Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:9])[CH:5]([F:8])[CH2:6][OH:7])[CH3:2].N1C=CN=C1.[Si:15](Cl)([C:28]([CH3:31])([CH3:30])[CH3:29])([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.O.C(=O)(O)[O-].[Na+]>ClCCl>[CH2:1]([O:3][C:4](=[O:9])[CH:5]([F:8])[CH2:6][O:7][Si:15]([C:28]([CH3:31])([CH3:30])[CH3:29])([C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH3:2]
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Reactant: CCOC(=O)C(F)CO
Agent: O=C([O-])O
Agent: [Na+]
Agent: c1c[nH]cn1
Solvent: ClCCl
Solvent: O
Product: CCOC(=O)C(F)CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A crude product of 2-fluoro-3-hydroxypropionic acid ethyl ester (13.06 g) was dissolved in dichloromethane (300 ml). Imidazole (17.2 g, 252.57 mmol) and tert-butyldiphenylsilyl chloride (25 ml, 96.14 mmol) were added to the solution under cooling on ice, and the reaction solution was stirred for 18 hours while raising the reaction solution temperature to room temperature. Saturated sodium bicarbonate water was added to the reaction solution and the resultant was extracted with dichloromethane. The extract was dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to yield 17.98 g (three steps, 57%) of the title compound in the form of a colorless clear oily product.
Reaction SMILES: [CH2:1]([N:3]([CH2:17][CH3:18])[CH2:4][CH2:5][CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-])=O)=[CH:10][CH:9]=1)[CH3:2].O.NN>C(O)C.[Ni]>[CH2:17]([N:3]([CH2:1][CH3:2])[CH2:4][CH2:5][CH2:6][O:7][C:8]1[CH:9]=[CH:10][C:11]([NH2:14])=[CH:12][CH:13]=1)[CH3:18]
Reactant: CCN(CC)CCCOc1ccc([N+](=O)[O-])cc1
Agent: [Ni]
Agent: NN
Solvent: O
Solvent: CCO
Product: CCN(CC)CCCOc1ccc(N)cc1
Temperature: 50 °C
Reaction time: 3 h

Procedure:
A solution of diethyl-[3-(4-nitro-phenoxy)-propyl]-amine (15.2 g, 60.4 mmol) is dissolved in absolute ethanol (350 mL) and to this solution is added hydrazine monohydrate (18 mL, 6 equiv.) followed by the addition of a small portion of Raney nickel. The reaction mixture is heated to 50° C. with stirring for 3 h until all gas evolution has ceased. The reaction mixture is filtered through celite to remove the Raney nickel. The filtrate is concentrated under reduced pressure to give the named compound as a greenish brown oil (quantitative). This material is carried on in subsequent steps without purification.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:15][CH2:14][CH:13]2[CH:10]([N:11](CC3C=CC=CC=3)[CH2:12]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>CCO.[OH-].[OH-].[Pd+2]>[C:1]([O:5][C:6]([N:8]1[CH2:15][CH2:14][CH:13]2[CH:10]([NH:11][CH2:12]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCC2CN(Cc3ccccc3)C2C1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CCO
Product: CC(C)(C)OC(=O)N1CCC2CNC2C1
Temperature: 50 °C
Reaction time: 48 h
Yield: 106.1 %

