Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:14][C@H:13]([OH:15])[CH2:12][C@@H:11]1[C@H:16]1[O:20][C:19]([CH3:22])([CH3:21])[N:18]([C:23](=[O:25])[CH3:24])[C@H:17]1[CH2:26][C:27]1[CH:32]=[C:31]([F:33])[CH:30]=[C:29]([F:34])[CH:28]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4].Br[CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([O:43][C:44]([F:47])([F:46])[F:45])[CH:38]=1>CN(C)C=O>[C:3]([O:7][C:8]([N:10]1[CH2:14][C@H:13]([O:15][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([O:43][C:44]([F:45])([F:46])[F:47])[CH:38]=2)[CH2:12][C@@H:11]1[C@H:16]1[O:20][C:19]([CH3:21])([CH3:22])[N:18]([C:23](=[O:25])[CH3:24])[C@H:17]1[CH2:26][C:27]1[CH:28]=[C:29]([F:34])[CH:30]=[C:31]([F:33])[CH:32]=1)=[O:9])([CH3:4])([CH3:5])[CH3:6]
Reactant: CC(=O)N1[C@@H](Cc2cc(F)cc(F)c2)[C@@H]([C@H]2C[C@@H](O)CN2C(=O)OC(C)(C)C)OC1(C)C
Reactant: FC(F)(F)Oc1cccc(CBr)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(=O)N1[C@@H](Cc2cc(F)cc(F)c2)[C@@H]([C@H]2C[C@@H](OCc3cccc(OC(F)(F)F)c3)CN2C(=O)OC(C)(C)C)OC1(C)C
Reaction time: 1 h
Yield: 102 %

Procedure:
Add 95% sodium hydride (0.008 g, 0.33 mmol) over 5 minutes to a solution of (2R,4R)-2-[(4S,5S)-3-acetyl-4-(3,5-difluorobenzyl)-2,2-dimethyloxazolidin-5-yl]-4-hydroxypyrrolidine-1-carboxylic acid tert-butyl ester (0.101 g, 0.22 mmol) and 1-bromomethyl-3-trifluoromethoxy-benzene (0.054 mL, 0.333 mmol) in N,N-dimethylformamide (1 mL). Stir 1 hour and partition with ethyl acetate and water, wash with saturated aqueous sodium chloride, dry with magnesium sulfate and purify on silica gel with ethyl acetate/hexane mixtures to give the desired compound as a foam (0.141 g, 100%).
Reaction SMILES: CC(C)=O.[OH:5][CH2:6][CH:7]([CH2:9][OH:10])[OH:8].[OH-].[Na+].[CH2:13](Cl)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C1(C)C=CC=CC=1.S(=O)(=O)(O)O.C(N(CC)CC)C>[CH2:13]([O:5][CH2:6][CH:7]([OH:8])[CH2:9][OH:10])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: OCC(O)CO
Reactant: ClCc1ccccc1
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)=O
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: OCC(O)COCc1ccccc1
Reaction time: 3 h
Yield: 84 %

Procedure:
Into a mixed solution of acetone (800 ml) and glycerin (199 g, 2.16 mol) was added 98% sulfuric acid (6.9 g) at about 25° C., and the mixture was stirred for 3 hours. To this reaction solution was added triethylamine (18.0 g), and the solvent was distilled off under reduced pressure. Into a solution prepared by suspending sodium hydroxide (98.5 g) in toluene (526 ml) was dropped the above-described concentration residue at 55 to 75° C. Into this reaction solution, benzyl chloride (229 g, 1.81 mol) was dropped at 95 to 105%, and the mixture was reacted for 5 hours while distilling components of lower boiling points off. After completion of the reaction, water (366 ml) was added, and the liquid was partitioned. To the resultant toluene layer was added 98% sulfuric acid (22.9 g) and water (571 ml), and the mixture was stirred at about 50° C. for 5 hours stirred, then, the toluene layer was concentrated under reduced pressure. To the residue was added heptane (267 ml), methanol (534 ml) and water (267 ml), and the mixture was liquid-partitioned. The aqueous layer was liquid-partitioned by further adding heptane (267 ml), and the resulting aqueous layer was concentrated under reduced pressure to remove methanol. To the concentrated liquid was added sodium chloride (46 g), and the mixture was extracted twice with ethyl acetate (267 ml). The resultant ethyl acetate solution was concentrated under reduced pressure to obtain a title compound (277 g, yield 84%).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([O:7][CH2:8][CH2:9][OH:10])[CH:2]=1.CN1CCOCC1.ClC(OC1C=CC([N+]([O-])=O)=CC=1)=O.[CH:31]([CH:34]1[C:39]2[N:40]=[CH:41][NH:42][C:38]=2[CH2:37][CH2:36][N:35]1[C:43](OCC1SC=CN=1)=[O:44])([CH3:33])[CH3:32].CCN(C(C)C)C(C)C>C(Cl)Cl>[CH:31]([CH:34]1[C:39]2[N:40]=[CH:41][NH:42][C:38]=2[CH2:37][CH2:36][N:35]1[C:43]([O:10][CH2:9][CH2:8][O:7][C:3]1[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=1)=[O:44])([CH3:33])[CH3:32]
Reactant: CC(C)C1c2nc[nH]c2CCN1C(=O)OCc1nccs1
Reactant: OCCOc1cccnc1
Agent: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: CN1CCOCC1
Product: CC(C)C1c2nc[nH]c2CCN1C(=O)OCCOc1cccnc1
Temperature: 25 °C
Reaction time: 5 h
Yield: 1.1 %

