Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:9][SiH:10]([Cl:12])[Cl:11].CS(O)(=O)=O>[Pt].C1(C)C=CC=CC=1>[CH2:1]([CH2:9][SiH:10]([Cl:12])[Cl:11])[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: C=Cc1ccccc1
Reactant: C[SiH](Cl)Cl
Agent: [Pt]
Agent: CS(=O)(=O)O
Solvent: Cc1ccccc1
Product: Cl[SiH](Cl)CCCc1ccccc1
Yield: 71 %

Procedure:
Reaction between styrene and methyldichlorosilane with platinum catalyst in the presence of trimethylsilyl ester of methanesulfonic acid. 624 mg Styrene and 732 mg methyldichlorosilane were introduced into a glass tube, and 51 mg of a trimethylsilyl ester of methanesulfonic acid was added with a microsyringe. 0.9 mg Of a toluene solution of a 0-valent platinum complex of divinylsiloxane (0.04 wt % platinum content) was added. The tube was sealed with Teflon tape and a rubber septum and placed in a 50° C. oil bath where it was heated for 30 minutes. After cooling, the tube contents were analyzed by gas chromatography revealing a styrene conversion of 95% and a phenethylmethyldichlorosilane yield of 71%. The ratio between the phenethylmethyldichlorosilane and the (α-methylbenzyl)methyldichlorosilane was 4.6:1.
Reaction SMILES: CS([O:5][CH2:6][CH2:7][C:8]([C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=1)([N:11]1[C:19]2[C:14](=[C:15]([NH:20][S:21]([CH3:24])(=[O:23])=[O:22])[CH:16]=[CH:17][CH:18]=2)[CH:13]=[CH:12]1)[CH2:9][CH3:10])(=O)=O.[CH3:32]O[Na]>CO>[Cl:31][C:28]1[CH:29]=[CH:30][C:25]([C:8]([N:11]2[C:19]3[C:14](=[C:15]([NH:20][S:21]([CH3:24])(=[O:22])=[O:23])[CH:16]=[CH:17][CH:18]=3)[CH:13]=[CH:12]2)([CH2:9][CH3:10])[CH2:7][CH2:6][O:5][CH3:32])=[CH:26][CH:27]=1
Reactant: CO[Na]
Reactant: CCC(CCOS(C)(=O)=O)(c1ccc(Cl)cc1)n1ccc2c(NS(C)(=O)=O)cccc21
Solvent: CO
Product: CCC(CCOC)(c1ccc(Cl)cc1)n1ccc2c(NS(C)(=O)=O)cccc21
Temperature: 40 °C

Procedure:
To a mixture of 3-(4-chlorophenyl)-3-(4-(methylsulfonamido)-1H-indol-1-yl)pentyl methanesulfonate (10 mg, 0.02 mmol), as described in Example 40 Step I, in methanol (2 mL) was added CH3ONa (21 mg, 0.4 mmol) at room temperature. Then the mixture was heated to 40° C. for 2 h. The solution was quenched with saturated ammonium chloride solution (10 mL), and extracted with ethyl acetate. The organic layers were washed with brine, dried over sodium sulfate, filtered and evaporated. The residue was purified by Prep-HPLC (Mobile phase: acetonitrile/water (0.03% TFA)) to afford the title compound as a white solid. LC/MS m/z=421.1 [M+H]+.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH:3]([CH2:7][OH:8])[CH2:2]1.[OH-].[Na+].[C:11](Cl)(=[O:15])[CH2:12][CH2:13][CH3:14]>O>[OH:8][CH2:7][CH:3]1[CH2:4][CH2:5][CH2:6][N:1]([C:11](=[O:15])[CH2:12][CH2:13][CH3:14])[CH2:2]1
Reactant: CCCC(=O)Cl
Reactant: OCC1CCCNC1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CCCC(=O)N1CCCC(CO)C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 66.9 %

