Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:5][C:6]([CH:8]1[CH2:12][CH2:11][CH2:10][N:9]1[C:13](=[O:30])[CH:14]([NH:19][C:20](=[O:29])[C:21]1[CH:26]=[CH:25][C:24]([NH2:27])=[C:23]([Cl:28])[CH:22]=1)[C:15]([CH3:18])([CH3:17])[CH3:16])=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[NH2:27][C:24]1[CH:25]=[CH:26][C:21]([C:20]([NH:19][CH:14]([C:15]([CH3:16])([CH3:17])[CH3:18])[C:13]([N:9]2[CH2:10][CH2:11][CH2:12][CH:8]2[C:6]([OH:7])=[O:5])=[O:30])=[O:29])=[CH:22][C:23]=1[Cl:28]
Reactant: CC(C)(C)OC(=O)C1CCCN1C(=O)C(NC(=O)c1ccc(N)c(Cl)c1)C(C)(C)C
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC(C)(C)C(NC(=O)c1ccc(N)c(Cl)c1)C(=O)N1CCCC1C(=O)O
Temperature: 25 °C
Reaction time: 3 h
Yield: 101 %

Procedure:
To a solution of 4 (15.9 g, 36.3 mmol) in CH2Cl2 (30 mL) was added TFA (trifluoroacetic acetic acid) (30 mL) and the solution stirred at room temperature for 3 hours under N2. The reaction was transferred to a beaker (1 L) and diluted with CH2Cl2 (60 mL). To the solution at 0° C. was added solid NaHCO3 (39 g, 46 mmol) and stirred for 15 minutes'before partitioning between EtOAc (300 mL) and H2O (300 mL). After extraction the aqueous layer was acidified to pH 4-5 and extracted with EtOAc. The organic layer was dried (MgSO4) and evaporated to dryness to give 5 as a white solid (14.0 g, quantitative yield): 1H-NMR (500 MHz, CDCl3) δ1.08 (s, 9H), 1.97-2.22 (m, 3H), 2.29-2.41 (m, 1H), 3.71-3.78 (m, 1H), 3.90-3.98 (m, 1H), 4.55-4.62 (m, 1H), 4.86 (d, 1H), 6.64 (d, 1H), 6.74 (d, 1H), 7.53 (d, 1H), 7.74 (s, 1H). Analytical HPLC (cyano column): 8.24 min. LC-MS (ES+) m/e=382.4 (M+H).
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([CH:9]=[CH:10][CH:11]=1)[NH2:8])([CH3:4])([CH3:3])[CH3:2].C([O:14][CH:15]=[C:16]([C:22](OCC)=O)[C:17]([O:19][CH2:20][CH3:21])=[O:18])C>C(O)C>[C:1]([C:5]1[CH:6]=[C:7]2[C:9]([C:15]([OH:14])=[C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH:22]=[N:8]2)=[CH:10][CH:11]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CCOC=C(C(=O)OCC)C(=O)OCC
Reactant: CC(C)(C)c1cccc(N)c1
Solvent: CCO
Product: CCOC(=O)c1cnc2cc(C(C)(C)C)ccc2c1O
Temperature: 25 °C

