Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]([Br:12])=[CH:3][CH2:4][CH:5]([CH:9]([CH3:11])[CH3:10])[C:6](O)=[O:7].S(Cl)([Cl:15])=O>C1C=CC=CC=1.CN(C)C=O>[Br:1][C:2]([Br:12])=[CH:3][CH2:4][CH:5]([CH:9]([CH3:11])[CH3:10])[C:6]([Cl:15])=[O:7]
Reactant: CC(C)C(CC=C(Br)Br)C(=O)O
Reactant: O=S(Cl)Cl
Solvent: c1ccccc1
Solvent: CN(C)C=O
Product: CC(C)C(CC=C(Br)Br)C(=O)Cl
Yield: 59 %

Procedure:
In 20 g of benzene were dissolved 2.0 g of α-(3,3-dibromoallyl) isovaleric acid, followed by the addition of 4.7 g of thionyl chloride and 2 drops of N,N-dimethylformamide. The mixture was refluxed overnight and, then, distilled to remove the low-boiling fraction. As the residue there was obtained α-(3,3-dibromoallyl)isovaleroyl chloride. This α-(3,3-dibromoallyl) isovaleroyl chloride was dissolved in 30 g of dry benzene and 1.5 g of α-ethynyl-3-phenoxybenzyl alcohol were added. This was further followed by the dropwise addition of 1.6 g of pyridine and the mixture was stirred at room temperature overnight. Thereafter, the reaction mixture was further stirred at 40°-50° C. for 2 hours, after which it was diluted with diethyl ether, washed with dilute hydrochloric acid and water, dried over anhydrous magnesium sulfate and distilled to remove the low-boiling fraction. The resultant viscous oil was purified by column chromatography to recover 2.0 g of α-ethynyl-3-phenoxybenzyl α-(3,3-dibromoallyl)isovalerate (Compound [10]) which was shown to have the properties indicated below [yield: 59% based on α-(3,3-dibromoallyl)isovaleric acid].
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]([NH:12][C:13]1[CH:18]=[C:17]([CH3:19])[C:16]([O:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([OH:33])=[C:28]([O:31][CH3:32])[CH:29]=3)[N:24]=[CH:23][CH:22]=2)=[CH:15][C:14]=1[CH3:34])=[O:11].C(=O)([O-])[O-].[K+].[K+].CC1C=CC(S(O[CH2:52][CH2:53][N:54]2[CH:58]=[CH:57][N:56]=[N:55]2)(=O)=O)=CC=1.O>CN(C)C=O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]([NH:12][C:13]1[CH:18]=[C:17]([CH3:19])[C:16]([O:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:33][CH2:52][CH2:53][N:54]4[CH:58]=[CH:57][N:56]=[N:55]4)=[C:28]([O:31][CH3:32])[CH:29]=3)[N:24]=[CH:23][CH:22]=2)=[CH:15][C:14]=1[CH3:34])=[O:11]
Reactant: COc1cc2c(Oc3cc(C)c(NC(=O)Nc4ccc(F)cc4F)cc3C)ccnc2cc1O
Reactant: Cc1ccc(S(=O)(=O)OCCn2ccnn2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1cc2c(Oc3cc(C)c(NC(=O)Nc4ccc(F)cc4F)cc3C)ccnc2cc1OCCn1ccnn1
Temperature: 80 °C
Reaction time: 5 h
Yield: 30 %

