Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][C:3]1[C:4]([CH3:38])=[C:5]([C:29]([O:36]C)=[C:30]([O:34][CH3:35])[C:31]=1[O:32][CH3:33])[CH2:6][C:7]1[CH:20]=[CH:19][C:10]([C:11]([N:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)=[O:12])=[C:9]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:8]=1.O=[N+]([O-])[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[Ce+4].[NH4+].[NH4+]>C(#N)C.O>[CH3:33][O:32][C:31]1[C:3](=[O:2])[C:4]([CH3:38])=[C:5]([CH2:6][C:7]2[CH:20]=[CH:19][C:10]([C:11]([N:13]3[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]3)=[O:12])=[C:9]([O:21][CH2:22][C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)[CH:8]=2)[C:29](=[O:36])[C:30]=1[O:34][CH3:35]
Reactant: COc1c(C)c(Cc2ccc(C(=O)N3CCCCC3)c(OCc3ccccc3)c2)c(OC)c(OC)c1OC
Agent: O=[N+]([O-])[O-]
Agent: [Ce+4]
Agent: [NH4+]
Solvent: CC#N
Solvent: O
Product: COC1=C(OC)C(=O)C(Cc2ccc(C(=O)N3CCCCC3)c(OCc3ccccc3)c2)=C(C)C1=O
Yield: 69.9 %

Procedure:
N-[4-(3,4,5,6-Tetramethoxy-2-methylbenzyl)-2-benzyloxybenzoyl]piperidine (129 mg, 0.2485 mmol) was dissolved in a mixed solution of acetonitrile (15 ml) and water (5 ml) and after adding thereto CAN (341 mg, 0.6222 mmol) at room temperature, the solution was stirred at room temperature for 1 hour. The reaction solution was diluted with water and then extracted with ether. The extract was washed with water and then dried, and the solvent was removed by distillation. The residue was purified by flash column chromatography (hexand:ethyl acetate=2:1) to obtain the titled compound (85 mg, 0.1738 mmol, 70%).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][CH:16]=1)[C:5]([CH:7]1[CH2:12][CH2:11][N:10]([CH3:13])[CH2:9][CH2:8]1)=[O:6].[C:17](Cl)(=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>C(Cl)Cl.C(O)(=O)C.CO>[C:17]([NH:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][CH:16]=1)[C:5]([CH:7]1[CH2:8][CH2:9][N:10]([CH3:13])[CH2:11][CH2:12]1)=[O:6])(=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: CN1CCC(C(=O)c2cccc(N)c2)CC1
Solvent: CO
Solvent: ClCCl
Solvent: CC(=O)O
Product: CN1CCC(C(=O)c2cccc(NC(=O)c3ccccc3)c2)CC1
Yield: 101.4 %

Procedure:
A mixture of 4-[3-aminobenzoyl]-1-methylpiperidine (25 mg, 0.115 mmol) and benzoyl chloride (39 μL, 0.336 mmol) in methylene chloride (1 mL) was mixed for 18 h at ambient temperature. The solution was diluted with 10% acetic acid in methanol and poured over a Varian Mega Bond Elut™ strong cation exchange column (Siegel, M. G.; Hahn, P. J.; Dressman, B. A.; Fritz, J. E.; Grunwell, J. R.; Kaldor, S. W. Tetrahedron Lett. 1997, 38, 3357-3360). The column was rinsed extensively with methanol to remove impurities, then treated with a 7M ammonia in methanol to elute the product from the column. The solvent was evaporated to give 37.6 mg (>100%) of the title compound.
Reaction SMILES: C(OC(N1C[C@H](O)C[C@H]1CO[Si](C(C)(C)C)(C)C)=O)C=C.C(OC(N1C[C@H](O)C[C@H]1CO)=O)C=C.O[C@H:37]1[C@@H:43]2[CH2:44][C:45](=[CH2:47])[CH2:46][N:42]2[C:41](=[O:48])[C:40]2[CH:49]=[C:50]([I:53])[CH:51]=[CH:52][C:39]=2[N:38]1NC(OCC(Cl)(Cl)Cl)=O.[Si](OC[C@@H]1CC(=C)CN1)(C(C)(C)C)(C)C>>[I:53][C:50]1[CH:51]=[CH:52][C:39]2[N:38]=[CH:37][C@@H:43]3[CH2:44][C:45](=[CH2:47])[CH2:46][N:42]3[C:41](=[O:48])[C:40]=2[CH:49]=1
Reactant: C=C1C[C@H]2[C@H](O)N(NC(=O)OCC(Cl)(Cl)Cl)c3ccc(I)cc3C(=O)N2C1
Agent: C=C1CN[C@H](CO[Si](C)(C)C(C)(C)C)C1
Agent: C=CCOC(=O)N1C[C@H](O)C[C@H]1CO
Agent: C=CCOC(=O)N1C[C@H](O)C[C@H]1CO[Si](C)(C)C(C)(C)C
Product: C=C1C[C@H]2C=Nc3ccc(I)cc3C(=O)N2C1

