Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[N+:14]([O-])=O)[CH:7]=1>CCO.CCOC(C)=O.[Pd]>[NH2:14][C:9]1[CH:10]=[N:11][CH:12]=[CH:13][C:8]=1[C:6]1[CH:5]=[C:4]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:22])([CH3:21])[CH3:23])[CH:3]=[C:2]([CH3:1])[CH:7]=1
Reactant: Cc1cc(NC(=O)OC(C)(C)C)cc(-c2ccncc2[N+](=O)[O-])c1
Agent: [Pd]
Solvent: CCO
Solvent: CCOC(C)=O
Product: Cc1cc(NC(=O)OC(C)(C)C)cc(-c2ccncc2N)c1
Reaction time: 8 h
Yield: 111.7 %

Procedure:
tert-butyl (3-(3-aminopyridin-4-yl)-5-methylphenyl) carbamate. A solution of tert-butyl (3-methyl-5-(3-nitropyridin-4-yl)phenyl)carbamate (198 mg, 0.60 mmol) in EtOH (5 mL) and EtOAc (5 mL) was degassed by bubbling N2 (g) through the solution for 10 min. Pd/C (10 wt %, 64 mg, 0.060 mmol) was added. A gas bag with a 3-way stopcock filled with H2 was attached to the flask. The flask was evacuated under vacuum and then back-filled with H2 (3×). The mixture was stiffed overnight at RT. The solution was degassed by bubbling N2 (g) through the solution for 10 min and was then filtered through celite. The solution was concentrated to afford tert-butyl (3-(3-aminopyridin-4-yl)-5-methylphenyl)carbamate (200 mg, 0.67 mmol, 111% yield) as an off-white foam. MS (ESI, pos. ion) m/z: 300.0 (M+1).
Reaction SMILES: [CH3:1][P:2]([CH2:5][N:6]1[CH2:11][CH2:10][N:9]([CH2:12][C:13]2[C:19]([C:20]([F:23])([F:22])[F:21])=[CH:18][C:16]([NH2:17])=[CH:15][CH:14]=2)[CH2:8][CH2:7]1)([CH3:4])=[O:3].[I:24][C:25]1[CH:26]=[C:27]([CH:31]=[CH:32][C:33]=1[CH3:34])[C:28](Cl)=[O:29].C(N(C(C)C)CC)(C)C.[I-]>ClCCl>[CH3:4][P:2]([CH2:5][N:6]1[CH2:7][CH2:8][N:9]([CH2:12][C:13]2[C:19]([C:20]([F:23])([F:21])[F:22])=[CH:18][C:16]([NH:17][C:28](=[O:29])[C:27]3[CH:31]=[CH:32][C:33]([CH3:34])=[C:25]([I:24])[CH:26]=3)=[CH:15][CH:14]=2)[CH2:10][CH2:11]1)([CH3:1])=[O:3]
Reactant: Cc1ccc(C(=O)Cl)cc1I
Reactant: CP(C)(=O)CN1CCN(Cc2ccc(N)cc2C(F)(F)F)CC1
Agent: [I-]
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: Cc1ccc(C(=O)Nc2ccc(CN3CCN(CP(C)(C)=O)CC3)c(C(F)(F)F)c2)cc1I
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
4-({4-[(dimethylphosphoryl)methyl]piperazin-1-yl}methyl)-5-(trifluoromethyl)aniline (yellow solid, 3.66 mmole, 1.0 eq.) was dissolved in 15 mL anhydrous dichloromethane. 3-iodo-4-methylbenzoyl chloride (1.58 grams, 5.64 mmole, 1.54 eq.) was added in one portion. At 0° C., under N2 protection, diisopropylethyl amine (2.4 mL, 14.0 mmole, 3.8 eq.) was added dropwise in 3 minutes. The reaction mixture was stirred at 0° C. under N2 for 30 minutes. It was then evaporated to remove most of the volatile components. The residue was purified via column chromatography (elution sequence: 100% dichloromethane-1% MeOH/dichloromethane/sat.NH3-10% MeOH/dichloromethane/sat.NH3). 40 mg of light yellow color oil was obtained and identified as the desire iodide. MS (LC/MS): 592.3 [M−].
Reaction SMILES: [Al+3].[Cl-].[Cl-].[Cl-].[CH3:5][CH:6]([CH2:10][CH3:11])[C:7](Cl)=[O:8].[C:12]1([S:18][CH3:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.O>C(Cl)(Cl)Cl>[CH3:19][S:18][C:12]1[CH:17]=[CH:16][C:15]([C:7](=[O:8])[CH:6]([CH3:5])[CH2:10][CH3:11])=[CH:14][CH:13]=1
Reactant: CCC(C)C(=O)Cl
Reactant: CSc1ccccc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: O
Solvent: ClC(Cl)Cl
Product: CCC(C)C(=O)c1ccc(SC)cc1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
To a suspension of AlCl3 (35.4 g) in CHCl3 (500 mL) at -10° C. was added dropwise 2-methylbutyryl chloride (31.3 g) followed by thioanisole (31.2 mL). The mixture was then stirred at r.t. for 20 min. and was then cooled back to 0° C. Water (200 mL) was then added over 30 min. The CHCl3 layer was separated and dried over MgSO4. After filtration and removal of the solvent, the residue was dried under vacuum at 80° C. for 2 h to give 35 g of the title compound.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:12]=[CH:11][CH:10]=[CH:9][C:5]=1[C:6]([OH:8])=[O:7])[CH3:2].S(Cl)(Cl)=O.[Cl:17][S:18](O)(=[O:20])=[O:19]>O>[Cl:17][S:18]([C:10]1[CH:11]=[CH:12][C:4]([O:3][CH2:1][CH3:2])=[C:5]([CH:9]=1)[C:6]([OH:8])=[O:7])(=[O:20])=[O:19]
Reactant: CCOc1ccccc1C(=O)O
Reactant: O=S(=O)(O)Cl
Solvent: O=S(Cl)Cl
Solvent: O
Product: CCOc1ccc(S(=O)(=O)Cl)cc1C(=O)O
Temperature: 25 °C
Reaction time: 18 h
Yield: 90.9 %

