Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.[C:11]1(B(O)O)[CH2:15][CH2:14][CH2:13][CH:12]=1.C([O-])([O-])=O.[Cs+].[Cs+].COCCOC>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.C(O)C>[C:11]1([C:2]2[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=2)[CH2:15][CH2:14][CH2:13][CH:12]=1
Reactant: O=[N+]([O-])c1ccc(Br)cc1
Reactant: OB(O)C1=CCCC1
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: [Cs+]
Solvent: COCCOC
Solvent: CCO
Product: O=[N+]([O-])c1ccc(C2=CCCC2)cc1
Temperature: 105 °C
Yield: 83.2 %

Procedure:
To 1-bromo-4-nitro-benzene (700 mg, 3.46 mmol), 1-cyclopentenylboronic acid (392 mg, 3.50 mmol), Pd(PPh3)4 (200 mg, 0.17 mmol), and Cs2CO3 (2258 g, 6.93 mmol) was added DME (8.4 mL) and ethanol (1.4 mL) and the reaction mixture was heated at 105° C. for 3 h. The reaction was concentrated in vacuo and purified by silica gel chromatography (0-100% ethyl acetate/hexanes) to provide 1-(1-cyclopentenyl)-4-nitro-benzene (545 mg, 83% yield). 1H NMR (400.0 MHz, CDCl3) δ 8.19-8.15 (m, 2H), 7.58-7.52 (m, 2H), 6.44-6.42 (m, 1H), 2.77-2.71 (m, 2H), 2.62-2.56 (m, 2H), 2.11-2.03 (m, 2H).
Reaction SMILES: [CH:1]1[S:2][CH:3]=[C:4]2[C:10]=1[C:9](=[O:11])[NH:8][C:7]1[CH:12]=[CH:13][CH:14]=[CH:15][C:6]=1[NH:5]2.[C:16](Cl)(=[O:19])[O:17][CH3:18]>O1CCOCC1.C1(C)C=CC=CC=1>[CH3:18][O:17][C:16]([N:5]1[C:6]2[CH:15]=[CH:14][CH:13]=[CH:12][C:7]=2[NH:8][C:9](=[O:11])[C:10]2=[CH:1][S:2][CH:3]=[C:4]12)=[O:19]
Reactant: COC(=O)Cl
Reactant: O=C1Nc2ccccc2Nc2cscc21
Solvent: C1COCCO1
Solvent: Cc1ccccc1
Product: COC(=O)N1c2ccccc2NC(=O)c2cscc21

Procedure:
From 4,9-dihydro-10H-thieno[3,4-b][1,5]benzodiazepin-10-one and methyl chlorocarbonate in a mixture of dioxane and toluene, 4,9-dihydro-4-methoxycarbonyl-10H-thieno[3,4-b][1,5]benzodiazepin-10-one was obtained;
Reaction SMILES: C([N:8]1[C:13](=[O:14])[CH:12]=[C:11]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:10]([Cl:21])=[N:9]1)C1C=CC=CC=1.[Cl-].[Al+3].[Cl-].[Cl-]>C1(C)C=CC=CC=1>[Cl:21][C:10]1[C:11]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:12][C:13](=[O:14])[NH:8][N:9]=1
Reactant: O=c1cc(-c2ccccc2)c(Cl)nn1Cc1ccccc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: Cc1ccccc1
Product: O=c1cc(-c2ccccc2)c(Cl)n[nH]1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 83.9 %

