Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:4]1[CH:5]=[CH:6][C:7]([O:14][CH2:15][CH2:16][CH2:17]C=C)=[C:8]([CH:13]=1)[C:9]([O:11][CH3:12])=[O:10])(=[O:3])[CH3:2].O=[O+][O-].CSC.[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=[O:27].[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.CN(C)[CH:49]=[O:50]>C(Cl)Cl.O>[C:1]([C:4]1[CH:5]=[CH:6][C:7]([O:14][CH2:15][CH2:16][CH2:17][C:49]([OH:50])=[O:27])=[C:8]([CH:13]=1)[C:9]([O:11][CH3:12])=[O:10])(=[O:3])[CH3:2]
Reactant: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Reactant: C=CCCCOc1ccc(C(C)=O)cc1C(=O)OC
Reactant: CN(C)C=O
Agent: O=[O+][O-]
Agent: c1cc[nH+]cc1
Solvent: O
Solvent: ClCCl
Solvent: CSC
Product: COC(=O)c1cc(C(C)=O)ccc1OCCCC(=O)O
Temperature: -78 °C
Reaction time: 20 h
Yield: 50 %

Procedure:
A sample of 0.203 g (0.775 mmol) of 5-acetyl-2-(4-pentenyloxy)benzoic acid, methyl ester is dissolved in 5 mL of methylene dichloride, under an argon atmosphere, and cooled to -78° C. in a dry ice acetone bath, with stirring. Next, ozone gas is passed through this solution for 10 minutes, until it turns a light bluish color. Then 0.5 mL of dimethyl sulfide is added to quench the reaction and it is allowed to warm to room temperature for 2 hours. The mixture is then evaporated under high vacuum, leaving the crude aldehyde product as an oil which is used "as is" for the second step. It is dissolved in 5 mL of N,N-dimethylformamide, and 1.02 g (2.71 mmol) of pyridinium dichromate is added. This reaction mixture is sealed and allowed to stand for 20 hours. It is next poured into 50 mL of water, extracted with ether, and the organic phase is washed with water again, dried with magnesium sulfate, filtered, and evaporated, which gives oily crystals. These are recrystallized from a mixture of ethyl acetate and hexane, producing 0.109 g (50%) of 5-acetyl-2-(3-carboxypropoxy)benzoic acid, methyl ester as white crystals: m.p. 111°-113° C.; IR (KBr) 1725, 1645 cm-1 ; 1HNMR (CDCl3) is consistent with the desired product; MS (FAB) m/e 281 (M+ +H). Analysis calculated for C14H16O6 : C, 60.00; H, 5.75; O, 34.25. Found: C, 59.96; H, 5.75; O, 34.27.
Reaction SMILES: C([O:3][C:4](=[O:21])[CH2:5][O:6][C:7]1[CH:20]=[CH:19][CH:18]=[C:17]2[C:8]=1[CH2:9][CH2:10][C:11]1[S:15][C:14]([SH:16])=[N:13][C:12]=12)C.Br[CH:23]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>>[C:25]1([CH:24]([S:16][C:14]2[S:15][C:11]3[CH2:10][CH2:9][C:8]4[C:17](=[CH:18][CH:19]=[CH:20][C:7]=4[O:6][CH2:5][C:4]([OH:3])=[O:21])[C:12]=3[N:13]=2)[CH2:23][C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: BrC(Cc1ccccc1)c1ccccc1
Reactant: CCOC(=O)COc1cccc2c1CCc1sc(S)nc1-2
Product: O=C(O)COc1cccc2c1CCc1sc(SC(Cc3ccccc3)c3ccccc3)nc1-2
Yield: 41 %

Procedure:
Using ethyl[(2-mercapto-4,5-dihydronaphtho[1,2-d]thiazol-6-yl)oxy]acetate and 1-bromo-1,2-diphenylethane, the procedure of Example 1 was otherwise repeated to synthesize the title compound. Yield 41%.
Reaction SMILES: [Br:1]/[CH:2]=[CH:3]/[C:4]1[C:5]([O:12]C)=[N:6][C:7]([O:10]C)=[N:8][CH:9]=1.[Na+].[I-]>CC(O)=O>[Br:1]/[CH:2]=[CH:3]/[C:4]1[C:5](=[O:12])[NH:6][C:7](=[O:10])[NH:8][CH:9]=1
Reactant: COc1ncc(/C=C/Br)c(OC)n1
Agent: [I-]
Agent: [Na+]
Solvent: CC(=O)O
Product: O=c1[nH]cc(/C=C/Br)c(=O)[nH]1
Yield: 64.5 %

