Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH2:10][CH2:11][C:12]1[NH:13][C:14]([S:20][C:21]2[CH:26]=[C:25]([Cl:27])[CH:24]=[C:23]([Cl:28])[CH:22]=2)=[C:15]([CH:17]([CH3:19])[CH3:18])[N:16]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:29](=O)([O-])[O-].[Li+].[Li+].S(OC)(OC)(=O)=O>C(#N)C>[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][C:12]1[N:13]([CH3:29])[C:14]([S:20][C:21]2[CH:26]=[C:25]([Cl:27])[CH:24]=[C:23]([Cl:28])[CH:22]=2)=[C:15]([CH:17]([CH3:19])[CH3:18])[N:16]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C([O-])[O-]
Reactant: CC(C)c1nc(CCCOCc2ccccc2)[nH]c1Sc1cc(Cl)cc(Cl)c1
Agent: [Li+]
Solvent: COS(=O)(=O)OC
Solvent: CC#N
Product: CC(C)c1nc(CCCOCc2ccccc2)n(C)c1Sc1cc(Cl)cc(Cl)c1
Temperature: 70 °C
Yield: 60 %

Procedure:
In 25 ml of dry acetonitrile was dissolved 5.0 g (11.5 mmol) of imidazole (101e), followed by addition of 1.7 g (23 ml) of lithium carbonate and 2.2 g (17.4 mmol) of dimethyl sulfate. The mixture was stirred under heating at 70° C. for 2 hours. The reactLion mixture was diluted with ice-water and extracted with diethyl ether. The extract was washed with water, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate) to provide 3.1 g (yield 60%) of 2-(3-benzyloxypropyl)-5-(3,5-dichlorophenyl-thio)-4-isopropyl-1-methyl-1H-imidazole (136a) as oil.
Reaction SMILES: [Cl:1][C:2]1[C:12]2[CH2:11][CH2:10][N:9](C(OC(C)(C)C)=O)[CH2:8][CH2:7][C:6]=2[N:5]=[CH:4][N:3]=1.Cl>C(Cl)Cl.O1CCOCC1>[Cl:1][C:2]1[C:12]2[CH2:11][CH2:10][NH:9][CH2:8][CH2:7][C:6]=2[N:5]=[CH:4][N:3]=1
Reactant: CC(C)(C)OC(=O)N1CCc2ncnc(Cl)c2CC1
Agent: Cl
Solvent: C1COCCO1
Solvent: ClCCl
Product: Clc1ncnc2c1CCNCC2
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of tert-butyl 4-chloro-5,6,8,9-tetrahydro-7H-pyrimido[4,5-d]azepine-7-carboxylate (2.0 g, 7.1 mmol) in DCM, a solution of 4N HCl in dioxane (10 mL) is added. The mixture is stirred for 4 hr at rt. The solvent is removed under vacuum to give the title compound (dichloride salt) as a white solid.
Reaction SMILES: [F:1][CH2:2][CH:3]([OH:40])[CH2:4][O:5][C@H:6]1[CH2:11][CH2:10][C@H:9]([N:12]2[C:17](=[O:18])[C:16]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([C:26]4[C:27]([C:32]#[N:33])=[CH:28][CH:29]=[CH:30][CH:31]=4)=[CH:22][CH:21]=3)=[C:15]([CH2:34][CH2:35][CH3:36])[N:14]3[N:37]=[CH:38][N:39]=[C:13]23)[CH2:8][CH2:7]1.[CH3:41]C(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.C(=O)([O-])O.[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+]>C(#N)C>[F:1][CH2:2][C:3]([OH:40])([CH3:41])[CH2:4][O:5][C@H:6]1[CH2:11][CH2:10][C@H:9]([N:12]2[C:17](=[O:18])[C:16]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([C:26]4[C:27]([C:32]#[N:33])=[CH:28][CH:29]=[CH:30][CH:31]=4)=[CH:22][CH:21]=3)=[C:15]([CH2:34][CH2:35][CH3:36])[N:14]3[N:37]=[CH:38][N:39]=[C:13]23)[CH2:8][CH2:7]1
Reactant: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Reactant: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n([C@H]2CC[C@H](OCC(O)CF)CC2)c2ncnn12
Agent: O=C([O-])O
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: CC#N
Product: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n([C@H]2CC[C@H](OCC(C)(O)CF)CC2)c2ncnn12
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A mixture of 4′-({4-[trans-4-(3-fluoro-2-hydroxypropoxy)cyclohexyl]-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl}methyl)biphenyl-2-carbonitrile (0.15 g), Dess-Martin periodinane (0.24 g) and acetonitrile (2 mL) was stirred at room temperature for 2 hr. Saturated aqueous sodium hydrogen carbonate solution and aqueous sodium thiosulfate solution were added to the reaction mixture. After evaporation of the solvent under reduced pressure, the residue was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was dissolved in tetrahydrofuran (2 mL). Methylmagnesium bromide (0.58 mL, 1.0 M tetrahydrofuran solution) was added dropwise at 0° C., and the mixture was stirred at room temperature for 2 hr. The reaction mixture was added to 1 M hydrochloric acid, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound as a colorless solid (0.10 g, 62%).
Reaction SMILES: [O:1]=[C:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.Cl.[CH2:18]([O:20][C:21](=[O:24])[CH2:22][NH2:23])[CH3:19]>>[O:1]=[C:2]1[CH2:3][CH2:4][N:5]([C:8]2[CH:9]=[CH:10][C:11]([C:12]([NH:23][CH2:22][C:21]([O:20][CH2:18][CH3:19])=[O:24])=[O:14])=[CH:15][CH:16]=2)[CH2:6][CH2:7]1
Reactant: CCOC(=O)CN
Reactant: O=C1CCN(c2ccc(C(=O)O)cc2)CC1
Agent: Cl
Product: CCOC(=O)CNC(=O)c1ccc(N2CCC(=O)CC2)cc1

