Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:12][C@H:11]([CH2:13][NH:14][C:15](=[O:17])[CH3:16])[O:10][C:9]2=[O:18])=[CH:4][C:3]=1[F:19].[N:20]([O-])=O.[Na+].Cl[Sn]Cl>CO.O.Cl>[F:19][C:3]1[CH:4]=[C:5]([N:8]2[CH2:12][C@H:11]([CH2:13][NH:14][C:15](=[O:17])[CH3:16])[O:10][C:9]2=[O:18])[CH:6]=[CH:7][C:2]=1[NH:1][NH2:20]
Reactant: O=N[O-]
Reactant: CC(=O)NC[C@H]1CN(c2ccc(N)c(F)c2)C(=O)O1
Agent: Cl
Agent: Cl[Sn]Cl
Agent: [Na+]
Solvent: CO
Solvent: O
Product: CC(=O)NC[C@H]1CN(c2ccc(NN)c(F)c2)C(=O)O1
Temperature: 25 °C
Yield: 70 %

Procedure:
3 g (11.22 mmol) of (S)—N-((3-(4-amino-3-fluorophenyl)-2-oxooxazolidin-5-yl) methyl)acetamide (7) was dissolved in a blend of 6 mL methanol, 12 mL water and 3 mL concentrated hydrochloric acid. The resultant mixture was stirred for 10 minutes in an ice-salt bath to maintain the internal temperature below −5° C. Then, a NaNO2 solution prepared in advance was slowly dropped into the mixture. After completion of the addition, the mixture was stirred in the ice-salt bath for another 30 minutes to prepare a reaction solution of diazonium salt. Meanwhile, 6.08 g of SnCl2 was dissolved in a concentrated hydrochloric acid under vigorous stirring in an ice-salt bath. The reaction solution of diazonium salt prepared above was slowly dropped into the SnCl2 solution in hydrochloric acid, and then the mixture was warmed naturally to room temperature and stirred for another 2 hours. After completion of the reaction, the reactant was buffered to a pH between 7 and 8 with 1 ON NaOH solution. After the solvent was evaporated in a rotary evaporator, the resultant material was repeatedly grinded with methanol. After the solvent methanol was rotary evaporated, the residue was recrystallized with ethanol and then filtered to afford a light yellow crystalline solid weighed 2.2 g, with a yield of 70%. The product was kept under low temperature and in a dry place.
Reaction SMILES: Br[CH2:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[C:6]#[N:7].BrCC1CCCCO1.[NH:19]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C@@:21]2([C:39]3[C:30](=[CH:31][C:32]4[O:37][CH2:36][CH2:35][O:34][C:33]=4[CH:38]=3)[O:29][CH2:28]2)[C:20]1=[O:40].N1C2C(=CC=CC=2)C2(COC3C=C4C(=CC2=3)CCO4)C1=O>>[O:40]=[C:20]1[C@:21]2([C:39]3[C:30](=[CH:31][C:32]4[O:37][CH2:36][CH2:35][O:34][C:33]=4[CH:38]=3)[O:29][CH2:28]2)[C:22]2[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=2)[N:19]1[CH2:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[C:6]#[N:7]
Reactant: N#Cc1cccc(CBr)c1
Reactant: O=C1Nc2ccccc2[C@]12COc1cc3c(cc12)OCCO3
Agent: BrCC1CCCCO1
Agent: O=C1Nc2ccccc2C12COc1cc3c(cc12)CCO3
Product: N#Cc1cccc(CN2C(=O)[C@@]3(COc4cc5c(cc43)OCCO5)c3ccccc32)c1

