Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][CH:2]1[CH2:13][C:5]2[N:6]=[C:7]([S:11][CH3:12])[NH:8][C:9](=O)[C:4]=2[CH2:3]1.P(Cl)(Cl)([Cl:16])=O>>[Cl:16][C:9]1[C:4]2[CH2:3][CH:2]([CH3:1])[CH2:13][C:5]=2[N:6]=[C:7]([S:11][CH3:12])[N:8]=1
Reactant: CSc1nc2c(c(=O)[nH]1)CC(C)C2
Reactant: O=P(Cl)(Cl)Cl
Product: CSc1nc(Cl)c2c(n1)CC(C)C2
Yield: 12 %

Procedure:
A solution of 6-methyl-2-(methylthio)-6,7-dihydro-3H-cyclopenta[d]pyrimidin-4(5H)-one (0.19 g, 0.97 mmol) in phosphorous oxychloride (5.0 mL) was heated to 95° C. for 1 hour. After cooling the reaction was concentrated, and the residue dissolved in ethyl acetate (50 mL) and washed with cold water (25 mL), 0.1 M aqueous sodium hydroxide (25 mL) and brine (20 mL). The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was chromatographed on silica gel (diethyl ether/hexanes, 1:10) and the product containing fractions concentrated. The residue thus obtained was purified further by preparative reverse phase HPLC (0.1% aqueous ammonium acetate-acetonitrile to give 4-chloro-6-methyl-2-(methylthio)-6,7-dihydro-5H-cyclopenta[d]pyrimidine (25 mg, 12% yield) as an oil. 1H NMR (400 MHz, d6-DMSO): 3.12 (m, 2H), 2.61 (m, 2H), 2.56 (s, 3H), 1.25 (m, 1H), 1.18 (d, 3H); MS (EI) for C9H11ClN2S: 215 (MH+).
Reaction SMILES: Br[C:2]1[C:6]2[N:7]=[C:8]([Cl:12])[N:9]=[C:10]([NH2:11])[C:5]=2[S:4][CH:3]=1.[NH2:13][C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[CH:18][CH:19]=1>>[NH2:13][C:14]1[CH:19]=[C:18]([C:2]2[C:6]3[N:7]=[C:8]([Cl:12])[N:9]=[C:10]([NH2:11])[C:5]=3[S:4][CH:3]=2)[CH:17]=[CH:16][CH:15]=1
Reactant: Nc1cccc(B(O)O)c1
Reactant: Nc1nc(Cl)nc2c(Br)csc12
Product: Nc1cccc(-c2csc3c(N)nc(Cl)nc23)c1
Yield: 68.5 %

Procedure:
The target compound (360 mg, 68% yield) was prepared in the same manner as Step 1 of Example 11 using 7-bromo-2-chlorothieno[3,2-d]pyrimidin-4-amine (500 mg, 1.90 mmol) and 3-aminophenylboronic acid (261 mg, 1.90 mmol).
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[N:10]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:9](=[O:19])[O:8][CH2:7][C:6]=2[CH:20]=1.[CH3:21][N:22]1[C:27](=[O:28])[CH:26]=[C:25]([C:29]2[CH:34]=[CH:33][N:32]=[CH:31][N:30]=2)[N:24]=[C:23]1[O:35][CH:36]1[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C(Cl)(Cl)Cl.[Pd].[Pd]>[CH3:21][N:22]1[C:27](=[O:28])[CH:26]=[C:25]([C:29]2[CH:34]=[CH:33][N:32]=[CH:31][N:30]=2)[N:24]=[C:23]1[O:35][CH:36]1[CH2:41][CH2:40][N:39]([C:2]2[CH:3]=[CH:4][C:5]3[N:10]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:9](=[O:19])[O:8][CH2:7][C:6]=3[CH:20]=2)[CH2:38][CH2:37]1
Reactant: C[Si](C)(C)CCOCN1C(=O)OCc2cc(Br)ccc21
Reactant: Cn1c(OC2CCNCC2)nc(-c2ccncn2)cc1=O
Agent: [Pd]
Agent: CC(C)(C)[O-]
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1
Solvent: ClC(Cl)Cl
Solvent: Cc1ccccc1
Product: Cn1c(OC2CCN(c3ccc4c(c3)COC(=O)N4COCC[Si](C)(C)C)CC2)nc(-c2ccncn2)cc1=O
Temperature: 150 °C
Reaction time: 0.5 h
Yield: 11.2 %

