Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]=[C:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH2:7][C:8]([O:10]CC)=O.[CH2:13]([N:17]([CH2:21][CH:22]([CH3:24])[CH3:23])[CH2:18][CH2:19][NH2:20])[CH:14]([CH3:16])[CH3:15]>>[CH3:15][CH:14]([CH3:16])[CH2:13][N:17]([CH2:21][CH:22]([CH3:24])[CH3:23])[CH2:18][CH2:19][NH:20][C:8](=[O:10])[CH2:7][N:3]1[CH2:4][CH2:5][CH2:6][C:2]1=[O:1]
Reactant: CC(C)CN(CCN)CC(C)C
Reactant: CCOC(=O)CN1CCCC1=O
Product: CC(C)CN(CCNC(=O)CN1CCCC1=O)CC(C)C

Procedure:
From 8.5 g. of ethyl 2-oxo-1-pyrrolidineacetate and 12.9 g. of 2-(diisobutylamino)ethylamine (British Pat. No. 614,164), following the procedure of Example 1, there is obtained N-[2-[bis(2-methylpropyl)amino]ethyl]-2-oxo-1-pyrrolidineacetamide; b.p. 155°-160° C./0.1 mm.
Reaction SMILES: [CH2:1]([O:8][C@@H:9]1[CH2:14][CH2:13][CH2:12][C@H:11]([O:15][C:16]2[C:21]([F:22])=[CH:20][C:19]([S:23]([N:26](CC3C=CC(OC)=CC=3OC)[C:27]3[CH:32]=[CH:31][N:30]=[CH:29][N:28]=3)(=[O:25])=[O:24])=[C:18]([F:44])[CH:17]=2)[C@H:10]1[C:45]1[N:49]([CH3:50])[N:48]=[CH:47][CH:46]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>ClCCl>[CH2:1]([O:8][C@@H:9]1[CH2:14][CH2:13][CH2:12][C@H:11]([O:15][C:16]2[C:21]([F:22])=[CH:20][C:19]([S:23]([NH:26][C:27]3[CH:32]=[CH:31][N:30]=[CH:29][N:28]=3)(=[O:24])=[O:25])=[C:18]([F:44])[CH:17]=2)[C@H:10]1[C:45]1[N:49]([CH3:50])[N:48]=[CH:47][CH:46]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COc1ccc(CN(c2ccncn2)S(=O)(=O)c2cc(F)c(O[C@H]3CCC[C@@H](OCc4ccccc4)[C@@H]3c3ccnn3C)cc2F)c(OC)c1
Agent: CC[SiH](CC)CC
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cn1nccc1[C@@H]1[C@@H](Oc2cc(F)c(S(=O)(=O)Nc3ccncn3)cc2F)CCC[C@H]1OCc1ccccc1
Yield: 96.9 %

Procedure:
The reaction and aftertreatment were conducted in the same manner as in Example 1b by using the 4-{[(1S*,2S*,3R*)-3-(benzyloxy)-2-(1-methyl-1H-pyrazol-5-yl)cyclohexyl]oxy}-N-(2,4-dimethoxybenzyl)-2,5-difluoro-N-(pyrimidin-4-yl)benzenesulfonamide (185 mg, 0.262 mmol) prepared in Example 100d, triethylsilane (0.30 mL), trifluoroacetic acid (3.0 mL) and dichloromethane (3.0 mL), to yield the title compound (141 mg, 97%) as a colorless solid.
Reaction SMILES: F[C:2]1[CH:3]=C[C:5]([N:8]2[C:16]3[CH:15]=[CH:14][N:13]=[CH:12][C:11]=3[N:10]=[CH:9]2)=[N:6][CH:7]=1.BrC1C=CC(F)=C[N:19]=1>>[N:6]1[CH:7]=[CH:2][CH:3]=[N:19][C:5]=1[N:8]1[C:16]2[CH:15]=[CH:14][N:13]=[CH:12][C:11]=2[N:10]=[CH:9]1
Reactant: Fc1ccc(-n2cnc3cnccc32)nc1
Reactant: Fc1ccc(Br)nc1
Product: c1cnc(-n2cnc3cnccc32)nc1

