Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: N([NH-])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:9](=[O:12])([O-])[O-:10].[K+].[K+].[CH3:15]I>CN(C=O)C>[CH3:15][O:10][C:9](=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CI
Reactant: [NH-]Nc1ccccc1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)c1ccccc1

Procedure:
Alternatively, treatment of isatoic acid XC with p-aminomethylbenzoic acid in water and triethylamine affords benzoic acid XCIII. Treatment of XCIII with sodium hydroxide, dioxane, methylchloroformate, and methanol affords an intermediate quinazolinedione carboxylic acid, the acid moiety of which is then converted to the anilinylamide moiety of XCIV using procedures analogous to those described for Scheme 16 above. Alternatively, the intermediate quanzolinedione carboxylic acid in DMF is treated with potassium carbonate and methyl iodide to produce an intermediate benzoic acid methyl ester, which is converted to an intermediate benzoic acid by treatment with sodium hydroxide, methanol, and water. The benzoic acid is then converted to the corresponding anilinylamide XCV using procedures analogous to those described for Scheme 16 above.
Reaction SMILES: C(OC([NH:8][CH2:9][C:10]([N:12]1[CH:21]([CH2:22][C:23]([O-:25])=[O:24])[C:20]2[N:19]=[CH:18][CH:17]=[C:16]([Cl:26])[C:15]=2[CH2:14][CH2:13]1)=[O:11])=O)(C)(C)C.[Na+]>O1CCOCC1.Cl>[Cl-:26].[C:23]([CH2:22][CH:21]1[C:20]2[N:19]=[CH:18][CH:17]=[C:16]([Cl:26])[C:15]=2[CH2:14][CH2:13][N:12]1[C:10](=[O:11])[CH2:9][NH3+:8])([OH:25])=[O:24]
Reactant: CC(C)(C)OC(=O)NCC(=O)N1CCc2c(Cl)ccnc2C1CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: C1COCCO1
Product: [Cl-]
Product: [NH3+]CC(=O)N1CCc2c(Cl)ccnc2C1CC(=O)O
Temperature: 25 °C
Reaction time: 48 h
Yield: 261.4 %

Procedure:
94-8. To a stirred suspension of sodium 2-(7-(2-((tert-butoxycarbonyl)amino)acetyl)-4-chloro-5,6,7,8-tetrahydro-1,7-naphthyridin-8-yl)acetate (540 mg, 1.41 mmol) in dioxane (10 mL), 4N HCl in dioxane (1.76 mL, 7.03 mmol) was added and the reaction mixture was stirred at RT for 48 h. The beige precipitate was filtered off washed with a small amount of diethyl ether (2×). The HCl salt was dried under high vacuo overnight to yield the title compound as beige solid (590 mg) containing a residual amount of NaCl. UPLC-MS: MS 284.1 (M+H+); UPLC rt 0.45 min.
Reaction SMILES: ClC(OC(C)C)=O.[CH2:8]([O:10][C:11]([C:13]1[CH:14]=[CH:15][C:16]2[S:21][CH:20]([CH2:22][CH2:23][CH2:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=3)[C:19](=[O:33])[N:18]([CH2:34][C:35]([OH:37])=O)[C:17]=2[CH:38]=1)=[O:12])[CH3:9].CN1CCOCC1.C[Si](C)(C)[O:48][NH2:49].Cl>O1CCCC1>[OH:48][NH:49][C:35](=[O:37])[CH2:34][N:18]1[C:17]2[CH:38]=[C:13]([C:11]([O:10][CH2:8][CH3:9])=[O:12])[CH:14]=[CH:15][C:16]=2[S:21][CH:20]([CH2:22][CH2:23][CH2:24][C:25]2[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=2)[C:19]1=[O:33]
Reactant: C[Si](C)(C)ON
Reactant: CCOC(=O)c1ccc2c(c1)N(CC(=O)O)C(=O)C(CCCc1ccc(OC)cc1)S2
Agent: CC(C)OC(=O)Cl
Agent: Cl
Solvent: C1CCOC1
Solvent: CN1CCOCC1
Product: CCOC(=O)c1ccc2c(c1)N(CC(=O)NO)C(=O)C(CCCc1ccc(OC)cc1)S2
Reaction time: 0.42 h

