Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:9][C@@H:10]1[C@@H:17]([O:18][C:19](=[O:26])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C@:16](C(SC)=S)(O)[C@@H:15]([CH2:32][O:33][C:34](=[O:41])[C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[O:14][C@@H:11]1[O:12][CH3:13])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(N=NC(C#N)(C)C)(C#N)C.C([SnH](CCCC)CCCC)CCC>C1(C)C=CC=CC=1>[C:1]([O:9][C@@H:10]1[C@@H:17]([O:18][C:19](=[O:26])[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:16][C@@H:15]([CH2:32][O:33][C:34](=[O:41])[C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[O:14][C@@H:11]1[O:12][CH3:13])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CO[C@H]1O[C@H](COC(=O)c2ccccc2)[C@](O)(C(=S)SC)[C@H](OC(=O)c2ccccc2)[C@H]1OC(=O)c1ccccc1
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Agent: CCCC[SnH](CCCC)CCCC
Solvent: Cc1ccccc1
Product: CO[C@H]1O[C@H](COC(=O)c2ccccc2)C[C@H](OC(=O)c2ccccc2)[C@H]1OC(=O)c1ccccc1

Procedure:
To a solution of the crude methyl 2,3,6-tri-O-benzoyl-4-(methylthio)thiocarbonyl-α-D-glucopyranoside (5.70 g, 9.55 mmol) in 120 mL of dry toluene was added AIBN (50 mg). Tributyl tin hydride (6.68 mL, 24.8 mmol) was added and the reaction was heated to reflux for 4 hours. The toluene was removed under reduced pressure. Acetonitrile (200 mL) was added and the mixture extracted with petroleum ether (5×100 mL) to remove all tin salts. After drying over anhydrous sodium sulfate, the solvent was removed under reduced pressure to yield a clear colorless oil which solidified on standing. Purification by flash column chromatography using 20% ethyl acetate in petroleum ether as the eluant gave the target compound as a white solid.
Reaction SMILES: C(OC(=O)[NH:7][C@@H:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14]([C:16]2[CH:39]=[C:38]([O:40][CH3:41])[C:19]3[N:20]([CH3:37])[C:21]([C:23]4[N:31]([CH2:32][C:33]([F:36])([F:35])[F:34])[C:26]5=[N:27][CH:28]=[CH:29][CH:30]=[C:25]5[CH:24]=4)=[N:22][C:18]=3[CH:17]=2)=[O:15])[CH2:9]1)(C)(C)C.C(O)(C(F)(F)F)=O>ClCCl.CO>[NH2:7][C@@H:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14]([C:16]2[CH:39]=[C:38]([O:40][CH3:41])[C:19]3[N:20]([CH3:37])[C:21]([C:23]4[N:31]([CH2:32][C:33]([F:36])([F:35])[F:34])[C:26]5=[N:27][CH:28]=[CH:29][CH:30]=[C:25]5[CH:24]=4)=[N:22][C:18]=3[CH:17]=2)=[O:15])[CH2:9]1
Reactant: COc1cc(C(=O)N2CCC[C@@H](NC(=O)OC(C)(C)C)C2)cc2nc(-c3cc4cccnc4n3CC(F)(F)F)n(C)c12
Solvent: CO
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COc1cc(C(=O)N2CCC[C@@H](N)C2)cc2nc(-c3cc4cccnc4n3CC(F)(F)F)n(C)c12
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 70.8 %