Procedure:
To a mixture of 6-bromo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,4-dihydro-2H-3,1-benzoxazin-2-one (620 mg, 1.7 mmol), 1-methyl-2-(piperidin-4-yloxy)-1H-[4,4′]bipyrimidinyl-6-one (500 mg, 1.7 mmol), tris(dibenzylideneacetone)dipalladium(0)-chloroform adduct (72 mg, 70 μmol), and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (130 mg, 0.28 mmol) in toluene (3.5 ml) was added sodium tert-butoxide (250 mg, 2.6 mmol) under nitrogen atmosphere. The mixture was stirred at 150° C. for 30 minutes utilizing Biotage microwave reactor. The mixture was filtered through a pad of Celite and concentrated in vacuo. The residue was purified by silica gel column chromatography (eluent; ethyl acetate) to afford 1-methyl-2-{[1-(2-oxo-1{[2-(trimethylsilyl)ethoxy]methyl}-1,4-dihydro-2H-3,1-benzoxazin-6-yl)piperidin-4-yl]oxy}-1H-[4,4′]bipyrimidinyl-6-one as a pale yellow solid (110 mg, 0.19 mmol, 11%).
Reaction SMILES: [Br:1][C:2]1[C:3](=[O:22])[NH:4][N:5]=[C:6]([O:9][CH2:10][CH2:11][S:12][C:13]2[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][CH:14]=2)[C:7]=1Br.[CH3:23][O:24][C:25]1[CH:26]=[C:27]([CH2:33][NH2:34])[CH:28]=[CH:29][C:30]=1[O:31][CH3:32]>O.O1CCOCC1>[Br:1][C:2]1[C:3](=[O:22])[NH:4][N:5]=[C:6]([O:9][CH2:10][CH2:11][S:12][C:13]2[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][CH:14]=2)[C:7]=1[NH:34][CH2:33][C:27]1[CH:28]=[CH:29][C:30]([O:31][CH3:32])=[C:25]([O:24][CH3:23])[CH:26]=1
Reactant: COc1ccc(CN)cc1OC
Reactant: O=c1[nH]nc(OCCSc2ccc([N+](=O)[O-])cc2)c(Br)c1Br
Solvent: C1COCCO1
Solvent: O
Product: COc1ccc(CNc2c(OCCSc3ccc([N+](=O)[O-])cc3)n[nH]c(=O)c2Br)cc1OC
Temperature: 25 °C
Yield: 61.6 %

Procedure:
1.5 g of 4,5-dibromo-6-[2-(4-nitrophenylthio)ethyloxy]-3(2H)-pyridazinone and 1.32 g of 3,4-dimethoxyphenylmethyl amine were disolved in water-dioxane (1:1) and refluxed for 7 hr. The reaction mixture was cooled to room temperature. The resulting crystals was collected by filtration and recrystallized from dioxane to give 1.1 g of the objective compound. Yield, 60%, Melting point, 170°-171° C.
Reaction SMILES: [CH2:1]([NH2:4])[CH:2]=[CH2:3].[N:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[CH2:11][C:12](N)=[S:13].O>C(O)C>[CH2:1]([NH:4][C:12](=[S:13])[CH2:11][C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][N:5]=1)[CH:2]=[CH2:3]
Reactant: NC(=S)Cc1ccccn1
Reactant: C=CCN
Solvent: CCO
Solvent: O
Product: C=CCNC(=S)Cc1ccccn1
Reaction time: 8 h

Procedure:
Allylamine (3.1 g.) is added with stirring to 4.0 g. of 2-(2-pyridyl)thioacetamide in 20 ml. of water at 0°C. The resulting mixture is allowed to stand overnight at 5°C., then 5 ml. of ethanol is added. The mixture is stirred for 5 hours and then extracted with dichloromethane. The extracts are dried and concentrated and the residue is chromatographed on a silica gel "dry-column" to give N-allyl-2-(2-pyridyl)thioacetamide.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[OH:11].[NH:12]([C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18])[CH2:13][C:14](O)=[O:15]>>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[O:11][C:14](=[O:15])[CH2:13][NH:12][C:17]([O:19][CH2:20][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)=[O:18]
Reactant: O=C(O)CNC(=O)OCc1ccccc1
Reactant: Oc1ccc2ccccc2c1
Product: O=C(CNC(=O)OCc1ccccc1)Oc1ccc2ccccc2c1
Yield: 72 %

