Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(=O)(O)[O-].[Na+].[Cl:6][C:7]1[CH:26]=[CH:25][C:10]2[O:11][C:12]3[CH:24]=[CH:23][CH:22]=[CH:21][C:13]=3[C@@H:14]3[C@H:19]([NH2:20])[CH2:18][CH2:17][CH2:16][N:15]3[C:9]=2[CH:8]=1.Cl[C:28]([O:30][CH2:31][Cl:32])=[O:29].C(OCC)(=O)C>C(Cl)Cl>[Cl:32][CH2:31][O:30][C:28](=[O:29])[NH:20][C@H:19]1[C@@H:14]2[N:15]([C:9]3[CH:8]=[C:7]([Cl:6])[CH:26]=[CH:25][C:10]=3[O:11][C:12]3[CH:24]=[CH:23][CH:22]=[CH:21][C:13]=32)[CH2:16][CH2:17][CH2:18]1
Reactant: O=C(Cl)OCCl
Reactant: N[C@@H]1CCCN2c3cc(Cl)ccc3Oc3ccccc3[C@H]12
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: O=C(N[C@@H]1CCCN2c3cc(Cl)ccc3Oc3ccccc3[C@H]12)OCCl
Temperature: 25 °C
Reaction time: 18 h
Yield: 83.9 %

Procedure:
100 μL of saturated aq. sodium bicarbonate was added to trans-7-chloro-2,3,4,14b-tetrahydro-1H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepine-1-amine (9.5 mg, 0.03 mmol) and chloromethyl chloroformate (64.2 μL, 0.42 mmol) in 250 μL of CH2Cl2. The resulting mixture was stirred at room temperature for 18 h. Subsequently, ethyl acetate was added and the organic layer was washed with water, dried (Na2SO4) and evaporated to give trans-(7-chloro-2,3,4,14b-tetrahydro-1H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepin-1-yl)carbamic acid chloromethyl ester (9.9 mg, 88%). Data: (m/z)=393 (M+H)+.
Reaction SMILES: [F:1][C:2]([F:43])([F:42])[C:3]1[CH:4]=[C:5]([CH:39]=[CH:40][CH:41]=1)[CH2:6][NH:7][C:8](=[O:38])[C:9]1[CH:14]=[CH:13][N:12]=[C:11]([C:15]2[CH:20]=[C:19]([N:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)[CH:18]=[CH:17][C:16]=2[NH:27][C:28](=[O:37])[C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([CH2:35]Br)[CH:30]=2)[CH:10]=1.[N:44]1([C:50](=[O:52])[CH3:51])[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1.[I-].[K+].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O>[C:50]([N:44]1[CH2:49][CH2:48][N:47]([CH2:35][C:31]2[CH:30]=[C:29]([CH:34]=[CH:33][CH:32]=2)[C:28]([NH:27][C:16]2[CH:17]=[CH:18][C:19]([N:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)=[CH:20][C:15]=2[C:11]2[CH:10]=[C:9]([CH:14]=[CH:13][N:12]=2)[C:8]([NH:7][CH2:6][C:5]2[CH:39]=[CH:40][CH:41]=[C:3]([C:2]([F:43])([F:42])[F:1])[CH:4]=2)=[O:38])=[O:37])[CH2:46][CH2:45]1)(=[O:52])[CH3:51]
Reactant: O=C(NCc1cccc(C(F)(F)F)c1)c1ccnc(-c2cc(N3CCCCC3)ccc2NC(=O)c2cccc(CBr)c2)c1
Reactant: CC(=O)N1CCNCC1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(=O)N1CCN(Cc2cccc(C(=O)Nc3ccc(N4CCCCC4)cc3-c3cc(C(=O)NCc4cccc(C(F)(F)F)c4)ccn3)c2)CC1
Temperature: 70 °C
Reaction time: 3 h
Yield: 52.3 %

