Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][CH:2]([NH:4][C:5]([CH:7]1[CH:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[O:8]1)=[O:6])[CH3:3].[CH3:16][O:17][C:18]1[CH:19]=[C:20](O)[CH:21]=[CH:22][CH:23]=1.[H-].[Na+].C1OCCOCCOCCOCCOCC[O:29]C1>C(#N)C>[OH:29][CH:7]([CH:9]([O:8][C:22]1[CH:21]=[CH:20][CH:19]=[C:18]([O:17][CH3:16])[CH:23]=1)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[C:5]([NH:4][CH:2]([CH3:1])[CH3:3])=[O:6]
Reactant: CC(C)NC(=O)C1OC1c1ccccc1
Reactant: C1COCCOCCOCCOCCOCCO1
Reactant: COc1cccc(O)c1
Agent: [H-]
Agent: [Na+]
Solvent: CC#N
Product: COc1cccc(OC(c2ccccc2)C(O)C(=O)NC(C)C)c1

Procedure:
This compound was prepared from N-(1-methylethyl)-3-phenyl-2-oxiranecarboxamide (10.3 g.), m-methoxyphenol (6.2 g.), sodium hydride (50% oil dispersion, 2.4 g.), 18-crown-6 (1.5 g.) and acetonitrile (500 ml.) as described in Example 12. The crude product (m.p. 118°-120°, yield 2.6 g.) was then recrystallized from ether with a small amount of tetrahydrofuran, giving 2.3 g. of the pure product, m.p. 132°-133°.
Reaction SMILES: [NH:1]([C:3]1[N:8]=[CH:7][CH:6]=[CH:5][N:4]=1)[NH2:2].C(N(CC)CC)C.C[O:17][C:18](=O)[N:19]=[C:20](SC)[C:21]([C:35]1[C:36]([F:47])=[C:37]2[C:42](=[C:43]([O:45][CH3:46])[CH:44]=1)[O:41][CH2:40][CH2:39][CH2:38]2)=[N:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[N:33]=[C:32]([CH3:34])[O:31][N:30]=2)=[CH:25][CH:24]=1>CN(C=O)C>[F:47][C:36]1[C:35]([CH:21]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([C:29]3[N:33]=[C:32]([CH3:34])[O:31][N:30]=3)=[CH:25][CH:24]=2)[C:20]2[NH:19][C:18](=[O:17])[N:1]([C:3]3[N:8]=[CH:7][CH:6]=[CH:5][N:4]=3)[N:2]=2)=[CH:44][C:43]([O:45][CH3:46])=[C:42]2[C:37]=1[CH2:38][CH2:39][CH2:40][O:41]2
Reactant: NNc1ncccn1
Reactant: COC(=O)N=C(SC)C(=Nc1ccc(-c2noc(C)n2)cc1)c1cc(OC)c2c(c1F)CCCO2
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COc1cc(C(Nc2ccc(-c3noc(C)n3)cc2)c2nn(-c3ncccn3)c(=O)[nH]2)c(F)c2c1OCCC2
Temperature: 85 °C
Reaction time: 8 h
Yield: 74 %