Procedure:
A mixture of 8-benzyl-3,8-diaza-bicyclo[4.2.0]octane-3-carboxylic acid tert-butyl ester (1.34 g, 4.44 mmol) and wet Pd(OH)2/C (20 wt %, 938 mg) in EtOH (30 mL) was shaken under 60 psi atmosphere of H2 for 2 days at 50° C. The reaction mixture was filtered and concentrated to give title compound (1.0 g, 94%). MS (ESI) mass calcd. for C11H20N2O2, 212.29; m/z found, 213.2 [M+H]+. 1H NMR (CDCl3): 4.32-4.0 (m, 1H), 3.93-3.17 (m, 5H), 3.10-2.70 (m, 3H), 1.98-1.67 (m, 2H), 1.56-1.36 (m, 9H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([CH2:29][CH2:30]CS([O-])(=O)=O)[CH2:13][CH2:12][N:11]([CH2:14][C:15]([C:17]3[CH:22]=[C:21]([O:23][CH3:24])[C:20]([O:25][CH3:26])=[C:19]([O:27][CH3:28])[CH:18]=3)=[O:16])[CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].Cl.[C:37]1([C:43]2([C:49]([NH2:51])=[O:50])[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]2)[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([CH2:29][CH2:30][N:46]3[CH2:45][CH2:44][C:43]([C:37]4[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=4)([C:49]([NH2:51])=[O:50])[CH2:48][CH2:47]3)[CH2:13][CH2:12][N:11]([CH2:14][C:15]([C:17]3[CH:18]=[C:19]([O:27][CH3:28])[C:20]([O:25][CH3:26])=[C:21]([O:23][CH3:24])[CH:22]=3)=[O:16])[CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: COc1cc(C(=O)CN2CCC(CCCS(=O)(=O)[O-])(c3ccc(Cl)c(Cl)c3)C2)cc(OC)c1OC
Reactant: NC(=O)C1(c2ccccc2)CCNCC1
Agent: Cl
Product: COc1cc(C(=O)CN2CCC(CCN3CCC(C(N)=O)(c4ccccc4)CC3)(c3ccc(Cl)c(Cl)c3)C2)cc(OC)c1OC

Procedure:
Prepare by the method of example 3.3 using 2-[3-(3,4-dichloro-phenyl)-1-(3,4,5-trimethoxy-phenacyl)-pyrrolidin-3-yl]-ethyl-methanesulfonate (0.6 mmol) and 4-phenyl-piperidine-4-carboxylic acid amide hydrochloride (0.72 mmol). Chromatograph on silica gel to give the title compound.
Reaction SMILES: B(F)(F)F.CCOCC.[OH:10][C:11]1[C:20]([CH3:21])=[C:19]2[C:14]([CH:15]=[C:16]([NH:23][C:24](=[O:33])[O:25][CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:17](=[O:22])[O:18]2)=[CH:13][C:12]=1[O:34][CH3:35].ClC(Cl)(Cl)C(=N)O[C@H:40]1[C@@H:45]2[O:46][C:47](=[O:49])[O:48][C@@H:44]2[C@@H:43]([O:50][CH3:51])[C:42]([CH3:53])([CH3:52])[O:41]1.C(N(CC)CC)C>C(Cl)Cl>[CH3:35][O:34][C:12]1[CH:13]=[C:14]2[C:19](=[C:20]([CH3:21])[C:11]=1[O:10][C@H:40]1[C@@H:45]3[O:46][C:47](=[O:49])[O:48][C@@H:44]3[C@@H:43]([O:50][CH3:51])[C:42]([CH3:53])([CH3:52])[O:41]1)[O:18][C:17](=[O:22])[C:16]([NH:23][C:24](=[O:33])[O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[CH:15]2
Reactant: COc1cc2cc(NC(=O)OCc3ccccc3)c(=O)oc2c(C)c1O
Reactant: CO[C@@H]1[C@H]2OC(=O)O[C@H]2[C@H](OC(=N)C(Cl)(Cl)Cl)OC1(C)C
Agent: FB(F)F
Solvent: CCOCC
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1cc2cc(NC(=O)OCc3ccccc3)c(=O)oc2c(C)c1O[C@@H]1OC(C)(C)[C@H](OC)[C@H]2OC(=O)O[C@@H]12
Temperature: 25 °C
Reaction time: 14 h
Yield: 95.1 %