Procedure:
Following the procedure as described in EXAMPLE 4 and making non-critical variations using 3-(bromomethyl)benzonitrile to replace 2-(bromomethyl)tetrahydro-2H-pyran, and (8S)-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one to replace 5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2′(1′H)-one, 3-{[(8S)-2′-oxo-2,3-dihydrospiro[furo[2,3-g][1,4]-benzodioxine-8,3′-indol]-1′(2′H)-yl]methyl}benzonitrile was obtained (75%) as a colorless solid: mp 94-96° C. (isopropyl alcohol); 1H NMR (300 MHz, CDCl3) δ 7.65-7.52 (m, 4H), 7.49-7.42 (m, 2H), 7.23-7.15 (m, 1H), 7.08-7.01 (m, 1H), 6.75-6.70 (m, 1H), 6.49 (s, 1H), 6.18 (s, 1H), 5.03 (d, J=15.8 Hz, 1H), 4.95-4.84 (m, 2H), 4.66 (d, J=9.0 Hz, 1H), 4.20-4.07 (m, 3H); 13C NMR (75 MHz, CDCl3) δ 177.6, 155.3, 144.8, 141.5, 138.4, 137.4, 132.1, 131.8, 130.9, 129.9, 129.0, 124.3, 123.9, 120.7, 118.4, 113.1, 111.4, 108.8, 99.5, 80.1, 64.5, 63.9, 58.0, 43.4, 29.7; MS (ES+) m/z 411.0 (M+1). Anal. Calcd. for C25H18N2O4: C, 73.16; H, 4.42; N, 6.83. Found: C, 72.92; H, 5.05; N, 6.50.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[NH:9][C:10]([NH:20][O:21][CH:22]1[CH2:27][CH2:26][CH2:25][CH2:24][O:23]1)=[N:11]C(=O)C1C=CC=CC=1.[OH-].[Na+]>O.C(O)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[NH:9][C:10]([NH2:11])=[N:20][O:21][CH:22]1[CH2:27][CH2:26][CH2:25][CH2:24][O:23]1
Reactant: O=C(N=C(NOC1CCCCO1)Nc1c(Cl)cccc1Cl)c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: NC(=NOC1CCCCO1)Nc1c(Cl)cccc1Cl
Yield: 87.5 %

Procedure:
38.5 g 1-(2,6-dichlorophenyl)-2-benzoyl-3-tetrahydropyranyloxyguanidine are heated to a boil with 900 ml 5% NaOH (in a mixture water/ethanol 1:1) for 2 hours. After cooling, 25.1 g 1-(2,6-dichlorophenyl)-2-tetrahydropyranyloxyguanidine having a melting point of 178°-180° C. is obtained.
Reaction SMILES: COC(=O)C(OCC)CC1C2SC=CC=2C(O)=CC=1.[CH2:20]([O:22][C:23]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:24]=1[C:30]1[O:31]C(C)=C(CCO)N=1)[CH3:21].C(I)C.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH2:20]([O:22][C:23]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:24]=1[CH:30]=[O:31])[CH3:21]
Reactant: CCOc1cc(F)ccc1-c1nc(CCO)c(C)o1
Agent: CCOC(Cc1ccc(O)c2ccsc12)C(=O)OC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCI
Product: CCOc1cc(F)ccc1C=O