Procedure:
Molten 2-ethoxybenzoic acid (25.0 g, 0.150 mol) was added to a stirred, ice-cooled mixture of thionyl chloride (11 ml, 0.151 mol) and chlorosulphonic acid (41.3 ml, 0.621 mol), whilst maintaining the temperature of the reaction mixture below 25° C. The resulting mixture was stirred at room temperature for 18 hours and then poured into a stirred mixture of ice (270 g) and water (60 ml) to give an off-white precipitate. Stirring was continued for 1 hour, then the product was collected by filtration, washed with water and dried under vacuum to provide the title compound (36.08 g). A reference sample, m.p. 115-116° C. was obtained by crystallisation from hexane:toluene. Found: C, 41.02; H, 3.27. C9H9ClO5S requires C, 40.84; H, 3.43%. δ (CDCl3): 1.64 (3H, t), 4.45 (2H, q), 7.26 (1H, d), 8.20 (1H, dd), 8.80 (1H, d).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9](Cl)[N:8]=[CH:7]2.[C:13]1([C:19](B(O)O)=[CH2:20])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:19]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[CH2:20])[N:8]=[CH:7]2
Reactant: Clc1ncc2cccc(Br)c2n1
Reactant: C=C(B(O)O)c1ccccc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Product: C=C(c1ccccc1)c1ncc2cccc(Br)c2n1
Temperature: 90 °C
Reaction time: 60 h
Yield: 14.9 %