Procedure:
After adding 23 mg of 2-hydrazinopyrimidine and 35 μl of triethylamine to a solution of 113 mg of [2-(5-fluoro-8-methoxychroman-6-yl)-2-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylimino]-1-methylsulfanylethylidene]carbamic acid methyl ester in 2 ml of DMF, the mixture was stirred overnight at 85° C. under a nitrogen atmosphere. The reaction mixture was concentrated, and the residue was dissolved in 5 ml of methanol and 0.5 ml of acetic acid. After adding 100 mg of sodium cyanotrihydroborate to the reaction mixture it was stirred at room temperature for 1 hour. Water was added to the reaction mixture and extraction was performed with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. The desiccating agent was filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by NAM silica gel column chromatography (methanol-ethyl acetate) to give 5-{(5-fluoro-8-methoxychroman-6-yl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-2-pyrimidin-2-yl-2,4-dihydro-[1,2,4]triazol-3-one (82 mg) as a light brown solid.
Reaction SMILES: [CH3:1][N:2]1[C@H:11]2[C@@:6]([CH3:17])([C:7]3[CH:15]=[CH:14][C:13]([SH:16])=[CH:12][C:8]=3[CH2:9][CH2:10]2)[CH2:5][CH2:4][C:3]1=[O:18].C(=O)([O-])[O-].[K+].[K+].Cl[C:26]1[S:27][C:28]2[CH:34]=[CH:33][C:32]([N+:35]([O-:37])=[O:36])=[CH:31][C:29]=2[N:30]=1.CN(C)C=O>C(OCC)(=O)C>[CH3:1][N:2]1[C@H:11]2[C@@:6]([CH3:17])([C:7]3[CH:15]=[CH:14][C:13]([S:16][C:26]4[S:27][C:28]5[CH:34]=[CH:33][C:32]([N+:35]([O-:37])=[O:36])=[CH:31][C:29]=5[N:30]=4)=[CH:12][C:8]=3[CH2:9][CH2:10]2)[CH2:5][CH2:4][C:3]1=[O:18]
Reactant: CN1C(=O)CC[C@]2(C)c3ccc(S)cc3CC[C@@H]12
Reactant: O=[N+]([O-])c1ccc2sc(Cl)nc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CN1C(=O)CC[C@]2(C)c3ccc(Sc4nc5cc([N+](=O)[O-])ccc5s4)cc3CC[C@@H]12
Yield: 58.1 %

Procedure:
A 15 mL round bottom flask was charged with (+)-(4aR)-(10bR)-4-methyl-8-mercapto-10b-methyl-1,2,3,4,4a,5,6,10b-octahydrobezo[f]quinolin-3-one (100 mg, 0.38 mmol), potassium carbonate (158 mg, 1.14 mmol), 2-chloro-5-nitrobenzothiazole (99 mg, 0.46 mmol) and 1 mL of anhydrous dimethylformamide, fitted with a reflux condenser, and the stirred mixture was heated at 60°, under nitrogen, for 18 h. The mixture was cooled, diluted with ethyl acetate (75 mL) and washed with brine (2×25 mL). The combined organic extracts were dried over sodium sulfate, concentrated, and purified by silica gel chromatography (ethyl acetate eluent) to give 97 mg (58%) of the title compound as an amorphous solid. mp 96°-100°. FDMS: m/e=439. α[D]589 =+61.35 (c=0.64, chloroform).
Reaction SMILES: [C:1]([OH:10])(=[O:9])[C@@H:2]([C@H:4]([C:6]([OH:8])=[O:7])[OH:5])[OH:3].[ClH:11].[CH3:12][CH2:13][CH:14]([N:16]1[N:21]=[CH:20][N:19]([C:22]2[CH:27]=[CH:26][C:25]([N:28]3[CH2:33][CH2:32][N:31]([C:34]4[CH:39]=[CH:38][C:37]([O:40][CH2:41][C@@H:42]5[O:46][C@:45]([C:53]6[CH:58]=[CH:57][C:56]([Cl:59])=[CH:55][C:54]=6[Cl:60])([CH2:47][N:48]6[N:52]=[CH:51][N:50]=[CH:49]6)[O:44][CH2:43]5)=[CH:36][CH:35]=4)[CH2:30][CH2:29]3)=[CH:24][CH:23]=2)[C:17]1=[O:18])[CH3:15].COC(C)(C)C>O1CCOCC1>[CH3:12][CH2:13][CH:14]([N:16]1[N:21]=[CH:20][N:19]([C:22]2[CH:27]=[CH:26][C:25]([N:28]3[CH2:33][CH2:32][N:31]([C:34]4[CH:39]=[CH:38][C:37]([O:40][CH2:41][C@@H:42]5[O:46][C@:45]([C:53]6[CH:58]=[CH:57][C:56]([Cl:59])=[CH:55][C:54]=6[Cl:60])([CH2:47][N:48]6[N:52]=[CH:51][N:50]=[CH:49]6)[O:44][CH2:43]5)=[CH:36][CH:35]=4)[CH2:30][CH2:29]3)=[CH:24][CH:23]=2)[C:17]1=[O:18])[CH3:15].[ClH:11].[C:1]([OH:10])(=[O:9])[CH:2]([CH:4]([C:6]([OH:8])=[O:7])[OH:5])[OH:3]
Reactant: O=C(O)[C@H](O)[C@@H](O)C(=O)O
Agent: CCC(C)n1ncn(-c2ccc(N3CCN(c4ccc(OC[C@H]5CO[C@](Cn6cncn6)(c6ccc(Cl)cc6Cl)O5)cc4)CC3)cc2)c1=O
Agent: Cl
Solvent: COC(C)(C)C
Solvent: C1COCCO1
Product: O=C(O)C(O)C(O)C(=O)O
Temperature: 25 °C

