Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([NH:5][C:6]1[N:14]=[C:13]2[C:9]([N:10]=[C:11]([O:21]C)[N:12]2[CH2:15][CH:16]2[CH2:20][CH2:19][O:18][CH2:17]2)=[C:8]([NH2:23])[N:7]=1)[CH2:2][CH2:3][CH3:4].Cl.O.[OH-].[Na+]>CO.O1CCOCC1.C(O)C>[NH2:23][C:8]1[N:7]=[C:6]([NH:5][CH2:1][CH2:2][CH2:3][CH3:4])[N:14]=[C:13]2[C:9]=1[NH:10][C:11](=[O:21])[N:12]2[CH2:15][CH:16]1[CH2:20][CH2:19][O:18][CH2:17]1
Reactant: CCCCNc1nc(N)c2nc(OC)n(CC3CCOC3)c2n1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: CCO
Solvent: C1COCCO1
Product: CCCCNc1nc(N)c2[nH]c(=O)n(CC3CCOC3)c2n1
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 58.7 %

Procedure:
N2-Butyl-8-(methoxy)-9-(tetrahydro-3-furanylmethyl)-9H-purine-2,6-diamine (98 mg) was dissolved in methanol (2 mL). To the resultant solution was added 4N hydrogen chloride in 1,4-dioxane (0.5 mL). The reaction mixture was then stirred at ambient temperature until completion (monitored by LCMS) over 2.5 hours. The reaction mixture was then evaporated under reduced pressure to give an oil. To this oil was added water (2 mL) and methanol (2 mL). The resultant solution was then neutralised using 2M sodium hydroxide solution. Further water (5 mL) was added when the product precipitated (pH 4-5). The white solid was isolated by filtration under suction and then washed with water (5 mL). The filter cake was then air-dried under suction to give (68 mg) that was dissolved in ethanol (2 mL). To this solution was added water (2 mL) to give a precipitate. The resultant suspension was heated (90° C., external) to reflux to give a solution. The resultant solution was refluxed for a few minutes before being allowed to cool to ambient room temperature to give a flocculent white solid. This solid was isolated by filtration under suction and the residues transferred using water (8 mL). The filter cake was air-dried under suction and was then dried under vacuo at 50° C. for 4 hours to give a white solid which was then transferred to a vial and dried further at 50° C. (16 hours) to give 55 mg of the title compound as a white solid.
Reaction SMILES: C(=O)(O)[O-].[Na+].[Cl:6][C:7]1[CH:26]=[CH:25][C:10]2[O:11][C:12]3[CH:24]=[CH:23][CH:22]=[CH:21][C:13]=3[C@@H:14]3[C@H:19]([NH2:20])[CH2:18][CH2:17][CH2:16][N:15]3[C:9]=2[CH:8]=1.Cl[C:28]([O:30][CH2:31][Cl:32])=[O:29].C(OCC)(=O)C>C(Cl)Cl>[Cl:32][CH2:31][O:30][C:28](=[O:29])[NH:20][C@H:19]1[C@@H:14]2[N:15]([C:9]3[CH:8]=[C:7]([Cl:6])[CH:26]=[CH:25][C:10]=3[O:11][C:12]3[CH:24]=[CH:23][CH:22]=[CH:21][C:13]=32)[CH2:16][CH2:17][CH2:18]1
Reactant: N[C@@H]1CCCN2c3cc(Cl)ccc3Oc3ccccc3[C@H]12
Reactant: O=C(Cl)OCCl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: O=C(N[C@@H]1CCCN2c3cc(Cl)ccc3Oc3ccccc3[C@H]12)OCCl
Temperature: 25 °C
Reaction time: 18 h
Yield: 83.9 %