Procedure:
10% cadmium-lead couple (109 mg, 0.875 mmol) was added to a stirred solution of the Troc-protected carbinolamine 13 (93 mg, 0.175 mmol) in THF (1 mL) and aqueous 1 N ammonium acetate (1 mL). After 45 minutes at room temperature TLC revealed complete reaction (70% EtOAc/Petroleum Ether). The mixture was diluted with EtOAc (30 mL), dried (MgSO4), filtered and evaporated in vacuo. The crude residue was purified by flash chromatography (70% EtOAc/Petroleum Ether) to provide the novel PBD (14, BSD-SJG, UP2023) as a white solid (27 mg, 46%): mp ° C.; 1H NMR (270 MHz, CDCl3+CD3OD) (11S,11aS isomer) δ 8.10 (d, 1H, J=1.46Hz), 7.65 (d, 1H, J=8.79 Hz), 6.86 (d, 1H, J=8.06 Hz), 5.14-5.10 (m, 2H), 4.66 (d, 1H, J=5.13 Hz), 4.34 (d, 1H, J=16.12 Hz), 4.23 (d, 1H, J=16.12 Hz), 3.80-3.71 (m, 1H), 3.34 (s, 3H), 3.03-2.86 (m, 1H), 2.65 (d, 1H, J=16.02 Hz); MS (EI), m/z (relative intensity) (N10-C11 imine form) 339 (M++1, 20), 338 (M+, 100), 337 (17), 323 (5), 311 (4), 310 (5), 257 (5), 230 (4), 229 (13), 211 (4), 203 (4), 202 (8), 184 (8), 183 (4), 103 (5), 82 (17), 81 (4), 80 (5), 76 (6), 75 (16), 74 (5), 55 (4), 53 (4); IR (NUJOL7) 3295 (br), 2923, 2853, 1716, 1615, 1506, 1457, 1377, 1317, 1278, 1238, 1169, 1118, 1063, 999, 895, 818, 751, 718 cm−1; exact mass calcd for C13H11N2OI m/e 337.9916, obsd m/e 337.9870.
Reaction SMILES: [CH2:1]([Mg]Br)[CH2:2][CH3:3].[F:6][C:7]([F:26])([F:25])[O:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]2[CH2:19][CH:18]3[CH2:20][C:21](=[O:23])[CH2:22][CH:17]3[C:16]2=[O:24])=[CH:11][CH:10]=1.O>C1COCC1>[OH:23][C:21]1([CH2:1][CH2:2][CH3:3])[CH2:22][CH:17]2[C:16](=[O:24])[N:15]([C:12]3[CH:13]=[CH:14][C:9]([O:8][C:7]([F:6])([F:25])[F:26])=[CH:10][CH:11]=3)[CH2:19][CH:18]2[CH2:20]1
Reactant: O=C1CC2CN(c3ccc(OC(F)(F)F)cc3)C(=O)C2C1
Reactant: CCC[Mg]Br
Solvent: C1CCOC1
Solvent: O
Product: CCCC1(O)CC2CN(c3ccc(OC(F)(F)F)cc3)C(=O)C2C1
Temperature: 35 °C
Reaction time: 8 h
Yield: 22.1 %