Procedure:
β-Naphthol and Z-Gly.OH were treated in the same manner as in Example 78 to obtain N-benzyloxycarbonyl glycine β-naphthyl ester (hereinafter represented by ##STR10## in a yield of 72%.
Reaction SMILES: [CH3:1][C:2]([CH3:7])([CH2:5][OH:6])[CH2:3][OH:4].[NH+]1C=CC=CC=1.C1(C)C=CC(S([O-])(=O)=O)=CC=1.O=[C:26]1[CH2:30][CH2:29][CH:28]([C:31]([O:33]C)=[O:32])[CH2:27]1.O>C1(C)C=CC=CC=1>[C:31]([CH:28]1[CH2:29][CH2:30][C:26]2([O:6][CH2:5][C:2]([CH3:7])([CH3:1])[CH2:3][O:4]2)[CH2:27]1)([OH:33])=[O:32]
Reactant: CC(C)(CO)CO
Reactant: COC(=O)C1CCC(=O)C1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: c1cc[nH+]cc1
Solvent: O
Solvent: Cc1ccccc1
Product: CC1(C)COC2(CCC(C(=O)O)C2)OC1

Procedure:
72.8 g (0.70 mole) of 2,2-dimethylpropane-1,3-diol and 12.2 g (0.05 mole) of pyridinium-4-toluenesulphonate are added one after another to 40.0 g (0.28 mole) of methyl 3-oxocyclopentane carboxylate OCCME in 560 ml of absolute toluene. The mixture is boiled for 1.5 hours in a water separator; after 30 minutes the solid is dissolved. Approximately 8 ml of H2O in total are separated out. After cooling, the solution is washed three times using 100 ml of H2O each time, the toluene phase is dried over MgSO4 and evaporated in vacuo. The oily residue is fractionally distilled in vacuo at 0.6 mbar over a metallised pin tube column 20 cm long.
Reaction SMILES: [CH2:1]([N:8]1[C:13](=[O:14])[C:12]2[C:15]([Br:19])=[C:16]([Br:18])[S:17][C:11]=2[N:10]=[C:9]1[CH:20](Br)[CH2:21][CH3:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:24][N:25]([CH3:29])[CH2:26][CH2:27][NH2:28]>C(O)C>[CH2:1]([N:8]1[C:13](=[O:14])[C:12]2[C:15]([Br:19])=[C:16]([Br:18])[S:17][C:11]=2[N:10]=[C:9]1[CH:20]([NH:28][CH2:27][CH2:26][N:25]([CH3:29])[CH3:24])[CH2:21][CH3:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCC(Br)c1nc2sc(Br)c(Br)c2c(=O)n1Cc1ccccc1
Reactant: CN(C)CCN
Solvent: CCO
Product: CCC(NCCN(C)C)c1nc2sc(Br)c(Br)c2c(=O)n1Cc1ccccc1