Procedure:
The title compound was prepared from 4-(4-oxo-piperidine-1-yl)-benzoic acid (which was obtained in Example 151) and glycine ethyl ester hydrochloride according to the procedure of Example 154 as a pale yellowish solid; 1H NMR (300 MHz, DMSO-d6) δ 1.20 (t, J=7.1 Hz, 3H), 2.43 (t, J=6.1 Hz, 4H), 3.72 (t, J=6.1 Hz, 4H), 3.95 (d, J=5.8 Hz, 2H), 4.10 (q, J=7.1 Hz, 2H), 7.04 (d, J=8.9 Hz, 2H), 7.77 (d, J=8.9 Hz, 2H), 8.63 (t, J=5.8 Hz, 1H); MS (ES) m/z: 305.2 (MH+); HRMS Calcd. for C18H22N2O4 (M+): 304.1423. Found: 304.1422.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[O:15][C:12]([CH:13]=O)=[CH:11][CH:10]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].[N+:16]([CH3:19])([O-])=O.C([O-])(=O)C.[NH4+]>C(O)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[O:15][C:12](/[CH:13]=[CH:19]/[NH2:16])=[CH:11][CH:10]=2)[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: O=Cc1ccc(-c2ccc(Cl)c(Cl)c2)o1
Reactant: C[N+](=O)[O-]
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: CC(=O)O
Product: N/C=C/c1ccc(-c2ccc(Cl)c(Cl)c2)o1
Temperature: 80 °C
Yield: 92.5 %

Procedure:
To a stirred solution of 5-(3,4-dichlorophenyl)furfural (1.18 g, 4.89 mmol) in acetic acid (30 ml) was added nitromethane (0.535 ml, 9.78 mmol) and ammonium acetate (1.13 g, 14.7 mmol). The reaction mixture was heated at 80° C. for 4.5 h. Cooled reaction mixture was poured onto ice water (30 ml) and thus formed precipitate was filtered, washed with water and dried under vacuum to give 1.15 g (83%) of the title compound. 1H-NMR (400 MHz; d6-DMSO): δ 7.37 (d, 1H), 7.43 (d, 1H), 7.76 (d, 1H), 7.95 (dd, 1H), 8.03 (d, 1H), 8.19 (d, 1H), 8.31 (d, 1H).
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10]2[C:14]([C:15]3[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][CH:16]=3)=[C:13]([CH3:22])[S:12][C:11]=2[CH:23]=1.[CH2:24]([NH:26][CH2:27][CH2:28][OH:29])[CH3:25]>>[Br:21][C:18]1[CH:19]=[CH:20][C:15]([C:14]2[C:10]3[CH:9]=[CH:8][C:7]([O:6][CH2:5][CH2:4][CH2:3][CH2:2][N:26]([CH2:24][CH3:25])[CH2:27][CH2:28][OH:29])=[CH:23][C:11]=3[S:12][C:13]=2[CH3:22])=[CH:16][CH:17]=1
Reactant: Cc1sc2cc(OCCCCBr)ccc2c1-c1ccc(Br)cc1
Reactant: CCNCCO
Product: CCN(CCO)CCCCOc1ccc2c(-c3ccc(Br)cc3)c(C)sc2c1