Procedure:
Boron trifluoride etherate (5.30 μL, 0.042 mmol) was added to 23a (50.0 mg, 0.14 mmol) and (3aR,4S,7R,7aR)-7-methoxy-6,6-dimethyl-2-oxo-tetrahydro-3aH-[1.3]dioxolo[4,5-c]pyran-4-yl 2,2,2-trichloroacetimidate (171 mg, 0.47 mmol) in anhydrous CH2Cl2 (3.00 mL). After stirring at room temperature for 14 hours, triethylamine (150 μL) was added and the solvent was concentrated. The residue was purified via column chromatography (SiO2, 40:1 CH2Cl2:Acetone) to give 25a as a colorless foam (74.0 mg, 95%): 1H NMR (CD2Cl2, 400 MHz) δ 8.29 (s, 1H), 7.64 (s, 1H), 7.47-7.39 (m, 5H), 6.91 (s, 1H), 5.52 (d, J=3.4 Hz, 1H), 5.26 (s, 2H), 5.23 (dd, J=8.4, 3.5 Hz, 1H), 4.95 (t, J=8.2 Hz, 1H), 3.92 (s, 3H), 3.60 (s, 3H), 3.33 (d, J=8.0 Hz, 1H), 2.42 (s, 3H), 1.38 (s, 3H), 1.33 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 157.6, 152.7, 152.1, 148.1, 144.8, 141.8, 134.5, 127.8, 127.7, 127.5, 127.3, 122.3, 120.2, 119.8, 115.1. 109.6, 105.2, 98.3, 82.0, 77.1, 66.5, 65.5, 59.4, 57.4, 55.1, 26.0, 20.9, 8.9; IR (film) νmax 2957, 2928, 2854, 2359, 2341, 1817, 1709, 1522, 1464, 1389, 1371, 1205, 1174, 1111, 1072, 1034, 957, 800 cm−1; HRMS (ESI+) m/z: [M+H]+ calcd for C28H29NO11, 556.1819. found, 556.1822.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10](=O)[CH:11]=[CH:12][C:13]2[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][CH:14]=2)=[CH:6][CH:5]=1)([O-])=O.S(=O)(=O)(O)O>[C].[Pd].CO>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([CH2:10][CH2:11][CH2:12][C:13]2[CH:14]=[CH:15][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:21][CH:22]=2)=[CH:8][CH:9]=1
Reactant: COC(=O)c1ccc(C=CC(=O)c2ccc([N+](=O)[O-])cc2)cc1
Agent: [Pd]
Agent: O=S(=O)(O)O
Solvent: CO
Product: COC(=O)c1ccc(CCCc2ccc(N)cc2)cc1
Reaction time: 24 h
Yield: 67 %

Procedure:
To a mixture of 5.0 g of methyl 4-[3-(4-nitrophenyl)-3-oxoprop-1-en-1-yl]benzoate and 150 mL of methanol was added dropwise 5.0 mL of concentrated sulfuric acid under ice cooling. In an argon atmosphere, 500 mg of 10% palladium carbon was added to the reaction mixture. After hydrogen (3 atm) purging was performed at room temperature, the mixture was stirred for 24 hours. The insoluble material was removed by filtration by using celite, and then the filtrate was concentrated under reduced pressure. A saturated aqueous sodium hydrogen carbonate solution was added to the residue under ice cooling to neutralize the residue, and then extraction was performed using ethyl acetate. The organic layer was washed with water and saturated brine and then dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the obtained residue was purified by silica gel column chromatography (chloroform), thereby obtaining 2.9 g of methyl 4-[3-(4-aminophenyl)propyl]benzoate.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][C:9]2[C:10]3[CH:17]=[C:16]([C@@H:18]4[O:26][C@H:25]([CH2:27][OH:28])[C@@H:23]([OH:24])[C@H:21]([OH:22])[C@H:19]4[OH:20])[CH:15]=[CH:14][C:11]=3[S:12][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:30]([O:32][CH2:33][CH3:34])=[O:31].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CC1C=C(C)C=C(C)N=1>[C:1]1([CH2:7][CH2:8][C:9]2[C:10]3[CH:17]=[C:16]([C@@H:18]4[O:26][C@H:25]([CH2:27][O:28][C:30]([O:32][CH2:33][CH3:34])=[O:31])[C@@H:23]([OH:24])[C@H:21]([OH:22])[C@H:19]4[OH:20])[CH:15]=[CH:14][C:11]=3[S:12][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: OC[C@H]1O[C@@H](c2ccc3scc(CCc4ccccc4)c3c2)[C@H](O)[C@@H](O)[C@@H]1O
Reactant: CCOC(=O)Cl
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Solvent: Cc1cc(C)nc(C)c1
Product: CCOC(=O)OC[C@H]1O[C@@H](c2ccc3scc(CCc4ccccc4)c3c2)[C@H](O)[C@@H](O)[C@@H]1O
Temperature: 25 °C
Reaction time: 7 h

