Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][Si:2]([CH3:29])([CH3:28])[CH2:3][CH2:4][O:5][C:6](=[O:27])[CH:7]([NH:22][C:23]([O:25][CH3:26])=[O:24])[CH2:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]([N+:19]([O-])=O)=[CH:11][CH:10]=1>CO.[Pd]>[CH3:29][Si:2]([CH3:1])([CH3:28])[CH2:3][CH2:4][O:5][C:6](=[O:27])[CH:7]([NH:22][C:23]([O:25][CH3:26])=[O:24])[CH2:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]([NH2:19])=[CH:11][CH:10]=1
Reactant: COC(=O)NC(Cc1ccc([N+](=O)[O-])c2ccccc12)C(=O)OCC[Si](C)(C)C
Agent: [Pd]
Solvent: CO
Product: COC(=O)NC(Cc1ccc(N)c2ccccc12)C(=O)OCC[Si](C)(C)C
Reaction time: 4 h

Procedure:
A mixture of 2-methoxycarbonylamino-3-(4-nitro-naphthalen-1-yl)-propionic acid 2-trimethylsilanyl-ethyl ester (1.1 g, 2.64 mmol), 10% palladium on C (0.056 g) in methanol (5 mL) was stirred under an atmosphere of hydrogen for 4 hours. The mixture was filtered through diatomaceous earth and the filter cake washed with methanol (2×25 mL). The combined methanol was concentrated under reduced pressure to provide the titled compound. MS (ESI(+)) m/e 389 (M+H)+.
Reaction SMILES: [I-].[CH3:2][S+](C)(C)=O.[H-].[Na+].[CH3:9][O:10][C:11]1([C:14]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)=[O:15])[CH2:13][CH2:12]1.O>CS(C)=O>[F:23][C:20]1[CH:21]=[CH:22][C:17]([CH2:16][C:14]2([C:11]3([O:10][CH3:9])[CH2:13][CH2:12]3)[CH2:2][O:15]2)=[CH:18][CH:19]=1
Reactant: C[S+](C)(C)=O
Reactant: COC1(C(=O)Cc2ccc(F)cc2)CC1
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: COC1(C2(Cc3ccc(F)cc3)CO2)CC1
Temperature: 25 °C
Yield: 70.3 %

Procedure:
15 ml of absolute dimethyl sulphoxide are added dropwise at 10° C. under a nitrogen atmosphere to a mixture of 2.2 g (10 mmol) of trimehylsulphoxonium iodide and 0.4 g (13 mmol) of sodium hydride (80% pure). After addition is complete, the mixture is allowed to warm to room temperature in the course of 10 minutes and a solution of 2 g (9.6 mmol) of 4-fluorobenzyl 1-methoxycyclopropyl ketone in 10 ml of absolute dimethyl sulphoxide is then added dropwise with stirring. The reaction mixture is then poured into water. The resulting mixture is extracted with ethyl acetate. The combined organic phases are washed with water, dried over sodium sulphate and concentrated by stripping off the solvent under reduced pressure. 1.5 g (70% of theory) of 2-(4-fluoro-benzyl)-2-(1-methoxy-cyclopropyl)-oxirane are obtained in this manner in the form of an oil. ##STR33##
Reaction SMILES: [C:1]([O:4][C:5]1[C:6](=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:7]([OH:9])=[O:8])(=[O:3])[CH3:2].Cl[CH2:15][C:16]([N:18]([CH2:21][CH3:22])[CH2:19][CH3:20])=[O:17].C(N(CC)CC)C.[I-].[Na+]>C(OCC)(=O)C>[C:1]([O:4][C:5]1[CH:13]=[CH:12][CH:11]=[CH:10][C:6]=1[C:7]([O:9][CH2:15][C:16]([N:18]([CH2:21][CH3:22])[CH2:19][CH3:20])=[O:17])=[O:8])(=[O:3])[CH3:2]
Reactant: CCN(CC)C(=O)CCl
Reactant: CC(=O)Oc1ccccc1C(=O)O
Agent: [I-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: CCN(CC)C(=O)COC(=O)c1ccccc1OC(C)=O
Yield: 70.5 %