Procedure:
To a solution of 2-benzyl-6-chloro-5-phenylpyridazin-3(2H)-one (1.45 g, 4.89 mmol) in toluene (15 mL) under argon at 90° C. was added aluminum chloride (1.629 g, 12.22 mmol) and the reaction was stirred for 20 min. It was then allowed to cool to room temperature and quenched with water, extracted with EtOAc, dried over MgSO4 and concentrated. The residue was purified by preparative HPLC to give the title compound as a white solid (847.6 mg). LCMS m/z=207 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 6.97 (s, 1H), 7.41-7.54 (m, 5H).
Reaction SMILES: [CH3:1][C:2]([O:4][C@H:5]1[C:14]2[C@@:15]3([CH3:30])[C@@H:26]([CH2:27][O:28][CH3:29])[O:25][C:23](=[O:24])[C:17]4=[CH:18][O:19][C:20]([C:21](=[O:22])[C:13]=2[C@@H:8]2[CH2:9][CH2:10][C@H:11]([OH:12])[C@@:7]2([CH3:31])[CH2:6]1)=[C:16]34)=[O:3].[CH2:32]([N:34]([CH2:39][CH3:40])[CH2:35][CH2:36][NH:37][CH3:38])[CH3:33]>C(Cl)Cl>[CH2:32]([N:34]([CH2:39][CH3:40])[CH2:35][CH2:36][N:37]([CH:18]=[C:17]1[C:16]2[C:15]([CH3:30])([C:14]3[CH:5]([O:4][C:2](=[O:3])[CH3:1])[CH2:6][C:7]4([CH3:31])[CH:8]([C:13]=3[C:21](=[O:22])[C:20]=2[OH:19])[CH2:9][CH2:10][CH:11]4[OH:12])[CH:26]([CH2:27][O:28][CH3:29])[O:25][C:23]1=[O:24])[CH3:38])[CH3:33]
Reactant: CCN(CC)CCNC
Reactant: COC[C@H]1OC(=O)c2coc3c2[C@@]1(C)C1=C(C3=O)[C@@H]2CC[C@H](O)[C@@]2(C)C[C@H]1OC(C)=O
Solvent: ClCCl
Product: CCN(CC)CCN(C)C=C1C(=O)OC(COC)C2(C)C1=C(O)C(=O)C1=C2C(OC(C)=O)CC2(C)C(O)CCC12
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a solution of 100 mg (0.23 mmol) 17-hydroxywortmannin in 2 mL CH2Cl2 is added N,N-Diethyl-N′-methyl-ethane-1,2-diamine (45 μL, 0.28 mmol). The reaction mixture is stirred at room temperature for 12 hours and then concentrated in vacuo. The residue is dissolved in EtOAc and precipitated with hexane. The precipitate is washed two times with hexane to give the product as a yellow solid. MS (ESI) m/z 561 (M+H).
Reaction SMILES: [CH3:1][C@H:2]1[NH:7][C@@H:6]([CH3:8])[CH2:5][N:4]([C:9]2[CH:10]=[CH:11][C:12]([Cl:16])=[C:13]([CH:15]=2)[NH2:14])[CH2:3]1.[Br:17][C:18]1[CH:23]=[CH:22][C:21]([S:24](Cl)(=[O:26])=[O:25])=[CH:20][CH:19]=1>N1C=CC=CC=1.ClCCl>[Br:17][C:18]1[CH:23]=[CH:22][C:21]([S:24]([NH:14][C:13]2[CH:15]=[C:9]([N:4]3[CH2:5][C@H:6]([CH3:8])[NH:7][C@H:2]([CH3:1])[CH2:3]3)[CH:10]=[CH:11][C:12]=2[Cl:16])(=[O:26])=[O:25])=[CH:20][CH:19]=1
Reactant: O=S(=O)(Cl)c1ccc(Br)cc1
Reactant: C[C@@H]1CN(c2ccc(Cl)c(N)c2)C[C@H](C)N1
Solvent: ClCCl
Solvent: c1ccncc1
Product: C[C@@H]1CN(c2ccc(Cl)c(NS(=O)(=O)c3ccc(Br)cc3)c2)C[C@H](C)N1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of 5-(cis-3,5-dimethyl-1-piperazinyl)-2-chloroaniline (D34) (108 mg, 0.45 mmol) in pyridine:dichloromethane (1:1, 4 ml) was treated with 4-bromobenzenesulfonyl chloride (138 mg, 0.54 mmol). The solution was stirred at room temperature for 2 hours, quenched with methanol and concentrated in vacuo. The residue was applied to a SCX cartridge (Varian bond-elute, 5 g) and washed with methanol and 2M ammonia in methanol. The combined basic fractions were concentrated in vacuo and the resulting residue was purified by column chromatography (FlashMaster) (dichloromethane to 5% methanol:dichloromethane) to afford some pure product. The impure fractions were purified further by MDAP, and combined with the above pure product to afford the title product (D35). MS (ES+) m/e 458/460/462 [M+H]+.
Reaction SMILES: [OH:1][CH:2]1[C:14]2[NH:13][C:12](=[O:15])[C:11](=[O:16])[NH:10][C:9]=2[C:8]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]1=2.[C:17]1([CH:23]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:24][CH2:25]O)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.O>C1C=CC=CC=1>[C:17]1([CH:23]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH2:24][CH2:25][O:1][CH:2]2[C:14]3[NH:13][C:12](=[O:15])[C:11](=[O:16])[NH:10][C:9]=3[C:8]3[CH:7]=[CH:6][CH:5]=[CH:4][C:3]2=3)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: O=c1[nH]c2c([nH]c1=O)C(O)c1ccccc1-2
Reactant: OCCC(c1ccccc1)c1ccccc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: c1ccccc1
Solvent: O
Product: O=c1[nH]c2c([nH]c1=O)C(OCCC(c1ccccc1)c1ccccc1)c1ccccc1-2
Yield: 12.5 %