Procedure:
Into a 50-mL round-bottom flask, was placed a solution of N-(3-(trifluoromethyl)benzyl)-2-(2-(3-(bromomethyl)benzamido)-5-(piperidin-1-yl)phenyl)isonicotinamide (100 mg, 0.15 mmol, 1.00 equiv) in N,N-dimethylformamide (2 mL), 1-(piperazin-1-yl)ethanone (59 mg, 0.46 mmol, 3.00 equiv), potassium iodide (12.7 mg, 0.08 mmol, 0.50 equiv), and potassium carbonate (42.4 mg, 0.31 mmol, 2.00 equiv). The resulting solution was stirred for 3 h at 70° C. in an oil bath. The reaction progress was monitored by LCMS. The resulting solution was diluted with 20 mL of water. The resulting solution was extracted with 3×20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3×20 mL of brine, dried over anhydrous sodium sulfate, and concentrated under vacuum. The crude product was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 54.8 mg (34%) of a yellow solid. 1H-NMR (400 MHz, CD3OD, ppm): 8.94-8.92 (d, J=4.2 Hz, 1H), 8.66-8.64 (d, J=6.6 Hz, 1H), 8.43 (s, 1H), 8.14-8.09 (m, 3H), 7.88-7.87 (m, 1H), 7.79-7.54 (m, 7H), 4.72 (s, 2H), 4.47 (s, 2H), 3.82 (s, 3H), 3.65-3.62 (t, J=4.2 Hz, 1H), 3.33-3.29 (m, 5H), 2.15 (s, 3H), 2.04-2.01 (t, J=5.2 Hz, 4H), 1.82-1.81 (d, J=5.2 Hz, 1H). MS (ES, m/z): 699 [M+H]+.
Reaction SMILES: ClC(Cl)(Cl)[C:3]([C:5]1[N:14]2[C:8]([CH2:9][N:10]([C:19]([C:21]3[CH:26]=[CH:25][C:24]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[CH3:33])=[C:23]([O:34][CH3:35])[CH:22]=3)=[O:20])[C:11]3[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=3[CH2:13]2)=[CH:7][CH:6]=1)=[O:4].[CH3:38][C:39]1[CH:46]=[CH:45][C:42]([CH2:43][NH2:44])=[CH:41][CH:40]=1>>[CH3:35][O:34][C:23]1[CH:22]=[C:21]([C:19]([N:10]2[C:11]3[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=3[CH2:13][N:14]3[C:5]([C:3]([NH:44][CH2:43][C:42]4[CH:45]=[CH:46][C:39]([CH3:38])=[CH:40][CH:41]=4)=[O:4])=[CH:6][CH:7]=[C:8]3[CH2:9]2)=[O:20])[CH:26]=[CH:25][C:24]=1[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[CH3:33]
Reactant: COc1cc(C(=O)N2Cc3ccc(C(=O)C(Cl)(Cl)Cl)n3Cc3ccccc32)ccc1-c1ccccc1C
Reactant: Cc1ccc(CN)cc1
Product: COc1cc(C(=O)N2Cc3ccc(C(=O)NCc4ccc(C)cc4)n3Cc3ccccc32)ccc1-c1ccccc1C
Yield: 84 %

