Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC(=O)[NH:7][CH2:8][C@H:9]([NH:25]C(OC(C)(C)C)=O)[CH2:10][CH2:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][C@H:21]([OH:24])[CH2:22][OH:23])=[CH:15][CH:14]=1)(C)(C)C.Cl>CCOCC>[NH2:25][C@@H:9]([CH2:8][NH2:7])[CH2:10][CH2:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][C@H:21]([OH:24])[CH2:22][OH:23])=[CH:15][CH:14]=1
Reactant: CC(C)(C)OC(=O)NC[C@@H](CCCc1ccc(OC[C@H](O)CO)cc1)NC(=O)OC(C)(C)C
Agent: Cl
Solvent: CCOCC
Product: NC[C@H](N)CCCc1ccc(OC[C@H](O)CO)cc1

Procedure:
{(R)-2-tert-Butoxycarbonylamino-5-[4-((R)-2,3-dihydroxy-propoxy)-phenyl]-pentyl}-carbamic acid tert-butyl ester (94 mg, 0.201 mmol) is stirred with a solution of 1 M HCl in Et2O (3 ml) for 18 hours and then loaded onto a 1 g SCX-2 cartridge washed with MeOH (30 ml), followed by 7M NH3 in MeOH (30 ml). The NH3 fraction is concentrated in vacuo to give the title compound, (R)-3-[4-((R)-4,5-Diamino-pentyl)-phenoxy]-propane-1,2-diol Intermediate H (R)-3-[4-((R)-4,5-Diamino-pentyl)-phenoxy]-propane-1,2-diol; [M+H]+ 269
Reaction SMILES: [CH3:1][C:2]1([CH3:15])[O:11][C:10]2[C:5](=[CH:6][C:7]([C:12]#[N:13])=[CH:8][CH:9]=2)[C@@H:4]2[O:14][C@H:3]12.[O:16]1[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[C:18](=[O:25])[NH:17]1>>[O:16]1[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[C:18]([O:25][C@@H:4]2[C:5]3[C:10](=[CH:9][CH:8]=[C:7]([C:12]#[N:13])[CH:6]=3)[O:11][C:2]([CH3:1])([CH3:15])[C@H:3]2[OH:14])=[N:17]1
Reactant: O=c1[nH]oc2ccccc12
Reactant: CC1(C)Oc2ccc(C#N)cc2[C@@H]2O[C@@H]21
Product: CC1(C)Oc2ccc(C#N)cc2[C@@H](Oc2noc3ccccc23)[C@@H]1O

Procedure:
Following the procedure in Example 1, using (S,S)-2,2-dimethyl-1a,7b-dihydro-2H-1,3-dioxa-cyclopropa[a]naphthalene-6-carbonitrile and benzo[d]isoxazol-3-one as starting materials, the title compound was prepared as a white solid.
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[C:5]([N:11]2[N:15]=[C:14]3[CH:16]=[CH:17][C:18]([CH3:20])=[CH:19][C:13]3=[N:12]2)[C:4]=1[OH:21].C(N(CC)CC)C.[C:29](Cl)(=[O:33])[C:30]([CH3:32])=[CH2:31]>C1COCC1>[C:29]([O:1][CH2:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[C:5]([N:11]2[N:15]=[C:14]3[CH:16]=[CH:17][C:18]([CH3:20])=[CH:19][C:13]3=[N:12]2)[C:4]=1[OH:21])(=[O:33])[C:30]([CH3:32])=[CH2:31]
Reactant: C=C(C)C(=O)Cl
Reactant: COc1cc(CO)c(O)c(-n2nc3ccc(C)cc3n2)c1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: C=C(C)C(=O)OCc1cc(OC)cc(-n2nc3ccc(C)cc3n2)c1O
Temperature: -10 °C
Reaction time: 2 h
Yield: 29.8 %

