Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[F:2][C:3]1[C:8]([C:9]2[C:10](=[O:16])[NH:11][C:12](=[O:15])[NH:13][CH:14]=2)=[CH:7][CH:6]=[C:5]([CH3:17])[N:4]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:25][CH2:26][CH:27]([O:30][CH3:31])[O:28][CH3:29]>CN(C=O)C>[CH3:29][O:28][CH:27]([O:30][CH3:31])[CH2:26][CH2:25][N:13]1[CH:14]=[C:9]([C:8]2[C:3]([F:2])=[N:4][C:5]([CH3:17])=[CH:6][CH:7]=2)[C:10](=[O:16])[NH:11][C:12]1=[O:15]
Reactant: Cc1ccc(-c2c[nH]c(=O)[nH]c2=O)c(F)n1
Reactant: COC(CCBr)OC
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(CCn1cc(-c2ccc(C)nc2F)c(=O)[nH]c1=O)OC
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 34.8 %

Procedure:
A mixture of 5-(2-fluoro-6-methyl-pyridin-3-yl)-1H-pyrimidine-2,4-dione hydrochloride (Prep 15, 667 mg, 2.59 mmol), and K2CO3 (358 mg, 2.59 mmol) in DMF (25 ml) was stirred 30 minutes at room temperature. Then 90% 3-Bromo-1,1dimethoxy-propane (432 μl, 2.85 mmol) was added in three portions during 3 days. Solvent was then removed under vacuum at 40° C. and the residue washed with ethyl acetate. The organic phase was dried (Na2SO4), filtered and evaporated. The crude was purified by flash chromatography eluting with DCM-MeOH—NH4OH (98-2-0.2) to give 291 mg of the title compound as a white solid (35% yield).
Reaction SMILES: Cl[CH2:2][CH2:3][N:4]1[C:12](=[O:13])[N:7]2[CH2:8][CH2:9][CH2:10][CH2:11][C:6]2=[N:5]1.[I-].[Na+].[F:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]([C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)=[C:24]2[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)=[CH:19][CH:18]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[F:36][C:33]1[CH:34]=[CH:35][C:30]([C:23]([C:20]2[CH:19]=[CH:18][C:17]([F:16])=[CH:22][CH:21]=2)=[C:24]2[CH2:29][CH2:28][N:27]([CH2:2][CH2:3][N:4]3[C:12](=[O:13])[N:7]4[CH2:8][CH2:9][CH2:10][CH2:11][C:6]4=[N:5]3)[CH2:26][CH2:25]2)=[CH:31][CH:32]=1
Reactant: O=c1n(CCCl)nc2n1CCCC2
Reactant: Fc1ccc(C(=C2CCNCC2)c2ccc(F)cc2)cc1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CC#N
Product: O=c1n(CCN2CCC(=C(c3ccc(F)cc3)c3ccc(F)cc3)CC2)nc2n1CCCC2
Yield: 88.5 %

Procedure:
2-(2-Chloroethyl)-5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyridin-3(2H)-one (26.8 g), 31.5 g of sodium iodide and 400 mλ of acetonitrile were refluxed for 30 minutes. To the reaction mixture were added 38.2 g of 4-[bis(4-fluorophenyl)methylene]piperidine and 27.6 g of potassium carbonate, followed by heating at reflux for 8 hours. The insoluble material was removed by filtration, and the filtrate was concentrated to dryness under reduced pressure. The residue was dissolved in 200 mλ of chloroform, and the solution was applied to a column contained with 550 g of silica gel and eluted with chloroform to obtain 53.0 g of the entitled compound as an oily substance.
Reaction SMILES: Cl[CH2:2][C:3]([N:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH2:8][CH2:7][CH2:6]1)=[O:4].[N+:15]([C:18]1[CH:19]=[CH:20][C:21]2[S:25][C:24]([SH:26])=[N:23][C:22]=2[CH:27]=1)([O-:17])=[O:16]>>[N:5]1([C:3](=[O:4])[CH2:2][S:26][C:24]2[S:25][C:21]3[CH:20]=[CH:19][C:18]([N+:15]([O-:17])=[O:16])=[CH:27][C:22]=3[N:23]=2)[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH2:8][CH2:7][CH2:6]1
Reactant: O=[N+]([O-])c1ccc2sc(S)nc2c1
Reactant: O=C(CCl)N1CCCc2ccccc21
Product: O=C(CSc1nc2cc([N+](=O)[O-])ccc2s1)N1CCCc2ccccc21
Yield: 56 %