Procedure:
A solution of 3-benzyl-5,6-dibromo-2-(1-bromopropyl)thieno[2,3-d]pyrimidin-4(3H)-one (2-5, 35 mg, 0.066 mmol, 1 equiv) and N,N-dimethylethylenediamine (17 mg, 0.198 mmol, 3 equiv) in ethanol (5 mL) was heated at reflux for 18 h. The reaction was concentrated, and the residue was partitioned between EtOAc and brine. The organic layer was dried (MgSO4) and concentrated to provide 3-benzyl-5,6-dibromo-2-{(1-([2-(dimethylamino)ethyl]amino}propyl)thieno-[2,3-d]pyrimidin-4(3H)-one (2-7) as a yellow gum. MS(M+1)=526.8.
Reaction SMILES: [C:1]([C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=1)([CH2:4][C:5]([CH3:8])([CH3:7])[CH3:6])([CH3:3])[CH3:2].[C:16]1([OH:22])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C=O.C(O)(=O)[C:26](O)=[O:27]>O.C1(C)C(C)=CC=CC=1.C1(C)C(C)=CC=CC=1>[C:1]([C:9]1[CH:10]=[CH:11][C:12]([OH:15])=[CH:13][CH:14]=1)([CH2:4][C:5]([CH3:8])([CH3:7])[CH3:6])([CH3:2])[CH3:3].[C:16]1([OH:22])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[OH:15][C:12]1[CH:11]=[CH:10][C:9]([C:1]([C:4]2[CH:5]=[CH:8][C:16]([OH:22])=[CH:17][CH:18]=2)([CH3:2])[CH3:3])=[CH:14][CH:13]=1.[CH2:26]=[O:27]
Reactant: O=C(O)C(=O)O
Agent: C=O
Agent: CC(C)(C)CC(C)(C)c1ccc(O)cc1
Solvent: Oc1ccccc1
Solvent: O
Solvent: Cc1ccccc1C
Product: CC(C)(c1ccc(O)cc1)c1ccc(O)cc1
Temperature: 170 °C

Procedure:
375 g. (1.8 moles) of p-tert-octylphenol, 75 g (0.8 mole) of phenol, 50 g (0.22 mole) of 4,4'-isopropylidene-biphenol (bisphenol A), 215 g (2.65 moles) of 37% formalin, 10 g of oxalic acid and 100 g of xylene were put into a reactor, and they were refluxed for 7 hours at the boiling point of the water-xylene azeotrope. The reaction mixture was then heated to 170° C. while removing water and the solvent, thereby giving a p-tert-octylphenol/phenol/bisphenol A/formaldehyde co-condensate having a softening point of 85° C.
Reaction SMILES: C([BH-](CC)CC)C.[Na+].[CH:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:12]=[CH:11][N:10]=1.[C:19]([O:23]CC)(=[O:22])[CH:20]=O.[OH-].[Na+].OO.[ClH:30]>C1COCC1.C1(C)C=CC=CC=1>[ClH:30].[CH:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]([CH2:20][C:19]([OH:23])=[O:22])=[CH:11][N:10]=1
Reactant: c1ccc2cnccc2c1
Reactant: CCOC(=O)C=O
Agent: CC[BH-](CC)CC
Agent: Cl
Agent: OO
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: O=C(O)Cc1cncc2ccccc12
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of sodium triethylborohydride (1M THF, 12.7 ml, 12.7 mmol) is added dropwise to a solution of isoquinoline (1.64 g, 12.7 mmol) in THF (25 ml). The reaction is stirred at room temperature for 1 hour, prior to dropwise addition of a solution of ethyl glyoxalate (1.43 g, 13.9 mmol) in toluene (previously heated at 110° C. for 1.5 hours). After a further 4 hours at room temperature, the reaction is cooled to 0° C. and sodium hydroxide (0.5M aqueous solution, 25.4 ml) followed by hydrogen peroxide (30% aqueous solution, 12.7 ml) is added, followed by stirring for 2 hours. The reaction is acidified with 1N HCl, washed with ethyl acetate three times, the aqueous phase is reduced in volume by evaporation and refrigerated overnight. The resultant precipitate is collected by filtration and dried to afford isoquinolin4-yl-acetic acid hydrochloride salt, MH+ 188.
Reaction SMILES: [Li+].[Br-].Br[C:4]1[CH:12]=[C:11]2[C:7]([C:8]([CH3:22])([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=3)[CH2:9][N:10]2[C:13](=[O:15])[CH3:14])=[CH:6][CH:5]=1.[Br-].[CH2:24]([Zn+])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>CN1C(=O)CCC1.C1COCC1.C(N1C=CN(C(C)C)C1=[Pd-3](Cl)(Cl)C1C(Cl)=CC=CN=1)(C)C>[CH2:24]([C:4]1[CH:12]=[C:11]2[C:7]([C:8]([CH3:22])([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=3)[CH2:9][N:10]2[C:13](=[O:15])[CH3:14])=[CH:6][CH:5]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: CC(=O)N1CC(C)(c2ccccn2)c2ccc(Br)cc21
Reactant: [Zn+]Cc1ccccc1
Agent: CC(C)n1ccn(C(C)C)c1=[Pd-3](Cl)(Cl)c1ncccc1Cl
Agent: [Br-]
Agent: [Li+]
Solvent: CN1CCCC1=O
Solvent: C1CCOC1
Product: CC(=O)N1CC(C)(c2ccccn2)c2ccc(Cc3ccccc3)cc21
Temperature: 25 °C
Reaction time: 16 h
Yield: 85.2 %