Procedure:
To a mixture of acetylsalicylic acid (5.4 g. 0.03 mole) and 2-chloro-N,N-diethylacetamide (4.5 g, 0.03 mole) in 40 ml of ethyl acetate was added triethylamine (4.2 ml, 0.03 mole) and sodium iodide (0.45 g, 0.003 mole). The mixture was refluxed for 4 h. After cooling the mixture was filtered and the filtrate washed with 2M hydrochloric acid, 5% sodium bicarbonate and water. After drying over anhydrous sodium sulphate the solution was evaporated in vacuo leaving an oil which crystallized by trituration with ethanol. Recrystallization from 80% ethanol afforded 6.2 g (70%) of the title compound. Mp 75°-76° C.
Reaction SMILES: [SH:1][C:2]1[CH:3]=[C:4]([C:8](=[O:10])[CH3:9])[CH:5]=[CH:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].F[C:18]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][CH:19]=1.O>CN(C)C=O>[N+:24]([C:21]1[CH:22]=[CH:23][C:18]([S:1][C:2]2[CH:3]=[C:4]([C:8](=[O:10])[CH3:9])[CH:5]=[CH:6][CH:7]=2)=[CH:19][CH:20]=1)([O-:26])=[O:25]
Reactant: CC(=O)c1cccc(S)c1
Reactant: O=[N+]([O-])c1ccc(F)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(=O)c1cccc(Sc2ccc([N+](=O)[O-])cc2)c1

Procedure:
A suspension of 3′-mercaptoacetophenone (Reference compound No. 4-1, 0.50 g, 3.3 mmol), potassium carbonate (0.55 g, 4.0 mmol) and 4-fluoronitrobenzene (0.42 mL, 4.0 mmol) in N,N-dimethylformamide (20 mL) was stirred at room temperature for 8.5 hours. Water (30 mL) was added to the reaction mixture, extracted with mixed solvent (30 mL) which consists of hexane and ethyl acetate (3:1). The organic layer was washed with brine (30 mL), dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to give the title reference compound (1.2 g) quantitatively as a yellow solid.
Reaction SMILES: Cl.[CH:2]1([CH2:5][N:6]([C@H:15]2[CH2:20][CH2:19][C@H:18]([OH:21])[CH2:17][CH2:16]2)[C:7]([C@H:9]2[CH2:14][CH2:13][CH2:12][NH:11][CH2:10]2)=[O:8])[CH2:4][CH2:3]1.[Cl:22][C:23]1[C:24]([CH3:33])=[C:25]([S:29](Cl)(=[O:31])=[O:30])[CH:26]=[CH:27][CH:28]=1.C(N(CC)CC)C>C(#N)C>[Cl:22][C:23]1[C:24]([CH3:33])=[C:25]([S:29]([N:11]2[CH2:12][CH2:13][CH2:14][C@H:9]([C:7]([N:6]([CH2:5][CH:2]3[CH2:3][CH2:4]3)[C@H:15]3[CH2:16][CH2:17][C@H:18]([OH:21])[CH2:19][CH2:20]3)=[O:8])[CH2:10]2)(=[O:31])=[O:30])[CH:26]=[CH:27][CH:28]=1
Reactant: O=C([C@H]1CCCNC1)N(CC1CC1)[C@H]1CC[C@H](O)CC1
Reactant: Cc1c(Cl)cccc1S(=O)(=O)Cl
Agent: Cl
Solvent: CC#N
Solvent: CCN(CC)CC
Product: Cc1c(Cl)cccc1S(=O)(=O)N1CCC[C@H](C(=O)N(CC2CC2)[C@H]2CC[C@H](O)CC2)C1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A mixture of (3S)—N-(cyclopropylmethyl)-N-(trans-4-hydroxycyclohexyl)piperidine-3-carboxamide hydrochloride (10 mg, 0.03 mmol), 3-chloro-2-methylbenzenesulfonyl chloride (7.1 mg, 0.03 mmol), triethylamine (11 μL, 0.08 mmol) in acetonitrile (0.2 mL) was stirred at r.t. for 1 hour, then purified with flash column. 5.1 mg (yield: 34%) final product was obtained. LCMS: m/z 468.9 (M+H)+.
Reaction SMILES: Cl[C:2]1[NH:6][C:5]2[CH:7]=[C:8]([C:11]([F:14])([F:13])[F:12])[CH:9]=[CH:10][C:4]=2[N:3]=1.[Cl:15][C:16]1[CH:17]=[C:18]([CH2:29][N:30]([CH3:34])[C:31](=[O:33])[CH3:32])[CH:19]=[N:20][C:21]=1[N:22]1[CH2:27][CH2:26][NH:25][C@H:24]([CH3:28])[CH2:23]1>C(O)C>[Cl:15][C:16]1[CH:17]=[C:18]([CH2:29][N:30]([CH3:34])[C:31](=[O:33])[CH3:32])[CH:19]=[N:20][C:21]=1[N:22]1[CH2:27][CH2:26][N:25]([C:2]2[NH:3][C:4]3[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[CH:7][C:5]=3[N:6]=2)[C@H:24]([CH3:28])[CH2:23]1
Reactant: CC(=O)N(C)Cc1cnc(N2CCN[C@H](C)C2)c(Cl)c1
Reactant: FC(F)(F)c1ccc2nc(Cl)[nH]c2c1
Solvent: CCO
Product: CC(=O)N(C)Cc1cnc(N2CCN(c3nc4cc(C(F)(F)F)ccc4[nH]3)[C@H](C)C2)c(Cl)c1