Procedure:
100 μL of saturated aq. sodium bicarbonate was added to trans-7-chloro-2,3,4,14b-tetrahydro-1H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepine-1-amine (9.5 mg, 0.03 mmol) and chloromethyl chloroformate (64.2 μL, 0.42 mmol) in 250 μL of CH2Cl2. The resulting mixture was stirred at room temperature for 18 h. Subsequently, ethyl acetate was added and the organic layer was washed with water, dried (Na2SO4) and evaporated to give trans-(7-chloro-2,3,4,14b-tetrahydro-1H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepin-1-yl)carbamic acid chloromethyl ester (9.9 mg, 88%). Data: (m/z)=393 (M+H)+.
Reaction SMILES: C([O:5][C:6](=[O:25])[C@@H:7]1[CH2:11][CH2:10][CH2:9][N:8]1[C:12](=[O:24])[CH:13]([CH3:23])[CH2:14][S:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)(C)(C)C>C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O>[CH2:16]([S:15][CH2:14][CH:13]([CH3:23])[C:12]([N:8]1[CH2:9][CH2:10][CH2:11][C@H:7]1[C:6]([OH:25])=[O:5])=[O:24])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: CC(CSCc1ccccc1)C(=O)N1CCC[C@H]1C(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: COc1ccccc1
Product: CC(CSCc1ccccc1)C(=O)N1CCC[C@H]1C(=O)O
Reaction time: 1 h

Procedure:
1-[3-(benzylthio)-2-methylpropanoyl]-L-proline tert. butyl ester (7.8 g.) is dissolved in a mixture of anisole (55 ml.) and trifluoroacetic acid (110 ml.). After one hour storage at room temperature, the solvent is removed in vacuo and the residue is dissolved in ether, washed several times with saturated sodium chloride, dried over magnesium sulfate and evaporated to dryness in vacuo to yield 1-[3-(benzylthio)-2-methylpropanoyl]-L-proline. Rf 0.5 (Silica gel, Benzene/acetic acid 3:1) Rf 0.5. (Silica gel, Methyl-ethylketone/acetic acid/pyridine/water 14:1:2:1).
Reaction SMILES: C([O-])(=[O:8])C1C=CC=NC=1.[Na+].[N:11]1[CH:16]=[CH:15][N:14]=[CH:13][C:12]=1[C:17]([OH:19])=[O:18].[Na:20]>>[OH:8][C:15]1[N:14]=[CH:13][C:12]([C:17]([OH:19])=[O:18])=[N:11][CH:16]=1.[Na:20]
Reactant: O=C(O)c1cnccn1
Reactant: O=C([O-])c1cccnc1
Agent: [Na+]
Agent: [Na]
Product: O=C(O)c1cnc(O)cn1
Temperature: 0 °C
Yield: 67 %

Procedure:
Pseudomonas acidovorans DSM 4746 was cultivated in a mineral salt medium (Table 1 below) under a continuous addition of sodium nicotinate (0.6 g/l/h) in a fermenter at a pH of 7.0 and at a temperature of 30° C. to an optical density, at 650 nm, of 10. Then the cells were centrifuged off and resuspended in a 2 liter solution, containing 1 mol (146 g) of pyrazinecarboxylic acid-sodium salt, at pH 7.0. The optical density at 650 nm was then 20. After an incubation time of 16 hours under aerobic conditions at pH 7.0 and a temperature of 30° C., no feedstock was able to be detected by UV-spectroscopy. A part of the formed 5-hydroxypyrazinecarboxylic acid-sodium salt crystallized already under these test conditions. The precipitated product was centrifuged off together with the biomass. The formed sediment was then resuspended in 500 ml of water and again centrifuged off. The cell-free supernatants were combined and concentrated by evaporation with a rotary evaporator to 300 ml and cooled to 0° C. The formed crystals were filtered off and dried. Altogether 0.67 mol (108 g) of 5-hydroxypyrazinecarboxylic acid-sodium salt was isolated, corresponding to a yield of 67 percent, relative to the amount of pyrazinecarboxylic acid-sodium salt used.
Reaction SMILES: C([O:4][CH2:5][C:6]1[CH:11]=[C:10]([O:12][CH3:13])[C:9]([O:14][CH2:15][CH2:16][Cl:17])=[CH:8][C:7]=1[CH2:18][O:19]C(=O)C)(=O)C.N>CO>[Cl:17][CH2:16][CH2:15][O:14][C:9]1[C:10]([O:12][CH3:13])=[CH:11][C:6]([CH2:5][OH:4])=[C:7]([CH2:18][OH:19])[CH:8]=1
Reactant: COc1cc(COC(C)=O)c(COC(C)=O)cc1OCCCl
Agent: N
Solvent: CO
Product: COc1cc(CO)c(CO)cc1OCCCl
Reaction time: 15 h
Yield: 94.5 %