Procedure:
In analogy to the procedure described in example 17 a], [rac]-2-ethoxy-3-(4-hydroxy-benzo[b]thiophen-7-yl)-propionic acid methyl ester was reacted with 2-[2-(2-ethoxy-4-fluoro-phenyl)-5-methyl-oxazol-4-yl]-ethanol (prepared from 4-fluoro-2-hydroxy-benzaldehyde [J. Chem. Soc., Perkin Trans. 1 (1994), (13), 1823-31] by i) treatment with ethyl iodide, potassium carbonate in N,N-dimethylformamide to give 2-ethoxy-4-fluoro-benzaldehyde; ii) conversion of the 2-ethoxy-4-fluoro-benzaldehyde into 2-[2-(2-ethoxy-4-fluoro-phenyl)-5-methyl-oxazol-4-yl]-ethanol in analogy to the sequence described in examples 21 a] to 21 e]) in the presence of triphenylphosphine and DEAD (diethyl azodicarboxylate) to yield [rac]-2-ethoxy-3-(4-{2-[2-(2-ethoxy-4-fluoro-phenyl)-5-methyl-oxazol-4-yl]-ethoxy}-benzo[b]thiophen-7-yl)-propionic acid methyl ester, which was further saponified in analogy to the procedure described in example 91 e] to yield [rac]-2-ethoxy-3-(4-{2-[2-(2-ethoxy-4-fluoro-phenyl)-5-methyl-oxazol-4-yl]-ethoxy-}-benzo[b]thiophen-7-yl)-propionic acid as light yellow solid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N+:4]([O-:32])[CH:5]=[C:6]([Cl:31])[C:7]=1[CH2:8][C@@H:9]([C:16]1[CH:21]=[CH:20][C:19]([O:22][CH:23]([F:25])[F:24])=[C:18]([O:26][CH2:27][CH:28]2[CH2:30][CH2:29]2)[CH:17]=1)[O:10][C:11](=[O:15])[CH2:12][CH2:13][OH:14].[C:33]([O:37][C:38]([N:40]([C:45]1[CH:53]=[CH:52][C:48]([C:49](O)=[O:50])=[CH:47][C:46]=1[O:54][CH2:55][CH:56]1[CH2:58][CH2:57]1)[S:41]([CH3:44])(=[O:43])=[O:42])=[O:39])([CH3:36])([CH3:35])[CH3:34].C(Cl)CCl>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:33]([O:37][C:38]([N:40]([C:45]1[CH:53]=[CH:52][C:48]([C:49]([O:14][CH2:13][CH2:12][C:11]([O:10][C@H:9]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH:23]([F:25])[F:24])=[C:18]([O:26][CH2:27][CH:28]3[CH2:30][CH2:29]3)[CH:17]=2)[CH2:8][C:7]2[C:2]([Cl:1])=[CH:3][N+:4]([O-:32])=[CH:5][C:6]=2[Cl:31])=[O:15])=[O:50])=[CH:47][C:46]=1[O:54][CH2:55][CH:56]1[CH2:57][CH2:58]1)[S:41]([CH3:44])(=[O:43])=[O:42])=[O:39])([CH3:36])([CH3:34])[CH3:35]
Reactant: O=C(CCO)O[C@@H](Cc1c(Cl)c[n+]([O-])cc1Cl)c1ccc(OC(F)F)c(OCC2CC2)c1
Reactant: CC(C)(C)OC(=O)N(c1ccc(C(=O)O)cc1OCC1CC1)S(C)(=O)=O
Agent: CN(C)c1ccncc1
Solvent: ClCCCl
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N(c1ccc(C(=O)OCCC(=O)O[C@@H](Cc2c(Cl)c[n+]([O-])cc2Cl)c2ccc(OC(F)F)c(OCC3CC3)c2)cc1OCC1CC1)S(C)(=O)=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 82.8 %

Procedure:
To a solution of (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-hydroxypropanoyloxy)ethyl)pyridine 1-oxide (0.311 g, 0.632 mmol), 4-(N-(tert-butoxycarbonyl)methylsulfonamido)-3-(cyclopropylmethoxy)benzoic acid (0.243 g, 0.632 mmol), and EDC (0.363 g, 1.895 mmol) in dry DCM (15 ml), DMAP (0.077 g, 0.632 mmol) was added and the resulting mixture was stirred at RT for 3 hours. The solvent was evaporated, and the residue was partitioned between EtOAc and a NaHCO3 sat. sol. The organic layer was washed with brine and dried over Na2SO4. The solvent was removed and the residue was purified by flash chromatography on silica gel column (DCM:MeOH:32% NH4OH=95:5:0.5) affording (S)-4-(2-(3-(4-(N-(tert-butoxycarbonyl)-methylsulfonamido)-3-(cyclopropylmethoxy)benzoyloxy)propanoyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (0.450 g, 0.523 mmol, 83% yield, MS/ESI+ 859.0 [MH]+).
Reaction SMILES: [NH2:1][C:2]1[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[Cl:13])=[O:5].[Cl:19][CH2:20][C:21](Cl)=O>C(O)(=O)C>[Cl:18][C:14]1[CH:15]=[CH:16][CH:17]=[C:2]2[C:3]=1[C:4](=[O:5])[N:6]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[Cl:13])[C:21]([CH2:20][Cl:19])=[N:1]2
Reactant: O=C(Cl)CCl
Reactant: Nc1cccc(Cl)c1C(=O)Nc1ccccc1Cl
Solvent: CC(=O)O
Product: O=c1c2c(Cl)cccc2nc(CCl)n1-c1ccccc1Cl
Yield: 65.4 %