Procedure:
To a solution of (R)-tert-butyl(1-(7-methoxy-1-methyl-2-(1-(2,2,2-trifluoroethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-benzo[d]imidazole-5-carbonyl)piperidin-3-yl)carbamate (4.31 g, 7.35 mmol) in dichloromethane (DCM) (20 ml) at 0° C. was added TFA (9 ml, 118 mmol) dropwise. The reaction mixture was stirred for 5 minutes and allowed to warm to room temperature and stirred for 3 hours. The reaction mixture was concentrated under vacuum to afford an oil. The oil was dissolved in methanol and split into two equal batches. These were passed through two separate 70 g SCX cartridges. The columns were washed with MeOH (2CV) and the product collected from both columns as the free base with 2M ammonia in methanol (3CV). The product was concentrated and dried under vacuum to afford the title compound as a white solid (2.53 g).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([N:9]2[C:13]3[N:14]=[C:15]([CH3:19])[N:16]=[C:17](Cl)[C:12]=3[C:11]([CH3:20])=[C:10]2[CH3:21])=[C:4]([CH3:22])[CH:3]=1.[NH:23]1[CH2:28][CH2:27][CH:26]([CH2:29][CH2:30][C:31]#[N:32])[CH2:25][CH2:24]1.C(N(CC)C(C)C)(C)C>CCO>[Br:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([N:9]2[C:13]3[N:14]=[C:15]([CH3:19])[N:16]=[C:17]([N:23]4[CH2:28][CH2:27][CH:26]([CH2:29][CH2:30][C:31]#[N:32])[CH2:25][CH2:24]4)[C:12]=3[C:11]([CH3:20])=[C:10]2[CH3:21])=[C:4]([CH3:22])[CH:3]=1
Reactant: N#CCCC1CCNCC1
Reactant: Cc1nc(Cl)c2c(C)c(C)n(-c3c(C)cc(Br)cc3C)c2n1
Solvent: CCO
Solvent: CCN(C(C)C)C(C)C
Product: Cc1nc(N2CCC(CCC#N)CC2)c2c(C)c(C)n(-c3c(C)cc(Br)cc3C)c2n1
Temperature: 100 °C
Yield: 78.8 %

Procedure:
A suspension of 7-(4-bromo-2,6-dimethyl-phenyl)-4-chloro-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidine (2.0 g), 3-(piperidin-4-yl)propionitrile (1.4 g) and N,N-diisopropylethylamine (1.4 g) in EtOH (4 mL) was heated at 100° C. in a sealed tube for 11 hours. After cooling to room temperature, the solvent was removed under reduced pressure. The residue was purified with column chromatography (silica gel: Wako gel C200, eluent: hexane:ethyl acetate:CHCl3=8/2/1) to obtain 3-{1-[7-(4-bromo-2,6-dimethyl-phenyl)-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-propionitrile (2.0 g) as a white crystal.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].[C:15](#[N:18])[CH:16]=[CH2:17]>[Cl-].C[N+](CCCCCCCC)(CCCCCCCC)CCCCCCCC.CC(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:14][CH2:13][N:12]([CH2:17][CH2:16][C:15]#[N:18])[CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: C=CC#N
Reactant: Clc1ccc(N2CCNCC2)cc1Cl
Agent: CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC
Agent: [Cl-]
Solvent: CC(C)O
Product: N#CCCN1CCN(c2ccc(Cl)c(Cl)c2)CC1
Yield: 98.5 %

Procedure:
A mixture of 1-(3,4-dichlorophenyl)piperazine (0.1 mol), 2-propenenitrile (0.15 mol), and N-methyl-N,N-dioctyl octanaminiumchloride (1 ml) in 2-propanol (150 ml) was stirred and refluxed for one hour. The solvent was evaporated and the residue was purified by column chromatography over silica gel (eluent: CH2Cl2 /CH3OH 95/5). The pure fractions were collected and the solvent was evaporated. The residue was stirred in diisopropylether/acetonitrile 10/1. The solvent was evaporated, yielding 28 g (98.5%) of 4-(3,4-dichlorophenyl)-1-piperazinepropanenitrile (interm. 3).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([OH:8])=[N:6][CH:7]=1.[O:9]1[CH2:14][CH2:13][CH:12](O)[CH2:11][CH2:10]1>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:8][CH:12]2[CH2:13][CH2:14][O:9][CH2:10][CH2:11]2)=[N:6][CH:7]=1
Reactant: OC1CCOCC1
Reactant: Oc1ccc(Br)cn1
Product: Brc1ccc(OC2CCOCC2)nc1