Procedure:
A suspension of 8-bromo-2-chloroquinazoline (Ark Pharm, Inc., Libertyville, Ill.; 2.00 g, 8.21 mmol), (1-phenylvinyl)boronic acid (Aldrich; 1.215 g, 8.21 mmol), potassium carbonate (2.384 g, 17.25 mmol), and Pd(PPh3)4 (0.190 g, 0.164 mmol) in toluene (75 mL) was stirred under argon at 90° C. for 2.5 d. The reaction was cooled to 25° C. and partitioned between EtOAc (200 mL) and water (100 mL). The organic layer was separated, sequentially washed with water (2×80 mL) and brine (80 mL), dried over Na2SO4, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0-100% hexanes/DCM) furnished 8-bromo-2-(1-phenylvinyl)quinazoline (380 mg, 1.221 mmol, 15% yield) as a yellow solid: 1H NMR (400 MHz, CDCl3) δ ppm 9.36 (1H, s), 8.20 (1H, s), 7.88 (1H, d, J=8.0 Hz), 7.58-7.65 (2H, m), 7.44-7.51 (2H, m), 7.40-7.44 (2H, m), 6.84 (1H, s), 5.99 (1H, s). m/z (ESI, +ve) 311.0 (M+H)+.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH:11]([CH:15]([CH3:17])[CH3:16])[C:12]([OH:14])=[O:13].C(N(CC)CC)C.[C:25]([CH:27]([C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([O:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[N:30]=1)O)#[N:26]>CCOCC>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH:11]([CH:15]([CH3:17])[CH3:16])[C:12]([O:14][CH:27]([C:25]#[N:26])[C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([O:35][C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)[N:30]=1)=[O:13]
Reactant: CC(C)C(C(=O)O)c1ccc2ccccc2c1
Reactant: N#CC(O)c1cccc(Oc2ccccc2)n1
Solvent: CCOCC
Solvent: CCN(CC)CC
Product: CC(C)C(C(=O)OC(C#N)c1cccc(Oc2ccccc2)n1)c1ccc2ccccc2c1
Reaction time: 18 h

Procedure:
To the acid chloride of 2-(2-naphthyl)-3-methylbutanoic acid (2.5 mmol) in ether is added 1.3 ml of triethylamine followed by the cyano(6-phenoxy-2-pyridyl)methanol in 5 ml of ether, from part A above, over about 2 minutes. The reaction mixture is stirred for about 18 hours and then quenched with saturated aqueous sodium bicarbonate. The organic phase is washed with aqueous sodium bicarbonate, water and brine, dried over calcium sulfate and solvent evaporated. The crude product is chromatographed on a circular chromatograph eluting with 20% ether/hexane to give cyano(6-phenoxy-2-pyridyl)methyl 2-(2-naphthyl)-3-methylbutanoate, MS m/e 436 (M+).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[NH:10][C:9](=O)O[C:6](=[O:7])[C:5]2=[CH:12][C:13]=1[I:14].C(O)(=O)C.C(N)=[NH:20]>CN(C)C=O>[OH:7][C:6]1[C:5]2[C:4](=[CH:3][C:2]([F:1])=[C:13]([I:14])[CH:12]=2)[N:10]=[CH:9][N:20]=1
Reactant: N=CN
Reactant: O=c1[nH]c2cc(F)c(I)cc2c(=O)o1
Solvent: CC(=O)O
Solvent: CN(C)C=O
Product: Oc1ncnc2cc(F)c(I)cc12
Temperature: 110 °C
Yield: 91.2 %

Procedure:
Dimethylformamide (0.5 liters), 4-fluoro-5-iodo-isatoic anhydride (45 grams, 147 mmoles), and formamidine acetate (45.92 grams, 441 mmoles), were combined in a one liter one-neck flask fitted with a magnetic stir bar. The mixture was placed under anhydrous nitrogen and heated at 110° C. for 6 hours. The mixture was allowed to cool, followed by concentrating the reaction mixture to one third its original volume on the rotary evaporator. The resulting mixture was poured onto 3 liters of ice water. The resulting precipitated solid was collected by suction filtration. The solid was washed with an additional one liter of distilled water. The resulting solid was dried under vacuum at 70° C. to yield 38.9 grams (91%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ: 12.43(s, 1H), 8.46(d, 1H), 8.12(s, 1H), 7.49(d, 1H). ESI-MS m/z 291 (M+1).
Reaction SMILES: Cl[CH2:2][C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([CH:12]([CH3:18])[C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:8][C:7]=1[OH:19])=[O:4].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O.O>[O:4]=[C:3]1[CH2:2][O:19][C:7]2[CH:8]=[C:9]([CH:12]([CH3:18])[C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:10]=[CH:11][C:6]=2[NH:5]1
Reactant: CCOC(=O)C(C)c1ccc(NC(=O)CCl)c(O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: O
Product: CCOC(=O)C(C)c1ccc2c(c1)OCC(=O)N2
Temperature: 25 °C

