Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:10][CH2:11]O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br:20]N1C(=O)CCC1=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[Br:20][CH2:11][CH2:10][C@@H:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14]
Reactant: O=C1CCC(=O)N1Br
Reactant: CC(C)(C)OC(=O)N[C@H](CCO)C(=O)OC(C)(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N[C@H](CCBr)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 34 %

Procedure:
A mixture of 1.39 g (5.05 mmol) tert-butyl N-(tert-butoxycarbonyl)-D-homoserinate (prepared according to J. Org. Chem. 1988, 53, 1900-1903), 899 mg N-bromo succinimide (5.05 mmol), and 1.68 g polymer bound triphenylphosphine (loading approx. 3 mmol/g, approx. 5.0 mmol) in dichloromethane (17 mL) was stirred overnight at room temperature. All solids were removed by filtration, and the filtrate was concentrated in vacuo. The residue was purified by column chromatography on silica gel (2.5→25% ethyl acetate in hexane) to give 580 mg of the title compound (34% yield).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:10][CH2:9][NH:8]1.[C:17]([OH:26])(=[O:25])[C@H:18]([C@@H:20]([C:22]([OH:24])=[O:23])[OH:21])[OH:19]>C(O)C>[OH:21][C@@H:20]([C@H:18]([OH:19])[C:17]([OH:26])=[O:25])[C:22]([OH:24])=[O:23].[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:10][CH2:9][NH:8]1
Reactant: c1ccc(C2NCCc3ccccc32)nc1
Agent: O=C(O)[C@@H](O)[C@H](O)C(=O)O
Solvent: CCO
Product: c1ccc([C@@H]2NCCc3ccccc32)nc1
Reaction time: 18 h

Procedure:
A solution of 22.2 g of (RS)-1-pyridin-2-yl-1,2,3,4-tetrahydro-isoquinoline in 500 ml of warm absolute ethanol was treated with 15.85 g of D-(-)-tartaric acid. After filtration of the slightly turbid solution, the clear solution obtained was left to stand at 20° C. for 6 h. and at 5° C. for a further 18 h. The precipitate formed was filtered off under suction and washed with absolute ethanol. A second crystallizate was obtained immediately from the mother liquor. The precipitates were combined (15.0 g, m.p. 155°-158° C.) and recrystallized from 900 ml of absolute ethanol. There were obtained 11.4 g of (R)-1-pyridin-2-yl-1,2,3,4-tetrahydro-isoquinoline (2S,3S)-2,3-dihydroxy-succinate (1:1) as a colorless product, m.p. 162°-165° C.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[NH2:7][C:8]1[N:16]=[C:15]2[C:11]([NH:12][CH:13]=[N:14]2)=[C:10]([Cl:17])[N:9]=1.[C:18]([O:26][CH2:27][CH2:28][O:29][CH2:30]Cl)(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.O>CN(C)C=O>[NH2:7][C:8]1[N:16]=[C:15]2[C:11]([N:12]=[CH:13][N:14]2[CH2:30][O:29][CH2:28][CH2:27][O:26][C:18](=[O:25])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[C:10]([Cl:17])[N:9]=1
Reactant: Nc1nc(Cl)c2[nH]cnc2n1
Reactant: O=C(OCCOCCl)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Nc1nc(Cl)c2ncn(COCCOC(=O)c3ccccc3)c2n1
Reaction time: 0.33 h
Yield: 19.6 %