Procedure:
A mixture of 3-t-butylaniline (67.6 g.) and diethyl ethoxymethylenemalonate was heated on the steam bath for 3 hours, the ethanol formed being collected by distillation. The resulting yellow oil was dissolved in diphenyl ether (200 ml.) and added during 0.5 hour to stirred diphenyl ether (800 ml.) at 250°-260°, the ethanol formed being collected by distillation. The mixture was stirred at 250°-260° for 0.5 hour, then allowed to cool to room temperature and diluted with an equal volume of petroleum ether (b.p. 60°-80°). THe precipitate was collected by filtration to give the novel compound ethyl 7-t-butyl-4-hydroxyquinoline-3-carboxylate, m.p. 279°-281°.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][C:17]=3[O:19][C@@H:20]3[O:46][C@H:45]([CH2:47][O:48][C:49](=[O:54])[C:50]([CH3:53])([CH3:52])[CH3:51])[C@@H:37]([O:38][C:39](=[O:44])[C:40]([CH3:43])([CH3:42])[CH3:41])[C@H:29]([O:30][C:31](=[O:36])[C:32]([CH3:35])([CH3:34])[CH3:33])[C@H:21]3[O:22][C:23](=[O:28])[C:24]([CH3:27])([CH3:26])[CH3:25])[CH:12]=[CH:11]2)=[CH:4][CH:3]=1.[C:55](=O)([O-])[O-].[Cs+].[Cs+].CI>CC(C)=O>[CH3:55][O:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][C:17]=3[O:19][C@@H:20]3[O:46][C@H:45]([CH2:47][O:48][C:49](=[O:54])[C:50]([CH3:53])([CH3:52])[CH3:51])[C@@H:37]([O:38][C:39](=[O:44])[C:40]([CH3:41])([CH3:42])[CH3:43])[C@H:29]([O:30][C:31](=[O:36])[C:32]([CH3:33])([CH3:34])[CH3:35])[C@H:21]3[O:22][C:23](=[O:28])[C:24]([CH3:26])([CH3:27])[CH3:25])[CH:12]=[CH:11]2)=[CH:4][CH:3]=1
Reactant: O=C([O-])[O-]
Reactant: CC(C)(C)C(=O)OC[C@H]1O[C@@H](Oc2cccc3ccn(CCc4ccc(O)cc4)c23)[C@H](OC(=O)C(C)(C)C)[C@@H](OC(=O)C(C)(C)C)[C@@H]1OC(=O)C(C)(C)C
Agent: [Cs+]
Solvent: CC(C)=O
Solvent: CI
Product: COc1ccc(CCn2ccc3cccc(O[C@@H]4O[C@H](COC(=O)C(C)(C)C)[C@@H](OC(=O)C(C)(C)C)[C@H](OC(=O)C(C)(C)C)[C@H]4OC(=O)C(C)(C)C)c32)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 100.1 %

Procedure:
A mixture of 1-[2-(4-hydroxyphenyl)ethyl]-7-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1H-indole (50 mg), cesium carbonate (43 mg) and methyl iodide (0.008 mL) in acetone (2 mL) was stirred at room temperature overnight. The reaction mixture was purified by column chromatography on aminopropylated silica gel (eluent: n-hexane/ethyl acetate=5/1) to give 1-[2-(4-methoxyphenyl)ethyl]-7-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1H-indole (51 mg). This material was dissolved in methanol (1 mL). To the solution were added water (0.1 mL) and lithium hydroxide monohydrate (13 mg), and the mixture was stirred at room temperature overnight. The reaction mixture was purified by column chromatography on silica gel (eluent: methylene chloride/methanol=8/1) to give the title compound (19 mg).
Reaction SMILES: [CH3:1][O:2][CH2:3][C:4]1[N:5]=[C:6]([CH3:26])[NH:7][C:8](=[O:25])[C:9]=1[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[C:18]([C:23]#[N:24])=[CH:19][CH:20]=[CH:21][CH:22]=2)=[CH:13][CH:12]=1.[H-].[Na+].CN(C)C=O.Br[CH2:35][C:36]1[S:37][CH:38]=[CH:39][CH:40]=1>C(OCC)(=O)C>[CH3:1][O:2][CH2:3][C:4]1[N:5]=[C:6]([CH3:26])[N:7]([CH2:35][C:36]2[S:37][CH:38]=[CH:39][CH:40]=2)[C:8](=[O:25])[C:9]=1[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[C:18]([C:23]#[N:24])=[CH:19][CH:20]=[CH:21][CH:22]=2)=[CH:13][CH:12]=1
Reactant: COCc1nc(C)[nH]c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
Reactant: BrCc1cccs1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COCc1nc(C)n(Cc2cccs2)c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 53.2 %

Procedure:
A mixture of 4′-{[4-(methoxymethyl)-2-methyl-6-oxo-1,6-dihydropyrimidin-5-yl]methyl}biphenyl-2-carbonitrile (1 g), sodium hydride (0.17 g) and N,N-dimethylformamide (10 mL) was stirred at room temperature for 10 min, 2-(bromomethyl)thiophene (4.5 g) was added, and the mixture was stirred at room temperature for 16 hr. The reaction mixture was diluted with ethyl acetate, washed with 5% aqueous potassium hydrogen sulfate solution 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 solid (0.68 g, 53%).
Reaction SMILES: [Br:1][C:2]1[CH:18]=[CH:17][C:5]([O:6][CH2:7][CH2:8][O:9][Si:10]([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11])=[CH:4][CH:3]=1.[C:19]1([N:25]([CH2:29][CH2:30][OH:31])[CH2:26][CH2:27][OH:28])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[Si:32](Cl)([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33].N1C=CN=C1>CN(C)C=O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][CH2:7][CH2:8][O:9][Si:10]([C:13]([CH3:14])([CH3:15])[CH3:16])([CH3:11])[CH3:12])=[CH:17][CH:18]=1.[CH3:16][C:13]([Si:10]([CH3:11])([CH3:12])[O:28][CH2:27][CH2:26][N:25]([CH2:29][CH2:30][O:31][Si:32]([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)([CH3:14])[CH3:15]
Reactant: OCCN(CCO)c1ccccc1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: CC(C)(C)[Si](C)(C)OCCOc1ccc(Br)cc1
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)OCCN(CCO[Si](C)(C)C(C)(C)C)c1ccccc1
Reaction time: 8 h
Yield: 100 %

