Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C@@H:2]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][S:11]([CH3:14])(=[O:13])=[O:12])=[C:6]([C:15]#[C:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[CH:5]=1)[CH3:3].C(N(CC)CC)C.[C:28]([C:32]1[CH:37]=[CH:36][C:35]([N:38]=[C:39]=[O:40])=[CH:34][CH:33]=1)([CH3:31])([CH3:30])[CH3:29]>C(Cl)Cl>[C:28]([C:32]1[CH:37]=[CH:36][C:35]([NH:38][C:39](=[O:40])[NH:1][C@@H:2]([C:4]2[CH:9]=[CH:8][C:7]([NH:10][S:11]([CH3:14])(=[O:13])=[O:12])=[C:6]([C:15]#[C:16][Si:17]([CH3:18])([CH3:20])[CH3:19])[CH:5]=2)[CH3:3])=[CH:34][CH:33]=1)([CH3:31])([CH3:29])[CH3:30]
Reactant: CC(C)(C)c1ccc(N=C=O)cc1
Reactant: C[C@@H](N)c1ccc(NS(C)(=O)=O)c(C#C[Si](C)(C)C)c1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C[C@@H](NC(=O)Nc1ccc(C(C)(C)C)cc1)c1ccc(NS(C)(=O)=O)c(C#C[Si](C)(C)C)c1
Temperature: 0 °C
Reaction time: 0.67 h
Yield: 38.5 %

Procedure:
(R)—N-[4-(1-Amino-ethyl)-2-trimethylsilanylethynylphenyl]methanesulfonamide (75.0 mg, 0.242 mmol, 1 eq.) and Triethylamine (67.5 μl, 0.484 mmol, 2 eq.) were dissolved in methylene chloride. The mixture was cooled down to 0° C. 4-tert-Butylphenyl isocyanate (47.2 μl, 0.266 mmol, 1.1 eq.) was added into the reaction mixture. The reaction mixture was stirred for 40 min. A reaction solvent was removed in vacuo. The residue was purified with column chromatography (n-Hx:EA=2:1) to yield title compound (45.3 mg, 39%) as a solid.
Reaction SMILES: C([O:8][C:9]1[CH:30]=[CH:29][C:12]([CH2:13][N:14]2[CH2:18][CH2:17][N:16]([CH:19]([CH:25]([CH3:27])[CH3:26])[C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:15]2=[O:28])=[CH:11][CH:10]=1)C1C=CC=CC=1.[H][H]>C(O)C.[OH-].[OH-].[Pd+2]>[OH:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:13][N:14]2[CH2:18][CH2:17][N:16]([CH:19]([CH:25]([CH3:27])[CH3:26])[C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:15]2=[O:28])=[CH:29][CH:30]=1
Reactant: CCOC(=O)C(C(C)C)N1CCN(Cc2ccc(OCc3ccccc3)cc2)C1=O
Reactant: [H][H]
Agent: [Pd+2]
Agent: [OH-]
Solvent: CCO
Product: CCOC(=O)C(C(C)C)N1CCN(Cc2ccc(O)cc2)C1=O
Yield: 96.9 %

Procedure:
Ethyl 2-(3-(4-benzyloxybenzyl)-2-oxoimidazolidin-1-yl)-3-methylbutyrate (400 mg; 0.97 mmol) was dissolved in ethanol (20 ml). Pd(OH)2 (100 mg; 0.71 mmol) was added thereto, and hydrogenation was carried out under about 1 atm. of hydrogen for 3 h. The catalyst was filtered off through kieselguhr and washed with ethanol (2×; 20 ml). The solvent was removed under reduced pressure. Purification of the residue by column chromatography (SiO2) resulted in ethyl 2-(3-(4-hydroxybenzyl)-2-oxoimidazolidin-1-yl)-3-methylbutyrate (300 mg; 0.94 mmol). MS: 321.35 (M+H); Rt: 1.24 min (method: gradient 0 min 96% H2O (0.05% TFA) 2.0 min 95% acetonitrile, 95% acetonitrile to 2.4 min, 4% acetonitrile 2.45 min; flow rate 1 ml/min; column 0.4 μL (YMC J'sphere ODS H80 20X2 1.4μ); 30° C.)
Reaction SMILES: [NH2:1][CH2:2][C@H:3]1[O:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1.Br[C:17]1[C:18]([NH2:24])=[N:19][CH:20]=[C:21]([Br:23])[N:22]=1.CCN(CC)CC>CS(C)=O>[NH2:24][C:18]1[C:17]([NH:1][CH2:2][C@H:3]2[O:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]2)=[N:22][C:21]([Br:23])=[CH:20][N:19]=1
Reactant: Nc1ncc(Br)nc1Br
Reactant: CC(C)(C)OC(=O)N1CCO[C@H](CN)C1
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1CCO[C@H](CNc2nc(Br)cnc2N)C1
Temperature: 150 °C
Reaction time: 9 h
Yield: 69.9 %

