Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]2[C:6]([N:10]3[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][CH2:18][CH2:19][O:20][C:21]4[CH:30]=[C:29]5[C:24]([CH2:25][CH2:26][C:27](=[O:31])[NH:28]5)=[CH:23][CH:22]=4)[CH2:12][CH2:11]3)=[CH:7][CH:8]=[CH:9][C:2]1=2.N1C=CC=CC=1.[CH:38]1([C:44](Cl)=[O:45])[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]1.O>ClCCl>[S:1]1[CH:5]=[CH:4][C:3]2[C:6]([N:10]3[CH2:11][CH2:12][N:13]([CH2:16][CH2:17][CH2:18][CH2:19][O:20][C:21]4[CH:30]=[C:29]5[C:24]([CH2:25][CH2:26][C:27](=[O:31])[N:28]5[C:44]([CH:38]5[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]5)=[O:45])=[CH:23][CH:22]=4)[CH2:14][CH2:15]3)=[CH:7][CH:8]=[CH:9][C:2]1=2
Reactant: O=C(Cl)C1CCCCC1
Reactant: O=C1CCc2ccc(OCCCCN3CCN(c4cccc5sccc45)CC3)cc2N1
Solvent: ClCCl
Solvent: O
Solvent: c1ccncc1
Product: O=C1CCc2ccc(OCCCCN3CCN(c4cccc5sccc45)CC3)cc2N1C(=O)C1CCCCC1

Procedure:
To a solution of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)-butoxy]-3,4-dihydro-1H-quinolin-2-one (1 g) synthesized in the same manner as in WO2006/112464 (Example 11) in dichloromethane (30 ml) was added pyridine (0.37 ml), with stirring under ice-cooling, cyclohexanecarbonyl chloride (0.46 ml) was added and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate, the solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=9:1) to give 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)-butoxy]-1-(cyclohexanecarbonyl)-3,4-dihydroquinolin-2(1H)-one (1.2 g).
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16](=[O:32])[NH:17][C:18]1[S:19][CH:20]=[C:21]([C:23]2[CH:28]=[CH:27][C:26]([N+:29]([O-])=O)=[CH:25][CH:24]=2)[N:22]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[Sn]Cl>CCO.CCOC(C)=O>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16](=[O:32])[NH:17][C:18]1[S:19][CH:20]=[C:21]([C:23]2[CH:24]=[CH:25][C:26]([NH2:29])=[CH:27][CH:28]=2)[N:22]=1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(Nc1nc(-c2ccc([N+](=O)[O-])cc2)cs1)C1CCCN1C(=O)OCc1ccccc1
Agent: Cl[Sn]Cl
Solvent: CCOC(C)=O
Solvent: CCO
Product: Nc1ccc(-c2csc(NC(=O)[C@@H]3CCCN3C(=O)OCc3ccccc3)n2)cc1
Temperature: 25 °C

Procedure:
400 mg (0.88 mmol) of 2-[4-(4-Nitro-phenyl)-thiazol-2-ylcarbamoyl]-pyrrolidine-1-carboxylic acid benzyl ester was dissolved in 30 mL of 1:1 mixture of EtOH/EtOAc. To this solution was added SnCl2 (0.7 g, 3.1 mmol). Reaction mixture was heated under reflux for 5 hours. After 5 hours reaction mixture was cooled to room temperature and evaporated. It was redissolved in EtOAc (150 mL) and washed using sat. K2CO3. Organic phase was isolated, washed using brine and water and evaporated to dryness to give Compound 5050. MS: 422.1 (M+H+).
Reaction SMILES: [N+:1]([O-:4])(O)=[O:2].[CH3:5][C:6]1[CH:7]=[C:8]([C:12]([F:15])([F:14])[F:13])[CH:9]=[CH:10][CH:11]=1>>[N+:1]([C:7]1[C:6]([CH3:5])=[CH:11][CH:10]=[CH:9][C:8]=1[C:12]([F:13])([F:15])[F:14])([O-:4])=[O:2]
Reactant: O=[N+]([O-])O
Reactant: Cc1cccc(C(F)(F)F)c1
Product: Cc1cccc(C(F)(F)F)c1[N+](=O)[O-]
Temperature: 10 °C