Procedure:
A procedure analogous to that used for 1a was used with the following materials: 2,2'-(phenylimino)diethanol (9.0 g, 50 mmol), t-butyldimethylsilyl chloride (18.1 g, 0.12 mol), imidazole (17.0 g, 0.25 mol), and dimethylformamide (50 mL). The reaction was stirred overnight for convenience. Workup as in 1a gave 3a as a pale oil (21.6 g, >100%). 1H NMR (CDCl3) δ7.21 (2H, d, J=8.4), 6.68 (3H, overlapping d, t), 3.77 (4H, d, J=6.6), 3.52 (4H, d, J=6.6), 0.92 (18H, s), 0.06 (12H, s). 13C NMR (CDCl3) δ147.8, 129.2, 115.7, 111.4, 60.3, 53.5, 25.9, 18.3, -5.3. FDMS (m/e) 409 (M+). It was used as 100% without purification.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]=[C:12]2[C:16](=[O:17])[C:15]3[CH:18]=[CH:19][C:20]([OH:22])=[CH:21][C:14]=3[O:13]2)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.[C:23](Cl)(=[O:26])[CH2:24][CH3:25].C(OCC)(=O)C>N1C=CC=CC=1>[CH3:10][O:9][C:7]1[CH:6]=[C:5]([CH:11]=[C:12]2[C:16](=[O:17])[C:15]3[CH:18]=[CH:19][C:20]([O:22][C:23](=[O:26])[CH2:24][CH3:25])=[CH:21][C:14]=3[O:13]2)[CH:4]=[C:3]([O:2][CH3:1])[CH:8]=1
Reactant: COc1cc(C=C2Oc3cc(O)ccc3C2=O)cc(OC)c1
Reactant: CCC(=O)Cl
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Product: CCC(=O)Oc1ccc2c(c1)OC(=Cc1cc(OC)cc(OC)c1)C2=O
Temperature: 25 °C

Procedure:
After 2-[(3,5-dimethoxyphenyl)methylene]-6-hydroxy-3(2H)-benzofuranone 0.525 g was dissolved in pyridine 5 ml, propionyl chloride 0.218 ml was added, and the mixture was refluxed for 1.5 hours. The reaction mixture was cooled to room temperature, ethyl acetate 50 ml was added, and the mixture was washed with 2N-hydrochloric acid 50 ml, saturated sodium bicarbonate solution 50 ml, and a saturated sodium chloride solution 50 ml. The ethyl acetate solution was dehydrated with anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was fractionated by silica gel column chromatography (silica gel: 50 g, eluted with solvent 500 ml of hexane:ethyl acetate=1:1) and the fraction was concentrated to dryness at a temperature of 40° C. under reduced pressure to obtain crystals. The crystals were recrystallized with ethyl acetate 5 ml/hexane 10 ml and filtered. The crystals were dried over phosphorous pentoxide at a temperature of 60° C. for five hours under reduced pressure to obtain the desired compound 275.1 mg.
Reaction SMILES: [OH:1][CH:2]([CH2:9][O:10][C:11]1[C:16]([CH3:17])=[CH:15][C:14]([C:18]2[O:19][C:20]([C:23]3[S:24][C:25]([CH2:28][CH:29]([CH3:31])[CH3:30])=[CH:26][CH:27]=3)=[N:21][N:22]=2)=[CH:13][C:12]=1[CH3:32])[CH2:3]OS(C)(=O)=O.[NH3:33]>C1COCC1.CO>[NH2:33][CH2:3][CH:2]([OH:1])[CH2:9][O:10][C:11]1[C:16]([CH3:17])=[CH:15][C:14]([C:18]2[O:19][C:20]([C:23]3[S:24][C:25]([CH2:28][CH:29]([CH3:30])[CH3:31])=[CH:26][CH:27]=3)=[N:21][N:22]=2)=[CH:13][C:12]=1[CH3:32]
Reactant: Cc1cc(-c2nnc(-c3ccc(CC(C)C)s3)o2)cc(C)c1OCC(O)COS(C)(=O)=O
Reactant: N
Solvent: C1CCOC1
Solvent: CO
Product: Cc1cc(-c2nnc(-c3ccc(CC(C)C)s3)o2)cc(C)c1OCC(O)CN