Procedure:
A suspension of potassium carbonate (4.1 g) and 2-amino-6-chloropurine (5.0 g) in dry dimethylformamide (120 ml) was stirred for 20 minutes. 2-Benzoyloxyethoxymethyl-chloride (6.3 g) was added and the resulting pink suspension stirred at room temperature for 6 days. The reaction mixture was then poured into a mixture of ice and water (210 ml) with vigorously stirring. The aqueous mixture was extracted with chloroform (3×200 ml), and the chloroform solution obtained was washed with a 5% acetic acid solution and then twice with water. The chloroform solution was dried over anhydrous sodium sulfate and evaporated in vacuo. The residue was redissolved in a minimal amount of chloroform and the resulting solution applied to a column containing silica gel (200 g) in chloroform. The column was eluted with 2% methanol/98% chloroform and the eluant collected in 30 ml cuts. The fractions containing 2-amino-6-chloro-9-(2-benzoyloxyethoxymethyl)purine (determined by TLC) were combined, evaporated and the residue recrystallized from benzene to give 2-amino-6-chloro-9-(2-benzoyloxyethoxymethyl)purine (2.0 g., m.p. 130°-133.5° C.).
Reaction SMILES: [C:1](=O)([O-])[O-].[K+].[K+].CI.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][N:19]([C:22]2[N:30]=[CH:29][N:28]=[C:27]3[C:23]=2[N:24]=[CH:25][NH:26]3)[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].C(OCC)(=O)C>CN(C)C=O.O>[C:9]([O:13][C:14]([N:16]1[CH2:17][CH2:18][N:19]([C:22]2[N:30]=[CH:29][N:28]=[C:27]3[C:23]=2[N:24]=[CH:25][N:26]3[CH3:1])[CH2:20][CH2:21]1)=[O:15])([CH3:12])([CH3:10])[CH3:11]
Reactant: CC(C)(C)OC(=O)N1CCN(c2ncnc3[nH]cnc23)CC1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Cn1cnc2c(N3CCN(C(=O)OC(C)(C)C)CC3)ncnc21
Temperature: 25 °C
Reaction time: 16 h
Yield: 84.9 %

Procedure:
Potassium carbonate (1.52 g) and methyl iodide (0.94 mL) were added to a solution of 4-(9H-purin-6-yl)-piperazine-1-carboxylic acid t-butyl ester (3.04 g) in N,N-dimethylformamide (100 mL), and this was stirred at room temperature for 16 hours. Ethyl acetate (300 mL) and water (100 mL) were added, the organic layer was washed twice with 100 mL of water and then once with 100 mL of saturated aqueous sodium chloride solution, and then dried over anhydrous magnesium sulfate. The organic layer was filtered, and concentrated under reduced pressure to give the title compound (2.70 g).
Reaction SMILES: [Cl:1][C:2]1[C:3]([F:31])=[C:4]([CH:8]2[C:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[CH:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10][CH:9]2[C:28](O)=[O:29])[CH:5]=[CH:6][CH:7]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[F:65][C:66]1[CH:72]=[CH:71][C:69]([NH2:70])=[CH:68][CH:67]=1>C(Cl)Cl>[F:65][C:66]1[CH:72]=[CH:71][C:69]([NH:70][C:28]([CH:9]2[CH:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=3[F:31])[C:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[CH:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10]2)=[O:29])=[CH:68][CH:67]=1
Reactant: CC(C)(C)CC1NC(C(=O)O)C(c2cccc(Cl)c2F)C1(C#N)c1ccc(Cl)cc1F
Reactant: Nc1ccc(F)cc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)CC1NC(C(=O)Nc2ccc(F)cc2)C(c2cccc(Cl)c2F)C1(C#N)c1ccc(Cl)cc1F
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
To a stirred solution of rac (2R,3S,4R,5S)-3-(3-Chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (100 mg, 0.17 mmol) in methylene chloride (10 mL), HATU (Aldrich, 98 mg, 0.26 mmol) was added followed by the addition of DIPEA (0.150 mL, 0.855 mmol) and 4-fluoro-aniline (Aldrich, 38 mg, 0.32 mmol). The mixture was stirred at rt for 1.5 hr. The reaction was quenched with addition of water. The mixture was extracted with methylene chloride (2×10 mL) and the extracts were dried with magnesium sulfate. The solvent was removed and the residue was purified on an ISCO machine (20 g column, 0-10% EtOAc/methylene chloride) to give a white solid. 67 mg.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][CH:21]=1)[CH2:5][O:6][C:7]1[CH:16]=[C:15]2[C:10]([C:11](=[O:18])[NH:12][C:13]([CH3:17])=[N:14]2)=[CH:9][CH:8]=1.NC1C=C(OCC2C=CC=C(F)C=2)C=CC=1C(O)=O.CCO[C:44]([C:46]([NH2:48])=[O:47])=O.Cl.C[O-].[Na+]>CO.O>[F:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][CH:21]=1)[CH2:5][O:6][C:7]1[CH:16]=[C:15]2[C:10]([C:11](=[O:18])[N:12]([CH2:44][C:46]([NH2:48])=[O:47])[C:13]([CH3:17])=[N:14]2)=[CH:9][CH:8]=1
Reactant: Cc1nc2cc(OCc3cccc(F)c3)ccc2c(=O)[nH]1
Reactant: CCOC(=O)C(N)=O
Agent: C[O-]
Agent: Cl
Agent: Nc1cc(OCc2cccc(F)c2)ccc1C(=O)O
Solvent: O
Solvent: CO
Product: Cc1nc2cc(OCc3cccc(F)c3)ccc2c(=O)n1CC(N)=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 97 %