Procedure:
A starting compound (N-(2,4-difluorophenyl)-N′-{4-[(7-hydroxy-6-methoxy-4-quinolyl)oxy]-2,5-dimethyl-phenyl}urea, 93 mg), potassium carbonate (138 mg), and 2-(1H-1,2,3-triazol-1-yl)ethyl 4-methyl-1-benzene-sulfonate (52 mg) were dissolved in N,N-dimethylformamide (1 ml), and the solution was stirred at 80° C. for 5 hr. Water was added to the reaction mixture, and the mixture was extracted with chloroform-propanol (3/1). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure. The residue was purified by HPLC by development with chloroform/methanol to give 33 mg (yield 30%) of the title compound.
Reaction SMILES: [F:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.[CH2:9]=[CH:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>C(OCC)(=O)C.CCCCCC>[C:11]1([CH2:10][CH2:9][NH:6][C:5]2[CH:7]=[CH:8][C:2]([F:1])=[CH:3][CH:4]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: C=Cc1ccccc1
Reactant: Nc1ccc(F)cc1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: Fc1ccc(NCCc2ccccc2)cc1
Yield: 84 %

Procedure:
According to GWM, 0.011 mol (=1.10 ml) of p-fluoroaniline and 0.011 mol (=1.25 ml) of styrene are reacted with one another. The product is isolated by column chromatography using ethyl acetate/n-hexane (1:1) as eluent, the product N-(2-phenylethyl)-(p-fluoro)aniline being obtained as brown liquid.
Reaction SMILES: C[O:2][C:3](=[O:27])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[O:12][CH2:13][CH2:14][CH2:15][CH2:16]/[CH:17]=[CH:18]/[C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=1.Cl.C(OCC)(=O)C>CO.[OH-].[K+]>[CH3:26][O:25][C:22]1[CH:23]=[CH:24][C:19](/[CH:18]=[CH:17]/[CH2:16][CH2:15][CH2:14][CH2:13][O:12][C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[CH2:5][CH2:4][C:3]([OH:27])=[O:2])=[CH:20][CH:21]=1
Reactant: COC(=O)CCc1ccccc1OCCCC/C=C/c1ccc(OC)cc1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: CCOC(C)=O
Product: COc1ccc(/C=C/CCCCOc2ccccc2CCC(=O)O)cc1
Yield: 95.6 %

Procedure:
A solution of 100 mg of 3-[2-[6-(4-methoxyphenyl)-(5E)5-hexenyloxy]-phenyl]-propionic acid methyl ester in 2 ml of methanol and 2 ml of in potassium hydroxide solution is stirred for 2 1/2 hours at room temperature. The reaction mixture is acidified to pH 1 with 2 n hydrochloric acid and shaken out with ethyl acetate, the organic phase is dried on sodium sulfate and concentrated by evaporation. 92 mg of the title compound is obtained as oil.
Reaction SMILES: CO.C[O-].[Na+].C(O)(=O)C.[CH:10]([NH2:12])=[NH:11].[F:13][CH:14]([CH2:23][CH2:24][CH2:25][CH3:26])[C:15](=O)[CH2:16][C:17](OCC)=[O:18]>CO>[F:13][CH:14]([C:15]1[N:12]=[CH:10][NH:11][C:17](=[O:18])[CH:16]=1)[CH2:23][CH2:24][CH2:25][CH3:26]
Reactant: N=CN
Reactant: CCCCC(F)C(=O)CC(=O)OCC
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: CCCCC(F)c1cc(=O)[nH]cn1
Temperature: 60 °C
Reaction time: 5 h
Yield: 67.1 %

Procedure:
To a solution in which 3.80 g of ethyl 4-fluoro-3-oxooctanoate had been dissolved in 10 ml of methanol were added 8.97 g of a 28% sodium methoxide methanol solution and 3.72 g of formamidine acetate, and the mixture was stirred at 60° C. for 5 hours. Then, the reaction mixture was concentrated under reduced pressure. To the concentrated solution were added 30 ml of water and 5.0 g of conc. hydrochloric acid, followed by cooling the mixture to 10 C, and the precipitated crystals were separated by filtration. These crystals were recrystallized from 20 ml of 2-propanol to obtain 2.30 g of 6-(1-fluoropentyl)-4-pyrimidone (isolated yield: 67.1%).
Reaction SMILES: [O:1]1[CH2:6][C:5](=S)[NH:4][C:3](=[O:8])[NH:2]1.[NH:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1>O1CCOCC1>[N:9]1([C:5]2[CH2:6][O:1][NH:2][C:3](=[O:8])[N:4]=2)[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1
Reactant: C1CCNCC1
Reactant: O=C1NOCC(=S)N1
Solvent: C1COCCO1
Product: O=C1N=C(N2CCCCC2)CON1
Temperature: 25 °C
Reaction time: 17 h
Yield: 53.5 %