Procedure:
A solution of methanesulfonic acid 2-hydroxy-3-{4-[5-(5-isobutyl-thiophen-2-yl)-[1,3,4]oxadiazol-2-yl]-2,6-dimethyl-phenoxy}-propyl ester (220 mg, 0.458 mmol) in THF (10 mL) and 7 N NH3 in methanol (10 mL) is stirred at 65° C. for 15 h. The solvent is evaporated and the residue is separated by chromatography on prep. TLC plates with DCM containing 6% of 7 N NH3 in methanol to give 1-amino-3-{4-[5-(5-isobutyl-thiophen-2-yl)-[1,3,4]oxadiazol-2-yl]-2,6-dimethyl-phenoxy}-propan-2-ol (110 mg) as a yellow oil; LC-MS: tR=0.83 min, [M+1]+=402.48.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([O:33][CH3:34])=[C:6]([C:8]([CH3:32])([CH3:31])[CH2:9][C:10]([OH:30])([C:26]([F:29])([F:28])[F:27])[CH:11]=[N:12][C:13]2[CH:22]=[CH:21][CH:20]=[C:19]3[C:14]=2[CH:15]=[CH:16][C:17]([C:23]([NH2:25])=[O:24])=[N:18]3)[CH:7]=1.[BH4-].[Na+]>O1CCCC1CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:33][CH3:34])=[C:6]([C:8]([CH3:31])([CH3:32])[CH2:9][C:10]([OH:30])([C:26]([F:28])([F:27])[F:29])[CH2:11][NH:12][C:13]2[CH:22]=[CH:21][CH:20]=[C:19]3[C:14]=2[CH:15]=[CH:16][C:17]([C:23]([NH2:25])=[O:24])=[N:18]3)[CH:7]=1
Reactant: COc1ccc(F)cc1C(C)(C)CC(O)(C=Nc1cccc2nc(C(N)=O)ccc12)C(F)(F)F
Agent: [BH4-]
Agent: [Na+]
Solvent: OCC1CCCO1
Product: COc1ccc(F)cc1C(C)(C)CC(O)(CNc1cccc2nc(C(N)=O)ccc12)C(F)(F)F
Reaction time: 20 h

Procedure:
253 mg (0.53 mmol) of 5-[4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentylidenamino]quinoline-2-carboxylic acid amide is dissolved in 10 ml of tetrahydrofuran-methanol (50%) and mixed with 101 mg (2.65 mmol) of sodium borohydride. After 20 hours, the solvent is removed in a vacuum. The subsequent recrystallization of the residue from ethyl acetate-methanol and purification of the mother liquor that is concentrated by evaporation on silica gel with hexane-ethyl acetate (0–50%) yield 116 mg (46% of theory) of the product.
Reaction SMILES: [H-].[Na+].[OH:3][C:4]([C:7]([C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=1)=[O:8])([CH3:6])[CH3:5].CS(C)=O.[CH2:20](Br)[CH:21]=[CH2:22]>O>[OH:3][C:4]([C:7]([C:9]1[CH:10]=[CH:11][C:12]([O:15][CH2:22][CH:21]=[CH2:20])=[CH:13][CH:14]=1)=[O:8])([CH3:5])[CH3:6]
Reactant: C=CCBr
Reactant: CC(C)(O)C(=O)c1ccc(O)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: C=CCOc1ccc(C(=O)C(C)(C)O)cc1
Reaction time: 0.25 h

