Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[CH2:2][C:3]([NH:5][CH2:6][C:7]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:8]=1[C:9](=[O:25])[N:10]([CH:17]1[CH2:22][CH2:21][C:20](=[O:23])[NH:19][C:18]1=[O:24])[C:11]2=[O:16])=[O:4].[N-:26]=[N+:27]=[N-:28].[Na+].[I-].[Na+]>CC(C)=O>[N:26]([CH2:2][C:3]([NH:5][CH2:6][C:7]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:8]=1[C:9](=[O:25])[N:10]([CH:17]1[CH2:22][CH2:21][C:20](=[O:23])[NH:19][C:18]1=[O:24])[C:11]2=[O:16])=[O:4])=[N+:27]=[N-:28]
Reactant: [N-]=[N+]=[N-]
Reactant: O=C(CCl)NCc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O
Agent: [I-]
Agent: [Na+]
Solvent: CC(C)=O
Product: [N-]=[N+]=NCC(=O)NCc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O
Yield: 90.8 %

Procedure:
A mixture of 2-chloro-N-{[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}acetamide (1.3 g, 3.57 mmol), sodium azide (0.3 g, 4.65 mmol) and sodium iodide (0.54 g, 3.57 mmol) in acetone (50 ml) was refluxed for 17 hours. The solvent was removed in vacuo and the residue was dissolved in EtOAc (60 ml). The EtOAc solution was washed with H2O (30 ml), brine (30 ml), and dried (MgSO4). The solvent was removed in vacuo to give 2-azido-N-{[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}acetamide (1.2 g, 90%) as a white solid: 1H NMR (CDCl3) δ d 8.48 (s, 1H), 7.84-7.68 (m, 31), 7.51 (t, J=6.3 Hz, 1H), 5.04-4.97 (dd, J=4.7 and 11.8 Hz, 1H), 4.80 (d, J=6.5 Hz, 2H), 3.97 (s, 2H), 2.95-2.74 (m, 3H) 2.20-2.15 (m, 1H).
Reaction SMILES: C(S[C:5]1[NH:6][C:7]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=2)=[C:8]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=2)[C:9]=1[CH2:10][CH:11]=[CH2:12])(=O)C.CC(C)=O>[Ni].C(O)C>[Cl:19][C:16]1[CH:15]=[CH:14][C:13]([C:8]2[C:9]([CH2:10][CH2:11][CH3:12])=[CH:5][NH:6][C:7]=2[C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=2)=[CH:18][CH:17]=1
Reactant: C=CCc1c(SC(C)=O)[nH]c(-c2ccc(Cl)cc2)c1-c1ccc(Cl)cc1
Agent: [Ni]
Solvent: CCO
Solvent: CC(C)=O
Product: CCCc1c[nH]c(-c2ccc(Cl)cc2)c1-c1ccc(Cl)cc1
Yield: 22.8 %

Procedure:
A mixture of 5 g Raney nickel, 0.8 g (2 m moles) of 2-acetylthio-3-allyl-4,5-bis(4-chlorophenyl)pyrrole and 50 ml acetone was heated at reflux under nitrogen for two hours. The mixture was diluted with ethanol and the catalyst was removed by filtration. The filtrate was concentrated by rotary evaporation. The residue was purified by chromatography on 50 g Silic AR CC-7, eluting with hexane/toluene (90/10), to give 0.15 g of white crystals, m.p. 90°-93°.
Reaction SMILES: C([N:7]1[N:11]2[C:12]3[C:26]4[CH:27]=[N:28][NH:29][C:25]=4[N:24]=[CH:23][C:13]=3[C:14](=[O:22])[N:15]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:10]2=[CH:9][CH:8]1[CH3:30])C1OC=CC=1.COCCOCCOC.[Se](=O)=O>>[CH3:30][C:8]1[CH:9]=[C:10]2[N:15]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:14](=[O:22])[C:13]3[CH:23]=[N:24][C:25]4[NH:29][N:28]=[CH:27][C:26]=4[C:12]=3[N:11]2[N:7]=1
Reactant: CC1C=C2N(c3ccccc3)C(=O)c3cnc4[nH]ncc4c3N2N1Cc1ccco1
Agent: O=[Se]=O
Solvent: COCCOCCOC
Product: Cc1cc2n(-c3ccccc3)c(=O)c3cnc4[nH]ncc4c3n2n1
Reaction time: 2 h