Procedure:
6 gms of 90% nitric acid is cooled to -5° C. and 2 gms of 3-methyl benzotrifluoride was added dropwise with stirring. The two phase system was allowed to warm to 10° C. during addition. After stirring 2 hours, the reaction mixture was poured onto ice, extracted with methylene chloride and washed with dilute aqueous sodium bicarbonate. After vacuum removal of solvent on a rotary evaporator, near quantitative oil was obtained which had isomer distribution:
Reaction SMILES: [N+:1]([C:4]1[CH:11]=[CH:10][CH:9]=[C:8]([N+:12]([O-:14])=[O:13])[C:5]=1[C:6]#[N:7])([O-])=O.N1[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1.O>CN(C)C=O>[N+:12]([C:8]1[CH:9]=[CH:10][CH:11]=[C:4]([N:1]2[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]2)[C:5]=1[C:6]#[N:7])([O-:14])=[O:13]
Reactant: N#Cc1c([N+](=O)[O-])cccc1[N+](=O)[O-]
Reactant: C1CCNCC1
Solvent: CN(C)C=O
Solvent: O
Product: N#Cc1c(N2CCCCC2)cccc1[N+](=O)[O-]
Temperature: 50 °C
Reaction time: 0.5 h

Procedure:
5.8 g of 2,6-dinitrobenzonitrile was dissolved in 30 ml of dimethylformamide, and 10.2 ml of piperidine was added to the solution. The mixture was stirred at 50° C. for 30 minutes while externally cooling because of heat generation. The reaction mixture was poured into water, and the precipitate thus formed was collected, washed with water and then with methanol, and dried to obtain 6.7 of 2-nitro-6-piperidinobenzonitrile (melting point: 122°-123° C.).
Reaction SMILES: [CH2:1]([C:3]1([CH:23]([CH3:27])[C:24](O)=[O:25])[CH:12]2[N:7]([CH2:8][CH2:9][C:10]3[C:19]4[C:14](=[CH:15][C:16]([N+:20]([O-:22])=[O:21])=[CH:17][CH:18]=4)[NH:13][C:11]=32)[CH2:6][CH2:5][CH2:4]1)[CH3:2].CN1CCOCC1.ClC(OCC)=O.[C:41]1([C@H:47]([NH2:49])[CH3:48])[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.C(NCC)C>C1(C)C=CC=CC=1.C(Cl)(Cl)Cl.O1CCCC1>[C:41]1([C@H:47]([NH:49][C:24](=[O:25])[CH:23]([C@@:3]2([CH2:1][CH3:2])[C@@H:12]3[N:7]([CH2:8][CH2:9][C:10]4[C:19]5[C:14](=[CH:15][C:16]([N+:20]([O-:22])=[O:21])=[CH:17][CH:18]=5)[NH:13][C:11]=43)[CH2:6][CH2:5][CH2:4]2)[CH3:27])[CH3:48])[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1
Reactant: C[C@@H](N)c1ccccc1
Reactant: CCC1(C(C)C(=O)O)CCCN2CCc3c([nH]c4cc([N+](=O)[O-])ccc34)C21
Agent: CCOC(=O)Cl
Solvent: CN1CCOCC1
Solvent: CCNCC
Solvent: ClC(Cl)Cl
Product: CC[C@@]1(C(C)C(=O)N[C@H](C)c2ccccc2)CCCN2CCc3c([nH]c4cc([N+](=O)[O-])ccc34)[C@@H]21
Temperature: 0 °C
Yield: 69.6 %

