Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[N:11]=[C:10](Cl)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[CH3:13][O:14][C:15]1[CH:21]=[CH:20][C:18]([NH2:19])=[CH:17][CH:16]=1>>[Cl:1][C:2]1[N:11]=[C:10]([NH:19][C:18]2[CH:20]=[CH:21][C:15]([O:14][CH3:13])=[CH:16][CH:17]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1
Reactant: COc1ccc(N)cc1
Reactant: Clc1nc(Cl)c2ccccc2n1
Product: COc1ccc(Nc2nc(Cl)nc3ccccc23)cc1

Procedure:
The title compound was prepared from 2,4-dichloroquinazoline (50 mg, 0.251 mmol) and 4-methoxyaniline (45 mg, 0.326 mmol) by a procedure similar to example 1b and was isolated as off white powder (55 mg, 77%). 1H NMR (CDCl3): 10.25 (s, 1H), 8.58 (d, J=8.4 Hz, 1H), 7.88 (t, J=7.2 Hz, 1H), 7.71-7.63 (m, 4H), 7.03-6.99 (m, 2H), 3.79 (s, 3H).
Reaction SMILES: [CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][CH:10]=[C:11]([C:18]4[CH:19]=[C:20]5[C:24](=[C:25]([O:27]C)[CH:26]=4)[CH2:23][N:22]([S:29]([C:32]4[CH:37]=[CH:36][C:35]([CH3:38])=[CH:34][CH:33]=4)(=[O:31])=[O:30])[CH2:21]5)[C:12]=3[O:14][CH:15]([F:17])[F:16])[C:7](=[O:39])[C:6]([C:40]([O:42]CC)=[O:41])=[CH:5]2)[CH2:3][CH2:2]1.B(Br)(Br)Br.[OH-].[Na+].Cl>C(Cl)Cl.C(O)C.O1CCOCC1.O.C(Cl)(Cl)Cl>[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][CH:10]=[C:11]([C:18]4[CH:19]=[C:20]5[C:24](=[C:25]([OH:27])[CH:26]=4)[CH2:23][N:22]([S:29]([C:32]4[CH:33]=[CH:34][C:35]([CH3:38])=[CH:36][CH:37]=4)(=[O:30])=[O:31])[CH2:21]5)[C:12]=3[O:14][CH:15]([F:17])[F:16])[C:7](=[O:39])[C:6]([C:40]([OH:42])=[O:41])=[CH:5]2)[CH2:3][CH2:2]1
Reactant: CCOC(=O)c1cn(C2CC2)c2c(OC(F)F)c(-c3cc4c(c(OC)c3)CN(S(=O)(=O)c3ccc(C)cc3)C4)ccc2c1=O
Agent: BrB(Br)Br
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Product: Cc1ccc(S(=O)(=O)N2Cc3cc(-c4ccc5c(=O)c(C(=O)O)cn(C6CC6)c5c4OC(F)F)cc(O)c3C2)cc1
Temperature: -30 °C
Reaction time: 0.08 h
Yield: 46 %