Procedure:
(R)-tert-butyl 2-(aminomethyl)morpholine-4-carboxylate (26 g, 124.83 mmol) was dissolved in DMSO (300 ml), and 3,5-dibromopyrazine-2-amine (37.8 g, 149.79 mmol) and Et3N (20.9 ml, 149.79 mmol) were added, followed by stirring at 150° C. for 9 hours. After the completion of the reaction, the reaction mixture was extracted with H2O, EA, and brine, followed by drying (Na2SO4), filtration, and concentration under reduced pressure, and the residue was purified by column chromatography (EA:Hex=1:1), to give (R)-tert-butyl 2-(((3-amino-6-bromopyrazine-2-yl)amino)methyl)morpholine-4-carboxylate (33.9 g, 70%).
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][C:11]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])([O:14][CH2:15][CH2:16][OH:17])[CH2:10][CH2:9]1)C1C=CC=CC=1.[H][H].C>C(O)C>[CH2:18]([C:11]1([O:14][CH2:15][CH2:16][OH:17])[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]1)[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24]
Reactant: [H][H]
Reactant: CCCCCCCC1(OCCO)CCN(Cc2ccccc2)CC1
Solvent: CCO
Product: CCCCCCCC1(OCCO)CCNCC1
Yield: 36.3 %

Procedure:
A solution of 40 g of 2-(1-benzyl-4-heptyl-4-piperidyloxy)-ethanol in 300 ml of absolute ethanol was reacted with hydrogen at 50° C in the presence of 0.4 g of 5% palladized charcoal until the theoretical amount of hydrogen was absorbed and the catalyst was then filtered off. The ethanol was distilled off and the residue was rectified to obtain 10.6 g of 2-(4-heptyl-4-piperidyloxy)-ethanol as a colorless oil boiling at 110°-130° C at 0.1 mm Hg.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]2[C:8]([CH:11]3[CH2:16][CH2:15][N:14]([CH2:17][CH3:18])[CH2:13][CH2:12]3)=[CH:9][NH:10][C:5]2=[CH:4][CH:3]=1.[F:19][C:20]1[CH:28]=[CH:27][C:23]([C:24](Cl)=[O:25])=[CH:22][CH:21]=1>>[F:19][C:20]1[CH:28]=[CH:27][C:23]([C:24]([NH:1][C:2]2[N:7]=[C:6]3[C:8]([CH:11]4[CH2:16][CH2:15][N:14]([CH2:17][CH3:18])[CH2:13][CH2:12]4)=[CH:9][NH:10][C:5]3=[CH:4][CH:3]=2)=[O:25])=[CH:22][CH:21]=1
Reactant: CCN1CCC(c2c[nH]c3ccc(N)nc23)CC1
Reactant: O=C(Cl)c1ccc(F)cc1
Product: CCN1CCC(c2c[nH]c3ccc(NC(=O)c4ccc(F)cc4)nc23)CC1

