Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16](=[O:30])[NH:17][C:18]2[S:26][C:21]3[CH2:22][NH:23][CH2:24][CH2:25][C:20]=3[C:19]=2[C:27]([NH2:29])=[O:28])=[CH:11][CH:10]=1.C(N(CC)CC)C.[C:38]([NH:45][CH2:46][CH2:47][CH2:48]Br)([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39]>CN(C=O)C>[C:27]([C:19]1[C:20]2[CH2:25][CH2:24][N:23]([CH2:48][CH2:47][CH2:46][NH:45][C:38](=[O:39])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42])[CH2:22][C:21]=2[S:26][C:18]=1[NH:17][C:16](=[O:30])[NH:15][C:12]1[CH:11]=[CH:10][C:9]([Cl:8])=[CH:14][CH:13]=1)(=[O:28])[NH2:29]
Reactant: NC(=O)c1c(NC(=O)Nc2ccc(Cl)cc2)sc2c1CCNC2
Reactant: CC(C)(C)OC(=O)NCCCBr
Solvent: O=C(O)C(F)(F)F
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)NCCCN1CCc2c(sc(NC(=O)Nc3ccc(Cl)cc3)c2C(N)=O)C1
Temperature: 25 °C
Reaction time: 14 h
Yield: 59.1 %

Procedure:
A solution of 2-[3-(4-Chlorophenyl)ureido]-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide trifluoroacetate (0.48 mmol) in anhydrous DMF was treated with triethyl amine (200 μL, 1.43 mmol) and N-Boc-bromopropylamine (114 mg, 0.48 mmol) and the reaction mixture was allowed to stir at room temperature for 14 h. Analytical HPLC showed close to 50% progression. Another 100 μL of triethyl amine and 70 mg of N-Boc-bromopropylamine were added and the reaction mixture was stirred at room temperature. Upon completion (48 h), DMF was removed under vacuo and the resultant crude mixture was diluted with DCM and washed with water (×2). The organic layer was dried (anhydrous Na2SO4) and concentrated to afford an oil which was purified by flash chromatography Isolera system (SiO2 gel as stationary phase, 40 g HP column, dry loading) using DCM-DCM/MeOH (0%-15% MeOH in DCM) to afford the title compound as a light brown solid (144 mg, 60% yield). 1H NMR (300 MHz, dmso-d6) δ 10.95 (s, 1H), 10.18 (s, 1H), 7.55-7.43 (m, 2H), 7.37-7.27 (m, 2H), 6.82 (s, 1H), 3.53-3.43 (m, 2H), 3.03-2.90 (m, 2H), 2.85-2.57 (m, 4H), 2.50-2.40 (m, 2H), 1.69-1.53 (m, 2H), 1.37 (s, 9H). LRMS [M+H]508.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]2[N:13]3[C:14]([CH2:17]Cl)=[N:15][N:16]=[C:12]3[CH2:11][N:10]=[C:9]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:8]=2[CH:25]=1)([O-:3])=[O:2].[I-].[K+].[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1>O1CCCC1>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]2[N:13]3[C:14]([CH2:17][N:28]4[CH2:33][CH2:32][O:31][CH2:30][CH2:29]4)=[N:15][N:16]=[C:12]3[CH2:11][N:10]=[C:9]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:8]=2[CH:25]=1)([O-:3])=[O:2]
Reactant: C1COCCN1
Reactant: O=[N+]([O-])c1ccc2c(c1)C(c1ccccc1)=NCc1nnc(CCl)n1-2
Agent: [I-]
Agent: [K+]
Solvent: C1CCOC1
Product: O=[N+]([O-])c1ccc2c(c1)C(c1ccccc1)=NCc1nnc(CN3CCOCC3)n1-2