Procedure:
In 10 ml of methylene chloride was suspended 0.28 g of ethyl 1-cyclopropyl-8-difluoromethoxy-7-[7-methoxy-2-(p-toluenesulfonyl)isoindolin-5-yl]-1,4-dihydro-4-oxoquinoline-3-carboxylate, and the suspension was cooled to -30° C., after which 1.3 ml of 1.0 M solution of boron tribromide in methylene chloride was added dropwise thereto over a period of 5 minutes, and the resulting mixture was stirred at 0° C. for 2 hours. The reaction mixture was added to a mixed solvent of 10 ml of chloroform and 10 ml of water, and the organic layer was separated. The organic layer obtained was washed with water, dried over anhydrous magnesium sulfate, and then distilled under reduced pressure to remove the solvent. The resulting residue was purified by a column chromatography (eluent; chloroform:acetone=5:1) and the crystals thus obtained were suspended in 1.5 ml of ethanol and 1.5 ml of dioxane, after which 0.74 ml of a 1N aqueous sodium hydroxide solution was added thereto and the resulting mixture was stirred at 60° C. for 30 minutes. To the reaction mixture was added 0.74 ml of 1N hydrochloric acid and the crystals were collected by filtration to obtain 0.12 g of light-brown 1-cyclopropyl-8-difluoromethoxy-7-[7-hydroxy-2-(p-toluenesulfonyl)isoindolin-5-yl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acid.
Reaction SMILES: [CH3:1][C:2]([CH3:17])([CH3:16])[C:3]#[C:4][C:5]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[CH:8]=[C:7]([F:14])[C:6]=1[NH2:15].N1C=CC=CC=1.[C:24](Cl)(=[O:28])[CH2:25][CH2:26][CH3:27]>C(Cl)Cl>[CH3:1][C:2]([CH3:17])([CH3:16])[C:3]#[C:4][C:5]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[CH:8]=[C:7]([F:14])[C:6]=1[NH:15][C:24](=[O:28])[CH2:25][CH2:26][CH3:27]
Reactant: CC(C)(C)C#Cc1cc([N+](=O)[O-])cc(F)c1N
Reactant: CCCC(=O)Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCCC(=O)Nc1c(F)cc([N+](=O)[O-])cc1C#CC(C)(C)C
Temperature: 0 °C
Reaction time: 5 h
Yield: 61.4 %

Procedure:
To a solution of 2-(3,3-dimethyl-but-1-ynyl)-6-fluoro-4-nitro-phenylamine (4.0 g, 17 mmol) and pyridine (2.7 g, 34 mmol) in anhydrous CH2Cl2 (30 mL) was added and butyryl chloride (1.8 g, 17 mmol) dropwise at 0° C. After stirring for 5 h at 0° C., the reaction mixture was poured into ice (50 g) and extracted with CH2Cl2 (30 mL×3). The combined organic extracts were dried over anhydrous Na2SO4 and evaporated under vacuum to give N-[2-(3,3-dimethyl-but-1-ynyl)-6-fluoro-4-nitro-phenyl]-butyramide (3.2 g, 62%), which was used in the next step without further purification. 1H NMR (300 MHz, DMSO) δ 8.10 (dd, J=1.5, 2.7 Hz, 1H), 7.95 (dd, J=2.4, 9.6 Hz, 1 H), 7.22 (brs, 1 H), 2.45 (t, J=7.5 Hz, 2 H), 1.82 (m, 2 H), 1.36 (s, 9 H), 1.06 (t, J=7.5 Hz, 3 H).
Reaction SMILES: Cl[C:2]1[C:7]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][N:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[NH2:14][C:15]1[CH:16]=[C:17]([CH:23]=[CH:24][C:25]=1[C:26]([F:29])([F:28])[F:27])[C:18]([O:20][CH2:21][CH3:22])=[O:19].CC(C)([O-])C.[Na+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:11]1[CH:12]=[CH:13][C:8]([C:7]2[C:2]([NH:14][C:15]3[CH:16]=[C:17]([CH:23]=[CH:24][C:25]=3[C:26]([F:27])([F:28])[F:29])[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[N:3][CH:4]=[CH:5][CH:6]=2)=[N:9][CH:10]=1
Reactant: CCOC(=O)c1ccc(C(F)(F)F)c(N)c1
Reactant: Clc1ncccc1-c1ccncn1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(C)[O-]
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: CCOC(=O)c1ccc(C(F)(F)F)c(Nc2ncccc2-c2ccncn2)c1
Temperature: 80 °C
Reaction time: 8 h