Procedure:
The title compound was synthesized according to General Procedure A using compound 4 as the electrophile and 5-nitrobenzo[d]thiazole-2-thiol (12) as the nucleophile to yield 31 as a pale yellow solid (56%): MS m/z: 386 (M+H)+. Anal. Calcd. For, C18H15N3O3S2: C, 56.09; H, 3.92; N, 10.90; S, 16.64. Found: C, 56.22; H, 3.95; N, 10.81; S, 16.67.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C@@H:12](/[CH:13]=[CH:14]/[C:15]2[CH:20]=[CH:19][C:18](I)=[CH:17][CH:16]=2)[CH2:11][O:10][C:9]1([CH3:23])[CH3:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:24][C:25]1[C:34]([Cl:35])=[CH:33][CH:32]=[C:31]2[C:26]=1[CH2:27][CH2:28][NH:29][C:30]2=[O:36].CNCCNC.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.[Cu]I>[Cl:24][C:25]1[C:34]([Cl:35])=[CH:33][CH:32]=[C:31]2[C:26]=1[CH2:27][CH2:28][N:29]([C:18]1[CH:19]=[CH:20][C:15](/[CH:14]=[CH:13]/[C@H:12]3[CH2:11][O:10][C:9]([CH3:23])([CH3:22])[N:8]3[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[CH:16][CH:17]=1)[C:30]2=[O:36]
Reactant: CC(C)(C)OC(=O)N1[C@@H](/C=C/c2ccc(I)cc2)COC1(C)C
Reactant: O=C1NCCc2c1ccc(Cl)c2Cl
Agent: [Cu]I
Agent: CNCCNC
Agent: O=P([O-])([O-])[O-]
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)N1[C@@H](/C=C/c2ccc(N3CCc4c(ccc(Cl)c4Cl)C3=O)cc2)COC1(C)C
Temperature: 120 °C
Yield: 61.1 %

Procedure:
A stirred suspension of (S)-4-[(E)-2-(4-iodo-phenyl)-vinyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (300 mg, Example 3a), 5,6-dichloro-3,4-dihydro-2H-isoquinolin-1-one (204 mg), copper(I) iodide (13 mg), N,N′-dimethylethylenediamine (15 μl) and potassium phosphate (356 mg) in toluene (3 ml) in a sealed tube was heated at 120° C. overnight. The mixture was then cooled to room temperature and was purified by column chromatography (SiO2; gradient: heptane/EtOAc) to give (S,E)-tert-butyl 4-(4-(5,6-dichloro-1-oxo-3,4-dihydroisoquinolin-2(1H)-yl)styryl)-2,2-dimethyloxazolidine-3-carboxylate (221 mg, 61%) as a yellow amorphous solid. MS (ISP): 541.2 ([{37Cl35Cl}M+Na]+), 539.2 ([{35Cl}M+Na]+), 519.3 ([{37Cl35Cl}M+H]+), 517.2 ([{35Cl}M+H]+), 463.2 ([{37Cl35Cl}M+H—C4H8]+), 461.2 ([{35Cl}M+H—C4H8]+), 419.2 ([{37Cl35Cl}M+H—C4H8—CO2]+), 417.2 ([{35Cl}M+H—C4H8—CO2]+).
Reaction SMILES: [Br:1]Br.[CH:3]([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH:12]([CH3:14])[CH3:13])[C:7]=1[OH:15])([CH3:5])[CH3:4].O>C(O)(=O)C>[Br:1][C:10]1[CH:11]=[C:6]([CH:3]([CH3:5])[CH3:4])[C:7]([OH:15])=[C:8]([CH:12]([CH3:14])[CH3:13])[CH:9]=1
Reactant: BrBr
Reactant: CC(C)c1cccc(C(C)C)c1O
Solvent: O
Solvent: CC(=O)O
Product: CC(C)c1cc(Br)cc(C(C)C)c1O
Reaction time: 6 h
Yield: 64.9 %