Procedure:
Intermediate 5 was prepared in a manner analogous to Intermediate 1, substituting 2-bromopyrimidine for 2-bromo-5-fluoropyridine. MS (ESI): mass calculated for C10H7N5, 198.07. m/z found 199.1 [M+H]+.
Reaction SMILES: [C:1]1([C:7]([CH:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[OH:10])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:17][C:18](OCC)=[O:19].O>CC(C)=O>[C:1]1([C:7]2[NH:17][C:18](=[O:19])[O:10][C:9]=2[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C(c1ccccc1)C(O)c1ccccc1
Reactant: CCOC(N)=O
Solvent: O
Solvent: CC(C)=O
Product: O=c1[nH]c(-c2ccccc2)c(-c2ccccc2)o1

Procedure:
Benzoin (31.8 g, 0.15 mol) and urethane (42.79 g, 0.45 mol) were heated to reflux for 3.0 hours. The hot mixture was poured into water (150 mL). Acetone (150 mL) was added and heat was applied until the mixture dissolved. The solution was cooled and filtered, producing a white solid which was used in the next step without further purification.
Reaction SMILES: [CH3:1][N:2]([C:9](=[O:19])[C:10]1[CH:15]=[CH:14][C:13]([N+:16]([O-])=O)=[CH:12][CH:11]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1>C(O)C.C(O)(=O)C.[Fe]>[CH3:1][N:2]([C:9](=[O:19])[C:10]1[CH:11]=[CH:12][C:13]([NH2:16])=[CH:14][CH:15]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: CN(C(=O)c1ccc([N+](=O)[O-])cc1)c1ccccc1
Agent: [Fe]
Solvent: CC(=O)O
Solvent: CCO
Product: CN(C(=O)c1ccc(N)cc1)c1ccccc1
Temperature: 80 °C
Reaction time: 3 h
Yield: 72.4 %

Procedure:
A mixture of N-methyl-N-(4-nitrobenzoyl)aniline (1.18 g) and iron powder (2.57 g) in a mixture of ethanol (30 ml) and acetic acid (6 ml) was stirred at 80° C. for 3 hours and the mixture was cooled to ambient temperature. The mixture was filtered through Celite and the filtrate was evaporated in vacuo. The residue was dissolved in chloroform and neutralized with saturated aqueous sodium hydrogen carbonate. The solution was filtered through Celite again and the organic phase of the filtrate was washed with brine, and dried over magnesium sulfate. The solvent was evaporated in vacuo and the residue was solidified with diethyl ether to give N-methyl-N-(4-aminobenzoyl)aniline (754 mg) as a pale yellow solid.
Reaction SMILES: [CH3:1][N:2]([CH2:16][C@H:17]1[CH2:22][CH2:21][C@H:20]([CH2:23][CH2:24]OS(C)(=O)=O)[CH2:19][CH2:18]1)[S:3]([C:6]1[CH:11]=[CH:10][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:8][CH:7]=1)(=[O:5])=[O:4].[NH:30]1[CH:34]=[CH:33][N:32]=[CH:31]1.[H-].[Na+]>CN(C)C=O>[N:30]1([CH2:24][CH2:23][C@H:20]2[CH2:21][CH2:22][C@H:17]([CH2:16][N:2]([CH3:1])[S:3]([C:6]3[CH:11]=[CH:10][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:8][CH:7]=3)(=[O:5])=[O:4])[CH2:18][CH2:19]2)[CH:34]=[CH:33][N:32]=[CH:31]1
Reactant: CN(C[C@H]1CC[C@H](CCOS(C)(=O)=O)CC1)S(=O)(=O)c1ccc(C(F)(F)F)cc1
Reactant: c1c[nH]cn1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CN(C[C@H]1CC[C@H](CCn2ccnc2)CC1)S(=O)(=O)c1ccc(C(F)(F)F)cc1