Procedure:
To a solution of 0.7 g (0.005 mole) of 6H-1,2,4-oxadiazin-3(2H)-one-5(4H)-thione in 10 ml of dry freshly distilled dioxane is added 0.44 g (0.0052 mole) of piperidine. After stirring for 17 hours at room temperature, the solution is filtered, washed with chloroform and dried to give a yield of 0.49 g (54 percent) of 5-(1-piperidinyl)-6H-1,2,4-oxadiazin-3(2H)-one.
Reaction SMILES: C[O:2][CH:3](OC)[CH2:4][O:5][C:6]([CH2:8][NH:9][C:10](=[O:18])[O:11][CH2:12][O:13][C:14](=[O:17])[CH2:15][CH3:16])=[O:7].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH:3]([CH2:4][O:5][C:6]([CH2:8][NH:9][C:10](=[O:18])[O:11][CH2:12][O:13][C:14](=[O:17])[CH2:15][CH3:16])=[O:7])=[O:2]
Reactant: CCC(=O)OCOC(=O)NCC(=O)OCC(OC)OC
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCC(=O)OCOC(=O)NCC(=O)OCC=O
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Compound 55 (268 mg, 0.91 mmol) was dissolved in 10 mL of CH2Cl2 and 5 mL of TFA (containing 5% H2O) was added. The mixture was stirred for 30 min at room temperature. The solution was then concentrated to dryness in vacuo to give the product 56 that was used immediately for the next step. 1H NMR (400 MHz, CDCl3) δ 1.15 (t, J=7.43 Hz, 3H), 2.40 (q, J=7.43 Hz, 2H), 4.16 (d, J=5.47 Hz, 2H), 4.78 (s, 2H), 5.75 (s, 2H), 6.30 (bs, 1H), 9.60 (s, 1H).
Reaction SMILES: C1C=C(Cl)C=C(C(OO)=[O:9])C=1.[C@@H:12]1([NH:18][C:19](=[O:24])[C:20]([F:23])([F:22])[F:21])[CH2:17][CH2:16][CH:15]=[CH:14][CH2:13]1>ClC1C=CC=CC=1>[F:21][C:20]([F:22])([F:23])[C:19]([NH:18][C@@H:12]1[CH2:17][CH2:16][C@H:15]2[C@H:14]([O:9]2)[CH2:13]1)=[O:24]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: O=C(N[C@H]1CC=CCC1)C(F)(F)F
Solvent: Clc1ccccc1
Product: O=C(N[C@@H]1CC[C@@H]2O[C@@H]2C1)C(F)(F)F
Temperature: 22.5 °C
Reaction time: 1 h
Yield: 78.2 %