Procedure:
A solution of ethyl 2-(4-(2-chloroacetamido)-3-hydroxyphenyl)propanoate (110 mg, 0.385 mmol) in acetone (10 mL) was added potassium carbonate (61 mg). the reaction mixture was refluxed for 3 hrs then cooled to room temperature. The mixture was diluted with H2O and extracted with EtOAc. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel using EtOAc:hexanes (1:2) as eluent.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][O:16][C:17]3[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][C:25]([O:27][CH3:28])=[O:26])=[CH:19][CH:18]=3)[CH:10]=2)=[C:4]([CH3:29])[CH:3]=1.[CH2:30]([O:32][CH2:33][CH2:34]O)[CH3:31].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[CH2:30]([O:32][CH2:33][CH2:34][O:1][C:2]1[CH:3]=[C:4]([CH3:29])[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][O:16][C:17]3[CH:18]=[CH:19][C:20]([CH2:23][CH2:24][C:25]([O:27][CH3:28])=[O:26])=[CH:21][CH:22]=3)[CH:10]=2)=[C:6]([CH3:8])[CH:7]=1)[CH3:31]
Reactant: COC(=O)CCc1ccc(OCc2cccc(-c3c(C)cc(O)cc3C)c2)cc1
Reactant: CCOCCO
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CCOCCOc1cc(C)c(-c2cccc(COc3ccc(CCC(=O)OC)cc3)c2)c(C)c1
Yield: 50.9 %

Procedure:
To a solution of methyl 3-[4-[(4′-hydroxy-2′,6′-dimethylbiphenyl-3-yl)methoxy]phenyl]propanoate (0.20 g, 0.51 mmol), 2-ethoxyethanol (0.099 mL, 1.02 mmol) and triphenylphosphine (0.18 g, 0.67 mmol) in tetrahydrofuran (4.0 mL) was added dropwise diethyl azodicarboxylate (40% toluene solution, 0.30 mL) at 0° C. with stirring and the mixture was stirred at room temperature for 12 hrs. The reaction mixture was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=3/1) to give the title compound (0.12 g, yield 51%) as a colorless oil.
Reaction SMILES: [Cl:1][SiH2:2][Cl:3].[CH2:4]=[CH:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]>Cl[Ni]Cl>[CH2:15]([SiH:2]([Cl:3])[Cl:1])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH3:4]
Reactant: Cl[SiH2]Cl
Reactant: C=CCCCCCCCCCC
Agent: Cl[Ni]Cl
Product: CCCCCCCCCCCC[SiH](Cl)Cl
Reaction time: 30 h

Procedure:
Dichlorosilane in an amount of 75.8 g (0.75 mol), 228.5 g of 1-dodecene (1.36 mol) and 0.05 mol % of a catalyst NiCl2 --(PPh3)2 (relative to dichlorosilane) were charged in a 500 ml pressure-proof stainless steel reactor and sealed. A reaction was carried out at 100° C. for 30 hours and the reacted liquid was distilled to obtain n-dodecyldichlorosilane (n--C12H25SiHCl2).
Reaction SMILES: [CH2:1]([NH2:5])[CH:2]([CH3:4])[CH3:3].[C:6]([CH2:9][N:10]1[C:14](=[O:15])[C:13](=[CH:16]OCC)[S:12][C:11]1=[S:20])([OH:8])=[O:7]>C(O)C>[C:6]([CH2:9][N:10]1[C:14](=[O:15])[C:13](=[CH:16][NH:5][CH2:1][CH:2]([CH3:4])[CH3:3])[S:12][C:11]1=[S:20])([OH:8])=[O:7]
Reactant: CCOC=C1SC(=S)N(CC(=O)O)C1=O
Reactant: CC(C)CN
Solvent: CCO
Product: CC(C)CNC=C1SC(=S)N(CC(=O)O)C1=O
Yield: 65.6 %