Procedure:
Propylmagnesium bromide (0.2 mL, 0.6 mmol, 3M) was added to a solution of 2-(4-trifluoromethoxy-phenyl)-hexahydro-cyclopenta[c]pyrrole-1,5-dione (0.1 g, 0.33 mmol) in THF (10 mL), and the mixture was stirred for 3 h at room temperature and overnight at 35° C. The solution was cooled, then poured into water (25 mL) and extracted with ether (3×20 mL), dried over Na2SO4. The solvent was removed and the residue was purified by prep-TLC (petroleum/ethyl acetate=1:1) to yield the title compound (25 mg, 21%). 1H NMR (300 MHz, CDCl3): δ 7.62-7.60 (m, 2H), 7.32-7.23 (m, 2H), 4.11 (t, 1H, J=9.5 Hz), 3.71-3.67 (m, 1H), 3.18 (t, 1H, J=9.5 Hz), 2.95 (d, 1H, J=9.6 Hz), 2.25-2.21 (m, 1H), 1.98-1.88 (m, 2H), 1.81-1.76 (m, 1H), 1.61-1.34 (m, 4H), 0.95 (t, 3H, J=7.2 Hz); LC-MS: 344.2 [M+1]+.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7](I)[C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[C:10]([O:16][C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=1)[CH:9]=2)=[O:4].[C:25]([Cu])#[N:26].C(Cl)Cl>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([C:25]#[N:26])[C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[C:10]([O:16][C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=1)[CH:9]=2)=[O:4]
Reactant: N#C[Cu]
Reactant: COC(=O)c1nc(I)c2cc(Oc3ccc(Cl)cc3)ccc2c1O
Solvent: CN(C)C=O
Solvent: ClCCl
Product: COC(=O)c1nc(C#N)c2cc(Oc3ccc(Cl)cc3)ccc2c1O
Temperature: 120 °C
Reaction time: 0.17 h

Procedure:
7-(4-Chloro-phenoxy)-4-hydroxy-1-iodo-isoquinoline-3-carboxylic acid methyl ester (100 mg, 0.22 mmol) and CuCN (39 mg, 0.44 mmol) were suspended in DMF (1.0 mL). The resulting mixture was heated at 120° C. for 7 minutes and then cooled to room temperature. The reaction crude was poured into CH2Cl2 (30 mL) and stirred vigorously for 10 minutes at room temperature. The resulting suspension was filtered through a pad of celite and the filtrate was washed with H2O and brine sequentially. The organic layer was dried over MgSO4, concentrated, and purified by flash chromatography (0-30% EtOAc/CH2Cl2) to give the title compound in 65 mg. MS: (−) m/z 353.25 (M−1).
Reaction SMILES: Br[C:2]1[N:7]2[N:8]=[CH:9][N:10]=[C:6]2[C:5]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[CH:14][CH:13]=2)=[N:4][CH:3]=1.CC1(C)C(C)(C)OB([C:32]2[C:33]3[CH:40]=[CH:39][CH:38]=[CH:37][C:34]=3[S:35][CH:36]=2)O1>>[S:35]1[CH:36]=[C:32]([C:2]2[N:7]3[N:8]=[CH:9][N:10]=[C:6]3[C:5]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([N:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)=[CH:14][CH:13]=3)=[N:4][CH:3]=2)[C:33]2[CH:40]=[CH:39][CH:38]=[CH:37][C:34]1=2
Reactant: CC1(C)OB(c2csc3ccccc23)OC1(C)C
Reactant: Brc1cnc(Nc2ccc(N3CCOCC3)cc2)c2ncnn12
Product: c1ccc2c(-c3cnc(Nc4ccc(N5CCOCC5)cc4)c4ncnn34)csc2c1

Procedure:
This compound may be prepared using methods as described for Compound 120, using (5-bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-(4-morpholin-4-ylphenyl)amine and 4,4,5,5-tetramethyl-2-benzo[b]thiophen-3-yl-[1,3,2]dioxaborolane in step 4. LCMS: Rt 0.84 min (95%), m/z (ESI) 402 (M+H)+.
Reaction SMILES: [NH2:1][NH2:2].O=[C:4]([CH2:8][CH2:9][C:10]([OH:12])=[O:11])[C:5](O)=[O:6]>>[O:6]=[C:5]1[NH:2][N:1]=[C:9]([C:10]([OH:12])=[O:11])[CH2:8][CH2:4]1
Reactant: NN
Reactant: O=C(O)CCC(=O)C(=O)O
Product: O=C1CCC(C(=O)O)=NN1
Yield: 99 %