Procedure:
This is a modification of the procedure of Schuster, Ingeborg I.; Parvez, Masood; Freyer, Alan J. J. Org. Chem. 1988, 53, 5819. A solution of bromine (6.3 mL, 119 mmol) in acetic acid (40 mL) was added dropwise to a stirred, room temperature solution of 2,6-diisopropylphenol (20 mL, 97.1 mmol of 90% tech. grade) in acetic acid (280 mL). After 6 h, water was added and the mixture was extracted with ether. The ether phase was dried and concentrated and the residue was flash chromatographed (petroleum ether: eluent) to provide 4-bromo-2,6-diisopropylphenol (16.2 g, 65%) as a red oil. This oil was dissolved in DMF (50 mL), iodomethane (11.7 mL, 189 mmol) and potassium carbonate (26.3 g, 117 mL) were added to it. This reaction mixture was stirred for 5 h and diluted with water. This mixture was extracted with ether and the ether extracts were dried, concentrated and flash chromatographed (petroleum ether: eluent) to provide the title compound as a colorless oil (15.4 g, 90%): NMR (CDCl3); δ 7.17 (s, 2H), 3.70 (s, 3H), 3.29 (septet, 1H), 1.20 (d, 12 H).
Reaction SMILES: F[C:2]1[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][C:3]=1[O:4][CH2:5][CH2:6][O:7][CH:8]1[CH2:13][CH2:12][CH2:11][CH2:10][O:9]1.[O:21]1[CH2:24][CH:23]([N:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)[CH2:22]1.C(=O)([O-])[O-].[K+].[K+]>CN1C(=O)CCC1>[N+:18]([C:15]1[CH:16]=[CH:17][C:2]([N:28]2[CH2:29][CH2:30][N:25]([CH:23]3[CH2:24][O:21][CH2:22]3)[CH2:26][CH2:27]2)=[C:3]([O:4][CH2:5][CH2:6][O:7][CH:8]2[CH2:13][CH2:12][CH2:11][CH2:10][O:9]2)[CH:14]=1)([O-:20])=[O:19]
Reactant: O=[N+]([O-])c1ccc(F)c(OCCOC2CCCCO2)c1
Reactant: C1CN(C2COC2)CCN1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN1CCCC1=O
Product: O=[N+]([O-])c1ccc(N2CCN(C3COC3)CC2)c(OCCOC2CCCCO2)c1
Temperature: 100 °C
Reaction time: 8 h

Procedure:
A mixture of 2-(2-(2-fluoro-5- nitrophenoxy)ethoxy)tetrahydro-2H-pyran XXII (1550 mg, 5.43 mmol), 1-(oxetan-3-yl)piperazine (772 mg, 5.43 mmol) and potassium carbonate (1126.41 mg, 8.15 mmol) in NMP (6 mL) was stirred at 100° C. for 8 h. The aqueous layer was separated and extracted with EtOAc. The combined organic extracts were washed with H2O (5× to remove NMP) and brine and dried over sodium sulfate. The resulting residue was purified by column chromatography ISCO Rf (24 g column) eluting with a gradient of 100% DCM—60:35:5 DCM:Et2O:MeOH to provide 1-(4-nitro-2-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethoxy)phenyl)-4-(oxetan-3-yl)piperazine XXIII.
Reaction SMILES: Cl.[CH3:2][N:3]([CH3:31])[CH2:4][CH2:5][N:6]1[C:13](=[O:14])[C@H:12]([OH:15])[C@H:11]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)[S:10][C:9]2=[CH:24][CH:25]=[CH:26][C:27]3=[CH:28][CH:29]=[CH:30][C:7]1=[C:8]23.[C:32](OC(=O)C)(=[O:34])[CH3:33]>>[C:32]([O:15][C@@H:12]1[C@H:11]([C:16]2[CH:17]=[CH:18][C:19]([O:22][CH3:23])=[CH:20][CH:21]=2)[S:10][C:9]2=[CH:24][CH:25]=[CH:26][C:27]3=[CH:28][CH:29]=[CH:30][C:7](=[C:8]23)[N:6]([CH2:5][CH2:4][N:3]([CH3:2])[CH3:31])[C:13]1=[O:14])(=[O:34])[CH3:33]
Reactant: COc1ccc([C@@H]2Sc3cccc4cccc(c34)N(CCN(C)C)C(=O)[C@@H]2O)cc1
Reactant: CC(=O)OC(C)=O
Agent: Cl
Product: COc1ccc([C@@H]2Sc3cccc4cccc(c34)N(CCN(C)C)C(=O)[C@@H]2OC(C)=O)cc1
Yield: 99 %