Procedure:
6.6 g. (0.22 mol) of sodium hydride (80% strength in paraffin oil) are added in portions to 36.0 g (0.2 mol) of 4-hydroxyphenyl 2-hydroxy-2-propyl ketone in 450 ml. of dimethyl sulfoxide under an inert gas and the mixture is stirred for 15 minutes at room temperature. 26.8 g. (0.22mol) of allyl bromide in 40 ml. of dimethyl sulfoxide are then added dropwise at 30°-40° C., and the mixture is stirred for 15 minutes. The reaction mixture is poured into 2 l of water and then extracted with methyl t-butyl ether. By removing the solvent, 41.5 g. of compound IIh are obtained.
Reaction SMILES: [NH2:1][C@@H:2]([C:5]([OH:7])=[O:6])[CH2:3][OH:4].[C:8]([O:16][CH2:17][CH2:18][O:19][C:20](ON1C(=O)CCC1=O)=[O:21])(=[O:15])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]>>[C:8]([O:16][CH2:17][CH2:18][O:19][C:20]([NH:1][C@H:2]([CH2:3][OH:4])[C:5]([OH:7])=[O:6])=[O:21])(=[O:15])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]
Reactant: N[C@H](CO)C(=O)O
Reactant: CCCCCCC(=O)OCCOC(=O)ON1C(=O)CCC1=O
Product: CCCCCCC(=O)OCCOC(=O)N[C@H](CO)C(=O)O
Yield: 55.5 %

Procedure:
Following the general procedure for the synthesis of acyloxyalkyl carbamates, D-serine (0.509 g, 4.8 mmol) and (2,5-dioxoazolidinyloxycarbonyloxy)ethyl heptanoate (1 g, 4.03 mmol) were reacted to provide 0.683 g (70% yield) of the title compound (36) as a colorless liquid after work-up and mass-guided preparative HPLC purification. 1H NMR (CDCl3, 400 MHz): δ=6.81 (q, 1H), 5.9 (t, 1H), 4.4 (br s, 1H), 4.14-3.98 (m, 2H), 2.36 (t, 2H), 1.63 (t, 2H), 1.5 (d, 3H), 1.3 (m, 6H), 0.85 (t, 3H). MS (ESI) m/z 327.97 (M+Na)+; 304.00 (M−H)−.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=3[N:12]=2)=[CH:4][CH:3]=1.[CH3:17][O-:18].[Na+].CS(C)=O>O>[CH3:17][O:18][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=3[N:12]=2)=[CH:4][CH:3]=1
Reactant: Clc1ccc(-c2nc3ccccc3o2)cc1
Reactant: C[O-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: COc1ccc(-c2nc3ccccc3o2)cc1
Yield: 88.8 %

Procedure:
A mixture of 1.15 g (5 mmoles) of 2-(p-chloro-phenyl)benzoxazole, 2.5 g of sodium methoxide and 10 ml of dimethyl sulfoxide is heated at 80° C.-90° C. under nitrogen atmosphere for one hour. The mixture is cooled and diluted with 100 ml of water. The title compound (1 g, 87 percent yield) precipitates and is recovered. It has a melting point of 99.5° C.-101.5° C.
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:17][CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:19]1[CH:20]=[CH:21][N:22]=[C:23]2[C:28]=1[N:27]=[C:26]([O:29][CH3:30])[CH:25]=[CH:24]2>>[CH2:1]([O:8][C:9]([N:11]1[CH2:17][CH2:16][CH2:15][N:14]([C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[C:26]([O:29][CH3:30])[N:27]=3)[N:22]=[CH:21][CH:20]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COc1ccc2nccc(Br)c2n1
Reactant: O=C(OCc1ccccc1)N1CCCNCC1
Product: COc1ccc2nccc(N3CCCN(C(=O)OCc4ccccc4)CC3)c2n1