Procedure:
In analogy to the procedure described in example 25.1, trans-methanesulfonic acid 2-(4-{[methyl-(4-trifluoromethyl-benzenesulfonyl)-amino]-methyl}-cyclohexyl)-ethyl ester (example 9.10) was reacted with imidazole in N,N-dimethylformamide in the presence of sodium hydride to yield trans-N-[4-(2-imidazol-1-yl-ethyl)-cyclohexylmethyl]-N-methyl-4-trifluoromethyl-benzenesulfonamide as yellowish solid, MS: 430 (MH+).
Reaction SMILES: [CH:1]1[CH:6]=[N+:5]([C@@H:7]2[O:11][C@H:10]([CH2:12][O:13][P:14]([O:17][P:18]([O:21][CH2:22][C@H:23]3[O:27][C@@H:26]([N:28]4[C:32]5[N:33]=[CH:34][N:35]=[C:36]([NH2:37])[C:31]=5[N:30]=[CH:29]4)[C@H:25]([O:38][P:39]([OH:42])([OH:41])=[O:40])[C@@H:24]3[OH:43])([OH:20])=[O:19])([OH:16])=[O:15])[C@@H:9]([OH:44])[C@H:8]2[OH:45])[CH:4]=[C:3]([C:46]([NH2:48])=[O:47])[CH:2]=1.P([O-])([O-])([O-])=O.[OH-].[Na+]>>[CH:34]1[N:35]=[C:36]([NH2:37])[C:31]2[N:30]=[CH:29][N:28]([C@@H:26]3[O:27][C@H:23]([CH2:22][O:21][P:18]([O:17][P:14]([O:13][CH2:12][C@H:10]4[O:11][C@@H:7]([N:5]5[CH:4]=[C:3]([C:46]([NH2:48])=[O:47])[CH2:2][CH:1]=[CH:6]5)[C@H:8]([OH:45])[C@@H:9]4[OH:44])([OH:16])=[O:15])([OH:20])=[O:19])[C@@H:24]([OH:43])[C@H:25]3[O:38][P:39]([OH:42])([OH:41])=[O:40])[C:32]=2[N:33]=1
Reactant: NC(=O)c1ccc[n+]([C@@H]2O[C@H](COP(=O)(O)OP(=O)(O)OC[C@H]3O[C@@H](n4cnc5c(N)ncnc54)[C@H](OP(=O)(O)O)[C@@H]3O)[C@@H](O)[C@H]2O)c1
Agent: O=P([O-])([O-])[O-]
Agent: [Na+]
Agent: [OH-]
Product: NC(=O)C1=CN([C@@H]2O[C@H](COP(=O)(O)OP(=O)(O)OC[C@H]3O[C@@H](n4cnc5c(N)ncnc54)[C@H](OP(=O)(O)O)[C@@H]3O)[C@@H](O)[C@H]2O)C=CC1
Temperature: 40 °C
Yield: 61.7 %

Procedure:
NADP+ (36.0 mg, 47.0 μmol) was placed in 2 mL of a 0.1 M phosphate buffer. The pH of this solution was adjusted to 8.3 with NaOH and then placed in an 80 mL Fisher-Porter bottle. The Fisher-Porter bottle was evacuated and refilled with argon three times then [Cl2Ru(TPPTS)2]2 (9.7 mg, 3.7 μmol) was added under a flow of argon. The Fisher-Porter bottle was evacuated and filled with 70 psi of H2 and heated to 40° C. for 3.0 hr. The volatiles were removed under reduced pressure and a sample dissolved in D2O. To this was added 20 μl of trimethylsilylpropionate standard solution. 1H NMR integration shows that 29.0 μmole of NADPH have been produced under these conditions.
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][C:5]([CH2:8][O:9][CH2:10][CH3:11])=[CH:4][N:3]=1.[NH:12]1[CH2:17][CH2:16][CH:15]([C@H:18]2[CH2:20][C@H:19]2[CH2:21][CH2:22][OH:23])[CH2:14][CH2:13]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O>[CH2:10]([O:9][CH2:8][C:5]1[CH:4]=[N:3][C:2]([N:12]2[CH2:17][CH2:16][CH:15]([C@H:18]3[CH2:20][C@H:19]3[CH2:21][CH2:22][OH:23])[CH2:14][CH2:13]2)=[N:7][CH:6]=1)[CH3:11]
Reactant: CCOCc1cnc(Cl)nc1
Reactant: OCC[C@@H]1C[C@@H]1C1CCNCC1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOCc1cnc(N2CCC([C@H]3C[C@H]3CCO)CC2)nc1
Temperature: 70 °C
Reaction time: 8 h