Procedure:
A mixture of 0.4 g of (±)-cis-2,3-dihydro-5-[2-(dimethylamino)ethyl]-3-hydroxy-2-(4-methoxyphenyl)naphtho[1,8-bc]-1,5-thiazocin-4-(5H)-one hydrochloride and 8 mL of acetic anhydride was heated at 100° for 17 hours. The reaction mixture was concentrated to dryness and to the residue water, followed by concentrated ammonium hydroxide were added. The aqueous suspension was extracted with ethyl acetate. The ethyl acetate solution was washed with brine, dried (magnesium sulfate) and removal of the solvent gave 0.4 g (99%) of (±)-cis-3-(acetyloxy)-2,3-dihydro-5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)naphtho[1,8-bc]-1,5-thiazocin-4(5H)-one. A sample of this compound was crystallized from ether, mp. 111°-112°.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11](SC)=[C:10]2[C:20]2[C:21]([CH3:26])=[N:22][O:23][C:24]=2[CH3:25])=[CH:5][CH:4]=1.SC1C=CC=CC=1C(O)=O.FC(F)(F)C(O)=O.[OH-].[Na+]>>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH:11]=[C:10]2[C:20]2[C:21]([CH3:26])=[N:22][O:23][C:24]=2[CH3:25])=[CH:7][CH:8]=1
Reactant: COc1ccc(-n2c(-c3c(C)noc3C)c(SC)c3ccccc32)cc1
Agent: O=C(O)c1ccccc1S
Agent: [Na+]
Agent: [OH-]
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc(-n2c(-c3c(C)noc3C)cc3ccccc32)cc1
Temperature: 25 °C
Yield: 86 %

Procedure:
4-(1-(4-Methoxyphenyl)-3-(methylthio)-1H-indol-2-yl)-3,5-dimethylisoxazole (the intermediate product of step (c) from the synthesis of Example 21, 140 mg, 0.38 mmol) and 2-mercaptobenzoic acid (118 mg, 0.77 mmol) were added to 5 ml of trifluoroacetic acid at RT. The mixture was stirred as a slurry at RT under an atmosphere of nitrogen over night. 2M NaOH and EtAc were added and the phases were separated. The solvents were evaporated and the residue was purified by flash chromatography with heptane/EtAc 4:1 as eluent to provide 4-(1-(4-methoxyphenyl)-1H-indol-2-yl)-3,5-dimethylisoxazole in 86% yield. ES/MS m/z: 319.1 (M+H)
Reaction SMILES: C(OC([N:8]1[C@H:20]([C:21]([OH:23])=[O:22])[CH2:19][C:18]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[C:10]=2[CH2:9]1)=O)(C)(C)C.Cl.O1CCOCC1.CCN(CC)CC>O>[F:31][C:28]1[CH:29]=[CH:30][C:25]([CH2:24][N:11]2[C:12]3[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:18]3[CH2:19][C@@H:20]([C:21]([OH:23])=[O:22])[NH:8][CH2:9][C:10]2=3)=[CH:26][CH:27]=1
Reactant: CC(C)(C)OC(=O)N1Cc2c(c3ccccc3n2Cc2ccc(F)cc2)C[C@H]1C(=O)O
Agent: Cl
Solvent: O
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Product: O=C(O)[C@@H]1Cc2c(n(Cc3ccc(F)cc3)c3ccccc23)CN1
Reaction time: 0.5 h
Yield: 90.1 %