Procedure:
Beginning with 0.015 gm (0.061 mMol) 5-amino-3-(1-ethylpiperidin-4-yl)pyrrolo[3,2-b]pyridine and 0.009 mL (0.080 mMol) 4-fluorobenzoyl chloride, the title compound was prepared essentially by the procedure described in Example 7.
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:6]=[N:7][N:8]([C:12]([CH3:15])([CH3:14])[CH3:13])[C:9]=1[CH2:10]Br)=[O:4].[CH3:16][O-:17].[Na+]>>[C:12]([N:8]1[C:9]([CH2:10][O:17][CH3:16])=[C:5]([C:3]([OH:2])=[O:4])[CH:6]=[N:7]1)([CH3:15])([CH3:14])[CH3:13]
Reactant: C[O-]
Reactant: COC(=O)c1cnn(C(C)(C)C)c1CBr
Agent: [Na+]
Product: COCc1c(C(=O)O)cnn1C(C)(C)C
Reaction time: 2.5 h
Yield: 88.6 %

Procedure:
A solution of 5-bromomethyl-1-tert-butyl-1H-pyrazole-4-carboxylic acid methyl ester (1.51 g, 5.48 mmol) (as prepared in Example 55, Step 1) in sodium methoxide (23.8 mL, 11.9 mmol, 0.5M solution in methanol) was warmed to 90° C. where it was stirred for 2.5 h. At this time, the reaction was concentrated in vacuo. The resulting white solids were taken up in water (100 mL) and extracted with ethyl acetate (1×150 mL). The organics were then washed with a saturated aqueous sodium bicarbonate solution (1×100 mL), water (1×100 mL) and a saturated aqueous sodium chloride solution (1×100 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. When it was discovered that the product was not in the organic extracts, the aqueous layers were combined and were acidified to pH=1 with concentrated aqueous hydrochloric acid and then were extracted with dichloromethane (1×150 mL). These organics were dried over magnesium sulfate, filtered and concentrated in vacuo to afford 1-tert-butyl-5-methoxymethyl-1H-pyrazole-4-carboxylic acid (1.03 g, 88%) as a white solid. The material was used without further purification.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([C:35]([NH:37][C:38]2[CH:39]=[C:40]([S:56]([OH:59])(=[O:58])=[O:57])[CH:41]=[C:42]3[C:47]=2[C:46]([S:48]([OH:51])(=[O:50])=[O:49])=[CH:45][C:44]([S:52]([OH:55])(=[O:54])=[O:53])=[CH:43]3)=[O:36])[CH:7]=[C:8]([C:10]([NH:12][C:13]2[CH:14]=[C:15]([S:31]([OH:34])(=[O:33])=[O:32])[CH:16]=[C:17]3[C:22]=2[C:21]([S:23]([OH:26])(=[O:25])=[O:24])=[CH:20][C:19]([S:27]([OH:30])(=[O:29])=[O:28])=[CH:18]3)=[O:11])[CH:9]=1)([O-])=O>[Pd].O>[NH2:1][C:4]1[CH:5]=[C:6]([C:35]([NH:37][C:38]2[CH:39]=[C:40]([S:56]([OH:59])(=[O:58])=[O:57])[CH:41]=[C:42]3[C:47]=2[C:46]([S:48]([OH:51])(=[O:49])=[O:50])=[CH:45][C:44]([S:52]([OH:55])(=[O:54])=[O:53])=[CH:43]3)=[O:36])[CH:7]=[C:8]([C:10]([NH:12][C:13]2[CH:14]=[C:15]([S:31]([OH:34])(=[O:32])=[O:33])[CH:16]=[C:17]3[C:22]=2[C:21]([S:23]([OH:26])(=[O:24])=[O:25])=[CH:20][C:19]([S:27]([OH:30])(=[O:28])=[O:29])=[CH:18]3)=[O:11])[CH:9]=1
Reactant: O=C(Nc1cc(S(=O)(=O)O)cc2cc(S(=O)(=O)O)cc(S(=O)(=O)O)c12)c1cc(C(=O)Nc2cc(S(=O)(=O)O)cc3cc(S(=O)(=O)O)cc(S(=O)(=O)O)c23)cc([N+](=O)[O-])c1
Agent: [Pd]
Solvent: O
Product: Nc1cc(C(=O)Nc2cc(S(=O)(=O)O)cc3cc(S(=O)(=O)O)cc(S(=O)(=O)O)c23)cc(C(=O)Nc2cc(S(=O)(=O)O)cc3cc(S(=O)(=O)O)cc(S(=O)(=O)O)c23)c1
Reaction time: 5 h

