Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [I:1][C:2]1[C:6]([CH2:7][C:8]2([C:21]([O:23]CC)=[O:22])[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[CH:5][N:4]([CH:26]([CH3:28])[CH3:27])[N:3]=1.[OH-].[Na+]>CO>[C:17]([O:16][C:14]([N:11]1[CH2:12][CH2:13][C:8]([CH2:7][C:6]2[C:2]([I:1])=[N:3][N:4]([CH:26]([CH3:27])[CH3:28])[CH:5]=2)([C:21]([OH:23])=[O:22])[CH2:9][CH2:10]1)=[O:15])([CH3:20])([CH3:18])[CH3:19]
Reactant: CCOC(=O)C1(Cc2cn(C(C)C)nc2I)CCN(C(=O)OC(C)(C)C)CC1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CC(C)n1cc(CC2(C(=O)O)CCN(C(=O)OC(C)(C)C)CC2)c(I)n1
Temperature: 25 °C
Reaction time: 18 h
Yield: 100.1 %

Procedure:
To a solution of 1-tert-butyl 4-ethyl 4-((3-iodo-1-isopropyl-1H-pyrazol-4-yl)methyl)piperidine-1,4-dicarboxylate (455 mg, 0.9 mmol) in methanol (20 mL) was added 2 N NaOH (5 mL). After stirring for 18 hours at room temperature, the methanol was removed under reduced pressure and the resultant slurry was taken up in 20 mL water, acidified with 2 N HCl and extracted with ethyl acetate (2×30 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated to yield 1-(tert-butoxycarbonyl)-4-((3-iodo-1-isopropyl-1H-pyrazol-4-yl)methyl)piperidine-4-carboxylic acid (430 mg) as a colorless solid. −APCI (M−H) 476.1; 1H NMR (400 MHz, CDCl3, δ): 7.11 (s, 1H), 4.45 (dquin, J=13.4, 6.7 Hz, 1H), 3.95 (br. s., 2H), 2.91 (m, 2H), 2.69 (s, 2H), 2.08 (m, 2H), 1.47 (m, 8H).
Reaction SMILES: I[Si](C)(C)C.C([O:8][P:9]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([NH:21][C:22]([C:24]2[O:25][C:26]3[CH:34]=[CH:33][CH:32]=[CH:31][C:27]=3[C:28](=[O:30])[CH:29]=2)=[O:23])=[CH:17][CH:16]=1)([O:11]CC)=[O:10])C>C(Cl)(Cl)(Cl)Cl>[P:9]([CH2:14][C:15]1[CH:16]=[CH:17][C:18]([NH:21][C:22]([C:24]2[O:25][C:26]3[CH:34]=[CH:33][CH:32]=[CH:31][C:27]=3[C:28](=[O:30])[CH:29]=2)=[O:23])=[CH:19][CH:20]=1)([OH:10])([OH:11])=[O:8]
Reactant: CCOP(=O)(Cc1ccc(NC(=O)c2cc(=O)c3ccccc3o2)cc1)OCC
Agent: C[Si](C)(C)I
Solvent: ClC(Cl)(Cl)Cl
Product: O=C(Nc1ccc(CP(=O)(O)O)cc1)c1cc(=O)c2ccccc2o1
Temperature: 0 °C
Reaction time: 1 h
Yield: 8.5 %

Procedure:
Iodotrimethylsilane [(CH3)3SiI] (3.17 g) was added at 0° C. to a mixture of N-(4-diethoxyphosphorylmethylphenyl)-4-oxo-4H-1 -benzopyran-2-carboxamide (2.99 g) and carbon tetrachloride (60 ml). This mixture was stirred at 0° C. for 1 hour and then at room temperature for 15 hours, after which it was concentrated under reduced pressure. The residue was dissolved in methanol (45 ml), poured over 4N HCl and stirred at room temperature for minutes. The separated crystals were collected by filtration and recrystallized from methanol to yield N-(4-phosphonomethylphenyl)-4-oxo-4H-1-benzopyran-2-carboxamide (0.22 g, 8.5%) as light yellow prisms having a melting point of 265° to 266° C.
Reaction SMILES: [C:1]([C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1)(=[O:3])[CH3:2].[O:13](C(OC(C)(C)C)=O)[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=O>C1COCC1>[C:1]([C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:13])[CH:5]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)c1c[nH]c2ccccc12
Reactant: CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
Solvent: C1CCOC1
Product: CC(=O)c1cn(C(=O)OC(C)(C)C)c2ccccc12