Procedure:
0.74 Gram (0.01 mole) of isobutylamine was added to a mixture of 1.2 g (0.005 mole) of 3-carboxymethyl-5-ethoxymethylidenerhodanine and 10 ml of ethanol, and the resulting mixture was subjected to reaction at a temperature of 50° to 60° C. for 1 hour. The reaction mixture was concentrated and the resulting residue was dried and dissolved into water. The solution was made neutral or weakly acidic with a dilute hydrochloric acid and the formed precipitate was separated by filtration. The precipitate was washed with water, dried and recrystallized from a mixture of ethyl acetate and petroleum ether (4/1 by volume) to give 0.9 g of 3-carboxymethyl-5-isobutylaminomethylidenerhodanine in the form of yellowish red crystal (yield: 64.3%).
Reaction SMILES: [F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=1)[CH2:6][O:7][CH2:8][C:9]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:15][CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.[CH:31]1([CH:34]=O)[CH2:33][CH2:32]1.C([BH3-])#N.[Na+]>CO.FC(F)(F)C(O)=O>[F:30][C:2]([F:29])([F:1])[C:3]1[CH:4]=[C:5]([CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=1)[CH2:6][O:7][CH2:8][C:9]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:15][CH2:14][CH2:13][N:12]([CH2:34][CH:31]2[CH2:33][CH2:32]2)[CH2:11][CH2:10]1
Reactant: FC(F)(F)c1cc(COCC2(c3ccccc3)CCCNCC2)cc(C(F)(F)F)c1
Reactant: O=CC1CC1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: O=C(O)C(F)(F)F
Product: FC(F)(F)c1cc(COCC2(c3ccccc3)CCCN(CC3CC3)CC2)cc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 41.5 %

Procedure:
Mixture of isomer A of 4-((3,5-bis(trifluoromethyl)benzyloxy)methyl)-4-phenylazepane (3 mg) and cyclopropanecarbaldehyde (1.4 mg) in methanol (0.15 mL) was stirred at room temperature for 0.5 hr, then sodium cyanoborohydride (1.0 M solution in THF, 0.02 mL) was added followed by 1 drop of trifluoroacetic acid. The mixture was stirred at room temperature for overnight and concentrated under vacuum. Then saturated sodium bicarbonate and dichloromethane was added to the mixture and the organic layer was separated. The aqueous layer was extracted with dichloromethane 2 times and the combined organic layers were dried over magnesium sulfate, filtered and concentrated under vacuum to give the product as a clear sticky oil (1.4 mg, 41% yield).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:58])[CH:4]([NH:9][C:10](=[O:57])[CH2:11][N:12]1[C:16]([CH3:27])([C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:20]=[CH:19][CH:18]=2)[C:15](=[O:28])[N:14]([CH2:29][CH2:30][CH2:31][C:32]2[N:33]=[CH:34][N:35](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[CH:36]=2)[C:13]1=[O:56])[CH2:5][CH2:6][S:7][CH3:8].C([SiH](C(C)C)C(C)C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:58])[CH:4]([NH:9][C:10](=[O:57])[CH2:11][N:12]1[C:16]([CH3:27])([C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:20]=[CH:19][CH:18]=2)[C:15](=[O:28])[N:14]([CH2:29][CH2:30][CH2:31][C:32]2[N:33]=[CH:34][NH:35][CH:36]=2)[C:13]1=[O:56])[CH2:5][CH2:6][S:7][CH3:8]
Reactant: COC(=O)C(CCSC)NC(=O)CN1C(=O)N(CCCc2cn(C(c3ccccc3)(c3ccccc3)c3ccccc3)cn2)C(=O)C1(C)c1cccc2ccccc12
Agent: CC(C)[SiH](C(C)C)C(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COC(=O)C(CCSC)NC(=O)CN1C(=O)N(CCCc2c[nH]cn2)C(=O)C1(C)c1cccc2ccccc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 94.8 %

