+](=O)[O-])ccc21
Product: CC(C)N1C(=O)CCCc2cc(Nc3ncc(Cl)c(N[C@@H]4CCCC[C@H]4NS(C)(=O)=O)n3)ccc21
Yield: 61 %

Procedure:
In an analogous procedure to Example 651, part c, 1-isopropyl-7-nitro-1,3,4,5-tetrahydro-benzo[b]azepin-2-one was combined with N-[(1R,2R)-2-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide to yield N-{(1R,2R)-2-[5-Chloro-2-(1-isopropyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide (66.83 mg, 61% yield) as a white powder. 1H-NMR (CDCl3) δ 7.93 (s, 1H), 7.40 (m, 2H), 7.12 (d, J=8.3 Hz, 1H), 6.99 (br s, 1H), 5.49 (d, J=7.5 Hz, 1H), 5.44 (m, 1H), 4.82 (m, 1H), 3.85 (br s, 1H), 3.23 (br s, 1H), 2.82 (m, 4H), 2.56 (m, 1H), 2.22 (m, 5H), 1.89 (m, 3H), 1.42 (d, J=6.6 Hz, 3H), 1.36 (br s, 3H), 1.03 (d, J=6.6 Hz, 3H). LC/MS (ESI+)=523 (M+H), MP=141-143° C.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]=[C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]=[CH:12][N:11]2[CH:20]=1.[N:21]([O-])=O.[Na+]>C(O)(=O)C.O>[NH2:21][C:20]1[N:11]2[CH:12]=[CH:13][C:14]3[C:19]([C:10]2=[N:9][C:8]=1[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[CH3:1])=[CH:18][CH:17]=[CH:16][CH:15]=3
Reactant: Cc1ccccc1-c1cn2ccc3ccccc3c2n1
Reactant: O=N[O-]
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: Cc1ccccc1-c1nc2c3ccccc3ccn2c1N
Reaction time: 1 h
Yield: 79.4 %

Procedure:
In a mixture of 30 ml of acetic acid and 6 ml of water was dissolved 2.5 g of 2-(2-methylphenyl)imidazo[2,1-a]isoquinoline with ice-cooling and stirring. A solution of 3.4 g of sodium nitrite in 12 ml of water was added portionwise to this solution and then the mixture was stirred at room temperature for 1 hour. The resulting crude crystals were collected by filtration and washing. The obtained powder was suspended in a mixture of 30 ml of acetic acid and 15 ml of water. To this suspension was added portionwise 6.3 g of zinc powder. After 1 hour, the reaction mixture was filtered, the filtrate was rendered alkaline by the addition of 28% ammonia water, and extracted with ethyl acetate. The extract was washed with water and saturated saline, and dried over anhydrous magnesium sulfate. The drying agent was removed by filtration, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel and recrystallized from ethyl acetate/petroleum ether to give 2.1 g of the title compound as orange needles.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([NH:16][C:17](=[O:26])[C:18]1[C:23]([F:24])=[CH:22][CH:21]=[CH:20][C:19]=1[F:25])[CH2:9][CH2:10]OS(C)(=O)=O.C(N(CC)CC)C.O>O1CCOCC1>[F:24][C:23]1[CH:22]=[CH:21][CH:20]=[C:19]([F:25])[C:18]=1[C:17]1[O:26][CH2:10][CH2:9][CH:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[Br:1])[N:16]=1
Reactant: CS(=O)(=O)OCCC(NC(=O)c1c(F)cccc1F)c1ccccc1Br
Solvent: C1COCCO1
Solvent: CCN(CC)CC
Solvent: O
Product: Fc1cccc(F)c1C1=NC(c2ccccc2Br)CCO1
Yield: 88.4 %