Procedure:
In a 100 ml round bottom 3-neck flask equipped with a magnetic stirrer and nitrogen inlet was dissolved 19.5 g (68.3 mmol) 2-(hydroxymethyl)-4-methoxy-6-(5-methyl-2H-benzo[d][1,2,3]triazol-2-yl)phenol in 200 ml anhydrous THF. Triethylamine (34 ml, 240 mmol) was added and the mixture was cooled to −10° C. Methacryloyl chloride (8.55 g, 81.8 mmol) was added dropwise and the mixture was stirred for 2 hr at 0° C. followed by 20 hours at ambient temperature. The solid was filtered and rinsed with diethyl ether and the filtrate was poured into 100 ml diethyl ether and washed with 0.5 N HCl and water. The organic layer was dried with magnesium sulfate, filtered, and concentrated via rotary evaporation. The crude product was recrystallized in ethanol to give 7.2 g (30%) of a light yellow solid. 1H NMR (CDCl3) delta: 11.28 (s, 1H, Ar—OH), 7.89 (s, 1H, Ar—H benzotriazole 4-position), 7.79 (d, 1H, Ar—H benzotriazole 6-position), 7.66 (s, 1H, Ar—H phenol 6-position), 7.26 (d, 1H, Ar—H benzotriazole 7-position), 7.03 (s, 1H, Ar—H phenol 4-position), 6.21 (s, 1H, C═C—H trans), 5.61 (s, 1H, C═C—H cis), 5.39 (s, 2H, Ar—CH2), 3.89 (s, 3H, Ar—OCH3), 2.54 (s, 3H, Ar—CH3), 2.01 (s, 3H, C═C—CH3).
Reaction SMILES: C([N:3](C(=O)C1C=CC(O)=CC=1)[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:5]=1[C@@H:12]1[CH2:21][CH2:20][C:19]2[CH:18]=[C:17]([O:22]C(=O)C(C)(C)C)[CH:16]=[CH:15][C:14]=2[CH2:13]1)C.[N:38]1([C:45](=O)[CH2:46]Cl)[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]1>>[N:38]1([CH2:45][CH2:46][O:10][C:8]2[CH:9]=[CH:4][C:5]([CH2:12][CH2:13][CH2:14][NH:3][C:4]3[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:5]=3[C@@H:12]3[CH2:21][CH2:20][C:19]4[CH:18]=[C:17]([OH:22])[CH:16]=[CH:15][C:14]=4[CH2:13]3)=[CH:6][CH:7]=2)[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]1
Reactant: CCN(C(=O)c1ccc(O)cc1)c1cc(OC)ccc1[C@@H]1CCc2cc(OC(=O)C(C)(C)C)ccc2C1
Reactant: O=C(CCl)N1CCCCCC1
Product: COc1ccc([C@@H]2CCc3cc(O)ccc3C2)c(NCCCc2ccc(OCCN3CCCCCC3)cc2)c1
Yield: 65.5 %