Procedure:
2-(3-Pyridyloxy)ethanol (0.62 g, 4.40 mmol) was dissolved in DCM (10.0 mL) at 0° C. and NMM (0.50 mL, 4.40 mmol) and 4-nitrophenyl chloroformate (0.90 g, 4.40 mmol) were added. The reaction mixture was stirred at room temperature for 5 h. A solution of Intermediate 1 (0.35 g, 2.10 mmol) and DIPEA (1.10 g, 1.50 mL, 8.50 mmol) in DCM (20 mL) was added and the resulting solution was stirred for 3 d. The solvents were removed in vacuo, the residue was dissolved in MeOH (4 mL) and 1 M aq NaOH solution (4 mL) and the reaction mixture was stirred for 2 h and concentrated in vacuo. The residue was dissolved in EtOAc (60 mL), the organic layer was washed with 1 M aq Na2CO3 solution (5×40 mL), dried (MgSO4) and the solvents were removed in vacuo. The residue was purified by column chromatography (normal phase, 20 g, Strata SI-1, silica gigatube, DCM (200 mL) followed by 2%, 4%, 5% and 10% MeOH in DCM (200 mL)) and reverse phase HPLC (YMC ODS-A 100×20 mm, 5 μm, 25 mL per min, gradient 0% to 40% (over 7 min) then 100% (3 min) MeOH in 10% MeOH/water) to give 2-(pyridin-3-yloxy)ethyl 4-isopropyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridine-5-carboxylate (7.4 mg, 1%) as a white solid.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH:4]([C:7]2[N:12]=[C:11]([C:13]([OH:15])=O)[CH:10]=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.[N:16]1([NH2:22])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1>>[N:16]1([NH:22][C:13]([C:11]2[CH:10]=[CH:9][CH:8]=[C:7]([CH:4]3[CH2:3][CH2:2][O:1][CH2:6][CH2:5]3)[N:12]=2)=[O:15])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1
Reactant: O=C(O)c1cccc(C2CCOCC2)n1
Reactant: NN1CCCCC1
Product: O=C(NN1CCCCC1)c1cccc(C2CCOCC2)n1

Procedure:
The title compound was synthesized in analogy to Example 1, using 6-(tetrahydro-pyran-4-yl)-pyridine-2-carboxylic acid and 1-piperidinamine (CAN 2213-43-6) as starting materials, MS (LC/MS): 290.2 [M+H]+.
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:8]([C:12]([NH:14][CH2:15][CH:16]3[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)=[O:13])=[C:7]([Cl:22])[CH:6]=[CH:5][C:4]=2[N:3]=1.[NH:23]1[CH2:28][CH2:27][CH:26]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:25][CH2:24]1>>[Cl:22][C:7]1[C:8]([C:12]([NH:14][CH2:15][CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)=[O:13])=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([N:23]1[CH2:28][CH2:27][CH:26]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:25][CH2:24]1)[CH:11]=[CH:10]2
Reactant: O=C(NCC1CCCCC1)c1c(Cl)ccc2nc(Cl)ccc12
Reactant: CCOC(=O)C1CCNCC1
Product: CCOC(=O)C1CCN(c2ccc3c(C(=O)NCC4CCCCC4)c(Cl)ccc3n2)CC1
Yield: 73.6 %