Procedure:
In a 250 ml RBF 2-chloro-5-(ethoxymethyl)pyrimidine (280 mg, 1.622 mmol) and 2-[(1S,2R)-2-(piperidin-4-yl)cyclopropyl]ethanol (334 mg, 1.622 mmol) were dissolved in DMF (1622 μl). Cesium carbonate (1586 mg, 4.87 mmol) was added and the mixture stirred at 70° C. overnight. The mixture was diluted with 4:1 water:brine (200 ml), extracted with EtOAc (3×100 ml), the organic fractions combined, washed with brine, dried over Na2SO4, filtered and the volatiles removed in vacuo. The mixture was purified on a 100 g Biotage HP-SiO2 cartridge using a gradient eluant of 0-100% EtOAc:hexanes to afford the title compound. LC/MS (m/z): 306 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[CH:13]=[CH:12][N:11](S(C3C=CC(C)=CC=3)(=O)=O)[C:8]2=[N:9][CH:10]=1)=[O:4].C[O-].[Na+]>CO>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[CH:13]=[CH:12][NH:11][C:8]2=[N:9][CH:10]=1)=[O:4]
Reactant: COC(=O)c1cnc2c(ccn2S(=O)(=O)c2ccc(C)cc2)c1
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: COC(=O)c1cnc2[nH]ccc2c1
Temperature: 65 °C

Procedure:
A suspension of 1-(Toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid methyl ester (5.4 g, 16 mmol) in MeOH (100 mL) with NaOMe in MeOH (20 mL, 25% wt., excess) was heated at 65° C. for 1 hour. The resulting material was concentrated from MeOH, diluted with H2O (100 mL), and pH adjusted to 6 with 1N HCl. The aqueous solution was partitioned with EtOAc (100 mL) and the organic extraction was dried over Na2SO4 and dried in vacuo. The residue was purified with flash chromatography over silica gel in an elution from 99:1 CH2Cl2:MeOH to 92:8 CH2Cl2:MeOH. Yield 1.8 g, beige powder.
Reaction SMILES: Cl[C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH:11]=[CH2:12].[CH3:13][NH2:14].O.Cl.CN>C1COCC1>[CH3:13][NH:14][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH:11]=[CH2:12]
Reactant: CN
Reactant: C=Cn1cnc2c(Cl)ncnc21
Agent: Cl
Solvent: C1CCOC1
Solvent: O
Product: C=Cn1cnc2c(NC)ncnc21
Temperature: 25 °C
Reaction time: 5 h

Procedure:
6-Chloro-9-vinylpurine (JOC 1968, 33, 1341) (0.54 g, 3 mmol), was added to methylamine (˜15 mmol, 2.0M in THF) in THF (5 mL) and the mixture was stirred for 5 h at rt. Water was added to dissolve the white precipitate (methylamine hydrochloride). The aqueous layer was extracted with ethyl acetate and the combined organic layers were dried over sodium sulfate, concentrated on a rotavap, and then subjected to silica gel column chromatography (5% methanol/methylene chloride) yielding the desired product.
Reaction SMILES: CO[C:3](=[O:23])[CH2:4][N:5]1[CH2:9][C:8]([OH:10])=[C:7]([C:11]2[CH2:15][N:14]([CH2:16][C:17]([O:19]C)=O)[C:13](=[O:21])[CH:12]=2)[C:6]1=[O:22].[NH:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1>>[OH:10][C:8]1[CH2:9][N:5]([CH2:4][C:3]([N:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)=[O:23])[C:6](=[O:22])[C:7]=1[C:11]1[CH2:15][N:14]([CH2:16][C:17]([N:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)=[O:19])[C:13](=[O:21])[CH:12]=1
Reactant: COC(=O)CN1CC(C2=C(O)CN(CC(=O)OC)C2=O)=CC1=O
Reactant: C1CCNCC1
Product: O=C1C=C(C2=C(O)CN(CC(=O)N3CCCCC3)C2=O)CN1CC(=O)N1CCCCC1