Procedure:
0.01 ml. of 1-furfuryl-2-methyl-4-phenyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]pyrido[3,4-e]pyrimidin-5(8H)-one is heated in 50 ml. of diethyleneglycol dimethyl ether containing 0.01 mol. of selenium dioxide at reflux temperature with stirring for 2 hours. The mixture is filtered hot and evaporated to dryness. Crystalline 2-methyl-4-phenyl-4H-pyrazolo[1,5-a]pyrazolo[4',3':5,6]pyrido[3,4-e]pyrimidin-5(8H)-one remains.
Reaction SMILES: [C:1](=[O:12])(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl.[NH2:13][C:14]([CH3:27])([CH3:26])[C:15]([NH:17][C:18]1[CH:23]=[CH:22][C:21]([Br:24])=[C:20]([CH3:25])[CH:19]=1)=[O:16].C(N(CC)CC)C.[Cl-].[NH4+]>ClCCl>[Br:24][C:21]1[CH:22]=[CH:23][C:18]([N:17]2[C:15](=[O:16])[C:14]([CH3:26])([CH3:27])[NH:13][C:1]2=[O:12])=[CH:19][C:20]=1[CH3:25]
Reactant: Cc1cc(NC(=O)C(C)(C)N)ccc1Br
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Agent: [Cl-]
Agent: [NH4+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1cc(N2C(=O)NC(C)(C)C2=O)ccc1Br
Temperature: 25 °C
Reaction time: 21 h
Yield: 287.3 %

Procedure:
Bis(trichloromethyl) carbonate (50.6 mg, 0.171 mmol) was added to a solution of 2-amino-N-(4-bromo-3-methyl-phenyl)-2-methyl-propionamide (132 mg, 0.487 mmol) and triethylamine (0.204 ml, 1.46 mmol) in dichloromethane (5.0 ml) at 0° C., and the mixture was stirred for 21 hours while gradually warming to room temperature. An aqueous ammonium chloride solution was added to the reaction mixture, followed by extraction with dichloromethane. The resulting residue was purified by silica gel column chromatography (dichloromethane-ethyl acetate) to give 3-(4-bromo-3-methyl-phenyl)-5,5-dimethyl-imidazolidine-2,4-dione (146 mg, 88%).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:11]([OH:13])=O)[CH:10]=2)[CH:7]=1.[CH3:14][CH:15]1[C:24]2[C:19](=[C:20]([C:25]3[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=3)[CH:21]=[CH:22][CH:23]=2)[CH2:18][CH2:17][NH:16]1>>[Br:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:11]([N:16]3[CH2:17][CH2:18][C:19]4[C:24](=[CH:23][CH:22]=[CH:21][C:20]=4[C:25]4[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=4)[CH:15]3[CH3:14])=[O:13])[CH:10]=2)[CH:7]=1
Reactant: CC1NCCc2c(-c3ccncc3)cccc21
Reactant: O=C(O)c1cc2ncc(Br)cn2n1
Product: CC1c2cccc(-c3ccncc3)c2CCN1C(=O)c1cc2ncc(Br)cn2n1