Procedure:
A solution of 14.0 g of the 2-[(acetyloxy)methyl]4-(2-chloroethoxy)-5-methoxybenzyl acetate in 600 mL of methanol is stirred and cooled in an ice bath while ammonia gas is bubbled in, until the solution is saturated. The flask is stoppered and stored in the refrigerator for 15 hours. The reaction mixture is evaporated to give a white solid which is dried and chromatographed on a silica gel column eluting with 2:1 hexanes/ethyl acetate, to give 9.87 g of [4-(2-chloroethoxy)-2-(hydroxymethyl)-5-methoxyphenyl]methanol as a white solid, m.p. 934° C.
Reaction SMILES: Cl.[CH2:2]([N:4]([CH2:7][CH:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]1=[O:18])[CH2:5][CH3:6])[CH3:3].[C:19]1([N:25]2[C:29]3(CCNCC3)[C:28](=[O:35])[NH:27][CH2:26]2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CO>[C:19]1([N:25]2[C:29]3([CH2:6][CH2:5][N:4]([CH2:7][CH:8]4[CH2:17][CH2:16][C:15]5[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=5)[C:9]4=[O:18])[CH2:2][CH2:3]3)[C:28](=[O:35])[NH:27][CH2:26]2)[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1
Reactant: O=C1NCN(c2ccccc2)C12CCNCC2
Reactant: CCN(CC)CC1CCc2ccccc2C1=O
Agent: Cl
Solvent: CO
Product: O=C1c2ccccc2CCC1CN1CCC2(CC1)C(=O)NCN2c1ccccc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 85.1 %

Procedure:
2-[(Diethylamino)methyl]-3,4-dihydro-1 (2H)-naphthalenone, hydrochloride (6.93 g) and 1-phenyl-1,3,8-triazaspiro-[4.5]decan-4-one (6.0 g.) are dissolved in 75 ml of methanol by brief heating, followed by stirring at room temperature for 16 hours. The resulting precipitate is filtered, washed with ethanol and dried at 80° C under vacuum to yield 8.58 g of the title compound, melting point 170°-173° C.
Reaction SMILES: [Si](Cl)(C)(C)C.BrCCBr.Br[C:11]1[S:12][CH:13]=[CH:14][N:15]=1.Br[C:17]1[CH2:22][CH2:21][CH2:20][C:19](=[O:23])[CH:18]=1.[Cl-].[NH4+]>[Zn].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.C1COCC1.CN(C)C(=O)C>[S:12]1[CH:13]=[CH:14][N:15]=[C:11]1[C:17]1[CH2:22][CH2:21][CH2:20][C:19](=[O:23])[CH:18]=1
Reactant: O=C1C=C(Br)CCC1
Reactant: Brc1nccs1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: C[Si](C)(C)Cl
Agent: [Cl-]
Solvent: BrCCBr
Solvent: C1CCOC1
Solvent: CC(=O)N(C)C
Product: O=C1C=C(c2nccs2)CCC1
Temperature: 60 °C
Reaction time: 0.08 h
Yield: 27.6 %