Procedure:
A suspension of 9-hydroxy-9H-indeno[1,2-b]pyrazine-2,3(1H, 4H)-dione. 1H2O (1.0 g, 4.26 mmol) in benzene (40 ml), 3,3-diphenyl-1-propanol (10 ml) and p-toluensulfonic acid (40 mg) was refluxed with water separation for 48 hours. The reaction mixture was evaporated in vacuo to dryness, the residue was suspended in ethanol (10 ml) and the precipitate was filtered off and washed with ethanol and dried to give 0.224 g (12.5%) of the title compound. M.p. 224°-228° C. 1H-NMR(DMSO-d6, δ): 2.14-2.32 (m, 2H), 3.0-3.22 (m, 2H), 4.13 (t, 1H), 5.22 (s, 1H), 7.0-7.5 (m, 14H), 12.12 (s, 1H), 12.26 (s, 1H).
Reaction SMILES: [CH3:1][O:2][CH:3]1[C:7]([C:8]([NH2:10])=[O:9])=[CH:6][S:5][CH2:4]1.S(Cl)(Cl)(=O)=O>C(Cl)(Cl)(Cl)Cl>[CH3:1][O:2][C:3]1[C:7]([C:8]([NH2:10])=[O:9])=[CH:6][S:5][CH:4]=1
Reactant: COC1CSC=C1C(N)=O
Solvent: O=S(=O)(Cl)Cl
Solvent: ClC(Cl)(Cl)Cl
Product: COc1cscc1C(N)=O
Yield: 75 %

Procedure:
1.59 parts of 3-methoxy-dihydrothiophene-4-carboxylic acid amide are reacted with 0.88 part by volume of sulfuryl chloride in 25 parts by volume of carbon tetrachloride in the course of 2 hours at 0° C. The end product is isolated from the reaction mixture by the method described in Example 1c. 1.17 parts (75% of theory) of 3-methoxythiophene-4-carboxylic acid amide are obtained.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH:6]([C:10]1[S:11][CH:12]=[CH:13][CH:14]=1)[C:7](Cl)=[O:8].[NH2:15][C@H:16]1[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[CH2:17]1>>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH:6]([C:10]1[S:11][CH:12]=[CH:13][CH:14]=1)[C:7]([NH:15][C@H:16]1[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][C:23]2[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=2)[CH2:17]1)=[O:8]
Reactant: O=C(Cl)C(c1cccs1)c1cccs1
Reactant: N[C@H]1CCN(CCc2ccc(F)cc2)C1
Product: O=C(N[C@H]1CCN(CCc2ccc(F)cc2)C1)C(c1cccs1)c1cccs1
Yield: 23.9 %

Procedure:
2,2-Di(2-thienyl)acetyl chloride (0.67 g) and (S)-3-amino-1-(2-(4-fluorophenyl)ethyl)pyrrolidine (0.42 g) were reacted under the same conditions as in Example 53 to give (S)-2,2-di(2-thienyl)-N-(1-(2-(4-fluorophenyl)ethyl)pyrrolidin-3-yl)acetamide (0.2 g), melting point 96-98° C.
Reaction SMILES: [CH3:1][N:2]1[C:11]([OH:12])=[C:5]2[N:6]=[CH:7][N:8]=[C:9]([SH:10])[C:4]2=[N:3]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22].C(Cl)(Cl)Cl>O>[CH3:1][N:2]1[C:11]([OH:12])=[C:5]2[N:6]=[CH:7][N:8]=[C:9]([S:10][CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])[C:4]2=[N:3]1
Reactant: CCOC(=O)CBr
Reactant: Cn1nc2c(S)ncnc2c1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClC(Cl)Cl
Solvent: O
Product: CCOC(=O)CSc1ncnc2c(O)n(C)nc12
Temperature: 25 °C
Reaction time: 4 h