Procedure:
Co-crystals of itraconazole HCl and tartaric acid were prepared. Approximately 212.7 mg of L-tartaric acid and 118 microL of 37% HCl were dissolved in 25 mL of hot dioxane. This solution was added to 1.0 g of cis-itraconazole dissolved in 50 mL of hot dioxane with stirring. The mixture was heated until a clear solution formed and was then allowed to cool to room temperature. Upon cooling, 50 mL tert-butyl methyl ether was added and the crystals were harvested by vacuum filtration on a Buchner funnel with #4 Whatman filter paper. The crystals were washed 3 times with 5 mL aliquots of cold tert-butyl methyl ether and left to air dry. Approximately 573 mg of a crystalline form of cis-itraconazole HCl-tartaric acid (1:1:0.5) co-crystal were obtained. (See FIGS. 20 and 21)
Reaction SMILES: CS(O)(=O)=O.[NH2:6][CH2:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[C:13](=[O:17])[N:12]([CH:18]1[CH2:23][CH2:22][C:21](=[O:24])[NH:20][C:19]1=[O:25])[CH2:11]2.[Cl:26][C:27]1[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:28]=1[N:34]=[C:35]=[O:36].C(N(CC)CC)C.Cl>C(#N)C>[Cl:26][C:27]1[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:28]=1[NH:34][C:35]([NH:6][CH2:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[C:13](=[O:17])[N:12]([CH:18]1[CH2:23][CH2:22][C:21](=[O:24])[NH:20][C:19]1=[O:25])[CH2:11]2)=[O:36]
Reactant: O=C=Nc1ccc(Cl)cc1Cl
Reactant: NCc1ccc2c(c1)CN(C1CCC(=O)NC1=O)C2=O
Agent: CS(=O)(=O)O
Agent: Cl
Solvent: CC#N
Solvent: CCN(CC)CC
Product: O=C1CCC(N2Cc3cc(CNC(=O)Nc4ccc(Cl)cc4Cl)ccc3C2=O)C(=O)N1
Reaction time: 2 h
Yield: 95.4 %