Procedure:
To a solution of 18.0 g of N-[1-(2-bromophenyl)-3-(methylsulfonyloxy)propyl]-2, 6-difluorobenzamide in 150ml of dioxane at room temperature, was added dropwise 4.5 g of triethylamine. The reaction mixture was refluxed for 2.5 hours. After cooling, the reaction mixture was poured into iced water and extracted with ethyl acetate. The ethyl acetate solution was washed with water, dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography to afford 12.5 g of 2-(2,6-difluorophenyl)-4-(2-bromophenyl)-5,6-dihydro-4H-1,3-oxazine.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[OH:8].C(=O)([O-])[O-].[K+].[K+].F[C:16]1[CH:23]=[CH:22][CH:21]=[CH:20][C:17]=1[C:18]#[N:19]>CN(C=O)C>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[O:8][C:16]1[CH:23]=[CH:22][CH:21]=[CH:20][C:17]=1[C:18]#[N:19]
Reactant: N#Cc1ccccc1F
Reactant: Oc1ccccc1Br
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: N#Cc1ccccc1Oc1ccccc1Br
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 91.7 %

Procedure:
To a solution of 2-bromophenol (6.0 mL, 51.7 mmol) in DMF (80 mL) was added potassium carbonate (7.16 g, 51.7 mmol), and the mixture was allowed to stir for 10 min ar rt. 2-Fluorobenzonitrile (5.62 mL, 82.6 mmol) was added and the mixture was heated to 100° C. for 40 h. The mixture was allowed to cool to rt, poured onto ice, filtered, washed with water, and dried to yield 13.0 g (91.7%) of title compound 2-(2-bromophenoxy)-benzonitrile 1j.
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:8]=[CH:7][N:6]([C:9]2[CH:14]=[CH:13][C:12]([O:15]COCC[Si](C)(C)C)=[C:11]([O:24][CH3:25])[CH:10]=2)[C:5](=[O:26])[CH:4]=1.CO.Cl.O1CCOCC1>C(Cl)Cl>[OH:15][C:12]1[CH:13]=[CH:14][C:9]([N:6]2[CH:7]=[CH:8][C:3]([CH2:2][OH:1])=[CH:4][C:5]2=[O:26])=[CH:10][C:11]=1[O:24][CH3:25]
Reactant: COc1cc(-n2ccc(CO)cc2=O)ccc1OCOCC[Si](C)(C)C
Agent: Cl
Solvent: CO
Solvent: C1COCCO1
Solvent: ClCCl
Product: COc1cc(-n2ccc(CO)cc2=O)ccc1O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of 4-(hydroxymethyl)-1-(3-methoxy-4-((2-(trimethylsilyl)ethoxy)-methoxy)phenyl)pyridin-2(1H)-one Part E of Procedure 1 (900 mg, 2.38 mmol) in CH2Cl2 (10 mL) and MeOH (10 mL) was added 4M HCl/Dioxane (10.7 mL, 43 mmol). After stirring at RT for 1 h, concentration under vacuum provided the crude phenol as a white solid. LC-MS, [M+H]+=428.
Reaction SMILES: ClS([N:5]=C=O)(=O)=O.[CH3:8][O:9][C:10]([C@H:12]1[CH2:17][CH2:16][C@H:15]([C:18](O)=O)[CH2:14][CH2:13]1)=[O:11]>C(Cl)Cl>[C:18]([C@H:15]1[CH2:16][CH2:17][C@H:12]([C:10]([O:9][CH3:8])=[O:11])[CH2:13][CH2:14]1)#[N:5]
Reactant: O=C=NS(=O)(=O)Cl
Reactant: COC(=O)[C@H]1CC[C@H](C(=O)O)CC1
Solvent: ClCCl
Product: COC(=O)[C@H]1CC[C@H](C#N)CC1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
Chlorosulfonyl isocyanate (1.0 mL, 0.012 mol) was added to a solution of trans-4-(methoxycarbonyl)cyclohexanecarboxylic acid (2.00 g, 0.0107 mol) in DCM cooled to 0° C. The resulting solution was heated at reflux for 15 minutes and then cooled 0° C. and treated dropwise with DM. The mixture was stirred at room temperature overnight then poured onto ice water and the organic phase separated and washed with a saturated solution of sodium bicarbonate. The solvent was removed in vacuo and the crude material was taken up in ethyl acetate, washed with 1N aq. NaOH (10 mL) and the ethyl acetate removed in vacuo. The resulting crude product was used in subsequent steps without further purification. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.36-1.70 (4H, m), 2.01-2.18 (4H, m), 2.24-2.54 (2H, m) and 3.68 (3H, s).
Reaction SMILES: [Cl:1][C:2]1[C:7]([N+:8]([O-])=O)=[CH:6][C:5]([N:11]2[C:15]([Cl:16])=[C:14]([Br:17])[C:13]([CH3:18])=[N:12]2)=[C:4]([F:19])[CH:3]=1.C(O)C.Cl>[Fe].O>[NH2:8][C:7]1[C:2]([Cl:1])=[CH:3][C:4]([F:19])=[C:5]([N:11]2[C:15]([Cl:16])=[C:14]([Br:17])[C:13]([CH3:18])=[N:12]2)[CH:6]=1
Reactant: Cc1nn(-c2cc([N+](=O)[O-])c(Cl)cc2F)c(Cl)c1Br
Agent: [Fe]
Agent: Cl
Solvent: CCO
Solvent: O
Product: Cc1nn(-c2cc(N)c(Cl)cc2F)c(Cl)c1Br
Yield: 95.4 %

