Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: N#N.[CH3:3][C:4]1([C:9]2[N:10]=[C:11]([CH2:14][OH:15])[S:12][CH:13]=2)[O:8][CH2:7][CH2:6][O:5]1.CCN(CC)CC.[S:23](Cl)([CH3:26])(=[O:25])=[O:24]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:3][C:4]1([C:9]2[N:10]=[C:11]([CH2:14][O:15][S:23]([CH3:26])(=[O:25])=[O:24])[S:12][CH:13]=2)[O:8][CH2:7][CH2:6][O:5]1
Reactant: CC1(c2csc(CO)n2)OCCO1
Reactant: CS(=O)(=O)Cl
Agent: CN(C)c1ccncc1
Agent: N#N
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC1(c2csc(COS(C)(=O)=O)n2)OCCO1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of [4-(2-methyl-[1,3]dioxolan-2-yl)-thiazol-2-yl]-methanol (925 mg, 4.60 mmol) in dry CH2Cl2 (20 mL) was treated at 0° C. with Et3N (0.83 mL, 5.94 mmol) followed by DMAP (57 mg, 0.46 mmol) and Ms-Cl (0.46 mL, 5.80 mmol). After stirring at 0° C. for 1 h, the reaction was quenched with water (10 mL). The org. layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (1:2 hept-EA) gave the title compound as a yellow oil. LC-MS-conditions 01: tR=0.73 min, [M+H]+=280.19.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5](Cl)=[O:6].[CH3:11][CH2:12][CH2:13][CH:14]([NH2:18])[CH2:15][CH2:16][CH3:17]>>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([NH:18][CH:14]([CH2:15][CH2:16][CH3:17])[CH2:13][CH2:12][CH3:11])=[O:6]
Reactant: O=C(Cl)c1cccc(Br)c1
Reactant: CCCC(N)CCC
Product: CCCC(CCC)NC(=O)c1cccc(Br)c1

Procedure:
Reaction of 3-bromobenzoyl chloride with heptan-4-amine gave 3-bromo-N-(heptan-4-yl)benzamide as a white solid which was used in the next step without additional purification. Yield (2.43 g, 90%).
Reaction SMILES: CS(O[CH2:6][CH2:7][N:8]1[CH:12]=[C:11]([C:13]2[CH:18]=[C:17]([C:19]([O:21]C)=[O:20])[CH:16]=[CH:15][N:14]=2)[N:10]=[CH:9]1)(=O)=O.[Cl:23][C:24]1[CH:25]=[C:26]2[C:31](=[CH:32][CH:33]=1)[NH:30][CH2:29][CH2:28][CH2:27]2>>[Cl:23][C:24]1[CH:25]=[C:26]2[C:31](=[CH:32][CH:33]=1)[N:30]([CH2:6][CH2:7][N:8]1[CH:12]=[C:11]([C:13]3[CH:18]=[C:17]([C:19]([OH:21])=[O:20])[CH:16]=[CH:15][N:14]=3)[N:10]=[CH:9]1)[CH2:29][CH2:28][CH2:27]2
Reactant: Clc1ccc2c(c1)CCCN2
Reactant: COC(=O)c1ccnc(-c2cn(CCOS(C)(=O)=O)cn2)c1
Product: O=C(O)c1ccnc(-c2cn(CCN3CCCc4cc(Cl)ccc43)cn2)c1
Yield: 9 %