Procedure:
To a solution of piperidin-3-yl-methanol (2.3 g, 20 mmol) in water (30 ml) is slowly added NaOH (1.2 g, 30 mmol). After total dissolution butyryl chloride (2.15 g, 2.11 ml, 20.2 mmol) is slowly added dropwise. The resulting mixture is allowed to stir overnight at rt. The water phase is extracted three times with dichloromethane. The combined organic phases are washed with brine and dried over Na2SO4. The solvents are evaporated in vacuo yielding the title compound (2.48 g) in 66% as a colourless oil which solidifies on standing: tR=1.52 min (LC-2), ESI-MS (pos.): m/z 208.00 [M+Na]+; 1H-NMR (CDCl3): The product is a (1:1) mixture of rotamers: δ (ppm) 0.92 (t, 3H, CH3), 1.21 (m, 0.5H), 1.33-1.52 (m, 2H), 1.57-1.84 (m, 5H), 2.26-2.32 (m, 2H, CH2C═O), 2.74 (dt, 0.5H), 2.87 (dd, 0.5H), 3.10 (dd, 1H), 3.26 (ddd, 1H), 3.39-3.45 (m, 1.5H), 3.51-3.59 (m, 1H), 3.91 (dd, 1H), 4.29 (dt, 0.5H).
Reaction SMILES: O[C:2]([CH3:11])([CH3:10])[CH2:3][CH2:4][CH2:5][CH:6]([CH3:9])[CH:7]=[O:8]>O>[CH3:9][CH:6]([CH2:5][CH2:4][CH:3]=[C:2]([CH3:11])[CH3:10])[CH:7]=[O:8]
Reactant: CC(C=O)CCCC(C)(C)O
Solvent: O
Product: CC(C)=CCCC(C)C=O

Procedure:
A process for preparing 6-hydroxy-2,6-dimethylheptanal defined by one of the structures: ##STR16## comprising the steps of (1) forming an emulsion of 2,6-dimethyl-5-heptenal with water using an emulsifying agent which is an alkali metal salt of a long chain fatty acid; (2) reacting sodium sulfite with the 2,6-dimethyl-5-heptenal in the presence of boric acid while it is in the emulsion whereby a sulfite-aldehyde addition salt of 2,6-dimethyl-5-heptenal is formed, the reaction taking place at a temperature of between 10° C. and 50° C., the mole ratio of sodium sulfite:2,6-dimethyl-5-heptenal varying between 1:1 up to 10:1; the concentration of sodium sulfite in the reaction mass being from 0.1 molar up to 3.0 molar and the concentration of 2,6-dimethyl-5-heptenal being from 0.5 molar up to 2.0 molar; and (3) hydrolyzing the resulting sulfite-aldehyde addition salt of 2,6-dimethyl-5-heptenal with hydrochloric acid using from 10% up to 50% hydrochloric acid, the mole ratio of HCl:sulfite addition salt of 2,6-dimethyl-6-hydroxy-heptanal being 0.5:1 up to 1.5:1 with the reaction temperature for the hydrolysis reaction varying from 0° C. up to 50° C.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:12])[CH2:5]P(OC)(OC)=O)[CH3:2].CC([O-])(C)C.[K+].[F:19][C:20]1[CH:27]=[C:26]([F:28])[CH:25]=[C:24]([F:29])[C:21]=1[CH:22]=O.[Cl-].[NH4+]>C1COCC1.CN(C=O)C.C1COCC1>[F:19][C:20]1[CH:27]=[C:26]([F:28])[CH:25]=[C:24]([F:29])[C:21]=1/[CH:22]=[CH:5]/[C:4]([O:3][CH2:1][CH3:2])=[O:12]
Reactant: O=Cc1c(F)cc(F)cc1F
Reactant: CCOC(=O)CP(=O)(OC)OC
Agent: CC(C)(C)[O-]
Agent: [Cl-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: CCOC(=O)/C=C/c1c(F)cc(F)cc1F
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 87 %