Procedure:
12.5 g (0.034 mol) of 1-(4-chloro-2-fluoro-5-nitrophenyl)-3-methyl-4-bromo-5-chloropyrazole (reference example 2) were added in the solution of 13.6 g of iron powder, 44 ml of ethanol, 20 ml of water and 0.2 ml of hydrochloric acid at 70° to 75° C., under stirring. After stirred for 2 hours at 75° C., the reaction mixture was filtered and the filtrate added with cold water was extracted with ethyl acetate. The ester layer was washed with water, concentrated and purified on column chromatography to obtain 11.0 g of brown crystal, melting point: 113° to 116° C. in yield of 96%.
Reaction SMILES: C(OC([NH:11][CH2:12][CH2:13][CH2:14][C@@H:15]([C:24]([OH:26])=O)[NH:16]C(OC(C)(C)C)=O)=O)C1C=CC=CC=1.[CH:27]1([S:32]([Cl:35])(=[O:34])=[O:33])[CH2:31][CH2:30][CH2:29][CH2:28]1.[NH:36]1[CH2:40][CH2:39][CH2:38][CH2:37]1>>[ClH:35].[NH2:16][C@H:15]([C:24](=[O:26])[N:36]1[CH2:40][CH2:39][CH2:38][CH2:37]1)[CH2:14][CH2:13][CH2:12][NH:11][S:32]([CH:27]1[CH2:31][CH2:30][CH2:29][CH2:28]1)(=[O:34])=[O:33]
Reactant: C1CCNC1
Reactant: O=S(=O)(Cl)C1CCCC1
Reactant: CC(C)(C)OC(=O)N[C@@H](CCCNC(=O)OCc1ccccc1)C(=O)O
Product: Cl
Product: N[C@@H](CCCNS(=O)(=O)C1CCCC1)C(=O)N1CCCC1

Procedure:
Starting from (S)-N5-(benzyloxycarbonyl)-N2-(tert-butyloxycarbonyl)-ornithine, cyclopentanesulphonyl chloride and pyrrolidine, the expected product is obtained according to the procedure described in Example 3.
Reaction SMILES: [CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][C:2]1=O.Cl.[CH2:12]([O:14][C:15](=[O:18])[CH2:16][NH2:17])[CH3:13].C([BH3-])#N.[Na+]>C(O)C>[CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH:2]1[NH:17][CH2:16][C:15]([O:14][CH2:12][CH3:13])=[O:18]
Reactant: O=C1Cc2ccccc2C1
Reactant: CCOC(=O)CN
Agent: Cl
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CCO
Product: CCOC(=O)CNC1Cc2ccccc2C1
Temperature: 25 °C
Yield: 50.4 %