Procedure:
9.2 g of mCPBA (70%) was charged to a vessel containing a cooled (10-15° C.) solution of 6 g of N-(cyclohex-3-en-1(R)-yl)-2,2,2-trifluoro-acetamide in 60 ml of chlorobenzene maintaining the temperature <30° C., and rinsed through with 3 ml of chlorobenzene. The mixture obtained was stirred at 20 to 25° C. for 1 h and the reaction was followed by TLC until completion. Upon completion of the reaction, the mixture obtained was heated to 38 to 42° C. for 2 h until reaction completion and cooled to 0 to −5° C., stirred for 30 min and the solid precipitate (mCBA) was filtered off and washed through with 2×3 ml of chlorobenzene. The resultant filtrate was washed with 30 ml of 10% sodium thiosulfate solution to remove peroxides, 2×30 ml of 5% NaHCO3 solution to ensure an pH of aqueous phase of >7, and 30 ml of H2O. The mixture obtained was concentrated to dryness. 5.08 g of 2,2,2-Trifluoro-N-(1R,3R,6S)-(7-oxa-bicyclo[4.1.0]hept-3-yl)-acetamide containing ca. 8% of anti (trans) epoxide in the form of a crystalline white solid was obtained.
Reaction SMILES: [C:1]([C:6]1[N:7](C)[S:8](=[O:18])(=[O:17])[C:9]2[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=2[C:11]=1[OH:12])([O:3]CC)=O.[NH2:20][C:21]1[CH:25]=[C:24]([CH3:26])[O:23][N:22]=1>C1(C)C(C)=CC=CC=1>[OH:12][C:11]1[C:10]2[CH:13]=[CH:14][CH:15]=[CH:16][C:9]=2[S:8](=[O:17])(=[O:18])[NH:7][C:6]=1[C:1](=[O:3])[NH:20][C:21]1[CH:25]=[C:24]([CH3:26])[O:23][N:22]=1
Reactant: CCOC(=O)C1=C(O)c2ccccc2S(=O)(=O)N1C
Reactant: Cc1cc(N)no1
Solvent: Cc1ccccc1C
Product: Cc1cc(NC(=O)C2=C(O)c3ccccc3S(=O)(=O)N2)no1

Procedure:
A mixture of 15.3 g. (0.06 mole) of 3-carbethoxy-4-hydroxy-2-methyl-2H-1,2-benzothiazine 1,1-dioxide, 5.9 g. (0.06 mole) of 3-amino-5-methylisoxazole, and 800 ml. of xylene was refluxed for 24 hr. in a Soxhlet apparatus, the thimble of which contained 20 g. of Linde type 4A molecular sieve. The mixture was cooled to 25° and the resulting precipitate was collected and washed with ether to give 11.5 g. of crude product, m.p. 242-248° dec. Recrystallization from 300 ml. of 1,4-dioxan gave 11.2 g. of crystalline product, m.p. 254-257° dec.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([NH:7][CH3:8])=[O:6].[H-].[Na+].Cl[C:15]1[CH:20]=[CH:19][C:18]([NH2:21])=[C:17]([N+:22]([O-:24])=[O:23])[CH:16]=1>CN(C=O)C>[NH2:21][C:18]1[CH:19]=[CH:20][C:15]([O:1][C:2]2[CH:3]=[C:4]([CH:9]=[CH:10][CH:11]=2)[C:5]([NH:7][CH3:8])=[O:6])=[CH:16][C:17]=1[N+:22]([O-:24])=[O:23]
Reactant: CNC(=O)c1cccc(O)c1
Reactant: Nc1ccc(Cl)cc1[N+](=O)[O-]
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CNC(=O)c1cccc(Oc2ccc(N)c([N+](=O)[O-])c2)c1
Temperature: 80 °C

Procedure:
To a solution of 3-hydroxy-N-methyl-benzamide (Step A, 700 mg, 4.6 mmol, 1.0 eq.) in anhydrous DMF (10 mL) was added NaH (200 mg, 5.1 mmol, 1.1 eq.). The reaction was stirred for 10 min. at RT after which 4-chloro-2-nitro-phenylamine (2.0 g, 11.6 mmol, 2.5 eq.) was added. The resulting mixture was heated to 80° C. for 4 h. The reaction was quenched with NaHCO3 (aq.), diluted with CH2Cl2 (50 mL), and washed with 1 N NaOH (25 mL). The organic layer was dried over MgSO4, filtered and concentrated. The crude was further purified by column chromatography (0-100% EtOAc in hexanes) to give pure 3-(4-amino-3-nitro-phenoxy)-N-methyl-benzamide.
Reaction SMILES: Br[CH2:2][C:3]1([CH3:16])[CH2:7][C:6]2[C:8]([CH3:15])=[C:9]([NH2:14])[C:10]([CH3:13])=[C:11]([CH3:12])[C:5]=2[O:4]1.[C:17]1([CH2:23][CH2:24][CH:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(N(CC)CC)C>C([O-])(O)=O.[Na+]>[CH3:16][C:3]1([CH2:2][N:28]2[CH2:29][CH2:30][CH:25]([CH2:24][CH2:23][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:26][CH2:27]2)[CH2:7][C:6]2[C:8]([CH3:15])=[C:9]([NH2:14])[C:10]([CH3:13])=[C:11]([CH3:12])[C:5]=2[O:4]1
Reactant: c1ccc(CCC2CCNCC2)cc1
Reactant: Cc1c(C)c2c(c(C)c1N)CC(C)(CBr)O2
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Product: Cc1c(C)c2c(c(C)c1N)CC(C)(CN1CCC(CCc3ccccc3)CC1)O2
Temperature: 180 °C
Reaction time: 15 h
Yield: 42.5 %