Procedure:
To the solution of ethyl[bis(methyloxy)phosphoryl]acetate (1.980 mL, 11.99 mmol) in THF-DMF (60 mL, v/v=5:1) at 0° C. was added t-BuOK (1.458 g, 12.99 mmol) portion wise. The resultant mixture was stirred at room temperature for 30 minutes, then mixed with a solution of 2,4,6-trifluorobenzaldehyde (1.6 g, 9.99 mmol) in THF (10 mL) at 0° C. It was allowed to warm to room temperature and the mixture was stirred for 45 min. It was mixed with aqueous ammonium chloride and then extracted with ethyl acetate. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by a flash column chromatography to give the title compound as a pale yellow oil (2.0 g, 87% yield). LCMS: rt=3.52 min, [M+H+]=231.1
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]2[N:11]([CH3:12])[CH2:10][CH2:9][N:5]2[C:6](=[O:8])[N:7]=1.[F:13][C:14]1[CH:15]=[C:16]([CH2:32][OH:33])[CH:17]=[C:18]([F:31])[C:19]=1[O:20][C:21]1[CH:22]=[N:23][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:25][CH:26]=1>>[F:13][C:14]1[CH:15]=[C:16]([CH:17]=[C:18]([F:31])[C:19]=1[O:20][C:21]1[CH:22]=[N:23][C:24]([C:27]([F:30])([F:28])[F:29])=[CH:25][CH:26]=1)[CH2:32][O:33][C:2]1[CH:3]=[C:4]2[N:11]([CH3:12])[CH2:10][CH2:9][N:5]2[C:6](=[O:8])[N:7]=1
Reactant: CN1CCn2c1cc(Cl)nc2=O
Reactant: OCc1cc(F)c(Oc2ccc(C(F)(F)F)nc2)c(F)c1
Product: CN1CCn2c1cc(OCc1cc(F)c(Oc3ccc(C(F)(F)F)nc3)c(F)c1)nc2=O

Procedure:
The title compound was prepared by a procedure similar to those described for E1 starting from 7-chloro-1-methyl-2,3-dihydroimidazo[1,2-c]pyrimidin-5(1H)-one and (3,5-difluoro-4-((6-(trifluoromethyl)pyridin-3-yl)oxy)phenyl)methanol.
Reaction SMILES: [O:1]=[C:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[S:4][N:3]1[C:11]1[CH:16]=[CH:15][C:14]([S:17]([NH2:20])(=[O:19])=[O:18])=[CH:13][CH:12]=1.[SH:21][CH:22]([CH3:30])[C:23]([NH:25][CH2:26][C:27]([OH:29])=[O:28])=[O:24]>>[S:17]([C:14]1[CH:15]=[CH:16][C:11]([NH:3][C:2]([C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[S:4][S:21][CH:22]([CH3:30])[C:23]([NH:25][CH2:26][C:27]([OH:29])=[O:28])=[O:24])=[O:1])=[CH:12][CH:13]=1)(=[O:19])(=[O:18])[NH2:20]
Reactant: NS(=O)(=O)c1ccc(-n2sc3ccccc3c2=O)cc1
Reactant: CC(S)C(=O)NCC(=O)O
Product: CC(SSc1ccccc1C(=O)Nc1ccc(S(N)(=O)=O)cc1)C(=O)NCC(=O)O
Yield: 92.3 %