Procedure:
To a solution of E-5-(2-bromovinyl)-2,4-dimethoxypyrimidine (2.45 g; 10 mmol) in AcOH (10 ml) was added NaI (3.3 g; 2.2 eq.; 22 mmol) and the solution heated under reflux for 3 h. The hot mixture was filtered and diluted with water (15 ml). After cooling, the precipitated product was filtered off, washed with acetone (50 ml) and ether (20 ml) and dried to give a pale yellow powder (1.40 g, 65%). Mp>320° C.; 60 MHz 1H-NMR, DMSO-6d, δ:7.60 (s, 1H, H-6); 7.30 (d, 1H, J=13 Hz, vinyl H); 6.80 (d, 1H, J=13 Hz, vinyl H).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([S:10](Cl)(=[O:12])=[O:11])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][N:24]([C:27]2[C:36]3[O:35][CH2:34][CH2:33][NH:32][C:31]=3[CH:30]=[CH:29][CH:28]=2)[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15].N1C=CC=CC=1.O>ClCCl>[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][N:24]([C:27]2[C:36]3[O:35][CH2:34][CH2:33][N:32]([S:10]([C:6]4[CH:7]=[CH:8][CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=4)(=[O:12])=[O:11])[C:31]=3[CH:30]=[CH:29][CH:28]=2)[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:15])[CH3:16]
Reactant: CC(C)(C)OC(=O)N1CCN(c2cccc3c2OCCN3)CC1
Reactant: O=[N+]([O-])c1cccc(S(=O)(=O)Cl)c1
Solvent: O
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(C)(C)OC(=O)N1CCN(c2cccc3c2OCCN3S(=O)(=O)c2cccc([N+](=O)[O-])c2)CC1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 102.2 %

Procedure:
3-Nitro-benzenesulfonyl chloride (122.9 mg, 0.55 mmol) was added in small portions under nitrogen to an ice-cold solution of 4-(3,4-dihydro-2H-benzo[1,4]oxazin-8-yl)-piperazine-1-carboxylic acid tert-butyl ester (161 mg, 0.504 mmol) and pyridine (88 mg, 1.11 mmol) in dichlormethane (2 mL). After 0.5 hour at ambient temperature, water was added. The organic phase was separated, washed with saturated aqueous solution of sodium bicarbonate (20 mL), dried (Na2SO4) and concentrated to give 4-[4-(3-nitro-benzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-yl]-piperazine-1-carboxylic acid tert-butyl ester as an oil (260 mg). MS: MH+=505.
Reaction SMILES: [C:1](=O)([O-])[O-].[Cs+].[Cs+].[CH2:7]([O:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][CH:23]([S:29]([CH3:32])(=[O:31])=[O:30])[C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:17][CH:16]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.IC.Cl>CN(C=O)C>[CH2:7]([O:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][C:23]([CH3:1])([S:29]([CH3:32])(=[O:30])=[O:31])[C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:17][CH:16]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: O=C([O-])[O-]
Reactant: CCOC(=O)C(CCc1ccc(OCc2ccccc2)cc1)S(C)(=O)=O
Agent: Cl
Agent: [Cs+]
Solvent: CI
Solvent: CN(C)C=O
Product: CCOC(=O)C(C)(CCc1ccc(OCc2ccccc2)cc1)S(C)(=O)=O
Reaction time: 0.5 h
Yield: 91 %