Procedure:
At −15° C., isopropyl chloroformate (2.84 ml) was added dropwise to a solution of {6-(ethoxycarbonyl)-2-[3-(4-methoxyphenyl)propyl]-3-oxo-2,3-dihydro-4H-1,4-benzothiazin-4-yl}acetic acid (10.64 g) and N-methylmorpholine (3.2 ml) in tetrahydrofuran (200 ml). After the dropwise addition of the whole isopropyl chloroformate, the resulting mixture was stirred for 25 minutes and then O-(trimethylsilyl)hydroxylamine (3.52 ml) was added dropwise thereto. After 3 hours, the reaction mixture was poured into a 0.5N aqueous hydrochloric acid solution and extracted with ethyl acetate. The oil layer was washed with a saturated aqueous sodium chloride solution, dehydrated over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by a silica gel chromatography (hexane/ethyl acetate=⅔ to ⅓). To the resulting yellow oil were added toluene and hexane to effect crystallization. The solid obtained was collected by filtration and concentrated under reduced pressure. Ethyl 4-[2-(hydroxyamino)-2-oxoethyl]-2-[3-(4-methoxyphenyl)propyl]-3-oxo-3,4-dihydro-2H-1,4-benzothiazine-6-carboxylate (8.24 g) was obtained as a yellow solid.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][S:4][CH2:5][C:6]1[N:10]=[C:9]([NH:11][C:12]([NH2:14])=[NH:13])[S:8][N:7]=1.[CH3:15][N:16]=[C:17]=[S:18]>C(O)C>[CH3:15][NH:16][C:17](=[S:18])[NH:1][CH2:2][CH2:3][S:4][CH2:5][C:6]1[N:10]=[C:9]([NH:11][C:12]([NH2:14])=[NH:13])[S:8][N:7]=1
Reactant: N=C(N)Nc1nc(CSCCN)ns1
Reactant: CN=C=S
Solvent: CCO
Product: CNC(=S)NCCSCc1nsc(NC(=N)N)n1

Procedure:
A solution of 3-[(2-aminoethyl)thiomethyl]-5-guanidino-1,2,4-thiadiazole (0.914 g.) in ethanol (10 ml.) was heated under reflux with methyl isothiocyanate (0.288 g.) for 20 minutes and the resulting solution was chromatographed on nine preparative Merck 60 F-254 silica plates (30 cm.×30 cm.) developed with toluene/ethanol/ethyl acetate/ammonia (s.g. 0.88) 60:40:20:10 v/v/v/v. The bands with an Rf value of 0.6 were scraped off, extracted with ethanol and the extracts evaporated to a gum which crystallised on trituration with ethyl acetate to give 3-[2-(3-methylthioureido)ethylthiomethyl]-5-guanidino-1,2,4-thiadiazole. The n.m.r. spectrum in d6 dimethyl sulphoxide using tetramethylsilane as an internal standard (δ=0) had the following resonances (δ): 2.76 (2H, triplet); 2.82 (3 H, singlet); 3.35 (2H, multiplet); 3.71 (2H, singlet); 7.12 and 7.5 (6 H, multiplets).
Reaction SMILES: Br[C:2]1[C:15]([CH3:16])=[CH:14][C:5]([O:6][CH2:7][CH2:8][N:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:4][C:3]=1[CH3:17].[Li]CCCC.CN([CH:26]=[O:27])C>C1COCC1>[CH3:17][C:3]1[CH:4]=[C:5]([O:6][CH2:7][CH2:8][N:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)[CH:14]=[C:15]([CH3:16])[C:2]=1[CH:26]=[O:27]
Reactant: Cc1cc(OCCN2CCCC2)cc(C)c1Br
Reactant: CN(C)C=O
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: Cc1cc(OCCN2CCCC2)cc(C)c1C=O
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
To a solution of 1-[2-(4-bromo-3,5-dimethyl-phenoxy)-ethyl]-pyrrolidine (176 mg) in THF (5 mL) was added n-BuLi (1.36 mL, 1.0 M solution in hexane) at −78° C. The mixture was stirred at −78° C. for 30 min, allowed to warm up to −40° C. for 5 min, and then cooled down to at −78° C. After 20 min. DMF (0.24 mL) was added. The mixture was stirred at −78° C. for 30 min and then allowed to warm up to room temperature for 1 h. The reaction was quenched with saturated NH4Cl aqueous solution and extracted with EtOAc. The organic extracts were washed with brine, dried over Na2SO4, and concentrated under reduced pressure to give 2,6-dimethyl-4-(2-pyrrolidin-1-yl-ethoxy)-benzaldehyde: MS (m/z) 248 (M+1).
Reaction SMILES: [O:1]1[CH2:6][CH2:5][N:4]([CH2:7][CH2:8][OH:9])[CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.[S:19](Cl)([CH3:22])(=[O:21])=[O:20]>ClCCl>[CH3:22][S:19]([O:9][CH2:8][CH2:7][N:4]1[CH2:5][CH2:6][O:1][CH2:2][CH2:3]1)(=[O:21])=[O:20]
Reactant: OCCN1CCOCC1
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CS(=O)(=O)OCCN1CCOCC1
Temperature: 25 °C
Reaction time: 15 h