Procedure:
0.371 g. (0.001 mole) of (-)-()1S,12bS)-1-ethyl-10-nitro-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizin-1-yl-propionic acid is added to a solution containing 0.111 g. (0.0011 moles) of N-methylmorpholine (redistilled from sodium) in 4 ml. of dry tetrahydrofuran while stirring under nitrogen, then the solution is cooled to 0° C. and 0.108 g. (0.001 mole) of ethyl chloroformate is rapidly added dropwise while stirring vigorously and keeping the inner temperature at or lower than 0° C. for 30 minutes, whereupon a solution containing 0.133 g. (0.0011 moles) of (R)-1-phenylethylamine in 1 ml. of dry tetrahydrofuran is dropwise added at 0° C. while stirring, finally the mixture is stirred at 0° C. for 30 minutes at room temperature for additional 4 hours. Thereupon the reaction mixture is evaporated on a rotating evaporator and after shaking thoroughly the residue with 10 ml. of dichloromethane and 5 ml. of water, the phases are separated. The dichloromethane solution is washed at first with 5 ml of 5% sodium carbonate solution, then three times with 5 ml of water each, dried over anhydrous magnesium sulphate and evaporated. The crude residue is purified by column chromatography on silica gel by using toluene containing 10% of diethylamine as eluant to give 0.33 g (69.6% yield) of the title compound, M.P.: 130°-132° C., [α]D23 =-140.5 (C=1.0 chloroform) with and Rf value of 0.43 (polygram sil G/UV 254: developed by toluene containing 10% of diethylamine: detected by UV light).
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]2[CH:10]=[C:9]([CH3:11])[C:8]([CH3:12])=[CH:7][C:5]=2[N:6]=1.[H-].[Na+].Br[CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18]>O1CCCC1>[CH3:1][C:2]1[N:3]([CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:4]2[CH:10]=[C:9]([CH3:11])[C:8]([CH3:12])=[CH:7][C:5]=2[N:6]=1
Reactant: CCOC(=O)CBr
Reactant: Cc1nc2cc(C)c(C)cc2[nH]1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOC(=O)Cn1c(C)nc2cc(C)c(C)cc21
Yield: 93.4 %

Procedure:
2,5,6-Trimethylbenzimidazole (9.4 g) and sodium hydride (2.1 g, 80% suspension in oil) were sonicated in dry tetrahydrofuran (150 ml) for 1 hour. Ethyl 2-bromoacetate (9.8 g) in dry tetrahydrofuran (50 ml) was added and the reaction sonicated at 40° C. for 2 hours. The reaction was partitioned between ethyl acetate (300 ml) and water (100 ml), the organic phase dried over magnesium sulphate and the solvent removed under reduced pressure to yield ethyl 2-(2,5,6-trimethylbenzimidazol-1-yl)acetate (13.5 g).
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C:12]1[CH:30]=[CH:29][C:15]2[C:16]3[C:24]([O:25][CH:26]([F:28])[F:27])=[CH:23][CH:22]=[CH:21][C:17]=3[O:18][CH:19]([OH:20])[C:14]=2[C:13]=1[Br:31])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:32]1(C)C(S(O)(=O)=O)=CC=CC=1>CO>[Br:31][C:13]1[C:14]2[CH:19]([O:20][CH3:32])[O:18][C:17]3[C:16]([C:15]=2[CH:29]=[CH:30][C:12]=1[NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[C:24]([O:25][CH:26]([F:28])[F:27])[CH:23]=[CH:22][CH:21]=3
Reactant: Cc1ccccc1S(=O)(=O)O
Reactant: O=C(Nc1ccc2c(c1Br)C(O)Oc1cccc(OC(F)F)c1-2)OCc1ccccc1
Solvent: CO
Product: COC1Oc2cccc(OC(F)F)c2-c2ccc(NC(=O)OCc3ccccc3)c(Br)c21

Procedure:
A solution of Example 27E (4.1 g, 8.3 mmol) and toluenesulfonic acid (1 g, 5.2 mmol) in methanol (100 mL) was stirred for 1 hour, and reduced in volume under reduced pressure. The solid was then collected by filtration to provide the titled compound. MS(ESI(−)Q1MS) m/z 504 and 506 (M−H)−.
Reaction SMILES: [Na].[OH:2][C:3]1[CH:10]=[CH:9][CH:8]=[CH:7][C:4]=1[CH:5]=[O:6].Cl.Cl.Cl[CH2:14][CH2:15][CH2:16][N:17]1[CH2:22][CH2:21][N:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:19][CH2:18]1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[C:23]1([N:20]2[CH2:19][CH2:18][N:17]([CH2:16][CH2:15][CH2:14][O:2][C:3]3[CH:10]=[CH:9][CH:8]=[CH:7][C:4]=3[CH:5]=[O:6])[CH2:22][CH2:21]2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: ClCCCN1CCN(c2ccccc2)CC1
Reactant: O=Cc1ccccc1O
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=Cc1ccccc1OCCCN1CCN(c2ccccc2)CC1
Reaction time: 15 h
Yield: 74.4 %