Procedure:
A mixture of 23.0 g of 8,8'-[(5-nitro-1,3-phenylene) bis(carbonylimino)]di-1,3,6-naphthalenetrisulfonic acid, hexasodium salt, 150 ml of water and 2.3 g of 10% palladium catalyst on carbon is hydrogenated at room temperature for 5 hours at an average pressure of 43 lbs, then is filtered through diatomaceous earth and washed with water. The filtrate is then concentrated to a small volume in vacuo, absolute ethanol is added and the resulting oil is triturated until a solid is formed. This material is filtered and washed with absolute ethanol followed by ether. The product is then oven dried at 120° C to give 8,8'-[(5-amino-1,3-phenylene)bis(carbonylimino)]di-1,3,6-naphthalenetrisulfonic acid, hexasodium salt.
Reaction SMILES: C(N(CC)CC)C.[CH3:8][N:9]=[C:10]=[O:11].[OH:12][C:13]1[N:17]=[C:16]([S:18][CH2:19][CH2:20][CH2:21][CH3:22])[S:15][N:14]=1>C(OC(C)C)(C)C>[CH3:8][NH:9][C:10]([N:14]1[C:13](=[O:12])[N:17]=[C:16]([S:18][CH2:19][CH2:20][CH2:21][CH3:22])[S:15]1)=[O:11]
Reactant: CCCCSc1nc(O)ns1
Reactant: CN=C=O
Solvent: CC(C)OC(C)C
Solvent: CCN(CC)CC
Product: CCCCSc1nc(=O)n(C(=O)NC)s1
Temperature: 20 °C
Reaction time: 2 h
Yield: 54 %

Procedure:
0.5 ml of triethylamine and 4.78 g of methyl isocyanate were added to a solution of 95 g of 3-hydroxy-5-n-butylthio-1,2,4-thiadiazole in 50 ml of isopropyl ether and the mixture was stirred for 2 hours at 20° C and was vacuum filtered. The recovered precipitate was washed with isopropyl ether and dried to obtain 11.2 g of 2-(N-methylcarbamoyl)-5-n-butylthio-1,2,4-thiadiazole-3-one melting at 102° C.
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH:10]1[CH2:15][NH:14][CH2:13][CH2:12][NH:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[S:23]1[CH:27]=[CH:26][CH:25]=[C:24]1[S:28](Cl)(=[O:30])=[O:29]>C(Cl)Cl>[CH2:1]([O:8][CH2:9][CH:10]1[NH:11][CH2:12][CH2:13][N:14]([S:28]([C:24]2[S:23][CH:27]=[CH:26][CH:25]=2)(=[O:30])=[O:29])[CH2:15]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=S(=O)(Cl)c1cccs1
Reactant: c1ccc(COCC2CNCCN2)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=S(=O)(c1cccs1)N1CCNC(COCc2ccccc2)C1
Temperature: 0 °C
Reaction time: 2 h
Yield: 50.3 %

Procedure:
A 250 mL round-bottomed flask was charged with 2-(benzyloxymethyl)piperazine (2.10 g, 10.1 mmol), triethylamine (1.42 mL, 10.2 mmol) and CH2Cl2 (50 mL). After cooling to 0° C., 2-thiophenesulfonyl chloride (1.84 g, 10.1 mmol, Sigma-Aldrich, St. Louis, Mo.) was added slowly via syringe. After 2 h, the mixture was concentrated and diluted with EtOAc (200 mL). The organic solution was washed with 1 N HCl (2×50 mL) and the combined acidic layers made basic with Na2CO3. The resulting basic solution was extracted with EtOAc (3×100 mL) and the combined organic layers were dried (MgSO4), filtered and concentrated to give 3-(benzyloxymethyl)-1-(thiophen-2-ylsulfonyl)piperazine (1.79 g) as a yellow tar.
Reaction SMILES: S(=O)(=O)(O)O.[Cl:6][C:7]1[CH:21]=[CH:20][CH:19]=[CH:18][C:8]=1[CH2:9][NH:10][C:11](=[O:17])[CH:12](OC)OC.C([O-])(O)=O.[Na+]>>[Cl:6][C:7]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:8]=1[CH:9]=[N:10][C:11]([OH:17])=[CH:12]2
Reactant: COC(OC)C(=O)NCc1ccccc1Cl
Agent: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Product: Oc1cc2cccc(Cl)c2cn1
Temperature: 60 °C
Reaction time: 5 h

