Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1)=[O:4].[CH2:12](Cl)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C([O-])([O-])=O.[K+].[K+].O>CCO>[CH2:12]([O:11][C:8]1[CH:7]=[CH:6][C:5]([C:3](=[O:4])[CH2:2][CH3:1])=[CH:10][CH:9]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: ClCc1ccccc1
Reactant: CCC(=O)c1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: O
Product: CCC(=O)c1ccc(OCc2ccccc2)cc1
Yield: 94 %

Procedure:
A mixture of 4-hydroxypropiophenone (20 g), benzyl chloride (16.1 ml), K2CO3 (12.9 g) and KI (2.21 g) in EtOH (80 ml) and H2O (1 ml) was stirred under reflux condition for 4 hours. The reaction mixture was cooled and filtered. Appeared crystal was dissovled with EtOAc and water. Organic layer was separated and washed with water and brine, dried over MgSO4 and filtered. Filtrate was evaporated under reduced pressure to give 30.0 g (94%) of 1-[4-(benzyloxy)phenyl]-1-propanone as a crystal.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:12][N:11]([C:13]([CH:15]3[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][CH2:23]SC)[CH2:17][CH2:16]3)=[O:14])[CH2:10][CH:9]2[N:26]([CH3:41])[C:27](=[O:40])[C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[C:30]([C:36]([F:39])([F:38])[F:37])[CH:29]=2)=[CH:4][CH:3]=1.Cl[C:43]1C=CC=C(C(OO)=O)C=1.[S:53](=[O:57])(=O)(O)[O-:54].[Na+].C(=O)([O-])[O-].[Na+].[Na+]>ClCCl.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[CH2:12][N:11]([C:13]([CH:15]3[CH2:16][CH2:17][N:18]([CH2:21][CH2:22][CH2:23][S:53]([CH3:43])(=[O:57])=[O:54])[CH2:19][CH2:20]3)=[O:14])[CH2:10][CH:9]2[N:26]([CH3:41])[C:27](=[O:40])[C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[C:30]([C:36]([F:37])([F:39])[F:38])[CH:29]=2)=[CH:6][CH:7]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: COc1ccc(C(=O)N(C)C2CN(C(=O)C3CCN(CCCSC)CC3)CC2c2ccc(Cl)cc2)cc1C(F)(F)F
Reactant: O=S(=O)([O-])O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: COc1ccc(C(=O)N(C)C2CN(C(=O)C3CCN(CCCS(C)(=O)=O)CC3)CC2c2ccc(Cl)cc2)cc1C(F)(F)F
Temperature: 25 °C
Reaction time: 72 h
Yield: 83 %

Procedure:
To a solution of N-{(3RS,4SR)-4-(4-chloro-phenyl)-1-[1-(3-methylsulfanyl-propyl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-4-methoxy-N-methyl-3-trifluoromethyl-benzamide (80 mg, 0.13 mmol) in dichloromethane (2 mL) was added under an atmosphere of nitrogen m-chloroperbenzoic acid (47 mg, 0.27 mmol) and stirred for 3 d at ambient temperature. Further addition of m-chloroperbenzoic acid (47 mg, 0.27 mmol) was followed by stirring for 3 h at ambient temperature. After the addition of an aqueous saturated solution of sodium bisulfate (10 mL) and water (10 mL) it was stirred for 1 h at ambient temperature. The reaction mixture was basified by addition of an aqueous solution of sodium carbonate (1 M). The aqueous layer was extracted with dichloromethane (20 mL) and the organic layers were washed with water (15 mL) and dried over sodium sulfate. Purification by chromatography (SiO2, heptane:(ethyl acetate:triethylamine=95:5):methanol=20:80:0 to 0:85:15) afforded the title compound (70 mg, 83%) as a light brown oil. MS m/e: 644.2 [M]+.
Reaction SMILES: [OH:1][C:2]1[C:7]([CH2:8][CH2:9][CH3:10])=[C:6]([OH:11])[CH:5]=[CH:4][C:3]=1[C:12](=[O:14])[CH3:13].[CH3:15][O:16][C:17](=[O:41])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][O:23][C:24]1[CH:29]=[CH:28][C:27]([C:30](=[O:32])[CH3:31])=[C:26]([O:33][CH2:34][CH2:35][CH2:36]Br)[C:25]=1[CH2:38][CH2:39][CH3:40].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O.CN(C)C=O>[CH3:15][O:16][C:17](=[O:41])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][O:23][C:24]1[CH:29]=[CH:28][C:27]([C:30](=[O:32])[CH3:31])=[C:26]([O:33][CH2:34][CH2:35][CH2:36][O:11][C:6]2[CH:5]=[CH:4][C:3]([C:12](=[O:14])[CH3:13])=[C:2]([OH:1])[C:7]=2[CH2:8][CH2:9][CH3:10])[C:25]=1[CH2:38][CH2:39][CH3:40]
Reactant: CCCc1c(OCCCCCC(=O)OC)ccc(C(C)=O)c1OCCCBr
Reactant: CCCc1c(O)ccc(C(C)=O)c1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: CN(C)C=O
Product: CCCc1c(OCCCOc2c(C(C)=O)ccc(OCCCCCC(=O)OC)c2CCC)ccc(C(C)=O)c1O
Yield: 67.9 %