Procedure:
A mixture of 3.88 g of 2-hydroxybenzaldehyde sodium salt, 7.00 g of 1-(3-chloropropyl)-4-phenylpiperazine dihydrochloride, 6.80 g of potassium carbonate and 50 ml of dimethylformamide is stirred at 60° to 70° C. for 15 hours under nitrogen atmosphere, and is concentrated under reduced pressure to remove solvent. Water is added to the residue, and the aqueous mixture is extracted with ether. The extract is washed with water, dried and concentrated under reduced pressure to remove solvent. The residue is purified by silica gel chromatography (solvent, chloroform:methanol=99:1). 5.42 g of 2-[3-(4-phenylpiperazin-1-yl)propyloxy]benzaldehyde are obtained as an oil.
Reaction SMILES: Br[C:2]1[C:11]2[C:6](=[CH:7][C:8]([Br:12])=[CH:9][CH:10]=2)[CH:5]=[C:4]([NH2:13])[N:3]=1.C([O-])=O.[NH4+]>CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Br:12][C:8]1[CH:7]=[C:6]2[C:11](=[CH:10][CH:9]=1)[CH:2]=[N:3][C:4]([NH2:13])=[CH:5]2
Reactant: Nc1cc2cc(Br)ccc2c(Br)n1
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: O=C[O-]
Solvent: CN(C)C=O
Product: Nc1cc2cc(Br)ccc2cn1
Temperature: 50 °C
Yield: 103.6 %

Procedure:
A mixture of 1,6-dibromoisoquinolin-3-amine (13.5 g, 45 mmol), ammonium formate (10.8 g, 172 mmol) and tetrakis(triphenylphosphine)palladium (0) (3.45 g, 3.0 mmol) in 50 mL of DMF were sealed in a 350 mL screw-cap flask and heated at 50° C. for 48 hours. To the reaction was added tetrakis(triphenylphosphine)palladium (0) (950 mg) and ammonium formate (3.0 g), and the mixture was heated at 50° C. for 48 hours. The mixture was cooled to room temperature and the solid was filtered, washed with a minimal amount of DMF, washed with Et2O and dried in vacuo at 50° C. to give the product as a yellow amorphous solid (10.4 g, 90%) LCMS (API-ES) m/z: 222.9, 224.9 [M+1]. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.81 (s, 1H), 7.80 (d, J=1.6 Hz, 1H), 7.73 (d, J=8.8 Hz, 1H), 7.22 (dd, J=8.6, 1.9 Hz, 1H), 6.55 (s, 1H), 6.12 (s, 2H).
Reaction SMILES: [CH3:1][C:2]1[C:6]2[CH:7]=[C:8]([N:11]3[CH2:15][CH2:14][CH2:13][CH2:12]3)[CH:9]=[CH:10][C:5]=2[S:4][C:3]=1[S:16]([NH:19][C:20]1[CH:21]=[C:22]([CH:28]=[CH:29][CH:30]=1)[C:23]([O:25]CC)=[O:24])(=[O:18])=[O:17].[Li+].[OH-].C(O)(=O)C>C1COCC1.O>[CH3:1][C:2]1[C:6]2[CH:7]=[C:8]([N:11]3[CH2:15][CH2:14][CH2:13][CH2:12]3)[CH:9]=[CH:10][C:5]=2[S:4][C:3]=1[S:16]([NH:19][C:20]1[CH:21]=[C:22]([CH:28]=[CH:29][CH:30]=1)[C:23]([OH:25])=[O:24])(=[O:17])=[O:18]
Reactant: CCOC(=O)c1cccc(NS(=O)(=O)c2sc3ccc(N4CCCC4)cc3c2C)c1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: Cc1c(S(=O)(=O)Nc2cccc(C(=O)O)c2)sc2ccc(N3CCCC3)cc12