Procedure:
Prepared according to the method of example 30, using 2,6-dichloro-N-(cyclohexylmethyl)-5-quinolinecarboxamide (Example 43(a)) (200 mg) and 4-piperidinecarboxylic acid, ethyl ester (470 mg) to afford the sub-titled compound as a solid (200 mg).
Reaction SMILES: [Cl:1][C:2]1[C:7]2[C:8](=[O:22])[N:9]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=3[O:20][CH3:21])[CH2:10][C:6]=2[C:5]([F:23])=[C:4](Cl)[N:3]=1.[NH2:25][C@H:26]1[CH2:31][CH2:30][CH2:29][CH2:28][C@H:27]1[NH:32][C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36].CCN(C(C)C)C(C)C>C(#N)C.CO>[Cl:1][C:2]1[C:7]2[C:8](=[O:22])[N:9]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=3[O:20][CH3:21])[CH2:10][C:6]=2[C:5]([F:23])=[C:4]([NH:25][C@H:26]2[CH2:31][CH2:30][CH2:29][CH2:28][C@H:27]2[NH:32][C:33](=[O:39])[O:34][C:35]([CH3:37])([CH3:36])[CH3:38])[N:3]=1
Reactant: CC(C)(C)OC(=O)N[C@@H]1CCCC[C@@H]1N
Reactant: COc1ccc(CN2Cc3c(F)c(Cl)nc(Cl)c3C2=O)c(OC)c1
Solvent: CO
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: COc1ccc(CN2Cc3c(F)c(N[C@H]4CCCC[C@H]4NC(=O)OC(C)(C)C)nc(Cl)c3C2=O)c(OC)c1
Temperature: 85 °C
Reaction time: 72 h
Yield: 34.5 %

Procedure:
A mixture of 4,6-dichloro-2-(2,4-dimethoxybenzyl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one (316 mg, 0.851 mmol) and cis-tert-butyl 2-aminocyclohexylcarbamate (365 mg, 1.703 mmol) and DIPEA (0.743 mL, 4.26 mmol) in ACN (2 mL) was stirred at 85° C. for 3 d. The resulting crude material was reconstituted in MeOH (1 mL) and purified by preparative HPLC. The fractions were collected and stripped to dryness via rotary evaporation to yield the title compound (161 mg, 34%). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.35 (br s, 10 H), 1.58 (br s, 2 H), 1.76 (br s, 2 H), 3.71-3.90 (m, 11 H), 4.33 (br s, 2 H), 4.51 (br s, 2 H), 6.43-6.72 (m, 3 H), 6.87 (br s, 1 H), 7.07 (br s, 1 H). [M+H] calc'd for C27H34ClFN4O5, 549; found, 549.
Reaction SMILES: Cl[CH2:2][C:3](=O)[CH:4]=[CH:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13](=[O:15])[CH3:14])=[CH:8][CH:7]=1.C[O:18][C:19]([NH:21][NH2:22])=[S:20]>C1(C)C=CC=CC=1>[C:13]([NH:12][C:9]1[CH:10]=[CH:11][C:6]([CH2:5][CH2:4][CH:3]2[CH2:2][S:20][C:19](=[O:18])[NH:21][NH:22]2)=[CH:7][CH:8]=1)(=[O:15])[CH3:14]
Reactant: COC(=S)NN
Reactant: CC(=O)Nc1ccc(C=CC(=O)CCl)cc1
Solvent: Cc1ccccc1
Product: CC(=O)Nc1ccc(CCC2CSC(=O)NN2)cc1

Procedure:
A mixture containing 4.0 g of 1-chloro-4-(4-acetamidophenyl)-2-oxo-3-butene (J. Org. Chem., 28, 2446, 1963) and 2.3 g of hydrazinecarbothioic acid O-methylester in 150 ml of toluene was refluxed for 3 h. The crystals were filtered and washed with toluene. Yield 3.0 g (65%), mp. 235°-240° C.
Reaction SMILES: [H-].[Na+].I[CH3:4].O.[N+:6]([C:9]1[CH:16]=[CH:15][C:12]([CH2:13][OH:14])=[CH:11][CH:10]=1)([O-:8])=[O:7]>O1CCCC1>[CH3:4][O:14][CH2:13][C:12]1[CH:11]=[CH:10][C:9]([N+:6]([O-:8])=[O:7])=[CH:16][CH:15]=1
Reactant: O=[N+]([O-])c1ccc(CO)cc1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: COCc1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 73.3 %