Procedure:
10 g of 2-methyl-3-hydroxy-7-mercapto-pyrazolo[4,3-d]pyrimidine and 8.36 g of anhydrous potassium carbonate were dissolved in 100 ml of water, and after an addition of 8.08 g of ethyl bromoacetate, the mixture was stirred at room temperature for 4 hours. After confirming the completion of the reaction by means of thin layer chromatography, the reaction mixture was shaked with chloroform, whereby by-products were extracted to the chloroform layer and thus removed. The aqueous layer was neutralized with 1:1 hydrochloric acid to bring the pH to a level of from 3 to 4. The precipitated crystals were collected by filtration and then washed with water. Then, the crystals were recrystallized from chloroform-acetone.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([CH:16]=[C:17]([C:20]([CH3:23])([CH3:22])[CH3:21])[C:18]=1[OH:19])[C:8]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=O)([CH3:4])([CH3:3])[CH3:2].[C:24]([NH:27][NH2:28])(=[O:26])[CH3:25]>>[C:24]([NH:27][N:28]=[C:8]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:7]1[CH:16]=[C:17]([C:20]([CH3:21])([CH3:22])[CH3:23])[C:18]([OH:19])=[C:5]([C:1]([CH3:2])([CH3:3])[CH3:4])[CH:6]=1)(=[O:26])[CH3:25]
Reactant: CC(=O)NN
Reactant: CC(C)(C)c1cc(C(=O)c2ccccc2)cc(C(C)(C)C)c1O
Product: CC(=O)NN=C(c1ccccc1)c1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1

Procedure:
3,5-di-t-butyl-4-hydroxybenzophenone and acetohydrazide were treated in the same way as in Example 7 to give 3,5-di-t-butyl-4-hydroxybenzophenone acetylhydrazone.
Reaction SMILES: [F:1][CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11](=[O:28])[CH2:12][CH2:13][C:14]1[N:15]=[C:16]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([OH:27])[CH:20]=2)[O:17][CH:18]=1.[CH2:29](Br)[CH:30]([CH3:32])[CH3:31]>>[F:1][CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11](=[O:28])[CH2:12][CH2:13][C:14]1[N:15]=[C:16]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH2:29][CH:30]([CH3:32])[CH3:31])[CH:20]=2)[O:17][CH:18]=1
Reactant: CC(C)CBr
Reactant: COc1ccc(-c2nc(CCC(=O)c3ccccc3OCCF)co2)cc1O
Product: COc1ccc(-c2nc(CCC(=O)c3ccccc3OCCF)co2)cc1OCC(C)C

Procedure:
Using the compound obtained in Example 271 and isobutyl bromide, white powdery 1-[2-(2-fluoroethoxy)phenyl]-3-[2-(3-isobutoxy-4-methoxyphenyl)oxazol-4-yl]propan-1-one was obtained following the procedure of Example 3.
Reaction SMILES: C[O:2][C:3](=[O:26])[CH2:4][CH2:5][N:6]1[CH2:10][CH2:9][CH2:8][C@H:7]1[CH2:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:15][CH:14]=1.[ClH:27]>O1CCOCC1>[ClH:27].[CH2:19]([C:16]1[CH:17]=[CH:18][C:13]([O:12][CH2:11][C@@H:7]2[CH2:8][CH2:9][CH2:10][N:6]2[CH2:5][CH2:4][C:3]([OH:26])=[O:2])=[CH:14][CH:15]=1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: COC(=O)CCN1CCC[C@H]1COc1ccc(Cc2ccccc2)cc1
Agent: Cl
Solvent: C1COCCO1
Product: O=C(O)CCN1CCC[C@H]1COc1ccc(Cc2ccccc2)cc1
Reaction time: 4 h
Yield: 60 %