Procedure:
This compound was prepared according to the method of Example 132 using 0.46 g (1.5 mmol) of 4-(3-oxo-3H-benzo[d]isothiazol-2-yl)benzenesulfonamide and 0.25 g (1.5 mmol) of 2-mercapto-propionylglycine. The product was washed with ether and dried in vacuo to give 0.65 g of the title compound, mp 254-256° C.
Reaction SMILES: [CH:1]1([N:6]2[CH2:12][C:11]3([CH2:14][CH2:13]3)[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[NH2:64][N:65]1[CH2:70][CH2:69][O:68][CH2:67][CH2:66]1>C(Cl)Cl>[CH:1]1([N:6]2[CH2:12][C:11]3([CH2:14][CH2:13]3)[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26]([NH:64][N:65]5[CH2:70][CH2:69][O:68][CH2:67][CH2:66]5)=[O:27])=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: NN1CCOCC1
Reactant: COc1cc(C(=O)O)ccc1Nc1ncc2c(n1)N(C1CCCC1)CC1(CC1)C(=O)N2C
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: COc1cc(C(=O)NN2CCOCC2)ccc1Nc1ncc2c(n1)N(C1CCCC1)CC1(CC1)C(=O)N2C
Temperature: 25 °C
Reaction time: 16 h
Yield: 45.3 %

Procedure:
4-(9′-Cyclopentyl-5′-methyl-6′-oxo-5′,6′,8′,9′-tetrahydrospiro[cyclopropane-1,7′-pyrimido[4,5-b][1,4]diazepine]-2′-ylamino)-3-methoxybenzoic acid (Intermediate 5) (50 mg, 0.11 mmol, 1 eq), DIPEA (38 μL, 0.23 mmol, 2 eq) and TBTU (40 mg, 0.12 mmol, 1.1 eq) were added to 5 mL DCM and the resulting solution stirred at rt for 15 min before the addition of 4-aminomorpholine (12 mg, 0.14 mmol, 1.2 eq). The RM was then stirred at rt for 16 hours before concentrating in vacuo and purifying by preparative RP-HPLC-MS (Preparative 1) to provide 4-(9′-cyclopentyl-5′-methyl-6′-oxo-5′,6′,8′,9′-tetrahydrospiro[cyclopropane-1,7′-pyrimido[4,5-b][1,4]diazepine]-2′-ylamino)-3-methoxy-N-morpholinobenzamide (26 mg, 44%).
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9][CH:8]1[NH:16][C:17](OCC)=O>O1CCCC1>[CH3:17][NH:16][CH:8]1[CH2:9][C:10]2[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:7]1
Reactant: CCOC(=O)NC1Cc2ccccc2C1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CNC1Cc2ccccc2C1
Yield: 221.8 %

Procedure:
To a suspension of 1.13 g (30 mmol) of anhydrous lithium aluminium hydride in 150 ml of tetrahydrofuran was added a solution of 2.2 g of ethyl indan-2-carbamate in 50 ml of the same solvent. The mixture was heated to reflux, allowed to cool, hydrolysed with an excess of aqueous 1N sodium hydroxide solution, and the mixture was filtered, concentrated and distilled at about 100 Pa at 150° C. 3.5 g of oil were obtained.
Reaction SMILES: [C:1]1([CH:7]2[C:15]3[CH:14]=[CH:13][N:12]=[CH:11][C:10]=3[CH:9]([OH:16])[O:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[BH4-].[Na+]>C(O)C.C(OCC)(=O)C>[OH:16][CH2:9][C:10]1[CH:11]=[N:12][CH:13]=[CH:14][C:15]=1[CH:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[OH:8]
Reactant: OC1OC(c2ccccc2)c2ccncc21
Agent: [BH4-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CCO
Product: OCc1cnccc1C(O)c1ccccc1
Reaction time: 1 h