Procedure:
To a stirred solution of 3-acetylindole (0.01 mol) in THF is added (BOC)2O (0.01 mol) and a tertiary amine base (0.01 mol), and the mixture is stirred. Reaction progress may be followed by TLC or HPLC. When a sufficient amount of desired product is formed, the mixture (or, optionally, the residue which is obtained after first rotary evaporating off the reaction solvent) is partitioned between ethyl acetate and an excess of about 0.1 M sodium hydroxide. The organic layer is washed with brine, dried over sodium sulfate, and rotary evaporated to give 3-acetyl-1-(tert-butoxycarbonyl)-indole, which may be purified, if needed or desired, by chromatography on silica gel or crystallization.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:15][CH2:16][C:17]([N:19]2[CH2:24][CH2:23][N:22]([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=3)[CH2:21][CH:20]2[CH3:33])=[O:18])=[C:6]([N:8]([C:13]#[N:14])[C:9](=[NH:12])SC)[CH:7]=1.[OH-].[NH4+:35]>CCO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:15][CH2:16][C:17]([N:19]2[CH2:24][CH2:23][N:22]([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=3)[CH2:21][C@H:20]2[CH3:33])=[O:18])=[C:6]([N:8]([C:13]#[N:14])[C:9]([NH2:35])=[NH:12])[CH:7]=1
Reactant: [NH4+]
Reactant: CSC(=N)N(C#N)c1cc(Cl)ccc1OCC(=O)N1CCN(Cc2ccc(F)cc2)CC1C
Agent: [OH-]
Solvent: CCO
Product: C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)COc1ccc(Cl)cc1N(C#N)C(=N)N
Temperature: 60 °C
Reaction time: 8 h

Procedure:
To a solution of 1-(5-chloro-2-{2-[4-(4-fluoro-benzyl)-2-methyl-piperazin-1-yl]-2-oxo-ethoxy}-phenyl)-N-cyano-S-methyl-isothiourea (0.045 g, 0.092 mmol) in EtOH (1 mL) was added ammonium hydroxide (0.100 mL) and the resulting solution was shaken at 60° C. overnight. The crude reaction mixture was purified directly via radial chromatography (2 mm plate) to give the title compound (0.027 g).
Reaction SMILES: [CH2:1]([O:6][CH2:7][CH:8]([OH:23])/[CH:9]=[CH:10]/[C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]2[NH:19][CH:20]=[CH:21][N:22]=2)=[CH:13][CH:12]=1)[CH2:2][CH2:3][CH2:4][CH3:5].Cl.[N:25]1[CH:30]=[CH:29][CH:28]=[C:27]([C:31](Cl)=[O:32])[CH:26]=1>N1C=CC=CC=1>[CH2:1]([O:6][CH2:7][CH:8]([O:23][C:31]([C:27]1[CH:26]=[N:25][CH:30]=[CH:29][CH:28]=1)=[O:32])/[CH:9]=[CH:10]/[C:11]1[CH:12]=[CH:13][C:14]([CH2:17][C:18]2[NH:19][CH:20]=[CH:21][N:22]=2)=[CH:15][CH:16]=1)[CH2:2][CH2:3][CH2:4][CH3:5]
Reactant: O=C(Cl)c1cccnc1
Reactant: CCCCCOCC(O)/C=C/c1ccc(Cc2ncc[nH]2)cc1
Agent: Cl
Solvent: c1ccncc1
Product: CCCCCOCC(/C=C/c1ccc(Cc2ncc[nH]2)cc1)OC(=O)c1cccnc1
Reaction time: 8 h

Procedure:
400 mg (1.3 mmol) of E-4-pentyloxy-1-[4-(1-imidazolylmethyl)phenyl]but-1-en-3-ol (5a) were dissolved in 10 ml of dry pyridine, and 409 mg (1.5 mmol) of 3-pyridinecarbonyl chloride hydrochloride were added. The mixture was stirred at room temp. for 8 h, and the solvent was substantially removed in vacuo, and the residue was partitioned between saturated aqueous sodium bicarbonate solution and methylene chloride. The aqueous phase was extracted twice with methylene chloride. Drying of the combined organic phases with magnesium sulfate and removal of the solvent in vacuo produced, after chromatography on silica gel (ethyl acetate/methanol=10:1, Rf=0.20), 380 mg (0.91 mmol, 70%) of ester 6a as a colorless oil.
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([CH3:12])[N:11]=1)[C:5]([O:7][CH3:8])=[O:6].[CH:13]1([C:16]([NH2:18])=[O:17])[CH2:15][CH2:14]1>>[CH:13]1([C:16]([NH:18][C:2]2[CH:3]=[C:4]([CH:9]=[C:10]([CH3:12])[N:11]=2)[C:5]([O:7][CH3:8])=[O:6])=[O:17])[CH2:15][CH2:14]1
Reactant: NC(=O)C1CC1
Reactant: COC(=O)c1cc(C)nc(Cl)c1
Product: COC(=O)c1cc(C)nc(NC(=O)C2CC2)c1
Yield: 66 %