Procedure:
Analogously to the procedure described in Example 2, from 4.8 g (0.015 mol) of 1,1',5,5'-tetrahydro-4-hydroxy-2,2'-dioxo-[3,4'-bi-2H-pyrrole]-1,1'-diacetic acid dimethyl ester and 25 ml of piperidine there is obtained 1,1',5,5'-tetrahydro-4-hydroxy-2,2'-dioxo-[3,4'-bi-2H-pyrrole]-1,1'-diacetic acid dipiperidide in the form of pale yellow microcrystals having a melting point of 150°-155° (decomposition).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:7](=[O:26])[C:8]2[CH:9]=[C:10]3[CH:22]=[C:21]([F:23])[C:20](F)=[C:19]([F:25])[C:11]3=[N:12][C:13]=2[N:14]([CH2:16][CH2:17][F:18])[CH:15]=1)=[O:5])[CH3:2].[C:27]1([CH:33]2[CH2:38][NH:37][CH2:36][CH2:35][NH:34]2)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C(=O)([O-])[O-].[Na+].[Na+].O>CS(C)=O>[CH2:1]([O:3][C:4]([C:6]1[C:7](=[O:26])[C:8]2[CH:9]=[C:10]3[CH:22]=[C:21]([F:23])[C:20]([N:37]4[CH2:36][CH2:35][NH:34][CH:33]([C:27]5[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=5)[CH2:38]4)=[C:19]([F:25])[C:11]3=[N:12][C:13]=2[N:14]([CH2:16][CH2:17][F:18])[CH:15]=1)=[O:5])[CH3:2]
Reactant: c1ccc(C2CNCCN2)cc1
Reactant: CCOC(=O)c1cn(CCF)c2nc3c(F)c(F)c(F)cc3cc2c1=O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: CCOC(=O)c1cn(CCF)c2nc3c(F)c(N4CCNC(c5ccccc5)C4)c(F)cc3cc2c1=O
Temperature: 100 °C
Reaction time: 2 h

Procedure:
(RS)-3-Ethoxycarbonyl-7,9-difluoro-1-(2-fluoroethyl)-4-oxo-8-(3-phenyl-1-piperazinyl)-1,4-dihydrobenzo[b][1,8]naphthyridine was prepared under the following conditions: a suspension of 3-ethoxycarbonyl-1-(2-fluoroethyl)-7,8,9-trifluoro-4-oxo-1,4-dihydrobenzo[b][1,8]naphthyridine (2.8 g), (RS)-2-phenylpiperazine (1.7 g) and sodium carbonate (1.1 g) in dimethyl sulphoxide (40 cc) is heated with stirring to a temperature in the region of 100° C. for 2 hours. After cooling to approximately 20° C., the reaction mixture is poured into water (200 cc) and extracted with trichloromethane (3×100 cc). The combined organic extracts are washed with water (1×50 cc) and concentrated under reduced pressure (20 kPa) at a temperature in the region of 40° C. The oily residue is taken up with ethanol (100 cc) and concentrated again under reduced pressure under the above conditions. The solid obtained is recrystallized in ethanol (100 cc) containing dimethylformamide (20%), drained and washed with ethanol (2×20 cc). The expected product (2.4 g) is obtained in the form of a yellow solid, m.p. 208° C.
Reaction SMILES: [H-].[Na+].[C:3](=[N:8][OH:9])([NH2:7])[CH2:4][CH2:5][CH3:6].[C:10]1([C:16]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[N:17]2[CH2:22][CH:21]([C:23](OC)=O)[CH2:20][N:19]=[CH:18]2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>C1COCC1>[C:33]1([C:16]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[N:17]2[CH2:22][CH:21]([C:23]3[O:9][N:8]=[C:3]([CH2:4][CH2:5][CH3:6])[N:7]=3)[CH2:20][N:19]=[CH:18]2)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1
Reactant: COC(=O)C1CN=CN(C(c2ccccc2)(c2ccccc2)c2ccccc2)C1
Reactant: CCCC(N)=NO
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCCc1noc(C2CN=CN(C(c3ccccc3)(c3ccccc3)c3ccccc3)C2)n1
Temperature: 0 °C
Reaction time: 18 h
Yield: 66.6 %