Procedure:
The ethyl 3-{[(3-methyl-5-pyrrolidin-1-yl-1-benzothiophen-2-yl)sulfonyl]amino}benzoate (4.7 mg, 0.01 mmol) was hydrolyzed with LiOH (2.6 mg, 0.06 mmol) in THF/water (1:1, 2 mL) at 55° C. over night. The reaction mixture was neutralized with acetic acid (3.6 μL) and the mixture was concentrated. The crude product was purified by preparative HPLC (ACE C8, 5 μm 21×50 mm, flow 25 ml/min, 50 mM NH4OAc in water/CH3CN) to give 2.7 mg (6% over two steps) of the title compound. MS (ESI+) calcd for C20H20N2O4S2 416.086449, found 416.086649.
Reaction SMILES: [CH3:1][NH:2][C:3]([C:5]1[CH:6]=[N:7][C:8]([O:11][C:12]2[C:22]([I:23])=[CH:21][C:15]3[CH2:16][CH2:17][NH:18][CH2:19][CH2:20][C:14]=3[CH:13]=2)=[CH:9][CH:10]=1)=[O:4].[C:24]1(=O)[CH2:27][CH2:26][CH2:25]1>C(O)(=O)C.CO>[CH:24]1([N:18]2[CH2:17][CH2:16][C:15]3[CH:21]=[C:22]([I:23])[C:12]([O:11][C:8]4[N:7]=[CH:6][C:5]([C:3]([NH:2][CH3:1])=[O:4])=[CH:10][CH:9]=4)=[CH:13][C:14]=3[CH2:20][CH2:19]2)[CH2:27][CH2:26][CH2:25]1
Reactant: O=C1CCC1
Reactant: CNC(=O)c1ccc(Oc2cc3c(cc2I)CCNCC3)nc1
Solvent: CO
Solvent: CC(=O)O
Product: CNC(=O)c1ccc(Oc2cc3c(cc2I)CCN(C2CCC2)CC3)nc1
Reaction time: 0.5 h

Procedure:
N-Methyl-6-(8-iodo-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yloxy)-3-pyridinecarboxamide (D43) (423 mg, 1.0 mmol) was dissolved in 2.5% acetic acid in methanol (5 ml) and treated dropwise with cyclobutanone (0.11 ml, 1.5 mmol). The mixture was stirred for 30 minutes and then (polystyrylmethyl)trimethylammonium cyanoborohydride (2.0 mmol/g, 1 g, 2 mmol) was added. The reaction mixture was stirred at room temperature for 18 hours, applied to a SCX ion exchange cartridge (Varian bond-elute, 10 g) and washed with methanol and then a mixture of 0.880 ammonia:methanol (1:9). The combined basic fractions were concentrated in vacuo and the resulting residue purified by column chromatography eluting with a mixture of 0.880 ammonia:methanol:dichloromethane (0.5:2.25:97.5) to afford the title compound (E225). MS (ES+) m/e 478 [M+H]+.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH3:34])[C@@H:9]([CH3:33])[C:10]([NH:12][C@@H:13]([CH:30]([CH3:32])[CH3:31])[C:14]([N:16]1[C:20]2=[N:21][CH:22]=[CH:23][CH:24]=[C:19]2[CH2:18][C@H:17]1[C:25]([O:27]CC)=[O:26])=[O:15])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].O.[OH-].[Li+]>C1COCC1.CO.O>[C:1]([O:5][C:6]([N:8]([CH3:34])[C@@H:9]([CH3:33])[C:10]([NH:12][C@@H:13]([CH:30]([CH3:31])[CH3:32])[C:14]([N:16]1[C:20]2=[N:21][CH:22]=[CH:23][CH:24]=[C:19]2[CH2:18][C@H:17]1[C:25]([OH:27])=[O:26])=[O:15])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CCOC(=O)[C@@H]1Cc2cccnc2N1C(=O)[C@@H](NC(=O)[C@H](C)N(C)C(=O)OC(C)(C)C)C(C)C
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: CC(C)[C@H](NC(=O)[C@H](C)N(C)C(=O)OC(C)(C)C)C(=O)N1c2ncccc2C[C@H]1C(=O)O
Reaction time: 1 h
Yield: 100.6 %