Procedure:
A mixture of 2.62 g of 1-(2,4-dihydroxy-3-propylphenyl)ethanone, 6.00 g of 6-[4-acetyl-3-(3-bromopropoxy)-2-propylphenoxy]hexanoic acid methyl ester and 3.70 g of anhydrous potassium carbonate in 100 ml of anhydrous acetone and 50 ml of anhydrous dimethylformamide was stirred at reflux for 20 hours. The reaction mixture was concentrated in vacuo and the residue was purified by liquid chromatography using 30% ethyl acetate-hexane to give 5.10 g (68% yield) of 6-[4-acetyl-3-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]-2-propylphenoxy]hexanoic acid methyl ester as an oil.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:19]=[CH:18][C:12]([O:13][CH2:14][CH:15]2[O:17][CH2:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O1CCOCC1.Cl.Cl.[CH3:28][O:29][C:30]1[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][C:31]=1[N:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1>C(N(CC)CC)C>[CH2:1]([O:8][C:9]1[CH:19]=[CH:18][C:12]([O:13][CH2:14][CH:15]([OH:17])[CH2:16][N:40]2[CH2:39][CH2:38][N:37]([C:31]3[CH:32]=[C:33]([CH3:36])[CH:34]=[CH:35][C:30]=3[O:29][CH3:28])[CH2:42][CH2:41]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COc1ccc(C)cc1N1CCNCC1
Reactant: c1ccc(COc2ccc(OCC3CO3)cc2)cc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Product: COc1ccc(C)cc1N1CCN(CC(O)COc2ccc(OCc3ccccc3)cc2)CC1
Yield: 89.5 %

Procedure:
Using 1.37 g of 1-(4-benzyloxyphenoxy)-2,3-epoxypropane, 50 ml of dioxane, 1.49 g of 1-(2-methoxy-5-methylphenyl)piperazine dihydrochloride and 1.6 ml of triethylamine, reaction and workup were carried out as in Example 1-A. Purification by column chromatography (silica gel, elution with ethyl acetate:hexane=1:1) gave 2.21 g of pale yellow oil.
Reaction SMILES: [CH3:1][Si](C=[N+]=[N-])(C)C.[Cl:8][C:9]1[CH:10]=[C:11]([CH:17]=[CH:18][CH:19]=1)[C@@H:12]([OH:16])[C:13]([OH:15])=[O:14]>CCCCCC.CO.C1C=CC=CC=1>[Cl:8][C:9]1[CH:10]=[C:11]([CH:17]=[CH:18][CH:19]=1)[C@@H:12]([OH:16])[C:13]([O:15][CH3:1])=[O:14]
Reactant: C[Si](C)(C)C=[N+]=[N-]
Reactant: O=C(O)[C@H](O)c1cccc(Cl)c1
Solvent: CO
Solvent: c1ccccc1
Solvent: CCCCCC
Product: COC(=O)[C@H](O)c1cccc(Cl)c1
Reaction time: 1 h