Procedure:
The title compound was prepared from 5-bromo-2-hydroxypyridine and tetrahydro-4H-pyran-4-ol in analogy to Example 9c): colorless solid.
Reaction SMILES: [OH:1][CH:2]1[CH2:7][C:6]([N+:14]([O-:16])=[O:15])([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:5][N:4]([CH3:17])[C:3]1=[O:18].C(N(C(C)C)C(C)C)C.[CH3:28][O:29][CH2:30]Cl>COCCOC>[CH3:28][O:29][CH2:30][O:1][CH:2]1[CH2:7][C:6]([N+:14]([O-:16])=[O:15])([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:5][N:4]([CH3:17])[C:3]1=[O:18]
Reactant: COCCl
Reactant: CN1CC(c2ccccc2)([N+](=O)[O-])CC(O)C1=O
Solvent: CCN(C(C)C)C(C)C
Solvent: COCCOC
Product: COCOC1CC(c2ccccc2)([N+](=O)[O-])CN(C)C1=O
Temperature: 60 °C
Reaction time: 1 h
Yield: 51 %

Procedure:
To a solution of 50 mg (0.2 mmol) rac-3-hydroxy-1-methyl-5-nitro-5-phenyl-piperidin-2-one and 52 ul (0.3 mmol) N-ethyl diisopropylamine in 1,2-dimethoxyethane were added 23 ul (0.3 mmol) chloromethyl methyl ether at room temperature. After 1 hour, the solution was heated in a 60° C. oil bath for 20 hours. The mixture was cooled to room temperature. 52 ul (0.3 mmol) N-ethyl diisopropylamine and 23 ul (0.3 mmol) chloromethyl methyl ether were added. The mixture was heated in a 60° C. oil bath for 4 hours. The solvent was removed in vacuo. The residue was taken in ethyl acetate. The mixture was washed once with water. The aqueous layer was extracted once with ethyl acetate. The combined extracts were dried over sodium sulfate, filtered and concentrated in vacuo. The crude oil was purified on silica gel (Eluent: Heptane/ethyl acetate 0 to 100%) to provide 30 mg (51%) of the title compound as a yellow oil. MS (m/e): 295.2 (MH+).
Reaction SMILES: S(Cl)([Cl:3])=O.[CH3:5][O:6][C:7]1[CH:8]=[C:9]([CH:12]=[C:13]([O:29][CH3:30])[C:14]=1[O:15][CH2:16][C:17]1[N:18]=[C:19]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[O:20][C:21]=1[CH3:22])[CH2:10]O.C1(C)C=CC=CC=1>O1CCCC1>[Cl:3][CH2:10][C:9]1[CH:8]=[C:7]([O:6][CH3:5])[C:14]([O:15][CH2:16][C:17]2[N:18]=[C:19]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[O:20][C:21]=2[CH3:22])=[C:13]([O:29][CH3:30])[CH:12]=1
Reactant: COc1cc(CO)cc(OC)c1OCc1nc(-c2ccccc2)oc1C
Reactant: O=S(Cl)Cl
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: COc1cc(CCl)cc(OC)c1OCc1nc(-c2ccccc2)oc1C
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Thionyl chloride (3.62 g) was added dropwise to a stirred suspension of 3,5-dimethoxy-4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl alcohol (9.00 g) in tetrahydrofuran (50 ml)-toluene (150 ml) at 0° C. After stirring at room temperature for 3 hours, the reaction mixture was concentrated. The residual crystals were dissolved in ethyl acetate and washed with aqueous sodium bicarbonate and water. The ethyl acetate layer was separated, dried (MgSO4), and concentrated to give 4-(4-chloromethyl-2,6-dimethoxyphenoxymethyl)-5-methyl-2-phenyloxazole as crystals. Recrystallization from acetone-hexane gave colorless needles (7.00 g, yield 74%). m.p. 118-119° C.
Reaction SMILES: B.[CH3:2][O:3][C:4]1[CH:19]=[CH:18][C:7]([CH2:8][C:9]2[CH:17]=[CH:16][C:12]([C:13](O)=[O:14])=[CH:11][CH:10]=2)=[CH:6][CH:5]=1.Cl>O1CCCC1>[CH3:2][O:3][C:4]1[CH:19]=[CH:18][C:7]([CH2:8][C:9]2[CH:17]=[CH:16][C:12]([CH2:13][OH:14])=[CH:11][CH:10]=2)=[CH:6][CH:5]=1
Reactant: COc1ccc(Cc2ccc(C(=O)O)cc2)cc1
Agent: B
Agent: Cl
Solvent: C1CCOC1
Product: COc1ccc(Cc2ccc(CO)cc2)cc1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
A solution of 110 ml. (0.11 m) of 1 M boron hydride (BH3) in tetrahydrofuran was slowly added to a solution of 24.2 g. (0.10 m) of 4-(4-methoxybenzyl)benzoic acid in 110 ml. of tetrahydrofuran at 0° C. The addition was complete in 20 minutes and the reaction mixture was stirred at room temperature for one hour. The reaction mixture was carefully acidified with hydrochloric acid and the solvent removed. The residue was partitioned between water and ether, and the ether layer was washed with aqueous sodium hydroxide, dried over anhydrous magnesium sulfate and concentrated to give 22.2 g. of 4-(4-methoxybenzyl)benzyl alcohol, m.p. 68°-72° C. when recrystallized from cyclohexane.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:12]([N:17]2[C:21](=[O:22])[C:20]3=[C:23]([N+:27]([O-:29])=[O:28])[CH:24]=[CH:25][CH:26]=[C:19]3[C:18]2=[O:30])[CH2:13][C:14](O)=[O:15])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2].Cl.[NH2:32][OH:33]>O1CCCC1>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:12]([N:17]2[C:21](=[O:22])[C:20]3=[C:23]([N+:27]([O-:29])=[O:28])[CH:24]=[CH:25][CH:26]=[C:19]3[C:18]2=[O:30])[CH2:13][C:14]([NH:32][OH:33])=[O:15])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2]
Reactant: NO
Reactant: CCOc1cc(C(CC(=O)O)N2C(=O)c3cccc([N+](=O)[O-])c3C2=O)ccc1OC
Agent: Cl
Solvent: C1CCOC1
Product: CCOc1cc(C(CC(=O)NO)N2C(=O)c3cccc([N+](=O)[O-])c3C2=O)ccc1OC
Yield: 76.8 %