Procedure:
The title compound was prepared in 9% yield from methyl 2-(1-{2-[(methylsulfonyl)oxy]ethyl}-1H-imidazol-4-yl)pyridine-4-carboxylate (PREPARATION 6) and 6-chloro-1,2,3,4-tetrahydroquinoline according to the procedure for the preparation of Example 58. 1HNMR (400 MHz, DMSO): δ 1.74 (2H, t, J=5.1 Hz), 2.64 (2H, t, J=6.5 Hz), 3.06 (2H, t, J=5.5 Hz), 3.63 (2H, t, J=6.2 Hz), 4.18 (2H, t, J=6.0 Hz), 6.62 (1H, d, J=8.9 Hz), 6.92 (1H, s), 6.94 (1H, t, J=8.7 Hz), 7.49 (1H, d, J=4.8 Hz), 7.69 (1H, s), 7.81 (1H, s), 8.23 (1H, s), 8.46 (1H, d, J=4.1 Hz). [M+H] Calc'd for C20H19ClN4O2, 384. Found, 384.
Reaction SMILES: [C:1]([O:4][CH:5]1[C:6]([OH:38])([CH3:37])[CH2:7][CH2:8][CH:9]([OH:36])[CH2:10][C:11]([O:13][CH:14](/[C:19](/[CH3:35])=[CH:20]/[CH:21]=[CH:22]/[CH:23]([CH3:34])[CH2:24][CH:25]2[O:33][CH:26]2[CH:27]([CH3:32])[CH:28]([OH:31])[CH2:29][CH3:30])[CH:15]([CH3:18])[CH:16]=[CH:17]1)=[O:12])(=[O:3])[CH3:2].CN(C1C=CC=CN=1)C.[S:48](Cl)([C:51]1[CH:57]=[CH:56][C:54]([CH3:55])=[CH:53][CH:52]=1)(=[O:50])=[O:49]>ClCCl.C(OCC)(=O)C>[C:1]([O:4][CH:5]1[C:6]([OH:38])([CH3:37])[CH2:7][CH2:8][CH:9]([OH:36])[CH2:10][C:11]([O:13][CH:14](/[C:19](/[CH3:35])=[CH:20]/[CH:21]=[CH:22]/[CH:23]([CH3:34])[CH2:24][CH:25]2[O:33][CH:26]2[CH:27]([CH3:32])[CH:28]([O:31][S:48]([C:51]2[CH:57]=[CH:56][C:54]([CH3:55])=[CH:53][CH:52]=2)(=[O:50])=[O:49])[CH2:29][CH3:30])[CH:15]([CH3:18])[CH:16]=[CH:17]1)=[O:12])(=[O:3])[CH3:2]
Reactant: CCC(O)C(C)C1OC1CC(C)/C=C/C=C(\C)C1OC(=O)CC(O)CCC(C)(O)C(OC(C)=O)C=CC1C
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: CCC(O)C(C)C1OC1CC(C)/C=C/C=C(\C)C1OC(=O)CC(O)CCC(C)(O)C(OC(C)=O)/C=C/C1C
Agent: CCC(OS(=O)(=O)c1ccc(C)cc1)C(C)C1OC1CC(C)/C=C/C=C(\C)C1OC(=O)CC(O)CCC(C)(O)C(OC(C)=O)/C=C/C1C
Agent: CN(C)c1ccccn1
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: CCC(OS(=O)(=O)c1ccc(C)cc1)C(C)C1OC1CC(C)/C=C/C=C(\C)C1OC(=O)CC(O)CCC(C)(O)C(OC(C)=O)C=CC1C
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A solution of (8E,12E,14E)-7-acetoxy-3,6,21-trihydroxy-6,10,12,16,20-pentamethyl-18,19-epoxytricosa-8,12,14-trien-11-olide (52.3 mg, 97.4 μmol) in dichloromethane (1.0 mL) was ice-cooled, and dimethylaminopyridine (37.4 mg, 306.1 μmol) was added thereto. After stirring for about 30 min., tosyl chloride (28.6 mg, 150.0 μmol) was added and the temperature was raised to room temperature. After stirring for 4 hours, the reaction mixture was diluted with ethyl acetate (10 mL), and washed with distilled water (2 mL) for two times and with brine (2 mL). The organic layer obtained was dried over anhydrous sodium sulfate, filtered and then concentrated. The crude product was purified by medium pressure column chromatography (toluene:acetone=10:1, MERCK Lobar, LiChroprepSi 60, 4 ml/min.) and a thin layer chromatography (MERCK Silicagel 60 F254, 0.5 mm, developing solution; ethyl acetate) to obtain the title Compound (8.8 mg, 12.7 μmol, 13.0%) as a colorless oil.
Reaction SMILES: [OH:1][C:2]1([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([C:34]([F:37])([F:36])[F:35])[CH:29]=2)[CH2:7][CH2:6][N:5]([CH:8]([F:27])[CH2:9][CH:10]([NH:19]CC2C=CC=CC=2)[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:12])[CH2:4][CH2:3]1.[ClH:38]>[Pd].C(O)C.[H][H]>[ClH:38].[OH:1][C:2]1([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([C:34]([F:37])([F:35])[F:36])[CH:29]=2)[CH2:7][CH2:6][N:5]([CH:8]([F:27])[CH2:9][CH:10]([NH2:19])[C:11]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)=[O:12])[CH2:4][CH2:3]1
Reactant: O=C(c1ccccc1)C(CC(F)N1CCC(O)(c2cccc(C(F)(F)F)c2)CC1)NCc1ccccc1
Reactant: [H][H]
Agent: [Pd]
Agent: Cl
Solvent: CCO
Product: NC(CC(F)N1CCC(O)(c2cccc(C(F)(F)F)c2)CC1)C(=O)c1ccccc1