Procedure:
To a solution of 1-[3-(2-phenylethyl)benzo[b]-thiophen-5-yl]-1-deoxy-β-D-glucopyranose (0.19 g) in 2,4,6-trimethylpyridine (2 mL) was added ethyl chloroform ate (1.1 mL) at 0° C., and the mixture was stirred at room temperature for 7 hours. The reaction mixture was poured into 10% citric acid aqueous solution, and the mixture was extracted with ethyl acetate. The organic layer washed with brine and dried over anhydrous magnesium sulfate. The solvent was removed, and the residue was purified by column chromatography on silica gel (eluent: dichloromethane/methanol=20/1) to give the title compound (0.16 g).
Reaction SMILES: [C:1]([CH2:5][OH:6])([F:4])([F:3])[F:2].C(Cl)(Cl)(Cl)Cl.B(F)(F)F>O>[F:2][C:1]([O:6][CH2:5][C:1]([F:4])([F:3])[F:2])([F:4])[F:3]
Reactant: OCC(F)(F)F
Agent: FB(F)F
Solvent: O
Solvent: ClC(Cl)(Cl)Cl
Product: FC(F)(F)COC(F)(F)F
Temperature: 150 °C
Reaction time: 8 h
Yield: 63 %

Procedure:
Fifty grams (0.50 mol) of CF3CH2OH, 192 g (1.25 mol) of CCl4, 280 g (14 mol) of HF, and 7 g (0.1 mol) of BF3 were charged to a 1.2 liter metal tube and the mixture was agitated at 150° C. and autogeneous pressure for 8 hours. The tube was cooled and 300 mL of water was pumped in. The tube was brought to room temperature and volatiles (108.6 g) were transferred under vacuum to a 1 liter stainless steel cylinder fitted with a needle valve. The contents of the cylinder were held at 25° C. while low boilers were transferred out at 1 atmosphere and distilled from CaCl2 through a low-temperature still. A 2.5 mL foreshot having a boiling point range of -14° to 2.5° C., largely CF2Cl2, was followed by 62.7 g of product, boiling point range of 2.5° to 15° C. (mainly 8° to 9° C.), then 8 mL with a boiling point range of 15° to 23.5° C., largely CFCl3. The main product cut was shown by NMR and GC/MS to be 84% CF3CH2OCF3 with 6% CF2Cl2 and 10% CFCl3 also present, so that 2,2,2-trifluoroethyl trifluoromethyl ether was obtained in 63% yield, 52.7 g.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([N+:9]([O-])=O)=[C:6]([CH:8]=1)[NH2:7].[C:12](=S)=[S:13].[OH-].[K+].O>CO.C(O)C.C(O)(=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:12]([SH:13])[NH:7][C:6]=2[CH:8]=1
Reactant: Nc1cc(Br)ccc1[N+](=O)[O-]
Reactant: S=C=S
Agent: [K+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: CO
Solvent: CCO
Product: Sc1nc2ccc(Br)cc2[nH]1

Procedure:
6.7 g of 4-bromo-1,2-benzenediamine obtained by reducing 5-bromo-2-nitroaniline was dissolved in 50 mL methanol, then 4.4 mL carbon disulfide was added thereto, a solution of 1.3 g potassium hydroxide in 40 mL ethanol was added little by little thereto, and the mixture was heated for 3.5 hours under reflux. The reaction mixture was made weakly acidic by adding iced water and acetic acid, and the precipitated crystals were filtered and washed with water to give 7.1 g of the title compound as colorless crystals.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH3:7][N:8]1[C:12]([NH:13][C:14]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[C:11](/[CH:33]=[CH:34]/[C:35]#[N:36])[CH:10]=[N:9]1.[F-].[Na+].O>O1CCCC1>[NH2:36][CH2:35][CH2:34][CH2:33][C:11]1[CH:10]=[N:9][N:8]([CH3:7])[C:12]=1[NH:13][C:14]([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)([C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: Cn1ncc(/C=C/C#N)c1NC(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Al+3]
Agent: [F-]
Agent: [H-]
Solvent: O
Solvent: C1CCOC1
Product: Cn1ncc(CCCN)c1NC(c1ccccc1)(c1ccccc1)c1ccccc1
Yield: 86.2 %