Procedure:
In the manner given in Preparation 48, 8-nitro-1-(chloromethyl)-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine, potassium iodide, and morpholine in tetrahydrofuran are reacted to give 8-nitro-1-(morpholinomethyl)-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine.
Reaction SMILES: [C:1]([Si:5]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[O:6][CH2:7][C:8]([C:11]1[CH:15]=[C:14]([NH:16][C:17](=[O:32])[C:18]([S:21]([CH2:24][CH:25]2[CH2:30][CH2:29][CH:28]([OH:31])[CH2:27][CH2:26]2)(=[O:23])=[O:22])([CH3:20])[CH3:19])[O:13][N:12]=1)([CH3:10])[CH3:9])([CH3:4])([CH3:3])[CH3:2].[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1>C(Cl)Cl.C(OCC)C>[C:1]([Si:5]([C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[O:6][CH2:7][C:8]([C:11]1[CH:15]=[C:14]([NH:16][C:17](=[O:32])[C:18]([CH3:20])([S:21]([CH2:24][CH:25]2[CH2:30][CH2:29][C:28](=[O:31])[CH2:27][CH2:26]2)(=[O:23])=[O:22])[CH3:19])[O:13][N:12]=1)([CH3:10])[CH3:9])([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C)(CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C)c1cc(NC(=O)C(C)(C)S(=O)(=O)CC2CCC(O)CC2)on1
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: CCOCC
Solvent: ClCCl
Product: CC(C)(CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C)c1cc(NC(=O)C(C)(C)S(=O)(=O)CC2CCC(=O)CC2)on1
Temperature: 25 °C
Reaction time: 18 h
Yield: 52.2 %

Procedure:
To a solution of 0.21 g (0.36 mmol) of N-{3-[2-(tert-butyl-diphenyl-silanyloxy)-1,1-dimethyl-ethyl]-isoxazol-5-yl}-2-(4-hydroxy-cyclohexylmethanesulfonyl)-2-methyl-propionamide in DCM (3 mL) is added pyridinium chlorochromate (0.15 g, 0.72 mmol) and the reaction mixture is stirred at room temperature for 18 h. The reaction is diluted with diethyl ether (6 mL) and stirred for 10 min. The mixture is filtered through a plug of silica and the filtrate is concentrated to afford 0.12 g of N-{3-[2-(tert-butyl-diphenyl-silanyloxy)-1,1-dimethyl-ethyl]-isoxazol-5-yl}-2-methyl-2-(4-oxo-cyclohexylmethanesulfonyl)-propionamide, which is used without further purification in the next step. Yield: 54%, ES-MS: 637 [M−H]
Reaction SMILES: [Cl:1][C:2]1[C:10]([CH3:11])=[N:9][C:8]2[N:4]([N:5]=[C:6]3[CH2:14][N:13]([C:15]([C:17]4[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=4[O:24][C@@H:25]4[CH2:29][CH2:28][NH:27][CH2:26]4)=[O:16])[CH2:12][C:7]3=2)[C:3]=1[CH3:30].[O:31]1[CH2:36][CH2:35][C:34](=O)[CH2:33][CH2:32]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(Cl)Cl>[Cl:1][C:2]1[C:10]([CH3:11])=[N:9][C:8]2[N:4]([N:5]=[C:6]3[CH2:14][N:13]([C:15]([C:17]4[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=4[O:24][C@@H:25]4[CH2:29][CH2:28][N:27]([CH:34]5[CH2:35][CH2:36][O:31][CH2:32][CH2:33]5)[CH2:26]4)=[O:16])[CH2:12][C:7]3=2)[C:3]=1[CH3:30]
Reactant: O=C1CCOCC1
Reactant: Cc1nc2c3c(nn2c(C)c1Cl)CN(C(=O)c1ccc(F)cc1O[C@@H]1CCNC1)C3
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Solvent: ClCCCl
Product: Cc1nc2c3c(nn2c(C)c1Cl)CN(C(=O)c1ccc(F)cc1O[C@@H]1CCN(C2CCOCC2)C1)C3
Yield: 44.5 %