Procedure:
The title compound was prepared in 84% yield in the manner of Example 36 from 2,2,2-trichloro-1-{10-[(2-methoxy-2′-methyl-1,1′-biphenyl-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}ethanone of Example 35 and 4-methylbenzylamine, m.p. 179-180° C. MS [(+)ESI, m/z]: 556 [M+H]+ Anal. Calcd for C36H33N3O3: C, 77.81; H, 5.99; N, 7.56. Found: C, 77.57; H, 6.01; N, 7.50.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[S:10]([NH:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][C:22]([O:24][CH3:25])=[O:23])=[CH:16][CH:15]=1)(=[O:12])=[O:11])([O-:3])=[O:2].[C:26]1([C:32]2[N:33]([CH2:41][C:42]3[CH:47]=[CH:46][C:45]([CH2:48]O)=[CH:44][CH:43]=3)[C:34]3[C:39]([CH:40]=2)=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[S:10]([N:13]([CH2:48][C:45]1[CH:44]=[CH:43][C:42]([CH2:41][N:33]2[C:34]3[C:39](=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH:40]=[C:32]2[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[CH:47][CH:46]=1)[C:14]1[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][C:22]([O:24][CH3:25])=[O:23])=[CH:16][CH:15]=1)(=[O:12])=[O:11])([O-:3])=[O:2]
Reactant: OCc1ccc(Cn2c(-c3ccccc3)cc3ccccc32)cc1
Reactant: COC(=O)CCc1ccc(NS(=O)(=O)c2ccccc2[N+](=O)[O-])cc1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COC(=O)CCc1ccc(N(Cc2ccc(Cn3c(-c4ccccc4)cc4ccccc43)cc2)S(=O)(=O)c2ccccc2[N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A solution of methyl 3-(4-{[(2-nitrophenyl)sulfonyl]amino}phenyl)propanoate (0.583 g, 1.60 mmol), {4-[(2-phenyl-1H-indol-1-yl)methyl]phenyl}methanol (0.470 g, 1.50 mmol) and triphenylphosphine (0.787 g, 3.00 mmol) in tetrahydrofuran (25 mL) was stirred under ice-cooling, and diethyl azodicarboxylate (40% toluene solution, 1.36 mL, 3.00 mmol) was added. The mixture was allowed to warm to room temperature and stirred for 3 hr. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (20%-60% ethyl acetate/hexane). Hexane-ethyl acetate was added to the obtained residue and the resultant insoluble material was filtered off. The filtrate was concentrated to give the title compound as a brown oil.
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][C:5]([C:8](=[O:16])[C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.[BrH:17].[OH-].[Na+]>O>[Br:17][C:2]1[N:7]=[CH:6][C:5]([C:8](=[O:16])[C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1
Reactant: Br
Reactant: O=C(c1ccc(F)cc1)c1ccc(Cl)nc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C(c1ccc(F)cc1)c1ccc(Br)nc1

Procedure:
2.35 g 6-chloro-3-(4-fluorobenzoyl)-pyridine (see Ex. 5) and 50 ml 47% aqueous HBr are refluxed for 1 hr. After this time a control by gas chromatography reveals no starting chloro-derivative is present. The reaction liquid is added to water, and a yellow solid is formed. The mixture is basified with concentrated NaOH, and the crystalline solid is filtered and recrystallised from methanol:water. Yield: 0.9 g title product, as white crystals, m.p. 97°-8° C.; UV (water): λmax. 278 nm, ε: 16,600; Br 28.34 (28.53); F 7.11 (6.78).
Reaction SMILES: C(N(CC)CC)C.[C:8](Cl)(=[O:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[NH2:17][C:18]1[CH:30]=[C:29]([CH2:31][CH2:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH:28]=[CH:27][C:19]=1[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21]>C(Cl)Cl>[C:8]([NH:17][C:18]1[CH:30]=[C:29]([CH2:31][CH2:32][CH2:33][C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH:28]=[CH:27][C:19]=1[C:20]([O:22][C:23]([CH3:25])([CH3:26])[CH3:24])=[O:21])(=[O:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: CC(C)(C)OC(=O)c1ccc(CCCc2ccccc2)cc1N
Reactant: O=C(Cl)c1ccccc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)c1ccc(CCCc2ccccc2)cc1NC(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 17 h