Procedure:
According to the method in example 31, 6-(4-Bromo-butoxy)-3-(4-bromo-phenyl)-2-methyl-benzo[b]thiophene and Ethyl-(2-hydroxy-ethyl)-amine were converted to yield 2-({4-[3-(4-Bromo-phenyl)-2-methyl-benzo[b]thiophen-6-yloxy]-butyl}-ethyl-amino)-ethanol, MS: 462 (MH+,1Br).
Reaction SMILES: C(OC([N:8]1[C:11]2([CH2:14][N:13]([C:15](=[O:27])[NH:16][C:17]34[CH2:26][CH:21]5[CH2:22][CH:23]([CH2:25][CH:19]([CH2:20]5)[CH2:18]3)[CH2:24]4)[CH2:12]2)[CH2:10][CH2:9]1)=O)(C)(C)C.[Cl:28][C:29]1[CH:34]=[CH:33][C:32]([S:35](Cl)(=[O:37])=[O:36])=[CH:31][CH:30]=1>>[C:17]12([NH:16][C:15]([N:13]3[CH2:14][C:11]4([N:8]([S:35]([C:32]5[CH:33]=[CH:34][C:29]([Cl:28])=[CH:30][CH:31]=5)(=[O:37])=[O:36])[CH2:9][CH2:10]4)[CH2:12]3)=[O:27])[CH2:18][CH:19]3[CH2:25][CH:23]([CH2:22][CH:21]([CH2:20]3)[CH2:26]1)[CH2:24]2
Reactant: O=S(=O)(Cl)c1ccc(Cl)cc1
Reactant: CC(C)(C)OC(=O)N1CCC12CN(C(=O)NC13CC4CC(CC(C4)C1)C3)C2
Product: O=C(NC12CC3CC(CC(C3)C1)C2)N1CC2(CCN2S(=O)(=O)c2ccc(Cl)cc2)C1

Procedure:
In analogy to the experimental procedure of example 6b) 6-(Adamantan-1-ylcarbamoyl)-1,6-diaza-spiro[3.3]heptane-1-carboxylic acid tert-butyl ester instead of tert-butyl 1-(2,4-dichlorobenzylcarbamoyl)-1,6-diazaspiro[3.3]heptane-6-carboxylate was converted using 4-chlorobenzene-1-sulfonyl chloride into the title compound which was obtained as an off-white sticky solid (29 mg, 35%). MS m/e: 450 (M+H)+.
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH:10]=[C:11]3[S:15][C:14](=S)[NH:13][C:12]3=[O:17])=[CH:9][C:4]=2[O:3][CH2:2]1.C([O-])([O-])=O.[Na+].[Na+].[CH2:24]([NH2:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>CCO.O>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH:10]=[C:11]3[S:15][C:14](=[N:31][CH2:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[NH:13][C:12]3=[O:17])=[CH:9][C:4]=2[O:3][CH2:2]1
Reactant: NCc1ccccc1
Reactant: O=C1NC(=S)SC1=Cc1ccc2c(c1)OCO2
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: O=C1NC(=NCc2ccccc2)SC1=Cc1ccc2c(c1)OCO2
Reaction time: 0.5 h

Procedure:
5-Benzo[1,3]dioxol-5-ylmethylene-2-thioxo-thiazolidin-4-one (100 mg, 0.37 mmol) were dissolved in EtOH/water, followed by 60 mg of Na2CO3. The reaction was stirred for 30 min and benzylamine (122 μl, 3 eq.) was added. The reaction mixture was refluxed for 2 h. and the solvents were evaporated. The crude was purified by Parallel Flex chromatography.
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([OH:13])[CH:7]=[CH:6]2.[CH2:14](Br)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>CN(C=O)C.C(=O)([O-])[O-].[Cs+].[Cs+]>[CH2:14]([O:13][C:8]1[CH:9]=[C:10]2[C:5](=[CH:6][CH:7]=1)[CH:4]=[C:3]([CH2:2][OH:1])[CH:12]=[CH:11]2)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: BrCc1ccccc1
Reactant: OCc1ccc2cc(O)ccc2c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: OCc1ccc2cc(OCc3ccccc3)ccc2c1
Reaction time: 24 h