Procedure:
To a mixture of lithium aluminum hydride (32.6 g) in tetrahydrofuran (1.3 L) was added (2E)-3-[1-methyl-5-(tritylamino)-1H-pyrazol-4-yl]-2-propenonitrile (101.6 g) under ice-cooling. The mixture was refluxed for 4 hours. After cooling on an ice bath, sodium fluoride (100 g) and water (100 ml) were added to the reaction mixture. The insoluble materials were removed by filtration. The filtrate was concentrated in vacuo to give 4-(3-aminopropyl)-1-methyl-5-tritylamino-1H-pyrazole (88.9 g). 1H-NMR(DMSO-d6) δ1.00–1.22 (2H, m), 1.70–1.90 (2H, m), 2.15–2.35 (2H, m), 2,74 (3H, s), 5.70 (1H, s), 6.97 (1H, s), 7.10–7.38 (15H, m)
Reaction SMILES: [OH-].[Na+].[CH2:3]([NH:9][S:10]([CH2:13][CH2:14][CH3:15])(=[O:12])=[O:11])[CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[Cl:16][C:17]([Cl:23])([S:21]Cl)[CH:18]([Cl:20])[Cl:19]>ClCCl>[CH2:3]([N:9]([S:21][C:17]([Cl:23])([Cl:16])[CH:18]([Cl:20])[Cl:19])[S:10]([CH2:13][CH2:14][CH3:15])(=[O:12])=[O:11])[CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: CCCCCCNS(=O)(=O)CCC
Reactant: ClSC(Cl)(Cl)C(Cl)Cl
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Product: CCCCCCN(SC(Cl)(Cl)C(Cl)Cl)S(=O)(=O)CCC
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A 3.8 g (0.047 mol) sample of 50% weight aqueous sodium hydroxide solution was added dropwise to a cooled (8° C) solution of 9.0 g (0.043 mcl) N-hexyl propanesulfonamide and 11.0 g (0.047 mol), 1,1,2,2-tetrachloroethylsulfenyl chloride in 150 ml dichloromethane. After the addition was completed, the reaction was stirred at about 25° C for 4 hours during which time a precipitate formed. The reaction mixture was then washed with water, dried over magnesium sulfate and evaporated under reduced pressure to give an oily residue. The residue was chromatographed through 250 g silica gel with 10% ethylether/90% hexane elution to give 7 g of the product as a yellow oil. the elemental analysis for the product showed: %S, calc. 15.8, found 16.2; %Cl, calc. 35.0, found 33.5. The product is tabulated in Table I as Compound No. 1.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)/[C:7](=[CH:11]\[C:12]1[CH:17]=[CH:16][C:15]([S:18]([CH3:20])=[O:19])=[CH:14][CH:13]=1)/[C:6]([CH3:21])=[C:5]2[CH2:22][CH2:23][O:24][NH2:25].[O:26]=[CH:27][CH2:28][C:29](O)=[O:30]>>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)/[C:7](=[CH:11]\[C:12]1[CH:17]=[CH:16][C:15]([S:18]([CH3:20])=[O:19])=[CH:14][CH:13]=1)/[C:6]([CH3:21])=[C:5]2[CH2:22][CH2:23][O:24][N:25]=[C:29]([OH:30])[CH2:28][CH:27]=[O:26]
Reactant: O=CCC(=O)O
Reactant: CC1=C(CCON)c2cc(F)ccc2/C1=C\c1ccc(S(C)=O)cc1
Product: CC1=C(CCON=C(O)CC=O)c2cc(F)ccc2/C1=C\c1ccc(S(C)=O)cc1