Procedure:
Cesium carbonate (9.30 g, 28.5 mmol) was added to ethyl 4-[4-(benzyloxy)phenyl]-2-(methylsulfonyl)butanoate (8.86 g, 23.5 mmol) in DMF (100 mL) and stirred for 30 minutes. Iodomethane was added to the reaction followed by stirring overnight at room temperature. The reaction mixture was poured into 1N aqueous HCl (100 mL) and extracted with EtOAc (3×100 mL). The combined organics were washed with saturated aqueous sodium thiosulfate (100 mL) then dried (MgSO4), filtered and concentrated in vacuo to afford a crude solid. The crude product was purified via silica gel chromatography using an eluant of ethyl acetate in heptane (10-100%) to afford the title compound as a white solid (8.35 g, 90.9%). LC-MS m/z 391.2 (M+1).
Reaction SMILES: [N:1]1([C:7]2[N:8]=[C:9]([CH2:14][C:15]([O-:17])=O)[NH:10][C:11](=[O:13])[CH:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[Na+].[NH:19]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:21]([CH2:28][N:29]([CH3:31])[CH3:30])[CH2:20]1.Cl.CN(C)CCCN=C=NCC>N1C=CC=CC=1.CN(C)C=O>[CH3:31][N:29]([CH2:28][CH:21]1[C:22]2[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=2)[N:19]([C:15](=[O:17])[CH2:14][C:9]2[NH:10][C:11](=[O:13])[CH:12]=[C:7]([N:1]3[CH2:2][CH2:3][O:4][CH2:5][CH2:6]3)[N:8]=2)[CH2:20]1)[CH3:30]
Reactant: CN(C)CC1CNc2ccccc21
Reactant: O=C([O-])Cc1nc(N2CCOCC2)cc(=O)[nH]1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: c1ccncc1
Product: CN(C)CC1CN(C(=O)Cc2nc(N3CCOCC3)cc(=O)[nH]2)c2ccccc21
Yield: 61.5 %

Procedure:
The product is prepared according to the procedure described in example 5, using 220 mg of sodium [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate, 300 mg of (2,3-dihydro-1H-indol-3-ylmethyl)dimethylamine and 210 mg of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride in a mixture of 0.14 ml of pyridine and 2.5 ml of N,N-dimethylformamide. 206 mg of 2-[2-(3-dimethylaminomethyl-2,3-dihydroindol-1-yl)-2-oxoethyl]-6-morpholin-4-yl-3H-pyrimidin-4-one are obtained in the form of a pink solid, the characteristics of which are the following:
Reaction SMILES: [N:1]([C:4]1[S:8][C:7]2[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:6]=2[C:5]=1[C:15]([O:17]C)=O)=[C:2]=[S:3].[CH3:19][C:20]1[N:24]([CH2:25][CH2:26][CH2:27][NH2:28])[CH:23]=[N:22][CH:21]=1>>[CH3:19][C:20]1[N:24]([CH2:25][CH2:26][CH2:27][N:28]2[C:15](=[O:17])[C:5]3[C:6]4[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][C:7]=4[S:8][C:4]=3[NH:1][C:2]2=[S:3])[CH:23]=[N:22][CH:21]=1
Reactant: Cc1cncn1CCCN
Reactant: COC(=O)c1c(N=C=S)sc2c1CCCCCC2
Product: Cc1cncn1CCCn1c(=S)[nH]c2sc3c(c2c1=O)CCCCCC3

Procedure:
The compound was synthesized starting from methyl 4,5,6,7,8,9-hexahydro-2-isothiocyanatocycloocta[b]thiophene-3-carboxylate (0.10 g, 0.36 mmol) and 3-(5-methyl-1H-imidazol-1-yl)propan-1-amine (5) (0.049 g, 0.36 mmol) as described above.
Reaction SMILES: Cl.[CH3:2][O:3][C:4](=[O:14])[CH2:5][CH:6]([NH2:13])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C(=O)([O-])[O-].[Na+].[Na+].C(N1[C:30](=[O:31])[C:29]2=[CH:32][CH:33]=[CH:34][CH:35]=[C:28]2[C:27]1=[O:36])(OCC)=O>O.C(#N)C>[C:27]1(=[O:36])[N:13]([CH:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH2:5][C:4]([O:3][CH3:2])=[O:14])[C:30](=[O:31])[C:29]2=[CH:32][CH:33]=[CH:34][CH:35]=[C:28]12
Reactant: COC(=O)CC(N)c1ccccc1
Reactant: CCOC(=O)N1C(=O)c2ccccc2C1=O
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CC#N
Product: COC(=O)CC(c1ccccc1)N1C(=O)c2ccccc2C1=O
Reaction time: 1 h
Yield: 39.4 %