Procedure:
Concentrated sulfuric acid (18 M; 7.0 mL) was added to N-(2-chlorobenzyl)-2,2-dimethoxyacetamide (2.21 g, 9.07 mmol) at ambient temperature, and the solution was stirred overnight at ambient temperature and at 60° C. for 5 h. The cooled reaction mixture was added to ≈50 mL of ice, and the pH of the yellow mixture was adjusted to 7 with NaHCO3 solution. The yellow precipitate was filtered off, washed with water, and dried in vacuo, giving the title compound as yellow solid. The material was used in the next step without further purification. 1H NMR (400 MHz, DMSO-d6): δ=11.13 (brs, 1H), 9.11 (s, 1H), 7.72 (d, J=8.4 Hz, 1H), 7.54 (dd, J=8.2, 7.2 Hz, 1H), 7.45 (dd, J=0.8, 7.2 Hz, 1H), 7.00 (s, 1H). MS(ES+): m/z=180.07/182.02 (100/38) [MH+]. HPLC: tR=2.45 min (polar—5 min, ZQ3).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.C([Li])(C)(C)C.[C:16](Cl)(=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C1COCC1>[NH:7]1[C:8]2[C:4](=[CH:3][C:2]([C:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[O:23])=[CH:10][CH:9]=2)[CH:5]=[CH:6]1
Reactant: Brc1ccc2[nH]ccc2c1
Reactant: O=C(Cl)c1ccccc1
Agent: [Li]C(C)(C)C
Solvent: C1CCOC1
Product: O=C(c1ccccc1)c1ccc2[nH]ccc2c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 35.4 %

Procedure:
5-Bromoindole(1.0 g, 5.10 mmol) was dissolved in THF (10 mL) and the resulting solution was cooled to −78° C. t-Butyl lithium (1.7 M in pentane, 10.5 mL, 17.9 mmol) was added dropwise and the solution stirred for 30 minutes before being added to a solution of benzoyl chloride (0.86 g, 6.12 mmol) in THF (10 mL) at −78° C. via cannula. The reaction mixture was allowed to warm to room temperature and was stirred overnight and was then quenched with saturated ammonium chloride and diluted with ethyl acetate. The organic phase was washed with water and brine, dried (Na2SO4), filtered and concentrated. Silica gel chromatography using 20% hexane in ethyl acetate as the eluent provided the title compound as a beige solid (0.40 g, 35%).
Reaction SMILES: [C:1]1([N:7]2[CH2:12][CH2:11][N:10]([C:13]([NH:15]C(=O)OCC)=[S:14])[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[OH-].[Na+]>>[C:1]1([N:7]2[CH2:8][CH2:9][N:10]([C:13](=[S:14])[NH2:15])[CH2:11][CH2:12]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CCOC(=O)NC(=S)N1CCN(c2ccccc2)CC1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: NC(=S)N1CCN(c2ccccc2)CC1
Temperature: 80 °C
Reaction time: 2 h
Yield: 62.6 %

