Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8]Cl)=[CH:4][N+:3]=1[O-:10].[CH3:11][N:12]1[CH2:18][CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.C([O-])([O-])=O.[K+].[K+]>C(#N)C>[Cl:1][C:2]1[N+:3]([O-:10])=[CH:4][C:5]([CH2:8][N:15]2[CH2:16][CH2:17][CH2:18][N:12]([CH3:11])[CH2:13][CH2:14]2)=[CH:6][CH:7]=1
Reactant: CN1CCCNCC1
Reactant: [O-][n+]1cc(CCl)ccc1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CN1CCCN(Cc2ccc(Cl)[n+]([O-])c2)CC1
Temperature: 25 °C
Reaction time: 84 h
Yield: 63.7 %

Procedure:
To a solution of 2-chloro-5-(chloromethyl)pyridine 1-oxide (940 mg, 5.28 mmol; described in: Tilley, J. W. et al, J. Heterocyclic Chem. 1979, 16, 333) in acetonitrile (30 mL) were added N-methylhomopiperazine (1.21 g, 10.6 mmol), and K2CO3 (730 mg, 5.28 mmol). The reaction mixture was stirred at room temperature for 3.5 days. The solvent was removed in vacuo, and the residue was partitioned between brine and ethyl acetate. The aqueous layer was extracted with another two portions of ethyl acetate and one portion of tetrahydrofuran. The combined organic layers were dried (Na2SO4), and evaporated to give 0.86 g (64% yield) of the title compound as an orange oil: 1H NMR (aceton-d6, 400 MHz) δ 8.30 (dd, J=2 Hz, 1 H), 7.60 (d, J=8 Hz, 1 H), 7.29 (dd, J=8, 2 Hz, 1 H), 3.65 (s, 2 H), 2.74-2.69 (m, 4 H), 2.62-2.54 (m, 4 H), 2.29 (s, 3 H), 1.81-1.75 (m, 2 H); MS (ES) m/z 256 (M++1).
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[C:16]([CH3:27])=[N:17][O:18][C:19]=2[C:20]2[CH:25]=[CH:24][C:23](Br)=[CH:22][CH:21]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:28]([O:30][C:31](=[O:51])[CH2:32][C:33]1([C:36]2[CH:41]=[CH:40][C:39](B3OC(C)(C)C(C)(C)O3)=[CH:38][CH:37]=2)[CH2:35][CH2:34]1)[CH3:29]>>[CH2:28]([O:30][C:31](=[O:51])[CH2:32][C:33]1([C:36]2[CH:41]=[CH:40][C:39]([C:23]3[CH:24]=[CH:25][C:20]([C:19]4[O:18][N:17]=[C:16]([CH3:27])[C:15]=4[NH:14][CH:11]4[CH2:12][CH2:13][N:8]([CH2:1][C:2]5[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=5)[CH2:9][CH2:10]4)=[CH:21][CH:22]=3)=[CH:38][CH:37]=2)[CH2:35][CH2:34]1)[CH3:29]
Reactant: CCOC(=O)CC1(c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)CC1
Reactant: Cc1noc(-c2ccc(Br)cc2)c1NC1CCN(Cc2ccccc2)CC1
Product: CCOC(=O)CC1(c2ccc(-c3ccc(-c4onc(C)c4NC4CCN(Cc5ccccc5)CC4)cc3)cc2)CC1

Procedure:
Prepared according to the procedure described in Example 1, Step 10, using (1-benzyl-piperidin-4-yl)-[5-(4-bromo-phenyl)-3-methyl-isoxazol-4-yl]-amine and {1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropyl}-acetic acid ethyl ester.
Reaction SMILES: [CH2:1]([O:3][CH:4]([O:7][CH2:8][CH3:9])[CH2:5][NH2:6])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[CH2:16](Br)[CH2:17][CH:18]([CH3:20])[CH3:19]>C(#N)C>[CH2:1]([O:3][CH:4]([O:7][CH2:8][CH3:9])[CH2:5][NH:6][CH2:16][CH2:17][CH:18]([CH3:20])[CH3:19])[CH3:2]
Reactant: CCOC(CN)OCC
Reactant: CC(C)CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCOC(CNCCC(C)C)OCC
Temperature: 65 °C
Reaction time: 8 h
Yield: 77.2 %