Procedure:
18.3 g of a 10% w/v solution of trimethylsilyldiazomethane in hexane were added dropwise to a solution of 28 g of (R)-3-chloromandelic acid (prepared as described in Preparation 46) in a mixture of 300 ml of methanol and 700 ml of benzene, and the resulting mixture was stirred for 1 hour. At the end of this time, the solvent was removed by distillation under reduced pressure, to give the title compound having [α]D23 -119.3° (c=1.00, chloroform) and an Rf=0.36 (thin layer chromatography over silica gel, using a 1:5 by volume mixture of ethyl acetate and hexane) as a crude product.
Reaction SMILES: [C:1]1([CH:8]=[CH:7][C:5]([OH:6])=[CH:4][CH:3]=1)[OH:2].Br[CH2:10][CH:11]([CH2:16][CH3:17])[CH2:12][CH2:13][CH2:14][CH3:15].[OH-].[K+].[CH2:20]([CH:22]([CH2:25][CH2:26][CH2:27][CH3:28])[CH2:23]O)[CH3:21]>O>[CH2:16]([CH:11]([CH2:12][CH2:13][CH2:14][CH3:15])[CH2:10][O:2][C:1]1[CH:8]=[CH:7][C:5]([O:6][CH2:23][CH:22]([CH2:20][CH3:21])[CH2:25][CH2:26][CH2:27][CH3:28])=[CH:4][CH:3]=1)[CH3:17]
Reactant: CCCCC(CC)CO
Reactant: CCCCC(CC)CBr
Reactant: Oc1ccc(O)cc1
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: CCCCC(CC)COc1ccc(OCC(CC)CCCC)cc1
Reaction time: 16 h
Yield: 42 %

Procedure:
Hydroquinone (37.9 g, 0.344 mol) is suspended in IMS (310 ml) and 1-bromo-2-ethylhexane (132.7 g, 0.687 mol) is added. A solution of KOH (49.9 g, 0.89 mol) in IMS (250 ml) is added slowly over 1 minute. The mixture is heated at reflux whilst monitoring reaction progress by HPLC. After 16 hours, further 1-bromo-2-ethylhexane (53.1 g, 0.27 mol) and solid KOH (20.0 g, 0.36 mol) are added then heated for 2 hours at reflux. The reaction mixture is allowed to cool, is poured into water (1.5 L) and extracted with toluene (500 ml). The organic layer is dried over MgSO4 then evaporated to yield a pale yellow oil. The oil is flashed through silica gel, eluting with 50/50 dichloromethane/hexane to give two product fractions. The initial fraction (35.3 g) co-eluted with 2-ethylhexan-1-ol by-product. The second fraction is evaporated to give pure 1,4-bis(2-ethylhexyloxy)benzene as a pale yellow oil (48.4 g, 42%). The initial fraction is further purified by bulb to bulb distillation to give further pure 1,4-bis(2-ethylhexyloxy)benzene as a pale yellow oil (25.3 g, 22%).
Reaction SMILES: C1(P(=O)(O)O)CCCCC1.C1C=C2C(C=C([O:21][C:22]([C:24]3[C:29]([OH:30])=[CH:28][CH:27]=CC=3)=[O:23])C=C2)=CC=1>C([O-])(=O)CCCCCCCCCCCCCCCCC.[Zn+2].C([O-])(=O)CCCCCCCCCCCCCCCCC>[CH3:27][CH2:28][CH:29]([OH:30])[CH2:24][C:22]([OH:23])=[O:21].[CH3:28][CH:29]([OH:30])[CH2:24][C:22]([OH:23])=[O:21]
Reactant: O=C(Oc1ccc2ccccc2c1)c1ccccc1O
Agent: CCCCCCCCCCCCCCCCCC(=O)[O-]
Agent: O=P(O)(O)C1CCCCC1
Agent: [Zn+2]
Product: CC(O)CC(=O)O
Product: CCC(O)CC(=O)O