Procedure:
The title compound is prepared in 66% yield (1.3 g, a pale yellow solid) from methyl 2-chloro-6-methylisonicotinate (1.5 g, 8.1 mmol) and cyclopropanecarboxamide by the similar manner in Step-1 of Carboxylic acid-4.
Reaction SMILES: [CH3:1][CH:2]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[CH2:16][CH2:15][CH:14]([CH2:17][C:18]2[CH:19]=[C:20]([CH:23]=[CH:24][CH:25]=2)[CH2:21]Cl)[CH2:13][CH2:12]1)[CH3:3].[C:26]1(=[O:32])[NH:31][CH:29]([CH3:30])[CH2:28][CH2:27]1.[Li]CCCC.CCCCCC>C1COCC1>[CH3:1][CH:2]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[CH2:16][CH2:15][CH:14]([CH2:17][C:18]2[CH:19]=[C:20]([CH2:21][N:31]3[CH2:29][CH2:30][CH2:28][CH2:27][C:26]3=[O:32])[CH:23]=[CH:24][CH:25]=2)[CH2:13][CH2:12]1)[CH3:3]
Reactant: CC1CCC(=O)N1
Reactant: CC(C)Oc1ccccc1N1CCC(Cc2cccc(CCl)c2)CC1
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CC(C)Oc1ccccc1N1CCC(Cc2cccc(CN3CCCCC3=O)c2)CC1

Procedure:
A solution of 3-[[1-[2-(1-methylethoxy)phenyl]-4-piperidinyl]methyl]benzyl chloride (5.25 g, 0.0147 mol) in THF (90 mL) was added dropwise to a solution of γ-valerolactam (2.06 g, 0.02 mol) in THF (50 mL) which had been treated at 0° C. with 1.6M n-BuLi/hexane (12 mL, 1 mol equiv). The resulting solution was heated to reflux for 3 h, cooled, and quenched with MeOH (20 mL). The solution was evaporated to dryness to give a yellow oil. The residue was chromatographed on silica gel using 99:1/CHCl3 :MeOH as eluant to give 1-[[3-[[1-[2-(1-methylethoxy)phenyl]-4-piperidinyl]methyl]phenyl]methyl]-piperidin-2-one as a light yellow oil, 1.41 g (23%). MS (Cl CH4): m/e 421 (MH+). 1H NMR (CDCl3): δ1.3 (d, 6H), 1.8 (m, 4H), 2.0 (m, 2H), 2.4 (s, 1H), 2.9 (m, 3H), 3.2 (m, 2H), 3.6 (s, 1H), 3.7 (d, 1H), 4.6 (m, 3H), 5.0 (s, 1H), 6.9 (m, 2H), 7.1 (m, 2H), 7.3-7.6 (m, 4H).
Reaction SMILES: Br[CH:2]1[CH2:7][CH2:6][CH2:5][NH:4][C:3]1=[O:8].[N-:9]=[N+:10]=[N-:11].[Na+].O>CN(C)C=O>[N:9]([CH:2]1[CH2:7][CH2:6][CH2:5][NH:4][C:3]1=[O:8])=[N+:10]=[N-:11]
Reactant: [N-]=[N+]=[N-]
Reactant: O=C1NCCCC1Br
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: [N-]=[N+]=NC1CCCNC1=O
Temperature: 60 °C
Reaction time: 8 h
Yield: 56.5 %