Procedure:
A mixture of 2-chloro-6-trifluoromethyl-1H-benzoimidazole (88 mg, 0.4 mmol, Example 1c) and N-[5-chloro-6-[(3R)-3-methyl-piperazin-1-yl]-pyridin-3-ylmethyl]-N-methyl-acetamide from step (b) above (148 mg, 0.5 mmol) in ethanol (2 mL) reacted under the conditions Example 3c to give the title compound. MS (ESI, pos. ion) m/z: 481 (M+1).
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]([N:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)=O)=[CH:9][C:4]=2[N:3]=[CH:2]1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[N:12]1([CH2:10][C:8]2[CH:7]=[CH:6][C:5]3[NH:1][CH:2]=[N:3][C:4]=3[CH:9]=2)[CH2:13][CH2:14][O:15][CH2:16][CH2:17]1
Reactant: O=C(c1ccc2[nH]cnc2c1)N1CCOCC1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: c1nc2cc(CN3CCOCC3)ccc2[nH]1
Temperature: 0 °C
Reaction time: 2 h
Yield: 89.3 %

Procedure:
To a stirred solution of (1H-benzoimidazol-5-yl)-morpholin-4-yl-methanone (1 g, 4.32 mmol) in THF (60 mL) at 0° C. was added LiAlH4 (2M in THF; 4.32 mL, 8.65 mmol) dropwise. The mixture was stirred 0° C. for 2 hours then warmed to room temperature for 2 hours. The mixture was cooled again to 0° C. and then quenched by addition of H2O (0.328 mL), followed by 15% aqueous NaOH solution (0.328 mL) and finally H2O (3×0.328 mL). The mixture was stirred for 1 hour and left to stand overnight. The mixture was diluted with THF, filtered, concentrated in vacuo and purified by SiO2 chromatography to give 5-morpholin-4-ylmethyl-1H-benzoimidazole (838 mg). Step 3 was performed by repeating procedures described for Example 1 then gave the title compound as a mixture of two regioisomers.
Reaction SMILES: Br[C:2]1[N:7]=[CH:6][C:5]([CH:8]=[O:9])=[CH:4][CH:3]=1.[C:10]([C:13]1[CH:14]=[CH:15][C:16]([F:22])=[C:17](B(O)O)[CH:18]=1)(=[O:12])[NH2:11].C([O-])([O-])=O.[Na+].[Na+]>COCCOC.CCO>[F:22][C:16]1[CH:17]=[CH:18][C:13]([C:10]([NH2:11])=[O:12])=[CH:14][C:15]=1[C:2]1[CH:3]=[CH:4][C:5]([CH:8]=[O:9])=[CH:6][N:7]=1
Reactant: NC(=O)c1ccc(F)c(B(O)O)c1
Reactant: O=Cc1ccc(Br)nc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: COCCOC
Product: NC(=O)c1ccc(F)c(-c2ccc(C=O)cn2)c1
Temperature: 80 °C