Procedure:
A mixture of γ-[4-hydroxy-4-(3-trifluoromethylphenyl)piperidin-1-yl]-2-benzylamino-4-fluorobutyrophenone (3.8 g), 10 % palladium on charcoal (1.0 g) and 35 % hydrochloric acid (2.0 g) in ethanol (45 ml) was vigorously stirred in hydrogen atmosphere at 25°C until an equimolar amount of hydrogen was consumed. The catalyst was filtered off, and the filtrate was concentrated under reduced pressure to afford γ-[4-hydroxy-4-(3-trifluoromethylphenyl)piperidin-1-yl]-2-amino-4-fluorobutyrophenon hydrochloride. M.P. 230° - 235°C (decomposition). The hydrochloride was shaken with a mixture of aqueous ammonia and ether. The ethereal layer was washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the free base, which was recyrstallized from aqueous ethanol. M.P. 105° - 107°C.
Reaction SMILES: [N:1]1([CH2:6][C@@H:7]([O:14][C:15]2[CH:24]=[CH:23][C:22]3[C:21](=[O:25])[CH2:20][CH2:19][CH2:18][C:17]=3[C:16]=2[CH2:26][S:27][C:28]2[CH:36]=[CH:35][C:31]([C:32](O)=[O:33])=[CH:30][CH:29]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.[NH2:37][CH2:38][C@@H:39]([OH:41])[CH3:40]>>[OH:41][C@@H:39]([CH3:40])[CH2:38][NH:37][C:32](=[O:33])[C:31]1[CH:35]=[CH:36][C:28]([S:27][CH2:26][C:16]2[C:17]3[CH2:18][CH2:19][CH2:20][C:21](=[O:25])[C:22]=3[CH:23]=[CH:24][C:15]=2[O:14][C@@H:7]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH2:6][N:1]2[CH:5]=[CH:4][N:3]=[CH:2]2)=[CH:29][CH:30]=1
Reactant: C[C@H](O)CN
Reactant: O=C(O)c1ccc(SCc2c(O[C@H](Cn3ccnc3)c3ccccc3)ccc3c2CCCC3=O)cc1
Product: C[C@H](O)CNC(=O)c1ccc(SCc2c(O[C@H](Cn3ccnc3)c3ccccc3)ccc3c2CCCC3=O)cc1
Yield: 86.4 %