Procedure:
The title compound is prepared by reaction of O-2-[Z-5-fluoro-2-methyl-1-(4-methylsulfinylphenyl)methylene-1H-inden-3-yl]ethyl hydroxylamine with 3-oxopropionic acid by the method of Example 1.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH3:10])[NH2:9])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:11][C:12]1[C:17]([Cl:18])=[CH:16][C:15]([Cl:19])=[CH:14][C:13]=1B(O)O.C(N(CC)CC)C>ClCCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[C:1]([O:5][C:6]([N:8]([CH3:10])[NH:9][C:13]1[CH:14]=[C:15]([Cl:19])[CH:16]=[C:17]([Cl:18])[C:12]=1[Cl:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: OB(O)c1cc(Cl)cc(Cl)c1Cl
Reactant: CN(N)C(=O)OC(C)(C)C
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: CCN(CC)CC
Solvent: ClCCCl
Product: CN(Nc1cc(Cl)cc(Cl)c1Cl)C(=O)OC(C)(C)C
Temperature: 50 °C
Yield: 54.3 %

Procedure:
A mixture of N-methyl-hydrazinecarboxylic acid tert-butyl ester (Intermediate 1; 500 mg, 3.4 mmol), 2,3,5-trichlorophenylboronic acid (Aldrich; 751 mg, 3.35 mmol), copper(II) acetate (621 mg, 3.4 mmol) and triethylamine (480 μL, 3.4 mmol) in 1,2-dichloroethane (4 mL) was heated in an oil bath at 50° C. for 3 h. The mixture was allowed to cool, and it was then adsorbed onto silica gel and purified by chromatography using an ISCO 40 g column, eluting with 20-40% ethyl acetate/hexanes, to give N-methyl-N′-(2,3,5-trichloro-phenyl)-hydrazinecarboxylic acid tert-butyl ester (592 mg, 53%) as a colorless oil that solidified on standing.
Reaction SMILES: [C:1]1([C:7](=O)[C:8]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3]C=1.[P]>C(Cl)(Cl)Cl>[C:8]([O:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)(=[O:9])[C:7]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:1]=1
Reactant: O=C(Oc1ccccc1)C(=O)c1ccccc1
Agent: [P]
Solvent: ClC(Cl)Cl
Product: O=C(Oc1ccccc1)c1ccccc1

Procedure:
The decarbonylation reaction of phenyl phenylglyoxylate (PPG) was repeated in the manner as described in Example 79, except that the organic phosphorus compound set forth in Table 12 was employed and the amount of chloroform was changed as set forth in Table 12. The results are also set forth in Table 12.
Reaction SMILES: [C:1]([O:5][C:6](=[O:23])[NH:7][CH:8]([C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([F:22])[CH:16]=1)[C:9](=[O:14])N(OC)C)([CH3:4])([CH3:3])[CH3:2].[I:24][C:25]1[CH:30]=[CH:29][C:28](I)=[CH:27][CH:26]=1>>[C:1]([O:5][C:6](=[O:23])[NH:7][CH:8]([C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([F:22])[CH:16]=1)[C:9]([C:28]1[CH:29]=[CH:30][C:25]([I:24])=[CH:26][CH:27]=1)=[O:14])([CH3:2])([CH3:3])[CH3:4]
Reactant: CON(C)C(=O)C(NC(=O)OC(C)(C)C)c1ccc(Cl)c(F)c1
Reactant: Ic1ccc(I)cc1
Product: CC(C)(C)OC(=O)NC(C(=O)c1ccc(I)cc1)c1ccc(Cl)c(F)c1