Procedure:
PHA pellets were compounded from formulations based on BIOPOL powder of Mw=895k, 0.1 phr DZB (cyclohexylphosphonic acid), 0.4 phr ZnSt (zinc stearate) and 10 phr ATC plasticizer. Plasticizer were determined at 170 C and 5 kg load. The powder blends prepared in a Pappenmeier high speed blender were fed in a Betol single screw extruder, using the conditions summarized in Tables 1 and 4. BIOPOL, pellets with Mw of 727k were obtained with output from 3.0 kg/hr at a screw speed of 40 rpm. The following results were obtained:
Reaction SMILES: [OH-].[Na+:2].[C:3]([OH:13])(=[O:12])[CH:4]=[CH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1>O>[C:3]([O-:13])(=[O:12])[CH:4]=[CH:5][C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1.[Na+:2]
Reactant: O=C(O)C=Cc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C([O-])C=Cc1ccccc1

Procedure:
In 300 ml of purified water, 1.64 g of sodium hydroxide was dissolved. In the resultant aqueous solution, 6.06 g of cinnamic acid (purity 99.9%, conjugate number 4) was thoroughly dissolved under stirring, to produce a sodium cinnamate aqueous solution. The pH value of this aqueous solution was adjusted to 11.0 with a 0.1 N sodium hydroxide aqueous solution. Then, a europium chloride aqueous solution obtained in advance by thoroughly dissolving 5.0 g of europium chloride (EuCl3.6H2O; purity 99.99%) in 100 ml of purified water was gradually added with stirring into the aforementioned sodium cinnamate aqueous solution at room temperature. Consequently, a white salt of europium cinnamate, [(C6H5CH=CHCOO)3Eu], was obtained in the form of a precipitate. Subsequently, the reaction solution was adjusted to pH 5.0 with 0.1 N hydrochloric acid and then thoroughly stirred. The europium cinnamate thus produced was separated by means of a glass filter, thoroughly washed with 500 ml of purified water and dried in vacuo at 80° to 100° C. for 20 to 24 hours.
Reaction SMILES: C(O[C:6]([C:8]1[C:17]([NH2:18])=[CH:16][C:15]2[C:10](=[CH:11][C:12]([O:28][CH3:29])=[C:13]([O:19][CH2:20][CH2:21][N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[CH:14]=2)[CH:9]=1)=[O:7])(C)(C)C.[CH:30]([NH2:32])=O>C(Cl)Cl.CO>[CH3:29][O:28][C:12]1[C:13]([O:19][CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[CH:14][C:15]2[CH:16]=[C:17]3[C:8]([C:6](=[O:7])[NH:32][CH:30]=[N:18]3)=[CH:9][C:10]=2[CH:11]=1
Reactant: COc1cc2cc(C(=O)OC(C)(C)C)c(N)cc2cc1OCCN1CCOCC1
Reactant: NC=O
Solvent: ClCCl
Solvent: CO
Product: COc1cc2cc3c(=O)[nH]cnc3cc2cc1OCCN1CCOCC1
Temperature: 178 °C

Procedure:
A mixture of 3.5 g (8.6 mmol) of 3-amino-7-methoxy-6-(2-morpholin-4-yl-ethoxy)-naphthalene-2-carboxylic acid tert-butyl ester and 60 ml of formamide is heated at 178° C. for 2 hours, then cooled. To this is added 4:1 methylene chloride/methanol. The resulting solution is washed several times with brine, dried over anhydrous sodium sulfate and evaporated to yield an oil. The oil is purified by silica gel chromatography, utilizing a gradient of 99:1 to 88:12 methylene chloride/methanol to give sticky solid, which is triturated with ethyl acetate to yield 1.5 g of 7-methoxy-8-(2-morpholin-4-yl-ethoxy)-3H-benzo[g]quinazolin-4-one as a tan solid, mp 230-232° C.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][OH:4].[Li+].CC([N-]C(C)C)C.F[C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=1[N+:21]([O-:23])=[O:22]>C1COCC1.O>[Cl:1][CH2:2][CH2:3][O:4][C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=1[N+:21]([O-:23])=[O:22]
Reactant: O=[N+]([O-])c1ccc(F)cc1F
Reactant: OCCCl
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: O=[N+]([O-])c1ccc(F)cc1OCCCl
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 91 %