Procedure:
In close analogy to the procedure described in Example 1, 6-bromo-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid is reacted with 1-Methyl-5-pyridin-4-yl-1,2,3,4-tetrahydro-isoquinoline to provide the title compound in moderate yield.
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:14]3[CH:15]=[N:16][C:17]([C:35]#[N:36])=[C:18]([O:19][CH:20]4[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][O:28]C5CCCCO5)[CH2:22][CH2:21]4)[C:13]=3[C:12]3[CH:37]=[C:38]([Br:41])[CH:39]=[N:40][C:11]2=3)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC1C=CC(S(O)(=O)=O)=CC=1>ClCCl.CO>[C:1]1([S:7]([N:10]2[C:14]3[CH:15]=[N:16][C:17]([C:35]#[N:36])=[C:18]([O:19][CH:20]4[CH2:21][CH2:22][N:23]([CH2:26][CH2:27][OH:28])[CH2:24][CH2:25]4)[C:13]=3[C:12]3[CH:37]=[C:38]([Br:41])[CH:39]=[N:40][C:11]2=3)(=[O:8])=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: N#Cc1ncc2c(c1OC1CCN(CCOC3CCCCO3)CC1)c1cc(Br)cnc1n2S(=O)(=O)c1ccccc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CO
Solvent: ClCCl
Product: N#Cc1ncc2c(c1OC1CCN(CCO)CC1)c1cc(Br)cnc1n2S(=O)(=O)c1ccccc1
Temperature: 40 °C
Yield: 107.8 %

Procedure:
To a solution of 9-benzenesulfonyl-3-bromo-5-{1-[2-(tetrahydropyran-2-yloxy)-ethyl]-piperidin-4-yloxy}-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (330 mg, 0.52 mmol) in dichloromethane (5 mL) and methanol (10 mL) was added tosic acid monhydrate (100 mg, 0.52 mmol) and the reaction mixture heated to 40° C. for 4 hours then concentrated in-vacuo. The resultant residue was was taken up in dichloromethane, diluted with saturated aqueous sodium bicarbonate (20 mL) and extracted with dichloromethane (3×20 mL). The combined organic layer was dried (Na2SO4), filtered, evaporated in-vacuo to afford the crude title compound as a pale yellow solid (312 mg) which was used without purification. 1H NMR (300 MHz, CDCl3): 9.56 (s, 1H), 8.77 (d, J=2.3 Hz, 1H), 8.63 (d, J=2.3 Hz, 1H), 8.23-8.22 (m, 2H), 7.64-7.63 (m, 1H), 7.52-7.51 (m, 2H), 5.16-5.14 (m, 1H), 3.65 (t, J=5.3 Hz, 2H), 2.96 (m, J=11.5 Hz, 2H), 2.61 (t, J=5.3 Hz, 2H), 2.39 (t, J=11.3 Hz, 2H), 2.25 (m, J=12.5 Hz, 2H), 2.03-2.01 (m, 2H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]=1[CH2:11][CH:10]([NH:13][C:14](=[O:16])[CH3:15])[CH2:9][CH2:8]2.C(Cl)Cl.[I:20]I>C(OC(F)(F)F)(=O)C.[Ag].O>[I:20][C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[C:12]2[C:7]=1[CH2:8][CH2:9][CH:10]([NH:13][C:14](=[O:16])[CH3:15])[CH2:11]2
Reactant: COc1cccc2c1CC(NC(C)=O)CC2
Reactant: II
Agent: [Ag]
Agent: CC(=O)OC(F)(F)F
Solvent: O
Solvent: ClCCl
Product: COc1ccc(I)c2c1CC(NC(C)=O)CC2
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a suspension of 2.19 g. (0.01 mol.) of N-(1,2,3,4-tetrahydro-8-methoxy-2-naphthalenyl) acetamide and 2.21 g (0.01 mole) of silver trifluoromethyl acetate in 80 ml. of methylene chloride was added dropwise a solution of iodine (2.52 g.; 0.02 mole) in 80 ml. of methylene chloride. The reaction mixture was stirred for one hour at room temperature, filtered and evaporated to leave an oil to which 100 ml. of water was added. After 30 minutes the oil solidified. The crystals were collected, dried and recrystallized from ethanol to give N-(1,2,3,4-tetrahydro-5-iodo-8-methoxy-2-naphthalenyl) acetamide as a white solid m.p. 202°-3°.
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[CH:7][C:6]([S:9](Cl)(=[O:11])=[O:10])=[CH:5][CH:4]=1)=[CH2:2].C(OC([N:23]1[CH:28]=[CH:27][N:26]([NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C:25](=[O:37])[CH2:24]1)=O)C1C=CC=CC=1>>[C:33]([O:32][C:30]([NH:29][N:26]1[CH2:27][CH2:28][N:23]([S:9]([C:6]2[CH:7]=[CH:8][C:3]([CH:1]=[CH2:2])=[CH:4][CH:5]=2)(=[O:11])=[O:10])[CH2:24][C:25]1=[O:37])=[O:31])([CH3:36])([CH3:34])[CH3:35]
Reactant: CC(C)(C)OC(=O)NN1C=CN(C(=O)OCc2ccccc2)CC1=O
Reactant: C=Cc1ccc(S(=O)(=O)Cl)cc1
Product: C=Cc1ccc(S(=O)(=O)N2CCN(NC(=O)OC(C)(C)C)C(=O)C2)cc1