Procedure:
To a degassed solution of LiBr (165 mg, 1.9 mmol) and (1,3-diisopropylimidazol-2-ylidene)(3-chloropyridyl)palladium (II) dichloride (8 mg, 0.012 mmol) in NMP (3 mL) under N2 were added a solution of 1-(6-bromo-3-methyl-3-pyridin-2-yl-2,3-dihydro-indol-1-yl)-ethanone (400 mg, 1.2 mmol) in THF (3 mL) and benzylzinc bromide (0.5 M in THF, 3.8 mL, 1.9 mmol). The reaction mixture was stirred at room temperature for 16 h and then partitioned between brine and EtOAc. The organic phase was separated, dried over MgSO4, filtered and concentrated in vacuo. Chromatography (50% EtOAc in Petrol) gave the title compound (350 mg) as a colourless gum. MS: [M+H]+=343.
Reaction SMILES: [CH3:1][C:2]1[C:7]2[NH:8][C:9](=O)[O:10][C:11](=[O:12])[C:6]=2[CH:5]=[C:4]([N+:14]([O-:16])=[O:15])[CH:3]=1.C[O-].[Na+].[NH4+].[Cl-]>CO>[CH3:9][O:10][C:11](=[O:12])[C:6]1[CH:5]=[C:4]([N+:14]([O-:16])=[O:15])[CH:3]=[C:2]([CH3:1])[C:7]=1[NH2:8]
Reactant: Cc1cc([N+](=O)[O-])cc2c(=O)oc(=O)[nH]c12
Agent: C[O-]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CO
Product: COC(=O)c1cc([N+](=O)[O-])cc(C)c1N
Temperature: 25 °C
Reaction time: 1 h
Yield: 98.6 %

Procedure:
To a suspension of 8-methyl-6-nitro-1H-benzo[d][1,3]oxazine-2,4-dione ((Example 295: step b) 1.04 g, 4.68 mmol) in methanol (30 mL) was added a solution of sodium methoxide (0.5 M, 0.94 mL, 4.7 mmol) in methanol. The mixture was stirred at ambient temperature for 1 hour and neutralized by addition of saturated NH4Cl. Methanol was removed under reduced pressure and the resulting mixture was filtered. The solids were washed with H2O (twice), dried in high vacuum to give the product (0.97 g, 99% yield) as a yellow solid. 1H NMR (DMSO) δ 8.48 (d, 1H, J=2.7 Hz), 8.02–8.01 (m, 1H), 7.75 (br s, 2H), 3.86 (s, 3H), 2.20 (s, 3H).
Reaction SMILES: [CH2:1]([O:3][C:4]([NH:6][NH:7][CH:8]([CH3:10])[CH3:9])=[O:5])[CH3:2].C(=O)(O)[O-].[Na+].C(Cl)Cl.[N:19]#[C:20]Cl>O>[CH2:1]([O:3][C:4]([NH:6][N:7]([CH:8]([CH3:10])[CH3:9])[C:20]#[N:19])=[O:5])[CH3:2]
Reactant: N#CCl
Reactant: CCOC(=O)NNC(C)C
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: CCOC(=O)NN(C#N)C(C)C
Yield: 87.7 %