Procedure:
To a solution of 6-bromo-3-pyridinecarboxaldehyde (336 mg, 1.80 mmol) in DME (8 mL) and EtOH (4 mL) under argon, was added (5-carbamoyl-2-fluorophenyl)boronic acid (300 mg, 1.64 mmol) followed by palladium tetrakistriphenylphosphine (190 mg, 0.16 mmol) and 2M Na2CO3 (4 mL). The mixture was heated to 80° C. for 16 h and then allowed to cool to rt. The mixture was partitioned between EtOAc (50 mL), THF (50 mL) and Na2CO3 (20 mL). The aqueous was extracted with EtOAc (50 mL) and the combined organics washed with brine (30 mL) and dried (MgSO4). The solvent was removed in vacuo and the residue purified by column chromatography (0.4% NH3: 4% MeOH: DCM) to give the title compound: RT=2.50 min; m/z (ES+)=245.0 [M+H]+.
Reaction SMILES: C[O:2][C:3]1[CH:4]=[C:5]([C:9]([CH3:16])([CH3:15])[CH2:10][C:11]([O:13][CH3:14])=[O:12])[CH:6]=[CH:7][CH:8]=1.C(S)CS.[Cl-].[Al+3].[Cl-].[Cl-]>ClCCCl>[OH:2][C:3]1[CH:4]=[C:5]([C:9]([CH3:16])([CH3:15])[CH2:10][C:11]([O:13][CH3:14])=[O:12])[CH:6]=[CH:7][CH:8]=1
Reactant: COC(=O)CC(C)(C)c1cccc(OC)c1
Agent: SCCS
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCCl
Product: COC(=O)CC(C)(C)c1cccc(O)c1
Temperature: 25 °C
Yield: 98.4 %

Procedure:
To a solution of methyl 3-(3-methoxyphenyl)-3-methylbutanoate 85.E (0.227 g, 1.02 mmol) in 1,2-dichloroethane (10 mL) was added 1,2-ethanedithiol (1.37 mL, 16.3 mmol) followed by aluminum chloride (1.09 g, 8.17 mmol) at 0° C. The reaction mixture was allowed to slowly warm to room temperature over four hours and was then quenched with saturated Rochelle's salt (potassium sodium tartrate) solution. The mixture was extracted (2×50 mL) with DCM. The combined organic layers were washed with water (1×40 mL) and brine (1×40 mL) and dried over magnesium sulfate. The filtrate was concentrated and the residue was purified by medium pressure chromatography (silica, 0 to 30% EtOAc:hexanes) to give methyl 3-(3-hydroxyphenyl)-3-methylbutanoate 85 (0.209 g, 98.3% yield). MS ESI (pos.) m/e: 226.0 (M+H2O)+.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[S:9][C:10]3[C:15]([N:16]=2)=[CH:14][CH:13]=[C:12]([C:17]2([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[CH2:19][CH2:18]2)[N:11]=3)[CH:5]=[C:4]([CH3:26])[C:3]=1[OH:27].[F-].[Cs+].[CH2:30]1[O:32][C@@H:31]1[CH2:33][OH:34]>CN(C=O)C>[CH3:26][C:4]1[CH:5]=[C:6]([C:8]2[S:9][C:10]3[C:15]([N:16]=2)=[CH:14][CH:13]=[C:12]([C:17]2([C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=4)[CH2:18][CH2:19]2)[N:11]=3)[CH:7]=[C:2]([CH3:1])[C:3]=1[O:27][CH2:30][C@H:31]([OH:32])[CH2:33][OH:34]
Reactant: Cc1cc(-c2nc3ccc(C4(c5ccccc5)CC4)nc3s2)cc(C)c1O
Reactant: OC[C@@H]1CO1
Agent: [Cs+]
Agent: [F-]
Solvent: CN(C)C=O
Product: Cc1cc(-c2nc3ccc(C4(c5ccccc5)CC4)nc3s2)cc(C)c1OC[C@H](O)CO
Temperature: 80 °C