Procedure:
Prepared according to Procedure B with 1f (1.00 g, 3.56 mmol) and chloroacetyl chloride (0.85 mL, 10.7 mmol) in acetic acid (15 mL). Purified by recrystallization from isopropanol to afford 791 mg of an off-white crystalline solid (65%). 1H NMR (CDCl3) δ: 7.70 (s, 1H); 7.68 (d, J=3.8 Hz, 1H); 7.61-7.65 (m, 1H); 7.55 (dd, J=2.7, 6.4 Hz, 1H); 7.51 (d, J=3.1 Hz, 1H); 7.50 (s, 2H); 4.35 (d, J=12 Hz, 1H), 4.05 (d, J=12 Hz, 1H). MS (ES): m/z 339.0 (M+).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C@@:8]([C@@H:11]2[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]2)([OH:10])[CH3:9])[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].I[CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C@@:8]([C@@H:11]2[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]2)([O:10][CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH3:9])[CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)N1CCC[C@@H]([C@@](C)(O)c2cccc(Cl)c2)C1
Reactant: CCOC(=O)CI
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOC(=O)CO[C@@](C)(c1cccc(Cl)c1)[C@@H]1CCCN(C(=O)OC(C)(C)C)C1
Temperature: 90 °C
Yield: 14.1 %

Procedure:
A mixture of (R)-tert-butyl 3-((R)-1-(3-chlorophenyl)-1-hydroxyethyl)piperidine-1-carboxylate (0.4395 g, 1.29 mmol), 60% NaH (1.320 g, 33 mmol), and ethyl iodoacetate (5.237 g, 24.5 mmol) in THF (20 mL) was heated at 90° C. for 18 h and then cooled to rt. The reaction mixture was then quenched with saturated brine and extracted with ethyl acetate (3×), dried over Na2SO4. After the solvent was evaporated under reduced pressure, the crude product was purified by reversed-phase HPLC to afford 0.0775 g (14%) of (R)-tert-butyl 3-((R)-1-(3-chlorophenyl)-1-(2-ethoxy-2-oxoethoxy)ethyl)piperidine-1-carboxylate. MS ESI +ve m/z 450 (M+Na).
Reaction SMILES: [Cl:1][C:2]1[C:3]2[C@H:10]([CH3:11])[CH2:9][CH2:8][C:4]=2[N:5]=[CH:6][N:7]=1.C1C=C(Cl)C=C(C(OO)=[O:20])C=1.[O-]S([O-])(=S)=O.[Na+].[Na+].C([O-])([O-])=O.[Na+].[Na+]>C(Cl)(Cl)Cl.O>[Cl:1][C:2]1[N:7]=[CH:6][N+:5]([O-:20])=[C:4]2[CH2:8][CH2:9][C@@H:10]([CH3:11])[C:3]=12
Reactant: C[C@@H]1CCc2ncnc(Cl)c21
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])[O-]
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: O
Solvent: ClC(Cl)Cl
Product: C[C@@H]1CCc2c1c(Cl)nc[n+]2[O-]
Temperature: 25 °C
Reaction time: 48 h
Yield: 53.1 %