Procedure:
Using the method in Example 172, 4-{[(2-{[(1S)-2-(1H-imidazol-1-yl)-1-phenylethyl]oxy}-5-oxo-5,6,7,8-tetrahydro-1-naphthalenyl)methyl]sulfanyl}benzoic acid (50 mg, 0.10 mmol, 0.20M in DMF) and (S)-1-amino-2-propanol (23 mg, 0.30 mmol, 0.6M in DMF) were combined to give 48 mg of the desired compound: Low resolution mass spectrum (LC-MS, APCI) m/z 556 [M+H]+.
Reaction SMILES: [CH3:1][C:2]1([C:8]([OH:10])=O)[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1.C1C=CC2N(O)N=[N:17]C=2C=1.C(Cl)CCl>CC#N.[NH4+].[OH-]>[CH3:1][C:2]1([C:8]([NH2:17])=[O:10])[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1
Reactant: On1nnc2ccccc21
Reactant: CC1(C(=O)O)CCOCC1
Agent: [NH4+]
Agent: [OH-]
Solvent: ClCCCl
Solvent: CC#N
Product: CC1(C(N)=O)CCOCC1
Temperature: 25 °C
Reaction time: 3 h
Yield: 71 %

Procedure:
A mixture of 4-methyltetrahydro-2H-pyran-4-carboxylic acid (2.60 g, 18.0 mmol), HOBt (2.76 g, 18.0 mmol) and EDC (4.49 g, 23.4 mmol) in MeCN (75 mL) was stirred at RT for 3 h, treated with NH4OH (˜15M, 7 mL, −105 mmol) and stirred at RT overnight. The mixture was concentrated to dryness, and the residue was partitioned between satd. Brine (40 mL) and DCM (100 mL). The aqueous was extracted with THF (50 mL) and DCM (5×30 mL). The combined organics were washed with 10% aq K2CO3 (50 mL), dried over Na2SO4 and concentrated in vacuo to afford 4-methyltetrahydro-2H-pyran-4-carboxamide (1.83 g, 70%). 1H NMR (400 MHz, DMSO-d6): δ 7.14 (s, 1H), 6.86 (s, 1H), 3.60 (dt, J=11.7, 4.5 Hz, 2H), 3.36 (m, 2H), 1.91-1.89 (m, 2H), 1.30 (m, 2H), 1.08 (s, 3H).
Reaction SMILES: [Mg].[CH2:2]([C@H:5]1[CH2:10][CH2:9][C@H:8]([C:11]2[CH:16]=[CH:15][C:14](Br)=[CH:13][CH:12]=2)[CH2:7][CH2:6]1)[CH2:3][CH3:4].[C:18](=[O:20])=[O:19].Cl>O1CCCC1>[CH2:2]([C@H:5]1[CH2:10][CH2:9][C@H:8]([C:11]2[CH:16]=[CH:15][C:14]([C:18]([OH:20])=[O:19])=[CH:13][CH:12]=2)[CH2:7][CH2:6]1)[CH2:3][CH3:4]
Reactant: CCC[C@H]1CC[C@H](c2ccc(Br)cc2)CC1
Reactant: O=C=O
Agent: Cl
Agent: [Mg]
Solvent: C1CCOC1
Product: CCC[C@H]1CC[C@H](c2ccc(C(=O)O)cc2)CC1

Procedure:
A Grignard reagent was prepared from a solution of 50 ml of dried tetrahydrofuran in which 0.88 g (36.7 mmol) of magnesium and 10.0 g (35.6 mmol) of 1-(trans-4-n-propylcyclohexyl)-4-bromobenzene were dissolved, and the Grignard reagent was put into dry ice. After vaporizing the dry ice, hydrochloric acid was added to the resultant to give a precipitate, and the precipitate was filtered, washed with water, dried, and recrystallized from toluene to give 7.5 g (30.5 mmol) of p-(trans-4-propylcyclohexyl)benzoic acid.
Reaction SMILES: [NH2:1][CH2:2][C:3]([OH:5])=[O:4].F[C:7]1[CH:12]=[CH:11][C:10]([N+:13]([O-:15])=[O:14])=[CH:9][CH:8]=1.C(=O)(O)[O-].[Na+]>O1CCOCC1.O>[N+:13]([C:10]1[CH:11]=[CH:12][C:7]([NH:1][CH2:2][C:3]([OH:5])=[O:4])=[CH:8][CH:9]=1)([O-:15])=[O:14]
Reactant: O=[N+]([O-])c1ccc(F)cc1
Reactant: NCC(=O)O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: O=C(O)CNc1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Yield: 72 %