Procedure:
0.28 mL of triethylamine and 0.12 mL of benzoyl chloride were added to 3 mL of methylene chloride solution containing 0.31 g of tert-butyl 2-amino-4-(3-phenylpropyl)benzoate sequentially while ice-cooled and stirred at room temperature for 17 hours. The solvent was evaporated under reduced pressure, and the obtained residue was purified with silica gel column chromatography [eluent; hexane:ethyl acetate=20:1] to obtain 0.48 g of tert-butyl 2-(benzamido)-4-(3-phenylpropyl)benzoate as while solid.
Reaction SMILES: [C:1](OC(=O)C)(=[O:3])C.[NH2:8][C:9]1[S:10][CH:11]=[C:12]([C:14](=[N:20][O:21][CH:22]2[CH2:24][CH2:23]2)[C:15]([O:17][CH2:18][CH3:19])=[O:16])[N:13]=1.C(OC(C)C)(C)C>C(O)=O>[CH:22]1([O:21][N:20]=[C:14]([C:12]2[N:13]=[C:9]([NH:8][CH:1]=[O:3])[S:10][CH:11]=2)[C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:24][CH2:23]1
Reactant: CC(=O)OC(C)=O
Reactant: CCOC(=O)C(=NOC1CC1)c1csc(N)n1
Solvent: CC(C)OC(C)C
Solvent: O=CO
Product: CCOC(=O)C(=NOC1CC1)c1csc(NC=O)n1
Temperature: 45 °C

Procedure:
A mixture of formic acid (13.1 ml) and acetic anhydride (32.6 ml) was warmed at 45° C. for 45 minutes. After the mixture was cooled until ambient temperature, ethyl 2-(2-aminothiazol-4-yl)-2-cyclopropyloxyiminoacetate (syn isomer)(22 g) was added thereto. The suspension was turned to a clear solution and soon a precipitate was appeared. To the suspension was added diisopropyl ether (50 ml) and the mixture was stirred at ambient temperature for additional an hour. The mixture was cooled in ice-bath and the precipitate was collected and washed with diisopropyl ether to give ethyl 2-cyclopropyloxyimino-2-(2-formamidothiazol-4-yl)acetate (syn isomer)(20.5 g).
Reaction SMILES: [H-].[Na+].[CH3:3][O:4][C:5]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:6]=1[CH2:13][N:14]([CH2:16][C:17]1[C:21]([F:22])=[C:20]([C:23]2[C:24]([F:29])=[N:25][CH:26]=[CH:27][CH:28]=2)[NH:19][CH:18]=1)[CH3:15].C1OCCOCCOCCOCCOC1.[N:45]1[CH:50]=[CH:49][CH:48]=[C:47]([S:51](Cl)(=[O:53])=[O:52])[CH:46]=1>O1CCCC1>[CH3:3][O:4][C:5]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:6]=1[CH2:13][N:14]([CH2:16][C:17]1[C:21]([F:22])=[C:20]([C:23]2[C:24]([F:29])=[N:25][CH:26]=[CH:27][CH:28]=2)[N:19]([S:51]([C:47]2[CH:46]=[N:45][CH:50]=[CH:49][CH:48]=2)(=[O:53])=[O:52])[CH:18]=1)[CH3:15]
Reactant: COc1ccc(CN(C)Cc2c[nH]c(-c3cccnc3F)c2F)c(OC)c1
Reactant: O=S(=O)(Cl)c1cccnc1
Agent: C1COCCOCCOCCOCCO1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1ccc(CN(C)Cc2cn(S(=O)(=O)c3cccnc3)c(-c3cccnc3F)c2F)c(OC)c1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 68.5 %