Procedure:
To a solution of (R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine (2.5 g, 14.8 mmol) in CHCl3 (60 mL) was added MCPBA (8.30 g, 37.0 mmol) in three portions. The mixture was stirred at room temperature for 2 days. The mixture was cooled to 0° C. and to this was added dropwise Na2S2O3 (10 g) in water (60 mL), followed by Na2CO3 (6 g) in water (20 mL). The reaction mixture was stirred for 20 minutes. The aqueous phase was extracted with CHCl3 (2×200 mL), and the combined organic phases were concentrated at low temperature (<25° C.). The residue was purified by silica gel chromatography, eluting with ethyl acetate-DCM/MeOH (20:1) to give (R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-oxide (1.45 g, 53%). 1H NMR (CDCl3, 400 MHz) δ 8.66 (s, 1H), 3.50 (m, 1H), 3.20 (m, 2H), 2.44 (m, 1H), 1.90 (m, 1H), 1.37 (d, J=7.2 Hz, 3H).
Reaction SMILES: [CH2:1]([N:4]1[C:9](=[O:10])[NH:8][C:7](=[O:11])[CH:6]=[N:5]1)[C:2]#[CH:3].[CH2:12]=[O:13]>CN(C)C=O>[CH2:1]([N:4]1[C:9](=[O:10])[N:8]([CH2:12][OH:13])[C:7](=[O:11])[CH:6]=[N:5]1)[C:2]#[CH:3]
Reactant: C#CCn1ncc(=O)[nH]c1=O
Reactant: C=O
Solvent: CN(C)C=O
Product: C#CCn1ncc(=O)n(CO)c1=O
Yield: 67.8 %

Procedure:
A mixture of 0.76 g 2-propargyl-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine, 15 ml 37% aqueous formalin and 7.5 ml dimethylformamide was heated under reflux for 1.5 hours. The solvent was removed under reduced pressure to obtain a white semi-solid. This semi-solid was purified by chromatography on silica gel using a chloroform/methyl alcohol (75:1) mixed solvent to obtain 0.61 g of a white semi-crystalline product.
Reaction SMILES: C([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:13]([O:15][CH3:16])=[O:14])[CH:11]=2)[C:6](=[C:17](OCC)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:5]1=[O:27])(=O)C.[CH3:28][N:29]([CH3:49])[CH2:30][CH2:31][C:32]([N:34]([CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[C:35]1[CH:40]=[CH:39][C:38]([NH2:41])=[CH:37][CH:36]=1)=[O:33]>>[CH3:49][N:29]([CH3:28])[CH2:30][CH2:31][C:32]([N:34]([C:35]1[CH:36]=[CH:37][C:38]([NH:41]/[C:17](=[C:6]2\[C:5](=[O:27])[NH:4][C:8]3[C:7]\2=[CH:12][CH:11]=[C:10]([C:13]([O:15][CH3:16])=[O:14])[CH:9]=3)/[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:39][CH:40]=1)[CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)=[O:33]
Reactant: CN(C)CCC(=O)N(Cc1ccccc1)c1ccc(N)cc1
Reactant: CCOC(=C1C(=O)N(C(C)=O)c2cc(C(=O)OC)ccc21)c1ccccc1
Product: COC(=O)c1ccc2c(c1)NC(=O)/C2=C(\Nc1ccc(N(Cc2ccccc2)C(=O)CCN(C)C)cc1)c1ccccc1

Procedure:
Prepared from 1-acetyl-3-(1-ethoxy-1-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-((2-dimethylamino-ethyl)-carbonyl)-N-benzyl-p-phenylenediamine Rf value: 0.1 (silica gel, methylene chloride/methanol=10:1) C31H34N4O4
Reaction SMILES: C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)[NH:8][CH2:9][CH2:10][S:11][C:12]([O:14]C2C=CC([N+]([O-])=O)=CC=2)=O)C=CC=CC=1.[CH2:36]([NH2:40])[CH:37]([CH3:39])[CH3:38]>>[CH2:36]([NH:40][C:12]([S:11][CH2:10][CH2:9][NH2:8])=[O:14])[CH:37]([CH3:39])[CH3:38]
Reactant: O=C(Oc1ccc([N+](=O)[O-])cc1)SCCNC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CC(C)CN
Product: CC(C)CNC(=O)SCCN