Procedure:
Glycine (5.31 g, 70.8 mmol) was added to a mixture of 1-fluoro-4-nitro-benzene (5.0 g, 35.4 mmol) and sodium bicarbonate (5.94 g, 70.8 mmol) in dioxane (10 mL) and water (60 mL) and heated at reflux for 6 h. The reaction mixture was cooled to room temperature and washed with ethyl acetate. The aqueous layer was acidified with 1N hydrochloric acid to pH ˜3 and extracted with ethyl acetate. The extract was washed with water, brine, dried over anhydrous sodium sulfate and concentrated to dryness to afford (4-nitro-phenylamino)-acetic acid (5.0 g, 72%) as a yellow solid.
Reaction SMILES: O.[NH2:2][NH2:3].[Cl:4][CH2:5][CH2:6][CH2:7][CH:8]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:9](OC)=[O:10]>C(O)C>[Cl:4][CH2:5][CH2:6][CH2:7][CH:8]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:9]([NH:2][NH2:3])=[O:10]
Reactant: NN
Reactant: COC(=O)C(CCCCl)c1ccccc1
Solvent: CCO
Solvent: O
Product: NNC(=O)C(CCCCl)c1ccccc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of methyl phenylacetate (2.0 g) in DMF (5 mL) was added to a solution of sodium hydride (containing mineral oil at 40%, 590 mg) in DMF (20 mL) under ice-cooling. The reaction solution was stirred for 10 minutes, further stirred at room temperature for 30 minutes and then ice-cooled again. A solution of 1-chloro-3-iodopropane (2.99 g) in DMF (5 mL) was added to the reaction mixture, and the reaction solution was stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, and the organic layer was separated. The resulting organic layer washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure to obtain a crude product of methyl 5-chloro-2-phenylpentanoate. Hydrazine monohydrate (8 mL) was added to a solution of the resulting crude methyl 5-chloro-2-phenylpentanoate (3.279 g) in ethanol (20 mL), and the reaction solution was stirred at room temperature overnight. The reaction solution was concentrated under reduced pressure. Saturated sodium bicarbonate water and ethyl acetate and were added to the residue, and the organic layer was separated. The resulting organic layer washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system) to obtain 730 mg of the title compound. The property values of the compound are as follows.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.[C:10](OC(=O)C)(=[O:12])[CH3:11]>>[C:10]([N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1)(=[O:12])[CH3:11]
Reactant: CC(=O)OC(C)=O
Reactant: c1ccc2c(c1)CCN2
Product: CC(=O)N1CCc2ccccc21
Temperature: 0 °C

Procedure:
To a 3-neck 500 ml round bottom flask containing 108.5 g (0.911 mol) indoline was added acetic anhydride at a rate such as to maintain a temperature below 25° C. After addition (one hour), the reddish sludge was poured into ice water, filtered and washed several times with water. It was allowed to dry overnight and recrystallized from 700 ml of ethanol and gave 116.6 g (72.4% by weight yield) of N-acetylindoline.
Reaction SMILES: [CH3:1][O:2]C1C=CC(C)=CC=1.[C-]#N.[Na+].[CH3:13][O:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=1>>[CH3:13][O:14][CH:15]([O:2][CH3:1])[C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=1
Reactant: COCc1ccc(OC)cc1
Reactant: COc1ccc(C)cc1
Agent: [C-]#N
Agent: [Na+]
Product: COc1ccc(C(OC)OC)cc1
Yield: 15 %