Procedure:
To a stirred solution of 3-amino-3-phenylpropionic acid methyl ester hydrochloride (0.50 g, 2.3 mmol) and sodium carbonate (0.25 g, 2.3 mmol) in 10 mL of water was added N-carboethoxyphthalimide (0.51 g, 2.3 mmol) in 7 mL of acetonitrile. The reaction progress was monitored by TLC (ethyl acetatethexane; 1:2) which showed that the reaction was complete in one hour. The reaction mixture was partially concentrated to remove the acetonitrile. The resulting slurry was filtered and the solid was washed with 20 mL of water. The solid was dried in vacuo (60° C., <1 mm) to afford 280 mg (39.4%) of methyl 3-phthalimido-3-phenylpropionate as a white powder: mp 75-76° C.; 1H NMR (DMSO-d6, 250 MHz) δ7.26-7.83 (m, 9H), 5.68-5.75 (m, 1H), 3.55 (S, 3H), 3.37-3.66 (m, 2H); 13C NMR (DMSO-d6) δ170.7, 167.6, 138.6, 134.7, 131.0, 128.6, 127.8, 126.9, 123.3, 51.6, 49.9, 35.3. Anal. Calcd for C18H15NO4: C, 69.89; H, 4.89; N, 4.53; Found: C, 69.69; H, 4.83; N, 4.49.
Reaction SMILES: [CH2:1]([C:3]1[CH:22]=[CH:21][C:6]([O:7][C:8]2[CH:20]=[CH:19][C:11]([C:12]([NH:14][CH2:15][C:16]([OH:18])=[O:17])=O)=[CH:10][CH:9]=2)=[CH:5][CH:4]=1)[CH3:2].C(OC(=O)C)(=O)C>C(OCC)(=O)C>[CH2:1]([C:3]1[CH:22]=[CH:21][C:6]([O:7][C:8]2[CH:20]=[CH:19][C:11]([C:12]3[O:17][C:16](=[O:18])[CH2:15][N:14]=3)=[CH:10][CH:9]=2)=[CH:5][CH:4]=1)[CH3:2]
Reactant: CCc1ccc(Oc2ccc(C(=O)NCC(=O)O)cc2)cc1
Solvent: CC(=O)OC(C)=O
Solvent: CCOC(C)=O
Product: CCc1ccc(Oc2ccc(C3=NCC(=O)O3)cc2)cc1
Temperature: 80 °C
Reaction time: 0.33 h
Yield: 63.9 %

Procedure:
A mixture of N-[4-(4-ethylphenoxy)benzoyl]glycine (200 mg, 0.668 mmol) prepared in Example 89 (89a) and acetic anhydride (0.38 mL, 4.03 mmol) was stirred at 80° C. for 20 minutes. Ethyl acetate was added to the reaction mixture, and then the mixture was cooled to room temperature. The solvent was evaporated, and then the residue was purified by silica gel column chromatography (hexane:ethyl acetate, 3:1, v/v) to give 2-[4-(4-ethylphenoxy)phenyl]-1,3-oxazol-5(4H)-one (120 mg, 0.427 mmol). All of this 2-[4-(4-ethylphenoxy)phenyl]-1,3-oxazol-5(4H)-one was dissolved in benzene (0.9 mL), and then 4-isopropoxybenzaldehyde (71 mg, 0.432 mmol) and triethylamine (24 μL, 0.172 mmol) were added thereto. The mixture was stirred at 90° C. for 2 hours. After the addition of water to the reaction solution, the mixture was extracted with a solvent mixture of hexane and ethyl acetate. The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated to give 181 mg of the title compound (brown oil, yield: 99%).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[NH:5][C:4](=[O:9])[C:3]=1[CH2:10][NH:11][C:12]([C:14]1[CH:19]=[C:18]([C:20]2[CH2:21][C:22]([CH3:29])([CH3:28])[NH:23][C:24]([CH3:27])([CH3:26])[CH:25]=2)[N:17]=[C:16]2[N:30]([CH:33]3[CH2:38][CH2:37][N:36](C(OC(C)(C)C)=O)[CH2:35][CH2:34]3)[N:31]=[CH:32][C:15]=12)=[O:13]>C(Cl)Cl.C(O)(C(F)(F)F)=O>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[NH:5][C:4](=[O:9])[C:3]=1[CH2:10][NH:11][C:12]([C:14]1[C:15]2[CH:32]=[N:31][N:30]([CH:33]3[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]3)[C:16]=2[N:17]=[C:18]([C:20]2[CH2:21][C:22]([CH3:28])([CH3:29])[NH:23][C:24]([CH3:26])([CH3:27])[CH:25]=2)[CH:19]=1)=[O:13]
Reactant: Cc1cc(C)c(CNC(=O)c2cc(C3=CC(C)(C)NC(C)(C)C3)nc3c2cnn3C2CCN(C(=O)OC(C)(C)C)CC2)c(=O)[nH]1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cc1cc(C)c(CNC(=O)c2cc(C3=CC(C)(C)NC(C)(C)C3)nc3c2cnn3C2CCNCC2)c(=O)[nH]1
Temperature: 25 °C
Reaction time: 1 h
Yield: 96.6 %