Procedure:
In a round bottom flask under nitrogen, 2-chloro-ethanol (8.3 mL, 120 mmoles) in THF (40 mL) was cooled to 0° C. LDA (60 mL, 120 mmoles) was added dropwise, while maintaining the temperature constant at 0° C. The mixture was stirred at this temperature for 15 minutes, followed by the addition of 2,4-difluoronitrobenzene (11 mL, 100 mmoles). The mixture was stirred at room temperature overnight. Reaction mixture was diluted with water, extracted with EtOAc, washed with brine (1×), dried over Na2SO4, and concentrated under vacuum, to afford the title compound as an off-white solid (20.0 g, 91 mmoles).
Reaction SMILES: [Cl:1][C:2]([F:13])([F:12])[C:3]1[N:8]=[CH:7][C:6]([CH:9](O)[CH3:10])=[CH:5][CH:4]=1.S(Cl)([Cl:16])=O>C(Cl)Cl>[Cl:1][C:2]([F:13])([F:12])[C:3]1[CH:4]=[CH:5][C:6]([CH:9]([Cl:16])[CH3:10])=[CH:7][N:8]=1
Reactant: CC(O)c1ccc(C(F)(F)Cl)nc1
Reactant: O=S(Cl)Cl
Solvent: ClCCl
Product: CC(Cl)c1ccc(C(F)(F)Cl)nc1
Reaction time: 1 h
Yield: 97.4 %

Procedure:
To a solution of 1-{6-[chloro(difluoro)methyl]-pyridin-3-yl}ethanol (0.78 g, 3.77 mmol) in CH2Cl2 (40 mL) was added thionyl chloride (0.54 mL, 7.54 mmol) dropwise at room temperature. After 1 hr, the reaction was quenched slowly with saturated NaHCO3 aqueous solution and the two phases were separated. The organic layer was dried over Na2SO4, filtered, concentrated, and dried in vacuum to give 0.83 g of the crude 2-[chloro(difluoro)methyl]-5-(1-chloroethyl)pyridine (D) as brown oil in 98 percent yield, which was directly used for the next step reaction. GC-MS: mass calcd for C8H7Cl2F2N [M]+ 225. Found 225.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([N:8]2[C@@H:12]([CH:13]([CH3:15])[CH3:14])[CH2:11][O:10][C:9]2=[O:16])[CH:5]=[CH:4][N:3]=1.[N:17]1([C:22]2[CH:23]=[C:24]([CH:28]([NH2:30])[CH3:29])[CH:25]=[CH:26][CH:27]=2)[CH:21]=[CH:20][CH:19]=[CH:18]1>CS(C)=O.CCOC(C)=O>[N:17]1([C:22]2[CH:23]=[C:24]([C@H:28]([NH:30][C:2]3[N:7]=[C:6]([N:8]4[C@@H:12]([CH:13]([CH3:15])[CH3:14])[CH2:11][O:10][C:9]4=[O:16])[CH:5]=[CH:4][N:3]=3)[CH3:29])[CH:25]=[CH:26][CH:27]=2)[CH:21]=[CH:20][CH:19]=[CH:18]1.[N:17]1([C:22]2[CH:23]=[C:24]([C@@H:28]([NH:30][C:2]3[N:7]=[C:6]([N:8]4[C@@H:12]([CH:13]([CH3:15])[CH3:14])[CH2:11][O:10][C:9]4=[O:16])[CH:5]=[CH:4][N:3]=3)[CH3:29])[CH:25]=[CH:26][CH:27]=2)[CH:21]=[CH:20][CH:19]=[CH:18]1
Reactant: CC(C)[C@H]1COC(=O)N1c1ccnc(Cl)n1
Reactant: CC(N)c1cccc(-n2cccc2)c1
Solvent: CCOC(C)=O
Solvent: CS(C)=O
Product: CC(C)[C@H]1COC(=O)N1c1ccnc(N[C@@H](C)c2cccc(-n3cccc3)c2)n1
Product: CC(C)[C@H]1COC(=O)N1c1ccnc(N[C@H](C)c2cccc(-n3cccc3)c2)n1