Procedure:
1-Phenyl-1,3-dihydro-furo[3,4-c]pyridin-3-ol (50 mg) was dissolved in ethanol (2 mL) and treated with sodium borohydride (13 mg). The reaction mixture was stirred for 1 hour and then diluted with ethyl acetate and washed with brine. The organic layer was dried over sodium sulfate, concentrated, and the residue purified by flash chromatography to yield (3-hydroxymethyl-pyridin-4-yl)-phenyl-methanol as a colorless foam.
Reaction SMILES: [C:1]([OH:12])(=O)[CH2:2][CH2:3][CH2:4][CH:5]=[CH:6][CH2:7][CH2:8][CH2:9][CH3:10].[C:13]([O-])(=[O:23])[CH2:14]CCC=CCCCC.C=CCCCC>Cl[Ru](=CC1C=CC=CC=1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)Cl>[C:13]([O:12][CH2:1][CH2:2][CH2:3][CH2:4][CH:5]=[CH:6][CH2:7][CH2:8][CH2:9][CH3:10])(=[O:23])[CH3:14]
Reactant: CCCCC=CCCCC(=O)[O-]
Reactant: CCCCC=CCCCC(=O)O
Agent: Cl[Ru](Cl)(=Cc1ccccc1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)[P](C1CCCCC1)(C1CCCCC1)C1CCCCC1
Solvent: C=CCCCC
Product: CCCCC=CCCCCOC(C)=O

Procedure:
For example, 5-hexenoic acid or an ester of 5-hexenoic acid (e.g. methyl 5-hexenoate, ethyl 5-hexenoate, etc.) could be used instead of 1-hexene, but the synthesis would entail a reduction of a carboxylic acid or an ester to an alcohol followed by acetylation. These syntheses are respectively shown in FIGS. 6 and 7. With reference to FIGS. 6 an 7, the 5-hexenoic acid or 5-hexenoate is reacted with 5-decene to form 5-decenoic acid or 5-decenoate, respectively, in the presence of Grubbs' catalyst and under vacuum. The resulting 5-decenoic acid or 5-decenoate are then reacted with 1-hexene, reduced, and acetylated to form 5-decenyl acetate. In addition, synthesizing 5-decenoic acid would have advantages because the salt of 5-decenoic acid could be recrystallized to increase the trans-isomer to greater than 90 percent trans-5-decenoic acid, which is then reduced and acetylated to greater than 90 percent trans-5-decenyl acetate.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][C:13]([OH:17])=[CH:14][CH:15]=3)[C:10]([CH3:19])([CH3:18])[CH2:9]2)=[CH:3][CH:2]=1.[CH3:20][N:21]([CH3:31])[C:22]1[CH:27]=[CH:26][C:25]([N:28]=[C:29]=[O:30])=[CH:24][CH:23]=1>>[CH3:20][N:21]([CH3:31])[C:22]1[CH:27]=[CH:26][C:25]([NH:28][C:29](=[O:30])[O:17][C:13]2[CH:12]=[C:11]3[C:16](=[CH:15][CH:14]=2)[N:8]([CH2:7][C:4]2[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=2)[CH2:9][C:10]3([CH3:19])[CH3:18])=[CH:24][CH:23]=1
Reactant: CC1(C)CN(Cc2ccncc2)c2ccc(O)cc21
Reactant: CN(C)c1ccc(N=C=O)cc1
Product: CN(C)c1ccc(NC(=O)Oc2ccc3c(c2)C(C)(C)CN3Cc2ccncc2)cc1

Procedure:
The title compound was synthesized from 1-(4-pyridylmethyl)-3,3-dimethylindolin-5-ol (20.0 mg, 0.09 mmol) using the same procedure employed for Example 2 (2), but with 4-dimethylaminophenylisocyanate instead of 4-isopropylphenylisocyanate. The product was obtained as a white solid (2.1 mg, 6%) having the following characteristics.
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.[O:9]1[CH2:14][CH2:13][C:12](=[O:15])[CH2:11][CH2:10]1>C1COCC1>[Br:8][C:6]1[CH:7]=[C:2]([C:12]2([OH:15])[CH2:13][CH2:14][O:9][CH2:10][CH2:11]2)[CH:3]=[N:4][CH:5]=1
Reactant: Brc1cncc(Br)c1
Reactant: O=C1CCOCC1
Solvent: C1CCOC1
Product: OC1(c2cncc(Br)c2)CCOCC1
Temperature: -10 °C
Reaction time: 0.5 h
Yield: 26 %