Procedure:
To a stirred solution of tert-butyl 4-(4-(((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-6-(2,2,6,6-tetramethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)piperidine-1-carboxylate (0.5 g, 0.8 mmol) in DCM (10 mL), TFA (0.3 mL) was added at 0° C. and reaction stirred at room temperature for 1 h. After completion of reaction, solvent was removed under reduced pressure and residue neutralized with saturated NaHCO3 solution Extraction was carried out using DCM; the combined organic layers were washed with water, brine and dried over anhydrous Na2SO4; filtered and concentrated under reduced pressure. Finally the residue was washed with diethyl ether to provide the desired compound (0.4 g, 95.7%).
Reaction SMILES: [Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[N:13]1([CH:19]([C:21]2[N:22]=[C:23]([CH2:43][CH2:44][CH3:45])[N:24]([CH2:28][C:29]3[CH:34]=[CH:33][C:32]([C:35]4[C:36]([C:41]#[N:42])=[CH:37][CH:38]=[CH:39][CH:40]=4)=[CH:31][CH:30]=3)[C:25](=[O:27])[CH:26]=2)[CH3:20])[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1>C(OCC)(=O)C>[N:13]1([CH:19]([C:21]2[N:22]=[C:23]([CH2:43][CH2:44][CH3:45])[N:24]([CH2:28][C:29]3[CH:34]=[CH:33][C:32]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=4[C:41]4[NH:3][C:4](=[O:7])[O:5][N:42]=4)=[CH:31][CH:30]=3)[C:25](=[O:27])[CH:26]=2)[CH3:20])[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1
Reactant: CCCc1nc(C(C)N2CCOCC2)cc(=O)n1Cc1ccc(-c2ccccc2C#N)cc1
Reactant: [NH3+]O
Reactant: O=C([O-])O
Agent: [Cl-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: CCCc1nc(C(C)N2CCOCC2)cc(=O)n1Cc1ccc(-c2ccccc2-c2noc(=O)[nH]2)cc1
Temperature: 40 °C
Reaction time: 0.5 h
Yield: 24.6 %

Procedure:
A mixture of hydroxylammonium chloride (0.71 g), sodium hydrogen carbonate (1.01 g) and dimethyl sulfoxide (10 mL) was stirred at 40° C. for 30 min, 4′-{[4-(1-morpholin-4-ylethyl)-6-oxo-2-propylpyrimidin-1(6H)-yl]methyl}biphenyl-2-carbonitrile (0.43 g) was added, and the mixture was stirred at 90° C. for 12 hr. The reaction mixture was diluted with ethyl acetate, washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in tetrahydrofuran (10 mL). N,N′-carbonyldiimidazole (0.24 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.22 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with water and then 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 amorphous solid (0.12 g, 26%).
Reaction SMILES: Cl.Cl[CH2:3][CH2:4][O:5][C:6]1[CH:7]=[CH:8][C:9]2[C:18]([CH:19]=1)=[N:17][C:16]1[C:11](=[CH:12][CH:13]=[C:14]([O:20][CH2:21][CH2:22]Cl)[CH:15]=1)[CH:10]=2.[CH3:24][N:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1>>[CH3:24][N:25]1[CH2:30][CH2:29][N:28]([CH2:3][CH2:4][O:5][C:6]2[CH:7]=[CH:8][C:9]3[C:18]([CH:19]=2)=[N:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:20][CH2:21][CH2:22][N:28]4[CH2:29][CH2:30][N:25]([CH3:24])[CH2:26][CH2:27]4)[CH:15]=2)[CH:10]=3)[CH2:27][CH2:26]1
Reactant: ClCCOc1ccc2cc3ccc(OCCCl)cc3nc2c1
Reactant: CN1CCNCC1
Agent: Cl
Product: CN1CCN(CCOc2ccc3cc4ccc(OCCN5CCN(C)CC5)cc4nc3c2)CC1
Temperature: 100 °C