Procedure:
Prepared by a procedure similar to Example 9, where sodium hydride (60% dispersion in mineral oil 108 mg, 2.7 mmol) and butyramidoxime (276 mg, 2.7 mmol) were suspended in dry THF in an oven dried round bottom flask with stirring under nitrogen at 0° C. After 15 minutes stirring the ice bath was removed and the grey suspension refluxed 45 minutes to give a white suspension. 1-Triphenylmethyl-1,4,5,6-tetrahydro-5-methoxycarbonylpyrimidine (1.04 g, 2.7 mmol) was added, dissolved in dry THF and reflux continued 18 hours. The solvents were evaporated in vacuo and the residue was chromatographed (silica, chloroform/methanol, 9:1) to yield 1-triphenylmethyl-1,4,5,6-tetrahydro-5-(3-n-propyl-1,2,4-oxadiazol-5-yl)pyrimidine 785 mg (67%). This product was dissolved in triflouroacetic acid (2 ml), with stirring at room temperature for 24 hours. The yellow solution was then evaporated in vacuo, and the residue recrystallized from methanol/ether to yield 240 mg (43%) white crystals, mp 126°-128° C. identified by 300 MHz nmr.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][C:10]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)([CH:14]=[CH:15][C:16]([O:18][CH3:19])=[O:17])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][C:10]([CH2:20][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)([CH2:14][CH2:15][C:16]([O:18][CH3:19])=[O:17])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: COC(=O)C=CC1(Cc2ccccc2)CN(C(=O)OC(C)(C)C)CCN1
Agent: [Pd]
Product: COC(=O)CCC1(Cc2ccccc2)CN(C(=O)OC(C)(C)C)CCN1
Reaction time: 17 h
Yield: 90 %

Procedure:
A methanolic solution of the compound of Example 201, Step A was hydrogenated (40 psi) in a Parr shaker over 10% Pd-C (35 mg). After 17 hours, the reaction was filtered through a pad of Celite® and then concentrated to give yellowish solid of the compound of the compound of Example 201, Step B (153 mg, 90%) which was a 1:2 mixture of ester and lactam: +APcl MS (M+1, ester)+ 363, (M+1, lactam)+ 331; 1H NMR (400 MHz, CDCl3) δ: 7.25-7.05 (arom, series of m, 5H), 3.54 (ester Me, s, 1H), 1.44 (lactam BOC, s, 6H),1.37 (ester BOC, s, 3H).
Reaction SMILES: [C:1]([O:9][C@H:10]1[CH2:34][CH2:33][C@@:32]2([CH3:35])[C@@H:12]([CH2:13][CH2:14][C:15]3[C:16]4[C@:28]([CH3:36])([CH2:29][CH2:30][C:31]=32)[C@@H:19]([C@H:20]([CH3:27])[CH2:21][CH2:22][CH2:23][CH:24]([CH3:26])[CH3:25])[CH2:18][C:17]=4[O:37][Si](C)(C)C)[CH2:11]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.I[CH2:43][C:44]([O:46][CH2:47][CH3:48])=[O:45].[F-].C([N+](C)(C)C)C1C=CC=CC=1>C1COCC1.CCCCCC>[C:1]([O:9][C@H:10]1[CH2:34][CH2:33][C@@:32]2([CH3:35])[C@@H:12]([CH2:13][CH2:14][C:15]3[C@@:16]4([CH2:43][C:44]([O:46][CH2:47][CH3:48])=[O:45])[C@:28]([CH3:36])([CH2:29][CH2:30][C:31]=32)[C@@H:19]([C@H:20]([CH3:27])[CH2:21][CH2:22][CH2:23][CH:24]([CH3:26])[CH3:25])[CH2:18][C:17]4=[O:37])[CH2:11]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)CCC[C@@H](C)[C@H]1CC(O[Si](C)(C)C)=C2C3=C(CC[C@@]21C)[C@@]1(C)CC[C@H](OC(=O)c2ccccc2)C[C@@H]1CC3
Reactant: CCOC(=O)CI
Agent: C[N+](C)(C)Cc1ccccc1
Agent: [F-]
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CCOC(=O)C[C@@]12C(=O)C[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CCC1=C2CC[C@H]2C[C@@H](OC(=O)c3ccccc3)CC[C@]12C
Temperature: -10 °C
Reaction time: 0.5 h
Yield: 31.6 %