Procedure:
4-(2-Chloropyridin-3-yl)pyrimidine (1.5 g, 7.8 mmol), ethyl 3-amino-4-(trifluoromethyl)benzoate (2.0 g, 8.6 mmol), Sodium tert-butoxide (1.1 g, 12 mmol), rac-2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (0.49 g, 0.78 mmol) were all mixed together in toluene (25 ml) and degassed under vacuum. Nitrogen was bubbled into the reaction for 5 minutes and then Palladium (II) acetate (0.088 g, 0.39 mmol) was added. The mixture was heated to 80° C. and stirred overnight. The reaction was diluted with ethyl acetate and washed with an aqueous saturated solution of sodium bicarbonate, water and brine. The organic layer was then dried with sodium sulfate and purified by column chromatography on silica gel using a gradient 5 to 40% ethyl acetate in hexanes to afford ethyl 3-(3-(pyrimidin-4-yl)pyridin-2-ylamino)-4-(trifluoromethyl)benzoate as a brown solid. MS m/z=389 [M+1]+. Calc'd for C19H15F3N4O2: 388.11.
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:12]=[CH:11][C:10]([Cl:13])=[C:9]2[C:5]=1[C:6](=[O:15])[C:7](=[O:14])[NH:8]2.Br[CH2:17][CH2:18][CH2:19][CH2:20][CH3:21].C(OCC)C>CN(C)C=O>[Cl:3][C:4]1[CH:12]=[CH:11][C:10]([Cl:13])=[C:9]2[C:5]=1[C:6](=[O:15])[C:7](=[O:14])[N:8]2[CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]
Reactant: CCCCCBr
Reactant: O=C1Nc2c(Cl)ccc(Cl)c2C1=O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOCC
Product: CCCCCN1C(=O)C(=O)c2c(Cl)ccc(Cl)c21
Reaction time: 0.5 h
Yield: 74.5 %

Procedure:
To a mixture of sodium hydride (0.17 g, 6.94 mmol, 60% dispersion in mineral oil) in anhydrous N,N-dimethylformamide (5.00 mL) was added a solution of 4,7-dichloro-1H-indole-2,3-dione (1.00 g, 4.60 mmol) in N,N-dimethylformamide (5.00 mL) at 0° C. The brown reaction mixture was stirred for 0.5 h followed by the addition of a solution of 1-bromopentane (0.84 g, 5.55 mmol) in anhydrous N,N-dimethylformamide (5.00 mL). The reaction mixture was stirred at ambient temperature for 16 h and poured into wet ethyl ether (30.0 mL). After the organic layer was separated, it was washed with water (2×20.0 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The gummy residue was dried under vacuum and the solid was triturated with ether to give the title compound (0.98 g, 98%): MS (ES+) m/z 286.2 (M+1).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]([OH:15])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:16][C:17]1[CH:18]=[C:19]([CH3:26])[CH:20]=[CH:21][C:22]=1[C:23]([OH:25])=[O:24]>>[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]([NH:16][C:17]1[CH:18]=[C:19]([CH3:26])[CH:20]=[CH:21][C:22]=1[C:23]([OH:25])=[O:24])=[O:15])=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: Cc1ccc(C(=O)O)c(N)c1
Reactant: CC(C)(C)OC(=O)NCCCCC(=O)O
Product: Cc1ccc(C(=O)O)c(NC(=O)CCCCNC(=O)OC(C)(C)C)c1

Procedure:
For the preparation of the starting material, 5-[1-(t-butoxy)formamido]valeric acid and 3-amino-p-toluic acid are coupled to give 3-[5-(1-t-butoxyformamido)valeramido]-p-toluic acid, m.p. 212° C., and the latter is coupled with β-alanine benzyl ester to give N-[3-[5-(1-t-butoxyformamido)valeramido]-p-toluoyl]-β-alanine benzyl ester, m.p. 112°-113° C.
Reaction SMILES: [Cl:1][C:2]1[C:10]([Cl:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[Cl:12][C:13]1[N:18]=[CH:17][C:16]([CH:19]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[CH2:20][NH2:21])=[CH:15][CH:14]=1>>[Cl:1][C:2]1[C:10]([Cl:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH:21][CH2:20][CH:19]([C:16]1[CH:17]=[N:18][C:13]([Cl:12])=[CH:14][CH:15]=1)[N:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1)=[O:6]
Reactant: O=C(O)c1cccc(Cl)c1Cl
Reactant: NCC(c1ccc(Cl)nc1)N1CCOCC1
Product: O=C(NCC(c1ccc(Cl)nc1)N1CCOCC1)c1cccc(Cl)c1Cl