Procedure:
To a suspension of sodium hydride (60% in oil, 1.57 g) in tetrahydrofuran (100 mL) was added dropwise a solution of 1-(2,4-dimethoxyphenyl)-N-{[4-fluoro-5-(2-fluoropyridin-3-yl)-1H-pyrrol-3-yl]methyl}-N-methylmethanamine (9.8 g) in tetrahydrofuran (30 mL) under ice-cooling. The reaction mixture was stirred at the same temperature for 10 min, and 15-crown-5 (8.66 g) was added dropwise. After further stirring for 10 min, pyridine-3-sulfonyl chloride (6.98 g) was added dropwise. After stirring for 15 min at the same temperature, ice water was added and the reaction mixture was extracted with ethyl acetate. The aqueous layer was weakly basified with saturated aqueous sodium hydrogen carbonate solution (100 mL), and extracted again with ethyl acetate. The combined extract was washed successively with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (eluent: hexane:ethyl acetate=6:1→3:1), and washed with diisopropyl ether to give the title compound as colorless crystals (yield 9.25 g, 69%).
Reaction SMILES: [CH3:1][N:2]1[CH2:15][CH2:14][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.[OH-].[K+].[CH3:18][C:19]1[S:20][C:21]([CH:24]=[CH2:25])=[CH:22][CH:23]=1>CN1C(=O)CCC1.O>[CH3:1][N:2]1[CH:15]=[CH:14][C:5]2[N:6]([CH2:25][CH2:24][C:21]3[S:20][C:19]([CH3:18])=[CH:23][CH:22]=3)[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1
Reactant: Cc1ccc2[nH]c3c(c2c1)CN(C)CC3
Reactant: C=Cc1ccc(C)s1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CN1CCCC1=O
Product: Cc1ccc2c(c1)c1c(n2CCc2ccc(C)s2)C=CN(C)C1
Temperature: 90 °C
Reaction time: 5 h

Procedure:
To a solution of 2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (150 mg, 0.75 mmol) in NMP (1 mL) were added powdered KOH (294 mg, 5.25 mmol) and 2-methyl-5-vinyl-thiophene (186 mg, 1.50 mmol), and the reaction mixture stirred at 90° C. for 5 h. The reaction mixture was diluted with water (15 mL) and extracted with EtOAc (3×20 mL). The combined organic layer was washed with water (5×25 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (3% MeOH-DCM) followed by reverse phase HPLC to yield 2,8-dimethyl-5-[2-(5-methyl-thiophen-2-yl)-ethyl]-2,5-dihydro-1H-pyrido[4,3-b]indole. 1H NMR (CD3OD, TFA salt) δ (ppm): 7.3 (d, 1H), 7.22 (s, 1H), 7.08 (d, 1H), 6.5 (d, 1H), 6.3 (d, 1H), 4.6 (d, 1H), 4.2-4.4 (m, 3H), 3.7 (m, 2H), 3.2 (m, 3H), 3.03 (s, 3H), 2.7 (m, 1H), 2.38-2.42 (m, 6H).
Reaction SMILES: [C:1](OCC)(=[O:10])[CH:2]=[CH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[H-].C([Al+]CC(C)C)C(C)C>CCCCCC.ClCCl>[C:4]1([CH:3]=[CH:2][CH2:1][OH:10])[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: CCOC(=O)C=Cc1ccccc1
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: ClCCl
Solvent: CCCCCC
Product: OCC=Cc1ccccc1
Yield: 104.5 %