Procedure:
The disclosed embodiments stem from the examination of several classes of compounds that quantitatively react with hydrazine to form stable organic products. The reaction of 2-ketoglutaric acid with hydrazine reacts to provide a greater than 99% yield of 6-oxo-1,4,5,6-tetrahydro-pyridazine-3-carboxylic acid (PCA) based on hydrazine as the limiting reagent. It has been found that this compound allows for the facile remediation of hydrazine under a variety of conditions. The focus of the disclosed embodiments concerns the use of 2-ketoglutaric acid or other dicarbonyl compounds for the remediation of hydrazine.
Reaction SMILES: [NH2:1][C:2]1[CH:15]=[CH:14][CH:13]=[CH:12][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1.[N+:16]([C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH2:22]Cl)([O-:18])=[O:17].[I-].[K+].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O>[N+:16]([C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH2:22][O:11][C:8]1[CH:7]=[CH:6][C:5]([O:4][C:3]2[CH:12]=[CH:13][CH:14]=[CH:15][C:2]=2[NH2:1])=[CH:10][CH:9]=1)([O-:18])=[O:17]
Reactant: Nc1ccccc1Oc1ccc(O)cc1
Reactant: O=[N+]([O-])c1cccc(CCl)c1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Nc1ccccc1Oc1ccc(OCc2cccc([N+](=O)[O-])c2)cc1
Temperature: 50 °C
Reaction time: 3 h
Yield: 45.3 %

Procedure:
To a solution of 4-(2-aminophenoxy)phenol (0.85 g, 4.2 mmol) in N,N-dimethylformamide (20 ml) were added 3-nitrobenzyl chloride (0.87 g, 5.1 mmol), potassium iodide (0.70 g, 4.2 mmol) and potassium carbonate (0.88 g, 6.4 mmol), followed by stirring at 50° C. for 3 hours. The reaction solution was poured into water and extracted with ethyl acetate, and the organic layer was washed with water and a saturated aqueous sodium chloride solution. After drying, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent; chloroform) to give 2-[4-(3-nitrobenzyloxy)phenoxy]aniline (0.64 g)
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:4]=[CH:5][C:6]([NH:10][C:11](=[O:16])[C:12]([CH3:15])([CH3:14])[CH3:13])=[N:7][C:8]=1[CH3:9].[F:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22]Br)=[CH:20][CH:19]=1>>[F:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22][O:1][CH2:2][C:3]2[CH:4]=[CH:5][C:6]([NH:10][C:11](=[O:16])[C:12]([CH3:13])([CH3:15])[CH3:14])=[N:7][C:8]=2[CH3:9])=[CH:20][CH:19]=1
Reactant: Cc1nc(NC(=O)C(C)(C)C)ccc1CO
Reactant: Fc1ccc(CBr)cc1
Product: Cc1nc(NC(=O)C(C)(C)C)ccc1COCc1ccc(F)cc1

Procedure:
This material was prepared in analogy to example 86 step A] from N-(5-hydroxymethyl-6-methyl-pyridin-2-yl)-2,2-dimethyl-propionamide (0.6 g, product of example 112 step B]) and 4-fluorobenzyl bromide (0.56 g) as an orange solid (0.8 g). MS (ESI): 231.3 (MH+).
Reaction SMILES: [C:1]([N:4]([CH3:32])[CH2:5][CH2:6][N:7]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[CH:15]=2)[C:10]([OH:25])=[C:9]([C:26](OCC)=[O:27])[C:8]1=[O:31])(=[O:3])[CH3:2].[NH2:33][CH:34]([CH3:37])[CH2:35][OH:36]>CCO>[C:1]([N:4]([CH3:32])[CH2:5][CH2:6][N:7]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[CH:15]=2)[C:10]([OH:25])=[C:9]([C:26]([NH:33][CH:34]([CH3:37])[CH2:35][OH:36])=[O:27])[C:8]1=[O:31])(=[O:3])[CH3:2]
Reactant: CC(N)CO
Reactant: CCOC(=O)c1c(O)c2ncc(Cc3ccc(F)cc3)cc2n(CCN(C)C(C)=O)c1=O
Solvent: CCO
Product: CC(=O)N(C)CCn1c(=O)c(C(=O)NC(C)CO)c(O)c2ncc(Cc3ccc(F)cc3)cc21
Temperature: 25 °C