Procedure:
N-triphenylmethyl-2-paranitrophenoxycarbonylthioethylamine (300 mg) and isobutylamine (185 μl) were subjected to similar reactions to those described in References 2 and 4 to give 2-isobutylaminocarbonylthioethylamine (crude formate: 256 mg) which was then dissolved in anhydrous methanol (5 ml). Triethylamine (376 μl) and mitomycin A (151 mg: 0.8 molar equivalent) were added to the solution. The reaction solution was treated in a similar manner to that described in Example 1 to obtain Compound 24 (71 mg) in the form of grayish blue powders with a yield of 33%.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][S:18]([CH3:21])(=[O:20])=[O:19])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[OH:22][C:23]1[CH:31]=[C:30]2[C:26]([CH:27]=[CH:28][NH:29]2)=[CH:25][CH:24]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[NH:29]1[C:30]2[C:26](=[CH:25][CH:24]=[C:23]([O:22][C:2]3[C:11]4[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][S:18]([CH3:21])(=[O:20])=[O:19])=[C:9]([O:12][CH3:13])[CH:10]=4)[N:5]=[CH:4][N:3]=3)[CH:31]=2)[CH:27]=[CH:28]1
Reactant: COc1cc2c(Cl)ncnc2cc1OCCCS(C)(=O)=O
Reactant: Oc1ccc2cc[nH]c2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1cc2c(Oc3ccc4cc[nH]c4c3)ncnc2cc1OCCCS(C)(=O)=O
Temperature: 90 °C
Yield: 50.7 %

Procedure:
A solution of 4-chloro-6-methoxy-7-(3-methylsulphonylpropoxy)quinazoline (200 mg, 0.6 mmol), (prepared as described for the starting material in Example 50), and 6hydroxyindole (97 mg, 0.73 mmol) in DMF (3 ml) containing potassium carbonate (125 mg, 0.91 mmol) was heated at 90° C. for 2.5 hours. After cooling, water was added. The precipitate was filtered, washed with water and dried under vacuum. The residue was triturated with ether, filtered, washed with ether and dried under vacuum to give 4-(indol-6-yloxy)-6-methoxy-7-(3-methylsulphonylpropoxy)quinazoline (130 mg, 50%).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([Br:9])=[CH:4][C:3]=1[OH:10].[Yb+3].FC(F)(F)S([O-])(=O)=O.FC(F)(F)S([O-])(=O)=O.FC(F)(F)S([O-])(=O)=O.[C:36](OC)(OC)(OC)[CH3:37]>CCO.CC(=O)OCC>[Br:9][C:5]1[C:6]([CH3:8])=[CH:7][C:2]2[N:1]=[C:36]([CH3:37])[O:10][C:3]=2[CH:4]=1
Reactant: Cc1cc(N)c(O)cc1Br
Reactant: COC(C)(OC)OC
Agent: O=S(=O)([O-])C(F)(F)F
Agent: [Yb+3]
Solvent: CCO
Solvent: CCOC(C)=O
Product: Cc1nc2cc(C)c(Br)cc2o1
Temperature: 90 °C

Procedure:
A mixture of 2-amino-5-bromo-4-methylphenol (42) (290 mg), trifluoromethanesulfonic acid Ytterbium (III) salt (20 mg, 1% mol) and trimethyl orthoacetate (216 μl, 1.5 eq.) in 2 ml EtOH was heated at 90° C. for 2 h. After cooling down to r.t., the reaction mixture was taken up in EA, washed with aq. NaHCO3 and brine, dried over Na2SO4, concentrated to dryness. The resulting brown solid was dissolved in DCM and subjected to silica gel column purification using 0-60% B (A: hexane; B: 50% EA in hexane) to furnish 148 mg 6-bromo-2,5-dimethylbenzoxazole (48) as pale brown solid.
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[C:12]2[C:7]([CH2:8][CH2:9][C:10](=[O:14])[NH:11]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].Br[CH2:16][CH2:17][O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CN(C=O)C.O>[Si:19]([O:18][CH2:17][CH2:16][N:11]1[C:12]2[C:7](=[CH:6][CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[CH:13]=2)[CH2:8][CH2:9][C:10]1=[O:14])([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20]
Reactant: O=C1CCc2ccc([N+](=O)[O-])cc2N1
Reactant: CC(C)(C)[Si](C)(C)OCCBr
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)OCCN1C(=O)CCc2ccc([N+](=O)[O-])cc21
Temperature: 25 °C
Reaction time: 48 h