Procedure:
Except for using 4-vinylphenylsulfonyl chloride instead of 6-chloronaphthalene-2-sulfonyl chloride and starting from 4-benzyloxycarbonyl-1-(tert-butoxycarbonylamino)-2-oxo-1,2,3,4-tetrahydropirazine (2.5 g), the process similar to that in Reference Example 5 was employed to obtain the title compound (2.12 g) as a colorless amorphous material.
Reaction SMILES: [CH2:1]([N:4]([CH2:8][C:9](=O)[CH3:10])[C:5](=[O:7])[CH3:6])[CH:2]=[CH2:3].C([O-])(=O)C.[Na+].Cl.[CH3:18][NH:19][OH:20]>O1CCOCC1.O>[C:5]([N:4]1[CH2:1][C:2]2([CH3:3])[CH:9]([CH2:10][O:20][N:19]2[CH3:18])[CH2:8]1)(=[O:7])[CH3:6]
Reactant: CNO
Reactant: C=CCN(CC(C)=O)C(C)=O
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: CC(=O)N1CC2CON(C)C2(C)C1

Procedure:
15.5 g (0.1 mol) of N-allyl-N-(2-oxopropyl)-acetamide are dissolved in 100 ml of dioxane, and 9 g of anhydrous sodium acetate and 9 g (0. 108 mol) of N-methylhydroxylamine hydrochloride in 10 ml of water are added. The mixture is heated under reflux overnight and cooled and the salts are filtered off with suction and washed with dioxane. The filtrate is concentrated, the residue is taken up in 100 ml of water and K2CO3 is added. The mixture is extracted with CHCl3, the extract is dried over K2CO3 and concentrated and the residue is distilled.
Reaction SMILES: [C:1]([C:3]1[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[CH:8][C:4]=1[C:5]([OH:7])=O)#[N:2].[CH3:14][CH2:15][CH2:16][CH:17]([NH2:21])[CH2:18][CH2:19][CH3:20]>>[C:1]([C:3]1[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[CH:8][C:4]=1[C:5]([NH:21][CH:17]([CH2:18][CH2:19][CH3:20])[CH2:16][CH2:15][CH3:14])=[O:7])#[N:2]
Reactant: COc1ccc(C(=O)O)c(C#N)c1
Reactant: CCCC(N)CCC
Product: CCCC(CCC)NC(=O)c1ccc(OC)cc1C#N
Yield: 73 %