Procedure:
A solution of ethyl 1-{2-[acetyl(methyl)amino]ethyl}-7-[(4-fluorophenyl)methyl]-4-hydroxy-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylate (0.019 g, 0.039 mmol) in EtOH (3 mL) under nitrogen was treated with 2-amino-1-propanol (0.02 mL, 0.27 mmol) for 30 min. (160° C. in a microwave vessel. After the reaction was cooled to ambient temperature the resulting suspension was concentrated in vacuo, triturated with Et2O:MeOH, filtered, and the filtered solid was washed with Et2O then thoroughly dried under high vacuum to provide the title compound as an off-white solid: 1H NMR (400 MHz, DMSO-d6 (90° C.) δ ppm 1.23 (d, J=6.86 Hz, 3 H), 1.85 (s, 3 H), 2.95 (s, 3 H), 3.50-3.55 (m, 4 H), 4.08-4.11 (m, 1 H), 4.18 (s, 2 H), 4.35 (s, 2 H), 4.69-4.72 (m, 1 H), 7.10-7.15 (m, 2 H), 7.37-7.42 (m, 2 H), 8.08 (s, 1 H), 8.55 (s, 1 H), 10.29 (d, J=4.53 Hz, 1 H), 17.15 (s, 1 H); ES+ MS: 471 (M+H+).
Reaction SMILES: [C:1]([O:4][CH2:5][CH:6]([NH:27]C(OC(C)(C)C)=O)[CH2:7][O:8][C:9]1[C:13]2[CH:14]=[C:15]([N:18](C)[C:19](OC(C)(C)C)=O)[CH:16]=[CH:17][C:12]=2[O:11][N:10]=1)(=[O:3])[NH2:2].O1CCOCC1.[ClH:41]>CO>[ClH:41].[NH2:27][CH:6]([CH2:5][O:4][C:1](=[O:3])[NH2:2])[CH2:7][O:8][C:9]1[C:13]2[CH:14]=[C:15]([NH:18][CH3:19])[CH:16]=[CH:17][C:12]=2[O:11][N:10]=1
Reactant: CN(C(=O)OC(C)(C)C)c1ccc2onc(OCC(COC(N)=O)NC(=O)OC(C)(C)C)c2c1
Agent: Cl
Solvent: C1COCCO1
Solvent: CO
Product: CNc1ccc2onc(OCC(N)COC(N)=O)c2c1

Procedure:
To a solution of 0.10 g of 3-(3-carbamoyloxy-2-tert-butoxycarbonylaminopropoxy)-5-(N-methyl-N-tert-butoxycarbonylamino)-1,2-benzoisoxazole in 5 ml of methanol is added 1.2 ml of a dioxane solution (2.2N) of hydrogen chloride at 5°-10° C., and they are subjected to reaction at 20°-25° C. overnight. The solvent is removed from the reaction mixture by distillation under reduced pressure, and the residue obtained is crystallized from 2-propanol, after which the crystals are collected by filtration to obtain 0.03 g of colorless, crystalline 3-(2-amino-3-carbamoyloxypropoxy)-5-methylamino-1,2-benzoisoxazole hydrochloride having a melting point of 179°-185° C.
Reaction SMILES: C(C1C=CC(O[CH:9]([C:21](=[O:26])[C:22]([CH3:25])([CH3:24])[CH3:23])[C:10]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=2[Cl:20])=[O:11])=CC=1)(O)=O.Cl.[CH2:30]([N:32]([CH2:40][CH3:41])[C:33]1[CH:38]=[CH:37][C:36]([NH2:39])=[CH:35][CH:34]=1)[CH3:31].S(OOS([O-])(=O)=O)([O-])(=O)=O.[K+].[K+]>[OH-].[Na+].C(O)C.O>[CH3:25][C:22]([CH3:23])([CH3:24])[C:21](=[O:26])[C:9](=[N:39][C:36]1[CH:35]=[CH:34][C:33]([N:32]([CH2:40][CH3:41])[CH2:30][CH3:31])=[CH:38][CH:37]=1)[C:10]([NH:12][C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=1[Cl:20])=[O:11]
Reactant: CCN(CC)c1ccc(N)cc1
Reactant: CC(C)(C)C(=O)C(Oc1ccc(C(=O)O)cc1)C(=O)Nc1ccc(Cl)cc1Cl
Agent: Cl
Agent: O=S(=O)([O-])OOS(=O)(=O)[O-]
Agent: [K+]
Solvent: O
Solvent: CCO
Product: CCN(CC)c1ccc(N=C(C(=O)Nc2ccc(Cl)cc2Cl)C(=O)C(C)(C)C)cc1
Reaction time: 1 h