Procedure:
The title compound was prepared from rac-[(4-chloro-3-fluoro-phenyl)-(methoxy-methyl-carbamoyl)-methyl]-carbamic acid tert-butyl ester (Intermediate 1) and 1,4-di-iodobenzene in analogy to Example 1a): MS (ISN): 487.9 (M−H)− and 413.9 ((M-tBuOH)−H)−.
Reaction SMILES: [CH:1]1([NH:4][C:5]([C:7]2[C:15]3[CH:14]=[C:13]([C:16]4[C:21]([Cl:22])=[CH:20][N:19]=[C:18](Cl)[N:17]=4)[S:12][C:11]=3[CH:10]=[CH:9][CH:8]=2)=[O:6])[CH2:3][CH2:2]1.[C:24]([O:28][C:29](=[O:35])[NH:30][CH2:31][CH2:32][CH2:33][NH2:34])([CH3:27])([CH3:26])[CH3:25].C(N(CC)C(C)C)(C)C>O1CCOCC1.ClCCl>[C:24]([O:28][C:29](=[O:35])[NH:30][CH2:31][CH2:32][CH2:33][NH:34][C:18]1[N:17]=[C:16]([C:13]2[S:12][C:11]3[CH:10]=[CH:9][CH:8]=[C:7]([C:5](=[O:6])[NH:4][CH:1]4[CH2:3][CH2:2]4)[C:15]=3[CH:14]=2)[C:21]([Cl:22])=[CH:20][N:19]=1)([CH3:27])([CH3:25])[CH3:26]
Reactant: CC(C)(C)OC(=O)NCCCN
Reactant: O=C(NC1CC1)c1cccc2sc(-c3nc(Cl)ncc3Cl)cc12
Solvent: CCN(C(C)C)C(C)C
Solvent: C1COCCO1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NCCCNc1ncc(Cl)c(-c2cc3c(C(=O)NC4CC4)cccc3s2)n1
Temperature: 97 °C
Yield: 65.1 %

Procedure:
A stirred suspension of 2-(2,5-dichloropyrimidin-4-yl)-benzo[b]thiophene-4-carboxylic acid cyclopropylamide (5.59 g, 15.3 mmol) in 1.4-dioxane (60 mL), (3-amino-propyl)-carbamic acid tert-butyl ester (2.70 mL, 2.69 mg, 15.5 mmol) in N,N-diisopropylethylamine (5.20 mL, 3.86 g, 29.9 mmol) is heated at 97° C. for 120 hours. The mixture is then cooled to room temperature, diluted with dichloromethane (120 mL), filtered, washed with dichloromethane (2×25 mL), and dried to provide {3-[5-chloro-4-(4-cyclopropylcarbamoyl-benzo[b]thiophen-2-yl)-pyrimidin-2-ylamino]-propyl}-carbamic acid tert-butyl ester (5.00 g, 65%). This intermediate (4.99 g, 9.94 mmol) is suspended in methanol (120 mL) and treated with 10% aqueous HCl (10 mL) and the mixture is heated at 100° C. for 24 hours. The mixture is then cooled to room temperature, quenched with 2 N NaOH (20 mL), filtered, washed with H2O (60 mL), dichloromethane (60 mL), and diethyl ether (60 mL), and dried to provide the title compound (3.99 g, 99%).
Reaction SMILES: C1(C)C=CC(S(O[CH2:11][CH2:12][O:13][C:14]2[C:19]([CH3:20])=[CH:18][C:17]([N+:21]([O-:23])=[O:22])=[CH:16][C:15]=2[CH3:24])(=O)=O)=CC=1.[CH:26]([NH2:29])([CH3:28])[CH3:27]>O1CCOCC1>[CH:26]([NH:29][CH2:11][CH2:12][O:13][C:14]1[C:15]([CH3:24])=[CH:16][C:17]([N+:21]([O-:23])=[O:22])=[CH:18][C:19]=1[CH3:20])([CH3:28])[CH3:27]
Reactant: CC(C)N
Reactant: Cc1ccc(S(=O)(=O)OCCOc2c(C)cc([N+](=O)[O-])cc2C)cc1
Solvent: C1COCCO1
Product: Cc1cc([N+](=O)[O-])cc(C)c1OCCNC(C)C
Temperature: 80 °C
Reaction time: 3 h