Procedure:
Prepared in a similar manner to example 4 using 2-cyano-4-methoxybenzoic acid and 4-Heptylamine. Yield: 73%. 1H NMR (CD3OD): 0.94 (t, 6H, J=7.3 Hz), 1.38 (m, 4H), 1.53 (m, 4H), 4.02 (s, 3H), 4.12 (m, 1H), 7.27 (d, 1H, J=9.40 Hz), 8.11 (d, 2H, J=2.21 Hz). MS (M+H, 275).
Reaction SMILES: CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]3[CH:17]=[CH:16][NH:15][C:12]3=[N:13][CH:14]=2)O1.Cl[C:20]1[C:25]([N:26]2[CH2:30][CH2:29][CH2:28][CH2:27]2)=[N:24][CH:23]=[CH:22][N:21]=1.C([O-])([O-])=O.[Cs+].[Cs+]>COCCOC.C(Cl)(Cl)Cl>[N:26]1([C:25]2[C:20]([C:9]3[CH:10]=[C:11]4[CH:17]=[CH:16][NH:15][C:12]4=[N:13][CH:14]=3)=[N:21][CH:22]=[CH:23][N:24]=2)[CH2:30][CH2:29][CH2:28][CH2:27]1
Reactant: Clc1nccnc1N1CCCC1
Reactant: CC1(C)OB(c2cnc3[nH]ccc3c2)OC1(C)C
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: COCCOC
Solvent: ClC(Cl)Cl
Product: c1cnc(N2CCCC2)c(-c2cnc3[nH]ccc3c2)n1
Temperature: 100 °C

Procedure:
The starting material 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (124) (50 mg, 0.2048 mmol, 1 eq) and 2-chloro-3-(pyrrolidin-1-yl)pyrazine (72) (33 mg, 0.184 mmol, 1 eq) in DME (8 mL) was degassed and purged under argon atmosphere for 10 min. To this reaction mixture was charged Cs2CO3 (133 mg, 0.409 mmol, 2 eq) followed by addition of Pd(dpp)Cl2 (6 mg, 0.00819 mmol, 0.04 eq) and degassing and purging under argon for additional 10 min. The reaction mixture was heated at 100° C. for 12 h in a sealed tube. After completion of the reaction, the reaction mixture was diluted with CHCl3 and filtered through Celite. The solvents were distilled off and the crude material was submitted for flash column purification in neutral alumina using 1% MeOH/CHCl3 to obtain pale yellow solid compound 5-(3-(pyrrolidin-1-yl)pyrazin-2-yl)-1H-pyrrolo[2,3-b]pyridine 128 in 10 mg quantity. The compound 128 was confirmed by 1HNMR and LCMS. 1H NMR (400 MHz, CDCl3) δ: 9.50 (s, 1H), 8.58 (d, J=1.95, 1H), 8.15 (d, J=1.58, 1H), 8.04 (m, J=2.56, 2H), 7.38 (m, J=3.45, 1H), 6.56 (m, J=1.58, 1H), 3.18 (m, J=6.70, 1H), 1.81 (m, J=2.92, 4H; MS m/z 265.9 (M+H)+.
Reaction SMILES: [CH:1]1([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=2[CH2:12][C:13]([OH:15])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:16][C@H:17]1[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:18]1>>[C:24]1([CH2:23][CH2:22][N:19]2[CH2:20][CH2:21][C@H:17]([NH:16][C:13](=[O:15])[CH2:12][C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=3[CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)[CH2:18]2)[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1
Reactant: O=C(O)Cc1ccccc1C1CCCC1
Reactant: N[C@H]1CCN(CCc2ccccc2)C1
Product: O=C(Cc1ccccc1C1CCCC1)N[C@H]1CCN(CCc2ccccc2)C1
Yield: 21.9 %