Procedure:
To a solution of 2,2-diethoxyethanamine 2.91 ml (20 mmol) in acetonitrile 50 ml, potassium carbonate 2.0 g (15 mmol) and a solution of isoamylbromide 1.26 ml (10 mmol) in acetonitrile 20 ml were added and the mixture was stirred at 65° C. overnight. The reaction mixture was concentrated in vacuo and the residue was diluted with ethyl acetate 100 ml and washed with water 100 ml and brine 100 ml. The organic phase was dried over magnesium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified on Büch silica gel column chromatography (n-hexane:ethyl acetate=90:10 to 80:20) to obtain the title compound 1.57 g (77%).
Reaction SMILES: [Na].[Cl:2][C:3]1[C:11]([Cl:12])=[C:10]2[C:6]([CH2:7][C:8]([CH3:20])([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:9]2=[O:13])=[CH:5][C:4]=1[OH:21].I[CH2:23][CH2:24][OH:25]>C(O)CC>[Cl:2][C:3]1[C:11]([Cl:12])=[C:10]2[C:6]([CH2:7][C:8]([CH3:20])([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:9]2=[O:13])=[CH:5][C:4]=1[O:21][CH2:23][CH2:24][OH:25]
Reactant: OCCI
Reactant: CC1(c2ccccc2)Cc2cc(O)c(Cl)c(Cl)c2C1=O
Agent: [Na]
Solvent: CCCO
Product: CC1(c2ccccc2)Cc2cc(OCCO)c(Cl)c(Cl)c2C1=O
Yield: 45 %

Procedure:
To a solution of sodium (1.76 g., 0.076 g. atom) in 1-propanol (250 ml.) is added 6,7-dichloro-5-hydroxy-2-methyl-2-phenyl-1-indanone (23.5 g., 0.076 mole) and 2-iodoethanol (14.5 g., 0.085 mole). The reaction mixture is refluxed 18 hours then evaporated at reduced pressure to give 12.0 g of 2-(6,7-dichloro-2-methyl-1-oxo-2-phenyl-5-indanyloxy)ethanol which melts at 188°-90° C. after recrystallization from ethanol.
Reaction SMILES: CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][N:18]=2)[N:15]=[CH:14][CH:13]=[C:12]3[N:19]2[CH2:24][CH2:23][CH2:22][C@H:21]([NH:25]C(=O)OC(C)(C)C)[CH2:20]2)O1.[NH2:34][C:35]1[CH:36]=[CH:37][C:38]([C:42]2[CH:43]=[C:44]([CH:51]=[CH:52][C:53]=2[F:54])[C:45]([NH:47][CH:48]([CH3:50])[CH3:49])=[O:46])=[N:39][C:40]=1Cl>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.COCCOC>[NH2:34][C:35]1[CH:36]=[CH:37][C:38]([C:42]2[CH:43]=[C:44]([CH:51]=[CH:52][C:53]=2[F:54])[C:45]([NH:47][CH:48]([CH3:50])[CH3:49])=[O:46])=[N:39][C:40]=1[C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][N:18]=1)[N:15]=[CH:14][CH:13]=[C:12]2[N:19]1[CH2:24][CH2:23][CH2:22][C@H:21]([NH2:25])[CH2:20]1
Reactant: CC(C)(C)OC(=O)N[C@H]1CCCN(c2ccnc3cnc(B4OC(C)(C)C(C)(C)O4)cc23)C1
Reactant: CC(C)NC(=O)c1ccc(F)c(-c2ccc(N)c(Cl)n2)c1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: c1ccc(P(c2ccccc2)[c-]2cccc2)cc1
Solvent: COCCOC
Solvent: ClCCl
Product: CC(C)NC(=O)c1ccc(F)c(-c2ccc(N)c(-c3cc4c(N5CCC[C@H](N)C5)ccnc4cn3)n2)c1
Yield: 21 %