Procedure:
The acid 3 (18.9 g, 44.5 mmol), 4M HCl in 1,4-dioxane solution (56 mL, 222.7 mmol), and 1,4-dioxane (85 mL) stirred at RT overnight. The reaction diluted with water (200 mL) and neutralized to pH 7 with Et3N. Water (400 mL) was added and the mixture stirred for 30 min. The solid was collected by filtration and washed with water (300 mL) to afford the amino acid 4 (13.0 g, 90%) as a pale yellow powder. 1H NMR (300 MHz, DMSO-d6): δ 8.95 (br s, 1H), 7.48 (d, 1H), 7.39 (d, 1H), 7.14-6.99 (m, 6H), 5.33 (s, 2H), 4.24 (d, 1H), 4.08 (d, 1H), 3.63-3.58 (m, 1H), 3.17-3.10 (m, 1H), 2.86-2.81 (m, 1H); LC-MS [M+H+ 325].
Reaction SMILES: [C:1]1([C@H:7]([CH2:11][CH3:12])[C:8]([OH:10])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.ON1C2C=CC=CC=2N=N1.CC[N+](CCCN(C)C)=C=N.[CH2:34]([N:41]1[CH2:45][C@H:44]2[C@H:46]([NH2:49])[CH2:47][CH2:48][C@H:43]2[CH2:42]1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>ClCCl>[CH2:34]([N:41]1[CH2:45][C@H:44]2[C@H:46]([NH:49][C:8](=[O:10])[C@H:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH2:11][CH3:12])[CH2:47][CH2:48][C@H:43]2[CH2:42]1)[C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1
Reactant: N[C@@H]1CC[C@H]2CN(Cc3ccccc3)C[C@H]21
Reactant: CC[C@H](C(=O)O)c1ccccc1
Agent: CC[N+](=C=N)CCCN(C)C
Agent: On1nnc2ccccc21
Solvent: ClCCl
Product: CC[C@H](C(=O)N[C@@H]1CC[C@H]2CN(Cc3ccccc3)C[C@H]21)c1ccccc1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
(S)-2-Phenylbutanoic acid (41.7 mg, 0.254 mmol), 1-hydroxybenzotriazole (38.9 mg, 0.254 mmol), and N-(3-dimethylaminopropyl)-N-ethylcarbodiimide (0.045 mL, 0.254 mmol) were combined in dichloromethane (1 mL). The reaction was stirred at room temperature for 10 minutes, and then (3aS,4R,6aR)-2-benzyloctahydrocyclopenta[c]pyrrol-4-amine (50 mg, 0.231 mmol) from Step E was added in 0.5 mL of dichloromethane. The reaction was stirred at room temperature for 20 hours, and then quenched with 0.5 mL of water. The organic layer was separated. The crude material was chromatographed using a silica gel cartridge (Analogix®, Burlington, Wis., RS-4) eluting with 1-10% methanol(ammonia)/dichloromethane to give the title compound: 1H NMR (400 MHz, pyridine-d5) δ ppm 8.47 (d, J=7.0, 1H), 7.59 (m, 2H), 7.42 (d, J=7.1, 2H), 7.34 (dd, J=7.6, 16.5, 4H), 7.25 (dt, J=5.0, 10.1, 2H), 4.45-4.29 (m, 1H), 3.62-3.51 (m, 2H), 3.44 (d, J=13.2, 1H), 2.85 (dd, J=2.7, 9.0, 1H), 2.58-2.50 (m, 1H), 2.50-2.42 (m, 2H), 2.40-2.31 (m, 1H), 2.31-2.22 (m, 2H), 1.97 (dq, J=6.1, 12.1, 1H), 1.85 (td, J=6.9, 13.6, 1H), 1.74 (dt, J=6.4, 14.3, 1H), 1.46 (dt, J=7.1, 19.2, 1H), 1.31 (dt, J=6.2, 20.5, 1H), 0.96 (dd, J=5.5, 9.1, 3H); MS (ESI+) m/z 363 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6](Cl)[CH:5]=[CH:4][C:3]=1[C:9]1[NH:13][N:12]=[N:11][N:10]=1.[N:14](O)=O.ClC1C=CC2C3N(N=NN=3)N=NC=2C=1.NC1C=C(C)C=CC=1C1NN=NN=1.CC1C=CC2C3N(N=NN=3)N=NC=2C=1.NC1C=C(OC)C(OC)=CC=1C1NN=NN=1.COC1C(OC)=CC2C3N(N=NN=3)N=NC=2C=1.NC1C=CC([N+]([O-])=O)=CC=1C1NN=NN=1.[N+](C1C=CC2N=NN3N=NN=C3C=2C=1)([O-])=O.NC1C=C(Cl)C(Cl)=CC=1C1NN=NN=1.ClC1C(Cl)=CC2C3N(N=NN=3)N=NC=2C=1.NC1C=C(C(F)(F)F)C=CC=1C1NN=NN=1>>[N:10]1[N:11]=[N:12][N:13]2[C:9]=1[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[N:1]=[N:14]2
Reactant: Nc1cc(Cl)ccc1-c1nnn[nH]1
Reactant: O=NO
Agent: COc1cc(N)c(-c2nnn[nH]2)cc1OC
Agent: COc1cc2nnn3nnnc3c2cc1OC
Agent: Cc1ccc(-c2nnn[nH]2)c(N)c1
Product: c1ccc2c(c1)nnn1nnnc21