Procedure:
To a 100 mL round bottom flask containing a stir bar was added 0.185 g of zinc dust (2.83 mmol) and 3 mL of N,N-dimethylacetamide. The flask was placed under nitrogen and 0.08 mL of TMS-chloride (0.63 mmol) and 0.05 mL of 1,2-dibromoethane (0.58 mmol) were added by syringe. The reaction was stirred for 5 min. and 0.09 mL of 2-bromothiazole (0.998 mmol) was added by syringe. The reaction was stirred for 1 hour at room temperature under nitrogen. To a separate 100 mL round bottom flask containing a stir bar was added 0.124 g of 3-bromocyclohex-2-enone (0.708 mmol) and 0.024 g of Pd(PPh3)2Cl2 (4.8 mol %), and 10 mL of anhydrous THF. The previously prepared organozinc species was added to the enone solution dropwise with removal of excess zinc using a syringe fitted with a cotton plug. The reaction was heated overnight at 60° C. in an oil bath with stirring under nitrogen atmosphere. The reaction was worked up by transferring the solution to a vial containing 10 mL of saturated ammonium chloride solution, and the product was extracted with ethyl acetate (2 times with 8 mL). The organic layer was dried with sodium sulfate, filtered, and solvent was concentrated under reduced pressure. The product was purified by flash chromatography using the Biotage system utilizing gradient elution (0% to 80% ethyl acetate/hexanes). Product fractions were combined and concentrated to yield a pale yellow solid (35 mg, 28%). 1H NMR (CDCl3, 300 MHz): δ 2.17 (quintet, J=6.3 Hz, 2H), 2.52 (t, J=6.3 Hz, 2H), 2.97 (td, J=6.3, 1.5 Hz, 2H), 6.69 (br s, 1H), 7.45 (d, J=3.0 Hz, 1H), 7.93 (d, J=3.0 Hz, 1H). 13C NMR (CDCl3, 75 MHz): δ 22.4, 27.0, 37.8, 121.4, 126.6, 144.4, 151.7, 166.7, 199.4. LCMS (ESI): mass calcd for (C9H9NOS) m/z 179.04; measured [M+H]+: m/z 180.03.
Reaction SMILES: [Br:1][C:2]1[CH:8]=[C:7]([N+:9]([O-])=O)[C:5]([NH2:6])=[C:4]([CH3:12])[CH:3]=1.Cl[Sn]Cl>CCO>[Br:1][C:2]1[CH:8]=[C:7]([NH2:9])[C:5]([NH2:6])=[C:4]([CH3:12])[CH:3]=1
Reactant: Cc1cc(Br)cc([N+](=O)[O-])c1N
Agent: Cl[Sn]Cl
Solvent: CCO
Product: Cc1cc(Br)cc(N)c1N
Temperature: 25 °C
Yield: 72.6 %

Procedure:
To a suspension of 4-bromo-2-methyl-6-nitroaniline (2.0 g, 8.7 mmol) in EtOH (20 mL) was added SnCl2 (5.0 g, 26.1 mmol). The reaction mixture was heated at reflux for 14 h, cooled to RT and concentrated in vacuo. The residue was diluted with EtOAc (100 mL) and partitioned between satd. aq. NaHCO3 solution (200 mL). The resulting slurry was filtered through a pad of Celite® and the wet cake was washed with EtOAc (3×50 mL). The filtrate was washed sequentially with satd. aq. NaHCO3, water, and brine, dried (MgSO4), filtered and concentrated in vacuo to afford 1.27 g (72%) of 5-bromo-3-methylbenzene-1,2-diamine (72) as yellow oil: MS (ESI) m/z=201.1 [M+1]+.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([CH2:8][OH:9])[CH:7]=1.[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=O.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1>ClCCl>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([CH:7]=1)[CH:8]=[O:9]
Reactant: Cc1ccc([N+](=O)[O-])c(CO)c1
Agent: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: Cc1ccc([N+](=O)[O-])c(C=O)c1
Temperature: 25 °C
Reaction time: 6 h
Yield: 79.3 %