Procedure:
A solution of (S)-3-(2-chloropyrimidin-4-yl)-4-isopropyloxazolidin-2-one (86 mg, 0.36 mmol) and 1-(3-(1H-pyrrol-1-yl)phenyl)ethanamine (100 mg, 0.537 mmol, 1.5 equiv) in DMSO (1 mL) was heated at 110° C. for 1½ h. The reaction mixture was diluted with EtOAc (8 mL) and washed with water (30 mL). After separation, the aqueous phase was extracted with EtOAc (3×8 mL). Combined organics were dried over Na2SO4, filtered and concentrated. Silica gel column chromatography (EtOAc/Heptane 10 to 50%) provided (S)-3-(2-((R)-1-(3-(1H-pyrrol-1-yl)phenyl)ethylamino)pyrimidin-4-yl)-4-isopropyloxazolidin-2-one and (S)-3-(2-((S)-1-(3-(1H-pyrrol-1-yl)phenyl)ethylamino)pyrimidin-4-yl)-4-isopropyloxazolidin-2-one.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:6][C:7]3[C:12]([C:13]=2[CH:14]=1)=[CH:11][CH:10]=[CH:9][CH:8]=3.C(=O)([O-])[O-].[K+].[K+].[CH2:21](Cl)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.O>O1CCCC1>[CH2:21]([N:6]1[C:5]2[CH:4]=[CH:3][C:2]([Br:1])=[CH:14][C:13]=2[C:12]2[C:7]1=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: ClCc1ccccc1
Reactant: Brc1ccc2[nH]c3ccccc3c2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: Brc1ccc2c(c1)c1ccccc1n2Cc1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 91.5 %

Procedure:
24 g of 3-bromocarbazole was dissolved in 100 ml of tetrahydrofuran. To this was added 14 g of potassium carbonate followed by 14 g of benzylchloride and allowed the reaction to stir at room temperature overnight. The reaction mixture was poured into water and the precipitated white solid was filtered, washed with methanol and dried under vacuum to obtain 30 g 9-benzyl-3-bromocarbazole (89%).
Reaction SMILES: [CH3:1][C:2]1[O:3][C:4]2[C:9]([C:10](=[O:12])[CH:11]=1)=[CH:8][CH:7]=[CH:6][C:5]=2[CH:13]=O.O=[C:16]([CH3:24])[CH2:17][C:18]([O:20][CH2:21][CH2:22][CH3:23])=[O:19].[NH2:25]/[C:26](/[CH3:30])=[CH:27]\[C:28]#[N:29].C(O)(=O)C>CC(O)C>[C:28]([C:27]1[CH:13]([C:5]2[CH:6]=[CH:7][CH:8]=[C:9]3[C:4]=2[O:3][C:2]([CH3:1])=[CH:11][C:10]3=[O:12])[C:17]([C:18]([O:20][CH2:21][CH2:22][CH3:23])=[O:19])=[C:16]([CH3:24])[NH:25][C:26]=1[CH3:30])#[N:29]
Reactant: CCCOC(=O)CC(C)=O
Reactant: Cc1cc(=O)c2cccc(C=O)c2o1
Reactant: C/C(N)=C/C#N
Solvent: CC(C)O
Solvent: CC(=O)O
Product: CCCOC(=O)C1=C(C)NC(C)=C(C#N)C1c1cccc2c(=O)cc(C)oc12