Procedure:
16 g (60%) of sodium hydride was dispersed in 20 ml of tetrahydrofuran. To this, 100 ml of a solution in which 50 g of p-nitrobenzyl alcohol was dissolved in tetrahydrofuran, was added in drops while cooling with ice. The mixture was stirred for one hour at room temperature, and thereafter 56 g of iodomethane was added in drops while cooling with ice, and the mixture was further stirred for 3 hours at room temperature. To the reaction solution was added water, and a mixture was extracted with ethyl acetate. The extracted solvent was distilled off under reduced pressure, and the resulting product was purified by silica gel chromatography to obtain 40 g of p-methoxymethylnitrobenzene.
Reaction SMILES: O.[NH2:2][NH2:3].Cl[C:5]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][N:6]=1>>[NH:2]([C:5]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][N:6]=1)[NH2:3]
Reactant: NN
Reactant: Cc1ccc(Cl)nc1
Solvent: O
Product: Cc1ccc(NN)nc1

Procedure:
5.7 ml (5.9 g, 117.6 mmol) of hydrazine hydrate are added to 1.0 g (7.8 mmol) of 2-chloro-5-methylpyridine, and the mixture is stirred at boiling point (bath temperature 150° C.) for 16 h. The reaction mixture is cooled and then concentrated on a rotary evaporator, and the residue is co-evaporated three times with in each case 10 ml of ethylene glycol monoethyl ether. The residue is then taken up in dichloromethane, the precipitate is separated off and the filtrate is concentrated under reduced pressure.
Reaction SMILES: Cl[C:2]1[CH:14]=[CH:13][C:5]([O:6][C:7]([CH3:12])([CH3:11])[C:8]([OH:10])=[O:9])=[CH:4][CH:3]=1.[OH-].[K+]>CO.O1CCOCC1.O.[Ni]>[O:6]([C:7]([CH3:12])([CH3:11])[C:8]([OH:10])=[O:9])[C:5]1[CH:13]=[CH:14][CH:2]=[CH:3][CH:4]=1
Reactant: CC(C)(Oc1ccc(Cl)cc1)C(=O)O
Agent: [Ni]
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: C1COCCO1
Solvent: O
Product: CC(C)(Oc1ccccc1)C(=O)O
Reaction time: 3.25 h
Yield: 9.5 %

Procedure:
To a solution of 20.0 g (0.93 mole) of 2-(4-chlorophenoxy)-2-methylpropionic acid (97%, clofibric acid, Aldrich) in 130 ml of methanol and 50 ml of dioxane was added a solution of 13.9 g (0.244 mole) of potassium hydroxide in 75 ml of water. To this solution were added 5 teaspoonfuls of Raney Nickel (Aldrich) and the mixture was hydrogenated at ambient temperature for 3.25 hr (H2 -uptake ceased). The reaction mixture was filtered through Celite® and the filtrate was concentrated under reduced pressure to a volume of 150 ml. This solution was extracted with 200 ml of ethyl ether and the ether was discarded. the aqueous layer pH was adjusted to 2 with concentrated hydrochloric acid solution and the resulting white solid was collected by filtration and dried to give 16 g (99%) of white solid. An analytical sample was prepared by recrystallizing from cyclohexane-petroleum ether (b.p. range 30°-60° C.) to give white crystals, mp 98°-100° C.
Reaction SMILES: Cl[CH2:2][C:3]1[C:8]([CH3:9])=[C:7]([O:10][CH2:11][CH2:12][CH2:13][O:14][CH3:15])[CH:6]=[CH:5][N:4]=1.[N:16]1[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[NH:18][C:17]=1[SH:25].[OH-].[Na+]>O>[CH3:15][O:14][CH2:13][CH2:12][CH2:11][O:10][C:7]1[CH:6]=[CH:5][N:4]=[C:3]([CH2:2][S:25][C:17]2[NH:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[N:16]=2)[C:8]=1[CH3:9]
Reactant: COCCCOc1ccnc(CCl)c1C
Reactant: Sc1nc2ccccc2[nH]1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: COCCCOc1ccnc(CSc2nc3ccccc3[nH]2)c1C
Temperature: 65 °C