Procedure:
A mixture of Example 80 (150 mg; 0.35 mmol; 1 eq.), tetrahydropyran-4-one (52 mg; 0.52 mmol; 1.5 eq.) and sodium triacetoxyborohydride (74 mg; 0.35 mmol; 1 eq.) in DCE (4 mL) was stirred at 50° C. for 16 hours. The reaction mixture was diluted with DCM, washed with sat. aq. NaHCO3, dried over magnesium sulfate and concentrated in vacuo. Purification by column chromatography (EA to EA/MeOH/TEA, 90/10/2) afforded the title compound (80 mg, 45%) as white foam. 1H NMR (DMSO-d6) δ 7.41-7.31 (m, 1H), 6.99 (dd, J=11.5, 2.2 Hz, 1H), 6.87 (td, J=8.4, 2.3 Hz, 1H), 5.03-4.94 (m, 1H), 4.85-4.77 (m, 2H), 4.75-4.44 (m, 2H), 3.74-3.59 (m, 2H), 3.22-3.06 (m, 2H), 2.85 (s, 1.5H), 2.81 (s, 1.5H), 2.79-2.64 (m, 3H), 2.62 (s, 1.5H), 2.56 (s, 1.5H), 2.35-2.15 (m, 2H), 2.14-2.00 (m, 1H), 1.82-1.68 (m, 1H), 1.63-1.50 (m, 2H), 1.31-1.03 (m, 2H). HPLC (max plot) 95.1%, Rt 2.83 min. UPLC/MS: (MS+) 514.5 ([M+H]+).
Reaction SMILES: [C:1]([N:4]([CH2:13][CH2:14][C:15]([OH:17])=O)[C:5]1[C:10]([CH3:11])=[CH:9][CH:8]=[CH:7][C:6]=1[CH3:12])(=[O:3])[CH3:2].[CH2:18]([C:20]1[CH:34]=[CH:33][CH:32]=[C:31]([CH2:35][CH3:36])[C:21]=1[NH:22][CH2:23][CH2:24][CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH3:19]>>[C:1]([N:4]([CH2:13][CH2:14][C:15]([N:22]([CH2:23][CH2:24][CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])[C:21]1[C:31]([CH2:35][CH3:36])=[CH:32][CH:33]=[CH:34][C:20]=1[CH2:18][CH3:19])=[O:17])[C:5]1[C:6]([CH3:12])=[CH:7][CH:8]=[CH:9][C:10]=1[CH3:11])(=[O:3])[CH3:2]
Reactant: CC(=O)N(CCC(=O)O)c1c(C)cccc1C
Reactant: CCOC(=O)CCCNc1c(CC)cccc1CC
Product: CCOC(=O)CCCN(C(=O)CCN(C(C)=O)c1c(C)cccc1C)c1c(CC)cccc1CC

Procedure:
Analogously to Example 1, by using equivalent quantities, reacting N-acetyl-3-(2,6-dimethylanilino)propionic acid and ethyl 4-(2,6-diethylanilino)butyrate and suitable processing produces ethyl N-[N-acetyl-3-(2,6-dimethylanilino)propionyl]-4-(2,6-diethylanilino)butyrate (oil), saponification of which and processing of the reaction product yields N-[N-acetyl-3-(2,6-dimethylanilino)propionyl]-4-(2,6-diethylanilino)butyric acid (M.P. 110° to 111°).
Reaction SMILES: [Cl:1][C:2]1[C:3]([F:19])=[C:4]([NH:12]C(=O)C(F)(F)F)[C:5]([N+:9]([O-:11])=[O:10])=[CH:6][C:7]=1[F:8]>C([O-])([O-])=O.[K+].[K+].CO.O>[Cl:1][C:2]1[C:3]([F:19])=[C:4]([C:5]([N+:9]([O-:11])=[O:10])=[CH:6][C:7]=1[F:8])[NH2:12]
Reactant: O=C(Nc1c([N+](=O)[O-])cc(F)c(Cl)c1F)C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Product: Nc1c([N+](=O)[O-])cc(F)c(Cl)c1F
Yield: 6.9 %