Procedure:
To a stirred mixture of 3-(5-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione methane sulfonate (0.37 g, 1.0 mmol) and 2,4-dichlorophenylisocyanate (0.19 g, 1.0 mmol) in acetonitrile (10 mL), was added triethylamine (0.28 mL, 2.0 mmol) at room temperature under nitrogen. After 2 h, 1 N aq. HCl (15 mL) was added and the solids were isolated by filtration, washed with water (3×20 mL) and dried in vacuo to give 1-(2,4-dichloro-phenyl)-3-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-urea as a white solid (0.44 g, 96% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 10/90 to 90/10 CH3CN/0.1% H3PO4 gradient over 15 mins, 8.99 min (96.51%); mp: 265-267° C.; 1H NMR (DMSO-d6) δ 1.89-2.06 (m, 1H, CHH), 2.29-2.47 (m, 1H, CHH), 2.54-2.70 (m, 1H, CHH), 2.78-3.06 (m, 1H, CHH), 4.32 (d, J=17.4 Hz, 1H, CHH), 4.38-4.53 (m, 3H, CHH, CH2), 5.11 (dd, J=5.0, 13.3 Hz, 1H, CH), 7.33 (dd, J=2.5, 9.1 Hz, 1H, Ar), 7.46 (d, J=7.7 Hz, 1H, Ar), 7.53 (s, 1H, Ar), 7.57 (d, J=2.5 Hz, 1H, Ar), 7.62 (t, J=5.8 Hz, 1H, NH), 7.71 (d, J=7.7 Hz, 1H, Ar), 8.20 (d, J=8.9 Hz, 1H, Ar), 8.26 (s, 1H, NH), 10.99 (br. s., 1H, NH); 13C NMR (DMSO-d6) δ 22.49, 31.20, 42.82, 47.13, 51.58, 121.63, 121.92, 122.02, 123.04, 125.33, 126.99, 127.50, 128.39, 130.45, 135.81, 142.48, 144.12, 154.67, 167.90, 170.99, 172.86; LCMS: MH=461/463/465; Anal Calcd for C21H18N4O4Cl2: C, 54.68; H, 3.93; N, 12.15; Cl, 15.37. Found: C, 54.37; H, 3.84; N, 12.15; Cl, 15.50.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][C:14]([OH:16])=O)=[CH:9][CH:8]=1.O.ON1C2C=CC=CC=2N=N1.CNCC1[S:32][C:33]([S:36]([NH2:39])(=[O:38])=[O:37])=CN=1.Cl.CN(C)CC[CH2:45][N:46]=[C:47]=[N:48][CH2:49][CH3:50]>CN(C)C=O>[NH2:39][S:36]([C:33]1[S:32][C:47]([N:46]([CH3:45])[C:14](=[O:16])[CH2:13][C:10]2[CH:9]=[CH:8][C:7]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)=[CH:12][CH:11]=2)=[N:48][C:49]=1[CH3:50])(=[O:38])=[O:37]
Reactant: CNCc1ncc(S(N)(=O)=O)s1
Reactant: O=C(O)Cc1ccc(-c2ccccn2)cc1
Reactant: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CN(C)C=O
Product: Cc1nc(N(C)C(=O)Cc2ccc(-c3ccccn3)cc2)sc1S(N)(=O)=O
Temperature: 25 °C
Reaction time: 18 h

Procedure:
At room temperature, 300 mg (1.41 mmol) of [4-(2-pyridinyl)phenyl]acetic acid and 190 mg (1.41 mmol) of 1-hydroxy-1H-benzotriazole hydrate are initially charged in 4 ml of dimethylformamide. 307 mg (1.48 mmol) of 2-methylaminomethyl-1,3-thiazole-5-sulphonamide and 284 mg (1.48 mmol) of N′-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride are added, and the mixture is stirred at room temperature for 18 h. The solvent is then removed under reduced pressure, the residue is taken up in toluene and the solvent is once more removed under reduced pressure. The residue is stirred with 15 ml of water and 3 ml of methanol and then filtered off, and the filtrate is re-extracted with 20 ml of dichloromethane. Solid and dichloromethane phase are combined and the solvent is removed under reduced pressure. This gives the compound of Example 38 in the form of a white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[CH:12](O)[C:13]1[S:14][CH:15]=[CH:16][CH:17]=1)[O:8][CH:7]([C:19]([F:22])([F:21])[F:20])[C:6]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:5]2.C([SiH](CC)CC)C.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>C(Cl)Cl.O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[CH2:12][C:13]1[S:14][CH:15]=[CH:16][CH:17]=1)[O:8][CH:7]([C:19]([F:22])([F:21])[F:20])[C:6]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:5]2
Reactant: CCOC(=O)C1=Cc2cc(Cl)c(C(O)c3cccs3)cc2OC1C(F)(F)F
Agent: CC[SiH](CC)CC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: O
Solvent: ClCCl
Product: CCOC(=O)C1=Cc2cc(Cl)c(Cc3cccs3)cc2OC1C(F)(F)F
Temperature: 25 °C
Reaction time: 24 h