Procedure:
7-(3-Fluoro-benzyloxy)-2-methyl-3H-quinazolin-4-one: To a mixture of 2-amino-4-(3-fluoro-benzyloxy)-benzoic acid (2.0 g, 7.7 mmol) and ethyl acetamidate HCl (1.9 g, 15.3 mmol) in methanol (30 mL) was added sodium methoxide (5.4 M, 0.83 g, 15.3 mmol) and the resulting mixture was heated under reflux for 19 h. After this time ethyl acetamidate HCl (1.9 g, 15.3 mmol) and sodium methoxide (5.4 M, 0.83 g, 15.3 mmol) was added and the resulting mixture heated for another 1 h. After cooling to rt the mixture was poured into water (40 mL) and then the resulting precipitate was stirred for 2 h, and filtered off to afford the title compound (2.1 g, 97%) as an off-white solid. MS: m/e=283.1 (M−H).
Reaction SMILES: [CH:1]([CH:13]1[CH2:18][C:17](=[O:19])[O:16][C:14]1=[O:15])=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].S([O-])([O-])(=O)=[O:21].[Na+:25].[Na+]>O>[Na+:25].[Na+:25].[CH:1]([CH:13]([CH2:18][C:17]([O-:16])=[O:19])[C:14]([O-:21])=[O:15])=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: O=S(=O)([O-])[O-]
Reactant: CCCCCCCCCCC=CC1CC(=O)OC1=O
Agent: [Na+]
Solvent: O
Product: CCCCCCCCCCC=CC(CC(=O)[O-])C(=O)[O-]

Procedure:
500 g of distilled water were mixed with 3500 g of n-Dodecenylsuccinic Anhydride (98% concentration, Milliken Chemical Company, Inman, S.C.) at 70 degrees Centigrade for approximately 16 hours. Following the 16 hour reaction period, 3070 g of a 1% sodium sulfate solution was added and mixed for one more hour and removed from heat. 1000 g of a 50% sodium hydroxide solution was then slowly added to the emulsion with constant mixing to form a 49% concentration of the n-Dodecenylsuccinic acid monosodium salt. From this, a representative sample was obtained and diluted to 6% concentration with distilled water and the pH was adjusted to 9 with sodium hydroxide solution to form the n-Dodecenylsuccinate Disodium Salt.
Reaction SMILES: [C:1]1(=[O:11])[NH:5][C:4](=[O:6])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.[CH2:12]=[O:13]>ClCCCl>[CH2:12]([N:5]1[C:1](=[O:11])[C:2]2=[CH:10][CH:9]=[CH:8][CH:7]=[C:3]2[C:4]1=[O:6])[OH:13]
Reactant: O=C1NC(=O)c2ccccc21
Reactant: C=O
Solvent: ClCCCl
Product: O=C1c2ccccc2C(=O)N1CO