Procedure:
From 2,3-dichlorobenzoic acid and 2-(6-chloro-3-pyridyl)-2-morpholin-4-yl-ethylamine.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:25])[C@@H:4]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=1)[N:5]([C:7](=[O:16])[C:8]1[CH:13]=[C:12]([CH3:14])[CH:11]=[C:10]([CH3:15])[CH:9]=1)[CH3:6].N[C@@H](C(O)=O)C[C:29]1[CH:34]=[CH:33][C:32](O)=[CH:31][CH:30]=1>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:25])[C@@H:4]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[CH:20][CH:19]=1)[N:5]([C:7](=[O:16])[C:8]1[CH:13]=[C:12]([CH3:14])[CH:11]=[C:10]([CH3:15])[CH:9]=1)[CH3:6]
Reactant: N[C@H](Cc1ccc(O)cc1)C(=O)O
Reactant: COC(=O)[C@@H](Cc1ccc(O)cc1)N(C)C(=O)c1cc(C)cc(C)c1
Solvent: ClCCl
Product: COC(=O)[C@@H](Cc1ccc(Oc2ccccc2)cc1)N(C)C(=O)c1cc(C)cc(C)c1

Procedure:
A solution of N-(3,5-dimethylbenzoyl)-N-methyl-(D)-tyrosine methyl ester (253 mg, 0.74 mmol) (prepared from (D)-tyrosine following the procedure described in example 55), Ph3Bi(OAc)2 [triphenylbismuth diacetate] (895 mg, 1.6 mmol) (prepared according to the literature procedure; H. Brunner, U. Obermann, and P. Winner, Organometallics 1989, 8, 821-826), and Cu powder (43 mg, 0.68 mmol) in methylene chloride (15 ml) is stirred at room temperature under nitrogen atmosphere overnight. This reaction mixture is concentrated in vacuo and the crude material is chromatographed on silica with hexane/ethylacetate (3:1) to give N-(3,5-dimethylbenzoyl)-N-methyl-O-phenyl-(D)-tyrosine methyl ester as a colorless oil. Hydrolysis of the methyl ester obtained above (294 mg, 0.70 mol) by lithium hydroxide hydrate (31 mg, 0.74 mol) gives a corresponding acid.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][C:11]([OH:13])=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].C([NH2:17])C#C.C(N=C=NC(C)C)(C)C.O>C1COCC1>[C:11]([NH2:17])(=[O:13])[C:10]#[CH:9].[C:6]([NH:8][CH2:9][CH2:10][C:11]([OH:13])=[O:12])([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:7]
Reactant: C#CCN
Agent: CC(C)(C)OC(=O)NCCC(=O)O
Agent: CC(C)N=C=NC(C)C
Solvent: C1CCOC1
Solvent: O
Product: C#CC(N)=O
Temperature: 25 °C
Reaction time: 16 h

Procedure:
N-Boc-β-alanine (1a) (1.05 g, 5.5 mmol) and propargyl amine (0.90 g, 16.5 mmol) were dissolved in THF (10 mL). Diisopropyl-carbodiimide (DIC, 695 g, 5.5 mmol) was added and the reaction mixture was stirred for 16 h at room temperature. Water was added (20 mL) and the product was extracted into EtOAc (3×30 mL). The combined EtOAc was dried (Na2SO4) and evaporated. The crude product was purified by silica column chromatography eluting with EtOAc:Heptane gradient (2:3)-(3:2.5) (v/v). Product yield 0.925 g, 74%.
Reaction SMILES: C1(S(O[C:11]2[CH:16]=[C:15]([CH3:17])[CH:14]=[C:13]([CH3:18])[CH:12]=2)(=O)=O)C=CC=CC=1.[CH3:19][NH:20][CH:21]=[O:22].CCCCCC>C(OCC)(=O)C>[CH3:18][C:13]1[CH:12]=[C:11]([N:20]([CH3:19])[CH:21]=[O:22])[CH:16]=[C:15]([CH3:17])[CH:14]=1
Reactant: CNC=O
Reactant: Cc1cc(C)cc(OS(=O)(=O)c2ccccc2)c1
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: Cc1cc(C)cc(N(C)C=O)c1
Yield: 93.1 %