Procedure:
To a solution of 2.0 g of 3-bromopiperidin-2-one in 30 ml of N,N-dimethylformamide was added 5.9 g of sodium azide, followed by stirring at 60° C. overnight. After cooling down to room temperature, water was added to the reaction mixture and then the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and the solvent was evaporated, to give 890 mg of the title compound as a yellow oil.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5](Br)=[CH:4][CH:3]=1.[Li]CCCC.[Cl:14][C:15]1[N:20]=[C:19]([Cl:21])[CH:18]=[CH:17][N:16]=1.CC(O)=O.O.C(C1C(=O)C(Cl)=C(Cl)C(=O)C=1C#N)#N.[OH-].[Na+]>CCOCC.C1COCC1>[Cl:14][C:15]1[N:20]=[C:19]([Cl:21])[CH:18]=[C:17]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[N:16]=1
Reactant: Clc1ccnc(Cl)n1
Reactant: Fc1ccc(Br)cc1
Agent: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Agent: [Li]CCCC
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCOCC
Solvent: O
Product: Fc1ccc(-c2cc(Cl)nc(Cl)n2)cc1
Temperature: -78 °C
Reaction time: 0.75 h

Procedure:
Dissolve 4-fluorobromobenzene (8.75 g, 0.05 moles) in anhydrous ether (80 mL) under nitrogen atmosphere and cool to −78° C. Add dropwise 1.6 M n-BuLi (34 mL, 0.055 moles) and stir at −78° C. for 45 min. Dissolve 2,4-dichloropyrimidine (7.45 g, 0.05 moles) in Et2O (100 mL) and add dropwise to the reaction mixture. Warm the reaction mixture to −30° C. and stir at this temperature for 30 min followed by 0° C. for 30 min. Quench the reaction mixture with AcOH (3.15 mL, 0.055 moles) and water (0.5 mL, 0.027 moles) dissolved in THF (5.0 mL). Add dropwise a THF (40 mL) solution of DDQ (11.9 g, 0.053 moles) to the reaction mixture. Bring the reaction mixture to room temperature and stir at room temperature for 30 min. Cool the reaction mixture to 0° C., add 3.0 N aq. NaOH (35 mL) and stir for 30 min. Decant the organic layer from the reaction mixture and wash the brown solid with Et2O (3×100 mL). Combine the organic layers, wash several times with saturated NaCl solution and dry with MgSO4. Filter and evaporate under vacuum to afford a brown colored solid. Purify by flash column chromatography using 5% EtOAc/hexane to afford the title product as a white solid.
Reaction SMILES: [NH:1]=[C:2]1[NH:6][C:5]([C:11]([F:14])([F:13])[F:12])([C:7]([F:10])([F:9])[F:8])[C:4](=[C:15]([F:20])[C:16]([F:19])([F:18])[F:17])[S:3]1.C(N(CC)CC)C.[N+:28]([C:31]1[CH:32]=[C:33]([CH:37]=[CH:38][CH:39]=1)[C:34](Cl)=[O:35])([O-:30])=[O:29]>C1(C)C=CC=CC=1>[N+:28]([C:31]1[CH:32]=[C:33]([CH:37]=[CH:38][CH:39]=1)[C:34]([NH:1][C:2]1[S:3][C:4](=[C:15]([F:20])[C:16]([F:17])([F:18])[F:19])[C:5]([C:7]([F:10])([F:9])[F:8])([C:11]([F:12])([F:13])[F:14])[N:6]=1)=[O:35])([O-:30])=[O:29]
Reactant: O=C(Cl)c1cccc([N+](=O)[O-])c1
Reactant: N=C1NC(C(F)(F)F)(C(F)(F)F)C(=C(F)C(F)(F)F)S1
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: O=C(NC1=NC(C(F)(F)F)(C(F)(F)F)C(=C(F)C(F)(F)F)S1)c1cccc([N+](=O)[O-])c1
Temperature: 103 °C
Reaction time: 3 h

Procedure:
In toluene (40 ml) were dissolved 2-imino-4,4-bis(trifluoromethyl)-5-(tetrafluoroethylidene)-1,3-thiazolidine (2.0 g) and triethylamine (1.0 ml), and a solution of 3-nitrobenzoyl chloride (1.3 g) dissolved in toluene (10 ml) was gradually added thereto under cooling and the mixture was stirred at 103° C. for 3 hours.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([N+:15]([O-])=O)=[CH:11][CH:10]=2)=[CH:4][CH:3]=1>C(O)C.[Pd]>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([NH2:15])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1
Reactant: Cc1ccc(Nc2ccc([N+](=O)[O-])cc2)cc1
Agent: [Pd]
Solvent: CCO
Product: Cc1ccc(Nc2ccc(N)cc2)cc1
Yield: 85 %