Procedure:
A solution of 6.35 g (20.8 mmol) of 3-chloro-2,4-difluoro-6-nitro(trifluoroacetamido)benzene in 60 mL of 7% K2CO3 methanol/water (3:2) was stirred at 25° C. for 4 h. The solution was evaporated to remove the methanol. Solid was observed in the residue and it was filtered and washed by water, and dried to leave 301 mg of crystalline yellow solid, mp 96°-97° C. 1H NMR (CDCl3), 6.07 (mb, 2), 7.815 (dd, 1, J=1.92, 9.13). More solid was observed after the mother aqueous solution was allowed to stand at room temperature overnight. It was filtered and washed by water, and dried to leave yellow solid (1.01 g). More solid was crystallized from the mother solution. It was collected three more times to leave 2.48 g of a yellow solid. 1H NMR is identical with above, total yield 3.80 g (87%).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH3:12])[CH:6]=[CH:5]2.[C:13]1([CH3:35])[CH:18]=[CH:17][C:16]([N:19]([C:28]2[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=2)[C:20]2[CH:27]=[CH:26][C:23]([CH:24]=O)=[CH:22][CH:21]=2)=[CH:15][CH:14]=1>>[C:31]1([CH3:34])[CH:32]=[CH:33][C:28]([N:19]([C:20]2[CH:21]=[CH:22][C:23]([CH3:24])=[CH:26][CH:27]=2)[C:16]2[CH:17]=[CH:18][C:13]([CH:35]=[CH:12][C:7]3[CH:6]=[CH:5][C:4]4[C:9](=[CH:10][CH:11]=[C:2]([CH3:1])[CH:3]=4)[N:8]=3)=[CH:14][CH:15]=2)=[CH:29][CH:30]=1
Reactant: Cc1ccc2nc(C)ccc2c1
Reactant: Cc1ccc(N(c2ccc(C)cc2)c2ccc(C=O)cc2)cc1
Product: Cc1ccc(N(c2ccc(C)cc2)c2ccc(C=Cc3ccc4cc(C)ccc4n3)cc2)cc1

Procedure:
By using 14 g of 6-methylquinaldine and 25 g of p-di(p-tolyl)aminobenzaldehyde and in the same manner as in Synthetic Example 1 the compound 2-[p-di(p-tolyl)aminostyryl]-6-methylquinoline was obtained. The yield was 24 g and the melting point thereof was 200°-202.5° C. This compound may also be used satisfactorily as a charge transport substance.
Reaction SMILES: [C:1]1([CH2:7][C:8]([C@H:10]2[CH2:14][CH2:13][CH2:12][O:11]2)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:15]([O:17][C:18]1[CH:19]=[C:20]([CH:23]=[C:24]([N+:27]([O-:29])=[O:28])[C:25]=1[OH:26])[CH:21]=O)[CH3:16].[NH2:30][C:31]([NH2:33])=[O:32]>C(O)C.Cl>[CH2:15]([O:17][C:18]1[CH:19]=[C:20]([CH:21]2[C:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[C:8]([C@H:10]3[CH2:14][CH2:13][CH2:12][O:11]3)[NH:33][C:31](=[O:32])[NH:30]2)[CH:23]=[C:24]([N+:27]([O-:29])=[O:28])[C:25]=1[OH:26])[CH3:16]
Reactant: O=C(Cc1ccccc1)[C@H]1CCCO1
Reactant: CCOc1cc(C=O)cc([N+](=O)[O-])c1O
Reactant: NC(N)=O
Agent: Cl
Solvent: CCO
Product: CCOc1cc(C2NC(=O)NC([C@H]3CCCO3)=C2c2ccccc2)cc([N+](=O)[O-])c1O
Yield: 4.9 %