Procedure:
3-(3-Ethoxy-4methoxyphenyl)-N-hydroxy-3-(3-nitrophthalimido)propionamide was prepared by the procedure of Example 1 from 3-(3-ethoxy-4-methoxyphenyl)-3-(3-nitrophthalimido)propanoic acid (3.64 g, 8.86 mmol), N,N′-carbonyldiimidazole (1.50 g, 9.25 mmol) and hydroxylamine hydrochloride (672 mg, 9.67 mmol) in tetrahydrofuran (20 mL) to afford 3-(3-ethoxy-4methoxyphenyl)-N-hydroxy-3-(3-nitrophthalimido)propionamide as a yellow solid (2.92 g, 77% yield): mp, 162.5-163.5° C.; 1H NMR (DMSO-d6) δ1.31 (t, J=6.9 Hz, 3H, CH3), 3.02 (dd, J=7.5, 14.8 Hz, 1H, CHH), 3.17 (dd, J=8.3, 14.8 Hz, 1H, CHH), 3.72 (s, 3H, CH3), 4.00 (q, J=6.9 Hz, 2H, CH2), 5.68 (t, J=7.7 Hz, 1H, NCH), 6.87-6.96 (m, 2H, Ar), 7.01 (br s, 1H, Ar), 8.05 (t, J=7.7 Hz, 1H, Ar), 8.15 (d, J=7.0 Hz, 1H, Ar), 8.27 (d, J=7.8 Hz, 1H, Ar), 8.82 (s, 1H, OH), 10.62 (br s, 1H, NH); 13C NMR (DMSO-d6) δ14.66, 33.92, 50.59, 55.46, 63.74, 111.69, 112.59, 119.89, 122.48, 126.91, 128.43, 130.42, 133.13, 136.35, 144.33, 147.67, 148.67, 162.99, 165.70, 165.87. Anal. Calcd for C20H19N3O8+0.4 mole ethyl acetate: C, 55.83; H, 4.86; N, 8.96. Found: C, 55.86; H, 4.94; N, 8.73.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8]#[C:9][C:10]2[CH2:11][C:12]3([O:23][N:24]=2)[CH2:16][CH2:15][N:14]([C:17]([N:19]([O:21][CH3:22])[CH3:20])=[O:18])[CH2:13]3)[CH:5]=[CH:6][CH:7]=1.Cl[C:26]1C=C(C#CC2CC3(CCNC3)ON=2)C=CC=1>>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]#[C:9][C:10]2[CH2:11][C:12]3([CH2:16][CH2:15][N:14]([C:17]([N:19]([O:21][CH3:22])[CH3:20])=[O:18])[CH2:13][CH2:26]3)[O:23][N:24]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: Clc1cccc(C#CC2=NOC3(CCNC3)C2)c1
Reactant: CON(C)C(=O)N1CCC2(CC(C#Cc3cccc(Cl)c3)=NO2)C1
Product: CON(C)C(=O)N1CCC2(CC1)CC(C#Cc1cccc(Cl)c1)=NO2
Yield: 74 %