Procedure:
73.0 g of 2-isopropylhydrazinecarboxylic acid ethyl ester and 42.0 g of sodium bicarbonate are stirred into 200 ml of methylene chloride and 400 ml of water. There is then introduced at room temperature in the course of 20 minutes, with continuous stirring, 30.8 g of gaseous cyanogen chloride. After an hour's stirring, the methylene chloride base is separated, dried over sodium sulphate and the solvent is distilled off in vacuo. There is obtained as residue 75.0 g (87.5% of theory) of 2-isopropyl-2-cyanohydrazinecarboxylic acid ethyl ester as colourless oil.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:19])[CH2:5][O:6][C:7]1[CH:12]=[C:11]([O:13][CH3:14])[C:10]([Cl:15])=[CH:9][C:8]=1[C:16](=O)[CH3:17])[CH3:2].CC([O-])(C)C.[K+].CCCCCC.CCOC(C)=O>C(COC)OC>[CH2:1]([O:3][C:4]([C:5]1[O:6][C:7]2[CH:12]=[C:11]([O:13][CH3:14])[C:10]([Cl:15])=[CH:9][C:8]=2[C:16]=1[CH3:17])=[O:19])[CH3:2]
Reactant: CCOC(=O)COc1cc(OC)c(Cl)cc1C(C)=O
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: COCCOC
Solvent: CCCCCC
Product: CCOC(=O)c1oc2cc(OC)c(Cl)cc2c1C
Yield: 40.9 %

Procedure:
The above prepared (2-acetyl-4-chloro-5-methoxy-phenoxy)-acetic acid ethyl ester-(6.05 g, 21.1 mmol) was dissolved in 45 mL of dimethoxyethane and treated at −15° C. with KOtBu (0.947 g, 0.4 eq.). After keeping for 45 Min. at −15° C. and 5 h at 0° C., the reaction mixture was poured onto crashed ice/HCl, twofold extracted with AcOEt, washed with water, dried over magnesium sulfate, and evaporated to dryness to leave 5.26 g of crude product. Flash chromatography (SiO2, hexane/AcOEt=9/1) of the latter afforded 2.32 g of the title compound as white crystals.
Reaction SMILES: O=C(CCC)OCC(OC(=O)CCC)COC(=O)CCC.[CH2:22]([O:30][C:31]1[CH:36]=[CH:35][C:34]([C:37]2[CH:42]=[CH:41][C:40]([CH:43]([OH:45])[CH3:44])=[CH:39][CH:38]=2)=[CH:33][CH:32]=1)[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29].C1(N=C=NC2CCCCC2)CCCCC1.[C:61](O)(=[O:67])[CH2:62][CH2:63][CH2:64][CH2:65][CH3:66]>CN(C)C1C=CN=CC=1.ClCCl>[CH2:22]([O:30][C:31]1[CH:36]=[CH:35][C:34]([C:37]2[CH:42]=[CH:41][C:40]([CH:43]([O:45][C:61](=[O:67])[CH2:62][CH2:63][CH2:64][CH2:65][CH3:66])[CH3:44])=[CH:39][CH:38]=2)=[CH:33][CH:32]=1)[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]
Reactant: CCCCCCCCOc1ccc(-c2ccc(C(C)O)cc2)cc1
Reactant: CCCCCC(=O)O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CCCC(=O)OCC(COC(=O)CCC)OC(=O)CCC
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: CCCCCCCCOc1ccc(-c2ccc(C(C)OC(=O)CCCCC)cc2)cc1
Temperature: 25 °C
Reaction time: 6 h