Procedure:
2-Indanone (25.1 g, 0.19 mol) and glycine ethyl ester hydrochloride (34.5 g, 0.247 mol) were dissolved in absolute ethanol (700 mL) and sodium cyanoborohydride (25.8 g, 0.41 mol) was added in portions to the solution. After addition the mixture was allowed to stir at room temperature over night. The ethanol was removed under reduced pressure and the residue treated with water and extracted into ethyl acetate. The organic extract was repeatedly washed with saturated aqueous solutions of sodium bicarbonate and sodium chloride before being dried over magnesium sulfate and filtered. After the solvent was stripped under vacuum an oil remained which was taken up in ether/ethanol (250/50 mL) and cooled by means of an ice-water bath. Ether previously saturated with anhydrous hydrogen chloride was slowly added to the solution. The precipitated product was filtered off and washed with cold ether/ethanol to yield a white solid (21 g) melting at 166°-168° C.
Reaction SMILES: [H-].[Na+].[N+:3]([C:6]1[CH:11]=[CH:10][C:9]([CH2:12][C:13]([OH:15])=[O:14])=[CH:8][CH:7]=1)([O-:5])=[O:4].OS(O)(=O)=O.Br[CH2:22][CH2:23][CH2:24]Br.[H-].CN([CH:30]=[O:31])C>O.CO>[N+:3]([C:6]1[CH:7]=[CH:8][C:9]([CH2:12][C:13]([O:15][CH3:22])=[O:14])=[CH:10][CH:11]=1)([O-:5])=[O:4].[N+:3]([C:6]1[CH:7]=[CH:8][C:9]([C:12]2([C:13]([O:31][CH3:30])=[O:15])[CH2:24][CH2:23][CH2:22]2)=[CH:10][CH:11]=1)([O-:5])=[O:4]
Reactant: O=C(O)Cc1ccc([N+](=O)[O-])cc1
Reactant: BrCCCBr
Reactant: CN(C)C=O
Agent: O=S(=O)(O)O
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: COC(=O)C1(c2ccc([N+](=O)[O-])cc2)CCC1
Product: COC(=O)Cc1ccc([N+](=O)[O-])cc1
Reaction time: 1.5 h

Procedure:
NaH (80% dispersion in mineral oil, 0.26 mol) was suspended in DMF under nitrogen atmosphere. Methyl 4-nitrophenylacetate (0.13 mol), that was prepared by refluxing 4-nitrophenylacetic acid (0.2 mol) with MeOH (100 mL) and conc. H2SO4 (1 mL) for 24 h, dissolved in DMF was added dropwise followed by 1,3-dibromopropane (0.13 mol) in DMF. stirring was continued at room temperature for 1.5 h. Excess hydride was then decomposed by the cautious addion of H2O. More H2O was added and extracted with toluene. The organic layer was washed with H2O, dried (MgSO4) and concentrated to give methyl 1-(4-nitrophenyl)-cyclobutanecarboxylate that was stirred with 0.5 M NaOH (128 mL) in THF overnight. THF was evaporated, the residue was dissolved in H2O and extracted with EtOAc. The aqueous layer was acidified and extracted with EtOAc. The organic layer was dried (MgSO4) and concentrated to give the desired product that was washed with EtOH/H2O. The yield was 0.7 g (12%); 1H NMR (CDCl3) δ 1.90 (m, 1H), 2.05-2.20 (m, 1H), 2.50-2.60 (m, 2H), 2.90 (m, 2H), 7.52 (d, 2H), 8.2 (d, 2H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([Mg]Br)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[C:13]1(=[O:23])[O:18][C:16](=[O:17])[C@H:15]2[CH2:19][CH:20]=[CH:21][CH2:22][C@@H:14]12.[NH4+].[Cl-].Cl>C1COCC1.C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:6]=[CH:7][C:8]=1[O:9][CH3:10])[C:13]([CH:14]1[CH:15]([C:16]([OH:18])=[O:17])[CH2:19][CH:20]=[CH:21][CH2:22]1)=[O:23]
Reactant: COc1ccc([Mg]Br)cc1OC
Reactant: O=C1OC(=O)[C@@H]2CC=CC[C@H]12
Agent: Cl
Agent: [Cl-]
Agent: [NH4+]
Solvent: ClCCl
Solvent: C1CCOC1
Product: COc1ccc(C(=O)C2CC=CCC2C(=O)O)cc1OC
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 10 %