Procedure:
Following the general procedure, 3,5-dimethylphenyl benzenesulfonate (131 mg, 0.5 mmol) was coupled with N-methylformamide (45 mg, 0.75 mmol) with the reaction time of 20 h. Chromatography on silica gel column with 4:1 hexane:ethyl acetate gave 76 mg (93%) of the title compound as a colorless oil.
Reaction SMILES: [C:1]([CH:4]([O:6][C:7]1[N:11]=[CH:10][N:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)[N:8]=1)[CH3:5])([OH:3])=O.[C:22](N1C=CN=C1)([N:24]1C=CN=[CH:25]1)=O.CNC>CN(C)C=O>[CH3:22][N:24]([CH3:25])[C:1]([CH:4]([O:6][C:7]1[N:11]=[CH:10][N:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)[N:8]=1)[CH3:5])=[O:3]
Reactant: CC(Oc1ncn(-c2cccc(C(F)(F)F)c2)n1)C(=O)O
Reactant: O=C(n1ccnc1)n1ccnc1
Agent: CNC
Solvent: CN(C)C=O
Product: CC(Oc1ncn(-c2cccc(C(F)(F)F)c2)n1)C(=O)N(C)C
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
Three g of the compound of Example 24 was dissolved in 20 ml of dimethylformamide, and 3.4 g of carbonyldiimidazole was added to it. The mixture was stirred at ambient temperature for 20 minutes, and then 4 ml of 40% aqueous dimethylamine was added and the mixture was stirred at ambient temperature for 1 day. It was then poured into ice-water, and the solid was collected, dried and recrystallized from ethanol to obtain 1.5 g of the desired product, m.p. 126°-127°.
Reaction SMILES: FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([N+:13]([O-:15])=[O:14])[C:8]=1[C:16]#[N:17])(=O)=O.[CH:20](/B(O)O)=[CH:21]/[CH3:22]>>[N+:13]([C:9]1[CH:10]=[CH:11][CH:12]=[C:7](/[CH:20]=[CH:21]\[CH3:22])[C:8]=1[C:16]#[N:17])([O-:15])=[O:14]
Reactant: C/C=C\B(O)O
Reactant: N#Cc1c(OS(=O)(=O)C(F)(F)F)cccc1[N+](=O)[O-]
Product: C/C=C\c1cccc([N+](=O)[O-])c1C#N

Procedure:
Prepared as in Example 129c from 2-cyano-3-nitrophenyl trifluoromethanesulfonate Example (129d) and cis-1-propen-1-ylboronic acid. The crude product was purified by chromatography on silica gel eluting with solvent gradient 0% to 100% DCM in hexanes, to give 0.80 g (97%) of (Z)-2-nitro-6-(prop-1-enyl)benzonitrile (97%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 8.25-8.30 (m, 1H), 7.90-7.98 (m, 2H), 6.25-6.70 (m, 1H), 6.17-6.28 (m, 1H), 1.78-1.82 (m, 3H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:13]([OH:15])=O)[CH2:12][CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[NH2:16][C@H:17]1[CH2:36][N:21]2[C:22]3[C:27]([C:28]([CH2:29][C:30]([O:32]CCC)=[O:31])=[C:20]2[CH2:19][CH2:18]1)=[CH:26][CH:25]=[CH:24][CH:23]=3>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([C:13]([NH:16][C@H:17]3[CH2:36][N:21]4[C:22]5[C:27]([C:28]([CH2:29][C:30]([OH:32])=[O:31])=[C:20]4[CH2:19][CH2:18]3)=[CH:26][CH:25]=[CH:24][CH:23]=5)=[O:15])[CH2:9][CH2:10][CH2:11][CH2:12]2)=[CH:6][CH:7]=1
Reactant: O=C(O)C1(c2ccc(F)cc2)CCCC1
Reactant: CCCOC(=O)Cc1c2n(c3ccccc13)C[C@H](N)CC2
Product: O=C(O)Cc1c2n(c3ccccc13)C[C@H](NC(=O)C1(c3ccc(F)cc3)CCCC1)CC2