Procedure:
Heterodisperse gel-type or macroporous anion exchangers are obtained, for example, by the phthalimide process according to U.S. Pat. No. 4,952,608, the contents of which are incorporated into the present application by reference. In this process, for example, phthalimide and formalin in 1,2-dichloroethane are first introduced and reacted to form N-methylolphthalimide. From this is produced bis(phthalimidomethyl) ether. First oleum, then polystyrene polymer beads crosslinked at 5% by weight are introduced. The suspension is heated to 70° C. and stirred for a further 18 hours. Dichloroethane is removed from the system by distillation. The resultant polymer beads are taken up in water, sodium hydroxide solution is added and the mixture is treated for 8 hours at 180° C. After they are cooled, the resultant aminomethylated polymer beads are extracted with water by washing.
Reaction SMILES: Cl.[Cl:2][CH2:3][CH2:4][NH:5][CH2:6][CH2:7][Cl:8].[O:9]=[P:10](Cl)([Cl:12])[Cl:11]>>[Cl:2][CH2:3][CH2:4][N:5]([CH2:6][CH2:7][Cl:8])[P:10]([Cl:12])([Cl:11])=[O:9]
Reactant: ClCCNCCCl
Reactant: O=P(Cl)(Cl)Cl
Agent: Cl
Product: O=P(Cl)(Cl)N(CCCl)CCCl

Procedure:
A mixture of bis(2-chloroethyl)amine hydrochloride (5 g) and POCl3 (13 mL) was heated at reflux for 12 hours, during which the mixture became a homogeneous solution. The excess POCl3 was removed by distillation (bp 105° C.), and then 4.93 g of the product was distilled (bp 110-114° C., 0.1 mm Hg). Recrystalliztion from acetone/hexane gave 4.5 g of the product as a colorless solid: mp 54.5-56° C. (lit. 54-56° C., Friedman, O. M., et. al., J. Am. Chem. Soc. 76 (1954):655-658); 1H NMR (CDCl3) δ 3.62-3.68 (m, 2), 3.71-3.77 (m, 6).
Reaction SMILES: C(N(CC)CC)C.[CH:8]([S:11]([C:14]1[CH:19]=[CH:18][C:17]([C:20]2[N:21]=[C:22]([C:41]#[CH:42])[C:23]([N:26](C(OC(C)(C)C)=O)C(=O)OC(C)(C)C)=[N:24][CH:25]=2)=[CH:16][CH:15]=1)(=[O:13])=[O:12])([CH3:10])[CH3:9].Br[C:44]1[CH:45]=[C:46]([CH:50]=[CH:51][CH:52]=1)[C:47]([NH2:49])=[O:48].C(O)(C(F)(F)F)=O>CN(C=O)C.CCOC(C)=O.[Cl-].[Na+].O.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:26][C:23]1[C:22]([C:41]#[C:42][C:44]2[CH:45]=[C:46]([CH:50]=[CH:51][CH:52]=2)[C:47]([NH2:49])=[O:48])=[N:21][C:20]([C:17]2[CH:16]=[CH:15][C:14]([S:11]([CH:8]([CH3:9])[CH3:10])(=[O:13])=[O:12])=[CH:19][CH:18]=2)=[CH:25][N:24]=1
Reactant: C#Cc1nc(-c2ccc(S(=O)(=O)C(C)C)cc2)cnc1N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Reactant: NC(=O)c1cccc(Br)c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Agent: [Cl-]
Solvent: CN(C)C=O
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: CC(C)S(=O)(=O)c1ccc(-c2cnc(N)c(C#Cc3cccc(C(N)=O)c3)n2)cc1
Temperature: 120 °C
Reaction time: 0.08 h
Yield: 17.5 %