Procedure:
To a mixture of (R)-2-phenyl-1-(tetrahydrofuran-2-yl)ethanone (Intermediate 94) (200 mg, 1.0 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (266 mg, 1.3 mmol), and urea (189 mg, 3.2 mmol) in absolute ethanol (3 mL) was added conc. HCl (one drop). The mixture was refluxed under N2 for 3.5 hrs. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (PE:EtOAc=10:1 to PE:EtOAc=1:2) and prep-HPLC (0.1% TFA as additive) to give Compound 176 (21 mg, yield 5%). 1H NMR (DMSO 400 MHz): δ 10.18 (s, 1H), 8.34 (s, 1H), 7.64 (s, 1H), 7.34-7.27 (m, 5H), 7.16-7.10 (m, 1H), 7.07-7.04 (m, 1H), 5.38 (s, 1H), 4.26-4.21 (m, 1H), 4.03-3.92 (m, 3H), 3.92-3.87 (m, 1H), 2.22-2.18 (m, 1H), 2.17-2.04 (m, 2H), 2.00-1.95 (m, 1H), 1.32-1.22 (m, 3H); MS (ESI): m/z 426.0[M+1]+.
Reaction SMILES: C(C1OC2C=CC(Br)=CC=2C=1)C1C=CC=CC=1.C(Cl)(=O)C1C=CC(OC)=CC=1.[CH2:29]([C:36]1[O:37][C:38]2[CH:54]=[CH:53][C:52]([Br:55])=[CH:51][C:39]=2[C:40]=1[C:41](=[O:50])[C:42]1[CH:47]=[CH:46][C:45]([O:48][CH3:49])=[CH:44][CH:43]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.[CH2:56]([N:58]([CH2:63][CH3:64])[CH2:59][CH2:60]CCl)[CH3:57]>>[CH2:29]([C:36]1[O:37][C:38]2[CH:54]=[CH:53][C:52]([Br:55])=[CH:51][C:39]=2[C:40]=1[C:41](=[O:50])[C:42]1[CH:47]=[CH:46][C:45]([O:48][CH2:49][CH2:57][CH2:56][N:58]([CH2:63][CH3:64])[CH2:59][CH3:60])=[CH:44][CH:43]=1)[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1
Reactant: COc1ccc(C(=O)c2c(Cc3ccccc3)oc3ccc(Br)cc23)cc1
Reactant: CCN(CC)CCCCl
Agent: Brc1ccc2oc(Cc3ccccc3)cc2c1
Agent: COc1ccc(C(=O)Cl)cc1
Product: CCN(CC)CCCOc1ccc(C(=O)c2c(Cc3ccccc3)oc3ccc(Br)cc23)cc1

Procedure:
2-Benzyl-5-bromobenzofuran is acylated with p-anisoyl chloride as described above and the resulting 2-benzyl-5-bromo-3-(4-methoxybenzoyl)benzofuran is demethylated and the product reacted with 3-diethylaminopropyl chloride as previously described to give the title compound.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:22])[CH:5]=[CH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([NH:13][C:14]([C:16]2[O:17][C:18](Br)=[CH:19][CH:20]=2)=[O:15])[CH:8]=1)[CH3:2].[F:23][C:24]1[CH:25]=[C:26](B(O)O)[CH:27]=[CH:28][CH:29]=1>>[CH2:1]([O:3][C:4](=[O:22])[CH:5]=[CH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([NH:13][C:14]([C:16]2[O:17][C:18]([C:28]3[CH:27]=[CH:26][CH:25]=[C:24]([F:23])[CH:29]=3)=[CH:19][CH:20]=2)=[O:15])[CH:8]=1)[CH3:2]
Reactant: CCOC(=O)C=Cc1cccc(NC(=O)c2ccc(Br)o2)c1
Reactant: OB(O)c1cccc(F)c1
Product: CCOC(=O)C=Cc1cccc(NC(=O)c2ccc(-c3cccc(F)c3)o2)c1

Procedure:
The furyl bromide (99) (125 mg, 0.34 mmol) was coupled to 3-fluoro-phenylboronic acid (48 mg, x 0.41 mmol) acid using Method E. The residue was purified by column chromatography eluting with 20% EtOAc in heptane to give the title compound.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[C:6]([OH:30])=[C:7]2[C:12](=[CH:13][N:14]=1)[N:11]([CH2:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:10](=[O:23])[C:9]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[CH:8]2)=[O:4].[Br:31]N1C(=O)CCC1=O>C(Cl)Cl>[CH3:1][O:2][C:3]([C:5]1[C:6]([OH:30])=[C:7]2[C:12](=[C:13]([Br:31])[N:14]=1)[N:11]([CH2:15][CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[C:10](=[O:23])[C:9]([C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)=[CH:8]2)=[O:4]
Reactant: COC(=O)c1ncc2c(cc(-c3ccccc3)c(=O)n2CCc2ccccc2)c1O
Reactant: O=C1CCC(=O)N1Br
Solvent: ClCCl
Product: COC(=O)c1nc(Br)c2c(cc(-c3ccccc3)c(=O)n2CCc2ccccc2)c1O
Yield: 80.5 %