Procedure:
To a solution of 6-hydroxy methyl-naphthalen-2-ol (16) (1 equi.) and benzyl bromide (2) (1 equi.) in DMF (3 mL/mmole), cesium carbonate (1.25 equi.) was added at room temperature. The reaction mixture was stirred at that temperature for 24 h, quenched with water, extracted with ethyl acetate:hexane(1:1), washed with brine, dried over MgSO4, and concentrated in vacuo. Purification by chromatography on silica gel (20% THF/hexanes) and recrystallization from EtOAc-Hexane (1:2) afforded (6-benzyloxy-naphthalen-2-yl)-methanol (17) a white solid (88%).
Reaction SMILES: Cl.[NH2:2][CH2:3][CH2:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[NH:7][CH:6]=1.[CH:14](C=O)=O>>[CH2:14]1[C:6]2[NH:7][C:8]3[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=3)[C:5]=2[CH2:4][CH2:3][NH:2]1
Reactant: NCCc1c[nH]c2ccccc12
Reactant: O=CC=O
Agent: Cl
Product: c1ccc2c3c([nH]c2c1)CNCC3

Procedure:
A stirred solution of 13 g (0.0756 mol) 1,2,3,4-tetrahydro-β-carboline, produced of tryptamine hydrochloride and glyoxal acid, as described by Ho and Walker (1988), and 2.6 g of Pd/C (10%) in 600 ml cumene were refluxed under nitrogen atmosphere for 90 minutes. After adding 100 ml ethanol the heated solution was filtered and the carbon was extracted with 3×30 ml heated ethanol. The combined liquid fractions were concentrated and the remainder crystallized from toluene for obtaining 10.5 g (82%) of norharman. The methylation in position 9 was carried out as described in literature (Ho B T, McIsaac W M, Walker K E, Estevez V, J Pharm Sci 57: 269, 1968), but with an improved processing: 1 g (5.95 mmol) of norharman was dissolved in 10 ml dry DMF under nitrogen atmosphere. Then 0.36 g (14.9 mmol) sodium hydride was added as a 60% dispersion in petroleum at 0° C. After the mixture cooled down to room temperature it was cooled down to −10° C. and 0.84 g (5.95 mmol) methyl iodide were added. After continued stirring for 12 hours, the mixture was again cooled down to room temperature. All volatile components were removed under reduced pressure. Then 100 ml of water were added and the mixture was extracted with 3×50 ml CHCl3. The combined organic fractions were washed with 5×20 ml water and concentrated for drying. The remainder was transferred into 100 ml of 2N hydrochloric acid. To isolate the educt of the desired methylated product an ion pair extraction of the HCl salt was carried out in CHCl3 and in a liquid/liquid extractor for 2 days. After removing the solvent 0.7 g (64%) of yellow crystals of 9-methyl-β-carboliniumhydrochloride were obtained.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][N:3]=1.[CH3:14][N:15]1[CH:19]=[C:18]([CH2:20][NH2:21])[CH:17]=[N:16]1.CCN(C(C)C)C(C)C>CC#N>[Cl:1][C:2]1[N:7]=[C:6]([NH:21][CH2:20][C:18]2[CH:17]=[N:16][N:15]([CH3:14])[CH:19]=2)[C:5]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][N:3]=1
Reactant: Cn1cc(CN)cn1
Reactant: CCOC(=O)c1cnc(Cl)nc1Cl
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)c1cnc(Cl)nc1NCc1cnn(C)c1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To a solution of ethyl 2,4-dichloropyrimidine-5-carboxylate (896 mg, 4 mmol) and (1-methyl-1H-pyrazol-4-yl)methanamine (445 mg, 4 mmol) in CH3CN (6 mL) at room temperature, DIEA (0.783 mL, 4.4 mmol) was added. The mixture was stirred at room temperature for 24 h, and was concentrated to give ethyl 2-chloro-4-((1-methyl-1H-pyrazol-4-yl)methylamino)pyrimidine-5-carboxylate as crude oil.
Reaction SMILES: [CH2:1]([O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][OH:10])[CH:2]=[CH2:3].[H-].[Na+].Br[CH2:14][C:15]([O:17][CH3:18])=[O:16]>C1COCC1>[CH3:18][O:17][C:15](=[O:16])[CH2:14][O:10][CH2:9][CH2:8][O:7][CH2:6][CH2:5][O:4][CH2:1][CH:2]=[CH2:3]
Reactant: COC(=O)CBr
Reactant: C=CCOCCOCCO
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: C=CCOCCOCCOCC(=O)OC
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 64.6 %