Procedure:
Triethylamine (151.3 mg, 208.4 μL, 1.495 mmol) was added to a stirred solution of tert-butyl N-[5-(4-(isopropylsulfonyl)phenyl)-3-ethynylpyrazin-2-yl]-N-tertbutoxycarbonyl-carbamate (75 mg, 0.1495 mmol), 3-bromobenzamide (44.85 mg, 0.2242 mmol), copper (I) iodide (3.417 mg, 0.01794 mmol) and PdCl2(PPh3)2 (5.247 mg, 0.007475 mmol) in DMF (1.5 mL) and the reaction was stirred at 120° C. for 5 minutes under fixed power (300 W) microwave conditions. The reaction mixture was cooled to ambient temperature and diluted with EtOAc and 1MHCl/brine (1:1). The layers were separated and the aqueous layer was extracted with ethyl acetate (×2). The combined organics extracts washed with brine (×2), dried over (MgSO4) and concentrated in vacuo. The residue was dissolved in DCM (5 mL) and TFA (1 mL, 12.98 mmol) was added. The reaction was stirred at ambient temperature for 40 hours. The solvent was removed in vacuo and the residue azeotroped with DCM (×2) and ether (×2). The material was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected, passed through a sodium bicarbonate cartridge and freeze-dried to give the title compound as a beige solid (11 mg, 17% Yield). 1H NMR (400.0 MHz, DMSO) δ 1.18 (d, 6H), 3.45 (sept, 1H), 7.22 (br s, 2H), 7.53 (br s, 1H), 7.57 (t, 1H), 7.91 (d, 2H), 7.94 (d, 2H), 8.10 (s, 1H), 8.24 (d, 2H), 8.29 (d, 1H) and 8.78 (s, 1H) ppm; MS (ES+) 421.1.
Reaction SMILES: [N:1]1[CH:2]=[CH:3][N:4]2[CH:9]=[C:8]([CH2:10][O:11][C:12]3[CH:17]=[CH:16][NH:15][C:14](=[O:18])[CH:13]=3)[CH:7]=[CH:6][C:5]=12.Br[C:20]1[CH:21]=[CH:22][C:23]2[C:24]3[CH2:33][N:32]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:31][CH2:30][C:25]=3[N:26]([CH3:29])[C:27]=2[CH:28]=1.OC1C=CC=C2C=1N=CC=C2.C([O-])([O-])=O.[Cs+].[Cs+]>CS(C)=O.[Cu]I>[N:1]1[CH:2]=[CH:3][N:4]2[CH:9]=[C:8]([CH2:10][O:11][C:12]3[CH:17]=[CH:16][N:15]([C:20]4[CH:21]=[CH:22][C:23]5[C:24]6[CH2:33][N:32]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:31][CH2:30][C:25]=6[N:26]([CH3:29])[C:27]=5[CH:28]=4)[C:14](=[O:18])[CH:13]=3)[CH:7]=[CH:6][C:5]=12
Reactant: O=c1cc(OCc2ccc3nccn3c2)cc[nH]1
Reactant: Cn1c2c(c3ccc(Br)cc31)CN(C(=O)OC(C)(C)C)CC2
Agent: [Cu]I
Agent: O=C([O-])[O-]
Agent: Oc1cccc2cccnc12
Solvent: CS(C)=O
Product: Cn1c2c(c3ccc(-n4ccc(OCc5ccc6nccn6c5)cc4=O)cc31)CN(C(=O)OC(C)(C)C)CC2
Temperature: 135 °C
Reaction time: 4.5 h
Yield: 28.4 %

Procedure:
A suspension of 4-(imidazo[1,2-a]pyridin-6-ylmethoxy)pyridin-2(1H)-one (270 mg, 1.12 mmol), tert-butyl 7-bromo-5-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate (493 mg, 1.35 mmol), CuI (257 mg, 1.35 mmol), 8-hydroxyquinoline (98 mg, 0.67 mmol) and Cs2CO3 (401 mg, 1.23 mmol) in DMSO (10 mL) was degassed under reduced pressure for 45 min. The suspension was put under Ar and heated at 135° C. with stirring for 4.5 h. The suspension was cooled, 40:9:1 CH2Cl2/MeOH/NH4OH (50 mL) was added, and the resulting suspension was stirred at 25° C. for 30 min. The suspension was passed through a plug of silica gel, and the filtrate was washed with brine. The solution was dried over Na2SO4 and concentrate under reduced pressure. Flash chromatography (silica gel, (1:1 EtOAc/hexanes)/(4:0.9:0.1 CH2Cl2/MeOH/NH4OH), 100:0 to 0:100) yielded the title compound (167 mg, 28%) as a yellow solid: 1H NMR (300 MHz, CDCl3) δ 8.34-8.25 (m, 1H), 7.79-7.61 (m, 3H), 7.58-7.50 (m, 1H), 7.40-7.25 (m, 3H), 7.07-6.69 (m, 1H), 6.17-6.10 (m, 1H), 6.09-6.02 (m, 1H), 5.11 (s, 2H), 4.65 (br s, 2H), 3.92-3.80 (m, 2H), 3.65 (s, 3H), 2.89-2.80 (m, 2H), 1.52 (s, 9H); ESI MS m/z 526 [M+H]+.
Reaction SMILES: O=[CH:2][C@H:3]([C@H:5]([C@@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])[OH:4].[CH2:13]([NH2:27])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26]>>[CH2:13]([NH:27][CH:2]1[O:10][C@H:9]([CH2:11][OH:12])[C@@H:7]([OH:8])[C@H:5]([OH:6])[C@@H:3]1[OH:4])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26]
Reactant: O=C[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Reactant: CCCCCCCCCCCCCCN
Product: CCCCCCCCCCCCCCNC1O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]1O