Procedure:
The title compound was synthesized using the method described for the compound of Example 110, replacing Compound 22c for Compound 27d. After evaporation, the crude was purified by means of automated flash chromatography (Isolera®TM-Biotage; gradient petroleum ether-EtOAc 8:2 to 6:4) to afford a pale yellow oil. Yield: 74%.
Reaction SMILES: Cl.[NH:2]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH:12]=[CH:13][C:14]([NH2:16])=[O:15])[C:3]([NH2:5])=[NH:4].Cl.Cl.[NH2:19][CH2:20][CH2:21][CH2:22][NH:23][CH2:24][CH2:25][CH2:26][CH2:27][NH:28][C:29](=[O:33])[CH:30](O)[OH:31].C(O)(=O)CCCC(O)=O.Cl.Cl.Cl.N(CCCCCCC=CC(NC(O)C(N)=O)=O)C(N)=N>O>[NH2:19][CH2:20][CH2:21][CH2:22][NH:23][CH2:24][CH2:25][CH2:26][CH2:27][NH:28][C:29](=[O:33])[CH:30]([NH:16][C:14](=[O:15])[CH:13]=[CH:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][NH:2][C:3]([NH2:5])=[NH:4])[OH:31]
Reactant: NCCCNCCCCNC(=O)C(O)O
Reactant: N=C(N)NCCCCCCC=CC(N)=O
Agent: Cl
Agent: N=C(N)NCCCCCCC=CC(=O)NC(O)C(N)=O
Agent: O=C(O)CCCC(=O)O
Solvent: O
Product: N=C(N)NCCCCCCC=CC(=O)NC(O)C(=O)NCCCCNCCCN
Temperature: 60 °C
Yield: 38.9 %

Procedure:
A mixture of 206.2 mg (0.84 mmole) of 9-guanidino-2-nonenamide hydrochloride, 291.0 mg (1.00 mmole) of N-[4-(3-aminopropyl)aminobutyl]-2,2-dihydroxyethanamide dihydrochloride, 109.6 mg (0.84 mmole) of glutaric acid and 0.2 ml of water was heated at 60° C. for 24 hours. After completion of the reaction, the reaction mixture was purified in a manner similar to that in Example 1 using CM-Sephadex® C-25 (Na-type) and Sephadex® LH-20 to obtain 135.0 mg (31.1% yield) of a white powder of N-[4-(3-aminopropyl)aminobutyl]-2-(9-guanidino-2-nonenamido-2-hydroxyethanamide trihydrochloride.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:14])[C:5]1[CH:10]=[C:9]([Cl:11])[C:8](N)=[C:7]([Cl:13])[CH:6]=1)[CH3:2].CS(O)(=O)=O.N(OCCC(C)C)=O.[SH:28][CH2:29][C:30]([OH:32])=[O:31]>C(O)(=O)C.ClCCl>[CH2:1]([O:3][C:4](=[O:14])[C:5]1[CH:10]=[C:9]([Cl:11])[C:8]([S:28][CH2:29][C:30]([OH:32])=[O:31])=[C:7]([Cl:13])[CH:6]=1)[CH3:2]
Reactant: O=C(O)CS
Reactant: CCOC(=O)c1cc(Cl)c(N)c(Cl)c1
Agent: CC(C)CCON=O
Agent: CS(=O)(=O)O
Solvent: CC(=O)O
Solvent: ClCCl
Product: CCOC(=O)c1cc(Cl)c(SCC(=O)O)c(Cl)c1
Reaction time: 0.5 h