Procedure:
A solution of (S)-ethyl 1-((S)-2-((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-3-methylbutanoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylate (1.9 g, 3.99 mmol, Eq: 1.00) in THF (36 mL) and MeOH (12 mL) was cooled in an ice bath. To this solution was added a solution of lithium hydroxide monohydrate (0.5 g, 11.9 mmol, Eq: 2.99) in water (12 mL) and the cooling bath was removed. After 1 h, the reaction was quenched by adding 0.1 M aqueous KHSO4 (200 mL) and the mixture was extracted with DCM (2×100 mL). The combined DCM layers were dried over Na2SO4 and concentrated in vacuo. The residue was azeotroped with n-heptane (1×100 mL) to give (S)-1-((S)-2-((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-3-methylbutanoyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid (1.8 g) as a white solid, m/z=449 (M+H).
Reaction SMILES: [C:1]([O:7][CH3:8])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].B(O)(O)O.[CH2:13](O)[CH2:14][C:15]#C.C(OC)(=O)CC(C)=O.C1(C)C=CC=CC=1>C1(C)C=CC=CC=1>[O:4]=[C:3]([CH3:5])[CH2:2][C:1]([O:7][CH2:8][CH2:15][C:14]#[CH:13])=[O:6]
Reactant: COC(=O)CC(C)=O
Reactant: C#CCCO
Agent: OB(O)O
Solvent: Cc1ccccc1
Product: C#CCCOC(=O)CC(C)=O
Yield: 71.7 %

Procedure:
Methyl acetoacetate (1 g, 8.6 mmol) was dissolved in 40 mL dry toluene. Boric acid (53 mg, 0.86 mmol) and 3-butyn-1-ol (1 g, 14.3 mmol) were added to the methyl acetoacetate/toluene solution under a N2 atmosphere and the mixture was refluxed for 24 hr using a Dean-Stark condenser. Solvents were then removed under reduced pressure. The crude product was purified by flash column chromatography (SiO2, hexane/ethylacetate:15/1) to obtain compound 2 (950 mg, 73% yield), a pale yellow to colorless liquid. 1H NMR 300 MHz (ppm, CDCl3): 4.21 (2H, t J=6.8 Hz), 3.48 (2H, s), 2.59-2.54 (2H, dt J=6.8, 2.7 Hz), 2.29 (3H, s), 2.00 (1H, t J=2.7). 13C NMR (CDCl3, 75 MHz): 200.22, 166.83, 79.70, 70.12, 62.99, 49.92, 30.16, 18.89. ESI-MS: (M+H)+=m/z 155.18 (calculated MW of C8H10O3: 154.16 Da).
Reaction SMILES: [CH3:1][N:2]1[C:6]([N+:7]([O-:9])=[O:8])=[CH:5][N:4]=[C:3]1[C:10](=[NH:14])OCC.[C:15]([NH:18][NH2:19])(=[O:17])[CH3:16]>CO>[CH3:1][N:2]1[C:6]([N+:7]([O-:9])=[O:8])=[CH:5][N:4]=[C:3]1[C:10]([NH:19][NH:18][C:15](=[O:17])[CH3:16])=[NH:14]
Reactant: CC(=O)NN
Reactant: CCOC(=N)c1ncc([N+](=O)[O-])n1C
Solvent: CO
Product: CC(=O)NNC(=N)c1ncc([N+](=O)[O-])n1C