Procedure:
3-[(S)-2-(4-Benzyl-phenoxymethyl)-pyrrolidin-1-yl]-propionic acid methyl ester (32.6 mg, 0.092 mmol) was added to a solution of HCl (conc.) in Dioxane (1:3, 2 mL). The reaction was run a 60° C. for 4 h. The Mixture was concentrated to dryness and dried in a vacuum over at 50° C. The residue was triturated with diethyl ether and dried to provide the title product (19 mg, 0.056 mmol, 60% yield); LCMS: m/z 339.44 (free amine). found 340 (M+1). 1H NMR (400 MHz, DMSO-d6) δ 1.77 1.837 (m, 1H), 1.93-1.96 (m, 1H), 1.99-2.04 (m, 1H), 2.20-2.25 (m, 1H), 2.80-2.85 (m, 1H), 3.16-3.18 (m, 1H), 3.31-3.41 (m, 1H), 3.56-3.88 (m, 6H), 4.25-4.32 (m, 2H), 6.90-6.92 (d, J=8.4, 2H), 7.16-7.21 (m, 5H), 7.26-7.29 (m, 2H), 10.34 (s, 1H).
Reaction SMILES: [Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.[C:9]([OH:17])(=[O:16])[C:10]([CH2:12][C:13](O)=[O:14])=[CH2:11]>CCCCCC.C(OCC)(=O)C>[Br:1][C:2]1[CH:8]=[CH:7][C:5]([N:6]2[C:13](=[O:14])[CH2:12][CH:10]([C:9]([OH:17])=[O:16])[CH2:11]2)=[CH:4][CH:3]=1
Reactant: Nc1ccc(Br)cc1
Reactant: C=C(CC(=O)O)C(=O)O
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: O=C(O)C1CC(=O)N(c2ccc(Br)cc2)C1
Temperature: 130 °C
Reaction time: 0.83 h
Yield: 95.1 %

Procedure:
A mixture of 4-bromoaniline (8.6 g) and itaconic acid (6.5 g) was stirred at 130° C. for 50 minutes. After cooling, a n-hexane-ethyl acetate mixed solution was added to the resulting solid. The compound was collected by filtration to obtain the title compound (13.5 g).
Reaction SMILES: [C:1](N1C=CN=C1)([N:3]1C=CN=C1)=O.[NH:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15]([S:22][C:23]2[CH:31]=[CH:30][CH:29]=[CH:28][C:24]=2[C:25](O)=[O:26])=[CH:14]1.CN>C1COCC1>[NH:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15]([S:22][C:23]2[CH:31]=[CH:30][CH:29]=[CH:28][C:24]=2[C:25]([NH:3][CH3:1])=[O:26])=[CH:14]1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: O=C(O)c1ccccc1Sc1c[nH]c2ccccc12
Agent: CN
Solvent: C1CCOC1
Product: CNC(=O)c1ccccc1Sc1c[nH]c2ccccc12
Temperature: 25 °C
Reaction time: 16 h

Procedure:
Carbonyldiimidazole (11 mmol) was added to a solution of 2-(1H-indol-3-ylsulfanyl)benzoic acid (Hamel, P.; Girard, M.; Tsou, N. N.; J. Heterocycl. Chem. 36, 1999, 643-652) (10 mmol) in dry THF (200 mL) and refluxed for 60 minutes under argon. Methyl amine (1M in THF; 40 ml) was added slowly to the reaction mixture and the mixture was stirred at room temperature for 16 hours. The mixture was evaporated in vacuo and the product purified by column chromatography on silica gel using ethyl acetate as an eluent.
Reaction SMILES: [CH3:1][C:2]([CH3:29])([CH3:28])[C:3]#[C:4]/[CH:5]=[CH:6]/[CH2:7]/[C:8](=[CH:11]\[CH2:12][CH2:13][CH2:14][CH2:15][O:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23]2[CH:27]=[CH:26][S:25][CH:24]=2)[CH:18]=1)/[CH2:9][OH:10].[C:30](OC(=O)C)(=[O:32])[CH3:31]>N1C=CC=CC=1>[C:30]([O:10][CH2:9]/[C:8](/[CH2:7]/[CH:6]=[CH:5]/[C:4]#[C:3][C:2]([CH3:29])([CH3:28])[CH3:1])=[CH:11]/[CH2:12][CH2:13][CH2:14][CH2:15][O:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23]2[CH:27]=[CH:26][S:25][CH:24]=2)[CH:18]=1)(=[O:32])[CH3:31]
Reactant: CC(C)(C)C#C/C=C/C/C(=C\CCCCOc1cccc(-c2ccsc2)c1)CO
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: CC(=O)OC/C(=C/CCCCOc1cccc(-c2ccsc2)c1)C/C=C/C#CC(C)(C)C
Temperature: 25 °C
Reaction time: 18 h
Yield: 91 %