Procedure:
700 mg (3.7 mmol) of 2-methyl-4-oxo-4H-chromene-8-carbaldehyde are dissolved with 536 mg (3.7 mmol) of propyl 3-oxobutanoate, 205 mg (3.7 mmol) of 3-aminocrotononitrile and 223 mg (3.7 mmol) of acetic acid in 20 ml of 2-propanol and heated under reflux under argon for 16 h. The solvent is removed in vacuo, and the residue is purified by preparative HPLC. 460 mg (32% of theory) of the title compound are obtained as a yellow solid.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=O.[OH-:13].[Na+].Cl.[NH2:16][CH2:17][C:18]([C:20]1[CH:25]=[CH:24][C:23]([S:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[CH:22][CH:21]=1)=O>O.C(O)C>[NH2:16][C:17]1[C:18]([C:20]2[CH:25]=[CH:24][C:23]([S:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[CH:22][CH:21]=2)=[N:7][C:8]2[C:4]([C:5]=1[C:6]([OH:11])=[O:13])=[CH:3][C:2]([F:1])=[CH:10][CH:9]=2
Reactant: O=C1Nc2ccc(F)cc2C1=O
Reactant: [OH-]
Reactant: NCC(=O)c1ccc(Sc2ccccc2)cc1
Agent: Cl
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: Nc1c(-c2ccc(Sc3ccccc3)cc2)nc2ccc(F)cc2c1C(=O)O
Temperature: 80 °C
Reaction time: 0.42 h
Yield: 35.5 %

Procedure:
To a suspension of 526 mg of 5-fluoroisatin in 4 ml of water was added 737 mg of sodium hydroxide in 6 ml of water. The resulting solution was heated to 80° C., then a solution of 1.254 g of 2-amino-1-[4-(phenylthio)phenyl]ethanone, hydrochloride in 8 ml of ethanol and 8 ml of water was added dropwise. After heating at reflux for 1 hour, the volatiles were removed in vacuo, 10 ml of water was added and the mixture filtered. A 60 ml portion of water was added to the filtrate which was then acidified to pH 4 with glacial acetic acid. After stirring for 25 minutes the solid was collected, washed with water and crystallized from 50 ml of hot acetonitrile, giving 442 mg of the desired product, mp 219°-221° C. (dec.).
Reaction SMILES: [CH3:1][C@@H:2]([C@@H:9]1[C@@:13]2([CH3:28])[CH2:14][CH2:15][CH2:16]/[C:17](=[CH:18]\[CH:19]=[C:20]3\[CH2:21][C@@H:22]([OH:27])[CH2:23][CH2:24][C:25]\3=[CH2:26])/[C@@H:12]2[CH2:11][CH2:10]1)[CH2:3][CH2:4][CH2:5][CH:6]([CH3:8])[CH3:7].N1C=CN=C1.Cl[Si:35]([CH2:40][CH3:41])([CH2:38][CH3:39])[CH2:36][CH3:37].[Cl-].[NH4+]>ClCCl>[CH2:36]([Si:35]([CH2:40][CH3:41])([CH2:38][CH3:39])[O:27][CH:22]1[CH2:23][CH2:24][C@@:25]2([CH3:26])[C:20](=[CH:19][CH:18]=[C:17]3[C@@H:16]2[CH2:15][CH2:14][C@@:13]2([CH3:28])[C@H:12]3[CH2:11][CH2:10][C@@H:9]2[C@@H:2]([CH3:1])[CH2:3][CH2:4][CH2:5][CH:6]([CH3:7])[CH3:8])[CH2:21]1)[CH3:37]
Reactant: CC[Si](Cl)(CC)CC
Reactant: C=C1CC[C@H](O)C/C1=C/C=C1\CCC[C@]2(C)[C@@H]([C@H](C)CCCC(C)C)CC[C@@H]12
Agent: [Cl-]
Agent: [NH4+]
Agent: c1c[nH]cn1
Solvent: ClCCl
Product: CC[Si](CC)(CC)OC1CC[C@@]2(C)C(=CC=C3[C@@H]4CC[C@H]([C@@H](C)CCCC(C)C)[C@@]4(C)CC[C@@H]32)C1
Reaction time: 12 h
Yield: 87.1 %