Procedure:
To a stirred solution of alcohol (9) (4.86 g, 33.2 mmol, 1.0 equiv.) in THF (70 mL) was carefully added NaH (60%, 1.60 g, 40.0 mmol, 1.2 equiv.) in small portions at room temperature. The reaction was then refluxed for 1 h (until H2 release ceased) then cooled to 0° C. Methyl bromoacetate (3.8 mL, 40.1 mmol, 1.2 equiv.) was then added dropwise. After 15 min at 0° C., the reaction was submitted to a EtOAc/H2O extraction. The combined organic phases were washed with brine, dried over anhydrous Na2SO4, filtered then evaporated under reduced pressure. Purification was achieved by distillation under high vacuum and provided 4.68 g (64%) of ester (14) as a colourless oil; bp=130-140 0° C. (0.09 Torr); 1H NMR (300 MHz, CDCl3) δ 5.91 (m, 1H), 5.28 (m, 1H), 5.18 (m, 1H), 4.17 (s, 2H), 4.02 (m, 2H), 3.75 (s, 3H), 3.75-3.58 (m, 8H); 13C NMR (75 MHz, CDCl3) δ 171.0, 134.8, 117.1, 72.3, 71.0, 70.8, 70.7, 69.5, 68.7, 51.8; IR (neat) 1754 cm−1; HRMS (ESI, m/z) calcd. for C10H19O5 (MH+) 219.1236, found 219.1227.
Reaction SMILES: [OH:1][CH2:2][C:3]1([CH2:15][OH:16])[CH2:9][CH2:8][O:7][C:6]2[CH:10]=[CH:11][CH:12]=[CH:13][C:5]=2[C:4]1=[O:14].C(N(CC)CC)C.[F:24][C:25]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=1[N:32]=[C:33]=[S:34]>O1CCCC1>[OH:16][CH2:15][C:3]1([CH2:2][O:1][C:33](=[S:34])[NH:32][C:26]2[CH:27]=[CH:28][C:29]([F:31])=[CH:30][C:25]=2[F:24])[CH2:9][CH2:8][O:7][C:6]2[CH:10]=[CH:11][CH:12]=[CH:13][C:5]=2[C:4]1=[O:14]
Reactant: Fc1ccc(N=C=S)c(F)c1
Reactant: O=C1c2ccccc2OCCC1(CO)CO
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: O=C1c2ccccc2OCCC1(CO)COC(=S)Nc1ccc(F)cc1F

Procedure:
To a solution of 4,4-bis(hydroxymethyl)-3,4-dihydro-2H-benzo[b]oxepin-5-one (500 mg, 2.25 mmol) in 28 ml of tetrahydrofuran were added, at room temperature, triethylamine (0.34 ml, 2.48 mmol) and 2,4-difluorophenyl isothiocyanate (734 μl, 5.63 mmol). The mixture was heated to reflux for 72 hours, concentrated and purified by column chromatography on silica gel (eluent: 1:2 tert-butyl methyl ether/cyclohexane). The product was obtained in a yield of 376 mg (43%).
Reaction SMILES: C[O:2][C:3](=[O:22])[C:4]1[CH:9]=[CH:8][C:7](F)=[C:6]([O:11][CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=2[Cl:21])[CH:5]=1.O.O.[OH-].[Li+].Cl.[CH3:28][S:29](C)=O>>[Cl:21][C:15]1[CH:16]=[C:17]([Cl:20])[CH:18]=[CH:19][C:14]=1[CH2:13][CH2:12][O:11][C:6]1[CH:5]=[C:4]([CH:9]=[CH:8][C:7]=1[S:29][CH3:28])[C:3]([OH:2])=[O:22]
Reactant: COC(=O)c1ccc(F)c(OCCc2ccc(Cl)cc2Cl)c1
Reactant: CS(C)=O
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Product: CSc1ccc(C(=O)O)cc1OCCc1ccc(Cl)cc1Cl