Procedure:
A mixture of 2,6-dimethyl-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenol (35.1 mg, 94 μmol) and cesium fluoride (0.72 mg, 4.7 μmol) in anhydrous DMF (0.5 mL) was stirred at 25° C. for 1 h. (R)-(+)-glycidol (98% ee) (6.6 μl, 99 μmol) was then added, and the resulting mixture was heated under argon at 80° C. for 2 d. Additional (R)-(+)-glycidol (6.56 μl, 98.9 μmol) was then added, and the reaction mixture was heated at 80° C. for 18 h. The reaction mixture was subsequently cooled to 25° C., filtered through Celite, diluted with DMSO (1.5 mL), and purified by rpHPLC (10-100% CH3CN/water+0.1% TFA) to provide (R)-3-(2,6-dimethyl-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenoxy)propane-1,2-diol as a white solid. MS (ESI) m/z: Calculated: 446.2; Observed: 447.0 (M++1).
Reaction SMILES: [CH3:1][O:2][CH:3]([C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:8]=1)[C:4]([OH:6])=O.[NH2:20][CH2:21][C:22]1[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][CH:23]=1>>[C:21]([C:22]1[CH:29]=[CH:28][C:25]([CH2:26][NH:27][C:4](=[O:6])[CH:3]([O:2][CH3:1])[C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([O:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:8]=2)=[CH:24][CH:23]=1)#[N:20]
Reactant: COC(C(=O)O)c1cccc(Oc2ccccc2)c1
Reactant: N#Cc1ccc(CN)cc1
Product: COC(C(=O)NCc1ccc(C#N)cc1)c1cccc(Oc2ccccc2)c1

Procedure:
(RS)-Methoxy-(3-phenoxy-phenyl)-acetic acid was coupled with 4-aminomethyl benzonitrile according to general procedure B to give (RS)-N-(4-cyano-benzyl)-2-methoxy-2-(3-phenoxy-phenyl)-acetamide. Light yellow oil. MS 373.3 ([M+H]+)
Reaction SMILES: C[O:2][C:3]1[C:11]2[O:10][CH:9]=[CH:8][C:7]=2[CH:6]=[CH:5][CH:4]=1.[I-].[Li+].Cl>N1C(C)=CC(C)=CC=1C>[OH:2][C:3]1[C:11]2[O:10][CH:9]=[CH:8][C:7]=2[CH:6]=[CH:5][CH:4]=1
Reactant: COc1cccc2ccoc12
Agent: Cl
Agent: [I-]
Agent: [Li+]
Solvent: Cc1cc(C)nc(C)c1
Product: Oc1cccc2ccoc12
Yield: 96.7 %

Procedure:
To a solution of 7-methoxybenzofuran (8.0 g) in collidine (80 ml) was added lithium iodide (14.5 g), and the mixture was refluxed under argon atmosphere for 1 day and cooled. To the mixture was added 1N hydrochloric acid, and the mixture was extracted with ethyl acetate (twice). The organic layer was washed with 1N hydrochloric acid (twice), water and saturated brine, and dried with magnesium sulfate. Under reduced pressure, the solvent was evaporated, and the residue was purified with silica gel column chromatography to give dark brown oil of 7-hydroxybenzofuran (7.0 g).
Reaction SMILES: [F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si]([O:26][C:27]1[C:32](/[CH:33]=[CH:34]\[C:35]2[CH:40]=[C:39]([O:41][CH3:42])[C:38]([O:43][CH3:44])=[C:37]([O:45][CH3:46])[CH:36]=2)=[CH:31][CH:30]=[C:29]([O:47][CH2:48][CH:49]=[CH2:50])[C:28]=1[O:51][Si](C(C)(C)C)(C)C)(C(C)(C)C)(C)C.C(O)(=O)C.O>C1COCC1>[OH:26][C:27]1[C:32](/[CH:33]=[CH:34]\[C:35]2[CH:36]=[C:37]([O:45][CH3:46])[C:38]([O:43][CH3:44])=[C:39]([O:41][CH3:42])[CH:40]=2)=[CH:31][CH:30]=[C:29]([O:47][CH2:48][CH:49]=[CH2:50])[C:28]=1[OH:51]
Reactant: C=CCOc1ccc(/C=C\c2cc(OC)c(OC)c(OC)c2)c(O[Si](C)(C)C(C)(C)C)c1O[Si](C)(C)C(C)(C)C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: CC(=O)O
Solvent: O
Solvent: C1CCOC1
Product: C=CCOc1ccc(/C=C\c2cc(OC)c(OC)c(OC)c2)c(O)c1O
Temperature: 25 °C