Procedure:
Ethyl (4-phenyl-1-piperazinyl)carbothioylcarbamate (13 g, 44 mmol) was added to conc. hydrochloric acid (44 mL), and the mixture was stirred for 2 hours at 80° C. The reaction mixture was made basic with an 8N-aqueous sodium hydroxide solution, and the crystal was collected by filtration. The crystal was washed with water, and dried to obtain a title compound (6.1 g, yield 63%).
Reaction SMILES: [NH2:1][C:2]1[N:7]2[N:8]=[C:9]([CH3:11])[CH:10]=[C:6]2[N:5]=[CH:4][C:3]=1[CH:12]=O.[C:14]1([CH2:20][C:21](OC)=[O:22])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.CC(C)([O-])C.[K+].C1(C)C=CC=CC=1>CN(C=O)C>[CH3:11][C:9]1[CH:10]=[C:6]2[N:5]=[CH:4][C:3]3[CH:12]=[C:20]([C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)[C:21](=[O:22])[NH:1][C:2]=3[N:7]2[N:8]=1
Reactant: COC(=O)Cc1ccccc1
Reactant: Cc1cc2ncc(C=O)c(N)n2n1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Product: Cc1cc2ncc3cc(-c4ccccc4)c(=O)[nH]c3n2n1
Temperature: 105 °C
Reaction time: 0.5 h

Procedure:
Into a round bottom flask was added 7-amino-2-methylpyrazolo[1,5-a]pyrimidine-6-carbaldehyde (1-2) (5.30 g, 30 mmol), methy phenylacetate (18.0 g, 120 mmol), potassium tert-butoxide (5.80 g, 60 mmol), and toluene (100 mL). The reaction mixture was heated to 105° C. while stirring under an atmosphere of nitrogen for 30 min. Then DMF (100 mL) was added and the mixture was stirred at 100° C. for 3 days. The reaction mixture was cooled to room temperature and concentrated in vacuo. The resulting residue was dissolved in DCM (600 mL) and then water (400 mL) was added to the solution. The precipitated solid was collected by filtration and the solid was washed with water (50 mL) and DCM (100 mL). The solid was dried over an oil pump for 2 days to give 2-methyl-7-phenylpyrazolo[1,5-a]pyrido[3,2-e]pyrimidin-8(9H)-one (1-3) as a yellow solid.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH2:7](Cl)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[CH2:15]([O:17][C:18]([CH:20]1[NH:25][C:24](=[O:26])[CH:23]([CH2:27][CH:28]([CH3:30])[CH3:29])[N:22]([OH:31])[C:21]1=[O:32])=[O:19])[CH3:16]>CN(C)C=O.C(OCC)(=O)C>[CH2:7]([C:20]1([C:18]([O:17][CH2:15][CH3:16])=[O:19])[NH:25][C:24](=[O:26])[CH:23]([CH2:27][CH:28]([CH3:29])[CH3:30])[N:22]([O:31][CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:21]1=[O:32])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: ClCc1ccccc1
Reactant: CCOC(=O)C1NC(=O)C(CC(C)C)N(O)C1=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCOC(=O)C1(Cc2ccccc2)NC(=O)C(CC(C)C)N(OCc2ccccc2)C1=O
Temperature: 25 °C
Reaction time: 16 h

Procedure:
7.60 g of potassium carbonate and 6.3 ml of benzyl chloride were added to 100 ml of a solution of 9.57 g of 3-ethoxycarbonyl-1-hydroxy-6-isobutylpiperazine-2,5-dione in anhydrous N,N-dimethylformamide, on ice-cooling. The mixture was stirred at room temperature for 16 hours. The reaction mixture was diluted with 450 ml of ethyl acetate, then washed three times with an aqueous solution saturated with sodium chloride, and dried with anhydrous magnesium sulfate. The resulting solution was subjected to distillation to remove the solvent. The residue was allowed to stand. The resulting crystals were collected by filtration and washed with methanol to obtain 4.51 g of (3RS,6SR)-3-benzyl-1-benzyloxy-3-ethoxycarbonyl-6-isobutylpiperazine-2,5-dione as colorless columnar crystals.
Reaction SMILES: [N+:1]([C:4]1[CH:11]=[CH:10][CH:9]=[CH:8][C:5]=1[CH:6]=O)([O-:3])=[O:2].[CH:12]1([C:15]([CH3:17])=[O:16])[CH2:14][CH2:13]1>>[CH:12]1([C:15]([CH:17]=[CH:6][C:5]2[CH:8]=[CH:9][CH:10]=[CH:11][C:4]=2[N+:1]([O-:3])=[O:2])=[O:16])[CH2:14][CH2:13]1
Reactant: O=Cc1ccccc1[N+](=O)[O-]
Reactant: CC(=O)C1CC1
Product: O=C(C=Cc1ccccc1[N+](=O)[O-])C1CC1