Procedure:
The title compound was prepared using analogous procedures described in Example 1 (Method A) from 1-(4-fluorophenyl)cyclopentanecarboxylic acid and propyl [(7R)-7-amino-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]acetate. MS (+ESI) m/z: 435.
Reaction SMILES: [CH3:1][N:2]1[C:6]([C:7]([NH2:9])=[O:8])=[C:5]([N+:10]([O-])=O)[C:4]([CH3:13])=[N:3]1>C(O)C.C(OCC)(=O)C.[Pd]>[NH2:10][C:5]1[C:4]([CH3:13])=[N:3][N:2]([CH3:1])[C:6]=1[C:7]([NH2:9])=[O:8]
Reactant: Cc1nn(C)c(C(N)=O)c1[N+](=O)[O-]
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CCO
Product: Cc1nn(C)c(C(N)=O)c1N
Reaction time: 5 h
Yield: 97.8 %

Procedure:
To a solution of 1,3-dimethyl-4-nitro-1H-pyrazole-5-carboxamide (730 mg, 3.96 mmol) in anhydrous ethanol (100 mL) and ethyl acetate (100 mL) was added 10 wt % Pd on carbon (100.0 mg). The reaction mixture was evacuated with vacuum and purged with H2 (3×), then stirred under H2 at 50 psi for 5 hours. The reaction mixture was then filtered through a pad of Celite®. The filtrate was concentrated in vacuo and the crude was purified by column chromotagraphy (Si-PPC, gradient 0 to 30% methanol in dichloromethane) to get the desired product (597.0 mg, 97.7%) as a solid. 1H NMR (DMSO-d6, 400 MHz) δ ppm 7.26 (br s, 2H), 4.03 (br s, 2H), 3.84 (s, 3H), 2.02 (s, 3H); LC-MS m/z (method A)=155.2 [M+H]+, RT=0.35 min.
Reaction SMILES: CON(C)[C:4](=[O:21])[CH:5]([C:13]1[CH:17]=[C:16]([S:18][CH3:19])[N:15]([CH3:20])[N:14]=1)[CH2:6][CH:7]1[CH2:12][CH2:11][O:10][CH2:9][CH2:8]1.[CH:23]([Mg]Br)=[CH2:24].Cl>O1CCCC1>[CH3:20][N:15]1[C:16]([S:18][CH3:19])=[CH:17][C:13]([CH:5]([CH2:6][CH:7]2[CH2:8][CH2:9][O:10][CH2:11][CH2:12]2)[C:4](=[O:21])[CH:23]=[CH2:24])=[N:14]1
Reactant: C=C[Mg]Br
Reactant: CON(C)C(=O)C(CC1CCOCC1)c1cc(SC)n(C)n1
Agent: Cl
Solvent: C1CCOC1
Product: C=CC(=O)C(CC1CCOCC1)c1cc(SC)n(C)n1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 83 %

Procedure:
To a solution of N-methoxy-N-methyl-2-[1-methyl-5-(methylsulfanyl)-1H-pyrazol-3-yl]-3-(tetrahydro-2H-pyran-4-yl)propanamide (0.80 g) in tetrahydrofuran (30 mL) was slowly added vinylmagnesium bromide (1.0M tetrahydrofuran solution: 7.3 ml) at room temperature under a nitrogen atmosphere, and the mixture was stirred for 30 min. The reaction mixture was poured into an ice-cooled 1N hydrochloric acid, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4), and concentrated. The obtained residue was subjected to silica gel column chromatography to give the title compound (0.60 g, yield 83%) as a colorless oil from the fraction eluted with ethyl acetate-hexane (4:1, volume ratio). MS: 295 (MH+).
Reaction SMILES: [CH2:1]([C:13]1[CH:14]=[CH:15][C:16]2[CH2:17][C:18]3[C:31]([C:32](=O)[C:33]=2[CH:34]=1)=[CH:30][C:29]1[CH2:28][C:27]2[C:22](=[CH:23][C:24]([CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH3:47])=[CH:25][CH:26]=2)[C:21](=O)[C:20]=1[CH:19]=3)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]>COCCOCCOC>[CH2:36]([C:24]1[CH:25]=[CH:26][C:27]2[C:22](=[CH:21][C:20]3[C:29]([CH:28]=2)=[CH:30][C:31]2[C:18](=[CH:17][C:16]4[C:33]([CH:32]=2)=[CH:34][C:13]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])=[CH:14][CH:15]=4)[CH:19]=3)[CH:23]=1)[CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH3:47]
Reactant: CCCCCCCCCCCCc1ccc2c(c1)C(=O)c1cc3c(cc1C2)C(=O)c1cc(CCCCCCCCCCCC)ccc1C3
Solvent: COCCOCCOC
Product: CCCCCCCCCCCCc1ccc2cc3cc4cc5cc(CCCCCCCCCCCC)ccc5cc4cc3cc2c1
Temperature: 60 °C
Reaction time: 16 h