Procedure:
2-Cyclopentylphenylacetic acid (0.39 g) and (S)-3-amino-1-(2-phenylethyl)pyrrolidine (0.3 g) were reacted under the same conditions as in Example 23 to give N-((S)-1-(2-phenylethyl)pyrrolidin-3-yl)-2-cyclopentylphenylacetamide (0.13 g), melting point 117-119° C.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][C:9](Cl)=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:12]([O:16][C:17](=[O:36])[NH:18][CH:19]1[CH2:24][CH2:23][N:22]([S:25]([C:28]2[CH:33]=[CH:32][C:31]([NH2:34])=[C:30]([Cl:35])[CH:29]=2)(=[O:27])=[O:26])[CH2:21][CH2:20]1)([CH3:15])([CH3:14])[CH3:13]>N1C=CC=CC=1.C(Cl)Cl>[C:12]([O:16][C:17](=[O:36])[NH:18][CH:19]1[CH2:20][CH2:21][N:22]([S:25]([C:28]2[CH:33]=[CH:32][C:31]([NH:34][C:9](=[O:10])[CH2:8][CH2:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[C:30]([Cl:35])[CH:29]=2)(=[O:27])=[O:26])[CH2:23][CH2:24]1)([CH3:15])([CH3:13])[CH3:14]
Reactant: CC(C)(C)OC(=O)NC1CCN(S(=O)(=O)c2ccc(N)c(Cl)c2)CC1
Reactant: O=C(Cl)CCc1ccccc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NC1CCN(S(=O)(=O)c2ccc(NC(=O)CCc3ccccc3)c(Cl)c2)CC1
Temperature: 60 °C
Reaction time: 12 h
Yield: 12.3 %

Procedure:
3-Phenyl propionyl chloride (0.29 g, 1.76 mmol) was added in one portion to a solution of [1-(4-amino-3-chloro-benzenesulfonyl)-piperidin-4-yl]-carbamic acid tert-butyl ester (0.57 g, 1.4 mmol) in Pyridine (5 ml) and the mixture was heated to 60° C. The mixture was stirred at this temperature under a nitrogen atmosphere for 12 hours. After this time the mixture was diluted with DCM (100 ml) and washed sequentially with HCl (1M solution, 50 ml), NaOH (1M solution, 50 ml) and brine (50 ml). The organic layer was separated, dried (MgSO4), filtered and concentrated. The resulting residue was purified by flash column chromatography (elution: 98% DCM, 2% Methanol) to give the title compound (0.09 g, 8% yield) as a white powder. Tr=2.41 min, m/z (ES+) (M+Na)+ 545.
Reaction SMILES: [Cl:1][C:2]1[C:3]([N+:12]([O-:14])=[O:13])=[C:4]([CH3:11])[C:5]([N+:8]([O-])=O)=[CH:6][CH:7]=1.C1CCCCC=1>[Pd].C(O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[C:4]([CH3:11])[C:3]=1[N+:12]([O-:14])=[O:13]
Reactant: Cc1c([N+](=O)[O-])ccc(Cl)c1[N+](=O)[O-]
Agent: [Pd]
Solvent: C1=CCCCC1
Solvent: CCO
Product: Cc1c(N)ccc(Cl)c1[N+](=O)[O-]
Temperature: 25 °C

Procedure:
A mixture of 3-chloro-2,6-dinitrotoluene (18.0 g), cyclohexene (51 mL), and 10% palladium on charcoal (4.5 g) in ethanol (350 mL) was heated at reflux under an atmosphere of nitrogen for 1.5 hr. The reaction mixture was cooled to room temperature, filtered through celite, then evaporated under reduced pressure. The residue was dissolved in ethyl ether and filtered through a short silica column. Evaporation of the ether afforded 14.8 g as an orange solid.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([C:13]1[CH:18]=[CH:17][C:16]([N:19]3[CH2:25][CH2:24][CH2:23][N:22]([CH3:26])[CH2:21][CH2:20]3)=[CH:15][CH:14]=1)[CH2:6][CH2:5]2.CS([CH2:31][C@H:32]1[CH2:36][CH2:35][CH2:34][O:33]1)(=O)=O>>[CH3:26][N:22]1[CH2:23][CH2:24][CH2:25][N:19]([C:16]2[CH:15]=[CH:14][C:13]([N:7]3[CH2:6][CH2:5][C:4]4[C:9](=[CH:10][CH:11]=[C:2]([O:1][CH2:31][C@H:32]5[CH2:36][CH2:35][CH2:34][O:33]5)[CH:3]=4)[C:8]3=[O:12])=[CH:18][CH:17]=2)[CH2:20][CH2:21]1
Reactant: CN1CCCN(c2ccc(N3CCc4cc(O)ccc4C3=O)cc2)CC1
Reactant: CS(=O)(=O)C[C@H]1CCCO1
Product: CN1CCCN(c2ccc(N3CCc4cc(OC[C@H]5CCCO5)ccc4C3=O)cc2)CC1