Procedure:
3β-benzoyloxy-15-trimethylsiloxy-5α-cholest-8,14-diene (1.93 g, 3.35 mmole) in THF (10 mL) and ethyl iodoacetate (0.79 mL, 6.7 mmole) was added at -10° C. to a mixture of benzyl trimethylammonium fluoride (850 mg, 5 mmole) in THF (15 mL). The mixture was stirred at -10° C. for 15 minutes and at ambient temperature for 30 minutes, diluted with hexane, filtered and the filtrate was concentrated. Using the workup described in Example 1(ii), 625 mg of 3β-benzoyloxy-14α-carbethoxymethyl-5α-cholest-8-en-15-one was obtained.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH2:32][C:33]1[CH:42]=[CH:41][C:36]([C:37]([O:39]C)=[O:38])=[CH:35][CH:34]=1)[S:9]([C:12]1[CH:17]=[C:16]([C:18](=[O:30])[NH:19][N:20]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH2:22][CH:21]2[CH3:29])[CH:15]=[CH:14][C:13]=1[Cl:31])(=[O:11])=[O:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Li+]>C(#N)C.O>[C:1]([O:5][C:6]([N:8]([CH2:32][C:33]1[CH:34]=[CH:35][C:36]([C:37]([OH:39])=[O:38])=[CH:41][CH:42]=1)[S:9]([C:12]1[CH:17]=[C:16]([C:18](=[O:30])[NH:19][N:20]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH2:22][CH:21]2[CH3:29])[CH:15]=[CH:14][C:13]=1[Cl:31])(=[O:11])=[O:10])=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: COC(=O)c1ccc(CN(C(=O)OC(C)(C)C)S(=O)(=O)c2cc(C(=O)NN3c4ccccc4CC3C)ccc2Cl)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: CC#N
Solvent: O
Product: CC1Cc2ccccc2N1NC(=O)c1ccc(Cl)c(S(=O)(=O)N(Cc2ccc(C(=O)O)cc2)C(=O)OC(C)(C)C)c1

Procedure:
Dissolve the compound obtained in Step A (1.30×10−3 mol) in a mixture of acetonitrile (45 ml) and water (9 ml). Add lithium hydroxide (1.30×10−2 mol) and heat at 50° C. with stirring. After heating for 5 hours, the dark-brown reaction mixture is poured into water (100 ml). Extract 3 times with ethyl acetate (50 ml). The organic phase is then washed with water and then with brine, dried over magnesium sulphate, filtered and evaporated to dryness under reduced pressure.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1Cl)=[CH:13][CH:12]=[CH:11][C:10]=2[N+:17]([O-])=O)=[O:5])[CH3:2].[Cl:20][C:21]1[CH:28]=[C:27]([Cl:29])[CH:26]=[CH:25][C:22]=1[CH2:23][NH2:24]>>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[NH:24][CH2:23][C:22]1[CH:25]=[CH:26][C:27]([Cl:29])=[CH:28][C:21]=1[Cl:20])=[CH:13][CH:12]=[CH:11][C:10]=2[NH2:17])=[O:5])[CH3:2]
Reactant: CCOC(=O)c1cnc2c([N+](=O)[O-])cccc2c1Cl
Reactant: NCc1ccc(Cl)cc1Cl
Product: CCOC(=O)c1cnc2c(N)cccc2c1NCc1ccc(Cl)cc1Cl
Yield: 88 %

Procedure:
The compound prepared in Example 3 was reacted with 2,4-dichloro-benzylamine according to the method as described in Example 4 and the obtained compound was treated as described in Example 14 to prepare the title compound (yield 88%).
Reaction SMILES: Cl[C:2]1[N:10]=[C:9]([NH2:11])[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C@@H:12]1[O:18][C@H:17]([CH2:19][OH:20])[C@@H:15]([OH:16])[C@H:13]1[OH:14].[C:21]1([CH:27]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:28][NH2:29])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(N(CC)CC)C>C(O)C>[C:30]1([CH:27]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:28][NH:29][C:2]2[C:3]3[N:4]=[CH:5][N:6]([C:7]=3[N:8]=[C:9]([NH2:11])[N:10]=2)[C@@H:12]2[O:18][C@H:17]([CH2:19][OH:20])[C@@H:15]([OH:16])[C@H:13]2[OH:14])[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1
Reactant: NCC(c1ccccc1)c1ccccc1
Reactant: Nc1nc(Cl)c2ncn([C@@H]3O[C@H](CO)[C@@H](O)[C@H]3O)c2n1
Solvent: CCO
Solvent: CCN(CC)CC
Product: Nc1nc(NCC(c2ccccc2)c2ccccc2)c2ncn([C@@H]3O[C@H](CO)[C@@H](O)[C@H]3O)c2n1