Procedure:
Other substituted tetrazolobenzotriazines of the general formula shown above are made by the procedure, of the foregoing examples using appropriately substituted 5-(2-aminophenyl)tetrazoles as starting materials. For example, in this way 5-(2-amino-4-chlorophenyl)tetrazole is reacted with nitrous acid to make 8-chlorotetrazolo[4,5-C][1,2,3]benzotriazine; 5-(2-amino-4-methylphenyl)tetrazole is reacted to make 8-methyltetrazolo[4,5-C][1,2,3]benzotriazine; 5-(2-amino-4,5-dimethoxyphenyl)tetrazole is reacted to make 8,9-dimethoxytetrazolo[4,5-C][1,2,3]benzotriazine; 5-(2-amino-5-nitrophenyl)tetrazole is reacted to make 9-nitrotetrazolo[4,5-C][1,2,3]benzotriazine; 5-(2-amino-4,5-dichlorophenyl)tetrazole is reacted to make 8,9-dichlorotetrazolo[4,5-C][1,2,3]benzotriazine; and 5-(2-amino-4-trifluoromethylphenyl)tetrazole is reacted to produce 8-trifluoromethyl)tetrazolo[4,5-C][1,2,3]benzotriazine. These substituted tetrazolobenzotriazine products have explosive properties similar to those of the products of Examples 1-3.
Reaction SMILES: [CH:1](=[CH:8][C:9](=[O:13])[C:10]([OH:12])=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClC(O[CH2:18][CH3:19])=O>>[CH:1](=[CH:8][C:9](=[O:13])[C:10]([O:12][CH2:18][CH3:19])=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOC(=O)Cl
Reactant: O=C(O)C(=O)C=Cc1ccccc1
Product: CCOC(=O)C(=O)C=Cc1ccccc1

Procedure:
Furthermore, the pyruvic acid compound (I) can also be produced, for example, in accordance with: (1) the process in which benzaldehyde and sodium pyruvate are condensed together to give benzalpyruvic acid, and the benzalpyruvic acid is then reacted with ethyl chloroformate to give ethyl benzalpyruvate, and the ethyl benzalpyruvate is then reduced [EP387058]; or (2) the process in which phenetyl bromide is reacted with carbon monoxide in the presence of a cobalt carbonyl catalyst [J. Mol. Cat., 88, 295(1994)]. The process for producing the pyruvic acid compound (I) as the starting material is not limited to these processes, either of which can be used as the production process for the starting material in the present invention.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]#[N:9])=[N:6][CH:7]=1.C(N(CC)CC)C.[S:17]1[CH:21]=[CH:20][CH:19]=[C:18]1[C:22](Cl)=[O:23]>ClCCl>[C:8]([C:5]1[N:6]=[CH:7][C:2]([NH:1][C:22]([C:18]2[S:17][CH:21]=[CH:20][CH:19]=2)=[O:23])=[CH:3][CH:4]=1)#[N:9]
Reactant: O=C(Cl)c1cccs1
Reactant: N#Cc1ccc(N)cn1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: N#Cc1ccc(NC(=O)c2cccs2)cn1
Temperature: 0 °C
Yield: 11.2 %