Procedure:
N-[4,4-dimethyl-2-[4-diethylaminophenyl]imino-3-oxopentanoyl]-2,4-dichloroaniline was prepared using a method analogous to that described in J. Korinek, J. Poskocil and J. Arient, Collection Czechoslov. Chem. Commun., 1979, 44, 1460. A solution of N-[2-[4-carboxyphenoxy]-4,4-dimethyl-3-oxopentanoyl]-2,4-dichloroaniline (10.0 g, 23.6 mmol, available from Eastman Kodak, Rochester, N.Y.) in a mixture of 1M aqueous sodium hydroxide solution (100 mL) and ethanol (50 mL), together with a solution of N,N-diethyl-p-phenylenediamine hydrochloride (5.20 g, 26 mmol) in ethanol (50 mL), was mixed all at once with a solution of potassium persulfate (7.0 g, 26 mmol) in water (250 mL) containing ethanol (50 mL). The yellow reaction mixture was stirred for one hour, and then extracted with dichloromethane (200 mL). The organic layer was separated and washed with a 50% saturated aqueous sodium chloride solution (200 mL) and dried over sodium sulfate. Evaporation of the solvent gave 11.4 g of crude material, which was taken up in dichloromethane (200 mL) and slurried with silica gel (40 g). After filtering, the solvent was removed to afford an oil (12 g) which was crystallized from hexanes (80 mL) to yield N-[4,4-dimethyl-2-[4-diethylaminophenyl]imino-3-oxopentanoyl]-2,4-dichloroaniline as an orange solid (7.1 g, 68% yield). The compound exhibited a maximum absorption in the visible region of the electromagnetic spectrum at 440 nm, ε=20,600. The structure of this compound was further confirmed by mass spectroscopy and by 1H and 13C NMR spectroscopy.
Reaction SMILES: [CH3:1][N:2]1[C:11]2[CH:10]=[C:9]([CH:12]=C)[CH:8]=[CH:7][C:6]=2[C:5]2=[N:14][O:15][C:16]([C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:18]=3[C:28]([F:31])([F:30])[F:29])=[C:4]2[CH2:3]1.[O:32]=[O+][O-].C(N(CC)CC)C>ClCCl>[CH3:1][N:2]1[C:11]2[CH:10]=[C:9]([CH:12]=[O:32])[CH:8]=[CH:7][C:6]=2[C:5]2=[N:14][O:15][C:16]([C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:18]=3[C:28]([F:31])([F:30])[F:29])=[C:4]2[CH2:3]1
Reactant: O=[O+][O-]
Reactant: C=Cc1ccc2c(c1)N(C)Cc1c-2noc1-c1onc(-c2ccccc2)c1C(F)(F)F
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CN1Cc2c(noc2-c2onc(-c3ccccc3)c2C(F)(F)F)-c2ccc(C=O)cc21
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
To a solution of 5-methyl-3-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-7-vinyl-4,5-dihydroisoxazolo[4,3-c]quinoline (Preparation 77F, 0.020 g, 0.047 mmol) in Dichloromethane (5 mL) at −78° C. was passed ozone from an ozone generator until the solution turned a deep blue. The reaction mixture then was purged with oxygen until the blue color disappeared, then with nitrogen for five minutes. The reaction mixture was allowed to warm to room temperature and triethylamine (5.07 μl, 0.036 mmol) was added. The reaction mixture was stirred at room temperature for fifteen minutes, and then concentrated under vacuum to give 5-methyl-3-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydroisoxazolo[4,3-c]quinoline-7-carbaldehyde as a tan solid. (0.015 mg, 0.035 mmol, 74%). The product had an HPLC ret. time=3.61 min. (condition B). LC/MS M+1=426.1 min
Reaction SMILES: P(Cl)(Cl)([Cl:3])=O.[Cl:6][C:7]1[CH:8]=[CH:9][C:10]2[NH:16][C:15](=O)[C:14]3=[CH:18][C:19]([CH3:21])=[CH:20][N:13]3[CH2:12][C:11]=2[CH:22]=1.CN(C)C1C=CC=CC=1>C1(OC)C=CC=CC=1>[Cl:6][C:7]1[CH:8]=[CH:9][C:10]2[N:16]=[C:15]([Cl:3])[C:14]3=[CH:18][C:19]([CH3:21])=[CH:20][N:13]3[CH2:12][C:11]=2[CH:22]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: Cc1cc2n(c1)Cc1cc(Cl)ccc1NC2=O
Solvent: COc1ccccc1
Solvent: CN(C)c1ccccc1
Product: Cc1cc2n(c1)Cc1cc(Cl)ccc1N=C2Cl
Temperature: 82.5 °C
Reaction time: 4 h
Yield: 90 %