Procedure:
Reduction of the nitro function of N-(4-methylphenyl)-4-nitroaniline (Indian J. Chem. (1981) 20B, 611-613) is carried out in the presence of Pd/C in ethanol, under the conditions described for intermediate 2.2. A grey solid is obtained with a yield of 85%.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:9]2[C:14]([C:15]([OH:17])=O)=[C:13]([CH3:18])[NH:12][C:11](=[O:19])[NH:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[C:35]3[C:30](=[CH:31][CH:32]=[C:33]([NH2:36])[CH:34]=3)[NH:29][N:28]=2)=[CH:23][CH:22]=1.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[F:20][C:21]1[CH:22]=[CH:23][C:24]([C:27]2[C:35]3[C:30](=[CH:31][CH:32]=[C:33]([NH:36][C:15]([C:14]4[CH:9]([C:4]5[CH:5]=[C:6]([F:8])[CH:7]=[C:2]([F:1])[CH:3]=5)[NH:10][C:11](=[O:19])[NH:12][C:13]=4[CH3:18])=[O:17])[CH:34]=3)[NH:29][N:28]=2)=[CH:25][CH:26]=1
Reactant: CC1=C(C(=O)O)C(c2cc(F)cc(F)c2)NC(=O)N1
Reactant: Nc1ccc2[nH]nc(-c3ccc(F)cc3)c2c1
Agent: Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC1=C(C(=O)Nc2ccc3[nH]nc(-c4ccc(F)cc4)c3c2)C(c2cc(F)cc(F)c2)NC(=O)N1

Procedure:
The titled compound was prepared following the procedure of Example 175 using 4-(3,5-Difluoro-phenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid, 3-(4-Fluoro-phenyl)-1H-indazole-5-ylamine, PyBroP and diisopropylethylamine in methylene chloride. MS (ESI) m/z=478 [M+H]+.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][N:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[CH2:11](Br)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[BH4-].[Na+]>C(#N)C>[CH2:11]([N:7]1[CH2:8][CH2:9][C:10]2[N:1]=[CH:2][CH:3]=[CH:4][C:5]=2[CH2:6]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: c1cnc2ccncc2c1
Reactant: BrCc1ccccc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CC#N
Product: c1ccc(CN2CCc3ncccc3C2)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 51.4 %

Procedure:
1,6-Naphthyridine (13.7 g, 105 mmol) and benzyl bromide (36.05 g, 210 mmol) were combined in acetonitrile (200 ml) and heated to reflux until no 1,6-naphthyridine was visible by thin layer chromatography. After removal of the solvent in vacuo, the residue was washed several times with ether and dissolved in methanol (700 ml). Water (250 ml) was added, and the solution cooled to 0°; portionwise addition of sodium borohydride (20.8 g, 550 mmol) brought about vigorous gas evolution and a slight rise in temperature. The reaction mixture was allowed to warm to room temperature and stir for 18 hours. The solvent was then removed in vacuo and the residue partitioned between water (750 ml) and methylene chloride (300 ml). The aqueous layer was extracted with additional methylene chloride (2×300 ml) and the combined organic extracts were washed once with water and once with saturated aqueous sodium chloride. Removal of solvent provided a dark amber foam, which was purified by column chromatography (99:1 methylene chloride:methanol) to yield the title product (12.1 g, 54 mmol, 51% yield).
Reaction SMILES: [N-:1]=[N+:2]=[N-:3].[Na+].[Cl:5][C:6]1[CH:13]=[CH:12][CH:11]=[CH:10][C:7]=1[CH2:8]Cl>CN(C=O)C>[Cl:5][C:6]1[CH:13]=[CH:12][CH:11]=[CH:10][C:7]=1[CH2:8][N:1]=[N+:2]=[N-:3]
Reactant: [N-]=[N+]=[N-]
Reactant: ClCc1ccccc1Cl
Agent: [Na+]
Solvent: CN(C)C=O
Product: [N-]=[N+]=NCc1ccccc1Cl
Temperature: 25 °C
Reaction time: 48 h