Procedure:
To a suspension of 5-amino-2-cyanopyridine (2.00 g, 16.8 mmol) in dry dichloromethane (50 mL) was added triethylamine (2.54 g, 25.21 mmol) and the mixture was stirred at 0° C. To the reaction mixture 2-thiophene carbonyl chloride (3.70 g, 25.21 mmol) was added drop wise over a period of 15 minutes, and the reaction mixture was stirred at 0° C. for about 1 hour and then at room temperature overnight. The reaction mixture was diluted with dichloromethane (50 mL) and washed with saturated sodium bicarbonate solution (50 mL) and water (50 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated to obtain the crude product, which was purified by column chromatography (silica gel, 20-50% ethyl acetate in petroleum ether as an eluent) to obtain N-(6-cyanopyridin-3-yl)thiophene-2-carboxamide (compound 25a) Yield: 0.430 g (7.74%) and N-(6-cyanopyridin-3-yl)-N-(thiophene-2-carbonyl)thiophene-2-carboxamide (compound 25b). Yield: 1.3 g (33.75%).
Reaction SMILES: [C:1]([CH:5]1[N:9]([CH2:10][CH2:11][CH:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)[C:8](=[O:17])[C:7]([C:18]2[NH:23][C:22]3[CH:24]=[CH:25][C:26]([NH:28][S:29]([CH3:32])(=[O:31])=[O:30])=[CH:27][C:21]=3[S:20](=[O:34])(=[O:33])[CH:19]=2)=[C:6]1[OH:35])([CH3:4])([CH3:3])[CH3:2].C(C1[N:44](CC2C=CC(F)=C(C)C=2)[C:43](=O)C(C2NC3C=CC(NS(C)(=O)=O)=CC=3S(=O)(=O)C=2)=C1O)(C)(C)C>>[C:1]([CH:5]1[N:9]([CH2:10][CH2:11][CH:12]2[CH2:13][CH2:14][CH2:15][CH2:16]2)[C:8](=[O:17])[C:7]([C:18]2[NH:23][C:22]3[CH:24]=[CH:25][C:26]([NH:28][S:29]([CH3:32])(=[O:30])=[O:31])=[CH:27][C:21]=3[S:20](=[O:34])(=[O:33])[C:19]=2[C:43]#[N:44])=[C:6]1[OH:35])([CH3:4])([CH3:2])[CH3:3]
Reactant: Cc1cc(CN2C(=O)C(C3=CS(=O)(=O)c4cc(NS(C)(=O)=O)ccc4N3)=C(O)C2C(C)(C)C)ccc1F
Reactant: CC(C)(C)C1C(O)=C(C2=CS(=O)(=O)c3cc(NS(C)(=O)=O)ccc3N2)C(=O)N1CCC1CCCC1
Product: CC(C)(C)C1C(O)=C(C2=C(C#N)S(=O)(=O)c3cc(NS(C)(=O)=O)ccc3N2)C(=O)N1CCC1CCCC1

Procedure:
N-{3-[5-tert-Butyl-1-(2-cyclopentyl-ethyl)-4-hydroxy-2-oxo-2,5-dihydro-1H-pyrrol-3-yl]-2-cyano-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,4]thiazin-7-yl}-methanesulfonamide was prepared from N-{3-[5-tert-butyl-1-(2-cyclopentyl-ethyl)-4-hydroxy-2-oxo-2,5-dihydro-1H-pyrrol-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,4]thiazin-7-yl}-methanesulfonamide (15c, R3=c-C5H9—(CH2)2) to afford 27 mg (16%) of I-28: LCMS RT 2.71 min, M−H.
Reaction SMILES: [CH2:1]1[CH:7]2[CH2:8][C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][C:14]=3[N:6]2[CH2:5][CH2:4][CH2:3][NH:2]1.[CH2:15](Br)[CH3:16].O>CN(C=O)C>[CH2:15]([N:2]1[CH2:3][CH2:4][CH2:5][N:6]2[C:14]3[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=3[CH2:8][CH:7]2[CH2:1]1)[CH3:16]
Reactant: c1ccc2c(c1)CC1CNCCCN21
Reactant: CCBr
Solvent: O
Solvent: CN(C)C=O
Product: CCN1CCCN2c3ccccc3CC2C1
Reaction time: 10 h