Procedure:
In 200 ml. of methanol, 12 g. (0.06 mole) of ethyl 1-methyl-5-nitro-2-imidazolecarboximidate and 4.9 g. (0.066 mole) of acetyl hydrazine are refluxed for 30 hours. The yellow compound is collected, washed with cold methanol and dried to give 12.97 g. of the title compound, melting point 294°C.
Reaction SMILES: [OH-].[Li+].[CH3:3][O:4][C:5]1[CH:14]=[CH:13][C:12]([C:15]2[S:16][CH:17]=[CH:18][CH:19]=2)=[CH:11][C:6]=1[C:7]([O:9]C)=[O:8]>C1(C)C=CC=CC=1.C(O)C.O>[CH3:3][O:4][C:5]1[CH:14]=[CH:13][C:12]([C:15]2[S:16][CH:17]=[CH:18][CH:19]=2)=[CH:11][C:6]=1[C:7]([OH:9])=[O:8]
Reactant: COC(=O)c1cc(-c2cccs2)ccc1OC
Agent: [Li+]
Agent: [OH-]
Solvent: Cc1ccccc1
Solvent: CCO
Solvent: O
Product: COc1ccc(-c2cccs2)cc1C(=O)O
Reaction time: 8 h

Procedure:
Lithium hydroxide (43 mg) was added to methyl 2-Methoxy-5-(thiophene-2-yl)benzoate (102 mg) in a solvent mixture of tetrahydrofuran/methanol/water (2/1/1, 3 ml), and they were stirred overnight. The solvent was evaporated, and the residue was added to 3 N hydrochloric acid. The white solid thus precipitated was taken by the filtration as the title compound.
Reaction SMILES: O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.[NH:15]([C:22]1[CH:30]=[C:29]([C:31](O)=[O:32])[C:28]([NH:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[CH:27][C:23]=1[C:24](O)=[O:25])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C1(C)C=CC=C(NC2C=C(C(O)=O)C(NC3C=C(C)C=CC=3)=CC=2C(O)=O)C=1.ClC1C=C(C=CC=1)NC1C=C(C(O)=O)C(NC2C=CC=C(Cl)C=2)=CC=1C(O)=O>>[CH:38]1[CH:39]=[C:40]2[C:31]([C:29]3[C:28]([NH:34][C:35]2=[CH:36][CH:37]=1)=[CH:27][C:23]1[C:24]([C:21]2[C:16]([NH:15][C:22]=1[CH:30]=3)=[CH:17][CH:18]=[CH:19][CH:20]=2)=[O:25])=[O:32]
Reactant: O=C(O)c1cc(Nc2ccccc2)c(C(=O)O)cc1Nc1ccccc1
Agent: Cc1cccc(Nc2cc(C(=O)O)c(Nc3cccc(C)c3)cc2C(=O)O)c1
Agent: O=C(O)c1cc(Nc2cccc(Cl)c2)c(C(=O)O)cc1Nc1cccc(Cl)c1
Agent: O=P12OP3(=O)OP(=O)(O1)OP(=O)(O2)O3
Product: O=c1c2ccccc2[nH]c2cc3c(=O)c4ccccc4[nH]c3cc12
Temperature: 85 °C

Procedure:
465 parts of polyphosphoric acid, containing 85.0% P2O5, are introduced into a pressure vessel. Then 83.8 parts of 2,5-dianilinoterephthalic acid, 4.6 parts of 2,5-di(3-toluidino)terephthalic acid and 4.6 parts of 2,5-di(3-chloro-anilino)terephthalic acid are introduced with stirring at from 80 to 90° C. and the mixture is heated at 125° C. for 1 hour during which ring closure takes place to form the quinacridone. The reaction mixture is then introduced into a second pressure vessel where it is hydrolyzed under pressure and with stirring with a mixture of 2095 parts of 30% phosphoric acid at 140° C. During this hydrolysis the temperature rises to 155° C. The mixture is stirred at 155° C. for 0.5 hour. Then it is cooled to 60° C. and the mixed crystal pigment is filtered off with suction, washed to neutrality with water and dried at 80° C.
Reaction SMILES: [C:1]([O:5][C:6](=[O:18])[NH:7][C:8]1[C:9]([N+:15]([O-:17])=[O:16])=[N:10][C:11]([Br:14])=[CH:12][CH:13]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:21]I>CN(C=O)C>[C:1]([O:5][C:6](=[O:18])[N:7]([C:8]1[C:9]([N+:15]([O-:17])=[O:16])=[N:10][C:11]([Br:14])=[CH:12][CH:13]=1)[CH3:21])([CH3:4])([CH3:2])[CH3:3]
Reactant: CI
Reactant: CC(C)(C)OC(=O)Nc1ccc(Br)nc1[N+](=O)[O-]
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CN(C(=O)OC(C)(C)C)c1ccc(Br)nc1[N+](=O)[O-]
Reaction time: 0.25 h
Yield: 88.7 %