Procedure:
Synthesized from pivalic acid (R)-6-{2-[ethyl(4-hydroxybenzoyl)amino]-4-methoxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-yl ester (20 mg) and 1-azepan-1-yl-2-chloroethanone (14 mg) according to an analogous synthetic method to Example 404 and purified by LC-MS, the title compound (6.9 mg) was obtained.
Reaction SMILES: Br[C:2]1[C:10]2[CH:9]=[CH:8][S:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.[Mg].II.CON(C)[C:17](=[O:22])[CH2:18][CH:19]1[CH2:21][CH2:20]1>O1CCCC1>[S:7]1[CH:8]=[CH:9][C:10]2[C:2]([C:17](=[O:22])[CH2:18][CH:19]3[CH2:21][CH2:20]3)=[CH:3][CH:4]=[CH:5][C:6]1=2
Reactant: CON(C)C(=O)CC1CC1
Reactant: Brc1cccc2sccc12
Agent: II
Agent: [Mg]
Solvent: C1CCOC1
Product: O=C(CC1CC1)c1cccc2sccc12
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A few drops of a solution of 4-bromobenzo[b]thiophene (2.84 g; prepared in a manner similar to that described in Example 9 Method A) in tetrahydrofuran (20 ml) was added under nitrogen to magnesium turnings (0.4 g). Two crystals of iodine were added and heat was applied to initiate the reaction. The remainder of the 4-bromobenzo[b]thiophene solution was added at reflux temperature over 20 minutes, then the mixture was heated under reflux for 2 hours. A solution of N-methoxy-N-methylcyclopropaneacetamide (2.0 g) in tetrahydrofuran (10 ml) was added, the mixture was heated under reflux for 2.5 hours, then it was stirred at ambient temperature for 18 hours and quenched by the addition of 2M hydrochloric acid (40 ml). The mixture was stirred at ambient temperature for 1 hour, then the product was extracted into ethyl acetate (3×30 ml). The combined extracts were washed with water (30 ml) and saturated aqueous sodium chloride solution (20 ml), dried (MgSO4), and the solvents were removed in vacuo. The residue was purified by flash chromatography over silica using petroleum ether (b.p. 60-80° C.) followed by a 95:5 mixture of petroleum ether (b.p. 60-80° C.) and ethyl acetate as eluants. Appropriate fractions were combined and the solvents removed in vacuo to give 1-(benzo[b]thiophen-4-yl)-2-cyclopropylethan-1-one (1.2 g) as a colourless oil which was used without further purification.
Reaction SMILES: [OH:1][N:2]=[C:3]1[S:7][C:6](=[C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[CH3:17])[C:9]#[N:10])[CH:5]=[CH:4]1.[Cl:18][C:19]([Cl:24])([Cl:23])[C:20](Cl)=[O:21].C(N(CC)CC)C>C1COCC1>[Cl:18][C:19]([Cl:24])([Cl:23])[C:20]([O:1][N:2]=[C:3]1[S:7][C:6](=[C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[CH3:17])[C:9]#[N:10])[CH:5]=[CH:4]1)=[O:21]
Reactant: Cc1ccccc1C(C#N)=C1C=CC(=NO)S1
Reactant: O=C(Cl)C(Cl)(Cl)Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: Cc1ccccc1C(C#N)=C1C=CC(=NOC(=O)C(Cl)(Cl)Cl)S1
Temperature: 5 °C
Reaction time: 0.33 h

Procedure:
1.0 g (4.1 mmol) of (5-Hydroxyimino-5H-thiophen-2-ylidene)-(2-methylphenyl)-acetonitrile, prepared as described in example 7.1, are dissolved in 11 ml of THF and cooled in an ice bath. After adding 0.83 g (4.5 mmol) of trichloroacetyl chloride to the solution, 0.63 g (6.2 mmol) of triethylamine are added dropwise, keeping the temperature below 5° C. While the reaction mixture is stirred at 5° C. for 20 min, a precipitate is formed. The precipitate is filtered off and washed with THF. The filtrate is concentrated by a rotary evaporator. The residue is diluted with 2-PrOH and stirred at room temperature for 15 min. After cooling the mixture in an ice bath, the solid is isolated by filtration and washed with 2-PrOH. The product is obtained in the form of a yellow solid, 165° C.(Dec). The structure is confirmed by the 1H-NMR spectrum (CDCl3). δ [ppm]: 2.39 (s, 3H), 6.23 (d, 1H), 6.86 (d, 1H), 7.19-7.4 (m, 4H).
Reaction SMILES: [C:1]([C:5]1[N:10]=[CH:9][C:8]([C:11]2[N:12]([C:32](Cl)=[O:33])[C@@:13]([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=3)([CH3:24])[C@@:14]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)([CH3:16])[N:15]=2)=[C:7]([O:35][CH2:36][CH3:37])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:38][CH:39]1[CH2:44][CH2:43][N:42]([CH:45]2[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]2)[CH2:41][CH2:40]1>>[C:1]([C:5]1[N:10]=[CH:9][C:8]([C:11]2[N:12]([C:32]([N:48]3[CH2:49][CH2:50][CH:45]([N:42]4[CH2:43][CH2:44][CH:39]([CH3:38])[CH2:40][CH2:41]4)[CH2:46][CH2:47]3)=[O:33])[C@@:13]([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=3)([CH3:24])[C@@:14]([C:17]3[CH:18]=[CH:19][C:20]([Cl:23])=[CH:21][CH:22]=3)([CH3:16])[N:15]=2)=[C:7]([O:35][CH2:36][CH3:37])[CH:6]=1)([CH3:3])([CH3:2])[CH3:4]
Reactant: CCOc1cc(C(C)(C)C)ncc1C1=N[C@@](C)(c2ccc(Cl)cc2)[C@@](C)(c2ccc(Cl)cc2)N1C(=O)Cl
Reactant: CC1CCN(C2CCNCC2)CC1
Product: CCOc1cc(C(C)(C)C)ncc1C1=N[C@@](C)(c2ccc(Cl)cc2)[C@@](C)(c2ccc(Cl)cc2)N1C(=O)N1CCC(N2CCC(C)CC2)CC1