Procedure:
The above ester (3.52 g) was treated with diisobutylaluminium hydride (40 ml of a 1M solution in hexane) in dichloromethane (40 ml) in the normal fashion to provide 3-phenylprop-2-en-1-ol (2.8 g). NMR 1H: 7.2(5H,m), 6.55(1H,d), 6.35 (1H,t), 4.25(2H,d), 1.97(1H,s).
Reaction SMILES: B(Br)(Br)Br.C[O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:17]([CH3:18])[C:16]([C:19]34[CH2:26][CH2:25][C:22]([CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])([CH2:23][CH2:24]3)[CH2:21][CH2:20]4)=[N:15][N:14]=2)=[C:9]([CH3:32])[CH:8]=1>C(Cl)Cl>[CH3:32][C:9]1[CH:8]=[C:7]([OH:6])[CH:12]=[CH:11][C:10]=1[C:13]1[N:17]([CH3:18])[C:16]([C:19]23[CH2:24][CH2:23][C:22]([CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])([CH2:25][CH2:26]2)[CH2:21][CH2:20]3)=[N:15][N:14]=1
Reactant: CCCCCC12CCC(c3nnc(-c4ccc(OC)cc4C)n3C)(CC1)CC2
Agent: BrB(Br)Br
Solvent: ClCCl
Product: CCCCCC12CCC(c3nnc(-c4ccc(O)cc4C)n3C)(CC1)CC2
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Boron tribromide (1M/CH2Cl2, 3.21 mL, 3.21 mmol) was added to a solution of 3-(4-methoxy-2-methylphenyl)4-methyl-5-(4-pentylbicyclo[2.2.2]oct-1-yl)-4H-1,2,4-triazole (2-F) (410 mg, 1.07 mmol) in methylene chloride (6 mL) at 0° C. The mixture was stirred at room temperature for 2 h. The solution was washed with water, 10% NaHCO3, dried (MgSO4) and concentrated in vacuo. The residue was purified by preparative TLC (silica gel, MeOH:methylene chloride, 5:95) to provide 3-methyl-4-[4-methyl-5-(4-pentylbicyclo[2.2.2]oct-1-yl)4H-1,2,4-triazol-3-yl]phenol (2-G). Mass spectrum: 393 (M+1); 1H NMR (500 MHz, CDCl3): δ 0.93 (t, 3H); 1.27 (m, 8H); 1.56 (m, 6H); 1.97 (s 3H); 2.12 (m, 6H); 3.50 (s, 3H); 6.65 (m, 2H); 6.98 (d, 1H) ppm.
Reaction SMILES: [CH3:1][C:2](Cl)([CH3:7])[C:3]([Cl:6])=[N:4][OH:5].[C:9](=O)([O-])[O-:10].[Ca+2]>CO>[CH3:1][C:2]([CH3:7])([O:10][CH3:9])[C:3]([Cl:6])=[N:4][OH:5]
Reactant: O=C([O-])[O-]
Reactant: CC(C)(Cl)C(Cl)=NO
Agent: [Ca+2]
Solvent: CO
Product: COC(C)(C)C(Cl)=NO
Yield: 79 %

Procedure:
A mixture of 50 g (0.32 mol) of 2-methyl-1,2-dichloro-1-oximino-propane, 50 g (0.5 mol) of finely powdered calcium carbonate and 500 ml of absolute methanol is heated at the boiling point for 30 minutes, while cooling under reflux. The mixture is filtered, the filtrate is concentrated and the residue is extracted several times with ether. The ether phase is dried over sodium sulphate and filtered and the filtrate is concentrated. 38.4 g of 2,2-dimethyl-2-methoxy-1-chloro-1-oximino-ethane are obtained in the form of white crystals of melting point 95° C., and the yield is 79% of theory:
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]2[O:23][C:17]3=[CH:18][N:19]=[C:20](Cl)[CH:21]=[C:16]3[CH2:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:24][O:25][C:26]1[CH:31]=[C:30](B(O)O)[CH:29]=[CH:28][N:27]=1>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]2[O:23][C:17]3=[CH:18][N:19]=[C:20]([C:30]4[CH:29]=[CH:28][N:27]=[C:26]([O:25][CH3:24])[CH:31]=4)[CH:21]=[C:16]3[CH2:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: COc1cc(B(O)O)ccn1
Reactant: CC(C)(C)OC(=O)N1CCC(C2Cc3cc(Cl)ncc3O2)CC1
Product: COc1cc(-c2cc3c(cn2)OC(C2CCN(C(=O)OC(C)(C)C)CC2)C3)ccn1