Procedure:
Tetrabutylammonium fluoride (0.24 mL, 0.24 mmol, 1M in THF) was added to a solution of 1,2-di(t-butyldimethylsilyloxy)-3-allyloxy-6-[(Z)-2-(3,4,5-trimethoxyphenyl)vinyl]-benzene (69 mg, 0.120 mmol) and glacial acetic acid (14 μL, 0.24 mmol) in THF 4 mL at 0° C. The reaction mixture was allowed to warm to rt overnight, then cooled to 0° C. and water was added. The reaction mixture was extracted with t-BuOMe (3×) and the organic phase was dried (Na2SO4) and evaporated to dryness. Purification by column chromatography (SiO2 3:7 EtOAc:cyclohexane) gave ZSB-84 (36 mg, 84%) as an 96:4 mixture of Z:E isomers:
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].S(=O)(=O)(O)O.[CH3:19][CH2:20]O>>[CH2:19]([O:5][C:4](=[O:6])[C:3]1[CH:7]=[CH:8][C:9]([N+:11]([O-:13])=[O:12])=[CH:10][C:2]=1[CH3:1])[CH3:20]
Reactant: CCO
Reactant: Cc1cc([N+](=O)[O-])ccc1C(=O)O
Agent: O=S(=O)(O)O
Product: CCOC(=O)c1ccc([N+](=O)[O-])cc1C

Procedure:
2-Methyl-4-nitrobenzoic acid (10 g, 55.2 mmol) in EtOH (200 mL) was treated with sulfuric acid (2 mL) and stirred at reflux until the reaction was complete. The mixture was worked-up and purified to give the title compound.
Reaction SMILES: [CH2:1]([O:3][C:4]([CH:6]1[CH2:11][CH2:10][CH2:9][CH2:8][C:7]1=[O:12])=[O:5])[CH3:2].[Br:13]C1CC(C(C)C)CCC1=O>>[CH2:1]([O:3][C:4]([CH:6]1[CH2:11][CH2:10][CH2:9][CH:8]([Br:13])[C:7]1=[O:12])=[O:5])[CH3:2]
Reactant: CCOC(=O)C1CCCCC1=O
Reactant: CC(C)C1CCC(=O)C(Br)C1
Product: CCOC(=O)C1CCCC(Br)C1=O

Procedure:
The bromination of 2-oxo-cyclohexane carboxylic acid ethyl ester takes place in a manner similar to that described above for the preparation of 2-bromo-4-isopropyl-cyclohexanone. The title compound is reacted as a crude product without further characterization.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:24]=[CH:23][CH:22]=[CH:21][C:10]=1[CH2:11][C:12]1[C:13](=[O:20])[NH:14][NH:15][C:16]=1[CH:17]([CH3:19])[CH3:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:25][C:26]([O:28][CH2:29][C@H:30]1[O:35][C@H:34](Br)[C@H:33]([O:37][C:38]([CH3:40])=[O:39])[C@@H:32]([O:41][C:42]([CH3:44])=[O:43])[C@@H:31]1[O:45][C:46]([CH3:48])=[O:47])=[O:27]>C(#N)C.C(=O)([O-])[O-].[Ag+2]>[CH:17]([C:16]1[NH:15][N:14]=[C:13]([O:20][C@@H:34]2[O:35][C@H:30]([CH2:29][O:28][C:26](=[O:27])[CH3:25])[C@@H:31]([O:45][C:46](=[O:47])[CH3:48])[C@H:32]([O:41][C:42](=[O:43])[CH3:44])[C@H:33]2[O:37][C:38](=[O:39])[CH3:40])[C:12]=1[CH2:11][C:10]1[CH:21]=[CH:22][CH:23]=[CH:24][C:9]=1[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)([CH3:19])[CH3:18]
Reactant: CC(C)c1[nH][nH]c(=O)c1Cc1ccccc1OCc1ccccc1
Reactant: CC(=O)OC[C@H]1O[C@H](Br)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Agent: [Ag+2]
Agent: O=C([O-])[O-]
Solvent: CC#N
Product: CC(=O)OC[C@H]1O[C@@H](Oc2n[nH]c(C(C)C)c2Cc2ccccc2OCc2ccccc2)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O