Procedure:
The crude oil from Example 170 Step 2 was dissolved in I mL of DCM. To this solution was added triethylsilane (41 μL, 0.26 mmol) and 20 μL of TFA and stirred at 25° C. After 24 h, the solution was stirred vigorously with solid NaHCO3 and H2O, which quenched the reaction. Stirring was stopped after 5 min, and the solution was allowed to separate into layers. The reaction mixture stood in this state for one day prior to workup. The organic layer was dried over MgSO4, filtered, and evaporated under reduced pressure to give an orange oil. The crude product was purified by flash chromatography to give reasonably pure compound.
Reaction SMILES: [NH2:1][C@@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([C:14]([O:16][CH3:17])=[O:15])[CH2:3]1.C(N(CC)CC)C.[C:25](Cl)(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.O>O1CCCC1>[C:25]([NH:1][C@@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:11])([CH3:12])[CH3:13])=[O:8])[C@H:4]([C:14]([O:16][CH3:17])=[O:15])[CH2:3]1)(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: COC(=O)[C@@H]1C[C@H](N)CN1C(=O)OC(C)(C)C
Reactant: O=C(Cl)c1ccccc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Solvent: O
Product: COC(=O)[C@@H]1C[C@H](NC(=O)c2ccccc2)CN1C(=O)OC(C)(C)C
Reaction time: 1 h

Procedure:
Methyl (2S,4S)-4-amino-1-tert-butoxycarbonylpyrrolidine-2-carboxylate [product of Reference Example 5(3), 2.4 g] and triethylamine (2.0 mL) were dissolved in tetrahydrofuran (20 mL), and benzoyl chloride (1.1 mL) was added thereto. The mixture was stirred for 1 hr. The reaction mixture was added to water and extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogencarbonate solution and dried. The solvent was evaporated under reduced pressure and the residue was purified by silica gel chromatography to give methyl (2S,4S)-4-benzoylamino-1-tert-butoxycarbonylpyrrolidine-2-carboxylate (1.63 g) as a white solid.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[C:17]([CH3:19])([CH3:18])[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:20]([O:22][CH3:23])=[O:21])[CH:14]=2)[NH:9]1.[F:24][C:25]1[CH:26]=[C:27]([S:31](Cl)(=[O:33])=[O:32])[CH:28]=[CH:29][CH:30]=1>N1C=CC=CC=1.ClCCl>[F:24][C:25]1[CH:26]=[C:27]([S:31]([NH:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[CH:8]2[C:17]([CH3:18])([CH3:19])[CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:20]([O:22][CH3:23])=[O:21])[CH:14]=3)[NH:9]2)(=[O:33])=[O:32])[CH:28]=[CH:29][CH:30]=1
Reactant: COC(=O)c1ccc2c(c1)CC(C)(C)C(c1ccccc1N)N2
Reactant: O=S(=O)(Cl)c1cccc(F)c1
Solvent: ClCCl
Solvent: c1ccncc1
Product: COC(=O)c1ccc2c(c1)CC(C)(C)C(c1ccccc1NS(=O)(=O)c1cccc(F)c1)N2
Temperature: 25 °C
Reaction time: 6 h
Yield: 131.7 %