Procedure:
Dissolve (5-methyl-2-nitrophenyl)methanol (10 g, 59.88 mmol) in dichloromethane (210 mL). Add 3 Å molecular sieves (54 g) and pyridinium dichromate (22.53 g, 59.88 mmol). Stir at room temperature for 6 hours. Pass the crude reaction mixture through a short silica gel column, and remove under reduced pressure. Purification of the residue by flash chromatography (silica gel, 10-20% ethyl acetate:hexane) gives 7.84 g (79%) of title compound as colorless oil. 1H NMR (CDCl3) δ 10.41 (m, 1H), 8.02 (m, 1H), 7.69 (s, 1H), 7.53 (d, 1H), 2.51 (s, 3H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:28]=[CH:27][C:6]([CH2:7][N:8]([C:22]2[S:23][CH:24]=[CH:25][N:26]=2)[S:9]([C:12]2[CH:13]=[CH:14][C:15]3[NH:20][CH2:19][CH2:18][O:17][C:16]=3[CH:21]=2)(=[O:11])=[O:10])=[CH:5][CH:4]=1.F[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[S:36]([CH3:39])(=[O:38])=[O:37].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]([C:22]2[S:23][CH:24]=[CH:25][N:26]=2)[S:9]([C:12]2[CH:13]=[CH:14][C:15]3[N:20]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=4[S:36]([CH3:39])(=[O:38])=[O:37])[CH2:19][CH2:18][O:17][C:16]=3[CH:21]=2)(=[O:11])=[O:10])=[CH:27][CH:28]=1
Reactant: COc1ccc(CN(c2nccs2)S(=O)(=O)c2ccc3c(c2)OCCN3)cc1
Reactant: CS(=O)(=O)c1ccccc1F
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccc(CN(c2nccs2)S(=O)(=O)c2ccc3c(c2)OCCN3c2ccccc2S(C)(=O)=O)cc1
Temperature: 90 °C
Yield: 48.8 %

Procedure:
To a solution of INTERMEDIate M (300 mg, 0.717 mmol) and 1-fluoro-2-(methylsulfonyl)benzene (149.0 mg, 0.861 mmol, Apollo) in DMF was added cesium carbonate (467.0 mg, 1.43 mmol). The reaction mixture was heated at 90° C. for 16 h. After completion, the reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (2×10 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to obtain the crude material which was purified by combiflash column chromatography (column size: 12 g; elution: 12% ethyl acetate in hexane) to provide N-(4-methoxybenzyl)-4-(2-(methylsulfonyl)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (200 mg, 48.8%) as yellow solid. MS (ESI, positive ion) m/z: 572.02 (M+1).
Reaction SMILES: C([Mg]Cl)(C)C.[CH:6]1([NH:9][C:10]2[C:14]3[CH:15]=[CH:16][CH:17]=[C:18](I)[C:13]=3[O:12][N:11]=2)[CH2:8][CH2:7]1.[B:20](OC(C)C)([O:25]C(C)C)[O:21]C(C)C.Cl>O1CCCC1.O>[CH:6]1([NH:9][C:10]2[C:14]3[CH:15]=[CH:16][CH:17]=[C:18]([B:20]([OH:25])[OH:21])[C:13]=3[O:12][N:11]=2)[CH2:8][CH2:7]1
Reactant: CC(C)OB(OC(C)C)OC(C)C
Reactant: Ic1cccc2c(NC3CC3)noc12
Agent: CC(C)[Mg]Cl
Agent: Cl
Solvent: O
Solvent: C1CCOC1
Product: OB(O)c1cccc2c(NC3CC3)noc12
Temperature: 0 °C
Reaction time: 1 h
Yield: 37.8 %

Procedure:
Isopropylmagnesium chloride (2.0 M in tetrahydrofuran, 2.83 mL, 5.7 mmol) was added dropwise over 20 minutes to a stirred solution of N-cyclopropyl-7-iodobenzo[d]isoxazol-3-amine (preparation 22 g, 0.50 g, 1.7 mmol) in tetrahydrofuran (10 mL) at −10° C. The mixture was stirred for 1 hour at 0° C. then triisopropyl borate (1.15 mL, 5.0 mmol) was added dropwise over 10 minutes and the mixture was stirred for 1 hour at 0° C. Then, the mixture was warmed to room temperature and stirred overnight. Water was then added, the mixture was cooled by means of an ice-water bath and the pH was adjusted to 1 with 2M aqueous hydrochloric acid. The mixture was extracted with ethyl acetate and the organic layer was washed with brine, dried (MgSO4) and evaporated. The residue was triturated with diethyl ether and the solid was filtered and dried to give the title compound (140 mg, 39%) as a white solid.
Reaction SMILES: C([N:9]1[CH2:14][CH2:13][CH:12]([C:15]2[N:16]=[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][N:18]3[CH:23]=2)[CH2:11][CH2:10]1)(=O)C1C=CC=CC=1.[OH-].[K+]>C(O)C>[N:16]1[C:15]([CH:12]2[CH2:13][CH2:14][NH:9][CH2:10][CH2:11]2)=[CH:23][N:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=12
Reactant: O=C(c1ccccc1)N1CCC(c2cn3ccccc3n2)CC1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: c1ccn2cc(C3CCNCC3)nc2c1
Yield: 47.7 %