Procedure:
A mixture of 5-hydroxy-2-oxo-1-phenethyl-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (57 mg, 0.14 mmol) and N-bromosuccinimide (27 mg, 0.15 mmol) in CH2Cl2 (0.8 mL) was refluxed for 3 h. Solvent was evaporated in vacuo, and the residue was purified by silica gel chromatography (5-40% EtOAc/hexanes) to give 54 mg of the title compound as a light yellow solid. MS: (−) m/z 477.13, 479.08 (M−1, 79/81Br).
Reaction SMILES: [CH:1]1([N:6]2[C:15]3[C:10](=[CH:11][C:12]([F:19])=[C:13]([F:18])[C:14]=3[O:16][CH3:17])[C:9](=[O:20])[C:8]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[N+:26]([O-])([O-:28])=[O:27].[K+]>OS(O)(=O)=O>[CH:1]1([N:6]2[C:15]3[C:10](=[C:11]([N+:26]([O-:28])=[O:27])[C:12]([F:19])=[C:13]([F:18])[C:14]=3[O:16][CH3:17])[C:9](=[O:20])[C:8]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:7]2)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: O=[N+]([O-])[O-]
Reactant: CCOC(=O)c1cn(C2CCCC2)c2c(OC)c(F)c(F)cc2c1=O
Agent: O=S(=O)(O)O
Agent: [K+]
Product: CCOC(=O)c1cn(C2CCCC2)c2c(OC)c(F)c(F)c([N+](=O)[O-])c2c1=O
Temperature: 0 °C
Reaction time: 1 h
Yield: 87 %

Procedure:
A solution of 15 (6.1 g, 17.4 mmol) in concentrated H2SO4 (60 mL) was treated portionwise at 0° C. with solid KNO3 (2.64 g, 26 mmol). After stirring at 0° C. for 1 h, the reaction mixture was poured into 500 mL of ice-water and the resulting precipitate was removed by filtration, washed with water and dissolved in CH2Cl2. The resulting solution washed with 5% NaHCO3, dried and evaporated to yield 16 as a yellow solid (6.0 g, 87%).
Reaction SMILES: Br[C:2]1[N:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6](=[O:12])[NH:7]2.[CH3:13][C:14]1[NH:15][CH:16]=[CH:17][N:18]=1.CN1CCCC1=O.C(=O)([O-])[O-].[K+].[K+]>[Cu].C(O)(=O)C.O>[CH3:13][C:14]1[N:15]([C:2]2[N:11]=[CH:10][CH:9]=[C:8]3[C:3]=2[CH:4]=[CH:5][C:6](=[O:12])[NH:7]3)[CH:16]=[CH:17][N:18]=1
Reactant: O=c1ccc2c(Br)nccc2[nH]1
Reactant: Cc1ncc[nH]1
Agent: [Cu]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN1CCCC1=O
Solvent: O
Solvent: CC(=O)O
Product: Cc1nccn1-c1nccc2[nH]c(=O)ccc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 42.6 %