Procedure:
A solution of (S)-tert-butyl 1-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,7-naphthyridin-4-yl)piperidin-3-ylcarbamate (1.0 equiv.), 3-(5-amino-6-chloropyridin-2-yl)-4-fluoro-N-isopropylbenzamide ((1.0 equiv.) and Pd(dppf)Cl2—CH2Cl2 (0.2 equiv.) in 3:1 DME/2M Na2CO3 was heated at 120° C. for 20 hours. Upon cooling, the solution was partitioned between EtOAc and Na2CO3(sat.) washed further with NaCl(sat.), dried over MgSO4, concentrated and purified by RP HPLC. Upon lyophilization, the Boc group was deprotected by treatment with 25% TFA/CH2Cl2, concentrated, purified by RP-HPLC and lyophilized to yield (S)-3-(5-amino-6-(4-(3-aminopiperidin-1-yl)-1,7-naphthyridin-6-yl)pyridin-2-yl)-4-fluoro-N-isopropylbenzamide (21%). LC/MS=500.3 (M+H), LC=2.36 min.
Reaction SMILES: [CH3:1][N:2]([CH2:4][C:5]([NH:7][NH2:8])=O)[CH3:3].Cl.C([O-])([O-])=O.[Cs+].[Cs+].[CH3:16][N:17]=[C:18]=[S:19]>CCO>[CH3:1][N:2]([CH2:4][C:5]1[N:17]([CH3:16])[C:18]([SH:19])=[N:8][N:7]=1)[CH3:3]
Reactant: CN(C)CC(=O)NN
Reactant: CN=C=S
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCO
Product: CN(C)Cc1nnc(S)n1C
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 33.8 %

Procedure:
N,N-dimethylglycine hydrazide hydrochloride (50 g, 0.263 mol) was stirred for 5 min in EtOH (525 mL). To this suspension was added Cs2CO3 (62.5 g, 0.192 mol) and the mixture was stirred at room temperature for 15 min. Methyl isothiocyanate (19.25 g, 0.263 mol) in EtOH (270 mL) was added to the pot and the reaction mixture was brought to reflux. The reflux condenser was removed and the EtOH was allowed to evaporate under atmospheric pressure (oil bath temperature 105-110° C.) over 3H to give a purple paste. The reaction was removed from heat and allowed to sit at room temperature overnight (18H), during which time the paste became a solid. The solid was mixed with CH2Cl2 (1.5 L) and filtered. The organic filtrate was concentrated under reduced pressure to give 31 g of a crude yellow oil. The oil was purified by column chromatography through silica gel, eluting with 4:1 CH2Cl2/MeOH to afford 15.3 g (34.9%) of the desired product. 1H NMR (DMSO-d6) d 2.17 (s, 6H) 3.46 (s, 5H) 13.57 (s, 1H). MS (APCI) calcd for C6H12N4S: 172.25; found (M−H+) 171.1.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[C:6]([S:10]([N:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH:14]2[CH2:19][CH2:20][CH2:21][S:22](Cl)(=[O:24])=[O:23])(=[O:12])=[O:11])=[C:5]([CH3:26])[CH:4]=1.[N:27]1[CH:32]=[CH:31][C:30]([N:33]2[CH2:38][CH2:37][C:36]3([CH2:43][CH2:42][NH:41][CH2:40][CH2:39]3)[CH2:35][CH2:34]2)=[CH:29][CH:28]=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[C:6]([S:10]([N:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH:14]2[CH2:19][CH2:20][CH2:21][S:22]([N:41]2[CH2:40][CH2:39][C:36]3([CH2:37][CH2:38][N:33]([C:30]4[CH:31]=[CH:32][N:27]=[CH:28][CH:29]=4)[CH2:34][CH2:35]3)[CH2:43][CH2:42]2)(=[O:24])=[O:23])(=[O:12])=[O:11])=[C:5]([CH3:26])[CH:4]=1
Reactant: COc1cc(C)c(S(=O)(=O)N2CCCCC2CCCS(=O)(=O)Cl)c(C)c1
Reactant: c1cc(N2CCC3(CCNCC3)CC2)ccn1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: COc1cc(C)c(S(=O)(=O)N2CCCCC2CCCS(=O)(=O)N2CCC3(CCN(c4ccncc4)CC3)CC2)c(C)c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
3-(1-(4-Methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)propane-1-sulfonyl chloride (1.3 mmol, 1 eq) in MC (5 ml) was added to a solution of 3-(pyridin-4-yl)-3,9-diazaspiro[5.5]undecane (1.56 mmol, 1.2 eq) and DIPEA (5.2 eq) at 0° C. and the mixture was stirred for 30 min. The reaction mixture was subsequently warmed to room temperature and stirred for 12 h. The reaction mixture was diluted with methylene chloride and washed with water and sat. sodium chloride solution. The organic phase was dried (Na2SO4) and concentrated in vacuo. The crude product obtained in this way was purified by column chromatography (silica gel). Yield: 0.4 g (50%). MS, Rt=3.8 min, m/z=614.9 [MH]+.
Reaction SMILES: [O-]O.[B].[CH3:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH:10]=[CH2:11].C([O:16]O)(C)(C)C>B#[W]>[CH2:11]1[O:16][CH:10]1[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH3:4]
Reactant: CC(C)(C)OO
Reactant: C=CCCCCCC
Agent: B#[W]
Agent: [B]
Agent: [O-]O
Product: CCCCCCC1CO1
Temperature: 90 °C
Yield: 36 %