Procedure:
A solution of 17 (59 mmol, 0.29 M) in THF was added dropwise to an ice-cooled solution of cis-1,2,3,6-tetrahydrophthalic anhydride in THF (120 mL) over a 1 hr period. After the addition was complete, the resulting mixture was stirred for another 30 min at 0° C. The reaction mixture was allowed to warm to rt and stirred overnight. The reaction was then stopped with sat. NH4Cl and the pH adjusted to 2 with concentrated HCl(aq) and then extracted with diethyl ether. The organic layer was washed with water and subsequently extracted with 1 M NaOH. The combined aqueous extract was acidified with concentrated HCl and extracted with EtOAc (3×100 mL). The organic layers were combined and dried over MgSO4, filtered, and concentrated under reduced pressure to afford oil. The oil was dissolved CH2Cl2 and filtered through silica gel to remove the dicarboxylic acid formed during workup. The product was recrystallized from diethyl ether to afford pure product (1.62 g, 10%) as a white solid; mp=109° C.; LRMS ESI [m−H]− cacld for C16H18O5 289, found m/z 289; 1H NMR (CDCl3, 500 MHz): δ 7.60-7.53 (m, 2 H), 6.92 (d, J=8.4 Hz, 1 H), 5.84-5.82 (m, 1 H), 5.71-5.68 (m, 1 H), 4.03-4.00 (m, 1 H), 3.98 (s, 3 H), 3.95 (s, 1 H), 3.10-3.07 (m, 1 H), 2.90-2.84 (m, 1 H), 2.54-2.44 (m, 3 H).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH:10]([NH:12][C:13](=[O:15])[CH3:14])[CH3:11])=[CH:5][CH:4]=1)#[CH:2].Br[C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][C:18]=1[O:25][CH3:26].N1CCCCC1>CC(C)=O.O.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>[CH3:24][O:23][C:20]1[CH:19]=[C:18]([O:25][CH3:26])[CH:17]=[CH:22][C:21]=1[C:2]#[C:1][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH:10]([NH:12][C:13](=[O:15])[CH3:14])[CH3:11])=[CH:5][CH:4]=1
Reactant: COc1ccc(Br)c(OC)c1
Reactant: C#Cc1ccc(CC(C)NC(C)=O)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CC(C)=O
Solvent: O
Solvent: C1CCNCC1
Product: COc1ccc(C#Cc2ccc(CC(C)NC(C)=O)cc2)c(OC)c1
Temperature: 60 °C
Reaction time: 1.5 h

Procedure:
A mixture of 36.2 mg (0.18 mmol) N-(1-(4-ethynylphenyl)propan-2-yl)acetamide (I58.3) and 300 μl acetone is added to 50.6 mg (0.15 mmol) 1-bromo-2,4-dimethoxybenzene followed by a suspension of 14.3 (0.02 mmol) bis(triphenylphosphine)dichloropalladium in 300 μl acetone and 600 μl water. After addition of 22.4 mg (0.20 mmol) piperidine the mixture is stirred in a sealed tube for 1.5 h at 60° C. The solvent is removed in vacuo and the residue is purified by HPLC (ACN/H2O/TFA).
Reaction SMILES: [O:1]=[C:2]1[C:6]2[C:7]([C:11]3[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=3)=[N:8][C:9](=O)[C:5]=2[C:4]([C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=2)=[N:3]1.[C:25](=[O:28])([O-])[O-].[K+].[K+].[C:31]1(C)C=CC(S(OC)(=O)=O)=CC=1.[N+](C1C=CC=CC=1)([O-])=O>>[O:1]=[C:2]1[C:6]2=[C:7]([C:11]3[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=3)[N:8]([CH3:9])[C:25](=[O:28])[C:5]2=[C:4]([C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=2)[N:3]1[CH3:31]
Reactant: O=C([O-])[O-]
Reactant: Cc1ccc(-c2nc(=O)c3c(-c4ccc(C)cc4)nc(=O)c2=3)cc1
Reactant: COS(=O)(=O)c1ccc(C)cc1
Agent: [K+]
Solvent: O=[N+]([O-])c1ccccc1
Product: Cc1ccc(C2=C3C(=O)N(C)C(c4ccc(C)cc4)=C3C(=O)N2C)cc1