Procedure:
1.88 g of 2,3,4,5,11,11a-hexahydro-1H-1,4-diazepino-[1,2-a]indole in 20 ml of DMF are stirred for one hour at 20° with 1.48 g of K tert.-butylate, 1.1 g of ethyl bromide are added and the solution is stirred for a further 10 hours. 200 ml of water are then added and the mixture is extracted several times with ethyl acetate. After drying and evaporating the organic phase, 2-ethyl-2,3,4,5,11,11a-hexahydro-1H-1,4-diazepino[1,2-a]indole is obtained. Hydrochloride, m.p. 204°.
Reaction SMILES: [F:1][C:2]([F:32])([F:31])[CH2:3][O:4][C:5]1[CH:6]=[C:7]([C:15]2[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[N:18]3[N:25]=[CH:26][C:27]([C:28]([OH:30])=O)=[C:17]3[N:16]=2)[CH:8]=[CH:9][C:10]=1[C:11]([F:14])([F:13])[F:12].[NH2:33][C:34]1[CH:35]=[C:36]([S:40]([NH:43][C:44]([CH3:48])([CH3:47])[CH2:45][OH:46])(=[O:42])=[O:41])[CH:37]=[CH:38][CH:39]=1>>[OH:46][CH2:45][C:44]([NH:43][S:40]([C:36]1[CH:35]=[C:34]([NH:33][C:28]([C:27]2[CH:26]=[N:25][N:18]3[C:19]([C:21]([F:23])([F:24])[F:22])=[CH:20][C:15]([C:7]4[CH:8]=[CH:9][C:10]([C:11]([F:13])([F:14])[F:12])=[C:5]([O:4][CH2:3][C:2]([F:1])([F:31])[F:32])[CH:6]=4)=[N:16][C:17]=23)=[O:30])[CH:39]=[CH:38][CH:37]=1)(=[O:42])=[O:41])([CH3:48])[CH3:47]
Reactant: CC(C)(CO)NS(=O)(=O)c1cccc(N)c1
Reactant: O=C(O)c1cnn2c(C(F)(F)F)cc(-c3ccc(C(F)(F)F)c(OCC(F)(F)F)c3)nc12
Product: CC(C)(CO)NS(=O)(=O)c1cccc(NC(=O)c2cnn3c(C(F)(F)F)cc(-c4ccc(C(F)(F)F)c(OCC(F)(F)F)c4)nc23)c1

Procedure:
The title compound was prepared from 5-[3-(2,2,2-trifluoro-ethoxy)-4-trifluoromethyl-phenyl]-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (example C.10) and 3-amino-N-(2-hydroxy-1,1-dimethyl-ethyl)-benzenesulfonamide (example B.8) according to general procedure II. Yellow solid. MS (ISP) 698.3 [(M−H−]; mp 251° C.
Reaction SMILES: [CH2:1]=[C:2]1[CH2:7][CH2:6][O:5][C:3]1=[O:4].[C:8]([OH:12])(=[O:11])[CH:9]=[CH2:10]>CS(C)=O>[CH2:1]=[C:2]1[CH2:7][CH:6]([CH3:8])[O:5][C:3]1=[O:4].[C:8]([OH:12])(=[O:11])[CH:9]=[CH2:10]
Reactant: C=C1CCOC1=O
Agent: C=CC(=O)O
Solvent: CS(C)=O
Product: C=C1CC(C)OC1=O

Procedure:
To a scintillation vial was added 267 mg of the poly(α-methylene-γ-butyrolactone-acrylic acid) prepared in Example 14 and 5.14 mL DMSO on a platform shaker. Once dissolved, the solution was pipetted onto a foil-lined steel panel and placed in a 100° C. oven. Vacuum was applied to remove the solvent over approximately 60 minutes. The result was a 2 cm×2 cm transparent poly(α-methylene-γ-valerolactone-acrylic acid) film.
Reaction SMILES: C[O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([C:14]([OH:16])=O)=[C:8]([CH3:13])[N:9]2[CH3:12])=[CH:5][CH:4]=1.B(Br)(Br)Br>>[CH:8]([NH:9][C:14]([C:7]1[C:6]2[C:10](=[CH:11][C:3]([OH:2])=[CH:4][CH:5]=2)[N:9]([CH3:12])[C:8]=1[CH3:13])=[O:16])([CH3:13])[CH3:7]
Reactant: COc1ccc2c(C(=O)O)c(C)n(C)c2c1
Agent: BrB(Br)Br
Product: Cc1c(C(=O)NC(C)C)c2ccc(O)cc2n1C

Procedure:
This material was prepared from 6-methoxy-1,2-dimethyl-1H-indol-3-carboxylic acid isopyropylamide 66a by treatment with BBr3 in a manner as previously described for example 1d. 1H NMR (300 MHz, CD3OD) δ 7.47 (1H, d, J=8.5 Hz), 6.74 (1H, d, J=2.1 Hz), 6.67 (1H, dd, J=2.1, 8.5 Hz), 4.22 (1H, m), 3.61 (3H, s), 2.56 (3H, s), 1.28 (3H, s), 1.26 (3H, s). LCMS (ESI+) [M+H]/z Calc'd 247. found 247.