Procedure:
A flask was charged with 2-morpholinoethanol (1.0 g, 7.1 mmol), DIEA (2.4 mL, 14 mmol) and dichloromethane (100 mL). Mesylchloride (0.64 mL, 8.3 mmol) was added in a dropwise fashion to the dichloromethane mixture and the reaction mixture was stirred at room temperature for 15 hours. Concentration of the reaction mixture gave rise to a quantitative yield of 2-morpholinoethyl methanesulfonate, which was used in the next step without any without further purification. EI (MS); 210 (MH+).
Reaction SMILES: [Cl:1][C:2]1[C:11]2[CH2:10][CH2:9][CH2:8][C:7](=[O:12])[C:6]=2[C:5]([CH2:13][CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:4]([CH3:20])[CH:3]=1.Cl.S(Cl)([Cl:25])(=O)=O>C(Cl)Cl>[Cl:1][C:2]1[C:11]2[CH2:10][CH2:9][CH:8]([Cl:25])[C:7](=[O:12])[C:6]=2[C:5]([CH2:13][CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:4]([CH3:20])[CH:3]=1
Reactant: O=S(=O)(Cl)Cl
Reactant: CCOC(=O)CCc1c(C)cc(Cl)c2c1C(=O)CCC2
Agent: Cl
Solvent: ClCCl
Product: CCOC(=O)CCc1c(C)cc(Cl)c2c1C(=O)C(Cl)CC2
Temperature: 25 °C
Reaction time: 2 h
Yield: 95.8 %