Procedure:
6-Hydroxy-2-[4-(4-methyl-[1,4]diazepan-1-yl)-phenyl]-3,4-dihydro-2H-isoquinolin-1-one and (R)-2-methanesulfonylmethyl-tetrahydrofuran were reacted according to Method K1. In this way the product was obtained with molecular weight 435.57 (C26H33N3O3); MS (ESI): 436 (M+H+).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13](=[O:14])[C:12]3[NH:15][N:16]=[C:17]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C:11]=3[N:10]=[C:9]2[C:24]2[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=2)=[CH:4][CH:3]=1.[C:31]([O-])([O-])=O.[K+].[K+].CI>C(#N)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:13](=[O:14])[C:12]3[N:15]([CH3:31])[N:16]=[C:17]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C:11]=3[N:10]=[C:9]2[C:24]2[CH:25]=[CH:26][C:27]([CH3:30])=[CH:28][CH:29]=2)=[CH:6][CH:7]=1
Reactant: O=C([O-])[O-]
Reactant: Cc1ccc(-c2nc3c(-c4ccccc4)n[nH]c3c(=O)n2-c2ccc(Br)cc2)cc1
Agent: [K+]
Solvent: CC#N
Solvent: CI
Product: Cc1ccc(-c2nc3c(-c4ccccc4)nn(C)c3c(=O)n2-c2ccc(Br)cc2)cc1

Procedure:
To a solution of 6-(4-bromo-phenyl)-3-phenyl-5-p-tolyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one (11.0 mg, 0.024 mmol) in acetonitrile (0.3 mL) are added K2CO3 (6.6 mg, 0.048 mmol) and MeI (5.99 μL, 0.096 mmol). The reaction mixture is stirred at room temperature for overnight before the removal of K2CO3 by filtration. The filtrate is concentrated and purified by preparative LC/MS to provide the title compound; 1H NMR (CDCl3, 400 MHz) δ 8.36 (d, 2H), 7.47 (t, 2H), 7.44 (d, 2H), 7.35 (t, 1H), 7.22 (d, 2H), 7.04 (m, 4H), 4.37 (s, 3H), 2.31 (s, 3H); HPLC-MS calculated for C25H19BrN4O (M+H+) 471.1. found: 471.1.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C:5]2=[N:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].O1CCO[CH2:26][CH2:25]1.O.O>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)(=O)C>[CH:25]([C:2]1[CH:3]=[C:4]2[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C:5]2=[N:6][CH:7]=1)=[CH2:26]
Reactant: CC(C)(C)OC(=O)N1CCc2cc(Br)cnc21
Reactant: C1COCCO1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCOC(C)=O
Product: C=Cc1cnc2c(c1)CCN2C(=O)OC(C)(C)C
Temperature: 80 °C
Reaction time: 8 h