Procedure:
In this example, the liquid phase epoxidation of an olefinic compound with an organic hydroperoxide was carried out in the presence of a catalytic amount of a boron containing substance in accordance with the instant invention. A 250 ml. flask equipped with a stirrer, thermometer, reflux condenser and dropping funnel was charged with 84 g. octene-1 and 1 g. tungsten boride (WB). The charged mixture was heated to 90° C. and 90% tertiary butyl hydroperoxide was added dropwise until a total of 25 g. had been added. The reaction mixture was then heated at reflux (108°-110° C. for 220 minutes with stirring. The heated mixture was allowed to cool and then the crude reaction product was analyzed. The analysis indicated a 36% yield of octene oxide based on the amount of charged hydroperoxide. The crude reaction product was filtered by conventional methods and the resulting filtrate was analyzed for metal content by atomic absorption analysis. No metals were detected in the filtrate.
Reaction SMILES: [Br:1][C:2]1[C:3](=[O:29])[N:4]([C:19]2[CH:20]=[C:21]([CH:25]=[CH:26][C:27]=2[CH3:28])[C:22](O)=[O:23])[C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17].[CH2:30]([CH2:32][NH2:33])[OH:31].CCN=C=NCCCN(C)C.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>C(Cl)Cl>[Br:1][C:2]1[C:3](=[O:29])[N:4]([C:19]2[CH:20]=[C:21]([CH:25]=[CH:26][C:27]=2[CH3:28])[C:22]([NH:33][CH2:32][CH2:30][OH:31])=[O:23])[C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17]
Reactant: NCCO
Reactant: Cc1ccc(C(=O)O)cc1-n1c(C)cc(OCc2ccc(F)cc2F)c(Br)c1=O
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1ccc(C(=O)NCCO)cc1-n1c(C)cc(OCc2ccc(F)cc2F)c(Br)c1=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 72.1 %