Procedure:
A mixture containing 5.6 g of 5-bromo-1,6-naphthyridin-2(1H)-one, 8 g of 2-methyl-1H-imidazole, 25 ml of N-methylpyrrolidinone, 3.4 g of anhydrous potassium carbonate and 50 mg of copper powder was refluxed for 6 hours, allowed to cool to room temperature and then poured into 100 ml of water. The resulting solution was neutralized by adding acetic acid and the resulting solution was allowed to stand overnight at room temperature. The solid that separated was collected, recrystallized from dimethylformamide and dried in a vacuum oven at 90°-95° C. to yield 2.4 g of 5-(2-methyl-1H-imidazol-1-yl)-1,6-naphthyridin-2(1H)-one, m.p. >310° C.
Reaction SMILES: [Br:1][C:2]1[N:3]=[C:4]([CH:7]=[O:8])[S:5][CH:6]=1.[CH2:9](O)[CH2:10][OH:11]>C1C=CC=CC=1.CC1C=CC(S(O)(=O)=O)=CC=1>[Br:1][C:2]1[N:3]=[C:4]([CH:7]2[O:11][CH2:10][CH2:9][O:8]2)[S:5][CH:6]=1
Reactant: O=Cc1nc(Br)cs1
Reactant: OCCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: c1ccccc1
Product: Brc1csc(C2OCCO2)n1
Temperature: 25 °C
Yield: 94.3 %

Procedure:
To a rb flask with an attached Dean-Stark trap containing molecular sieves, 4A (0.25 g) was added 4-bromothiazole-2-carbaldehyde (4.4 g, 22.91 mmol). The starting material was dissolved in Benzene (45 ml) and Ethylene glycol (1.406 ml, 25.2 mmol) was added followed by pTsOH (0.218 g, 1.146 mmol). The mixture was heated to reflux for 3 h. The mixture was cooled to rt, and was partitioned with sat. aq. NaHCO3. The mixture was washed 2× with sat. NaHCO3 (40 mL), then once with sat. NaCl (40 mL). The organic layer was dried with Na2SO4. The drying agent was removed by filtration, and the mixture was concentrated under reduced pressure. The residue was purified by biotage flash chromatography using a 40+M column and a 0 to 20% EtOAc in hexanes gradient. The product, 4-bromo-2-(1,3-dioxolan-2-yl)thiazole (5.1 g, 21.60 mmol, 94% yield), was collected as a light-yellow oil.
Reaction SMILES: Br[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[CH3:8][CH:9]([NH2:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(N(C(C)C)C(C)C)C>C1(C)C=CC=CC=1>[C:10]1([C@H:9]([NH:16][CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4])[CH3:8])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: CC(N)c1ccccc1
Reactant: CCOC(=O)CBr
Solvent: CCN(C(C)C)C(C)C
Solvent: Cc1ccccc1
Product: CCOC(=O)CN[C@H](C)c1ccccc1
Temperature: 25 °C
Yield: 62.3 %

Procedure:
Ethyl bromoacetate (4.14 g; 24.8 mmol) was treated with (R) α-methylbenzylamine (3 g, 24.8 mmol) and ethyldiisopropylamine (3.2 g; 24.8 mmol) in toluene (100 mL). After heating at reflux for 18 hours, the mixture was cooled to room temperature and concentrated under reduced pressure. The residue was purified by flash chromatography (SiO2, 20% ethyl acetate/pentane) to provide the title compound (3.2 g, 63% yield). MS (DCI/NH3) m/z 208 (M+H)+.
Reaction SMILES: [Cl:1][S:2]([OH:5])(=O)=[O:3].[N+:6]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[OH:15])([O-:8])=[O:7]>>[OH:15][C:10]1[CH:11]=[CH:12][C:13]([S:2]([Cl:1])(=[O:5])=[O:3])=[CH:14][C:9]=1[N+:6]([O-:8])=[O:7]
Reactant: O=S(=O)(O)Cl
Reactant: O=[N+]([O-])c1ccccc1O
Product: O=[N+]([O-])c1cc(S(=O)(=O)Cl)ccc1O
Temperature: 60 °C
Reaction time: 18 h
Yield: 63.5 %