Procedure:
To a stirred solution of (6-bromo-2-nitro-pyridin-3-yl)-carbamic acid tert-butyl ester (6) (290 mg, 0.91 mmol) in DMF (10 mL), NaH (57 mg, 1.36 mmol, 57% dispersion in oil) was added at 0° C. After stirring for 15 minutes, methyl iodide (79 μL, 1.27 mmol) was added and the reaction mixture was stirred for 1 hour. The reaction mixture was then quenched with saturated ammonium chloride solution (15 mL) and extracted with ethyl acetate (2×40 mL). The combined organic extracts were washed with water, brine, dried over MgSO4, and concentrated in vacuo. The residue was purified by flash column chromatography using 20% ethyl acetate in hexane to give compound (7) (268 mg) as a pale yellow solid.
Reaction SMILES: [C:1]([SH:9])(=[S:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:10][C:11]([CH2:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[CH2:12]>C(Cl)(Cl)(Cl)Cl>[C:1]([S:9][C:11]([CH3:12])([CH2:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH3:10])(=[S:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C=C(C)CC(C)(C)C
Reactant: S=C(S)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: CC(C)(C)CC(C)(C)SC(=S)c1ccccc1
Temperature: 70 °C
Yield: 31.7 %

Procedure:
A mixture of dithiobenzoic acid (5 g), 2,4,4-trimethylpentene (7.3 g) and carbon tetrachloride (25 mL) was heated at 70° C. for two days. The resultant mixture was reduced to a crude oil. Purification of the residue, by column chromatography (Kieselgel-60, 70-230 mesh, petroleum spirit 40-60° C. eluent) gave 2,4,4-trimethylpent-2-yl dithiobenzoate (17) (2.74 g, 31.7% yield) as a dark red oil. 1H-nmr (CDCl3) d (ppm): 1.08 (s, 9H, 3×CH3), 1.77 (s, 6H, 2×CH3), 2.20 (s, 2H, CH2), 7.35 (dd, 2H, meta-ArH), 7.49 (dd, 1H, para-ArH) and 7.85 (d, 2H, ortho-ArH). 13C-nmr (CDCl3) d (ppm): 28.3, 31.5, 32.8, 50.5, 57.7, 126.6, 128.1, 131.5 and 147.9. The signal due to C═S (d>220.0 ppm) was beyond the frequency range of the spectrum.
Reaction SMILES: Br[CH:2](Br)[C:3]1[CH:7]=[C:6]([C:8]([O:10]CC)=[O:9])[N:5]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[N:4]=1.[OH-:22].[Li+]>C1COCC1.O>[CH:2]([C:3]1[CH:7]=[C:6]([C:8]([OH:10])=[O:9])[N:5]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[N:4]=1)=[O:22]
Reactant: [OH-]
Reactant: CCOC(=O)c1cc(C(Br)Br)nn1-c1ccc(OC)cc1
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: COc1ccc(-n2nc(C=O)cc2C(=O)O)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 33 %

Procedure:
Ethyl 3-(dibromomethyl)-1-(4-methoxyphenyl)-1H-pyrazole-5-carboxylate (0.34 g, 0.813 mmol) was dissolved in 2 mL THF and lithium hydroxide (34 mg, 0.816 mmol) was dissolved in 0.5 mL water and added to the methanolic solution. After stirring at room temperature for 16 hours the solvent was evaporated, the residue was dissolved in 10 mL of water, acidified with 1N HCl and extracted with EtOAc to give 66 mg (33%) of the desired product after evaporation. 1H NMR (CDCl3): δ 10.06 (s, 1H); 7.56 (s, 1H); 7.40 (d, J=9.1, 2H); 7.01 (d, J=9.1, 2H); 4.54 (s, 2H); 3.88 (s, 3H).