Procedure:
According to procedure F and starting from [1,4]diazepane-1-carboxylic acid benzyl ester and 8-bromo-2-methoxy-[1,5]naphthyridine the title compound was isolated as a brown oil (4.18 g, 62%).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:22]([CH2:23][C:24]#[C:25][CH3:26])[C:21]3[C:20](=[O:27])[NH:19][C:18](=[O:28])[N:17]([CH3:29])[C:16]=3[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].Br[CH2:37][CH2:38][O:39]C1CCCCO1>CN(C)C=O.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([C:14]2[N:22]([CH2:23][C:24]#[C:25][CH3:26])[C:21]3[C:20](=[O:27])[N:19]([CH2:37][CH2:38][OH:39])[C:18](=[O:28])[N:17]([CH3:29])[C:16]=3[N:15]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: BrCCOC1CCCCO1
Reactant: CC#CCn1c(N2CCN(C(=O)OC(C)(C)C)CC2)nc2c1c(=O)[nH]c(=O)n2C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC#CCn1c(N2CCN(C(=O)OC(C)(C)C)CC2)nc2c1c(=O)n(CCO)c(=O)n2C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
4-[3-Methyl-7-(2-butynyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl]piperazine-1-carboxylic acid tert-butyl ester (0.30 g) and potassium carbonate (0.21 g) were dissolved in N,N-dimethylformamide (10 ml), and 2-(2-bromoethoxy)tetrahydro-2H-pyran (0.23 ml) was added thereto. After stirring at room temperature overnight, the reaction mixture was diluted with ethyl acetate, washed with water, and dried over magnesium sulfate. After removing the solvent by distillation, ethanol (10 ml) and pyridinium p-toluenesulfonate (60 mg) were added to the resulting residue, and the reaction mixture was stirred at 60° C. for 3 hours. The reaction solution was distilled. The residue was purified by silica gel column chromatography to obtain 0.14 g of the title compound from a fraction eluted with hexane-ethyl acetate (1:5).
Reaction SMILES: [CH:1]1[C:15](=[NH:16])[N:14]=[C:13]2[N:3]([C@@H:4]3[O:8][C@H:7]([CH2:9][OH:10])[C@@H:6]([OH:11])[C@@H:5]3[O:12]2)[CH:2]=1.Cl.C(N)(C)(C)C.[OH2:23]>>[CH:1]1[C:15]([NH2:16])=[N:14][C:13](=[O:12])[N:3]([C@@H:4]2[O:8][C@H:7]([CH2:9][OH:10])[C@@H:6]([OH:11])[C@@H:5]2[OH:23])[CH:2]=1
Reactant: O
Reactant: N=c1ccn2c(n1)O[C@H]1[C@H](O)[C@@H](CO)O[C@H]12
Agent: Cl
Solvent: CC(C)(C)N
Product: Nc1ccn([C@@H]2O[C@H](CO)[C@@H](O)[C@@H]2O)c(=O)n1
Temperature: 25 °C
Reaction time: 2 h
Yield: 83 %

Procedure:
2,2'-O-cyclocytidine hydrochloride (6.5 g) was dissolved in 35 mL water at 80° C. The solution was cooled to room temperature and t-butylarnine (2.8 g) was added and the mixture stirred for 2 hours. Thereafter, the solvent was evaporated under vacuum and ethanol (16 g) was added. The mixture was stirred at room temperature for 12 hours. Filtration of the resulting precipitation yielded 5 g of pure cytarabine after drying, which corresponds to a yield of 83%. The product was characterized by comparison of its melting point, and NMR and IR spectra with those previously reported for cytarabine.
Reaction SMILES: [C:1]([CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH:14]([N:16]2[CH2:21][CH2:20][O:19][CH:18]([C:22]3[N:23]=[C:24]([Cl:27])[S:25][CH:26]=3)[CH2:17]2)[CH3:15])=[CH:9][CH:8]=1)([O:3]C)=[O:2].[OH-].[Na+].Cl.C(Cl)Cl>CO>[C:1]([CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH:14]([N:16]2[CH2:21][CH2:20][O:19][CH:18]([C:22]3[N:23]=[C:24]([Cl:27])[S:25][CH:26]=3)[CH2:17]2)[CH3:15])=[CH:9][CH:8]=1)([OH:3])=[O:2]
Reactant: COC(=O)COc1ccc(CC(C)N2CCOC(c3csc(Cl)n3)C2)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CO
Product: CC(Cc1ccc(OCC(=O)O)cc1)N1CCOC(c2csc(Cl)n2)C1