Procedure:
In an autoclave, a mixture of 2-bromomethyl-2,3-dihydro-2,4,6,7-tetramethyl-5-benzofuranamine (1.5 g), 4-(2-phenylethyl)piperidine (2.0 g), and triethylamine (5.3 g) was stirred under argon gas at 180° C. for 15 hours. After cooling, the reaction mixture was diluted with saturated aqueous NaHCO3 and extracted with ethyl acetate. The extract was washed with saturated aqueous NaCl and dried over MgSO4 and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=1:1) and recrystallized from diisopropyl ether to provide 0.88 g of the title compound. Yield 42%.
Reaction SMILES: [C:1]([C:6]1[CH:7]=[C:8]2[C:17]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[NH:11][CH2:10][N:9]2[CH:18]=1)([O:3][CH2:4][CH3:5])=[O:2].Cl[C:20]([O:22][CH2:23][CH3:24])=[O:21].[OH-].[Na+]>CC(C)=O.O>[C:1]([C:6]1[CH:7]=[C:8]2[C:17]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[N:11]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH2:10][N:9]2[CH:18]=1)([O:3][CH2:4][CH3:5])=[O:2]
Reactant: CCOC(=O)c1cc2n(c1)CNc1ccccc1-2
Reactant: CCOC(=O)Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(C)=O
Product: CCOC(=O)c1cc2n(c1)CN(C(=O)OCC)c1ccccc1-2
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
A solution of the product of Example IV (1.2 g, 0.005 m) and ethyl chloroformate (6.0 g, 0.0553 m) in acetone (20 ml) and H2O (50 ml) was treated with NaOH (0.1 ml aq. 30%) and the mixture stirred at room temperature for 15 min. The acetone was removed in vacuo and the aqueous residue cooled in an ice-bath. A solid formed and this was filtered, washed with water, and dried in vacuo. The crude product (1.0 g) was crystallized from methanol to afford the desired product; m.p. 80°-82° C.
Reaction SMILES: [C:1]([NH2:9])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:10]([OH:14])(=[O:13])[CH:11]=[O:12]>CC(C)=O>[C:1]([NH:9][CH:11]([OH:12])[C:10]([OH:14])=[O:13])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=CC(=O)O
Reactant: NC(=O)c1ccccc1
Solvent: CC(C)=O
Product: O=C(NC(O)C(=O)O)c1ccccc1

Procedure:
A mixture of commercially available benzamide 35 and glyoxylic acid 41 was heated at reflux in acetone to give pure N-benzoyl-2-hydroxyglycine 65 as a colourless solid in quantitative yield (Scheme 4.12). The 1H n.m.r. spectrum supported formation of the α-hydroxyglycine derivative 65 with the appearance of a methine (H2) doublet and broad amide (NH) doublet at δ 5.60 and δ 9.26 respectively. Spectroscopic data were in agreement with those reported in the literature.209
Reaction SMILES: [CH3:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([N+:11]([O-:13])=[O:12])=[CH:8][CH:9]=2)[NH:4][N:3]=1.F[B-](F)(F)F.[CH3:19][O+](C)C>CC(C)=O>[CH3:19][N:3]1[C:2]([CH3:1])=[C:10]2[C:5]([CH:6]=[C:7]([N+:11]([O-:13])=[O:12])[CH:8]=[CH:9]2)=[N:4]1
Reactant: Cc1n[nH]c2cc([N+](=O)[O-])ccc12
Reactant: C[O+](C)C
Agent: F[B-](F)(F)F
Solvent: CC(C)=O
Product: Cc1c2ccc([N+](=O)[O-])cc2nn1C
Reaction time: 3 h
Yield: 75.4 %