Procedure:
In a manner analogous to the method described in examples 8, (4S,5R)-2-(6-tert-butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl chloride (example 51) was coupled with 4-methyl-[1,4′]bipiperidinyl (Aldrich) to give the title compound. HR-MS (ES, m/z) calculated for C40H52Cl2N5O2 [(M+H)+] 704.3493, observed 704.3492.
Reaction SMILES: [N+](=[CH:3][C:4](=[O:8])[CH2:5][CH2:6][CH3:7])=[N-].[C:9]1([CH3:19])[C:10]([S:15]([OH:18])(=[O:17])=[O:16])=[CH:11][CH:12]=[CH:13][CH:14]=1>C(Cl)(Cl)Cl>[O:8]=[C:4]([CH2:5][CH2:6][CH3:7])[CH2:3][O:18][S:15]([C:10]1[C:9]([CH3:19])=[CH:14][CH:13]=[CH:12][CH:11]=1)(=[O:16])=[O:17]
Reactant: CCCC(=O)C=[N+]=[N-]
Reactant: Cc1ccccc1S(=O)(=O)O
Solvent: ClC(Cl)Cl
Product: CCCC(=O)COS(=O)(=O)c1ccccc1C
Yield: 59.9 %

Procedure:
A 1.0 g quantity of 1-diazo-2-pentanone is dissolved in 50 ml of chloroform, and 2.2 g of o-toluenesulfonic acid is slowly added to the solution. The same procedure as in Example 1 is thereafter repeated to afford 1.37 g of 2-oxopentyl-o-toluene sulfonate in the form of a transparent colorless oil (Compound 29).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.Br[C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][C:20]=1[Cl:21])[CH:16]=[O:17].C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:21][C:20]1[CH:19]=[CH:18][C:15]([CH:16]=[O:17])=[CH:14][C:13]=1[C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1
Reactant: COc1ccc(B(O)O)cc1
Reactant: O=Cc1ccc(Cl)c(Br)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: Cc1ccccc1
Product: COc1ccc(-c2cc(C=O)ccc2Cl)cc1
Yield: 62.6 %

Procedure:
To a degassed solution of 4-methoxybenzeneboronic acid (1.51 g, 10 mmol), 3-bromo-4-chlorobenzaldehyde (2 g, 9.13 mmol), and potassium carbonate (3.13 g, 22.8 mmol) in toluene/ethanol 2/1, (60 mL), Pd(PPh3)4 (130 mg, 1 mol %) is added and the mixture is degassed for further 5 minutes. The mixture is then refluxed for 2 days. The mixture was partitioned between ethyl acetate and water and extracted. The organic solvent was dried over sodium sulphate, removed under reduced pressure, and the residue purified by column chromatography (heptane/ethyl acetate 19/1 to afford 1.41 g of product.
Reaction SMILES: [CH3:1][C:2]([C@@H:4]1[C@@:8]2([CH3:24])[CH2:9][CH2:10][C@@H:11]3[C@:21]4([CH2:22]O)[C:15](=[CH:16][C:17]([CH2:19][CH2:20]4)=[O:18])[CH2:14][CH2:13][C@H:12]3[C@@H:7]2[CH2:6][CH2:5]1)=[O:3].CCOC([S-])=[S:29].[K+]>>[SH:29][CH2:22][C@@:21]12[C@@H:11]3[C@H:12]([C@H:7]4[C@:8]([CH3:24])([CH2:9][CH2:10]3)[C@@H:4]([C:2](=[O:3])[CH3:1])[CH2:5][CH2:6]4)[CH2:13][CH2:14][C:15]1=[CH:16][C:17](=[O:18])[CH2:19][CH2:20]2
Reactant: CCOC(=S)[S-]
Reactant: CC(=O)[C@H]1CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(CO)[C@H]3CC[C@]12C
Agent: [K+]
Product: CC(=O)[C@H]1CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(CS)[C@H]3CC[C@]12C