Procedure:
To 3,5-dibromopyridine (592 mg, 2.50 mmol) in 2 mL of THF at −20° C. is added 1.3M i-PrMgCl_LiCl solution (1.83 mL, 2.4 mmol) in one portion. The mixture is allowed to stir for 30 min., warming to −10° C. The mixture is cooled to −20° C. and tetrahydro-pyran-4-one (0.23 mL, 3.00 mmol) is added. The reaction is quenched with 50 mL of saturated aqueous NH4Cl and diluted with 200 mL EtOAc. The organic phase is washed with 2×100 mL of H2O, 1×100 mL of brine. The organic phase is dried with MgSO4, filtered and concentrated. The crude material is applied to a silica column and purified (0-10% MeOH/CH2Cl2) to give 168 mg of 4-(5-bromo-pyridin-3-yl)-tetrahydro-pyran-4-ol.
Reaction SMILES: [CH:1]([C:4]1[N:5]=[C:6]([NH2:9])[S:7][CH:8]=1)([CH3:3])[CH3:2].[Br:10]Br.C([O-])(O)=O.[Na+]>C(Cl)(Cl)Cl>[Br:10][C:8]1[S:7][C:6]([NH2:9])=[N:5][C:4]=1[CH:1]([CH3:3])[CH3:2]
Reactant: BrBr
Reactant: CC(C)c1csc(N)n1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: CC(C)c1nc(N)sc1Br
Temperature: 25 °C
Reaction time: 60 h

Procedure:
A solution of 4-isopropyl-thiazol-2-ylamine (2.0 g, 14 mmol) in 30 mL CHCl3 was added dropwise to a stirring solution of bromine ((2.697 g, 17 mmol) in 15 mL CHCl3. The reaction mixture was stirred for 60 hours at room temperature. The reaction mixture was poured into saturated aqueous NaHCO3, and extracted wtih methylene chloride. The combined organic extracts were washed with saturated aqueous NaHCO3 and brine, dried (MgSO4), filtered and concentrated under reduced pressure to give 2.05 g of 5-bromo-4-isopropyl-thiazol-2-ylamine as an oil.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]([C:15]2[O:16][C:17]([C:20]3[S:24][C:23]([C:25]([O:27]C)=[O:26])=[CH:22][CH:21]=3)=[CH:18][N:19]=2)=[O:14])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>CO.C(Cl)Cl>[C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]([C:15]2[O:16][C:17]([C:20]3[S:24][C:23]([C:25]([OH:27])=[O:26])=[CH:22][CH:21]=3)=[CH:18][N:19]=2)=[O:14])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: COC(=O)c1ccc(-c2cnc(C(=O)CCCCCCc3ccccc3)o2)s1
Solvent: CO
Solvent: ClCCl
Product: O=C(CCCCCCc1ccccc1)c1ncc(-c2ccc(C(=O)O)s2)o1
Yield: 43.5 %

Procedure:
The title compound was prepared from methyl 5-(2-(7-phenylheptanoyl)oxazol-5-yl)thiophene-2-carboxylate (7 mg, 0.018 mmol) following General Procedure E. Preparative thin layer chromatography (10% MeOH/CH2Cl2) yielded the title compound as a white solid (3 mg, 41%): 1H NMR (THF-d8, 500 MHz) δ 7.73 (d, 1H, J=3.5 Hz), 7.72 (s, 1H), 7.55 (d, 1H, J=4.0 Hz), 7.22-7.08 (m, 5H), 3.03 (t, 2H, J=7.0 Hz), 2.60 (t, 2H, J=7.5 Hz), 1.73-1.71 (m, 2H), 1.65-1.61 (m, 2H), 1.42-1.40 (m, 4H); 13C NMR NMR (THF-d8, 125 MHz) δ 185.1, 164.0, 155.8, 147.0, 141.0, 134.8, 132.7, 132.1, 126.7, 126.5, 124.9, 123.9, 123.3, 37.0, 34.3, 30.0, 27.6, 27.5, 22.2; MALDI-FTMS m/z 384.1272 (M+H+, C21H22NO4S, requires 384.1264).
Reaction SMILES: Br[C:2]1[NH:3][C:4](=[O:11])[C:5]2[NH:6][CH:7]=[N:8][C:9]=2[N:10]=1.[C:12]1([SH:18])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(C(C)C)CC)(C)C>CO>[C:12]1([S:18][C:2]2[NH:3][C:4](=[O:11])[C:5]3[NH:6][CH:7]=[N:8][C:9]=3[N:10]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: O=c1[nH]c(Br)nc2nc[nH]c12
Reactant: Sc1ccccc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CO
Product: O=c1[nH]c(Sc2ccccc2)nc2nc[nH]c12
Temperature: 90 °C
Reaction time: 8 h
Yield: 88.9 %