Procedure:
A solution of ethyl 3-(4-chloro-2-methyl-8-oxo-5,6,7,8-tetrahydronaphthalen-1-yl)propanoate (5.70 g, 20.3 mmoles) in CH2Cl2 (20 ml) was saturated with dry gaseous HCl and sulfuryl chloride (16.4 ml, 27.5 g, 203 mmoles) was added dropwise and stirred at room temperature for 2 hours. The solvent and excess sulfuryl chloride were evaporated in vacuo then chased with dry toluene two times to leave 6.40 g of title compound as a gum. Exact mass calculated for C16H17O3Cl (parent-HCl): 292.0866; Found: 292.0869
Reaction SMILES: [C:1]([CH:6]([C:30]1[CH:35]=[CH:34][C:33]2[O:36][CH2:37][O:38][C:32]=2[CH:31]=1)[O:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][N:15]2[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=3[N:17](C(OCC)=O)[C:16]2=[O:29])=[CH:10][CH:9]=1)([O:3]CC)=[O:2].C(O)C.[OH-].[Na+].Cl>C(Cl)Cl>[C:1]([CH:6]([C:30]1[CH:35]=[CH:34][C:33]2[O:36][CH2:37][O:38][C:32]=2[CH:31]=1)[O:7][C:8]1[CH:9]=[CH:10][C:11]([CH2:14][N:15]2[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=3[NH:17][C:16]2=[O:29])=[CH:12][CH:13]=1)([OH:3])=[O:2]
Reactant: CCOC(=O)C(Oc1ccc(Cn2c(=O)n(C(=O)OCC)c3ccccc32)cc1)c1ccc2c(c1)OCO2
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CCO
Product: O=C(O)C(Oc1ccc(Cn2c(=O)[nH]c3ccccc32)cc1)c1ccc2c(c1)OCO2
Temperature: 25 °C
Reaction time: 8 h
Yield: 76.5 %

Procedure:
A round bottom flask was charged with 0.025 g (0.05 mmol) of the product of step C, 0.5 mL of ethanol and the flask and its contents were placed in a sonicator bath. Methylene chloride (0.3 mL) was then added in order to completely dissolve the starting material. Next, 20 μL of a 5.0 N solution of sodium hydroxide were added and the reaction was stirred at room temperature overnight. The reaction mixture was then adjusted to pH=5 with dropwise addition of 6 N hydrochloric acid, and then concentrated in vacuo. The residue was suspended in water to dissolve inorganic salts and filtered. The flitrate was washed with methanol and dried in vacuo to afford 0.016 g (80%) of the title compound.
Reaction SMILES: [CH2:1]([C@:3]12[CH2:11][CH2:10][C@@H:9]3[C@@H:12]4[C:17]([CH2:18][CH2:19][C@H:8]3[C@@H:7]1[CH2:6][CH2:5][C:4]2=[O:21])=[CH:16][C:15](=[O:20])[CH2:14][CH2:13]4)[CH3:2].O1CCO[CH2:24][CH2:23]1.C(OCC)(OCC)OCC.C(=O)([O-])O.[Na+]>C(O)C.N1C=CC=CC=1>[CH2:23]([O:20][C:15]1[CH2:14][CH2:13][C@H:12]2[C:17](=[CH:18][CH2:19][C@H:8]3[C@H:7]4[C@@:3]([CH2:1][CH3:2])([C:4](=[O:21])[CH2:5][CH2:6]4)[CH2:11][CH2:10][C@@H:9]32)[CH:16]=1)[CH3:24]
Reactant: CC[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)CC[C@@H]43)[C@@H]1CCC2=O
Reactant: C1COCCO1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(OCC)OCC
Solvent: c1ccncc1
Solvent: CCO
Product: CCOC1=CC2=CC[C@@H]3[C@H](CC[C@]4(CC)C(=O)CC[C@@H]34)[C@H]2CC1

Procedure:
—Pyridinium-toluenesulfonate (5.0 g) was added to a solution of 13-ethylgon-4-ene-3,17-dione [Hoffmann-La Roche and Co.; AG, DE 1806410 (1967); 100.0 g] in a mixture of ethanol (600 ml), dioxane (800 ml) and triethyl orthoformate (199 ml). After 4.5 h stirring at room temperature pyridine (100 ml) was added and the reaction mixture was poured into a saturated aqueous solution of sodium hydrogencarbonate. The product was extracted into ethyl acetate; the combined organic phases were washed with water and brine, dried over magnesium sulfate and concentrated under reduced pressure, to give 3-ethoxy-13-ethylgona-3,5-dien-17-one (146.3 g). The product was used in the following step without further purification.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[Cl:11][C:12]1[CH:13]=[C:14]([C@H:19]([CH2:37][CH2:38][OH:39])[CH2:20][N:21]([CH3:36])[C:22]([C:24]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH:27]=[C:26]([C:34]#[N:35])[CH:25]=2)=[O:23])[CH:15]=[CH:16][C:17]=1[Cl:18].C(N(CC)CC)C>C(Cl)Cl>[Cl:11][C:12]1[CH:13]=[C:14]([C@H:19]([CH2:37][CH:38]=[O:39])[CH2:20][N:21]([CH3:36])[C:22]([C:24]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH:27]=[C:26]([C:34]#[N:35])[CH:25]=2)=[O:23])[CH:15]=[CH:16][C:17]=1[Cl:18]
Reactant: CN(C[C@@H](CCO)c1ccc(Cl)c(Cl)c1)C(=O)c1cc(C#N)cc2ccccc12
Agent: O=C(Cl)C(=O)Cl
Solvent: CS(C)=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CN(C[C@@H](CC=O)c1ccc(Cl)c(Cl)c1)C(=O)c1cc(C#N)cc2ccccc12
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 97.5 %