Procedure:
To a stirred solution of 18.5 g (0.11 mol) of 3-methyl-6-nitro-1H-indazole in 350 ml acetone, at room temperature, was added 20 g (0.14 mol) of trimethyloxonium tetraflouroborate. After the solution was allowed to stir under argon for 3 hours, the solvent was removed under reduced pressure. To the resulting solid was added saturated aqueous NaHCO3 (600 ml) and a 4:1 mixture of chloroform-isopropanol (200 ml), and the mixture was agitated and the layers were separated. The aqueous phase was washed with additional chloroform: isopropanol (4×200 ml) and the combined organic phase was dried (Na2SO4). Filtration and removal of solvent gave a tan solid. The solid was washed with ether (200 ml) to afford 2,3-dimethyl-6-nitro-2H-indazole as a yellow solid (15.85 g, 73%). 1H NMR (300 MHz, d6DMSO) δ 8.51 (s, 1H), 7.94 (d, J=9.1 Hz, 1H), 7.73 (d, J=8.9 Hz, 1H), 4.14 (s, 3H), 2.67 (s, 3H). MS (ES+, m/z) 192 (M+H).
Reaction SMILES: Br[C:2]1[N:16]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[C:5]2=[CH:6][N:7]=[C:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:9]([OH:10])=[C:4]2[C:3]=1Br>C(O)C.[Pd]>[F:24][C:21]1[CH:20]=[CH:19][C:18]([CH2:17][N:16]2[C:5]3=[CH:6][N:7]=[C:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:9]([OH:10])=[C:4]3[CH:3]=[CH:2]2)=[CH:23][CH:22]=1
Reactant: CCOC(=O)c1ncc2c(c1O)c(Br)c(Br)n2Cc1ccc(F)cc1
Agent: [Pd]
Solvent: CCO
Product: CCOC(=O)c1ncc2c(ccn2Cc2ccc(F)cc2)c1O
Reaction time: 23 h
Yield: 98 %

Procedure:
A suspension of ethyl 2,3-dibromo-1-(4-fluorobenzyl)-4-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxylate (52.0 g, 0.110 mol) and 10% Pd/C (0.5 g) in ethanol (2.0 L) was shaken in a Parr shaker under hydrogen (39 psi) for 23 h. The catalyst was removed by filtration. On concentration of the filtrate, the product precipitated out. It was collected by filtration and dried under vacuum to provide the title compound. (34 g, 98% yield) 1H NMR (DMSO-d6) δ ppm 11.66 (s, 1H), 8.89 (s, 1H), 8.14 (d, J=3.0 Hz, 1H) 7.37 (d, J=5.7 Hz, 2H), 7.19 (d, J=6.6 Hz, 2H), 7.11 (d, J=3.0 Hz, 1H), 5.71 (s, 2H), 4.45 (q, J=7.1 Hz, 2H), 1.37 (t, J=7.2 Hz, 3H). LC/MS (API-ES, M+H+): 315.1.
Reaction SMILES: [CH3:1][C:2]1[O:3][C:4]([C:17](OC)=[O:18])=[C:5]([C:7]2[CH:16]=[CH:15][C:14]3[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=3[CH:8]=2)[N:6]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].O>C(OCC)C>[CH3:1][C:2]1[O:3][C:4]([CH2:17][OH:18])=[C:5]([C:7]2[CH:16]=[CH:15][C:14]3[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=3[CH:8]=2)[N:6]=1
Reactant: COC(=O)c1oc(C)nc1-c1ccc2c(c1)CCCC2
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: CCOCC
Product: Cc1nc(-c2ccc3c(c2)CCCC3)c(CO)o1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 90 %