Procedure:
2-(2,6-Dimethyl-4-nitrophenoxy)ethyl p-toluenesulfonate (10.0 g) solution in dioxane (15 ml) was added with isopropylamine (10 ml) and the mixture was stirred for 3 hours in an autoclave at 80° C. After being concentrated , the reaction mixture was dissolved into ethyl acetate (50 ml) and extracted with 1N HCl (150 ml). Resultant aqueous layer was added with 1N sodium hydroxide (200 ml) and extracted with chloroform (200 ml). After being dehydrated with anhydrous magnesium sulfate (20 g), chloroform layer was concentrated under vacuum to dryness to obtain N-isopropyl-[2-(2,6-dimethyl-4-nitrophenoxy)]ethylamine (5.5 g) as yellowish solid.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)([CH3:10])[CH3:9])=[CH:4][CH:3]=1.C([Li])(CC)C.C1CCCCC1.CN([CH:30]=[O:31])C>O1CCCC1.C(OCC)(=O)C.O.C(O)(=O)C>[CH3:9][C:8]([C:5]1[CH:6]=[CH:7][C:2]([CH:30]=[O:31])=[CH:3][CH:4]=1)([N:11]1[CH2:15][CH2:14][CH2:13][CH2:12]1)[CH3:10]
Reactant: CN(C)C=O
Reactant: CC(C)(c1ccc(Br)cc1)N1CCCC1
Agent: [Li]C(C)CC
Solvent: C1CCCCC1
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(C)(c1ccc(C=O)cc1)N1CCCC1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 41.4 %

Procedure:
A solution of EXAMPLE 40B (0.4 g, 1.5 mmol)) in tetrahydrofuran (5 mL) was cooled to −78° C. and treated with a 1.3 M solution of sec-butyl lithium in cyclohexane (1.8 mL, 2.3 mmol). The mixture was stirred for 30 minutes at −78° C. and treated with N,N′-dimethylformamide (0.4 mL, 5.2 mmol). The mixture was warmed to ambient temperature over 1.5 hours, acetic acid (1 mL) added and the mixture stirred at ambient temperature for 10 minutes. Water (2 mL) was added and the mixture diluted with ethyl acetate. The organic layer was separated, washed with saturated sodium bicarbonate, water and brine, and concentrated. The residue was purified by flash chromatography on silica gel using 10-60% hexane/ethyl acetate to give the title compound (0.135 g, 42%). MS (ESI) m/e 218 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]=[C:7]([O:9][CH3:10])[C:6]([C:11]([OH:13])=[O:12])=[CH:5][N:4]=1.[CH2:14](N(CC)CC)C>CN(C)C=O>[CH3:1][O:2][C:3]1[N:8]=[C:7]([O:9][CH3:10])[C:6]([C:11]([O:13][CH3:14])=[O:12])=[CH:5][N:4]=1
Reactant: COc1ncc(C(=O)O)c(OC)n1
Reactant: CCN(CC)CC
Solvent: CN(C)C=O
Product: COC(=O)c1cnc(OC)nc1OC
Temperature: 0 °C
Reaction time: 1 h
Yield: 51.1 %

Procedure:
To a suspension of 2,4-Bis(methyloxy)-5-pyrimidinecarboxylic acid (Prep31, 1.000 g, 5.43 mmol) in N,N-Dimethylformamide (DMF) (35 mL) at 0° C. N,N′-Carbonyldiimidazole (1.321 g, 8.15 mmol) was added and the mixture was stirred for 1 hour at 0° C., then left stirring at rt. After 4 h Triethylamine (2.271 mL, 16.29 mmol) and N,N′-Carbonyldiimidazole (1.321 g, 8.15 mmol), were added to the white suspension. After other 4 h, N,N′-Carbonyldiimidazole (1.321 g, 8.15 mmol) of another batch was added to the suspension. The reaction was left overnight at rt. The solution was then concentrated in vacuo and methanol was added. The solution was stirred at reflux for 2 h. Then the mixture was evaporated in vacuo, the residue was dissolved in DCM and washed with NaHCO3 sat. sol. and then with H2O. Organic phase was dried with Na2SO4 anhydrous, filtered and evaporated in vacuo to obtain 550 mg of the title compound, which was used in the following step without further purification.