Procedure:
0.11 g(0.13 mmol) of 2-(2-{3-[3-(1-triphenylmethyl-imidazol-4-yl)-propyl]-5-methyl-5-naphthalen-1-yl-2,4-dioxo-imidazolidin-1-yl}-acetylamino)-4-methylsulfanyl-butyric acid methyl ester prepared in Example 1-3) and 0.053 ml(0.26 mmol) of triisopropylsilane were dissolved in 5 ml of methylene chloride. Then, 5 ml of trifluoroacetic acid was added thereto and the resulting solution was stirred for one hour at room temperature. The organic solvent was removed under reduced pressure and saturated potassium carbonate[K2CO3] solution was added. The solution was extracted with 10 of ethyl acetate and the solvent was removed under reduced pressure. The residue was subjected to chromatography using a solvent mixture of methanol-methylene chloride(5:95) as the eluent to obtain 0.068 g(Yield: 95%) of the title compound.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[C:7]([CH2:9][C:10](OC)=[O:11])#[N:8]>CC(OC)(C)C>[N:1]1([C:10](=[O:11])[CH2:9][C:7]#[N:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1
Reactant: C1COCCN1
Reactant: COC(=O)CC#N
Solvent: COC(C)(C)C
Product: N#CCC(=O)N1CCOCC1
Temperature: 55 °C
Yield: 90.2 %

Procedure:
A nitrogen inerted reactor equipped with reflux condenser, nitrogen inlet and mechanical stirring is charged with morpholine (1.2 mol), methyl cyanoacetate (1.0 mol) and MtBE (52 mL). The homogeneous solution is heated to ca. 55° C. and stirred at that temperature for 12 to 18 hours. MtBE (33 mL) is added over ca. 15 minutes, and the solution is slowly cooled below 50° C. where nucleation becomes evident. Additional MTBE (66 μL) is added over a 1-hour period. During this time, the reaction is allowed to cool to near ambient temperature. After complete MtBE addition, the reaction is cooled with stirring to ca. 0° C. The resulting precipitate is collected via filtration and the cake is washed with additional MtBE (ca. 40 mL). The solid is dried under vacuum at ca. 45° C. to provide 3-morpholin-4-yl-3-oxo-propionitrile (139 g). This material is used in subsequent steps without further purification.
Reaction SMILES: [CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][C:9]([C:11]([OH:13])=O)=[CH:10][C:5]=2[N:4]=[CH:3]1.[NH:14]1[CH2:19][CH2:18][CH2:17][C@@H:16]2[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:25]=3[CH2:26][C@H:15]12.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>>[N:14]1([C:11]([C:9]2[CH:8]=[CH:7][C:6]3[N:2]([CH3:1])[CH:3]=[N:4][C:5]=3[CH:10]=2)=[O:13])[CH2:19][CH2:18][CH2:17][C@@H:16]2[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:25]=3[CH2:26][C@H:15]12
Reactant: c1ccc2c(c1)C[C@@H]1NCCC[C@H]21
Reactant: Cn1cnc2cc(C(=O)O)ccc21
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Product: Cn1cnc2cc(C(=O)N3CCC[C@@H]4c5ccccc5C[C@@H]43)ccc21
Yield: 90 %

Procedure:
The title compound is prepared from 1-methyl-1H-benzoimidazole-5-carboxylic acid and cis-2,3,4,4a,9,9a-hexahydro-1H-indeno[2,1-b]pyridine following a procedure analogous to that described in Example 1 [2-(7-aza-1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate is used]. Yield: 90% of theory; LC (method 4): tR=1.62 min; Mass spectrum (ESI+): m/z=332 [M+H]+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]([CH3:17])[CH2:10][CH:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[CH:5][C:4]=1[NH2:18].[C:19]([N:27]=[C:28]=[S:29])(=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>CC(C)=O>[C:19]([NH:27][C:28]([NH:18][C:4]1[CH:5]=[C:6]([N:9]([CH3:17])[CH2:10][CH:11]2[CH2:12][CH2:13][O:14][CH2:15][CH2:16]2)[CH:7]=[CH:8][C:3]=1[O:2][CH3:1])=[S:29])(=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: COc1ccc(N(C)CC2CCOCC2)cc1N
Reactant: O=C(N=C=S)c1ccccc1
Solvent: CC(C)=O
Product: COc1ccc(N(C)CC2CCOCC2)cc1NC(=S)NC(=O)c1ccccc1
Reaction time: 1 h
Yield: 71.1 %