Procedure:
18.8 mg of (E,E)-2-(6,6-dimethyl-2-hepten-4-ynyl)-7-[3-(3-thienyl)phenoxy]-2-hepten-1-ol obtained in Example 2 is dissolved in 2 ml of pyridine, 1 ml of acetic anhydride is added, and the mixture is stirred at room temperature for 18 hours. The reaction solution is concentrated under reduced pressure, water and ethyl acetate are added to the residue for extraction, the organic layer is taken, washed successively with 1N hydrochloric acid, saturated aqueous sodium bicarbonate solution and saturated saline and dried over anhydrous magnesium sulfate, and the solvent is distilled off under reduced pressure. The residue is purified by preparative thin layer chromatography [Kieselgel 60 F254, Art. 5717 (produced by Merck Co.); hexane/ethyl acetate=5/1] to obtain 18.8 mg (yield: 91%) of the captioned compound as a colorless oily matter.
Reaction SMILES: [NH:1](C(OCC1C=CC=CC=1)=O)[C@H:2]([C:6]([NH:8][C@H:9]([C:22]([O:24][CH3:25])=[O:23])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:13][CH:12]=1)=[O:7])[CH:3]([CH3:5])[CH3:4].[ClH:36]>CO.[H][H]>[NH2:1][C@H:2]([C:6]([NH:8][C@H:9]([C:22]([O:24][CH3:25])=[O:23])[CH2:10][C:11]1[CH:12]=[CH:13][C:14]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[CH:15][CH:16]=1)=[O:7])[CH:3]([CH3:5])[CH3:4].[ClH:36]
Reactant: COC(=O)[C@H](Cc1ccc(OC(C)(C)C)cc1)NC(=O)[C@@H](NC(=O)OCc1ccccc1)C(C)C
Reactant: [H][H]
Agent: Cl
Solvent: CO
Product: COC(=O)[C@H](Cc1ccc(OC(C)(C)C)cc1)NC(=O)[C@@H](N)C(C)C
Reaction time: 8 h

Procedure:
Pd-on-charcoal catalyst is added to a solution of 65 g (0.134 mole) of Z-Val-Tyr(But)-OMe in 300 ml of methanol and hydrogen is passed through the solution at pH 4.5 (autotitrator) while stirring and adding approx. 2 N methanolic hydrochloric acid, until no further methanolic hydrochloric acid is taken up. The catalyst is then filtered off and the filtrate is concentrated. The residue is triturated with ether, in the course of which the substance dissolves and, after standing overnight at 4°, precipitates out in crystalline form. The crystals are filtered off and dried over P2O5. The substance is hygroscopic. Yield 44.1 g (85%), melting point 88°-102°, [α]D21 =+31.0° (c=1, methanol).
Reaction SMILES: [CH:1]1[C:5]2=[C:6]([OH:15])[C:7]3[CH:14]=[CH:13][C:11](=[O:12])[O:10][C:8]=3[CH:9]=[C:4]2[O:3][CH:2]=1.Cl[CH2:17][CH2:18][CH2:19][C:20]#[N:21].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CC(=O)CC>[C:20]([CH2:19][CH2:18][CH2:17][O:15][C:6]1[C:7]2[CH:14]=[CH:13][C:11](=[O:12])[O:10][C:8]=2[CH:9]=[C:4]2[O:3][CH:2]=[CH:1][C:5]=12)#[N:21]
Reactant: N#CCCCCl
Reactant: O=c1ccc2c(O)c3ccoc3cc2o1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CCC(C)=O
Product: N#CCCCOc1c2ccoc2cc2oc(=O)ccc12
Reaction time: 0.29 h