Procedure:
2-Nitrobenzaldehyde is condensed with methyl cyclopropyl ketone to give 2-(2-nitrophenyl)vinyl cyclopropyl ketone. The latter is reduced selectively with hydroxylamine and hydroxylamine O-sulfonic acid in dilute sodium hydroxide solution to yield 2-(2-nitrophenyl)ethyl cyclopropyl ketone, which is then reduced with sodium borohydride to 2-(2-nitrophenyl)ethyl cyclopropyl carbinol. The carbinol is treated in the usual way with phosphorus tribromide and zinc bromide to afford 4-[6-(2-nitrophenyl)-3-hexenyl] bromide. The latter is reacted with potassium iodide, potassium carbonate and 3,5-heptanedione to produce 4-[6-(2-nitrophenyl)-3-hexenyl]-3,5-heptanedione which is selectively reduced with hydroxylamine and hydroxylamine O-sulfonic acid to give the title compound.
Reaction SMILES: C([O:8][CH2:9][CH:10]([CH3:24])[CH2:11][CH2:12][CH2:13][C:14]1([CH3:23])[O:22][CH:15]1[CH2:16][CH2:17][C:18](=[O:21])[CH2:19][Br:20])C1C=CC=CC=1.O(CC(C)CCCC(C)=CCCC(=O)CBr)[Si:26]([C:39]([CH3:42])([CH3:41])[CH3:40])([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>>[O:8]([CH2:9][CH:10]([CH3:24])[CH2:11][CH2:12][CH2:13][C:14]1([CH3:23])[O:22][CH:15]1[CH2:16][CH2:17][C:18](=[O:21])[CH2:19][Br:20])[Si:26]([C:39]([CH3:42])([CH3:41])[CH3:40])([C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
Reactant: CC(=CCCC(=O)CBr)CCCC(C)CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Reactant: CC(CCCC1(C)OC1CCC(=O)CBr)COCc1ccccc1
Product: CC(CCCC1(C)OC1CCC(=O)CBr)CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C

Procedure:
Following the procedure for the preparaton of 11-benzyloxy-1-bromo-6,10-dimethyl-5,6-epoxy-undecan-2-one, but employing 11-t-butyldiphenylsiloxy-1-bromo-6,10 -dimethyl-2-oxo-undec-5-ene (1.6 g) in place of 11-benzyloxy-1-bromo-6,10-dimethyl-2-oxo-undec-5-one, 11-t-butyldiphenylsiloxy-1-bromo-6,10-dimethyl-5,6-epoxy-undecan-2-one (1.3 g) is obtained as a yellow oil:
Reaction SMILES: Cl[C:2]1[C:3]2[S:22][CH2:21][CH2:20][C:4]=2[N:5]=[C:6]([N:8]2[CH2:13][CH2:12][N:11](C3C=CC=CC=3)[CH2:10][CH2:9]2)[N:7]=1.[CH:23]1([NH:29]C2C3SCCC=3N=C(N3CCN(C4C=CC(C(OCC)=O)=CC=4)CC3)N=2)CCC[CH2:25][CH2:24]1>O1CCOCC1>[N:8]1([C:6]2[N:7]=[C:2]([CH2:25][CH2:24][CH2:23][NH2:29])[C:3]3[S:22][CH2:21][CH2:20][C:4]=3[N:5]=2)[CH2:9][CH2:10][NH:11][CH2:12][CH2:13]1
Reactant: CCOC(=O)c1ccc(N2CCN(c3nc4c(c(NC5CCCCC5)n3)SCC4)CC2)cc1
Reactant: Clc1nc(N2CCN(c3ccccc3)CC2)nc2c1SCC2
Solvent: C1COCCO1
Product: NCCCc1nc(N2CCNCC2)nc2c1SCC2
Yield: 78.9 %