Procedure:
Other compounds can be prepared by starting with 19-hydroxyprogesterone. This is converted to the corresponding trifluoromethanesulfonate ester and the sulfonate is displaced with potassium ethyl xanthogenate. Hydrolysis of the resulting xanthogenate then gives the desired 19-mercaptopregn-4-ene-3,20-dione. This 19-mercapto compound can then be reacted with the appropriate acid halide or anhydride to give the corresponding ester.
Reaction SMILES: [CH:1](=[C:4]1[CH2:9][CH2:8][CH:7]([CH2:10][CH2:11]O)[CH2:6][CH2:5]1)[CH2:2][CH3:3].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Br:32]C(Br)(Br)Br>C(#N)C>[Br:32][CH2:11][CH2:10][CH:7]1[CH2:8][CH2:9][C:4](=[CH:1][CH2:2][CH3:3])[CH2:5][CH2:6]1
Reactant: BrC(Br)(Br)Br
Reactant: CCC=C1CCC(CCO)CC1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CC#N
Product: CCC=C1CCC(CCBr)CC1

Procedure:
40.4 g of 2-(4-propylidenecyclohexyl)ethanol, 69.5 g of triphenylphosphine and 500 ml of acetonitrile were cooled to -5° C. A solution of 99.5 g of tetrabromomethane in 100 ml of acetonitrile was then added with stirring, and the mixture was stirred at RT overnight. The solvent was then removed, and the residue was subjected to conventional work-up, giving 1-(2-bromo-ethyl)-4-propylidenecyclohexane.
Reaction SMILES: C([O:3][C:4](=O)[CH2:5][CH2:6][C:7]([C:26]#[N:27])([C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=1)[CH2:8][CH2:9][CH2:10][O:11][CH:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1)C>CCO.[NH4+].[OH-].[Ni]>[Cl:25][C:20]1[CH:19]=[C:18]([C:7]2([CH2:8][CH2:9][CH2:10][O:11][CH:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)[CH2:26][NH:27][C:4](=[O:3])[CH2:5][CH2:6]2)[CH:23]=[CH:22][C:21]=1[Cl:24]
Reactant: CCOC(=O)CCC(C#N)(CCCOC1CCOCC1)c1ccc(Cl)c(Cl)c1
Agent: [Ni]
Agent: [NH4+]
Agent: [OH-]
Solvent: CCO
Product: O=C1CCC(CCCOC2CCOCC2)(c2ccc(Cl)c(Cl)c2)CN1
Reaction time: 64.5 h
Yield: 84.8 %

Procedure:
Raney Ni is added to a solution of cyanoester (5) (8.5 g, 19.84 mmol) in absolute EtOH (200 mL) and concentrated NH4OH (40 mL). The mixture was subjected to a H2 (51.8 psi) Par for 64.5 hours. The reaction mixture was filtered through celite, and N2 gas was passed through the solution to remove NH3. EtOH was then evaporated, and water is azeotropically removed with toluene. The crude oil is purified by flash chromatography (Ch2Cl2-MeOH/95:5) to give a colorless solid (6.5 g, 84.8% yield), mp ˜45° C.
Reaction SMILES: C1(C([S:9][CH2:10][CH:11]([O:15][CH2:16][CH3:17])[O:12][CH2:13][CH3:14])=O)C=CC=CC=1.[OH-].[Na+]>C1COCC1.O>[SH:9][CH2:10][CH:11]([O:15][CH2:16][CH3:17])[O:12][CH2:13][CH3:14]
Reactant: CCOC(CSC(=O)c1ccccc1)OCC
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: CCOC(CS)OCC