Procedure:
To a solution of 70 mg of 1-benzoyl-4-(imidazo[1,2-a]pyridin-2-yl)-piperidine (from Step A) in 4 mL of ethanol was added 1 mL of 45% KOH solution. The reaction was refluxed for 14 hours. After concentration, the mixture was partitioned between EtOAc and water. Aqueous layer was extracted with EtOAc (3×). The combined organic phase was washed with brine, dried over MgSO4 and concentrated to give 22 mg of the title compound as a viscous oil.
Reaction SMILES: [C@H:1]1([O:12][C@H:13]2[C@H:22]([OH:23])[C@@H:21]([CH2:24][O:25][C@H:26]3[O:34][C@H:33]([CH2:35][OH:36])[C@@H:31]([OH:32])[C@H:29]([OH:30])[C@@H:27]3[OH:28])[O:20][C@H:15]([O:16][CH2:17][CH2:18][NH2:19])[C@H:14]2[OH:37])[O:9][C@H:8]([CH2:10][OH:11])[C@@H:6]([OH:7])[C@H:4]([OH:5])[C@@H:2]1[OH:3].[CH2:38]([O:45][C:46]([NH:48][C@H:49]([C:77](ON1C(=O)CCC1=O)=[O:78])[CH2:50][CH2:51][CH2:52][CH2:53][NH:54][C:55](=[O:76])[CH2:56][CH2:57][CH2:58][CH2:59][C:60]([NH:62][CH2:63][CH2:64][O:65][C@@H:66]1[O:74][C@@H:73]([CH3:75])[C@@H:71]([OH:72])[C@@H:69]([OH:70])[C@@H:67]1[OH:68])=[O:61])=[O:47])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>CN(C=O)C>[CH2:38]([O:45][C:46]([NH:48][C@H:49]([C:77]([NH:19][CH2:18][CH2:17][O:16][C@H:15]1[O:20][C@H:21]([CH2:24][O:25][C@H:26]2[O:34][C@H:33]([CH2:35][OH:36])[C@@H:31]([OH:32])[C@H:29]([OH:30])[C@@H:27]2[OH:28])[C@@H:22]([OH:23])[C@H:13]([O:12][C@H:1]2[O:9][C@H:8]([CH2:10][OH:11])[C@@H:6]([OH:7])[C@H:4]([OH:5])[C@@H:2]2[OH:3])[C@@H:14]1[OH:37])=[O:78])[CH2:50][CH2:51][CH2:52][CH2:53][NH:54][C:55](=[O:76])[CH2:56][CH2:57][CH2:58][CH2:59][C:60]([NH:62][CH2:63][CH2:64][O:65][C@@H:66]1[O:74][C@@H:73]([CH3:75])[C@@H:71]([OH:72])[C@@H:69]([OH:70])[C@@H:67]1[OH:68])=[O:61])=[O:47])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1
Reactant: NCCO[C@H]1O[C@H](CO[C@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]2O)[C@@H](O)[C@H](O[C@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]2O)[C@@H]1O
Reactant: C[C@@H]1O[C@@H](OCCNC(=O)CCCCC(=O)NCCCC[C@H](NC(=O)OCc2ccccc2)C(=O)ON2C(=O)CCC2=O)[C@@H](O)[C@H](O)[C@@H]1O
Solvent: CN(C)C=O
Product: C[C@@H]1O[C@@H](OCCNC(=O)CCCCC(=O)NCCCC[C@H](NC(=O)OCc2ccccc2)C(=O)NCCO[C@H]2O[C@H](CO[C@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]3O)[C@@H](O)[C@H](O[C@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]3O)[C@@H]2O)[C@@H](O)[C@H](O)[C@@H]1O
Temperature: 25 °C
Reaction time: 18 h