Procedure:
7-Nitro-3,4-dihydroquinolin-2(1H)-one, (2-bromoethoxy)(tert-butyl)dimethylsilane, potassium carbonate, potassium iodide and water were added to DMF, followed by stirring at room temperature for 2 days and then stirred at 40° C. for 3 days. By post-treating the reaction liquid, 1-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-7-nitro-3,4-dihydroquinolin-2(1H)-one was obtained.
Reaction SMILES: [H-].[Na+].[CH:3]1[C:16]2[C:15](=[O:17])[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[NH:8][C:7]=2[CH:6]=[CH:5][CH:4]=1.[CH2:18]([O:20][CH:21]([O:26][CH2:27][CH3:28])[CH2:22][CH2:23][CH2:24]Cl)[CH3:19].O>CN(C)C=O>[CH2:18]([O:20][CH:21]([O:26][CH2:27][CH3:28])[CH2:22][CH2:23][CH2:24][N:8]1[C:7]2[C:16](=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:15](=[O:17])[C:14]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]1=2)[CH3:19]
Reactant: O=c1c2ccccc2[nH]c2ccccc12
Reactant: CCOC(CCCCl)OCC
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(CCCn1c2ccccc2c(=O)c2ccccc21)OCC
Reaction time: 2 h

Procedure:
A suspension of 1.44 g of sodium hydride in 100 ml of dimethylformamide is treated within 10 minutes with 9.75 g of 9-acridanone and held at 50° for 2 hours. At 120° there are then added 9.5 g of 4,4-diethoxybutyl chloride. After 16 hours, the mixture is cooled, poured into water and extracted with dichloromethane. The extract is dried over sodium sulfate and evaporated. The residue is extracted with hexane and crystallized twice from hexane. There is obtained 10-(4,4-diethoxybutyl)-9-acridanone of metling point 73°-74.5°.
Reaction SMILES: [CH3:1][S:2]([O:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH2:12][CH2:13]CS([O-])(=O)=O)(=[O:4])=[O:3].[CH3:19][N:20]1[C:25]([N:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)=[CH:24][C:23](=[O:32])[N:22]([CH3:33])[C:21]1=[O:34]>C(Cl)(Cl)Cl>[CH3:19][N:20]1[C:25]([N:26]2[CH2:31][CH2:30][N:29]([CH2:13][CH2:12][C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=3[O:5][S:2]([CH3:1])(=[O:3])=[O:4])[CH2:28][CH2:27]2)=[CH:24][C:23](=[O:32])[N:22]([CH3:33])[C:21]1=[O:34]
Reactant: CS(=O)(=O)Oc1ccccc1CCCS(=O)(=O)[O-]
Reactant: Cn1c(N2CCNCC2)cc(=O)n(C)c1=O
Solvent: ClC(Cl)Cl
Product: Cn1c(N2CCN(CCc3ccccc3OS(C)(=O)=O)CC2)cc(=O)n(C)c1=O
Temperature: 90 °C
Reaction time: 2 h
Yield: 163.3 %