Procedure:
4-Amino-3,5-dichlorobenzoic acid ethyl ester (17.7 g) was dissolved in a mixture of acetic acid (75 mL) and dichloromethane (75 mL) and then methanesulfonic acid (22 mL) was added. 3-Methylbutyl nitrite (10 mL) was added to the solution while the temperature was kept at 0-5° C. After 30 min, mercaptoacetic acid (38 mL) was added at 0-5° C. Then a part of the dichloromethane was removed by distillation which was stopped when the internal temperature of the mixture was 80° C. and this temperature was kept for additional 45 min. The mixture was cooled and the rest of the solvents were evaporated under vacuum. Toluene (300 mL), water (200 mL) and hydrochloric acid (6 M, 80 mL) were added. The organic phase was separated and then extracted with potassium bicarbonate solution (1 M, 200 mL) which was acidified with hydrochloric acid (6M, 50 mL). The product was extracted to toluene (100 mL) which was dried (sodium sulphate) and evaporated to dryness (yield 5.1 g). 1H-NMR (400 MHz, DMSO-d6) d=1.33 (t, J=7.0 Hz, 3H), 3.74 (s, 2H), 4.34 (q, J=7.0 Hz, 2H), 7.97 (s, 2H), 12.5 (b, 1H).
Reaction SMILES: [CH2:1]([OH:23])[C@H:2]1[O:7][C@@H:6]([O:8][C@H:9]2[C@H:14]([OH:15])[C@@H:13]([OH:16])[C@H:12]([OH:17])[O:11][C@@H:10]2[CH2:18][OH:19])[C@H:5]([OH:20])[C@@H:4]([OH:21])[C@@H:3]1[OH:22].[C:24](Cl)(=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(Cl)Cl>N1C=CC=CC=1.CN(C1C=CN=CC=1)C>[C:24]([O:20][C@@H:5]1[C@@H:4]([O:21][C:24](=[O:31])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@H:3]([O:22][C:24](=[O:31])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@@H:2]([CH2:1][O:23][C:24](=[O:31])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[O:7][C@H:6]1[O:8][C@@H:9]1[C@@H:10]([CH2:18][O:19][C:24](=[O:31])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[O:11][CH:12]([O:17][C:24](=[O:31])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@H:13]([O:16][C:24](=[O:31])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@H:14]1[O:15][C:24](=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)(=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: O=C(OC[C@H]1O[C@@H](O[C@H]2[C@H](OC(=O)c3ccccc3)[C@@H](OC(=O)c3ccccc3)C(OC(=O)c3ccccc3)O[C@@H]2COC(=O)c2ccccc2)[C@H](OC(=O)c2ccccc2)[C@@H](OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 21.6 %

Procedure:
Cellobiose (1.0 g, 2.92 mmol) was dissolved in dry pyridine (20 mL) at 0° C. DMAP (cat.) was added. Benzoyl chloride (2.5 equiv., 58 mmol, 6.8 mL) was added dropwise and the solution stirred at room temperature overnight. The solution was poured onto a mixture of ice-water and DCM. The organic layer was washed with NaHCO3(sat.) (×7), brine, H2SO4 (5%) (×2), followed by brine. The solution was dried (Na2SO4) and the solvent evaporated. The product was passed through a short silica plug to remove the remaining benzoyl chloride and the solvent was evaporated to yield 740 mg (22%) of the white solid product which was reacted on without further purification or characterisation.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[O:9][CH2:10][CH2:11]Br)=[CH:4][CH:3]=1.[CH3:20][O:21][C:22]1[CH:23]=[C:24]([CH:28]2[CH2:32][CH2:31][CH2:30][NH:29]2)[CH:25]=[CH:26][CH:27]=1.C(=O)([O-])[O-].[K+].[K+]>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[O:9][CH2:10][CH2:11][N:29]2[CH2:30][CH2:31][CH2:32][CH:28]2[C:24]2[CH:25]=[CH:26][CH:27]=[C:22]([O:21][CH3:20])[CH:23]=2)=[CH:4][CH:3]=1
Reactant: Fc1ccc(C(OCCBr)c2ccc(F)cc2)cc1
Reactant: COc1cccc(C2CCCN2)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: COc1cccc(C2CCCN2CCOC(c2ccc(F)cc2)c2ccc(F)cc2)c1
Yield: 52 %