Procedure:
To this 2-chloromethyl-4-(3-methoxypropoxy)-3-methylpyridin solution was added 2-benzimidazole thiol (8.71 g (58.0 mmol)) at room temperature. A 25% aqueous sodium hydroxide solution (40.6 g) was added gradually as the temperature (internal temperature) was gradually raised to 65° C. The reaction mixture was stirred for about an hour and a half at 65° C. (internal temperature). Water (60.0 ml) was added to the reaction mixture at 65° C., after which 25% aqueous sodium hydroxide solution (0.2 g) was added and stirred. This reaction mixture was allowed to stand, and the water layer was separated. The organic layer was washed with water (20.0 ml) twice, and toluene (79.6 ml) and methanol (21.5 ml) were added to the organic layer to obtain a 2-[{4-(3-methoxypropoxy)-3-methylpyridin-2-yl}methylthio]-1H-benzimidazole solution.
Reaction SMILES: [OH:1][C:2]1[C:7]([CH2:8][CH2:9][CH3:10])=[C:6]([OH:11])[CH:5]=[CH:4][C:3]=1[C:12](=[O:14])[CH3:13].Br[CH2:16][C:17]1[CH:18]=[C:19]([CH:24]=[CH:25][CH:26]=1)[C:20]([O:22][CH3:23])=[O:21]>>[CH3:23][O:22][C:20](=[O:21])[C:19]1[CH:24]=[CH:25][CH:26]=[C:17]([CH2:16][O:11][C:6]2[CH:5]=[CH:4][C:3]([C:12](=[O:14])[CH3:13])=[C:2]([OH:1])[C:7]=2[CH2:8][CH2:9][CH3:10])[CH:18]=1
Reactant: COC(=O)c1cccc(CBr)c1
Reactant: CCCc1c(O)ccc(C(C)=O)c1O
Product: CCCc1c(OCc2cccc(C(=O)OC)c2)ccc(C(C)=O)c1O

Procedure:
1-(2,4-dihydroxy-3-propylphenyl)ethanone was allowed to react with methyl 3-bromomethylbenzoate according to the procedure of Example 69 and the product was purified by recrystallization from methylene chloride-ether to give 3-[(4-acetyl-3-hydroxy-2-propylphenoxy)methyl]benzoic acid methyl ester, the title compound, mp 141°-143°, in 89% yield. Analysis Calculated for C20H22O5 : C, 70.16; H, 6.48. Found: C, 69.99; H, 6.41.
Reaction SMILES: Cl[CH2:2][C:3]1[C:4]([C:17]([F:20])([F:19])[F:18])=[N:5][C:6]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)=[N:7][CH:8]=1.[C:21]1(=[O:31])[NH:25][C:24](=[O:26])[C:23]2=[CH:27][CH:28]=[CH:29][CH:30]=[C:22]12.[K]>CN(C)C=O>[Cl:16][C:12]1[CH:11]=[C:10]([NH:9][C:6]2[N:5]=[C:4]([C:17]([F:20])([F:19])[F:18])[C:3]([CH2:2][N:25]3[C:21](=[O:31])[C:22]4[C:23](=[CH:27][CH:28]=[CH:29][CH:30]=4)[C:24]3=[O:26])=[CH:8][N:7]=2)[CH:15]=[CH:14][CH:13]=1
Reactant: O=C1NC(=O)c2ccccc21
Reactant: FC(F)(F)c1nc(Nc2cccc(Cl)c2)ncc1CCl
Agent: [K]
Solvent: CN(C)C=O
Product: O=C1c2ccccc2C(=O)N1Cc1cnc(Nc2cccc(Cl)c2)nc1C(F)(F)F
Temperature: 25 °C
Reaction time: 20 h