Procedure:
A solution of oxalyl chloride (15.9 g, 125.4 mmol) dissolved in DCM (350 mL) was cooled to −78° C. DMSO (19.6 g, 251 mmol) was added dropwise over 10 minutes while maintaining the temperature of the reaction mixture below −70° C. The mixture was stirred for 30 min at −78° C. A solution of N-[(S)-2-(3,4-dichlorophenyl)-4-hydroxybutyl]-N-methyl-3-cyano-1-naphthamide (26.8 g, 62.7 mmol) was dissolved in DCM (350 mL) and added dropwise over 30 min while maintaining the temperature of the mixture below −70° C. The mixture was allowed to stir for one h at −78° C., then warmed to −50° C. and stirred for another 30 minutes. The mixture was cooled to −78° C. and a solution of triethylamine (25.4 g, 251 mmol) dissolved in DCM (70 mL) was added dropwise over 10 min. The mixture was then allowed to warm gradually to ambient temperature and stir for 20 hours. The mixture was then washed with 0.5N hydrochloric acid (2×250 mL), water (250 mL), and saturated sodium bicarbonate (250 mL). The organic layer was dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by chromatography (silica gel; 0-20% Et2O in DCM) to provide the desired product as a light yellow foam (26.0 g, 97%). MS: 425 (M+H). 1H-NMR (DMSO-d6) δ2.63 (bs, 3H, NCH3); 2.99-3.93 (m, 5H, CH); 6.91-7.15 (m, 1H, aromatic); 7.33-7.81 (m, 6H, aromatic); 8.62 (s, 1H, aromatic); 9.45 and 9.73 (singlets, 1H total, CHO).
Reaction SMILES: Cl[C:2]1[N:25]=[C:5]2[C:6]([C:10]3[CH:15]=[CH:14][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:12][C:11]=3[O:20][CH2:21][CH:22]([F:24])[F:23])=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.[C:26]([O:30][C:31]([N:33]1[CH2:39][CH2:38][C:37]2[CH:40]=[CH:41][C:42]([NH2:44])=[CH:43][C:36]=2[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:28])[CH3:27]>>[C:26]([O:30][C:31]([N:33]1[CH2:39][CH2:38][C:37]2[CH:40]=[CH:41][C:42]([NH:44][C:2]3[N:25]=[C:5]4[C:6]([C:10]5[CH:15]=[CH:14][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:12][C:11]=5[O:20][CH2:21][CH:22]([F:24])[F:23])=[CH:7][CH:8]=[CH:9][N:4]4[N:3]=3)=[CH:43][C:36]=2[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:27])[CH3:28]
Reactant: CS(=O)(=O)c1ccc(-c2cccn3nc(Cl)nc23)c(OCC(F)F)c1
Reactant: CC(C)(C)OC(=O)N1CCc2ccc(N)cc2CC1
Product: CC(C)(C)OC(=O)N1CCc2ccc(Nc3nc4c(-c5ccc(S(C)(=O)=O)cc5OCC(F)F)cccn4n3)cc2CC1