Procedure:
0.55 g (0.0013 mol) of N-[2-(4-carbomethoxymethoxyphenyl)-1-methylethyl]-2-(2-chloro-thiazol-4-yl)morpholine are stirred in 4 ml of methanol and 4 ml of 1N sodium hydroxide solution at room temperature for 10 minutes. The mixture is then neutralised with 4 ml of 1N hydrochloric acid, and the product is obtained by extraction with methylene chloride.
Reaction SMILES: Br[C:2]1[N:6]([NH:7][C:8](=[O:18])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[O:15][CH2:16][CH3:17])[C:5]([CH2:19][CH2:20][CH3:21])=[N:4][C:3]=1[CH3:22].[Cu][C:24]#[N:25].N1C=CC=CC=1.[I-].[K+]>C(OCC)(=O)C>[C:24]([C:2]1[N:6]([NH:7][C:8](=[O:18])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[O:15][CH2:16][CH3:17])[C:5]([CH2:19][CH2:20][CH3:21])=[N:4][C:3]=1[CH3:22])#[N:25]
Reactant: N#C[Cu]
Reactant: CCCc1nc(C)c(Br)n1NC(=O)c1ccccc1OCC
Agent: [I-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Product: CCCc1nc(C)c(C#N)n1NC(=O)c1ccccc1OCC
Temperature: 100 °C
Reaction time: 6 h

Procedure:
N-(5-Bromo-4-methyl-2-propylimidazol-1-yl)-2-ethoxybenzamide from Example 2a (0.5 g, 1.2 mmol) and copper(I) cyanide (0.3 g, 3.5 mmol) are introduced into 12.5 ml of pyridine and heated at 100° C. for 6 hours. Potassium iodide (23 mg, 0.56 mmol) is added to the mixture, which is then stirred for a further 6 hours at 100° C. The reaction mixture is cooled to room temperature and, after addition of 50 ml of ethyl acetate, washed with dilute alkaline H2O2 solution. The aqueous phase is re-extracted with ethyl acetate, and the combined ethyl acetate phase is concentrated, finally azeotroped with toluene and again concentrated.
Reaction SMILES: FC(F)(F)C([N:5]1[CH2:11][CH:10]([CH:12]([CH3:14])[CH3:13])[C:9]2[CH:15]=[C:16]([Br:21])[C:17]([O:19][CH3:20])=[CH:18][C:8]=2[CH2:7][CH2:6]1)=O.[OH-].[Na+]>[Cl-].[Na+].O>[Br:21][C:16]1[C:17]([O:19][CH3:20])=[CH:18][C:8]2[CH2:7][CH2:6][NH:5][CH2:11][CH:10]([CH:12]([CH3:14])[CH3:13])[C:9]=2[CH:15]=1
Reactant: COc1cc2c(cc1Br)C(C(C)C)CN(C(=O)C(F)(F)F)CC2
Agent: [Cl-]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: COc1cc2c(cc1Br)C(C(C)C)CNCC2
Reaction time: 8 h
Yield: 1117.7 %

Procedure:
A solution of N-trifluoroacetyl-8-bromo-1-isopropyl-7-methoxy-2,3,4,5-tetrahydro-1H-3-benzazepine (0.013 g, 0.03 mmol) methanol (0.5 mL) was treated with 15% aqueous NaOH (0.5 mL), and stirred overnight at 20 C. The product mixture was diluted with brine (5 mL), extracted twice with EtOAc (5 mL), dried with MgSO4, and concentrated to give 0.10 g of a clear oil. 1H NMR (400 MHz, CD3OD) d 7.08 (s, 1H), 6.64 (s, 1H), 3.72 (s, 3H), 3.2-3.10 (m, 3H), 2.7-2.5 (m, 3H), (m, 2H), 0.96 (d, 3H), 0.63 (d, 3H). MS calculated for C14H20BrNO+H: 298, observed: 298.
Reaction SMILES: [CH3:1][CH:2]1[C:6](=[O:7])[C:5]([OH:8])=[C:4]([CH3:9])[O:3]1.[CH2:10]=[O:11].C(O)(=O)C(O)=O>O>[OH:11][CH2:10][C:4]1([CH3:9])[C:5](=[O:8])[C:6]([OH:7])=[C:2]([CH3:1])[O:3]1
Reactant: C=O
Reactant: CC1=C(O)C(=O)C(C)O1
Agent: O=C(O)C(=O)O
Solvent: O
Product: CC1=C(O)C(=O)C(C)(CO)O1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A mixture of 10 g of 2,5-dimethyl-4-hydroxy-3-(2H)-furanone, 20 ml of a 37% formaldehyde aqueous solution, 50 ml of water and 0.7 g of oxalic acid was stirred for 18 hours at room temperature. After working up the reaction mixture, the crude reaction product was purified by column chromatography over polyamide. Elution with pentane-dichloromethane 80/20 yielded the pure 2-hydroxymethyl-2,5-dimethyl-4-hydroxy-3-(2H)-furanone, which was recrystallized from ethyllactate m.p. 124°-125° C.