Procedure:
3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-4-methylbenzoic acid (from Step 4 above) (1.9 g, 4.10 mmol) was dissolved in 20 ml of CH2Cl2. Ethanolamine (297 μl, 4.92 mmol) was added, followed, in order, by EDCI (0.764 g, 4.92 mmol), 1-hydroxybenzotriazole (0.665 g, 4.92 mmol) and triethylamine (1.14 ml, 8.20 mmol). The reaction was stirred at room temperature overnight. The reaction was quenched with NH4Cl and extracted 3 times with ethyl acetate. The combined organic layer was then washed with saturated NaHCO3 (aq.) and extracted 3 times with ethyl acetate. The organic layers were combined and washed with H2O and extracted 3 times with ethyl acetate. The organic layers were combined and dried over Na2SO4 and evaporated. The resulting residue was triturated with diethyl ether/hexane to obtain a solid, which was dried in vacuo to give a white solid (1.5 g, 72%). 1H NMR (300 MHz, CDCl3) δ 7.93 (dd, J=7.85, 1.61 Hz, 1H), 7.65 (d, J=1.61 Hz, 1H), 7.62 (app q, J=8.26 Hz, 1H), 7.40 (d, J=8.06 Hz, 1H), 7.39-7.30 (m, 1H), 7.03-6.97 (m, 1H), 6.88-6.81 (m, 1H), 6.25 (s, 1H), 5.20 (s, 2H), 3.70-3.52 (m, 1H), 3.16-3.12 (m, 2H), 2.10 (s, 3H), 1.98 (s, 3H); ES-MS m/z 507 (M+H). ES-HRMS m/z 507.0719 (M+H calcd for C23H22BrF2N2O4 requires 507.0726).
Reaction SMILES: [NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[O:12][CH2:13][C:14]([CH3:19])([CH3:18])[C:15]([OH:17])=O)[N:5]=[C:4]([CH3:20])[C:3]=1[C:21]([O:23][CH2:24][CH3:25])=[O:22].[CH:26]1([NH2:34])[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1>>[CH2:24]([O:23][C:21]([C:3]1[C:4]([CH3:20])=[N:5][C:6]2[C:11]([C:2]=1[NH2:1])=[C:10]([O:12][CH2:13][C:14]([CH3:18])([CH3:19])[C:15]([NH:34][CH:26]1[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1)=[O:17])[CH:9]=[CH:8][CH:7]=2)=[O:22])[CH3:25]
Reactant: NC1CCCCCCC1
Reactant: CCOC(=O)c1c(C)nc2cccc(OCC(C)(C)C(=O)O)c2c1N
Product: CCOC(=O)c1c(C)nc2cccc(OCC(C)(C)C(=O)NC3CCCCCCC3)c2c1N

Procedure:
Prepared as in Example 24a from 3-((4-amino-3-(ethoxycarbonyl)-2-methylquinolin-5-yl)oxy)-2,2-dimethylpropanoic acid (Example 47b) and cyclooctanamine as a brown solid (46%). MS 456 (MH+).
Reaction SMILES: C(O[C:4]([C:6]1[CH:11]=[C:10]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([Cl:18])[CH:13]=2)[CH:9]=[C:8]([CH3:19])[N:7]=1)=[O:5])C.[NH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH3:27])[N:22]=1>>[CH3:27][C:23]1[N:22]=[C:21]([NH:20][C:4]([C:6]2[CH:11]=[C:10]([C:12]3[CH:17]=[CH:16][N:15]=[C:14]([Cl:18])[CH:13]=3)[CH:9]=[C:8]([CH3:19])[N:7]=2)=[O:5])[CH:26]=[CH:25][CH:24]=1
Reactant: Cc1cccc(N)n1
Reactant: CCOC(=O)c1cc(-c2ccnc(Cl)c2)cc(C)n1
Product: Cc1cccc(NC(=O)c2cc(-c3ccnc(Cl)c3)cc(C)n2)n1

Procedure:
The title compound, was prepared from 2′-Chloro-6-methyl-[4,4′]bipyridinyl-2-carboxylic acid ethyl ester in accordance with the general method of example 26, step 6 using 2-amino-6methylpyridine instead of 3-chloroaniline to yield the final compound as a white crystalline, MS (ISP): m/e=339.2, 341.1 (M+H)+.
Reaction SMILES: B(F)(F)F.CC[O:7][CH2:8][CH3:9].NC1[CH:12]=[C:13](C)[C:14]([Cl:17])=[N:15][CH:16]=1.N(OC(C)(C)C)=O.CCCCC>COCCOC>[Cl:17][C:14]1[C:13]([CH3:12])=[CH:9][C:8]([OH:7])=[CH:16][N:15]=1
Reactant: CCOCC
Reactant: Cc1cc(N)cnc1Cl
Agent: CC(C)(C)ON=O
Agent: FB(F)F
Solvent: COCCOC
Solvent: CCCCC
Product: Cc1cc(O)cnc1Cl
Reaction time: 0.25 h
Yield: 151.6 %