Procedure:
Under a N2 atmosphere add phosphoryl chloride (124 g, 819 mmol) to a mixture of 7-chloro-2-methyl-5,10-dihydro-11H-pyrrolo[2,1-c][1,4]benzodiazepin-11-one (100 g, 405 mmol), N,N-dimethylaniline (138 g, 1.14 mol) and anisole (550 mL). Heat to 80-85° C. and stir for 4 hr. to 6 hr. Concentrate to a total of 1.5 volumes to 2.5 volumes while maintaining the temperature below 75° C. Cool to 15-25° C. Add dichloromethane (600 mL) dropwise and stir for 1 hr. Add the resulting mixture to water (600 mL) while maintaining the temperature between 10° C. and 35° C. Stir for 1 hr. and then separate the layers. Extract the aqueous layer with dichloromethane (600 mL). Wash the combined organic layers with 1.0 N HCl (600 g) followed by 7% NaHCO3 (600 g). Filter the organic layer through diatomite (20 g to 30 g) and silica gel (60 g to 100 g). Concentrate the resulting filtrate to a total of 1.5 volumes to 2.5 volumes while maintaining the temperature below 45° C. Add heptane (270 g to 410 g) and concentrate the resulting filtrate to a total of 1.5 volumes to 2.5 volumes while maintaining the temperature below 45° C. Add heptane (150 g to 210 g), cool to 5° C. to 10° C., and stir for 2 hr. to 3 hr. Filter, rinse the filter the cake with heptane, and dry under vacuum, at below 45° C., to obtain the title compound as a pale yellow solid (90% to 95% yield)
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@@H:18]([O:19][C:20](=[O:22])[CH3:21])[C@H:17]([O:23][C:24](=[O:26])[CH3:25])[CH2:16][S:15][C@H:6]1[O:7][C:8]1[CH:9]=[N:10][CH:11]=[C:12](Br)[CH:13]=1)(=[O:3])[CH3:2].[CH3:27][O:28][C:29]1[N:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1>>[C:1]([O:4][C@@H:5]1[C@@H:18]([O:19][C:20](=[O:22])[CH3:21])[C@H:17]([O:23][C:24](=[O:26])[CH3:25])[CH2:16][S:15][C@H:6]1[O:7][C:8]1[CH:9]=[N:10][CH:11]=[C:12]([C:32]2[CH:33]=[N:34][C:29]([O:28][CH3:27])=[CH:30][CH:31]=2)[CH:13]=1)(=[O:3])[CH3:2]
Reactant: COc1ccc(B(O)O)cn1
Reactant: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](OC(C)=O)CS[C@H]1Oc1cncc(Br)c1
Product: COc1ccc(-c2cncc(O[C@@H]3SC[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]3OC(C)=O)c2)cn1

Procedure:
By carrying out the operation analogously to example 1, starting from 5-bromo-3-pyridinyl 2,3,4-tri-O-acetyl-5-thio-β-D-xylopyranoside obtained according to preparation IX and 6-methoxy-3-pyridineboronic acid, the desired product is obtained in the form of a white solid (yield=72%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[CH2:9][N:10]1[C:22]2[CH:21]=[CH:20][CH:19]=[C:18]([OH:23])[C:17]=2[C:16]2[C:11]1=[CH:12][CH:13]=[CH:14][C:15]=2[C:24]([O:26]C)=O.[OH-].[NH4+:29]>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[CH2:9][N:10]1[C:22]2[CH:21]=[CH:20][CH:19]=[C:18]([OH:23])[C:17]=2[C:16]2[C:11]1=[CH:12][CH:13]=[CH:14][C:15]=2[C:24](=[O:26])[NH2:29]
Reactant: COC(=O)c1cccc2c1c1c(O)cccc1n2Cc1c(Cl)cccc1Cl
Reactant: [NH4+]
Agent: [OH-]
Solvent: C1CCOC1
Product: NC(=O)c1cccc2c1c1c(O)cccc1n2Cc1c(Cl)cccc1Cl
Yield: 65 %