Procedure:
A cold (0° C.) solution of sodium azide (1.45 g, 22.3 mmol) in 50 ml of DMF was treated with 2-chlorobenzyl chloride (2.4 ml, 18.6 mmol). The reaction mixture was stirred at room temperature for 2 days, under N2 and then partitioned between EtOAc and H2O. The resultant layers were separated and the organic layer was dried over Na2SO4, filtered and then concentrated in vacuo.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][C:2]1=[O:10].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.C1COCC1.[Br:26][C:27]1[CH:28]=[C:29]2[C:34](=[CH:35][CH:36]=1)[C:32](=O)[O:31][CH2:30]2.Cl>C(COC)OC.O.C1COCC1>[Br:26][C:27]1[CH:28]=[C:29]2[C:34](=[CH:35][CH:36]=1)[C:32](=[C:3]1[C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[NH:1][C:2]1=[O:10])[O:31][CH2:30]2
Reactant: O=C1OCc2cc(Br)ccc21
Reactant: O=C1Cc2ccccc2N1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: Cl
Agent: [Li+]
Solvent: COCCOC
Solvent: C1CCOC1
Solvent: O
Product: O=C1Nc2ccccc2C1=C1OCc2cc(Br)ccc21
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 77.2 %

Procedure:
To a stirred solution of oxindole (3.13 g, 23.5 mmol) in anhydrous dimethoxyethane (20 ml) under nitrogen was added 1.0M LiHMDS/THF solution (49 ml, 49 mmol). The mixture was stirred at room temperature for 10 minutes, and 5-bromophthalide (3.00 g, 14.1 mmol) was added. The reaction mixture was stirred at room temperature for 3 hours and then poured into a mixture of THF (50 ml) and 2M HCl aqueous solution (50 ml). After heated at reflux for 1 hour and then cooled to room temperature, the resulting mixture was poured into water (100 ml). The resulting solid was filtered, washed with water and dried under vacuum to give 3-(5-bromo-3H-isobenzofuran-1-ylidene)-1,3-dihydro-indol-2-one as a yellow solid (3.57 g, 77%).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[CH:6]=[CH:5]2.C=O.[CH2:21]([NH:23][CH2:24]C)[CH3:22]>C(O)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[CH:6]=[C:5]2[CH2:24][NH:23][CH2:21][CH3:22]
Reactant: CCNCC
Reactant: CCCCCCCCn1ccc2cc(Br)ccc21
Agent: C=O
Solvent: CC(=O)O
Product: CCCCCCCCn1cc(CNCC)c2cc(Br)ccc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 40 %

Procedure:
To a stirred solution of 5-bromo 1-octyl 1H-indole (2 mmol) in acetic acid (10 ml) was added formaldehyde (0.5 ml) and diethyl amine (4 mmol), reaction was stirred at RT overnight, reaction were monitored by TLC. Reaction was quenched by methylene chloride 20 ml, and 15 ml of water and pH was adjusted to 9 using 1N NaOH solution. Added more methylene chloride and organic layer was washed with water. Combined organic layer was washed with brine, dried (Na2SO4) and concentrated under reduced pressure to obtain the crude residue. The crude material was purified by column chromatography in chloroform and Methanol solvent system to get oily product. Product was confirmed by LC-MS and NMR. Yield 40 to 60%.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[CH:5][C:4]([C:7]2[O:8][C:9]([N+:12]([O-:14])=[O:13])=[CH:10][CH:11]=2)=[N:3]1.C1N2CN3CN(C2)CN1C3.FC(F)(F)[C:27](O)=[O:28].C(=O)([O-])[O-].[Na+].[Na+]>>[CH3:1][N:2]1[CH:6]=[C:5]([CH:27]=[O:28])[C:4]([C:7]2[O:8][C:9]([N+:12]([O-:14])=[O:13])=[CH:10][CH:11]=2)=[N:3]1
Reactant: Cn1ccc(-c2ccc([N+](=O)[O-])o2)n1
Reactant: O=C(O)C(F)(F)F
Agent: C1N2CN3CN1CN(C2)C3
Agent: O=C([O-])[O-]
Agent: [Na+]
Product: Cn1cc(C=O)c(-c2ccc([N+](=O)[O-])o2)n1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 79 %