Procedure:
To a stirred solution of methyl 2-(2-aminophenyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinoline-6-carboxylate (1.0 g, 3.22 mmol, 1.0 eq.) in pyridine (5 mL) and dichloro methane (20 mL) at 0° C. was dropwise a solution of 3-fluorobenzene-1-sulfonyl chloride (940 mg, 4.83 mmol, 1.5 eq.) in dichloromethane (30 mL). The mixture was stirred at room temperature for 6 h. Thin layer chromatography and LC-MS showed reaction completed. The mixture was quenched with 50 mL water and extracted with ethyl acetate (100 mL×3). The combined organic layers were dried over anhydrous sodium sulfate and evaporated to afford 1.987 g of methyl 2-(2-(3-fluorophenylsulfonamido)phenyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinoline-6-carboxylate (pyridine included) as light yellow solid, which was used in next step without further purification.
Reaction SMILES: [CH2:1]([CH:8]1[O:12][C:11](=[O:13])[CH:10]=[C:9]1[OH:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:15](=O)[CH2:16][CH2:17][CH2:18][CH3:19].[NH:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23]([CH2:30][CH2:31][NH:32][C:33](=[O:35])[CH3:34])=[CH:22]1>>[CH2:1]([CH:8]1[O:12][C:11](=[O:13])[C:10]([CH:15]([C:22]2[NH:21][C:29]3[C:24]([C:23]=2[CH2:30][CH2:31][NH:32][C:33](=[O:35])[CH3:34])=[CH:25][CH:26]=[CH:27][CH:28]=3)[CH2:16][CH2:17][CH2:18][CH3:19])=[C:9]1[OH:14])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCCCC=O
Reactant: CC(=O)NCCc1c[nH]c2ccccc12
Reactant: O=C1C=C(O)C(Cc2ccccc2)O1
Product: CCCCC(C1=C(O)C(Cc2ccccc2)OC1=O)c1[nH]c2ccccc2c1CCNC(C)=O

Procedure:
Using general procedure C, 5-benzyl-4-hydroxy-5H-furan-2-one (Lit. 13) was reacted with pentanal and N-[2-(1H-indol-3-yl)-ethyl]-acetamide) to give the title compound as a white solid. MS: 459.3 ([M−H]−).
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][CH:6]=1)(=[O:4])=[O:3].CN(C)C=O.C(Cl)(=O)C(Cl)=O.[CH3:25][C:26]1[O:30][C:29]([CH:31]([NH:33][OH:34])[CH3:32])=[CH:28][CH:27]=1.C(N(CC)CC)C.Cl>C(Cl)Cl>[OH:34][N:33]([CH:31]([C:29]1[O:30][C:26]([CH3:25])=[CH:27][CH:28]=1)[CH3:32])[C:9](=[O:11])[C:8]1[CH:7]=[CH:6][C:5]([S:2]([CH3:1])(=[O:3])=[O:4])=[CH:13][CH:12]=1
Reactant: CS(=O)(=O)c1ccc(C(=O)O)cc1
Reactant: Cc1ccc(C(C)NO)o1
Agent: Cl
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: Cc1ccc(C(C)N(O)C(=O)c2ccc(S(C)(=O)=O)cc2)o1
Temperature: 0 °C
Reaction time: 1 h
Yield: 22.7 %