Procedure:
A mixture of 8.5 grams of 3,10-didodecyl-7,14-dihydropentacene-5,12-dione and 250 mL of 2-methoxyethyl ether was stirred and flushed with nitrogen for 15 minutes. To this was added 4.46 grams of sodium borohydride. The resulting mixture was heated to 60° C. for 18 hours. The mixture was cooled to room temperature, and 42 mL of methanol was added slowly. The resulting mixture was stirred at room temperature for 30 minutes. To this was added 1.2 grams of sodium borohydride, and stirring was continued at room temperature for 16 hours. To the resulting mixture was added 60 mL of acetic acid, and the mixture was heated at 60° C. for one hour. To this mixture was added 43 mL of concentrated hydrochloric acid, and heating was continued at 60° C. for one hour. To the resulting mixture was added 100 mL of water and the mixture cooled to room temperature and the solid was collected by filtration and dried to give 2,9-didodecylpentacene.
Reaction SMILES: [CH2:1]([Mg]Br)[CH2:2][CH:3]=[CH2:4].[CH:7](=[O:12])[CH2:8][CH2:9][CH:10]=[CH2:11]>O1CCCC1>[CH2:4]=[CH:3][CH2:2][CH2:1][CH:7]([OH:12])[CH2:8][CH2:9][CH:10]=[CH2:11]
Reactant: C=CCCC=O
Reactant: C=CCC[Mg]Br
Solvent: C1CCOC1
Product: C=CCCC(O)CCC=C
Temperature: 25 °C

Procedure:
3-Butenyl-magnesium bromide (125 mL, 0.5 M in tetrahydrofuran, 62.5 mmol) was added drop wise to a stirred and cooled (−78° C.) solution of pent-4-enal (4 g, 48.07 mmol) in dry tetrahydrofuran (160 mL). After the addition, the solution was warmed to room temperature and then quenched with NH4Cl solution. The mixture was partitioned with diethyl ether and the organic phase was washed with brine, dried (MgSO4), filtered, and evaporated. The residue was purified over silica gel using 5-15% diethyl ether in hexanes to give the title compound as an oil.
Reaction SMILES: C([O:3][C:4](=[O:22])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([Br:13])=[CH:9][C:8]=1[CH2:14][NH:15][CH2:16][C:17]([O:19]CC)=O)C.[CH2:23]([N:31]=[C:32]=[O:33])[CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>>[Br:13][C:10]1[CH:11]=[CH:12][C:7]([O:6][CH2:5][C:4]([OH:3])=[O:22])=[C:8]([CH2:14][N:15]2[CH2:16][C:17](=[O:19])[N:31]([CH2:23][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:32]2=[O:33])[CH:9]=1
Reactant: CCOC(=O)CNCc1cc(Br)ccc1OCC(=O)OCC
Reactant: O=C=NCCc1ccccc1
Product: O=C(O)COc1ccc(Br)cc1CN1CC(=O)N(CCc2ccccc2)C1=O

Procedure:
Prepared from 4-bromo-2-[(ethoxycarbonylmethylamino)methyl]phenoxyacetic acid ethyl ester and phenethylisocyanate according to GP12: LC/MS (an10p8): Rt 2.2 min, m/z 445 [M−H]−; 1H NMR (DMSO-d6): δ 2.84 (t, J=7.2 Hz, 2H), 3.59 (t, J=7.2 Hz, 2H), 3.94 (s, 2H), 4.45 (s, 2H), 4.76 (s, 2H), 6.93 (d, J=8.6 Hz, 1H), 7.17-7.46 (m, 7H), 12.45 (br. s, 1H).
Reaction SMILES: P(=[S:5])([O-])([O-])[O-].[Na+].[Na+].[Na+].Cl.[CH3:10][O:11][N:12]=[C:13]1[CH2:17][CH2:16][N:15]([C:18](=[NH:21])[CH2:19][Cl:20])[CH2:14]1.Cl>O>[ClH:20].[CH3:10][O:11][N:12]=[C:13]1[CH2:17][CH2:16][N:15]([C:18](=[NH:21])[CH2:19][SH:5])[CH2:14]1
Reactant: CON=C1CCN(C(=N)CCl)C1
Reactant: [O-]P([O-])([O-])=S
Agent: Cl
Agent: [Na+]
Solvent: O
Product: CON=C1CCN(C(=N)CS)C1
Temperature: 25 °C
Reaction time: 1 h
Yield: 77 %