Procedure:
9.5 Parts of 1,4-diketo-3,6-di-(4'-methylphenyl)pyrrolo-[3,4-c]-pyrrole, 9 parts of anhydrous potassium carbonate, 24 parts of methyl p-toluenesulfonate and 110 parts of nitrobenzene are stirred at 200° C. for 1/2 hour. After the mixture has been cooled, the dye is filtered off and washed with a little nitrobenzene and then with methanol and hot water. After drying, 5.8 parts of 1,4-diketo-2,5-dimethyl-3,6-di-(4'-methylphenyl)-pyrrolo-[3,4-c]-pyrrole are obtained in the form of yellowish-tinged red crystals of melting point 260° C. (formula XIV). The dye gives pure yellow shades of good fastness properties on PES by the method described in Example 1. ##STR18##
Reaction SMILES: [C:1]([NH:4][N:5]=[C:6]([C:14]1[CH:19]=[CH:18][C:17]([O:20][S:21]([C:24]([F:27])([F:26])[F:25])(=[O:23])=[O:22])=[CH:16][CH:15]=1)[C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][CH:8]=1)(=[O:3])[CH3:2].[H-].[Na+].[H][H].Cl[C:33]([N:36]([S:44]N(C(Cl)(C)C)CCC(OCC)=O)[CH2:37][CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])([CH3:35])[CH3:34]>O1CCCC1>[C:1]([N:4]([S:44][N:36]([CH2:37][CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])[CH:33]([CH3:34])[CH3:35])[N:5]=[C:6]([C:14]1[CH:19]=[CH:18][C:17]([O:20][S:21]([C:24]([F:25])([F:27])[F:26])(=[O:23])=[O:22])=[CH:16][CH:15]=1)[C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][CH:8]=1)(=[O:3])[CH3:2]
Reactant: CCOC(=O)CCN(SN(CCC(=O)OCC)C(C)(C)Cl)C(C)(C)Cl
Reactant: CC(=O)NN=C(c1ccc(Cl)cc1)c1ccc(OS(=O)(=O)C(F)(F)F)cc1
Reactant: [H][H]
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOC(=O)CCN(SN(N=C(c1ccc(Cl)cc1)c1ccc(OS(=O)(=O)C(F)(F)F)cc1)C(C)=O)C(C)C
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 45.6 %

Procedure:
A solution of 4-chloro-4'-trifluoromethylsulfonyloxybenzophenone-N-acetylhydrazone (0.5 g) in tetrahydrofuran (6 ml) was stirred at room temperature under a nitrogen atmosphere, during which an oily mixture (50 mg) of sodium hydride containing 60% (w/w) sodium hydride was added to the solution at a time. After stirring at room temperature for 15 minutes and finding no evolution of hydrogen gas, the mixture was cooled to -78° C., and chloro-{N-(2-ethoxycarbonylethyl)-N-isopropylamino}sulfide (0.3 g) was added dropwise over 3 minutes. The reaction mixture was warmed to room temperature over 4 hours, and then poured into ice-water. Further, a saturated saline solution was added thereto. The aqueous layer was extracted with ethyl acetate, and the extract was combined with the organic layer. The combined organic layer was dried over anhydrous magnesium sulfate, and concentrated. The residue was subjected to silica gel chromatography, which afforded 0.2 g of 4-chloro-4'-trifluoromethylsulfonyloxybenzophenone -N-ac etyl -N- {N '-(2-ethoxycarbonylethyl)-N'-isopropylaminosulfenyl}hydrazone (compound 24).
Reaction SMILES: [N+:1]([C:4]1[CH:11]=[CH:10][C:7]([CH:8]=O)=[CH:6][CH:5]=1)([O-:3])=[O:2].Cl.[C:13]1([N:19]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[NH2:20])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>C([O-])(=O)C.[K+].C(O)C>[C:13]1([N:19]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[N:20]=[CH:8][C:7]2[CH:10]=[CH:11][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=2)[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: O=Cc1ccc([N+](=O)[O-])cc1
Reactant: NN(c1ccccc1)c1ccccc1
Agent: CC(=O)[O-]
Agent: Cl
Agent: [K+]
Solvent: CCO
Product: O=[N+]([O-])c1ccc(C=NN(c2ccccc2)c2ccccc2)cc1

Procedure:
p-nitrobenzaldehyde and N,N-diphenylhydrazine hydrochloride were heated in the presence of potassium acetate as a catalyst in ethanol to obtain p-nitrobenzaldehyde-N,N-diphenylhydrazone.