Procedure:
20 g of D-mannose and 35 g of tetradecylamine were reacted as described in Example 44 to give N-tetradecylmannopyranosylamine. In a second reaction step, the glycosylamine (7.5 g) was reacted with 6.0 g of oleoyl chloride as described in Example 11 to give the glycosylamide.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:13]([N+:14]([O-:16])=[O:15])=[CH:12][C:6]2[CH2:7][CH2:8][NH:9][CH2:10][CH2:11][C:5]=2[CH:4]=1.[CH3:17][C:18]([CH3:20])=O.C(O)(=O)C.CO.C([BH3-])#N.[Na+]>>[CH:18]([N:9]1[CH2:10][CH2:11][C:5]2[CH:4]=[C:3]([O:2][CH3:1])[C:13]([N+:14]([O-:16])=[O:15])=[CH:12][C:6]=2[CH2:7][CH2:8]1)([CH3:20])[CH3:17]
Reactant: COc1cc2c(cc1[N+](=O)[O-])CCNCC2
Reactant: CC(C)=O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: COc1cc2c(cc1[N+](=O)[O-])CCN(C(C)C)CC2
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of 7-Methoxy-8-nitro-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.15 g, 0.00067 mol), Acetone (0.10 mL, 0.0014 mol), Acetic acid (0.1 mL, 0.002 mol) and Methanol (10 mL, 0.2 mol) was added Sodium cyanoborohydride (50 mg, 0.0008 mol). The mixture was stirred at room temperature for 4 hours. The reaction mixture was evaporated and the residue was partitioned between water (20 mL) and dichloromethane (20 mL). The organic layers were dried over magnesium sulfate, filtered and evaporated. The mixture was purified via silica gel chromatography using amine modified silica gel 10%→100% Ethyl Acetate:Hexane solvent gradient. 3-Isopropyl-7-methoxy-8-nitro-2,3,4,5-tetrahydro-1H-benzo[d]azepine isolated as a yellow oil.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Cl:11])[NH:7][CH:6]=[CH:5]2.C(=O)([O-])[O-].[Na+].[Na+].[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1.[NH4+].[Cl-]>CCO.C1(C)C=CC=CC=1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:11][C:10]1[CH:9]=[C:8]2[C:4]([CH:5]=[CH:6][NH:7]2)=[CH:3][C:2]=1[C:23]1[CH:24]=[CH:25][C:20]([O:19][CH3:18])=[CH:21][CH:22]=1
Reactant: Clc1cc2[nH]ccc2cc1Br
Reactant: COc1ccc(B(O)O)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Cl-]
Solvent: Cc1ccccc1
Solvent: CCO
Solvent: O
Product: COc1ccc(-c2cc3cc[nH]c3cc2Cl)cc1
Temperature: 90 °C
Yield: 39.1 %