Procedure:
The compound is prepared from 3,6-bis(2-chloroethoxy)acridine hydrochloride and N-methylpiperazine as described in Example 15, except that the mixture is heated at 100° C. for 24 hours to attain reaction and that the free base is isolated.
Reaction SMILES: NC1C=CC(OC2C=C[CH:10]=[CH:9][C:8]=2[C:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2OC2C=CC(N)=CC=2)([CH3:15])[CH3:14])=CC=1.[CH:32]1[C:37]([C:38]([C:40]2[CH:45]=[CH:44][C:43]3[C:46]([O:48][C:49](=[O:50])[C:42]=3[CH:41]=2)=[O:47])=[O:39])=[CH:36][C:35]2[C:51]([O:53][C:54](=[O:55])[C:34]=2[CH:33]=1)=[O:52].C(OC(=O)C)(=O)C.[N:63]1C=CC=CC=1.[CH3:69][C:70]([N:72](C)C)=O>O>[CH3:14][C:13]1([CH3:15])[C:16]2[CH:17]=[C:18]([NH2:63])[CH:19]=[CH:20][C:21]=2[C:9]([C:33]2[CH:34]=[CH:54][C:70]([NH2:72])=[CH:69][CH:32]=2)([CH3:10])[CH2:8]1.[CH:32]1[C:37]([C:38]([C:40]2[CH:45]=[CH:44][C:43]3[C:46]([O:48][C:49](=[O:50])[C:42]=3[CH:41]=2)=[O:47])=[O:39])=[CH:36][C:35]2[C:51]([O:53][C:54](=[O:55])[C:34]=2[CH:33]=1)=[O:52]
Reactant: CC(C)(c1ccccc1Oc1ccc(N)cc1)c1ccccc1Oc1ccc(N)cc1
Reactant: c1ccncc1
Reactant: CC(=O)N(C)C
Agent: O=C(c1ccc2c(c1)C(=O)OC2=O)c1ccc2c(c1)C(=O)OC2=O
Solvent: O
Solvent: CC(=O)OC(C)=O
Product: CC1(C)CC(C)(c2ccc(N)cc2)c2ccc(N)cc21
Temperature: 0 °C

Procedure:
In a 500-ml four-neck flask equipped with a thermometer, a stirrer and a calcium chloride tube, 32.8 g (0.08 mole) of 2,2-bis(4-aminophenoxyphenyl)propane, 5.08 g (0.02 mole) of 3,3',5,5'-tetramethyl-4,4'-diaminodiphenylmethane and 100 g of dimethylacetamide were placed and stirred. Subsequent to dissolution of the diamine, 41.8 g (0.08 mole) of 1,10-(decamethylene)bis(trimellitate dianhydride) and 6.44 g (0.2 mole) of benzophenonetetracarboxylic dianhydride were added little by little while cooling the flask over an ice bath. Subsequent to the completion of the addition, they were reacted for 3 hours over the ice bath and further for 4 hours at room temperature. Then, 25.5 g (0.25 mole) of acetic anhydride and 19.8 g (0.25 mole) of pyridine were added, followed by stirring at room temperature for 2 hours. The reaction mixture was then poured into water. A precipitated polymer was collected by filtration and dried, whereby a polyimide resin (A3) was obtained.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[CH:12]=[CH:11][C:10]([C:13]3[N:18]=[C:17]([OH:19])[N:16]4[CH:20]=[CH:21][N:22]=[C:15]4[CH:14]=3)=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.C=O.[C:25](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>O1CCCC1.CN(C)C(=O)C.ClCCl>[CH3:25][N:1]1[CH2:2][CH2:3][CH:4]([C:7]2[CH:8]=[CH:9][C:10]([C:13]3[N:18]=[C:17]([OH:19])[N:16]4[CH:20]=[CH:21][N:22]=[C:15]4[CH:14]=3)=[CH:11][CH:12]=2)[CH2:5][CH2:6]1
Reactant: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Reactant: Oc1nc(-c2ccc(C3CCNCC3)cc2)cc2nccn12
Agent: C=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)N(C)C
Solvent: ClCCl
Solvent: C1CCOC1
Product: CN1CCC(c2ccc(-c3cc4nccn4c(O)n3)cc2)CC1
Reaction time: 0.5 h
Yield: 86.6 %