Procedure:
Heat 1.0 g of 1-methyl-3-(5-nitro-2-furyl)pyrazole together with 0.73 g of hexamethylenetetramine and 11.6 g of trifluoroacetic acid for 4.5 hours at boiling point. Add the resulting 4-pyrazolylmethyleneammonium-salt-containing solution to 31 ml of ice water. Stir the thus-obtained admixture for 15 minutes, and make it alkaline with concentrated sodium carbonate solution. Filter off the precipitate and wash it with water until it is neutral to obtain 1-methyl-3-(5-nitro-2-furyl)pyrazole-4-carboxaldehyde [melting point: 181° to 182° C] with a yield of 79%.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[CH:8][C:7](F)=[C:6]([N+:11]([O-:13])=[O:12])[CH:5]=1.CN(C=O)C.C(=O)([O-])[O-].[K+].[K+].[NH2:26][CH:27]([CH2:30][CH3:31])[CH2:28][CH3:29]>O>[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[CH:8][C:7]([NH:26][CH:27]([CH2:30][CH3:31])[CH2:28][CH3:29])=[C:6]([N+:11]([O-:13])=[O:12])[CH:5]=1
Reactant: CCC(N)CC
Reactant: COC(=O)c1ccc(F)c([N+](=O)[O-])c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCC(CC)Nc1ccc(C(=O)OC)cc1[N+](=O)[O-]
Reaction time: 3 h
Yield: 97.4 %

Procedure:
To a solution of 5.38 g of 4-fluoro-3-nitro-benzoic acid methyl ester in 25 ml of abs. DMF was added 5.60 g of potassium carbonate, followed by 2.67 g of 3-aminopentane. After 3 h at rt, the mixture was poured into water, and extracted with ethyl acetate three times. The combined organic phases were washed with water, dried over sodium sulphate and concentrated to yield 7.01 g (97%) of 4-(1-Ethyl-propylamino)-3-nitro-benzoic acid methyl ester as a light brown oil.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[CH2:7][CH2:8][CH2:9][N:10]1C(=O)C2=CC=CC=C2C1=O.NN>C(Cl)(Cl)Cl>[NH2:10][CH2:9][CH2:8][CH2:7][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][N:1]=1
Reactant: O=C1c2ccccc2C(=O)N1CCCc1cnccn1
Agent: NN
Solvent: ClC(Cl)Cl
Product: NCCCc1cnccn1
Temperature: 25 °C
Reaction time: 20 h
Yield: 89.7 %

Procedure:
N-[3-(2-Pyrazinyl)propyl]phthalimide (521 mg, 1.95 mmol) was dissolved in chloroform (15 mL) followed by addition of anhydrous hydrazine (1.5 mL), and then the mixture was stirred at room temperature for 20 hours. The resulting precipitate was removed by filtration, and the filtrate was washed with water and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and 2-(3-aminopropyl)pyrazine (240 mg; yield 90%) was thus obtained.
Reaction SMILES: [OH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=2)[CH2:4][CH2:3]1.Cl[C:19]1[CH:27]=[CH:26][C:22]([C:23]([NH2:25])=[O:24])=[CH:21][N:20]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.C1(C)C=CC=CC=1>[OH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][CH2:9][CH2:10][C:11]2[CH:12]=[CH:13][C:14]([O:17][C:19]3[CH:27]=[CH:26][C:22]([C:23]([NH2:25])=[O:24])=[CH:21][N:20]=3)=[CH:15][CH:16]=2)[CH2:4][CH2:3]1
Reactant: Oc1ccc(CCN[C@H]2CC[C@H](O)CC2)cc1
Reactant: NC(=O)c1ccc(Cl)nc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: Cc1ccccc1
Product: NC(=O)c1ccc(Oc2ccc(CCN[C@H]3CC[C@H](O)CC3)cc2)nc1

Procedure:
Heat a mixture of the phenol (121.2 mg, 0.52 mmol), 6-chloronicotinamide (121.0 mg, 0.77 mmol), and K2CO3 (213.5 mg, 1.55 mmol) in 3:1 DMF/toluene (6.0 mL) at 165° C. for 3 hours. Quench the reaction with a small amount of H2O and concentrate to dryness, using xylenes to remove DMF azeotropically. Dissolve the residue in MeOH and filter. Concentrate the filtrate and purify by flash chromatography, eluting with 75:15:10 EtOAc/CH2Cl2/2.0 M NH3 in MeOH, to afford the title compound (79.1 mg, 43%): MS ES+ 356.0 (M+H)+, HRMS calcd for C20H26N3O3 356.1974 (M+H)+, found 356.1959, time 0.34 min; HPLC [YMC-Pack Pro C-18 (150×4.6 mm, S-5 microm), acetonitrile in water containing 0.01% concentrated HCl at 1.0 mL/min, 5-95% over 19 min], tR=5.81 min, 100% purity.