Procedure:
The preceding thiobenzoyl derivative (V) (17.2 g) was dissolved in 100 ml THF followed by the addition of 6 g NaOH in 20 ml H2O. The mixture was refluxed under N2 for 15 h, then cooled and diluted with water (200 ml) and the product extracted with ether (3×200 ml). The extract was dried, the solvent removed in vacuo and the residue distilled in vacuo to yield 7.1 g of pure (VI), b.p. 60-62°/18 mm. It was characterized by 1H NMR δ(ppm in CDCl3):
Reaction SMILES: [CH:1]1[N:6]=[C:5](Cl)[C:4]2[N:8]=[CH:9][N:10]([C@@H:11]3[O:15][C@H:14]([CH2:16][OH:17])[C@@H:13]([OH:18])[C@H:12]3[OH:19])[C:3]=2[N:2]=1.[NH2:20][CH:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:23][CH2:22]1.C(N(CC)CC)C>C(O)C>[C@H:21]1([NH:20][C:5]2[C:4]3[N:8]=[CH:9][N:10]([C:3]=3[N:2]=[CH:1][N:6]=2)[C@@H:11]2[O:15][C@H:14]([CH2:16][OH:17])[C@@H:13]([OH:18])[C@H:12]2[OH:19])[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:23][CH2:22]1
Reactant: NC1CCc2ccccc21
Reactant: OC[C@H]1O[C@@H](n2cnc3c(Cl)ncnc32)[C@H](O)[C@@H]1O
Solvent: CCO
Solvent: CCN(CC)CC
Product: OC[C@H]1O[C@@H](n2cnc3c(N[C@@H]4CCc5ccccc54)ncnc32)[C@H](O)[C@@H]1O
Reaction time: 20 h
Yield: 59.7 %

Procedure:
For 20 hours, 1.83 g 6-chloropurine riboside, 0.95 g (R) (-)-1-aminoindane and 0.862 g triethylamine are refluxed in 50 ml absolute ethanol under nitrogen atmosphere. The solvent is evaporated to dryness and residue is treated with 50 ml cold water. The solid material is filtered, dissolved in excess ethanol, and volatiles are evaporated under reduced pressure to remove water. Residue upon treatment with ethanol affords solid material. It is filtered and dried. One more crop of the same material is obtained from the mother liquor yielding 1.46 g (60% of theory) of N(6) [1-(R)-indanyl]adenosine having a melting point of 185°-187° C.
Reaction SMILES: Cl.[NH2:2][CH:3]([C@H:9]([CH2:17]C)[CH2:10][CH:11]([CH3:16])[CH2:12][CH2:13][CH:14]=[CH2:15])[C:4]([O:6][CH2:7][CH3:8])=[O:5].CCN(C(C)C)C(C)C.[O:28](C(OC(C)(C)C)=O)[C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=O>C(Cl)Cl>[C:32]([O:31][C:29]([NH:2][CH:3]([C@H:9]([CH3:17])[CH2:10][CH:11]([CH3:16])[CH2:12][CH2:13][CH:14]=[CH2:15])[C:4]([O:6][CH2:7][CH3:8])=[O:5])=[O:28])([CH3:35])([CH3:34])[CH3:33]
Reactant: C=CCCC(C)C[C@@H](CC)C(N)C(=O)OCC
Reactant: CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
Agent: Cl
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: C=CCCC(C)C[C@@H](C)C(NC(=O)OC(C)(C)C)C(=O)OCC
Temperature: 25 °C
Reaction time: 8 h
Yield: 62.5 %

Procedure:
A solution of (3R)-ethyl 2-amino-3-ethyl-5-methylnon-8-enoate hydrochloride (2.99 g, 10.77 mmole) in DCM (20 mL) was added DIPEA (1.08 mL, 10.77 mmole) followed by (BOC)2O (2.39 mL, 10.77 mmole) at room temperature. The reaction mass was stirred at room temperature for overnight. The reaction mass was diluted with DCM and washed with water. The organic layer was dried over anhydrous Na2SO4 and evaporated under reduced pressure to get crude compound. The crude compound was purified by column chromotography (Silica gel, 20% ethyl acetate in pet-ether) to get 2.3 g, (62.5%) of (3R)-ethyl 2-(tert-butoxycarbonylamino)-3,5-dimethylnon-8-enoate as an oily liquid. MS: MS m/z 342.4 (M++1).
Reaction SMILES: [CH3:1][S:2][C:3]1[N:8]=[C:7]([CH2:9][C:10](=[O:12])[CH3:11])[CH:6]=[CH:5][N:4]=1.[CH3:13][N:14]([CH:16](OC)OC)[CH3:15]>>[CH3:13][N:14]([CH3:16])[CH:15]=[C:9]([C:7]1[CH:6]=[CH:5][N:4]=[C:3]([S:2][CH3:1])[N:8]=1)[C:10](=[O:12])[CH3:11]
Reactant: CSc1nccc(CC(C)=O)n1
Reactant: COC(OC)N(C)C
Product: CSc1nccc(C(=CN(C)C)C(C)=O)n1
Temperature: 80 °C
Reaction time: 2 h
Yield: 49.3 %