Procedure:
1.77 g of trisodium phosphorothioate were added to an ice-cooled solution of 2.1 g of 2-(3-methoxyiminopyrrolidin-1-yl)-2-iminoethylchloride hydrochloride in 12 ml of water, and the mixture was stirred at room temperature for about one hour. 9.8 ml of 1N hydrochloric acid were then added, and the mixture was heated at 65° C. for 30 minutes. The resulting solution was concentrated under reduced pressure, the concentrate was mixed with 9.8 ml of isopropanol, insolubles were filtered off, and the filtrate was concentrated under reduced pressure. Ether was added to the concentrate, and the crystals which separated out were collected by filtration and reprecipitated from a mixture of ethanol and ether, giving 1.6 g of 2-(3-methoxyiminopyrrolidin-1-yl)-2-iminoethylmercaptan hydrochloride.
Reaction SMILES: O.[ClH:2].Cl.[O:4]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[CH2:7][CH2:6][C@@H:5]1[CH2:14][NH:15][CH2:16][CH2:17][CH2:18][NH:19][C:20]1[N:25]=[CH:24][CH:23]=[CH:22][N:21]=1.[O:26]1[C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=2[CH2:29][CH2:28][C@@H:27]1[CH2:36][NH:37][CH2:38][CH2:39][CH2:40][NH:41][C:42]1[N:47]=[CH:46][CH:45]=[CH:44][N:43]=1.Cl.Cl.Cl.[H][H]>CO.CC(O)C.[Pd]>[OH2:4].[ClH:2].[ClH:2].[O:26]1[C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=2[CH2:29][CH2:28][C@@H:27]1[CH2:36][NH:37][CH2:38][CH2:39][CH2:40][NH:41][C:42]1[NH:47][CH2:46][CH2:45][CH2:44][N:43]=1.[O:4]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[CH2:7][CH2:6][C@@H:5]1[CH2:14][NH:15][CH2:16][CH2:17][CH2:18][NH:19][C:20]1[NH:25][CH2:24][CH2:23][CH2:22][N:21]=1.[ClH:2].[ClH:2]
Reactant: [H][H]
Reactant: c1cnc(NCCCNC[C@H]2CCc3ccccc3O2)nc1
Agent: [Pd]
Agent: Cl
Solvent: O
Solvent: CC(C)O
Solvent: CO
Product: c1ccc2c(c1)CC[C@H](CNCCCNC1=NCCCN1)O2
Yield: 296.9 %

Procedure:
A mixture of 3.6 g of (-)-(R)-N-[(3,4-dihydro-2H-1-benzopyran-2-yl)methyl]-N'-(2-pyrimidinyl)-1,3-propanediamine dihydrochloride hemihydrate in 150 ml of methanol and 20 ml of 2-propanol saturated with HCl was hydrogenated in the presence of 1.5 g of palladium-on-charcoal catalyst (2%). After the calculated amount of hydrogen was taken up, the catalyst was filtered off and the filtrate was evaporated. The product was crystallized from acetonitrile, filtered off and dried, yielding 2.7 g (74.0%) of (-)-(R)-N-[(3,4-dihydro-2H-1-benzopyran-2-yl)methyl]-N'-(1,4,5,6-tetrahydro-2-pyrimidinyl)-1,3-propanediamine dihydrochloride hemihydrate; mp. 200.2° C. [α]D20 =-60.97° (conc.=1% in CH3OH) (comp. 62).