Procedure:
Racemic(±)-4-octyloxy-4'-(1-hydroxyethyl)biphenyl (m.p. 110.9°-111.9° C.) and tributyrin were biochemically transesterified. The obtained 7.0 g (21 mmol) of optically active (-)-4-octyloxy-4'-(1-hydroxyethyl)biphenyl (m.p. 123.6° C., [α]D 24.5 -27.0° (c 1.0, CHCl3)), 7.5 g(36 mmol) of N,N'-dicyclohexylcarbodiimide (abbreviated as DCC) and 1.0 g of 4-dimethylaminopyridine (abbreviated as DMAP) were dissolved in 200 ml of dichloromethane. To the solution, 3.4 g (29 mmol) of caproic acid was added, and the mixture was stirred for six hours at room temperature. The deposited crystals were filtered, 200 ml of water was added to the filtrate, and the organic layer was separated. 6N hydrochloric acid was added to the organic solution, and then the solution was neutralized with the aqueous solution of 2N sodium hydroxide. The neutralized solution was washed with water until the washed water became neutral. The solvent and low-boiling fractions were distilled away from the obtained solution. The residue was recrystallized from ethanol and the desired (-)-4-octyloxy-4'-(1-hexanoyloxyethyl)biphenyl 6.8 g was obtained. The melting point of the obtained biphenyl was 60.8° C. and its specific optical rotation was -78.4° at 25.3° C. for D line (c 0.88, C2H5OH).
Reaction SMILES: [C-:1]#[N:2].[K+].[F:4][C:5]1[CH:10]=[C:9](F)[C:8]([N+:12]([O-:14])=[O:13])=[CH:7][C:6]=1[N:15]1[C:20](=[O:21])[CH:19]=[C:18]([C:22]([F:25])([F:24])[F:23])[N:17]([CH3:26])[C:16]1=[O:27]>CS(C)=O>[C:1]([C:9]1[C:8]([N+:12]([O-:14])=[O:13])=[CH:7][C:6]([N:15]2[C:20](=[O:21])[CH:19]=[C:18]([C:22]([F:25])([F:24])[F:23])[N:17]([CH3:26])[C:16]2=[O:27])=[C:5]([F:4])[CH:10]=1)#[N:2]
Reactant: [C-]#N
Reactant: Cn1c(C(F)(F)F)cc(=O)n(-c2cc([N+](=O)[O-])c(F)cc2F)c1=O
Agent: [K+]
Solvent: CS(C)=O
Product: Cn1c(C(F)(F)F)cc(=O)n(-c2cc([N+](=O)[O-])c(C#N)cc2F)c1=O
Temperature: 25 °C
Reaction time: 10 h
Yield: 47.1 %

Procedure:
Potassium cyanide (0.5 g) was added to a solution of 3-[2,4-difluoro-5-nitrophenyl]-1-methyl-6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (2.5 g) in 50 ml of anhydrous dimethyl sulfoxide. The reaction mixture was subsequently stirred for 10 hours at room temperature, more potassium cyanide (0.16 g) being added after 5 hours. For working-up, most of the solvent was removed at 80° C. under a high vacuum. The residue was taken up in 150 ml of water, washed three times using in each case 30 ml of water, dried over sodium sulfate and concentrated. Chromatography on silica gel (dichloromethane as eluent) and crystallization using petroleum ether gave 1.2 g of the desired product; m.p.: 155-157° C. The following compounds of Table 3 were prepared in a similar manner:
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([O:8][C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[NH:14][CH:13]=[CH:12]3)[CH:5]=[CH:4][N:3]=1.ClC1N=CN=C(OC2C=C3C(=CC=2)NC=C3)C=1>>[Cl:1][C:2]1[N:7]=[C:6]([O:8][C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[NH:14][CH2:13][CH2:12]3)[CH:5]=[CH:4][N:3]=1
Reactant: Clc1nccc(Oc2ccc3[nH]ccc3c2)n1
Agent: Clc1cc(Oc2ccc3[nH]ccc3c2)ncn1
Product: Clc1nccc(Oc2ccc3c(c2)CCN3)n1

Procedure:
Utilising a similar procedure, but employing 5-[(2-chloro-4-pyrimidinyl)oxy]-1H-indole in lieu of 5-[(6-chloro-4-pyrimidinyl)oxy]-1H-indole afforded 5-[(2-chloro-4-pyrimidinyl)oxy]-2,3-dihydro-1H-indole, as an oil.
Reaction SMILES: [N:1]([CH:4]1[CH2:9][CH2:8][CH2:7][C:6]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([N:18]3[C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=4[CH2:22][N:21]4[CH:29]=[CH:30][CH:31]=[C:20]4[CH2:19]3)=[O:17])=[CH:12][C:11]=2[CH3:32])=[C:5]1[CH3:33])=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1.O>[NH2:1][CH:4]1[CH2:9][CH2:8][CH2:7][C:6]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([N:18]3[C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=4[CH2:22][N:21]4[CH:29]=[CH:30][CH:31]=[C:20]4[CH2:19]3)=[O:17])=[CH:12][C:11]=2[CH3:32])=[C:5]1[CH3:33]
Reactant: CC1=C(c2ccc(C(=O)N3Cc4cccn4Cc4ccccc43)cc2C)CCCC1N=[N+]=[N-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: C1CCOC1
Product: CC1=C(c2ccc(C(=O)N3Cc4cccn4Cc4ccccc43)cc2C)CCCC1N
Temperature: 25 °C
Reaction time: 8 h
Yield: 36.7 %