Procedure:
Proceeding as in Example 9, using 9.8 g (30 mmole) of 1-[bis(4-fluorophenyl)methoxy]-2-bromoethane, 5.3 g (30 mmole) of (2-(3-methoxyphenyl)pyrrolidine and 8.3 g (60 mmole) of potassium carbonate, there was obtained after silica gel column filtration, 6.7 g (yield: 52%) of 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-2-(3-methoxyphenyl)pyrrolidine.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([S:11](Cl)(=O)=O)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[Na+].[I-].FC[C:19]([O:21][C:22](=O)[CH2:23]F)=O>CC(C)=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([S:11][S:11][C:5]2[CH:6]=[CH:23][C:22]([O:21][CH3:19])=[C:3]([O:2][CH3:1])[CH:4]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]
Reactant: O=C(CF)OC(=O)CF
Reactant: COc1ccc(S(=O)(=O)Cl)cc1OC
Agent: [I-]
Agent: [Na+]
Solvent: CC(C)=O
Product: COc1ccc(SSc2ccc(OC)c(OC)c2)cc1OC
Temperature: 25 °C
Reaction time: 1 h

Procedure:
3,4-dimethoxyphenylsulfonyl chloride (2.3 mmol) was dissolved in acetone (60 mL), and then NaI (3.4 g, 23 mmol) and fluoroacetic anhydride (1.45 mL, 6.9 mmol) were added and the mixture was stirred at room temperature for one hour. The reaction solution was concentrated, water was added, extraction was performed with ether and the organic layer was further washed with aqueous sodium thiosulfate, water and saturated saline. After drying over magnesium sulfate and vacuum concentration, the residue was purified with a silica gel column (hexane) to obtain 3,4-dimethoxyphenyldisulfide as a light yellow crystalline compound (58% yield). The NMR and mass spectral data for the obtained compound were as follows:
Reaction SMILES: N[C:2]1[S:3][C:4]2[CH:10]=[C:9]([C:11]([O:13][CH3:14])=[O:12])[CH:8]=[C:7]([O:15][CH3:16])[C:5]=2[N:6]=1.OP(O)(O)=O.N([O-])=O.[Na+].[Na+].[Cl-:27]>O.[O-]S([O-])(=O)=O.[Cu+2]>[Cl:27][C:2]1[S:3][C:4]2[CH:10]=[C:9]([C:11]([O:13][CH3:14])=[O:12])[CH:8]=[C:7]([O:15][CH3:16])[C:5]=2[N:6]=1
Reactant: COC(=O)c1cc(OC)c2nc(N)sc2c1
Reactant: [Cl-]
Agent: [Cu+2]
Agent: O=N[O-]
Agent: O=P(O)(O)O
Solvent: O
Product: COC(=O)c1cc(OC)c2nc(Cl)sc2c1