Procedure:
To a solution of 300 mg 3-[2-(2,4-Dichloro-phenyl)-ethoxy]-4-fluoro-benzoic acid methyl ester in 0.5 ml DMSO 70 mg NaSMe were added and stirred over night. After addition of 0.3 ml H2O and 20 mg lithium hydroxide monohydrate the solution was stirred for 5 h and then acidified with diluted HCl. The mixture was extracted with ethyl acetate, the organic layer dried over Na2SO4. Removal of the solvent yielded the acid as a yellow solid.
Reaction SMILES: P([N:17]=[N+:18]=[N-:19])(=O)(OC1C=CC=CC=1)OC1C=CC=CC=1.C1CCN2C(=NCCC2)CC1.[N:31]1[C:40]2[C:35](=[CH:36][C:37]([CH:41](O)[CH3:42])=[CH:38][CH:39]=2)[CH:34]=[CH:33][CH:32]=1>C1(C)C=CC=CC=1>[N:17]([CH:41]([C:37]1[CH:36]=[C:35]2[C:40](=[CH:39][CH:38]=1)[N:31]=[CH:32][CH:33]=[CH:34]2)[CH3:42])=[N+:18]=[N-:19]
Reactant: CC(O)c1ccc2ncccc2c1
Reactant: [N-]=[N+]=NP(=O)(Oc1ccccc1)Oc1ccccc1
Solvent: C1CCC2=NCCCN2CC1
Solvent: Cc1ccccc1
Product: CC(N=[N+]=[N-])c1ccc2ncccc2c1
Temperature: 25 °C
Reaction time: 10 h

Procedure:
In a 50 mL round bottom flask under N2 was dissolved diphenyl phosphorazidate (2.44 ml, 11.3 mmol), DBU (1.69 ml, 11.3 mmol) and 1-(quinolin-6-yl)ethanol (1.65 g, 9.53 mmol) (Prepared according to B. P. Lugovkin,/Zhurnal Obshchei Khimii 25 (1955) 392-397) in 20 mL of PhMe stirred at rt for 10 h. The crude mixture was directly purified by MPLC (ISCO) with Hexanes:AcOEt 100:0 to 0:100. MS m/z=199.2 [M+1]+. Calc'd for C11H10N4: 198.1.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[CH2:6][CH2:5]2.[BH4-].[Na+]>CO>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH:7]([OH:11])[CH2:6][CH2:5]2
Reactant: O=C1CCc2cc(Br)ccc21
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: OC1CCc2cc(Br)ccc21
Yield: 92.9 %

Procedure:
5-Bromo-2,3-dihydro-1H-inden-1-one (210 g, 1000 mmol) was suspended in 1 L methanol, and sodium borohydride (41.6 g, 1100 mmol) was added gradually within about 1 hour with stirring. The solvent was removed at 50° C. under reduced pressure after being stirred for another 1 hour. Ethyl acetate (1 L) was added followed by saturated sodium bicarbonate solution (500 mL). After being stirred for some time, the solution was transferred to a separatory funnel and the aqueous phase was removed. The organic phase was washed with saturated sodium bicarbonate solution twice and with brine twice, dried (magnesium sulfate) and finally concentrated to obtain 198 g (93%) of the subtitle compound.
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].O[CH2:7][CH2:8][C:9]1[S:10][C:11]2[CH:42]=[CH:41][CH:40]=[CH:39][C:12]=2[N:13]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([NH:24][C:25](=[O:38])[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[CH:20][CH:19]=2)[C:14](=[O:16])[CH:15]=1>C(N(CC)CC)C>[CH3:1][S:2]([CH2:7][CH2:8][C:9]1[S:10][C:11]2[CH:42]=[CH:41][CH:40]=[CH:39][C:12]=2[N:13]([CH2:17][C:18]2[CH:19]=[CH:20][C:21]([NH:24][C:25](=[O:38])[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)=[CH:22][CH:23]=2)[C:14](=[O:16])[CH:15]=1)(=[O:4])=[O:3]
Reactant: O=C(Nc1ccc(CN2C(=O)C=C(CCO)Sc3ccccc32)cc1)c1ccccc1-c1ccccc1
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)CCC1=CC(=O)N(Cc2ccc(NC(=O)c3ccccc3-c3ccccc3)cc2)c2ccccc2S1