Procedure:
To a solution of 2-bromohypoxanthine (10.0 g, 46.5 mmol) in methanol (200 mL) was added thiophenol (9.55 mL, 93.0 mmol) and diisopropylethylamine (20.2 mL, 116.3 mmol). The reaction was stirred at 90° C. for overnight. The solvent was removed under reduced pressure and the solid was collected by filtration and washed with hexanes (100 mL×2). The collected solid was further purified by re-crystallization from methanol to afford desired product (10.1 g, 89% yield). 1H NMR (400 MHz, (CD3)2SO) δ 7.50(m, 3H), 7.62 (m, 2H), 7.97 (s, 1H); MS (ES) calc'd for C11H8N4OS [MH+] 245.05, found: 245.05.
Reaction SMILES: [Br:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([CH2:9][CH2:10][CH:11]([OH:13])[CH3:12])=[CH:4][C:3]=1[CH3:14].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>ClCCl>[Br:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([CH2:9][CH2:10][C:11](=[O:13])[CH3:12])=[CH:4][C:3]=1[CH3:14]
Reactant: Cc1cc(CCC(C)O)cc(C)c1Br
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Product: CC(=O)CCc1cc(C)c(Br)c(C)c1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a solution of 4-(4-bromo-3,5-dimethylphenyl)butan-2-ol (130 mg) in dichloromethane (8 mL) is added at 0° C. 1,1-dihydro-1,1,1-triacetoxy-1,2-benziodoxol-3(1H)-on (Dess-Martin periodinan, 1.4 mL of a 15% solution in dichloromethane). The mixture is stirred for 12 hours at room temperature. The solvents are evaporated in vacuo. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 99:1→70:30) to give the title compound. Yield: 100 mg; LC (method 8): tR=0.44 min; Mass spectrum (ESI+): m/z=255 [M+H]+.
Reaction SMILES: [CH:1]1([CH:6]=[C:7]([C:18]2[NH:34][C:21]3=[N:22][CH:23]=[C:24]([CH2:26][CH:27]4[CH2:31][O:30][C:29]([CH3:33])([CH3:32])[O:28]4)[CH:25]=[C:20]3[CH:19]=2)[C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:10][CH:9]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[H][H]>[Pd].CO>[CH:1]1([CH2:6][CH:7]([C:18]2[NH:34][C:21]3=[N:22][CH:23]=[C:24]([CH2:26][CH:27]4[CH2:31][O:30][C:29]([CH3:32])([CH3:33])[O:28]4)[CH:25]=[C:20]3[CH:19]=2)[C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:10][CH:9]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: [H][H]
Reactant: CC1(C)OCC(Cc2cnc3[nH]c(C(=CC4CCCC4)c4ccc(S(C)(=O)=O)cc4)cc3c2)O1
Agent: [Pd]
Solvent: CO
Product: CC1(C)OCC(Cc2cnc3[nH]c(C(CC4CCCC4)c4ccc(S(C)(=O)=O)cc4)cc3c2)O1
Temperature: 25 °C
Yield: 86.1 %