Procedure:
Commercially available 7-dehydrocholesterol (10.6 g, 27.6 mmol) was dissolved in dichloromethane (90 mL), and then imidazole (3.75 g, 55.1 mmol) and chlorotriethylsilane (6.94 mL, 41.3 mmol) were added at room temperature, followed by stirring for 12 hours. A saturated aqueous ammonium chloride solution was added to the reaction mixture, followed by extraction with chloroform twice. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to yield a residue. The residue was purified by silica gel column chromatography to obtain the title compound (12.0 g, 87%).
Reaction SMILES: [CH3:1][CH:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.C(N(CC)CC)C.[Br:15][C:16]1[CH:17]=[C:18]2[C:23](=[CH:24][CH:25]=1)[N:22]=[C:21](Cl)[CH:20]=[C:19]2[CH3:27]>O1CCOCC1>[Br:15][C:16]1[CH:17]=[C:18]2[C:23](=[CH:24][CH:25]=1)[N:22]=[C:21]([N:5]1[CH2:6][CH2:7][CH:2]([CH3:1])[CH2:3][CH2:4]1)[CH:20]=[C:19]2[CH3:27]
Reactant: CC1CCNCC1
Reactant: Cc1cc(Cl)nc2ccc(Br)cc12
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Product: Cc1cc(N2CCC(C)CC2)nc2ccc(Br)cc12

Procedure:
0.24 mL (2.0 mmol) of 4-methylpiperidine and 0.28 mL (2.0 mmol) of triethylamine are added to a solution of 0.51 g (2.0 mmol) of 6-bromo-2-chloro-4-methylquinoline in 15 mL of 1,4-dioxane and the reaction mixture is refluxed overnight. After cooling, the precipitate is filtered off, the filtrate is evaporated down, the residue is combined with acetonitrile and MTBE, filtered to remove insoluble ingredients, and the filtrate is evaporated down again. Yield: 0.69 g (100% of theoretical); C16H19BrN2 (M=319.240); calc.: molpeak (M+H)+: 319/321 (Br); found: molpeak (M+H)+: 319/321 (Br); HPLC-MS: 4.7 min (method B).
Reaction SMILES: [C:1]([N:6]1[CH2:11][CH2:10][C:9]([C:15]([O:17][CH2:18][CH3:19])=[O:16])(C(O)=O)[CH2:8][CH2:7]1)([O:3][CH2:4][CH3:5])=[O:2].C([N:22]1[CH2:27]COCC1)C.ClC(OCC(C)C)=[O:30].[N-]=[N+]=[N-].[Na+]>O1CCCC1.O.C1(C)C=CC=CC=1>[C:1]([N:6]1[CH2:7][CH2:8][C:9]([C:15]([O:17][CH2:18][CH3:19])=[O:16])([N:22]=[C:27]=[O:30])[CH2:10][CH2:11]1)([O:3][CH2:4][CH3:5])=[O:2]
Reactant: CCN1CCOCC1
Reactant: CC(C)COC(=O)Cl
Reactant: CCOC(=O)N1CCC(C(=O)O)(C(=O)OCC)CC1
Agent: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: CCOC(=O)N1CCC(N=C=O)(C(=O)OCC)CC1
Temperature: 100 °C
Reaction time: 0.33 h

Procedure:
A solution of 1.25 g of 1,4-dicarbethoxypiperidine-4-carboxylic acid in 10 ml of dry tetrahydrofuran was cooled to ice temperature and was treated with 0.7 ml of N-ethylmorpholine then 0.7 ml of isobutyl chloroformate. The mixture was stirred at ice temperature for 20 minutes and then a solution of 0.59 g of sodium azide in 7 ml of water added. The mixture was stirred at ice temperature for 15 minutes and then at room temperature for a further 30 minutes. The mixture was then shaken with 20 ml of toluene and the toluene extract washed with a further portion of water and then with saturated sodium chloride solution. After drying over anhydrous magnesium sulphate the toluene solution was reduced to approximately half its volume and then heated at 100° C. for 1 hour. The toluene was evaporated and there was obtained 1.148 g of 1,4-dicarbethoxy-4-isocyanatopiperidine in the form of an oil.