Procedure:
The title compound is prepared from 4-(5-chloro-2,3-dihydro-furo[2,3-c]pyridin-2-yl)-piperidine-1-carboxylic acid tert-butyl ester and 2-methoxypyridine-4-boronic acid following a procedure analogous to that described in Example 28. LC (method 10): tR=1.76 min; Mass spectrum (ESI+): m/z=412 [M+H]+.
Reaction SMILES: [CH2:1]1[O:8][CH:2]1[CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].[NH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][NH2:16]>C(O)C>[CH2:15]([NH:16][CH2:1][CH:2]([OH:8])[CH2:3][CH2:4][CH2:5][CH2:6][CH3:7])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][NH:9][CH2:1][CH:2]([OH:8])[CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]
Reactant: CCCCCC1CO1
Reactant: NCCCCCCN
Solvent: CCO
Product: CCCCCC(O)CNCCCCCCNCC(O)CCCCC

Procedure:
In a manner similar to that of Example 1, condensation of 1-heptene oxide (71.8 g.) and hexamethylenediamine (32 g.) and recrystallization of the resulting product from ethanol gave N,N'-(1,6-hexylene)-bis[2-hydroxyheptylamine] (I: R = CH3 (CH2)4, R' = H, X = (CH2)6, Z = H) (16.5 g., m.p. 131.2°-134.2° C.).
Reaction SMILES: [NH2:1][CH2:2][C:3]1[N:7]=[C:6]([CH2:8][N:9]([CH2:13][CH2:14][CH3:15])[CH2:10][CH2:11][CH3:12])[O:5][N:4]=1.[CH:16](OC)=[O:17]>>[CH2:10]([N:9]([CH2:8][C:6]1[O:5][N:4]=[C:3]([CH2:2][NH:1][CH:16]=[O:17])[N:7]=1)[CH2:13][CH2:14][CH3:15])[CH2:11][CH3:12]
Reactant: CCCN(CCC)Cc1nc(CN)no1
Reactant: COC=O
Product: CCCN(CCC)Cc1nc(CNC=O)no1
Yield: 79 %

Procedure:
A solution of 15.6 g (73.5 mmol) of (3-aminomethyl-1,2,4-oxadiazol-5-ylmethyl)-dipropylamine in 100 ml of methyl formate was heated at reflux for seven hours. Subsequently, the solution was evaporated and the residue was chromatographed (silica gel, methylene chloride/methanol 19:1). There were obtained 14 g (79%) of N-(5-dipropylaminomethyl-1,2,4-oxadiazol-3-ylmethyl)-formamide, Rf=0.28 (silica gel, methylene chloride/methanol 19:1).
Reaction SMILES: [C:1]1(=O)[CH:6]2[C:7]3[C:12]([C:13](=O)[N:5]2[CH2:4][CH2:3][NH:2]1)=[CH:11][CH:10]=[CH:9][CH:8]=3.B.O.Cl>O1CCCC1>[CH2:1]1[CH:6]2[C:7]3[C:12]([CH2:13][N:5]2[CH2:4][CH2:3][NH:2]1)=[CH:11][CH:10]=[CH:9][CH:8]=3
Reactant: O=C1NCCN2C(=O)c3ccccc3C12
Agent: B
Agent: Cl
Solvent: C1CCOC1
Solvent: O
Product: c1ccc2c(c1)CN1CCNCC21
Reaction time: 18 h
Yield: 85.2 %