Procedure:
7-{8-[2-(2,2-Difluoro-ethoxy)-4-methanesulfonyl-phenyl]-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino}-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylic acid tert-butyl ester was prepared from 2-chloro-8-[2-(2,2-difluoro-ethoxy)-4-methanesulfonyl-phenyl]-[1,2,4]-triazolo[1,5-a]pyridine (0.371 g, 1.20 mmol) and 7-amino-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylic acid tert-butyl ester (0.253 g, 652 mmol) in a manner analogous to Example 311a and 311b to give product (0.285 g, 71%): 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.58 (s, 1H), 8.82 (d, 1H), 7.94 (d, 1H), 7.74 (s, 1H), 7.68 (m, 2H), 7.48 (d, 1H), 7.37 (s, 1H), 7.05 (m, 2H), 6.27 (br m, 1H), 4.52 (m, 2H), 3.45 (m, 4H), 2.77 (m, 4H), 2.50 (s, 3H), 1.41 (s, 9H). MS=614 (MH)+.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]([O:12][CH2:13][CH2:14][CH3:15])=[C:8]([CH:11]=1)[CH2:9][OH:10])([O-])=O.OCC1C=C(C=CC=1OC)N>>[OH:10][CH2:9][C:8]1[CH:11]=[C:4]([CH:5]=[CH:6][C:7]=1[O:12][CH2:13][CH2:14][CH3:15])[NH2:1]
Reactant: CCCOc1ccc([N+](=O)[O-])cc1CO
Agent: COc1ccc(N)cc1CO
Product: CCCOc1ccc(N)cc1CO
Yield: 37 %

Procedure:
This compound was prepared by reduction of 5-nitro-2-propyloxy-benzylalcohol using the method described for the preparation of 3-hydroxymethyl-4-methoxyaniline in 37% yield: 1H NMR (DMSO-d6, 500 MHz) δ 6.66 (d, 1H, J=2.5 Hz), 6.60 (d, 1H, J=8.6 Hz), 6.35 (dd, 1H, J=2.7 and 8.5 Hz), 4.79 (t, 1H, J=5.8 Hz), 4.54 (br, 2H), 4.37 (d, 2H, J=6.1 Hz), 3.74 (t, 2H, J=6.4 Hz), 1.65 (m, 2H), 0.94 (t, 3H, J=7.4 Hz).
Reaction SMILES: [Cl:1][C:2]1[C:9]([Cl:10])=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=O.[F:11][CH2:12][C:13](=O)[CH2:14][C:15]([O:17][CH3:18])=[O:16].[NH2:20][C:21]([CH3:31])=[CH:22][C:23]([O:25][CH:26]1[CH2:30][CH2:29][CH2:28][CH2:27]1)=[O:24]>C(OCC)(=O)C>[Cl:1][C:2]1[C:9]([Cl:10])=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]1[C:22]([C:23]([O:25][CH:26]2[CH2:30][CH2:29][CH2:28][CH2:27]2)=[O:24])=[C:21]([CH3:31])[NH:20][C:13]([CH2:12][F:11])=[C:14]1[C:15]([O:17][CH3:18])=[O:16]
Reactant: COC(=O)CC(=O)CF
Reactant: O=Cc1cccc(Cl)c1Cl
Reactant: CC(N)=CC(=O)OC1CCCC1
Solvent: CCOC(C)=O
Product: COC(=O)C1=C(CF)NC(C)=C(C(=O)OC2CCCC2)C1c1cccc(Cl)c1Cl
Reaction time: 2.5 h
Yield: 28.6 %