Procedure:
A mixture of 1.25 g of 6-chloro-2-amino-9-(β-D-ribofuranosyl)purine, 0.899 g of 2,2-diphenylethylamine and 0.503 g of triethylamine is heated under reflux in 30 ml of absolute ethanol under a nitrogen atmosphere for 18 hours. The solvent is evaporated to dryness and residue is treated with 50 ml of cold water. The insoluble organic material is filtered, dried, and purified by medium pressure liquid chromatography on silica gel. The product is eluted with 10% methanol-chloroform. Evaporation of the solvent from the pure fractions affords a colorless solid material. Crystallization from a mixture of CHCl3 -2-propanol (10:1) and hexane affords N6 -(2,2-diphenylethyl)-2-aminoadenosine, mp 134°-137° C.
Reaction SMILES: [NH2:1][C:2]1[C:3](=[O:14])[C:4]2[C:9]([C:10](=[O:13])[C:11]=1Cl)=[CH:8][CH:7]=[CH:6][CH:5]=2.[Cl:15][C:16]1[CH:24]=[CH:23][C:19]([C:20](Cl)=[O:21])=[CH:18][CH:17]=1.S(=O)(=O)(O)O>O1CCOCC1>[Cl:15][C:16]1[CH:24]=[CH:23][C:19]([C:20]2[O:21][C:11]3[C:10](=[O:13])[C:9]4[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=4[C:3](=[O:14])[C:2]=3[N:1]=2)=[CH:18][CH:17]=1
Reactant: NC1=C(Cl)C(=O)c2ccccc2C1=O
Reactant: O=C(Cl)c1ccc(Cl)cc1
Agent: O=S(=O)(O)O
Solvent: C1COCCO1
Product: O=C1c2ccccc2C(=O)c2oc(-c3ccc(Cl)cc3)nc21
Yield: 33.6 %

Procedure:
To a solution of 5.0 g (24 mmol) of 2-amino-3-chloro-1,4-dihydro-1,4-dioxonaphthalene in 60 mL of dioxane, one adds at ambient temperature 15.3 mL (120 mmol) of 4-chlorobenzoic acid chloride and 0.5 mL of concentrated sulfuric acid. The reaction mixture is heated to reflux for 4 h, then evaporated to dryness, redissolved in 200 mL of dichloromethane, and neutralized at cold temperature with 100 mL of 10N sodium hydroxide. The organic phase is then washed three times with water and dried over calcium chloride. The red powder so obtained is purified on a flash column (support: silica; conditioning: heptane; eluant: dichloromethane/heptane, 70/30). The yellow crystals obtained after evaporation of the solvent are uncolored and recrystallized in dichloromethane to produce 2.5 g of 2-(4-chlorophenyl)-4,9-dihydro-4,9-dioxo-naphtho[2,3-d]oxazole in the form of yellow crystals.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[O:11][CH3:12].[CH2:13]([N:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1)[CH3:14]>O>[CH2:13]([N:15]1[CH2:20][CH2:19][N:18]([C:2]2[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=2[O:11][CH3:12])[CH2:17][CH2:16]1)[CH3:14]
Reactant: COc1cc([N+](=O)[O-])ccc1Br
Reactant: CCN1CCNCC1
Solvent: O
Product: CCN1CCN(c2ccc([N+](=O)[O-])cc2OC)CC1

Procedure:
2-Bromo-5-nitroanisole (4.7 g, 20 mmol) and N-ethyl-piperazin (10.3 ml) is stirred for 13 h at 110° C. under N2-atmosphere. Water (80 ml) is added and the mixture extracted twice with CH2Cl2 (2×80 ml). The organic phases are washed with water and brine, dried (Na2SO4) and concentrated. Column chromatography (SiO2; CH2Cl2/MeOH 19:1→9:1) gives the title compound: m.p.: 84-85° C.