Procedure:
A mixture of 1 g of 2-(2-methanesulfonyloxyphenyl)ethylmethane sulfonate and 0.65 g of 1,3-dimethyl-6-(piperazin-1-yl)-2,4(1H,3H)-pyrimidinedione was stirred at 90° C. for 2 hours and then allowed to stand for cooling. The resultant reaction mixture was dissolved in 50 ml of chloroform, and then washed with 10 ml of a 1N aqueous sodium hydroxide solution. The chloroform layer was washed with water, dried over anhydrous sodium sulfate and then concentrated under reduced pressure, and the residue was purified through a silica gel column chromatograph (chloroform/methanol=40/1 in volume ratio), thereby obtaining 2.0 g of 1,3-dimethyl-6-[4-(2-[2-methanesulfonyloxyphenyl]ethyl)piperazin-1-yl]-2,4(1H,3H)-pyrimidinedione.
Reaction SMILES: [OH-:1].[Na+:2].[C:3]1([C:9]2[NH:10][CH:11]=[C:12]([CH2:14][C:15]([OH:24])([P:20]([OH:23])(=[O:22])[OH:21])[P:16]([OH:19])(=[O:18])[OH:17])[N:13]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1>O>[OH2:17].[OH2:1].[C:3]1([C:9]2[NH:10][CH:11]=[C:12]([CH2:14][C:15]([OH:24])([P:20]([OH:22])(=[O:21])[OH:23])[P:16]([O-:19])(=[O:17])[O-:18])[N:13]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Na+:2].[Na+:2]
Reactant: O=P(O)(O)C(O)(Cc1c[nH]c(-c2ccccc2)n1)P(=O)(O)O
Reactant: [OH-]
Agent: [Na+]
Solvent: O
Product: O=P([O-])([O-])C(O)(Cc1c[nH]c(-c2ccccc2)n1)P(=O)(O)O

Procedure:
10 ml of 2N aqueous sodium hydroxide solution are added, with stirring, to a suspension of 3,36 g of 2-(2-phenylimidazol-4-yl)-1-hydroxy-ethane-1,1-diphosphonic acid in 10 ml of water. The resulting solution is evaporated to dryness. The residue is triturated with 40 ml of methanol. The crystalline precipitate formed is filtered off and dried yielding disodium 2-(2-phenylimidazol-4-yl)-1-hydroxyethane-1,1-diphosphonate-dihydrate m.p. 281°-283° C. (dec.).
Reaction SMILES: [CH:1]1[C:6]([CH2:7][CH2:8][OH:9])=[CH:5][CH:4]=[C:3]([OH:10])[CH:2]=1.N1C=CC=CC=1.ClC(Cl)([O:20][C:21](=[O:27])[O:22]C(Cl)(Cl)Cl)Cl.Cl>C(Cl)Cl>[CH:1]1[C:6]([CH2:7][CH2:8][OH:9])=[CH:5][CH:4]=[C:3]([OH:10])[CH:2]=1.[C:21](=[O:20])([O-:27])[O-:22]
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Agent: Cl
Agent: OCCc1ccc(O)cc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: O=C([O-])[O-]
Reaction time: 0.25 h

Procedure:
In a 250 mL 3-necked round-bottomed flask equipped with a mechanical stirrer, and a liquid addition device were placed 10 g (0.073 mol) of tyrosol, 22 ml (0.277 mol) of pyridine, 60 mL of DCM and stirred for 15 min to get a clear solution. Triphosgene (7.0 g, 0.071 mol of phosgene) was dissolved in 25 mL of DCM and the solution was introduced into the reaction flask over 2-3 hours. After the addition was complete, the 100 mL of 0.2 M aqueous HCl was added to the reaction mixture and stirred for 5 min. After allowing the layers to separate, the top aqueous layer was removed and discarded. The washing was repeated with three additional 100 portions of 0.2 M aqueous HCl. The reaction mixture was then dried over anhydrous magnesium sulfate and then precipitated with 100 mL of hexane. The resulting viscous oil was stirred with 200 mL of fresh hexane until the product solidified into a white solid. The product was transferred to a glass dish dried in a vacuum oven at 60° C. The polymer had a HPSEC polystyrene equivalent Mw of 7500 da and Mn of 5700 da (THF as mobile phase) and glass transition temperature (Tg) of 48° C. A number of oligomers and polymers ranging in Mw from 750 da to 40,000 da were prepared using this method.