Procedure:
2,3-Dichlorobenzaldehyde (1.31 g, 7.5 mmoles), methyl 4-fluoro-3-oxobutanoate (1.0 g, 7.5 mmoles) and cyclopentyl 3-amino-2-butenoate (1.26 g, 7.5 mmoles) were heated at 90° with stirring under nitrogen for 2.5 hours. The reaction mixture was dissolved in ethyl acetate, dried (MgSO4) and the solvent was removed in vacuo. The residue was chromatographed on silica eluting with ethyl acetate/methylene chloride mixtures. The title compound (0.95 g) was obtained after crystallisation from petroleum ether (60°-80) mp 148°-50°.
Reaction SMILES: [CH2:1]([NH:8][C:9](=[O:16])[NH:10][O:11][CH2:12][C:13]([OH:15])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:17][C@@H:18]([CH3:42])[C:19]([N:21]([C@@H:33]([CH3:41])[CH:34]([O:38][CH2:39][CH3:40])[O:35][CH2:36][CH3:37])[CH2:22][C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25][CH:24]=1)=[O:20]>>[CH2:1]([NH:8][C:9]([NH:10][O:11][CH2:12][C:13]([NH:17][C@@H:18]([CH3:42])[C:19]([N:21]([C@@H:33]([CH3:41])[CH:34]([O:38][CH2:39][CH3:40])[O:35][CH2:36][CH3:37])[CH2:22][C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25][CH:24]=1)=[O:20])=[O:15])=[O:16])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)CONC(=O)NCc1ccccc1
Reactant: CCOC(OCC)[C@H](C)N(Cc1cccc2ccccc12)C(=O)[C@H](C)N
Product: CCOC(OCC)[C@H](C)N(Cc1cccc2ccccc12)C(=O)[C@H](C)NC(=O)CONC(=O)NCc1ccccc1

Procedure:
According to the procedure described in the synthesis method of Compound II-15, 2-(3-benzylureidooxy)acetic acid (Compound VI-1) 94 mg (0.42 mmol) was coupled with (S)-2-amino-N—((S)-1,1-diethoxypropan-2-yl)-N-(naphthalen-1-ylmethyl)propanamide (Compound IV-10) 100 mg (0.28 mmol) to obtain the title compound.
Reaction SMILES: [OH:1][C:2]1[C:10]2[NH:9][C:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[C:7]3[CH2:17][CH2:18][C:19](=[O:20])[C:5]([C:6]=23)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:28][C:29]([O:31][CH3:32])=[O:30].O>CS(C)=O>[CH3:32][O:31][C:29]([CH2:28][O:1][C:2]1[C:10]2[NH:9][C:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[C:7]3[CH2:17][CH2:18][C:19](=[O:20])[C:5]([C:6]=23)=[CH:4][CH:3]=1)=[O:30]
Reactant: COC(=O)CBr
Reactant: O=C1CCc2c(-c3ccccc3)[nH]c3c(O)ccc1c23
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: O
Product: COC(=O)COc1ccc2c3c(c(-c4ccccc4)[nH]c13)CCC2=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 85 %

Procedure:
A portion (1.09 g) of the compound obtained in Example 75 was dissolved in dimethylsulfoxide (20 ml) and to the solution were added potassium carbonate (1.14 g) and methyl bromoacetate (0.43 ml). The mixture was stirred for 1 hour at room temperature. After adding water, the reaction mixture was extracted three times with ethyl acetate. The organic layer was washed with water and saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the residue was crystallized from ether to yield 1.18 g (85%) of the titled compound as a yellowish brown powder.
Reaction SMILES: SCC1C=CC(C[PH2+]C[CH2:10][CH:11]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:12]2C=CC=CC=2)=CC=1.[C:26]1([OH:32])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.CC(C)=[O:35]>>[OH:32][C:26]1[CH:31]=[CH:30][C:29]([C:11]([C:18]2[CH:23]=[CH:22][C:21]([OH:35])=[CH:20][CH:19]=2)([CH3:12])[CH3:10])=[CH:28][CH:27]=1
Reactant: CC(C)=O
Reactant: SCc1ccc(C[PH2+]CCC(c2ccccc2)c2ccccc2)cc1
Reactant: Oc1ccccc1
Product: CC(C)(c1ccc(O)cc1)c1ccc(O)cc1
Temperature: 75 °C
Reaction time: 2 h