Procedure:
A mixture of 2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-vinyl]-5-(2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrrolo[2,3-b]pyridine (310 mg, 0.65 mmol) and 10% palladium on activated carbon (100 mg) in methanol (250 mL) was heated at 50° C. under 50 bar of hydrogen in a steel bomb pressure for 8 h. The mixture was cooled to room temperature. The catalyst was removed by filtration and washed with ethyl acetate. The filtrate was concentrated in vacuo to afford 2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-5-(2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrrolo[2,3-b]pyridine (270 mg, 86.8%) as a white solid: LC/MS m/e calcd for C27H34N2O4S [M+H]+ 483.65, observed 483.3.
Reaction SMILES: C([O:3][CH:4]([O:19]CC)[C:5]#[C:6][C:7](=[O:18])/[CH:8]=[CH:9]/[C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=1)C.CCOCC.O>O1CCOCC1.Br>[CH3:17][O:16][C:13]1[CH:12]=[CH:11][C:10](/[CH:9]=[CH:8]/[C:7](=[O:18])/[CH:6]=[CH:5]/[C:4]([OH:19])=[O:3])=[CH:15][CH:14]=1
Reactant: CCOC(C#CC(=O)/C=C/c1ccc(OC)cc1)OCC
Agent: Br
Solvent: C1COCCO1
Solvent: CCOCC
Solvent: O
Product: COc1ccc(/C=C/C(=O)/C=C/C(=O)O)cc1

Procedure:
A solution of 1.0 g (3.47 mmol) of (E)-6,6-diethoxy-1-(p-methoxyphenyl)-1-hexen-4-yn-3-one in 4 ml of dioxane and 2 ml of 2.2N aqueous hydrobromic acid was stirred at 30° for 18 hours and subsequently treated with 20 ml of ether and 10 ml of water. The aqueous phase was extracted twice with ethyl acetate. The combined organic fractions were dried over magnesium sulphate, filtered and evaporated. The residue was chromatographed on 80 g of silica gel with acetonitrile/water (1:1). The fractions containing the product were extracted with ethyl acetate. The combined ethyl acetate extracts were dried over magnesium sulphate, filtered and evaporated. The residue was recrystallized from ethyl acetate/hexane, whereby there was obtained (E,E)-6-(p-methoxyphenyl)-4-oxo-2,5-hexadienoic acid of melting point 138°-139°.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:20])[C:7]=1[S:8][C:9]1[S:13][C:12]([C:14]([OH:16])=O)=[CH:11][C:10]=1[N+:17]([O-:19])=[O:18].[S:21]1[CH:25]=[CH:24][CH:23]=[C:22]1[CH2:26][CH2:27][NH2:28]>>[Cl:20][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([Cl:1])[C:7]=1[S:8][C:9]1[S:13][C:12]([C:14]([NH:28][CH2:27][CH2:26][C:22]2[S:21][CH:25]=[CH:24][CH:23]=2)=[O:16])=[CH:11][C:10]=1[N+:17]([O-:19])=[O:18]
Reactant: O=C(O)c1cc([N+](=O)[O-])c(Sc2c(Cl)cncc2Cl)s1
Reactant: NCCc1cccs1
Product: O=C(NCCc1cccs1)c1cc([N+](=O)[O-])c(Sc2c(Cl)cncc2Cl)s1

Procedure:
Prepared according to the procedure described for example 50 from 5-[(3,5-dichloro-4-pyridyl)sulfanyl]-4-nitro-thiophene-2-carboxylic acid (100 mg, 0.28 mmol) and Thiophene-2-ethylamine (41 mg, 0.32 mmol). The title compound was obtained as a solid (35 mg, 27% yield). 1H NMR (400 MHz, d6-DMSO) δ: 9.00 (1H, m), 8.99 (2H, m), 8.41 (1H, s), 7.33 (1H, m), 6.94 (2H, m), 3.44 (2H, m), 3.02 (2H, m). MS m/z: 458.00, 459.99 [M+H]+.