Procedure:
A solution of the 9-[(2,6-dichlorophenyl)methyl]-4-hydroxy-5-carbomethoxy carbazole (240 mg, 0.6 mM) in 5 mL THF and 20 mL concentrated aqueous ammonium hydroxide was stirred at room temperature for 22 hours. The resultant precipitate was collected by filtration and dried in vacuo to afford 151 mg (65%) of the 9-[(2,6-dichlorophenyl)methyl]-4-hydroxy-5-carbamoyl carbazole as a yellow solid. 1H NMR (DMSO-d6) δ 10.35 (s, 1H), 8.8 (br s, 1H), 8.4 (br s, 1H), 7.7 (d, 1H, J=8 Hz), 7.6-7.3 (m, 5H), 7.25 (t, 1H, J=8 Hz), 6.85 (d, 1H, J=8 Hz), 6.55 (d, 1H, J=8 Hz), and 5.85 (s, 2H). IR (KBr, cm−1) 3429, 1631, and 1597. MS (ES) m/e 385, 387.
Reaction SMILES: [H-].[Na+].CN1C(=O)N(C)CCC1.[CH2:12]([OH:17])[C:13]#[C:14][CH2:15][OH:16].[CH:18]([C:21]1[CH:22]=[CH:23][C:24]([S:27]([NH:30][C:31]2[C:36]([C:37]3[CH:42]=[CH:41][C:40]([CH3:43])=[CH:39][CH:38]=3)=[C:35](Cl)[N:34]=[C:33]([C:45]3[CH:50]=[CH:49][N:48]=[CH:47][CH:46]=3)[N:32]=2)(=[O:29])=[O:28])=[N:25][CH:26]=1)([CH3:20])[CH3:19]>CN(C=O)C>[CH:18]([C:21]1[CH:22]=[CH:23][C:24]([S:27]([NH:30][C:31]2[C:36]([C:37]3[CH:42]=[CH:41][C:40]([CH3:43])=[CH:39][CH:38]=3)=[C:35]([O:16][CH2:15][C:14]#[C:13][CH2:12][OH:17])[N:34]=[C:33]([C:45]3[CH:46]=[CH:47][N:48]=[CH:49][CH:50]=3)[N:32]=2)(=[O:28])=[O:29])=[N:25][CH:26]=1)([CH3:20])[CH3:19]
Reactant: Cc1ccc(-c2c(Cl)nc(-c3ccncc3)nc2NS(=O)(=O)c2ccc(C(C)C)cn2)cc1
Reactant: OCC#CCO
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CN1CCCN(C)C1=O
Product: Cc1ccc(-c2c(NS(=O)(=O)c3ccc(C(C)C)cn3)nc(-c3ccncc3)nc2OCC#CCO)cc1

Procedure:
To a slurry of 0.34 g of sodium hydride in 15 ml of DMF and 4 ml of DMPU 2.4 g of 2-butyne-1,4-diol was added at room temperature. The mixture was stirred until no more gas evolved. Then 0.67 g of 5-isopropyl-N-[6-chloro-5-(p-tolyl)-2-(4-pyridyl)-4-pyrimidinyl]-2-pyridine sulfonamide was added and the mixture was stirred at 90° C. for 48 h. The solvent was removed in vacuo and the residue was taken up in 100 ml of 10% aqueous acetic acid. The mixture was extracted three times with 100 ml of ethyl acetate. The combined organic layers were washed with water and brine, dried over MgSO4 and evaporated. The resulting brown oil was purified by column chromatography on silica gel eluting with DCM containing 4-10% of methanol. This furnished a fraction which after recrystallisation from DCM: ethyl acetate gave 43 mg of 5-isopropyl-N-[6-(4-hydroxy-2-butynyloxy)-5-(p-tolyl)-2-(4-pyridyl)-4-pyrimidinyl]-2-pyridine sulfonamide as pale yellow crystals. A second fraction gave 456 mg of 5-isopropyl-N-[6-(4-hydroxy-2-butynyloxy)-5-(p-tolyl)-2-(4-pyridyl)-4-pyrimidinyl]-2-pyridine sulfonamide with about 90% purity as a brown oil. LC-MS: tR=4.53 min, [M+1]+=530.23, [M−1]−=528.21.