Procedure:
1.0 g (4.4 mmol) of (2-chloro-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)propylamine (V) and 1.9 g (21.8 mmol) of piperazine (VI) are placed in 10 mL of dioxane, then reacted for 0.7 hours at 150° C. in the microwave. Then the reaction mixture is extracted with water and ethyl acetate, and the organic phase is dried and evaporated to dryness. The residue is triturated with petroleum ether and suction filtered. 0.97 g of product VII (80%) is obtained as a powder.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([OH:21])=[C:6]([CH:20]=1)[C:7]([C:9]1[C:14]([CH:15]2[O:19][CH2:18][CH2:17][O:16]2)=[CH:13][CH:12]=[CH:11][N:10]=1)=O.Cl.[C:23]([O:27][NH2:28])([CH3:26])([CH3:25])[CH3:24].N1CCCC1>C(O)CC>[C:23]([O:27]/[N:28]=[C:7](\[C:9]1[C:14]([CH:15]2[O:19][CH2:18][CH2:17][O:16]2)=[CH:13][CH:12]=[CH:11][N:10]=1)/[C:6]1[CH:20]=[C:2]([Br:1])[CH:3]=[CH:4][C:5]=1[OH:21])([CH3:26])([CH3:25])[CH3:24]
Reactant: O=C(c1cc(Br)ccc1O)c1ncccc1C1OCCO1
Reactant: CC(C)(C)ON
Agent: Cl
Solvent: CCCO
Solvent: C1CCNC1
Product: CC(C)(C)O/N=C(/c1cc(Br)ccc1O)c1ncccc1C1OCCO1
Yield: 80 %

Procedure:
A solution of 2-(5-bromo-2-hydroxybenzoyl)-3-(1,3-dioxolan-2-yl)pyridine (2.92 g), O-t-butyl-hydroxylamine hydrochloride (2.09 g) and pyrrolidine (1.78 g) in n-propanol (40 ml) was heated for 2 hours under reflux. The reaction mixture was concentrated, to which was added water, followed by subjecting the mixture to extraction with ethyl acetate. The extract solution was washed with a saturated aqueous saline solution, dried (anhydrous sodium sulfate), and concentrated. The concentrate was purified by means of a silica gel column chromatography (eluent: ethyl acetate/hexane) to give (Z)-2-(5-bromo-2-hydroxybenzoyl)-3-(1,3-dioxolan-2-yl)pyridine O-t-butyloxime (2.81 g) (Compound 134).
Reaction SMILES: [CH3:1][C:2]1[N:3]([CH3:15])[C:4]2[C:5]([N:14]=1)=[C:6]1[C:11](=[CH:12][CH:13]=2)[N:10]=[CH:9][CH:8]=[CH:7]1>Cl.C(O)C.[Pt](=O)=O>[CH3:1][C:2]1[N:3]([CH3:15])[C:4]2[C:5]([N:14]=1)=[C:6]1[C:11](=[CH:12][CH:13]=2)[NH:10][CH2:9][CH2:8][CH2:7]1
Reactant: Cc1nc2c3cccnc3ccc2n1C
Agent: O=[Pt]=O
Agent: Cl
Solvent: CCO
Product: Cc1nc2c3c(ccc2n1C)NCCC3
Temperature: 25 °C
Reaction time: 24 h

Procedure:
A mixture of 2,3-dimethyl-3H-imidazo[4,5-f]quinoline (0.40 g, 2.03 mmol) and platinum(IV) oxide (24 mg, 0.11 mmol) in HCl (6 N, 2 mL) and ethanol (10 mL) was stirred at room temperature under H2 for 24 h. Then ethanol was removed under reduced pressure and the residue was dissolved in EtOAc (20 mL) and sat. NaHCO3 (3 mL), filtered through Celite, washed with EtOAc (10 mL×3), and separated. The water layer was then extracted with EtOAc (10 mL×3). The combined organic layers were dried with Na2SO4 and filtered; and the solvent was removed under reduced pressure to give a yellow solid. The residue was used in the next step without further purification (320 mg). MS (ESI): m/z 202 [M+H]+.