Procedure:
800 mg (3.956 mmol) of 5-hydroxypsoralen and 0.7 ml (655.5 mg, 6.33 mmol) of 4-chlorobutyronitrile were refluxed in 50 ml of 2-butanone in the presence of an excess (2.6 g) of anhydrous potassium carbonate and catalytic amounts of potassium iodide for 48 hours. The progress of the reaction was monitored by thin layer chromatography. After 48 hours the reaction mixture was concentrated under reduced pressure. The residual oily layer was cooled, diluted with water and acidified with concentrated hydrochloric acid to pH 1. The slurry was stirred for 15-20 min and then filtered. The solids were washed with water to neutral pH, dried by suction and then further washed with petroleum ether. The dried solids were dissolved in refluxing methanol, treated with charcoal and recrystallized from methanol.
Reaction SMILES: CS(O[CH2:6][C@H:7]1[N:14]([S:15]([C:18]2[CH:19]=[CH:20][CH:21]=[C:22]3[C:27]=2[N:26]=[CH:25][CH:24]=[CH:23]3)(=[O:17])=[O:16])[CH2:13][C:12]2[CH:28]=[CH:29][CH:30]=[CH:31][C:11]=2[CH2:10][O:9][CH2:8]1)(=O)=O.CS(C)=O.C([O-])([O-])=O.[Cs+].[Cs+].[NH:42]1[CH:46]=[CH:45][CH:44]=[N:43]1>CC(=O)OCC>[N:42]1([CH2:6][C@H:7]2[N:14]([S:15]([C:18]3[CH:19]=[CH:20][CH:21]=[C:22]4[C:27]=3[N:26]=[CH:25][CH:24]=[CH:23]4)(=[O:16])=[O:17])[CH2:13][C:12]3[CH:28]=[CH:29][CH:30]=[CH:31][C:11]=3[CH2:10][O:9][CH2:8]2)[CH:46]=[CH:45][CH:44]=[N:43]1
Reactant: CS(=O)(=O)OC[C@@H]1COCc2ccccc2CN1S(=O)(=O)c1cccc2cccnc12
Reactant: c1cn[nH]c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: CS(C)=O
Product: O=S(=O)(c1cccc2cccnc12)N1Cc2ccccc2COC[C@H]1Cn1cccn1
Temperature: 110 °C
Yield: 32.9 %

Procedure:
Compound 17a (100 mg, 0.21 mmol) was added to DMSO (1 mL) and Cs2CO3 (500 mg, 1.5 mmol). 1H-Pyrazole (70 mg, 1.0 mmol) was added in the mixture and sealed in a microwave tube. The mixture was heated to 110° C. for 30 min under microwave irradiation. The reaction mixture was poured into ice/water (50 mL) and extracted with EA (3×50 mL) and washed with brine (2×50 mL) and dried over anhydrous Na2SO4. The residue was purified by CC eluting with PE:EA=3:1 to give compound 17 as white solid (30 mg, 32% yield). 1H-NMR (400 MHz, CD3OD) δ: 8.73 (d, J=1.6 Hz, 1H), 8.33 (d, J=7.2 Hz, 1H), 8.20 (d, 1H), 7.97 (d, 1H), 7.52-7.50 (m, 2H), 7.40-7.38 (m, 2H), 6.80 (d, 1H), 6.70 (t, 1H), 6.14 (s, 1H), 5.10 (m, 1H), 4.92 (d, J=14.4 Hz, 1H), 4.80 (m, 2H), 4.43 (d, J=14.4 Hz, 1H), 4.35 (q, 1H), 4.22 (q, 1H), 3.76 (d, 1H), 3.66 (d, 1H). MS (ESI+) m/z: 435.0 [M+H]+.
Reaction SMILES: C(N(CC)CC)C.I[C:9]1[CH:19]=[CH:18][C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][CH:10]=1.[CH2:20]([OH:24])[CH2:21][C:22]#[CH:23]>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OCC)(=O)C>[OH:24][CH2:20][CH2:21][C:22]#[C:23][C:9]1[CH:19]=[CH:18][C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][CH:10]=1
Reactant: CCOC(=O)c1ccc(I)cc1
Reactant: C#CCCO
Agent: Cl[Pd]Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: CCOC(=O)c1ccc(C#CCCO)cc1
Reaction time: 2.5 h
Yield: 100.8 %