Procedure:
To a suspension of 4-(2-benzyloxybenzyl)-5-isopropyl-1,2-dihydropyrazol-3-one (114 mg) and acetobromo-α-D-glucose (173 mg) in acetonitrile (2 mL) was added silver carbonate (127 mg), and the mixture was stirred under shading the light at room temperature for 3 days. The reaction mixture was purified by column chromatography on aminopropyl silica gel (eluent: ethyl acetate/hexane=1/1) to give 5-isopropyl-4-(2-benzyloxybenzyl)-3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-1H-pyrazole. To a solution of 5-isopropyl-4-(2-benzyloxybenzyl)-3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-1H-pyrazole in tetrahydrofuran (1 mL) and methanol (0.5 mL) was added sodium methoxide (28% methanol solution, 50 μL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: dichloromethane/methanol=10/1-5/1) to give the title compound (22 mg).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[CH:34]=[CH:33][C:17]([CH2:18][N:19]3[CH2:28][CH2:27][C:26]4[C:21](=[CH:22][CH:23]=[C:24]([C:29]([O:31][CH3:32])=[O:30])[CH:25]=4)[CH2:20]3)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>CO.[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:15]=[CH:16][C:17]([CH2:18][N:19]3[CH2:28][CH2:27][C:26]4[C:21](=[CH:22][CH:23]=[C:24]([C:29]([O:31][CH3:32])=[O:30])[CH:25]=4)[CH2:20]3)=[CH:33][CH:34]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: COC(=O)c1ccc2c(c1)CCN(Cc1ccc(C3=CCN(C(=O)OC(C)(C)C)CC3)cc1)C2
Agent: [Pd]
Solvent: CO
Product: COC(=O)c1ccc2c(c1)CCN(Cc1ccc(C3CCN(C(=O)OC(C)(C)C)CC3)cc1)C2
Temperature: 25 °C
Reaction time: 2 h
Yield: 87.3 %

Procedure:
A solution of methyl 2-{4-[1-(tert-butoxycarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]benzyl}-1,2,3,4-tetrahydroisoquinoline-6-carboxylate (228 mg, 0.493 mmol) in MeOH (5.0 mL) was degassed thoroughly and palladium on carbon (5% Pd/C, 15.6 mg, 0.0025 mmol) was added. The mixture was stirred at rt under an atmosphere of hydrogen gas for 2 h. The reaction mixture was filtered through a pad of Celite, and the filtrate was concentrated to give methyl 2-{4-[1-(tert-butoxycarbonyl)piperidin-4-yl]benzyl}-1,2,3,4-tetrahydroisoquinoline-6-carboxylate (200 mg, 87%) which was used without purification. LC-MS: (FA) ES+ 465.
Reaction SMILES: [NH2:1][C:2]([NH2:4])=[O:3].N.[NH2:6][C:7]([NH:9][C:10]([NH2:12])=[O:11])=[O:8]>>[NH2:6][C:7]([NH:9][C:10]([NH2:12])=[O:11])=[O:8].[NH:1]1[C:10](=[O:11])[NH:9][C:7](=[O:8])[NH:4][C:2]1=[O:3]
Reactant: NC(N)=O
Agent: N
Agent: NC(=O)NC(N)=O
Product: O=c1[nH]c(=O)[nH]c(=O)[nH]1