Procedure:
In a 40 mL vial, 2-aminoethyl α-D-mannopyranosyl-(1→3)-[α-D-mannopyranosyl-(1→6)]-α-D-mannopyranoside (883 mg, 1.612 mmol) was dissolved in DMF (10 mL). To the above solution at 0° C. was added a solution of 2,5-dioxopyrrolidin-1-yl N2-[(benzyloxy)carbonyl]-N6-[6-({2-[(α-L-fucopyranosyl)oxy]ethyl}amino)-6-oxohexanoyl]-L-lysinate (700 mg, 1.008 mmol) in DMF (10 mL) dropwise. After stirring at rt for 18 hr, the mixture was concentrated. The residue was purified by HPLC (waters Delta Pak C4 300 A, 15 um, 50×250 mm column, flow rate 85 ml/min, gradient 8-30% ACN/water in 25 min) to give the title compound. UPLC Method B: m/e=1127.335 [M+1]; Rt=2.83 min.
Reaction SMILES: [C:1]([O:5][C:6](=[O:27])[N:7]([CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])[CH2:8][C:9]1([C:12]2[CH:17]=[CH:16][C:15]([CH2:18][OH:19])=[CH:14][CH:13]=2)[CH2:11][CH2:10]1)([CH3:4])([CH3:3])[CH3:2]>C(OCC)C.[O-2].[O-2].[Mn+4]>[C:1]([O:5][C:6](=[O:27])[N:7]([CH2:8][C:9]1([C:12]2[CH:17]=[CH:16][C:15]([CH:18]=[O:19])=[CH:14][CH:13]=2)[CH2:11][CH2:10]1)[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])([CH3:2])([CH3:3])[CH3:4]
Reactant: CCCCCCCN(CC1(c2ccc(CO)cc2)CC1)C(=O)OC(C)(C)C
Agent: [Mn+4]
Agent: [O-2]
Solvent: CCOCC
Product: CCCCCCCN(CC1(c2ccc(C=O)cc2)CC1)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 76.5 %

Procedure:
To a stirred solution of heptyl-[1-(4-hydroxymethyl-phenyl)-cyclopropylmethyl]-carbamic acid tert-butyl ester (850 mg, 2.24 mmol) in anhydrous diethyl ether (25 mL) under an nitrogen atmosphere was added activated manganese dioxide (Aldrich, 2.25 g). The solution was allowed to stir at room temperature for 2 hours. An additional 1 g of manganese dioxide was added and the mixture was stirred for 2 hours. The heterogeneous black mixture was filtered through a Celite plug and was washed exhaustively with methylene chloride. The clear filtrate was concentrated to a crude yellow tinged oil. The crude mixture was purified by flash chromatography (15% ethyl acetate/hexanes) to give [1-(4-formyl-phenyl)-cyclopropylmethyl]-heptyl-carbamic acid tert-butyl ester as a clear oil (640 mg, 77%).
Reaction SMILES: Cl[C:2]1[NH:3][C:4]2[N:5]([N:9]=[C:10]([CH3:24])[C:11]=2[CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[C:14]=2[CH3:23])[C:6](=[O:8])[CH:7]=1.[NH:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1>C(O)C.C(OCC)(=O)C.Cl>[CH3:24][C:10]1[C:11]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[C:14]=2[CH3:23])=[C:4]2[N:3]=[C:2]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[CH:7]=[C:6]([OH:8])[N:5]2[N:9]=1
Reactant: Cc1nn2c(=O)cc(Cl)[nH]c2c1Cc1cccc(C(F)(F)F)c1C
Reactant: C1COCCN1
Agent: Cl
Solvent: CCO
Solvent: CCOC(C)=O
Product: Cc1nn2c(O)cc(N3CCOCC3)nc2c1Cc1cccc(C(F)(F)F)c1C