Procedure:
A mixture of 5-(chloromethyl)-N-(3-chlorophenyl)-4-(trifluoromethyl)pyrimidin-2-amine (544 mg), potassium phthalimide (626 mg), and N,N-dimethylformamide (5.44 mL) was stirred at room temperature for 20 hours. The reaction liquid was concentrated under reduced pressure, and then to the residue was added ethyl acetate (150 mL), followed by washing with water (50 mL) three times, and then with saturated brine (30 mL). The organic layer was dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure to obtain crude 2-({2-[(3-chlorophenyl)amino]-4-(trifluoromethyl)pyrimidin-5-yl}methyl)-1H-isoindole-1,3(2H)-dione as a pale yellow powder.
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[Br:12][C:13]1[CH:14]=[C:15]([C:19]([N:21]2[C:29]3[C:24](=[CH:25][C:26]([F:30])=[CH:27][CH:28]=3)[CH2:23][CH2:22]2)=[O:20])[CH:16]=[N:17][CH:18]=1>C(Cl)Cl>[Br:12][C:13]1[CH:18]=[N+:17]([O-:9])[CH:16]=[C:15]([C:19]([N:21]2[C:29]3[C:24](=[CH:25][C:26]([F:30])=[CH:27][CH:28]=3)[CH2:23][CH2:22]2)=[O:20])[CH:14]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: O=C(c1cncc(Br)c1)N1CCc2cc(F)ccc21
Solvent: ClCCl
Product: O=C(c1cc(Br)c[n+]([O-])c1)N1CCc2cc(F)ccc21
Temperature: 25 °C
Reaction time: 4 h

Procedure:
0.19 g (1.1 mmol) m-chloroperbenzoic acid were added to 0.32 g (0.98 mmol) (5-bromo-pyridin-3-yl)-(5-fluoro-2,3-dihydro-indol-1-yl)-methanone in 5.0 mL DCM and the mixture was stirred for 4 h at RT. In addition, a further 95 mg (0.55 mmol) m-chloroperbenzoic acid were added to the reaction mixture and it was stirred for 48 h at RT. Then the reaction mixture was diluted with DCM and extracted with 1N aqueous sodium hydroxide solution. The organic phase was dried on sodium sulphate, evaporated down and dried under HV.
Reaction SMILES: [OH:1][CH:2]1[CH:6]2[O:7][CH2:8][CH:9]([N:10]3[C:18](=[O:19])[C:17]4[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=4)[C:11]3=[O:20])[CH:5]2[O:4][CH2:3]1.C(N(CC)CC)C.[CH3:28][S:29](Cl)(=[O:31])=[O:30]>ClCCl.CN(C)C1C=CN=CC=1>[CH3:28][S:29]([O:1][CH:2]1[CH2:3][O:4][CH:5]2[CH:9]([N:10]3[C:18](=[O:19])[C:17]4[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=4)[C:11]3=[O:20])[CH2:8][O:7][CH:6]12)(=[O:31])=[O:30]
Reactant: O=C1c2ccccc2C(=O)N1C1COC2C(O)COC21
Reactant: CS(=O)(=O)Cl
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)OC1COC2C1OCC2N1C(=O)c2ccccc2C1=O
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 77.9 %

Procedure:
Under a N2 atmosphere, to a solution of 2-(6-hydroxyhexahydrofuro[3,2-b]furan-3-yl)isoindoline-1,3-dione (2.35 g, 8.54 mmol) in dichloromethane (40 mL) were added triethylamine (1.30 g, 12.8 mmol) and N,N-dimethylpyridin-4-amine (209.2 mg, 1.7 mmol) and the mixture was cooled to 0° C. and then methanesulfonyl chloride (0.8 mL, 10.0 mmol) was added to the mixture. The resulting mixture was stirred at 0° C. for 30 min, then moved to room temperature overnight. The mixture was diluted with dichloromethane (100 mL), washed with 1M HCl (100 mL), water (100 mL) and brine (100 mL). The separated organic phase was dried over anhydrous Na2SO4, and then concentrated in vacuo. The residue was purified by silica gel column chromatography (MeOH/DCM (v/v)=1/200) to give the title compound as a white solid (2.35 g, 77.9%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][S:10]([C:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]([NH2:23])=[CH:15][CH:14]=2)(=[O:12])=[O:11])=[CH:5][CH:4]=1.[CH3:24][O:25][C:26]1[CH:34]=[CH:33][C:29]([C:30](Cl)=[O:31])=[CH:28][CH:27]=1.CCN(CC)CC>C(Cl)Cl>[CH3:24][O:25][C:26]1[CH:34]=[CH:33][C:29]([C:30]([NH:23][C:16]2[C:17]3[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:13]([S:10](=[O:12])(=[O:11])[NH:9][C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=3)=[CH:14][CH:15]=2)=[O:31])=[CH:28][CH:27]=1
Reactant: COc1ccc(NS(=O)(=O)c2ccc(N)c3ccccc23)cc1
Reactant: COc1ccc(C(=O)Cl)cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1ccc(NS(=O)(=O)c2ccc(NC(=O)c3ccc(OC)cc3)c3ccccc23)cc1
Yield: 32.4 %