Procedure:
To a solution of methyl [2-methyl-4-(5,6,7,8-tetrahydronaphthalen-2-yl)-5-oxazolyl]carboxylate (4.5 g) in diethyl ether (90 mL) was added lithium aluminum hydride (0.63 g) at 0° C. After stirring the reaction mixture at room temperature for 30 min, water (3.2 mL) was added, and the precipitated solid was removed by filtration. The filtrate was concentrated and the obtained solid was washed with isopropyl ether to give [2-methyl-4-(5,6,7,8-tetrahydronaphthalen-2-yl)-5-oxazolyl]methanol (3.63 g, yield 90%) as crystals. Recrystallization from ethanol gave colorless crystals. melting point: 132–133° C.
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][NH:7][S:8]([C:11]1[CH:16]=[CH:15][C:14](Br)=[CH:13][CH:12]=1)(=[O:10])=[O:9].[F:18][C:19]([F:30])([F:29])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1B(O)O>>[OH:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][NH:7][S:8]([C:11]1[CH:16]=[CH:15][C:14]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=2[C:19]([F:30])([F:29])[F:18])=[CH:13][CH:12]=1)(=[O:10])=[O:9]
Reactant: OB(O)c1ccccc1C(F)(F)F
Reactant: O=S(=O)(NCCCCCO)c1ccc(Br)cc1
Product: O=S(=O)(NCCCCCO)c1ccc(-c2ccccc2C(F)(F)F)cc1

Procedure:
Using a method analogous to that described in Example 40, 4-bromophenyl-sulfonic acid-(5-hydroxypentyl)-amide and 2-trifluoromethylphenyl boronic acid were reacted to give the title compound as a white solid. δC (DMSO, 62.9 MHz): 22.6, 28.9, 32.0, 42.7, 60.5, 121.9, 126.2, 126.5, 127.1, 128.8, 129.8, 132.0, 132.6, 139.2, 140.2 and 143.1.
Reaction SMILES: [CH2:1]([CH2:5][PH:6](Cl)=[O:7])[CH:2]=[CH:3][CH3:4].[O-:9][C:10]#[N:11].[Na+]>C(#N)C>[CH2:1]([CH2:5][PH:6]([N:11]=[C:10]=[O:9])=[O:7])[CH:2]=[CH:3][CH3:4]
Reactant: CC=CCC[PH](=O)Cl
Reactant: N#C[O-]
Agent: [Na+]
Solvent: CC#N
Product: CC=CCC[PH](=O)N=C=O
Reaction time: 4.5 h
Yield: 70.3 %

Procedure:
170 g (1.1 mol) of crotylmethylphosphinic acid chloride were dissolved in 300 ml of acetonitrile and heated with 73 g (1.1 mol) of sodium cyanate to 55° C. with stirring. After 4.5 hours, the precipitate was filtered off by suction and washed with acetonitrile; the filtrate was concentrated and the residue distilled at a temperature of 76°-78° C. and at a pressure of 27 Pa. 123 g of crotylmethylphosphinic acid isocyanate (70% of theory) were obtained.
Reaction SMILES: [NH:1]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C@H:2]([C:17]([OH:19])=[O:18])[CH2:3][CH2:4][CH2:5][NH:6]C(OCC1C=CC=CC=1)=O>CO.[H][H]>[NH:1]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C@H:2]([C:17]([OH:19])=[O:18])[CH2:3][CH2:4][CH2:5][NH2:6]
Reactant: [H][H]
Reactant: CC(C)(C)OC(=O)N[C@@H](CCCNC(=O)OCc1ccccc1)C(=O)O
Solvent: CO
Product: CC(C)(C)OC(=O)N[C@@H](CCCN)C(=O)O