Procedure:
To a stirred solution of 1.70 g (6.8 mmol) 4-methoxy-N1-methyl-N1-(tetrahydro-pyran-4-ylmethyl)-benzene-1,3-diamine in 30 ml acetone was added dropwise 1.0 ml (7.50 mmol) benzoyl isothiocyanate and stirring continued for 1 h at room temperature. The mixture was then concentrated in vacuo and the residue subjected to column chromatography (1/1 hexane/ethyl acetate) to afford 2.0 g (71%) 1-benzoyl-3-{2-methoxy-5-[methyl-(tetrahydro-pyran-4-ylmethyl)-amino]-phenyl}-thiourea as a yellow oil. ES-MS m/e (%): 436 (M+Na+, 13), 414 (M+H+, 100).
Reaction SMILES: [N:1]1[C:11]2[S:10][C:9]3[CH:12]=[C:13]([CH:16]([CH3:20])[C:17]([OH:19])=[O:18])[CH:14]=[CH:15][C:8]=3[CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.Cl.C(=O)([O-])O.[Na+].[CH2:27](O)[CH3:28]>>[N:1]1[C:11]2[S:10][C:9]3[CH:12]=[C:13]([CH:16]([CH3:20])[C:17]([O:19][CH2:27][CH3:28])=[O:18])[CH:14]=[CH:15][C:8]=3[CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1
Reactant: CCO
Reactant: CC(C(=O)O)c1ccc2c(c1)Sc1ncccc1CC2
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Product: CCOC(=O)C(C)c1ccc2c(c1)Sc1ncccc1CC2
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To 40 mg of 2-(5,6-dihydro benzo[b]pyrido[3,2-f]thiepin-9-yl)-propionic acid was added 15 ml of ethanol containing hydrogen chloride and the mixture was stirred at room temperature for 3 hours. The solvent was distilled off to obtain the residue, to which was added ice-water, and the resulting mixture was alkalified with 5% sodium hydrogencarbonate and extracted with ethyl acetate. The extract was washed with water and dried over anhydrous sodium sulfate. The solvent was distilled off to obtain oily substance, which was chromatographed over silica gel, eluted with benzene/chloroform(1/1), and there was obtained 35 mg of ethyl 2-(5,6-dihydro benzo[b]pyrido[3,2-f]thiepin-9-yl)-propionate as oil.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2([CH3:23])[C:14]3[C:15]([CH3:22])=[C:16]([NH2:21])[C:17]([CH3:20])=[C:18]([CH3:19])[C:13]=3[O:12][CH2:11]2)=[CH:6][CH:5]=1)([CH3:3])[CH3:2]>C(OCC)(=O)C.CCCCCC>[CH:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2([CH3:23])[C:14]3[C:15]([CH3:22])=[C:16]([NH:21][C:13](=[O:12])[CH2:14][C:10]([CH3:23])([CH3:11])[CH3:7])[C:17]([CH3:20])=[C:18]([CH3:19])[C:13]=3[O:12][CH2:11]2)=[CH:6][CH:5]=1)([CH3:3])[CH3:2]
Reactant: Cc1c(C)c2c(c(C)c1N)C(C)(c1ccc(C(C)C)cc1)CO2
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: Cc1c(C)c2c(c(C)c1NC(=O)CC(C)(C)C)C(C)(c1ccc(C(C)C)cc1)CO2
Yield: 37 %

Procedure:
Using 3-(4-isopropylphenyl)-3,4,6,7-tetramethyl-2,3-dihydro-1-benzofuran-5-amine obtained in Reference Example 34, the title compound was synthesized in the same manner as in Example 1. Yield: 37%. Melting point: 194-195° C. (ethyl acetate-hexane).