Procedure:
In the article "Nuclear Cyanation of Methylanisoles" by k. Yoshida, M. Shigi and T. Fueno in J. Org. Chem., 1975, Vol. 40, No. 1, pp. 63-66, the reaction of 4-methoxytoluene (Ic) in a methanolic solution of NaCN or Na acetate is described. In this reaction, 4-(methoxymethyl)-anisole and, in a material (current) yield of 15% (24%) of the theoretical, anisaldehyde-dimethylacetal (IIc) are also formed, in addition to the respective ring-substitution products.
Reaction SMILES: C([Li])CCC.CCCCCC.[CH2:12]([C:14]([C:26]1[CH:31]=[CH:30][C:29]([OH:32])=[C:28]([CH3:33])[CH:27]=1)([C:17]1[CH:22]=[CH:21][C:20]([C:23]#[CH:24])=[C:19]([CH3:25])[CH:18]=1)[CH2:15][CH3:16])[CH3:13].[CH3:34][C:35]([CH3:39])([CH3:38])[CH:36]=[O:37].[Cl-].[NH4+]>O1CCCC1>[CH2:12]([C:14]([C:26]1[CH:31]=[CH:30][C:29]([OH:32])=[C:28]([CH3:33])[CH:27]=1)([C:17]1[CH:22]=[CH:21][C:20]([C:23]#[C:24][CH:36]([OH:37])[C:35]([CH3:39])([CH3:38])[CH3:34])=[C:19]([CH3:25])[CH:18]=1)[CH2:15][CH3:16])[CH3:13]
Reactant: C#Cc1ccc(C(CC)(CC)c2ccc(O)c(C)c2)cc1C
Reactant: CC(C)(C)C=O
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CCC(CC)(c1ccc(O)c(C)c1)c1ccc(C#CC(O)C(C)(C)C)c(C)c1
Reaction time: 0.5 h
Yield: 82.7 %

Procedure:
A 2.44 M solution of n-butyllithium in hexane (42.8 mL, 104.5 mmol) was added to a solution of 4-[1-ethyl-1-(4-ethynyl-3-methyl-phenyl)-propyl]-2-methyl-phenol (Example 1-(3); 12.22 g, 41.8 mmol) in tetrahydrofuran (300 mL) at 0° C., and the mixture was stirred at the same temperature for 30 minutes. Trimethylacetaldehyde (13.79 mL, 125.4 mmol) was added at 0° C., and the mixture was stirred at the same temperature for 30 minutes. A saturated aqueous ammonium chloride solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by a silica gel column (hexane/ethyl acetate=9/1 to 3/1) to give the title compound (13.08 g, 83%).
Reaction SMILES: [CH:1]1([NH2:4])[CH2:3][CH2:2]1.Br[CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:11][CH:10]=1>O1CCCC1>[C:12]1([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:11]=[CH:10][C:9]([O:8][CH2:7][CH2:6][NH:4][CH:1]2[CH2:3][CH2:2]2)=[CH:14][CH:13]=1
Reactant: NC1CC1
Reactant: BrCCOc1ccc(-c2ccccc2)cc1
Solvent: C1CCOC1
Product: c1ccc(-c2ccc(OCCNC3CC3)cc2)cc1
Temperature: 50 °C
Yield: 96.3 %

Procedure:
To a mixture of 5.15 g (90.2 mmol) of cyclopropylamine and 2.5 ml (18.04 mmol) of thiethylamine in 50 ml of tetrahydrofurane is added 5 g (18.04 mmol) of 4-(2-bromoethoxy)biphenyl. The reaction mixture is heated at 50° C. for 5 hrs. The solvent and the excess of cyclopropylamine are then removed under vacuum and the residue is dissolved in ethyl acetate. The organic solution is acidified to pH=4 by adding a 1N solution of HCl. The abundant obtained white precipate is filtered, washed by water and to diisopropyl ether and dried under vacuum to yield 4.4 g (96% yield) of N-[2-(biphenyl-4-yloxy)ethyl]cyclo-propanamine as its hydrochloride salt. mp (melting point)=252° C.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]([O:14][CH2:15][C:16]2[CH:25]=[CH:24][C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:17]=2)[CH:11]([C:26]2[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH2:34][CH2:35][O:36][CH2:37][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=3[O:44][CH3:45])=[CH:28][CH:27]=2)[CH:10]([CH2:46][OH:47])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:48](Br)[CH:49]=[CH2:50]>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]([O:14][CH2:15][C:16]2[CH:25]=[CH:24][C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:17]=2)[CH:11]([C:26]2[CH:27]=[CH:28][C:29]([O:32][CH2:33][CH2:34][CH2:35][O:36][CH2:37][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=3[O:44][CH3:45])=[CH:30][CH:31]=2)[CH:10]([CH2:46][O:47][CH2:50][CH:49]=[CH2:48])[CH2:9]1)=[O:7])([CH3:2])([CH3:4])[CH3:3]
Reactant: C=CCBr
Reactant: COc1ccccc1COCCCOc1ccc(C2C(CO)CN(C(=O)OC(C)(C)C)CC2OCc2ccc3ccccc3c2)cc1
Product: C=CCOCC1CN(C(=O)OC(C)(C)C)CC(OCc2ccc3ccccc3c2)C1c1ccc(OCCCOCc2ccccc2OC)cc1