Procedure:
To a solution of boron trifluoride diethyl etherate (5.8 mL, 47.5 mmol) in DME (18 mL) at −14° C. was added dropwise a solution of 5-amino-2-chloro-3-methylpyridine (4.5 g, 31.7 mmol) in DME (60 mL). The mixture was stirred for 15 minutes and then a solution of t-butyl nitrite (4.5 mL, 38 mmol) in DME (60 mL) was added dropwise. The mixture was stirred for 1 hour at 0° C., then pentane (100 mL) was added to give a solid. The solid was collected by filtration and dried to give the title compound (6.9 g): 1H NMR (MeOH-d4, 300 MHz) δ2.58 (s, 3H), 8.86 (d, J=2.1 Hz, 1H), 9.41 (d, J=2.4 Hz, 1H).
Reaction SMILES: [C:1]([O:5][C:6](=[O:19])[NH:7][C@@H:8]([C@@H:16]1[CH2:18][O:17]1)[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].[NH:20]1[CH:24]=[CH:23][CH:22]=[N:21]1>>[C:1]([O:5][C:6](=[O:19])[NH:7][C@H:8]([CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C@@H:16]([OH:17])[CH2:18][N:20]1[CH:24]=[CH:23][CH:22]=[N:21]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N[C@H](Cc1ccccc1)[C@@H]1CO1
Reactant: c1cn[nH]c1
Product: CC(C)(C)OC(=O)N[C@H](Cc1ccccc1)[C@@H](O)Cn1cccn1

Procedure:
Using general procedure 3, [(1R)-1-{(2R)-oxiran-2-yl}-2-phenyl-ethyl]carbamic acid tert-butylester (0.15 g, 0.59 mmol) and pyrazole (0.194 g, 2.85 mmol) gives the title compound.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]=[N:10][C:11]2[CH:19]=[C:15]([C:16](Cl)=[O:17])[C:14]([OH:20])=[CH:13][CH:12]=2)=[CH:5][CH:4]=1.[NH2:21][C:22]1[CH:23]=[CH:24][C:25]2[NH:29][CH:28]=[N:27][C:26]=2[CH:30]=1>>[N:27]1[C:26]2[CH:30]=[C:22]([NH:21][C:16](=[O:17])[C:15]3[CH:19]=[C:11]([N:10]=[N:9][C:6]4[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=4)[CH:12]=[CH:13][C:14]=3[OH:20])[CH:23]=[CH:24][C:25]=2[NH:29][CH:28]=1
Reactant: COc1ccc(N=Nc2ccc(O)c(C(=O)Cl)c2)cc1
Reactant: Nc1ccc2[nH]cnc2c1
Product: COc1ccc(N=Nc2ccc(O)c(C(=O)Nc3ccc4[nH]cnc4c3)c2)cc1

Procedure:
5-(4-Methoxyphenylazo)salicoyl chloride and 6-aminobenzimidazole were reacted together as described for Preparation 7. The product was crystallized in aqueous pyridine, m.p. 274°, λmax (methanol)=350 nm.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[N:7]1[CH2:12][CH2:11][N:10]([CH2:13][C:14]2[NH:18][C:17]3[CH:19]=[CH:20][CH:21]=[CH:22][C:16]=3[N:15]=2)[CH2:9][CH2:8]1.[N:23]1([C:28](Cl)=[O:29])[CH2:27][CH2:26][CH2:25][CH2:24]1.C(N(CC)CC)C>ClCCl>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[N:7]1[CH2:8][CH2:9][N:10]([CH2:13][C:14]2[N:15]([C:28]([N:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)=[O:29])[C:16]3[CH:22]=[CH:21][CH:20]=[CH:19][C:17]=3[N:18]=2)[CH2:11][CH2:12]1
Reactant: O=C(Cl)N1CCCC1
Reactant: c1ccc(N2CCN(Cc3nc4ccccc4[nH]3)CC2)nc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(N1CCCC1)n1c(CN2CCN(c3ccccn3)CC2)nc2ccccc21
Temperature: 25 °C
Yield: 46.6 %