Procedure:
To a solution of naphthalenyl amine (10) (65 mg, 0.2 mmol) in CH2Cl2 (5 mL) was added p-methoxybenzoyl chloride (45 uL, 0.24 mmol) and Et3N (50 uL, 0.4 mmol). The resultant solution was stirred at 25° C. overnight. The solvent was removed in vacuo and the residue was purified using HPLC to give the title compound (30 mg) as pale yellow solid. 1H NMR (300 MHz, MeOD) δ 8.73 (d, 1H), 8.08 (m, 4H), 7.70 (m, 3H), 7.10 (d, 2H), 6.90 (d, 2H), 6.70 (d, 2H), 3.84 (s, 3H), 3.60 (s, 3H); LC/MS m/z 463 (M+H)+.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:15]([CH3:19])([CH3:18])[CH:16]=O)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Br-].[CH2:21]([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[CH2:22][CH2:23][CH2:24][CH2:25][CH3:26]>>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([CH3:19])([CH3:18])[CH:16]=[CH:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCCCCC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CC(C)(C=O)c1cccc(OCc2ccccc2)c1
Agent: [Br-]
Product: CCCCCC=CC(C)(C)c1cccc(OCc2ccccc2)c1
Yield: 67.5 %

Procedure:
Similarly, 1-benzyloxy-3-(1,1-dimethyloct-2-enyl)benzene (13.5 g., 70%) is prepared from 15.75 g. (0.062 mol.) of 2-(3-benzyloxyphenyl)-2-methylpropionaldehyde and 37.5 g. (0.0899 mol.) of hexyltriphenylphosphonium bromide. The produce is an oil.
Reaction SMILES: [C:1]([O:5][C:6]([C@@:8]12[CH2:15][CH2:14][C@H:13]([F:16])[C@H:12]1[C:11](=O)[N:10]([C@@H](C1C=CC=CC=1)C)[CH2:9]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(O)C.O.[CH2:30]([O:37][C:38](Cl)=[O:39])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>O1CCCC1.C(N(CC)CC)C>[C:1]([O:5][C:6]([C@@:8]12[CH2:15][CH2:14][C@H:13]([F:16])[C@@H:12]1[CH2:11][N:10]([C:38]([O:37][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:39])[CH2:9]2)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: O=C(Cl)OCc1ccccc1
Reactant: C[C@H](c1ccccc1)N1C[C@]2(C(=O)OC(C)(C)C)CC[C@H](F)[C@H]2C1=O
Solvent: O
Solvent: CCN(CC)CC
Solvent: CCO
Product: CC(C)(C)OC(=O)[C@@]12CC[C@H](F)[C@@H]1CN(C(=O)OCc1ccccc1)C2
Reaction time: 2 h
Yield: 85.2 %

Procedure:
{(1S,5R,6S)-6-Fluoro-4-oxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3,3,0]octan-1-yl}carboxylic acid tert-butyl ester (402 mg, 1.16 mmol) was dissolved in tetrahydrofuran (20 mL), and a 1 M borane-tetrahydrofuran complex (5.79 mL, 5.79 mmol) was added dropwise in a nitrogen atmosphere. After two hours, a 1 M borane-tetrahydrofuran complex (3.47 mL, 3.47 mmol) was added; after 14 hours, a 1 M borane-tetrahydrofuran complex (3.47 mL, 3.47 mmol) was further added. After stirring for 2.5 hours, ethanol (18 mL), water (2 mL), and triethylamine (2 mL) were added, and the mixture was stirred at 80° C. for two hours. The reaction solution was evaporated under reduced pressure, and a saturated ammonium chloride solution was added to the resulting residue, followed by extraction with ethyl acetate. The organic layer was washed with water and brine and then dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the resulting residue was dissolved in dichloromethane (2.8 mL). Benzyloxycarbonyl chloride (1.03 g, 6.04 mmol) was added, and the mixture was stirred at 40° C. for 14 hours. The reaction solution was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (25% ethyl acetate/hexane) to give 359 mg of the title compound as a colorless oil.