Procedure:
[4-(3-Azido-2-methyl-cyclohex-1-en-1-yl)-3-methyl-phenyl]-(10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-methanone of Step A (0.290 g, 0.663 mmol) was dissolved in 7 mL of a 10:1 mixture of tetrahydrofuran and water. Polymer-supported triphenylphosphine (0.287 g, approximately 0.862 mmol) was added and the reaction stirred at room temperature overnight. The mixture was filtered and concentrated, and the residue purified by flash column chromatography on silica gel, eluting with 3% ammonium hydroxide and 20% methanol in chloroform. A yellow oil was isolated which was triturated with 1:1 diethyl ether/petroleum ether to afford the title compound (0.100 g) as a white solid.
Reaction SMILES: [Cl:1][S:2]([OH:5])(=O)=[O:3].[CH3:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([CH3:13])[C:8]=1[NH:14][C:15]([CH2:17][Cl:18])=[O:16]>>[Cl:18][CH2:17][C:15]([NH:14][C:8]1[C:7]([CH3:6])=[C:12]([S:2]([Cl:1])(=[O:5])=[O:3])[CH:11]=[CH:10][C:9]=1[CH3:13])=[O:16]
Reactant: Cc1cccc(C)c1NC(=O)CCl
Reactant: O=S(=O)(O)Cl
Product: Cc1ccc(S(=O)(=O)Cl)c(C)c1NC(=O)CCl
Reaction time: 1.5 h

Procedure:
To chlorosulfonic acid (75 mL, 1.15 mol) was added with stirring solid 2-chloro-2',6'-acetoxylidide over a 30 minute period at 25°-30° C. and the reaction mixture was stirred at 60°-65° C. for 1.5 hours. The reaction was cooled, added to ice and extracted with ethyl acetate/methyl ethyl ketone. The combined extracts were washed with water and brine; dried, and the solvent was removed in vacuo; the residual product (61.4 g, 69%) was a white solid, m.p. 147.5°-149° C.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7].C(=O)([O-])[O-].[K+].[K+].[CH2:17]1[CH:27]2[N:21]([C:22]3[CH:35]=[CH:34][CH:33]=[CH:32][C:23]=3[O:24][C:25]3[CH:31]=[CH:30][CH:29]=[CH:28][C:26]=32)[CH2:20][CH2:19][NH:18]1>CC(=O)CC.C1C=CC=CC=1>[CH2:9]([O:8][C:6](=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2][N:18]1[CH2:19][CH2:20][N:21]2[C:22]3[CH:35]=[CH:34][CH:33]=[CH:32][C:23]=3[O:24][C:25]3[CH:31]=[CH:30][CH:29]=[CH:28][C:26]=3[CH:27]2[CH2:17]1)[CH3:10]
Reactant: c1ccc2c(c1)Oc1ccccc1N1CCNCC21
Reactant: CCOC(=O)CCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: c1ccccc1
Solvent: CCC(C)=O
Product: CCOC(=O)CCCCN1CCN2c3ccccc3Oc3ccccc3C2C1
Yield: 97 %

Procedure:
Ethyl 5-bromopentanoate (1.66 g, 0.0079 mol) and potassium carbonate (1.75 g, 0.0127 mol) were added to a solution of 1,3,4,14b-tetrahydro-2H-dibenzo[b,f]pyrazino[1,2-d][1,4]-oxazepine (1.6 g, 0.0063 mol prepared similarly as described in Neth. Appl. 6709520, Chem. Abs. 70, 115192 (1969)) in 2-butanone (45 ml) and the reaction mixture was heated at 70-80° C. for 17 h. The mixture was diluted with benzene (50 ml), the solid was filtered off, washed with benzene (2×10 ml) and the filtrate was evaporated in vacuo. The residue (3.2 g) was purified by column chromatography on silica gel (100 g) using benzene and a mixture of benzene and chloroform (1:1) as eluents to afford 2.35 g (97%) crude 5-(1,3,4,14b-tetrahydro-2H-dibenzo[b,f]-pyrazino[1,2-d][1,4]oxazepin -2-yl)pentanoic acid ethyl ester.