Procedure:
A 1000-mL 3-necked round-bottom flask was charged with a solution of methyl 2-amino-4-methoxybenzo[d]thiazole-6-carboxylate (5 g, 21.01 mmol, 1.00 equiv) and H3PO4 (40 mL). To this is added of a solution of NaNO2 (4.5 g, 65.22 mmol, 3.00 equiv) in water (10 mL) dropwise at 0°C. The resulting solution was stirred fo(1 h at 0°C. A solution of CuSO4 (10 g, 62.50 mmol, 5.00 equiv) in water (10 mL) was then added dropwise at 0°C., followed by a solution of NaCl (18.5 g, 318.97 mmol, 15.00 equiv) in water (10 mL) dropwise at 0°C. The resulting solution was stirred fo(1 h at room temperature, and then diluted with 100 mL of water. The aqueous solution was extracted with dichloromethane (2×50 mL) and the combined organic layer was concentrated under vacuum. The residue was purified by silica gel chromatography eluting with ethyl acetate/petroleum ether (3:1) to give methyl 2-chloro-4-methoxybenzo[d]thiazole-6-carboxylate as a white solid. (ES, m/z): Calc'd for C10H8ClNO3S [M+1]+=258, found 258. 1H-NMR (CDCl3, ppm): 3.98(s, 1H), 4.10(s, 1H), 7.28(s, 1H), 7.60(d, 1H, J=1.2), 8.12(d, 1H, J=1.2).
Reaction SMILES: C(OC([NH:8][C@:9]([CH3:31])([CH2:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])=[CH:19][CH:18]=1)[CH2:10][CH2:11][C:12]([OH:14])=[O:13])=O)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[NH2:8][C@:9]([CH3:31])([CH2:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])=[CH:19][CH:18]=1)[CH2:10][CH2:11][C:12]([OH:14])=[O:13]
Reactant: CCCCCCCOc1ccc(CC[C@](C)(CCC(=O)O)NC(=O)OC(C)(C)C)cc1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCCCCCCOc1ccc(CC[C@@](C)(N)CCC(=O)O)cc1
Temperature: 25 °C
Reaction time: 6.5 h

Procedure:
To a stirred solution of (R)-4-tert-butoxycarbonylamino-6-(4-heptyloxy-phenyl)-4-methyl-hexanoic acid (24 mg, 0.06 mMol) in CH2Cl2 (2 ml) is added trifluoroacetic acid (0.1 ml). The mixture is stirred at RT for 6.5 hours. After that time, the reaction mixture is concentrated under reduced pressure to give the title compound as an amorphous white powder. The crude product is sufficiently pure to be used without further purification.
Reaction SMILES: [C:1](=[O:27])(OC1C=CC([N+]([O-])=O)=CC=1)[O:2][CH:3]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14](=[O:16])[NH2:15])=[CH:10][N:9]=2)[CH2:4]1.[CH:28]([N:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1)([CH3:30])[CH3:29]>C(Cl)Cl>[CH:28]([N:31]1[CH2:36][CH2:35][N:34]([C:1]([O:2][CH:3]2[CH2:7][CH2:6][N:5]([C:8]3[CH:13]=[CH:12][C:11]([C:14](=[O:16])[NH2:15])=[CH:10][N:9]=3)[CH2:4]2)=[O:27])[CH2:33][CH2:32]1)([CH3:30])[CH3:29]
Reactant: CC(C)N1CCNCC1
Reactant: NC(=O)c1ccc(N2CCC(OC(=O)Oc3ccc([N+](=O)[O-])cc3)C2)nc1
Solvent: ClCCl
Product: CC(C)N1CCN(C(=O)OC2CCN(c3ccc(C(N)=O)cn3)C2)CC1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To a solution of 1-(5-carbamoylpyridin-2-yl)-pyrrolidin-3-yl 4-nitrophenyl carbonate (0.37 g, 1 mmol) in DCM (5 ml) was added 1-isopropylpiperazine (0.13 g, 1 mmol). The resulting solution was stirred under N2 at room temperature for 24 h. The reaction mixture was then filtered and the filter cake was washed with DCM. The combined filtrates were concentrated to afford the crude product. After further purified by preparative HPLC, the title compound was obtained as a yellow solid (36 mg, 10%). [1H NMR (500 MHz, CDCl3) δ8.60 (d, 1H), 7.94 (dd, 1H), 7.72 (s, 1H), 7.09 (s, 1H), 6.48 (d, 1H), 5.25 (s, 1H), 3.66 (m, 2H), 3.55 (m, 2H), 3.31 (m, 4H), 2.63 (m, 1H), 2.36 (m, 4H), 2.21 (m, 1H), 2.10 (m, 1H), 0.92 (d, 6H, J=6.5 Hz); LCMS RtA=1.58 min, [M+H]+=362.2].