Procedure:
3,4-Dihydropyrazino[2,1-a]isoindole-1,6(2H,10bH)-dione (described in Example 6, 14 g, 0.0674 mol) is added portionwise to 700 ml of 1 M borane in tetrahydrofuran over a 0.5 hr period and then refluxed with stirring for 18 hr. The reaction is cooled, water is added dropwise until the hydrolysis is complete and then 140 ml of 6 N hydrochloric acid is added cautiously. Most of the tetrahydrofuran is distilled off until the distillation temperature reaches 90° C. Then 6 N sodium hydroxide (140 ml) is added and the solution is extracted with chloroform. The chloroform extract is washed with water, dried and evaporated to give the title compound (10 g), nmr (CDCl3) δ 2.63(s), 2.6-4.3(m) and 7.3(m). The title compound is treated with a solution of hydrogen bromide in diethyl ether to give a solid. The solid is crystallized from ethanol to obtain the hydrobromide salt of the title compound, mp 155°-160° C. The title compound (8.9 g) is dissolved in a solution of ethanol containing maleic acid (6.45 g), charcoal is added and the mixture is filtered. The filtrate is evaporated and the residue is crystallized from ethanol-diethyl ether to obtain the maleate salt of the title compound, mp 133°-136° C., Anal. Calc'd. for C11H14N2.C4H4O4 : C, 62.06%, H, 6.25% N, 9.65% and Found: C, 62.00% H, 6.29% N, 9.70%.
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][N:11]([C:14]2([CH3:27])[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)[CH2:10][C@@H:9]1[CH3:28])C1C=CC=CC=1.C(O)(=O)C>CO>[CH3:27][C:14]1([N:11]2[CH2:12][CH2:13][NH:8][C@@H:9]([CH3:28])[CH2:10]2)[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:21])[CH2:16][CH2:15]1
Reactant: C[C@H]1CN(C2(C)CCN(C(=O)OC(C)(C)C)CC2)CCN1Cc1ccccc1
Solvent: CO
Solvent: CC(=O)O
Product: C[C@H]1CN(C2(C)CCN(C(=O)OC(C)(C)C)CC2)CCN1
Reaction time: 18 h
Yield: 99.7 %

Procedure:
A solution of t-butyl 4-[(3S)-4-benzyl-3-methylpiperazin-1-yl]-4-methylpiperidine-1-carboxylate (45.5 g, 0.118 mol) in methanol (320 mL) and acetic acid (35 mL, ˜5 equiv) in a 2.25 L Parr bottle was charged with H2 to 60 psi and the mixture shaken for 18 hr. The reaction mixture was filtered through a pad of Celite and the pad was washed with methanol. The filtrate was concentrated under vacuum. The residual oil was dissolved in DCM (500 mL) and washed with aqueous sodium hydroxide (300 mL). The aqueous phase was back-extracted with methylene chloride (200 mL). The combined organic solution was washed with brine (500 mL), dried with sodium sulfate and the solvent was removed under vacuum to give 35 g (100%) of product as a pale yellow viscous oil that slowly crystallized. 1H NMR (400 MHz, CDCl3) δ (ppm) 3.44 (m, 2H), 3.36 (m, 2H), 2.97 (dt, 1H), 2.84 (dd, 1H), 2.78 (m, 1H), 2.71 (brd, 2H), 2.16 (dt, 1H), 1.81 (t, 2H), 1.76 (m, 1H), 1.45 (s, 9H), 1.34 (m, 3H), 1.03 (d, 3H), 0.90 (s, 3H); MS (EI) 298.2 (M+1).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[CH:4][C:3]=1[CH2:11][O:12][CH2:13][CH2:14][O:15][CH3:16]>C1COCC1.[Pd]>[F:1][C:2]1[CH:7]=[C:6]([CH:5]=[CH:4][C:3]=1[CH2:11][O:12][CH2:13][CH2:14][O:15][CH3:16])[NH2:8]
Reactant: COCCOCc1ccc([N+](=O)[O-])cc1F
Agent: [Pd]
Solvent: C1CCOC1
Product: COCCOCc1ccc(N)cc1F
Reaction time: 16 h
Yield: 71.9 %

Procedure:
To a stirred solution of 2-fluoro-1-((2-methoxyethoxy)methyl)-4-nitrobenzene (4.0 g, 1.0 eq) in THF (50 mL) was added 10% Pd—C and the reaction mixture was stirred under H2 gas balloon at for 16 h. The reaction mixture was passed through celite pad and the solvent evaporated to get 3-fluoro-4-((2-methoxyethoxy)methyl)aniline (2.50 g, 72%) as solid (TLC system: EtOAc/PE (1:1), Rf: 0.3).