Procedure:
To a solution of 4-(methylsulfonyl) benzoic acid (3.1 g, 15.5 mmol) in 100 mL of methylene chloride was added dimethylformamide (1.2 mL, 15.5 mmol). The reaction vessel was cooled to 0° C. and oxalyl chloride (3.1 mL, 35 mmol) was added. The mixture stirred 1 h at 0° C. and was added to a solution of N-(1-(5-methyl-fur-2-yl)ethyl) hydroxylamine (2.6 g, 18.6 mmol) and triethylamine (3.3 mL, 23.3 mmol) in 75 mL methylene chloride at 0° C. The mixture stirred 1.5 h and was poured into 2M HCl (100 mL). The aqueous layer was extracted with methylene chloride (3×, 100 mL) and the combined organic extract was washed with saturated sodium bicarbonate solution (1×100 mL) and brine (1×100 mL). The solution was dried over MgSO4, filtered and evaporated. The material was recrystallized from ethyl acetate to yield 1.14 g of a white solid; m.p.=177° C.; 1H NMR (300 MHz, DMSO-d6) 9.85 (bs, 1H), 7.97 (d, J=8.41 Hz, 2H), 7.83 (d, J=9.01 Hz, 2H), 6.24 (d, J=3.60 Hz, 1H), 6.02 (m, 1H), 5.71 (bs, 1H), 3.26 (s, 3H), 2.24 (s, 3H), 1.47 (d, J=6.91 Hz, 3H). MS (M+H)+ =324; Analysis calc'd for C15H17NO5 : C, 55.20; H, 5.25; N, 4.29. Found: C, 55.07; H, 5.20; N, 4.23.
Reaction SMILES: CN(C)[CH:3]=[CH:4][C:5]([C:7]1[C:12](=[O:13])[C:11]([O:14][CH3:15])=[CH:10][N:9]([C:16]2[CH:21]=[CH:20][C:19]([N:22]3[CH:26]=[CH:25][CH:24]=[N:23]3)=[CH:18][C:17]=2[O:27][CH3:28])[N:8]=1)=O.[F:30][C:31]([F:41])([F:40])[C:32]1[CH:33]=[C:34]([NH:38][NH2:39])[CH:35]=[CH:36][CH:37]=1.C(O)(C(F)(F)F)=O>C(O)C>[CH3:15][O:14][C:11]1[C:12](=[O:13])[C:7]([C:5]2[N:38]([C:34]3[CH:35]=[CH:36][CH:37]=[C:32]([C:31]([F:40])([F:41])[F:30])[CH:33]=3)[N:39]=[CH:3][CH:4]=2)=[N:8][N:9]([C:16]2[CH:21]=[CH:20][C:19]([N:22]3[CH:26]=[CH:25][CH:24]=[N:23]3)=[CH:18][C:17]=2[O:27][CH3:28])[CH:10]=1
Reactant: NNc1cccc(C(F)(F)F)c1
Reactant: COc1cc(-n2cccn2)ccc1-n1cc(OC)c(=O)c(C(=O)C=CN(C)C)n1
Solvent: CCO
Solvent: O=C(O)C(F)(F)F
Product: COc1cc(-n2cccn2)ccc1-n1cc(OC)c(=O)c(-c2ccnn2-c2cccc(C(F)(F)F)c2)n1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a suspension of 3-[3-(dimethylamino)prop-2-enoyl]-5-methoxy-1-[2-methoxy-4-(1H-pyrazol-1-yl)phenyl]pyridazin-4(1H)-one (136 mg) in ethanol (1.5 mL) was added dropwise a solution of 3-(trifluoromethyl)phenylhydrazine (0.049 mL) and TFA (0.15 mL) in ethanol (1.5 mL), and the mixture was stirred at room temperature for 3 hr. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (NH, ethyl acetate), and recrystallized from ethanol/water to give the title compound (123 mg).
Reaction SMILES: [NH2:1][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([C:19]#[N:20])[C:3]=1[S:21]([C:24]([F:27])([F:26])[F:25])(=[O:23])=[O:22].Cl.[NH2:29][OH:30].C(N(CC)CC)C.[Cl-].[Na+]>O1CCOCC1.O>[NH2:1][C:2]1[N:6]([C:7]2[C:8]([Cl:18])=[CH:9][C:10]([C:14]([F:16])([F:17])[F:15])=[CH:11][C:12]=2[Cl:13])[N:5]=[C:4]([C:19](=[N:29][OH:30])[NH2:20])[C:3]=1[S:21]([C:24]([F:26])([F:25])[F:27])(=[O:23])=[O:22]
Reactant: NO
Reactant: N#Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c(N)c1S(=O)(=O)C(F)(F)F
Agent: Cl
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Solvent: CCN(CC)CC
Product: NC(=NO)c1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c(N)c1S(=O)(=O)C(F)(F)F
Temperature: 25 °C
Yield: 88.4 %