Procedure:
To a suspension of 7-(4-(piperidin-4-yl)phenyl)imidazo[1,2-c]pyrimidin-5-ol (1.03 g, 3.50 mmol) in tetrahydrofuran (35 mL) and N,N-dimethylacetamide (2.5 mL) was added formaldehyde (5.21 mL, 70.0 mmol) followed by sodium triacetoxyborohydride (3.71 g, 17.5 mmol) and the reaction was allowed proceed at ambient temperature with stirring under nitrogen for 30 minutes. Aqueous saturated sodium bicarbonate was added slowly and gas evolution was observed. To the aqueous was added dichloromethane (100 mL) and a thick white precipitate was observed. The organic was collected and a second extraction with dichloromethane yielded a homogenous milky mixture. The biphasic mixture was filtered and the solid was washed with dichloromethane and retained. The biphasic mixture was separated and the aqueous was extracted with DCM. The organic layers were combined, dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting crude material was triturated with diethyl ether and the resulting solids were collected by means of vacuum filtration. The two crops of solids were combined to afford 7-(4-(1-methylpiperidin-4-yl)phenyl)imidazo[1,2-c]pyrimidin-5-ol (0.935 g, 3.03 mmol, 86.6% yield). MS (apci) m/z=309.2 (M+H).
Reaction SMILES: [C:1]([O:5][C:6](=[O:23])[CH2:7][CH:8]([OH:22])[CH2:9][C@H:10]([OH:21])[CH2:11][O:12][C:13](=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([CH3:4])([CH3:3])[CH3:2].CO[C:26](OC)([CH3:28])[CH3:27].CC(C)=O.C1(C)C=CC(S(O)(=O)=O)=CC=1>O.C(#N)C>[C:1]([O:5][C:6](=[O:23])[CH2:7][C@H:8]1[CH2:9][C@@H:10]([CH2:11][O:12][C:13](=[O:20])[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[O:21][C:26]([CH3:28])([CH3:27])[O:22]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: COC(C)(C)OC
Reactant: CC(C)(C)OC(=O)CC(O)C[C@H](O)COC(=O)c1ccccc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CC(C)=O
Solvent: CC#N
Solvent: O
Product: CC(C)(C)OC(=O)C[C@H]1C[C@@H](COC(=O)c2ccccc2)OC(C)(C)O1
Temperature: 40 °C
Reaction time: 16 h

Procedure:
To a solution composed of 108 mg (90.2 weight %, 0.3 mmol) of the (5S)-6-benzoyloxy-3,5-dihydroxyhexanoic tert-butyl ester produced in Example 15, 62.4 mg (0.6 mmol) of 2,2-dimethoxypropane, and 5 mL of acetone was added 5.7 mg (0.03 mmol) of p-toluenesulfonic acid.1H2O, and the mixture was stirred at 40° C. for 16 hours. This reaction mixture was analyzed by high-performance liquid chromatography (column: Develosil ODS-HG-3 4.6×250 mm, product of Nomura Chemical, eluent: water/acetonitrile=50/50, flow rate: 1.0 mL/min, detector: UV 220 nm, column temperature: 40° C.). The compositional yield values were as follows.
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]=1[NH:11][CH2:10][CH2:9][CH2:8]2.[H-].[Na+].[CH2:15]([Li])CCC.CI>O1CCCC1>[CH3:15][N:11]1[C:12]2[C:7](=[CH:6][CH:5]=[CH:4][C:3]=2[CH2:2][OH:1])[CH2:8][CH2:9][CH2:10]1
Reactant: OCc1cccc2c1NCCC2
Reactant: [Li]CCCC
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CI
Product: CN1CCCc2cccc(CO)c21
Reaction time: 2 h

Procedure:
To 8-hydroxymethyl-1,2,3,4-tetrahydroquinoline (8.03 g) and sodium hydride (60% in oil) (1.97 g) was added tetrahydrofuran (100 ml) under ice-cooling and argon atmosphere, and the mixture was stirred for 2 hours at 70° to 75° C. At -70° C., n-butyllithium (20 ml) was added to the reaction mixture by use of a syringe, and 30 minutes after addition, a solution of methyl iodide (6.98 g) in tetrahydrofuran (30 ml) was added thereto, and the mixture was stirred for 20 hours at room temperature. After distilling off tetrahydrofuran, the resulting residue was extracted with chloroform, and dried over anhydrous magnesium sulfate. The solvent was distilled off, and the resulting residue was purified by silica gel column chromatography [eluent: n-hexane-ethyl acetate (4:1)]to give 1-methyl-8-hydroxymethyl-1,2,3,4-tetrahydroquinoline (5.00 g).