Procedure:
In an analogous manner to that described in Example 13 (g), by alkylating (3SR,4RS,5RS)-3-hydroxymethyl-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-5-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylic acid tert-butyl ester with allylbromide there was obtained (3SR,4RS,5RS)-3-allyloxymethyl-4-[4-[3-(2-methoxy-benzyloxy )-propoxy]-phenyl]-5-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylic acid tert-butyl ester as a colorless oil; MS: 682 (M+H)+.
Reaction SMILES: Cl.Cl[CH2:3][C:4]1[N:8]2[CH:9]=[C:10]([CH3:13])[CH:11]=[CH:12][C:7]2=[N:6][C:5]=1[C:14]1[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=1.[CH3:21][C:22]1[S:26][C:25]([SH:27])=[N:24][N:23]=1>>[CH3:13][C:10]1[CH:11]=[CH:12][C:7]2[N:8]([C:4]([CH2:3][S:27][C:25]3[S:26][C:22]([CH3:21])=[N:23][N:24]=3)=[C:5]([C:14]3[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=3)[N:6]=2)[CH:9]=1
Reactant: Cc1nnc(S)s1
Reactant: Cc1ccc(-c2nc3ccc(C)cn3c2CCl)cc1
Agent: Cl
Product: Cc1ccc(-c2nc3ccc(C)cn3c2CSc2nnc(C)s2)cc1

Procedure:
The title compound was prepared according to Method A and the experimentals described for compound 139 from 3-(chloromethyl)-6-methyl-2-p-tolylimidazo[1,2-a]pyridine hydrochloride and 5-methyl-1,3,4-thiadiazole-2-thiol. m/e− 367 for C19H19N4S2 [M+H]+; 1H-NMR (400 MHz, CDCl3) δ 8.27 (s, 1H), 7.86 (d, J=8.0 Hz, 2H), 7.55 (d, J=9.1 Hz, 1H), 7.28 (d, J=8.0 Hz, 2H), 7.09 (dd, J=1.4, 9.1 Hz, 1H), 5.83 (s, 2H), 2.40 (s, 3H), 2.37 (s, 3H), 2.33 (s, 3H) ppm; 13C-NMR (100 MHz, CDCl3, δ) 186.983, 156.637, 146.840, 144.588, 138.165, 131.265, 129.597, 128.800, 128.649, 122.931, 122.787, 116.971, 113.923, 44.131, 21.557, 18.638, 16.606 ppm.
Reaction SMILES: C(N(CC)CC)C.I[C:9]1[CH:18]=[CH:17][C:16]2[NH:15][C:14](=[O:19])[C:13]3[NH:20][CH:21]=[CH:22][C:12]=3[C:11]=2[CH:10]=1.[CH2:23]([C:25]([O-:27])=[O:26])[CH3:24].[C:28]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=1)#[CH:29]>O1CCOCC1.[Cu](I)I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[O:19]=[C:14]1[C:13]2[NH:20][CH:21]=[CH:22][C:12]=2[C:11]2[CH:10]=[C:9]([C:29]#[C:28][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=3)[CH:18]=[CH:17][C:16]=2[NH:15]1.[CH2:23]([C:25]([O-:27])=[O:26])[CH3:24]
Reactant: O=c1[nH]c2ccc(I)cc2c2cc[nH]c12
Reactant: C#Cc1ccccn1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: I[Cu]I
Agent: CCC(=O)[O-]
Solvent: C1COCCO1
Solvent: CCN(CC)CC
Product: O=c1[nH]c2ccc(C#Cc3ccccn3)cc2c2cc[nH]c12
Temperature: 100 °C
Reaction time: 0.25 h
Yield: 45.2 %