Procedure:
5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulfonylpyrazole (0.86 g, 1.90 mmol) was dissolved in 10 ml of 1,4-dioxane and hydroxylamine hydrochloride (0.22 g, 3.17 mmol) and triethylamine (0.45 ml, 3.24 mmol) were added, and then the mixture was stirred at room temperature. Ten hours after stirring, hydroxyamine hydrochloride (0.08 g, 1.2 mmol) and triethylamine (0.14 ml, 1.01 mmol) were further added. After the completion of adding, the solution was stirred at room temperature for 23 hours. Thirty milliliters of water and 15 ml of an aqueous saturated sodium chloride solution were added and then the reaction mixture was extracted twice with 30 ml of ethyl acetate. The ethyl acetate layer was washed with 20 ml of an aqueous saturated sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent was distilled off to obtain a colorless crystal. This crystal was washed with a hexane-ethyl acetate mixed solvent (volume ratio=1:1) to obtain 0.82 g (1.68 mmol) of the title compound as a colorless crystal. Yield 89%.
Reaction SMILES: [CH2:1](O)[CH:2]=[CH:3][CH2:4][CH2:5][CH2:6][CH2:7]CCCC.O[CH2:14][CH:15]=[CH:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]([O:26][CH3:27])=[O:25]>>[C:24]([O:26][CH3:27])(=[O:25])[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]/[CH:16]=[CH:15]\[CH2:14][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].[C:24]([OH:26])([OH:25])=[CH:23][CH2:22][CH3:21]
Reactant: CCCCCCCCC=CCO
Reactant: COC(=O)CCCCCCCC=CCO
Product: CCC=C(O)O
Product: CCCCCCCC/C=C\CCCCCCCC(=O)OC

Procedure:
A mixture of 2-undecen-1-ol and methyl 11-hydroxy-9-undecenoate (0.5 ml, obtained from the cross-metathesis of methyl oleate with butenediol; composition: 8.7% methyl oleate, 13.2% 9-octadecene and 1,18-dimethyl-9-octadecenedicarboxylic acid, 61.2% alcohol cross-metathesis products, 16.9% aldehyde cross-metathesis products) and 4.5 ml of ethylene glycol are combined. Further samples are taken for GC, GC-MS and GPC. By means of a magnetic stirrer, the reaction mixture is stirred at 120° C. for 60 minutes. After 5, 30 and 60 minutes the samples for GC, GC-MS and GPC measurements are taken and the reaction is stopped. Conversion of both alcohol cross-metathesis products after 60 minutes: 90%. Total yield (over two steps) of the 2-decyl-[1,3]dioxolane (protected undecanal): 67%; total yield (over two steps) of the methyl undecanoate-11-[1,3]dioxolane (protected methyl 11-oxoundecanoate): 69%; by-products (oligomers): 5%.
Reaction SMILES: [CH:1]1([N:7]=[C:8]=[N:9][CH:10]2[CH2:15][CH2:14][CH2:13]CC2)CCCCC1.[CH2:16](O)C>>[CH3:16][N:7]([C:8]1[CH:13]=[CH:14][CH:15]=[CH:10][N:9]=1)[CH3:1]
Reactant: C(=NC1CCCCC1)=NC1CCCCC1
Reactant: CCO
Product: CN(C)c1ccccn1

Procedure:
Alternatively, a compound of the formula XXXII may be esterified by reaction with ethanol in the presence of dicyclohexylcarbodiimide and a catalyst such as dimethylaminopyridine to give a compound of the formula ##STR73##
Reaction SMILES: [CH:1]([Cl:10])([F:9])[C:2]([F:8])([F:7])[C:3]([Cl:6])([F:5])[F:4].[H][H]>>[CH2:1]([F:9])[C:2]([F:8])([F:7])[CH:3]([F:5])[F:4].[CH:1]([Cl:10])([F:9])[C:2]([F:8])([F:7])[C:3]([Cl:6])([F:5])[F:4]
Reactant: [H][H]
Agent: FC(Cl)C(F)(F)C(F)(F)Cl
Product: FCC(F)(F)C(F)F

Procedure:
HCFC-225cb was reduced using the reactor and procedures of Example 2 except that the catalyst was prepared from 0.5% Pd/alumina mixed with 50 cc glass helices. The organics flow rate was 4 cc/hr. with a hydrogen flow rate of 90±10 cc/min. The temperature was maintained at 190°±3° C. for 144 hours. HFC-245ca in an 87-92% selectivity and greater than 98% conversion of HCFC-225cb resulted. As the data from Example 4, shown on Table I below indicate, the Pd/alumina catalyst is stable for 144 hours towards the reduction of HCFC-225cb to HFC-245ca.