Procedure:
Under an argon atmosphere, to a mixture of 1100 mg of tert-butyl 5-bromo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-1-carboxylate, 1062 mg of a 2,4,6-trivinylboroxine/pyridine complex, 1020 mg of potassium carbonate, 3 mL of 1,4-dioxane/water (4/1) was added 215 mg of tetrakis(triphenylphosphine)palladium. The reaction mixture was stirred at 80° C. overnight. To the reaction mixture were added water and ethyl acetate and the aqueous layer was separated. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane/ethyl acetate) to obtain 783 mg of tert-butyl 5-vinyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-1-carboxylate as a yellow oil.
Reaction SMILES: [CH3:1][C:2]1([CH3:31])[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=2)[C:5]2[C:14]([OH:30])=[CH:15][C:16]([CH:18]([CH2:20][CH2:21][CH2:22][C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)[CH3:19])=[CH:17][C:4]=2[O:3]1.[C:32](OC(=O)C)(=[O:34])[CH3:33]>N1C=CC=CC=1>[C:32]([O:30][C:14]1[C:5]2[C:6]([C:8]3[CH:9]=[CH:10][N:11]=[CH:12][CH:13]=3)=[CH:7][C:2]([CH3:1])([CH3:31])[O:3][C:4]=2[CH:17]=[C:16]([CH:18]([CH2:20][CH2:21][CH2:22][C:23]2[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=2)[CH3:19])[CH:15]=1)(=[O:34])[CH3:33]
Reactant: CC(=O)OC(C)=O
Reactant: CC(CCCc1ccc(F)cc1)c1cc(O)c2c(c1)OC(C)(C)C=C2c1ccncc1
Solvent: c1ccncc1
Product: CC(=O)Oc1cc(C(C)CCCc2ccc(F)cc2)cc2c1C(c1ccncc1)=CC(C)(C)O2
Temperature: 25 °C
Reaction time: 8 h

Procedure:
4.17 g. (0.01 mole) of the hydroxy compound of Example 3 was dissolved in 8 ml. of dry pyridine to which was added 1.22 g. (0.012 mole) of acetic anhydride. The reaction was stirred at room temperature overnight, evaporated, treated with benzene and evaporated again. The residue was taken up in ether, washed with water, dried over magnesium sulfate and evaporated. The compound was then purified on a Florosil activated aluminum magnesium silicate column using methanolbenzene as an eluting solvent to obtain a glass residue. IR and Raman spectra confirmed the structure.
Reaction SMILES: [NH:1]1[CH:8]=[CH:7][C:5](=[O:6])[NH:4][C:2]1=[O:3].[I:9]Cl>CO>[I:9][C:7]1[C:5](=[O:6])[NH:4][C:2](=[O:3])[NH:1][CH:8]=1
Reactant: O=c1cc[nH]c(=O)[nH]1
Reactant: ClI
Solvent: CO
Product: O=c1[nH]cc(I)c(=O)[nH]1
Reaction time: 3 h
Yield: 80.4 %

Procedure:
A mixture of uracil (28.6 mmol, 3.2 g) and iodine monochloride (49.2 mmol, 7.988 g) in methanol (120 mL) was refluxed for 40 hr. The solvent was removed under vacuum and the residue was crystallized from ethanol:water (1:1, 150 mL) and stored in the refrigerator for 3 h. The resulting needles were collected by filtration and were washed with ethanol:water (1:1 mixture, 50 mL), water (30 mL), hexane (30 mL) and then dried in air to obtain 5.47 g (80%) of 5-iodo uracil as a white needles (mp 278-282° C., Lit. 274-276° C., Synthetic communication 1988, 18, 855-867). EI-HRMS m/e calcd for C4H3IN2O2 (M+) 237.9239, found 237.9244.
Reaction SMILES: [C:1](Cl)(=O)[CH3:2].[Br:5][C:6]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:7]=1[CH:8]=[CH:9][N:10]=[C:11]2[NH:16][NH2:17].CC1N2C=CC3C(C2=NN=1)=CC=CC=3Cl>>[CH3:1][C:2]1[N:10]2[CH:9]=[CH:8][C:7]3[C:12]([C:11]2=[N:16][N:17]=1)=[CH:13][CH:14]=[CH:15][C:6]=3[Br:5]
Reactant: CC(=O)Cl
Reactant: NNc1nccc2c(Br)cccc12
Agent: Cc1nnc2c3cccc(Cl)c3ccn12
Product: Cc1nnc2c3cccc(Br)c3ccn12

Procedure:
3-Methyl-7-bromo-s-triazolo-[3,4-a]-isoquinoline was prepared from acetyl chloride and 5-bromo-1-hydrazinoisoquinoline by a method generally similarto that described below for the preparation of 3-methyl-7-chloro-s-triazolo-[3,4-a]-isoquinoline. Yield, 78.5%; m.p. 203°-204°C.