Procedure:
When molten urea is heated first at atmospheric pressure and thereafter under vacuum, there is a rapid evolution of ammonia upon the application of the vacuum. This indicates the presence of a substantial quantity of biuret precursor moieties generated during the pyrolysis at atmospheric pressure. These active bodies then react under the influence of reduced pressure to give enhanced yields of biuret without excessive production of cyanuric acid.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH2:19][CH:20]=[CH2:21])[CH2:9][C:10]1[CH:11]=[CH:12][CH:13]=[C:14]2[C:18]=1[NH:17][CH:16]=[CH:15]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH2:24](Br)[CH:25]=[CH2:26]>CN(C)C=O.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]([CH2:19][CH:20]=[CH2:21])[CH2:9][C:10]1[CH:11]=[CH:12][CH:13]=[C:14]2[C:18]=1[N:17]([CH2:26][CH:25]=[CH2:24])[CH:16]=[CH:15]2)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: C=CCN(Cc1cccc2cc[nH]c12)C(=O)OC(C)(C)C
Reactant: C=CCBr
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: C=CCN(Cc1cccc2ccn(CC=C)c12)C(=O)OC(C)(C)C
Temperature: 22 °C
Reaction time: 0.5 h
Yield: 90.6 %

Procedure:
To a 0° C. solution of N-[tert-butoxycarbonyl]N-allyl N-[(1H-indol-7-yl)methyl]amine (6.6 g, 23 mmol) in anhydrous dimethylformamide was added slowly sodium hydride (60% dispersion in mineral oil, 1.75 g, 43.7 mmol). The mixture was warmed to 20-24° C. and stirred for 30 minutes, followed by the addition of allyl bromide (4.0 mL, 46 mmol). The reaction was then stirred at 20-24° C. overnight. The reaction mixture was diluted with ethyl acetate (450 mL), washed with water (2×100 mL), saturated aqueous sodium chloride (150 mL), and the organic layer dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was subjected to silica gel chromatography, eluting with 10% ethyl acetate in hexanes. Fractions containing product were combined and concentrated under reduced pressure to provide 6.8 g (91%) of the desired compound as a light brown oil.
Reaction SMILES: [C:1]([NH:4][C:5]1[C:13]2[C:12]([C:14]([O:16]CC=C)=[O:15])=[C:11]([O:20][C:21]3[N:26]=[C:25]([O:27][CH3:28])[CH:24]=[C:23]([O:29][CH3:30])[N:22]=3)[CH:10]=[CH:9][C:8]=2[NH:7][C:6]=1[CH3:31])(=[O:3])[CH3:2].CC1(C)CC(=O)CC(=O)C1>O1CCCC1>[C:1]([NH:4][C:5]1[C:13]2[C:12]([C:14]([OH:16])=[O:15])=[C:11]([O:20][C:21]3[N:26]=[C:25]([O:27][CH3:28])[CH:24]=[C:23]([O:29][CH3:30])[N:22]=3)[CH:10]=[CH:9][C:8]=2[NH:7][C:6]=1[CH3:31])(=[O:3])[CH3:2]
Reactant: C=CCOC(=O)c1c(Oc2nc(OC)cc(OC)n2)ccc2[nH]c(C)c(NC(C)=O)c12
Agent: CC1(C)CC(=O)CC(=O)C1
Solvent: C1CCOC1
Product: COc1cc(OC)nc(Oc2ccc3[nH]c(C)c(NC(C)=O)c3c2C(=O)O)n1
Temperature: 25 °C
Reaction time: 4 h
Yield: 92.4 %

Procedure:
0.49 g of allyl 3-acetylamino-5-[(4,6-dimethoxypyrimidin-2-yl)oxy]-2-methylindol-4-carboxylate was dissolved in 10 ml of tetrahydrofuran, and 0.1 g of dimedone and 0.01 g of tetrakistriphenylphosphine palladium were added thereto. The mixture was stirred at room temperature for 4 hours. Crystals obtained by concentration under reduced pressure, was washed with isopropyl ether to obtain 0.41 g (yield: 93%) of the desired compound. mp: 230°-233° C.