Procedure:
Boc-Orn-OH (0.51 g) [obtained by catalytically reducing Boc-Orn(Z)-OH in methanol in a stream of hydrogen using 10% Pd-carbon as a catalyst] was dissolved in DMF, and the solution was cooled with ice. TEA (0.61 ml) and PhCOONB [prepared from PhCOOH (0.30 g), HONB (0.47 g) and DCC (0.54 g)] were added thereto, followed by stirring overnight. The reaction solution was concentrated, and the residue was dissolved in AcOEt. The resulting solution was washed with 10% aqueous citric acid. After washing with water, the solution was dried with Na2SO4 and concentrated. Then, ether and dicyclohexylamine (438 μl) were added to the residue to separate out a precipitate, which was collected by filtration.
Reaction SMILES: CO[C:3]([CH2:5][C:6]([NH:8][C:9]1[CH:10]=[N:11][CH:12]=[CH:13][C:14]=1[C:15]([OH:17])=O)=[O:7])=O.[CH3:18][C:19]1[CH:24]=[CH:23][C:22]([NH2:25])=[C:21]([NH2:26])[CH:20]=1>>[OH:17][C:15]1[C:14]2[C:9](=[CH:10][N:11]=[CH:12][CH:13]=2)[NH:8][C:6](=[O:7])[C:5]=1[C:3]1[NH:26][C:21]2[CH:20]=[C:19]([CH3:18])[CH:24]=[CH:23][C:22]=2[N:25]=1
Reactant: COC(=O)CC(=O)Nc1cnccc1C(=O)O
Reactant: Cc1ccc(N)c(N)c1
Product: Cc1ccc2nc(-c3c(O)c4ccncc4[nH]c3=O)[nH]c2c1

Procedure:
The title compound was synthesized as described in Example 50 using 3-[2-(methoxycarbonyl)acetylamino]-pyridine-4-carboxylic acid and 4-methyl-1,2-phenylenediamine. The crude product was purified by reversed-phase HPLC (DMSO/5% TFA). LC/MS m/z 293.3 (MH+), Rt 1.99 minutes.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH2:10])[CH3:9])=[CH:4][CH:3]=1.[C:11]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)(=O)[CH3:12].O>C1(C)C=CC=CC=1.[Cl-].[Zn+2].[Cl-]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([N:10]=[C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH3:12])[CH3:9])=[CH:4][CH:3]=1
Reactant: C[C@@H](N)c1ccc(Cl)cc1
Reactant: CC(=O)c1ccccc1
Agent: [Cl-]
Agent: [Zn+2]
Solvent: O
Solvent: Cc1ccccc1
Product: CC(=N[C@H](C)c1ccc(Cl)cc1)c1ccccc1
Yield: 47.2 %

Procedure:
0.3 g of zinc chloride is added to a solution of 20 g (0.128 mol) of (R)-1-(4-chlorophenyl)-ethylamine (97% ee) and 15.6 g (0.13 mol) of acetophenone in 70 ml of toluene at room temperature with stirring, and the mixture is then refluxed for 74 hours at the water separator. The reaction mixture is then filtered. The filtrate is evaporated under reduced pressure to give 15.56 g (47% of theory) of (R)-[1-(4-chlorophenyl)-ethyl]-[1-phenyl-ethylidene]-amine.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[SH:9].[Br:10][C:11]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:12]=1I>>[Br:10][C:11]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:12]=1[S:9][C:3]1[CH:4]=[CH:5][C:6]([CH3:8])=[CH:7][C:2]=1[Cl:1]
Reactant: Cc1ccc(S)c(Cl)c1
Reactant: Fc1ccc(I)c(Br)c1
Product: Cc1ccc(Sc2ccc(F)cc2Br)c(Cl)c1

Procedure:
Prepared from 2-chloro-4-methyl-benzenethiol and 2-bromo-4-fluoro-1-iodo-benzene.