Procedure:
To a solution of 5-chloro-2-methyl-3-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}pyrazolo[1,5-a]pyrimidin-7(4H)-one (55 mg, 0.155 mmol) in ethanol (1.5 mL) was added morpholine (40.4 mg, 0.464 mmol) in a microwave reaction vessel. It was sealed and irradiated (microwave) at 145° C. for 3 hour. The reaction mixture was then diluted with ethyl acetate (15 mL) and 5% HCl solution (3 mL). Two layers were separated. Organic layer was dried, concentrated and purified with silica gel column (methanol/DCM, 0-10%). The titled compound was obtained. (37 mg, 59%); LC/MS: MS (ES+) m/e 407 (MH+); 1H NMR (400 MHz, DMSO-d6) δ ppm 2.08 (s, 3H) 2.45 (s, 3H) 3.31 (d, J=4.80 Hz, 3H) 3.29 (br. s., 1H) 3.69 (br. s., 1H) 3.67 (d, J=5.05 Hz, 3H) 3.96 (s, 2H) 5.07 (s, 1H) 7.15 (br. s., 1H) 7.25-7.32 (m, 1H) 7.54 (d, J=7.83 Hz, 1H).
Reaction SMILES: [C:1]([O:20][CH:21]1[CH2:26][CH2:25][N:24]([OH:27])[CH2:23][CH2:22]1)(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].C(=O)([O-])[O-].[CH2:32](Br)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>C(O)C>[C:1]([O:20][CH:21]1[CH2:26][CH2:25][N:24]([O:27][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH2:23][CH2:22]1)(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: CCCCCCCCCCCCCCCCCC(=O)OC1CCN(O)CC1
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Solvent: CCO
Product: CCCCCCCCCCCCCCCCCC(=O)OC1CCN(OCc2ccccc2)CC1

Procedure:
The general procedure of Example 1 is repeated using 1-hydroxypiperidin-4-yl stearate, poassium carbonate and benzyl bromide in ethanol solvent to give the title compound.
Reaction SMILES: [F:1][C:2]([F:25])([F:24])[CH2:3][N:4]([CH2:19][C:20]([F:23])([F:22])[F:21])[C:5]1[CH:6]=[CH:7][C:8]([C:16](O)=[O:17])=[N:9][C:10]=1[O:11][CH2:12][CH:13]1[CH2:15][CH2:14]1.[NH2:26][C:27]([CH2:34][CH3:35])([CH2:32][CH3:33])[C:28]([NH:30][CH3:31])=[O:29]>>[CH2:32]([C:27]([NH:26][C:16]([C:8]1[CH:7]=[CH:6][C:5]([N:4]([CH2:3][C:2]([F:1])([F:25])[F:24])[CH2:19][C:20]([F:22])([F:21])[F:23])=[C:10]([O:11][CH2:12][CH:13]2[CH2:14][CH2:15]2)[N:9]=1)=[O:17])([C:28](=[O:29])[NH:30][CH3:31])[CH2:34][CH3:35])[CH3:33]
Reactant: CCC(N)(CC)C(=O)NC
Reactant: O=C(O)c1ccc(N(CC(F)(F)F)CC(F)(F)F)c(OCC2CC2)n1
Product: CCC(CC)(NC(=O)c1ccc(N(CC(F)(F)F)CC(F)(F)F)c(OCC2CC2)n1)C(=O)NC

Procedure:
The title compound was synthesized in analogy to Example 1, using 5-[bis-(2,2,2-trifluoro-ethyl)-amino]-6-cyclopropylmethoxy-pyridine-2-carboxylic acid (Example 162 b) and 2-amino-2-ethyl-N-methyl-butyramide (Example 70 b) as starting materials, MS (EI): m/e=499.2 [M+H]+.