Procedure:
To a stirred solution of Example 1A (0.66 g, 2.2 mmol) in dichloromethane (7 mL) was added 1-pyrrolidinecarbonyl chloride (0.28 mL, 2.2 mmol) and triethylamine (0.625 mL, 4.5 mmol). The mixture was heated in a sealed vial for 17 hours, allowed to cool to room temperature, diluted dichloromethane, washed with 5% NaHCO3, dried and concentrated under reduced pressure. The residue was purified by flash column on SiO2 eluting with 20% hexanes/ethyl acetate to give 0.4 g (40%)of the title compound. mp 120-121° C. 1H NMR (CDCl3, 300 MHz) δ 1.79-2.10 (m, 4H), 2.70 (m, 4H), 3.13 (m, 1H), 3.35-3.78 (bm, 8H), 4.32 (m, 1H), 6.65 (m, 2H), 7.30 (m, 3H), 7.49 (m, 1H), 7.76 (m, 1H), 8.28 (m, 1H). MS (DCI/NH3) m/z 391 (M+H)+. Anal. Calcd for C22H26N6O.½H2O: C, 66.14; H, 6.81; N, 21.04. Found: C, 66.22; H, 6.68; N, 21.11.
Reaction SMILES: C([N:4](C(=O)C)[C:5]1[N:9]([C:10](=[N:24]OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:11][CH2:12][N:13]2[C:17](=[O:18])[C:16]3=[CH:19][CH:20]=[CH:21][CH:22]=[C:15]3[C:14]2=[O:23])[N:8]=[C:7]([CH3:36])[C:6]=1[Cl:37])(=O)C.[OH-:41].[Na+]>CO>[C:14]([C:15]1[CH:22]=[CH:21][CH:20]=[CH:19][C:16]=1[C:17]([NH:13][CH2:12][CH2:11][CH:10]1[N:24]=[N:4][C:5]2=[C:6]([Cl:37])[C:7]([CH3:36])=[N:8][N:9]12)=[O:18])([OH:41])=[O:23]
Reactant: CC(=O)N(C(C)=O)c1c(Cl)c(C)nn1C(CCN1C(=O)c2ccccc2C1=O)=NOS(=O)(=O)c1ccc(C)cc1
Reactant: [OH-]
Agent: [Na+]
Solvent: CO
Product: Cc1nn2c(c1Cl)N=NC2CCNC(=O)c1ccccc1C(=O)O
Yield: 49 %

Procedure:
380 mg (0.65 mmol) of 5-bisacetylamino-4-chloro-3-methyl-1-(3-phthalimido-O-tosyl-propanehydroximoyl)pyrazole, mixed with 15 ml methanol and 15 ml of 2N sodium hydroxide solution, are heated under reflux for 10 minutes. The solution is then filtered, neutralised and freed of methanol under vacuum. The crystals which precipitate from the aqueous solution are separated off and washed with water. They may be recrystallised from a 1:1 water/ethanol mixture. 110 mg (49%) of 3-[2-[2-carboxy-benzamido)ethyl]-7-chloro-6-methyl-pyrazolo[5,1-c][1,2,4]triazole with a m. pt. of 162°-166° C. are obtained.
Reaction SMILES: [O:1]=[C:2]1[NH:8][C:7]2[C:9]3[CH2:10][CH2:11][CH2:12][CH2:13][C:14]=3[CH:15]=[CH:16][C:6]=2[N:5]([C:17]2[CH:22]=[CH:21][C:20]([NH:23][S:24]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[N+:33]([O-:35])=[O:34])(=[O:26])=[O:25])=[CH:19][CH:18]=2)[C:4](=[O:36])[CH2:3]1.IC.[C:39](=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[O:1]=[C:2]1[NH:8][C:7]2[C:9]3[CH2:10][CH2:11][CH2:12][CH2:13][C:14]=3[CH:15]=[CH:16][C:6]=2[N:5]([C:17]2[CH:18]=[CH:19][C:20]([N:23]([CH3:39])[S:24]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[N+:33]([O-:35])=[O:34])(=[O:26])=[O:25])=[CH:21][CH:22]=2)[C:4](=[O:36])[CH2:3]1
Reactant: O=C([O-])[O-]
Reactant: O=C1CC(=O)N(c2ccc(NS(=O)(=O)c3ccccc3[N+](=O)[O-])cc2)c2ccc3c(c2N1)CCCC3
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CI
Product: CN(c1ccc(N2C(=O)CC(=O)Nc3c2ccc2c3CCCC2)cc1)S(=O)(=O)c1ccccc1[N+](=O)[O-]
Yield: 71.7 %