Procedure:
To a 70 ml pressure-resistant reactor, 0.35 g of Catalyst 7 prepared in (2), 6.63 g of phenol, and 0.37 g of acetone were charged, and the reactor was pressurized with nitrogen gas under 0.5 MPa of a gauge pressure, and then the reaction was conducted with heating and stirring at 75° C. for 2 hours. Thereafter, the resultant was cooled to room temperature. After the pressure discharge, the reaction solution was taken out, and analytically quantified by a liquid chromatography method. As a result, the conversion of acetone was 94.8% and the selectivity of pp′-bisphenol A was 94.1%.
Reaction SMILES: FC(F)(F)C(O)=O.C(OC(=O)[N:17]([CH2:20][CH2:21][CH2:22][N:23]([CH3:25])[CH3:24])[CH2:18][CH3:19])C1C=CC=CC=1.[ClH:27].[H][H]>C(O)C.[Pd]>[ClH:27].[ClH:27].[CH2:18]([NH:17][CH2:20][CH2:21][CH2:22][N:23]([CH3:25])[CH3:24])[CH3:19]
Reactant: [H][H]
Reactant: CCN(CCCN(C)C)C(=O)OCc1ccccc1
Agent: [Pd]
Agent: Cl
Solvent: O=C(O)C(F)(F)F
Solvent: CCO
Product: CCNCCCN(C)C
Yield: 89.5 %

Procedure:
To a solution of the (3-dimethylaminopropyl)-ethyl-carbamic acid benzyl ester trifluoroacetate (0.84 g, 2.2 mmol) in ethanol (30 mL) and concentrated hydrochloric acid (0.5 mL, 6 mmol) was added palladium on carbon (10%, 50 mg). The suspension was shaken under 50 psi hydrogen. When the consumption of hydrogen was observed to have ceased, the mixture was filtered through a pad of diatomaceous earth and then concentrated under reduced pressure to give N′-ethyl-N,N-dimethylpropane-1,3-diamine dihydrochloride (400 mg, 89%) as a white solid. MS (ES+): m/z (M+H)=131.3 To a suspension of the N′-ethyl-N,N-dimethylpropane-1,3-diamine dihydrochloride (0.26 g, 1.3 mmol) in dichloromethane (5 mL) was added triethylamine (0.51 mL, 3.9 mmol). After stirring for 10 minutes, the mixture was treated with 17-hydroxywortmannin (0.28 g, 0.65 mmol). After stirring overnight at room temperature, the mixture was concentrated under reduced pressure and then purified by reverse-phase HPLC (employing a gradient elution of 5% acetonitrile/95% water to 95% acetonitrile over 45 minutes). The title compound was obtained as a rust-colored solid (11.6 mg). MS (ES+): m/z (M+H)=561.4.
Reaction SMILES: [C:1]1([C:7]#[C:8][CH3:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>C1(C)C=CC=CC=1>[C:1]1([C:7]#[C:8][C:9]2[CH:5]=[CH:6][CH:1]=[CH:2][CH:3]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC#Cc1ccccc1
Solvent: Cc1ccccc1
Product: C(#Cc1ccccc1)c1ccccc1
Temperature: 80 °C
Reaction time: 24 h
Yield: 78.2 %

Procedure:
In a dry 10 mL Schlenk-tube, which has been flooded with argon, [Mo(≡N)(OSiPh3)3(phen)].0.5 toluene (58.8.0 μmol, 68.3 mg) and dried CuCl2 (58.8 μmol, 7.9 mg) were suspended in 2.5 mL of toluene. After addition of 1-phenyl-1-propine (588 μmol, 68.3 mg), the reaction solution was stirred for 24 h at 80° C. and was filtered after cooling over a short silica gel column (2 cm). The filtrate was concentrated and the residue was purified by column chromatography (hexane). 41.0 mg of tolane (78%) were isolated as a white solid, the spectroscopic and analytical data of which were identical to those of a commercial sample. M.p.=59-61° C.