Procedure:
To 50 ml of triethylamine were added 5.52 g of ethyl p-iodobenzoate, 1.54 g of 3-butyn-1-ol, 41 mg of cuprous iodide and 77 mg of bis(triphenylphosphine) palladium chloride, and the mixture was stirred for 2.5 hours under nitrogen flow. After adding 50 ml of ethyl acetate, the mixture was filtered to remove the precipitate, washed three times with 30 ml of water, dried over magnesium sulfate, and evaporated under a reduced pressure to obtain 4.4 g of ethyl p-(4-hydroxy-1-butynyl)benzoate as a colorless oil.
Reaction SMILES: [Cl:1][C:2]1[C:3]2[CH:13]=[CH:12][C:11](=[O:14])[N:10]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=3[F:22])[C:4]=2[N:5]=[C:6]([S:8][CH3:9])[N:7]=1.C1C=C(Cl)C=C(C(OO)=[O:31])C=1>C(Cl)Cl>[Cl:1][C:2]1[C:3]2[CH:13]=[CH:12][C:11](=[O:14])[N:10]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=3[F:22])[C:4]=2[N:5]=[C:6]([S:8]([CH3:9])=[O:31])[N:7]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CSc1nc(Cl)c2ccc(=O)n(-c3ccc(F)cc3F)c2n1
Solvent: ClCCl
Product: CS(=O)c1nc(Cl)c2ccc(=O)n(-c3ccc(F)cc3F)c2n1
Reaction time: 0.17 h
Yield: 77.7 %

Procedure:
To a solution of 4-chloro-8-(2,4-difluorophenyl)-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one (2.5 g, 7.6 mmol) in DCM (100 ml) was added m-CPBA (2.2 g, 10.2 mmol). The mixture was stirred for 10 min and evaporated. Flash chromatography (EtOAc) provided the title compound as a yellow solid (2.1 g, 80%): LC-MS m/z 356 (M+H)+ retention 2.43 min.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([SH:8])=[CH:4][CH:3]=1.[OH-].[K+].[F:11][C:12]([F:16])=[C:13]([F:15])[Cl:14].[OH-].[Na+]>O.CC(C)=O>[F:11][C:12]([F:16])([S:8][C:5]1[CH:6]=[CH:7][C:2]([CH3:1])=[CH:3][CH:4]=1)[CH:13]([F:15])[Cl:14]
Reactant: FC(F)=C(F)Cl
Reactant: Cc1ccc(S)cc1
Agent: [K+]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(C)=O
Product: Cc1ccc(SC(F)(F)C(F)Cl)cc1

Procedure:
A hot solution (60° C.) of 248 g (2 moles) of 4-methylthiophenol, 44.8 g of 85% potassium hydroxide, and 280 ml of acetone were placed in an autoclave. An amount of 256 g (2.2 moles) of trifluorochloroethylene was introduced in 1 h under pressure with agitation at 50°-55° C. After 1 h the reaction mixture was poured out in a solution of 1200 ml of water and 80 g (2 moles) of sodium hydroxide. The final product was extracted with ether, the ether solution was dried, and the solvent was evaporated. The residual oil was distilled at 120° C./1 mm.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][C:11]#[N:12])[CH:5]=1.Cl>CCO.O=[Pt]=O>[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][CH2:11][NH2:12])[CH:5]=1
Reactant: COC(=O)c1cccc(CC#N)c1
Agent: O=[Pt]=O
Agent: Cl
Solvent: CCO
Product: COC(=O)c1cccc(CCN)c1
Reaction time: 2.5 h
Yield: 84.8 %

Procedure:
A solution of 3-cyanomethyl-benzoic Acid methyl ester (1.36 g) in EtOH (25 mL) was saturated with HCl (g) and PtO2 (200 mg) was added. The reaction was hydrogenated on a Parr shaker at 50 psi for 2.5 h. The catalyst was removed via filtration through Celite and the solvent was removed in vacuo. The resulting solid was stirred in Et2O and the mixture was filtered to yield the title compound as a white solid (1.18 g). MS 180 (M+1).