Procedure:
N-[4-(2,4-Dioxo-1,2,3,4,8,9,10,11-octahydro-naphtho[1,2-b][1,4]diazepin-5-yl)phenyl]-2-nitro-benzenesulfonamide (150 mg, 0.30 mmol) obtained in Example 151, iodomethane (22 μL, 0.36 mmol), and potassium carbonate (45 mg, 0.33 mmol) were stirred in anhydrous DMF (3 mL) for 16 hours. After the disappearance of the starting materials was confirmed, a post-treatment was performed in a conventional manner to obtain the title compound (112 mg, yield 73%).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1)[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H][H]>CO.[Rh]>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][CH:14]1[CH2:15][CH2:16][CH:17]([OH:20])[CH2:18][CH2:19]1)[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O
Reactant: [H][H]
Agent: [Rh]
Solvent: CO
Product: CC(C)(C)OC(=O)N[C@@H](CC1CCC(O)CC1)C(=O)O

Procedure:
0.74 g (7.17 mmol) of rhodium was added to a solution of 7.00 g (24.88 mmol) of (S)-2-tert-butoxycarbonylamino-3-(4-hydroxyphenyl)propionic acid in 50 ml of methanol, and hydrogenation was carried out at 50 C/6 bar pressure of hydrogen. After conversion was complete, the catalyst was filtered off and the filtrate was concentrated. The product was pure enough for further reactions.
Reaction SMILES: [CH:1]1([C:4]2[N:5]=[CH:6][C:7]([C:15]([OH:17])=O)=[N:8][C:9]=2[O:10][CH2:11][CH:12]2[CH2:14][CH2:13]2)[CH2:3][CH2:2]1.[CH3:18][C:19]([NH2:30])([CH3:29])[CH2:20][CH:21]([C:23]1[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=1)[CH3:22]>>[CH3:18][C:19]([NH:30][C:15]([C:7]1[CH:6]=[N:5][C:4]([CH:1]2[CH2:2][CH2:3]2)=[C:9]([O:10][CH2:11][CH:12]2[CH2:13][CH2:14]2)[N:8]=1)=[O:17])([CH3:29])[CH2:20][CH:21]([C:23]1[CH:24]=[CH:25][N:26]=[CH:27][CH:28]=1)[CH3:22]
Reactant: CC(CC(C)(C)N)c1ccncc1
Reactant: O=C(O)c1cnc(C2CC2)c(OCC2CC2)n1
Product: CC(CC(C)(C)NC(=O)c1cnc(C2CC2)c(OCC2CC2)n1)c1ccncc1

Procedure:
The title compound was synthesized in analogy to Example 69, using 5-cyclopropyl-6-cyclopropylmethoxy-pyrazine-2-carboxylic acid (Example 10 g 10 mg, 0.043 mmol) and 1,1-dimethyl-3-pyridin-4-yl-butylamine (12 mg, 0.064 mmol) as starting materials and isolated (10 mg, 59.38%) as white solid; LC-MS (UV peak area, ESI) 99.2%, 395.2 (M+H)+.