Procedure:
A mixture of 5-bromo-6-chloro-1H-indole (3.20 g, 13.9 mmol), sodium carbonate (3.68 g, 34.7 mmol), and 4-methoxyphenylboronic acid (2.41 g, 15.9 mmol) in EtOH (18 mL), toluene (18 mL) and water (18 mL) was degassed with N2 for 15 minutes, treated with tetrakis(triphenylphosphine)palladium(0) (1.20 g, 0.99 mmol) and heated to 90° C. for 23 hours. The cooled reaction mixture was poured into half-saturated NH4Cl solution (200 mL) and extracted with dichloromethane (3×120 mL). The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The resulting dark solid was purified by flash chromatography (5-20% EtOAc/heptane) to give the title compound (1.40 g, 39%) as a white solid. MS (ES+) 258.5 (M+H)+. 1H NMR (500 MHz, CDCl3) δ 8.16 (br. s., 1H), 7.56 (s, 1H), 7.42 (d, J=8.1 Hz, 2H), 7.24 (s, 1H), 6.98 (d, J=8.1 Hz, 2H), 6.55 (br. s., 1H), 3.88 (s, 3H).
Reaction SMILES: [NH:1]1[CH:5]=[C:4]([CH:6]([C:8]2[CH:9]=[C:10]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH:11]=[CH:12][C:13]=2[O:14][CH3:15])[OH:7])[N:3]=[CH:2]1>ClCCl.[O-2].[O-2].[Mn+4]>[NH:1]1[CH:5]=[C:4]([C:6]([C:8]2[CH:9]=[C:10]([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)[CH:11]=[CH:12][C:13]=2[O:14][CH3:15])=[O:7])[N:3]=[CH:2]1
Reactant: COc1ccc(-c2ccccc2)cc1C(O)c1c[nH]cn1
Agent: [Mn+4]
Agent: [O-2]
Solvent: ClCCl
Product: COc1ccc(-c2ccccc2)cc1C(=O)c1c[nH]cn1
Temperature: 25 °C
Reaction time: 14 h
Yield: 90 %

Procedure:
1H-Imidazol-4-yl(4-methoxy[1,1′-biphenyl]-3-yl)methanol (0.94 g) was dissolved in dichloromethane (100 ml) and manganese dioxide (5.52 g) was added. The mixture was stirred at room temperature for 14 h, filtrated and concentrated. To the obtained residue was added ethyl acetate and the mixture was crystallized to give the title compound (0.84 g) as a colorless solid.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=1.[F-:11].[K+].C(#N)C>[Br-].C1([P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOCC>[F:11][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=1
Reactant: [F-]
Reactant: O=[N+]([O-])c1ccc(Cl)nc1
Agent: [Br-]
Agent: [K+]
Agent: c1ccc([P+](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CC#N
Solvent: CCOCC
Product: O=[N+]([O-])c1ccc(F)nc1
Yield: 51.5 %

Procedure:
2-Chloro-5-nitropyridine (100 g, 0.656 mol, Aldrich), potassium fluoride (84.1 g, 1.45 mol, Aldrich), tetraphenylphosphonium bromide (95.3 g, 0.227 mol, Aldrich), and acetonitrile (1.5 L) were combined and heated at reflux until consumption of the 2-chloro-5-nitropyridine was complete. The volume of the mixture was reduced to 750 mL, diluted with 2 L of ether, filtered and concentrated. The resultant residue was triturated with hot hexane, and the combined hexane extracts were concentrated to give of the title compound (48 g, 54%): 1H NMR (CDCl3, 300 MHz) δ 7.15 (dd, J=3, 6 Hz, 1H), 8.64 (m, 1H), 9.15 (d, J=1.6 Hz, 1H).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[H-].[Na+].[C:11]([O:15][C:16](=[O:19])[CH2:17]Br)([CH3:14])([CH3:13])[CH3:12]>CN(C)C=O>[C:11]([O:15][C:16](=[O:19])[CH2:17][O:8][C:5]1[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][CH:4]=1)([CH3:14])([CH3:13])[CH3:12]
Reactant: CC(C)(C)OC(=O)CBr
Reactant: Oc1ccc(Br)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)COc1ccc(Br)cc1
Temperature: 75 °C
Yield: 82.9 %

Procedure:
4-Bromophenol (20.4 g, 118 mmol) dissolved in dry N,N-dimethylformamide was carefully treated with sodium hydride (4 g, 167 mmol). t-Butylbromoacetate (23 g, 118 mmol) was added and the mixture heated to 75° C. for 90 minutes. The reaction was concentrated in vacuo and the residue partitioned between ethyl acetate and water. The organic phase was washed with saturated ammonium acetate and concentrated in vacuo to yield 28.1 g of tert-butyl(4-bromophenoxy)acetate.