Procedure:
1-(2-Methylsulfanyl-pyrimidin-4-yl)-propan-2-one (17) (1.93 g, 10.59 mmol) was taken up in DMF-DMA (20 mL, 149 mmol) and the resulting reaction was warmed to 80° C. and stirred for 2 hours. The solvent was evaporated and the crude residue partitioned between DCM and water. The organic layer was washed with brine, dried with sodium sulfate, and concentrated. The crude residue was purified by flash column chromatography with a gradient of 1-12% MeOH in DCM to give the desired product as a brown/orange oil (1.24 g, 49%). MS (ES+): m/z=238.2/239.3 (100/30) [MH+]. HPLC: tR=0.78 minute over 3 minutes. Purity: 100% [HPLC (LC/MS) at 220 nm].
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)(=O)[CH3:2].[Cl:10][C:11]1[CH:12]=[C:13]([CH:15]=[CH:16][CH:17]=1)[NH2:14].C1C=CC=CC=1>O>[Cl:10][C:11]1[CH:12]=[C:13]([CH:15]=[CH:16][CH:17]=1)[N:14]=[C:1]([CH3:2])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: Nc1cccc(Cl)c1
Reactant: CC(=O)c1ccccc1
Solvent: c1ccccc1
Solvent: O
Product: CC(=Nc1cccc(Cl)c1)c1ccccc1

Procedure:
A solution of acetophenone (130 ml), m-chloroaniline (130 ml) and benzene (200 ml) was refluxed in the presence of molecular sieve (50 g) with continuous removal of water. m-Chloro-N-(α-methyl benzylidene) aniline (XIX) was obtained by fractional distillation. XIX had a boiling point of 110° C. at 0.025 millimeter.
Reaction SMILES: [CH:1]([N:3]1[C:7](=[O:8])[C:6]2=[CH:9][CH:10]=[CH:11][CH:12]=[C:5]2[C:4]1=[O:13])=[CH2:2].C(N(CC)CC)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.Br[C:44]1[CH:45]=[CH:46][C:47]2[C:48]3[N:56]([CH2:57][C:58]([CH3:61])([OH:60])[CH3:59])[C:55]([CH2:62][CH3:63])=[N:54][C:49]=3[CH:50]=[N:51][C:52]=2[CH:53]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(#N)C>[CH2:62]([C:55]1[N:56]([CH2:57][C:58]([OH:60])([CH3:61])[CH3:59])[C:48]2[C:47]3[CH:46]=[CH:45][C:44]([CH:2]=[CH:1][N:3]4[C:7](=[O:8])[C:6]5[C:5](=[CH:12][CH:11]=[CH:10][CH:9]=5)[C:4]4=[O:13])=[CH:53][C:52]=3[N:51]=[CH:50][C:49]=2[N:54]=1)[CH3:63]
Reactant: C=CN1C(=O)c2ccccc2C1=O
Reactant: CCc1nc2cnc3cc(Br)ccc3c2n1CC(C)(C)O
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CCc1nc2cnc3cc(C=CN4C(=O)c5ccccc5C4=O)ccc3c2n1CC(C)(C)O
Temperature: 120 °C
Yield: 77.1 %