Procedure:
Methanesulfonyl chloride (0.04 ml, 0.55 mM) was added to Compound 23 as prepared in Example 22 (0.280 g, 0.55 mM) and triethylamine (0.15 ml, 1.1 mM) following the procedure described in Example 29 to give the solid product. m/z (MH+) 587.
Reaction SMILES: [Na].[CH:2]1([CH2:8][CH2:9][CH2:10]Br)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.O.[CH2:13]([OH:16])[CH2:14][OH:15]>C1(C)C(C)=CC=CC=1>[CH:2]1([CH2:8][CH2:9][CH2:10][O:15][CH2:14][CH2:13][OH:16])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1
Reactant: BrCCCC1CCCCC1
Reactant: OCCO
Agent: [Na]
Solvent: O
Solvent: Cc1ccccc1C
Product: OCCOCCCC1CCCCC1
Temperature: 100 °C
Reaction time: 4 h
Yield: 82.5 %

Procedure:
85 ml of xylene are added to a solution of 15.75 g of sodium in 182.2 g of ethylene glycol. The mixture is heated to 100° C., and a solution of 140.5 g of 3-cyclohexylpropyl bromide in 70 ml of xylene is added dropwise within 3 hours. When the addition has ended, the mixture is boiled for 4 hours under reflux, cooled, and then 500 ml of water are added. The mixture is extracted with twice 500 ml of petroleum ether, the combined organic phases are dried over sodium sulphate and the remaining oil is purified by chromatography on silica gel (migrating agent: 80:20 petroleum ether/ethyl acetate). 105.3 g of 2-(3-cyclohexylpropyloxy)-ethanol are obtained.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([NH2:9])=[O:8])=[CH:5][CH:4]=1.Br[CH:13]([CH3:21])[C:14](=O)[CH2:15][C:16]([O:18][CH3:19])=[O:17]>ClCCl>[CH3:19][O:18][C:16](=[O:17])[CH2:15][C:14]1[N:9]=[C:7]([C:6]2[CH:10]=[CH:11][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[O:8][C:13]=1[CH3:21]
Reactant: COC(=O)CC(=O)C(C)Br
Reactant: COc1ccc(C(N)=O)cc1
Solvent: ClCCl
Product: COC(=O)Cc1nc(-c2ccc(OC)cc2)oc1C
Temperature: 120 °C
Yield: 15.1 %

Procedure:
A mixture of 725 mg (4.80 mmol) of 4-methoxybenzamide and 1.0 g (4.80 mmol) of methyl 4-bromo-3-oxo-pentanoate was heated neat at 120° C. for 2 h. The resulting dark slurry was cooled to RT, diluted with 2 mL of dichloromethane and purified by silica gel flash column chromatography using hexane/EtOAc 3/1 as eluent to afford 189 mg of the title compound as a yellow solid: low resolution MS (FAB)m/e 285 (MH+), 284 (M+).
Reaction SMILES: C([O:9][C@H:10]1[C@@H:14]([O:15]C(=O)C2C=CC=CC=2)[C@H:13]([CH2:24][O:25]C(=O)C2C=CC=CC=2)[O:12][C@H:11]1[N:34]1[CH:41]=[CH:40][C:38](=[S:39])[NH:37][C:35]1=[O:36])(=O)C1C=CC=CC=1>N.CO>[C@@H:11]1([N:34]2[CH:41]=[CH:40][C:38](=[S:39])[NH:37][C:35]2=[O:36])[O:12][C@@H:13]([CH2:24][OH:25])[C@H:14]([OH:15])[C@@H:10]1[OH:9]
Reactant: O=C(OC[C@@H]1O[C@@H](n2ccc(=S)[nH]c2=O)[C@@H](OC(=O)c2ccccc2)[C@H]1OC(=O)c1ccccc1)c1ccccc1
Agent: N
Solvent: CO
Product: O=c1[nH]c(=S)ccn1[C@@H]1O[C@@H](CO)[C@H](O)[C@@H]1O
Yield: 67.1 %

Procedure:
Compound 19 (0.61 g, 1.06 mmol) in NH3 /MeOH (40 ml) was stirred at room temperature overnight. The solvent was evaporated and the residue was purified on preparative plates using MeOH/CHCl3 (20%) to give pure compound 21 (0.185 g, 66.5%) as yellow foam.