Procedure:
20 mg (0.11 mmol) of copper iodide, 28 mg (0.27 mmol) of triethylamine and 14 mg (0.02 mmol) of dichlorobis(triphenylphosphine)-palladium (II) are added to a suspension of 80 mg (0.21 mmol) of 8-iodo-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-ethyl carboxylate in 2.4 ml of anhydrous dioxan, then this mixture is degassed under argon. After 15 minutes, 32 mg (0.31 mmol) of 2-ethynyl-pyridine are added, then the mixture is heated at 100° C. for 3 hours. The raw reaction product is then filtered on celite, the filtrate is evaporated to dryness and the residue is purified by chromatography on silica (eluent ethyl acetate) to give 34 mg (46%) of 4-oxo-8-pyridin-2-ylethynyl-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-ethyl carboxylate in the form of a brown solid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([C:12]2[C:13]([CH2:17][CH2:18][CH2:19]CS([O-])(=O)=O)=[N:14][O:15][N:16]=2)=[O:11])[CH:5]=[CH:6][C:7]=1[F:8].CCN(C(C)C)C(C)C.[NH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1>C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([C:12]2[C:13]([CH2:17][CH2:18][CH2:19][N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)=[N:14][O:15][N:16]=2)=[O:11])[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: C1COCCN1
Reactant: O=C(Nc1ccc(F)c(Cl)c1)c1nonc1CCCCS(=O)(=O)[O-]
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: O=C(Nc1ccc(F)c(Cl)c1)c1nonc1CCCN1CCOCC1
Temperature: 70 °C
Yield: 53.2 %

Procedure:
3-(4-[(3-Chloro-4-fluorophenyl)amino]carbonyl-1,2,5-oxadiazol-3-yl)propylmethanesulfonate (19 mg, 0.051 mmol) was dissolved in anhydrous ACN (100 μL,) followed by addition of DIPEA (44 μL, 0.26 mmol) and morpholine (6.7 μL, 76.8 μmol). The reaction was stirred and heated at 70° C. for 3 h. The reaction was concentrated and purified with silica gel chromatography (60-100% ethyl acetate/hex) to give the desired product (10 mg, 54%). LCMS for C16H19ClFN4O3(M+H)+: m/z=369.1.
Reaction SMILES: [OH:1][CH2:2][CH2:3][C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[CH2:9])=[CH:6][CH:5]=1.C(N(CC)CC)C.[C:19](Cl)([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[O:20]>C1C=CC=CC=1>[C:19]([O:1][CH2:2][CH2:3][C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[CH2:9])=[CH:6][CH:5]=1)([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[O:20]
Reactant: CCOC(=O)C(=O)Cl
Reactant: C=Cc1ccc(CCO)cc1
Solvent: c1ccccc1
Solvent: CCN(CC)CC
Product: C=Cc1ccc(CCOC(=O)C(=O)OCC)cc1
Temperature: 10 °C
Reaction time: 2 h

Procedure:
A 200 ml flask equipped with a stirrer, a thermometer and a dropping funnel was charged with 14.8 g (0.1 mol) of p-hydroxyethylstyrene, 150 ml of benzene and 10.1 g (0.1 mol) of triethylamine and cooled to 10° C. To the mixture was added dropwise with stirring 13.7 g (0.1 mol) of ethoxalyl chloride for one hour at 10° C. to precipitate a hydrochloride of triethylamine (white solid). After mixting at room temperature for 2 hours, 80 g of hexane was added to complete precipitation of the hydrochloride. The hydrochloride is removed by filteration and the resultant filtrate was condensed to obtain the aimed compound. The compound was identified by 1H NMR (360 Mz) and IR. ##STR6##