Procedure:
A thick walled glass tube, equipped with a stir bar, was charged with palladium (II) acetate (64 mg, 0.29 mmol), acetonitrile (50 mL), N-vinylphthalimide (1.19 g, 6.89 mmol), triethylamine (2.4 mL, 17 mmol), tri-o-tolylphosphine (260 mg, 0.86 mmol) and 1-(7-bromo-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol (2.00 g, 5.74 mmol). The reaction mixture was purged with nitrogen and the tube was sealed and heated at 120° C. in an oil bath for 16 hours. The reaction was cooled to ambient temperature and silica gel (20 g) was added followed by concentration under reduced pressure. The sample absorbed on silica was purified by chromatography using a HORIZON HPFC system (silica cartridge, eluting with a 0-7% gradient of methanol in dichloromethane). The recovered solid was washed with 1% aqueous sodium carbonate to provide 1.95 g of 2-{2[2-ethyl-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-yl]ethenyl}-1H-isoindole-1,3(2H)-dione as a bright yellow solid. MS (APCI) m/z 441 (M+H)+.
Reaction SMILES: [N:1]1([CH2:7][C:8]2[CH:34]=[CH:33][C:11]([NH:12]/[C:13](=[C:20]3\[C:21](=[O:32])[NH:22][C:23]4[C:28]\3=[CH:27][CH:26]=[C:25]([C:29](O)=[O:30])[CH:24]=4)/[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:35]([CH2:37][NH2:38])[OH:36].C(N(C(C)C)CC)(C)C>>[N:1]1([CH2:7][C:8]2[CH:34]=[CH:33][C:11]([NH:12]/[C:13](=[C:20]3\[C:21](=[O:32])[NH:22][C:23]4[C:28]\3=[CH:27][CH:26]=[C:25]([C:29](=[O:30])[NH:38][CH2:37][CH2:35][OH:36])[CH:24]=4)/[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)=[CH:10][CH:9]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: O=C1Nc2cc(C(=O)O)ccc2/C1=C(/Nc1ccc(CN2CCCCC2)cc1)c1ccccc1
Reactant: NCCO
Solvent: CCN(C(C)C)C(C)C
Product: O=C1Nc2cc(C(=O)NCCO)ccc2/C1=C(/Nc1ccc(CN2CCCCC2)cc1)c1ccccc1

Procedure:
Prepared from 3-Z-[1-(4-(piperidin-1-yl-methyl)-anilino)-1-phenyl-methylene]-6-carboxy-2-indolinone and ethanolamine/diisopropylethylamine Rf value: 0.5 (aluminium oxide, methylene chloride/methanol=20:1) C30H32N4O3
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:10]2[CH2:15][C:14]([CH3:17])([CH3:16])[NH:13][C:12]([CH3:19])([CH3:18])[CH2:11]2)[CH:5]=[C:6]([CH3:9])[C:7]=1[OH:8].[C:20](Cl)(=[O:28])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27]>[Na].C1(C)C(C)=CC=CC=1>[CH3:1][C:2]1[CH:3]=[C:4]([CH:10]2[CH2:15][C:14]([CH3:17])([CH3:16])[NH:13][C:12]([CH3:19])([CH3:18])[CH2:11]2)[CH:5]=[C:6]([CH3:9])[C:7]=1[O:8][C:20](=[O:28])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27]
Reactant: Cc1cc(C2CC(C)(C)NC(C)(C)C2)cc(C)c1O
Reactant: CCCCCCCC(=O)Cl
Agent: [Na]
Solvent: Cc1ccccc1C
Product: CCCCCCCC(=O)Oc1c(C)cc(C2CC(C)(C)NC(C)(C)C2)cc1C

Procedure:
20 Parts of 4-(3',5'-dimethyl-4'-hydroxyphenyl)-2,2,6,6-tetramethylpiperidine were dissolved in 1000 parts of sodium dried xylene and heated to reflux whilst stirred. 6.3 Parts of octanoyl chloride dissolved in a small amount of xylene were added to the refluxing solution dropwise. The solution was heated at reflux overnight, allowed to cool and filtered. The filtrate was evaporated to low bulk, dissolved in ether and washed with 2% aqueous sodium hydroxide and water. The organic phase was dried over magnesium sulphate and evaporated under reduced pressure. The residue was distilled under reduced pressure to yield 10.3 parts of the desired product having boiling point 175°-178°/0.05 mm and the following elemental analysis