Procedure:
To a solution of chlorosulfonic acid (12.0 mL, 180 mmol) at 0° C. was added 2-nitrophenol (8.35 g, 60.0 mmol) in small portions over 1 h. The reaction was heated to 60° C. for 20 minutes and allowed to stir for 18 h at 25° C. The reaction was quenched by pouring it into 100 g of ice. The reaction was extracted with chloroform (3×), washed with cold water (2×), dried over MgSO4, filtered, and concentrated to give 9.06 g (64%) of the title compound.
Reaction SMILES: [CH2:1]([O:5][CH:6]([C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=1)[CH3:7])[CH:2]([CH3:4])[CH3:3].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)CC)C.[NH2:48][CH2:49][C:50]1[C:51]([OH:58])=[N:52][C:53]([CH3:57])=[CH:54][C:55]=1[CH3:56]>ClCCl>[OH:58][C:51]1[C:50]([CH2:49][NH:48][C:12](=[O:14])[C:11]2[CH:10]=[CH:9][C:8]([CH:6]([O:5][CH2:1][CH:2]([CH3:3])[CH3:4])[CH3:7])=[CH:16][CH:15]=2)=[C:55]([CH3:56])[CH:54]=[C:53]([CH3:57])[N:52]=1
Reactant: Cc1cc(C)c(CN)c(O)n1
Reactant: CC(C)COC(C)c1ccc(C(=O)O)cc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1cc(C)c(CNC(=O)c2ccc(C(C)OCC(C)C)cc2)c(O)n1
Reaction time: 0.5 h
Yield: 58.2 %

Procedure:
A solution of 4-(1-isobutoxyethyl)benzoic acid (132 mg, 0.59 mmol) in dichloromethane (50 mL) was added 2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (35 mg, 0.5 mmol), triethylamine (32 mg, 0.7 mmol), stirred for 30 minutes. Then 3-(aminomethyl)-4,6-dimethylpyridin-2-ol (27 mg, 0.4 mmol) was added and the mixture was stirred at room temperature for 12 hours. The mixture was washed with water (50 mL), dried over sodium sulphate, concentrated. The residue was purified through column chromatography (silica gel, dichloromethane/methanol=20:1) to give the product N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)-4-(1-isobutoxyethyl)benzamide (83 mg, 40%) as white solid. LRMS (M+H+) m/z: calcd 356.13. found 356. HPLC Purity (214 nm): 97%. 1H NMR (300 MHz, CD3OD) δ 7.76 (d, J=8.1 Hz, 2H), 7.38 (d, J=8.1 Hz, 2H), 6.10 (s, 1H), 4.49-4.43 (m, 3H), 3.14-3.00 (m, 2H), 2.37 (s, 3H), 2.24 (s, 3H), 1.84-1.79 (m, 2H), 1.39 (d, J=6.3 Hz, 3H), 0.88 (d, J=6.6 Hz, 6H).
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[CH:33]=[CH:32][C:9]3[N:10]=[C:11]([C:13]4[N:18]=[CH:17][C:16]([O:19][CH2:20][C@@H:21]([NH:23][C:24](=O)[O:25]C(C)(C)C)[CH3:22])=[CH:15][C:14]=4[F:31])[O:12][C:8]=3[CH:7]=2)[CH2:3][CH2:2]1.[N:34]1C=CC=CC=1>>[CH:1]1([CH2:4][O:5][C:6]2[CH:33]=[CH:32][C:9]3[N:10]=[C:11]([C:13]4[N:18]=[CH:17][C:16]([O:19][CH2:20][C@@H:21]([NH:23][C:24]([NH2:34])=[O:25])[CH3:22])=[CH:15][C:14]=4[F:31])[O:12][C:8]=3[CH:7]=2)[CH2:2][CH2:3]1
Reactant: C[C@@H](COc1cnc(-c2nc3ccc(OCC4CC4)cc3o2)c(F)c1)NC(=O)OC(C)(C)C
Reactant: c1ccncc1
Product: C[C@@H](COc1cnc(-c2nc3ccc(OCC4CC4)cc3o2)c(F)c1)NC(N)=O

Procedure:
Using tert-butyl [(1S)-2-({6-[6-(cyclopropylmethoxy)-1,3-benzoxazol-2-yl]-5-fluoropyridin-3-yl}oxy)-1-methylethyl]carbamate, and in the same manner as in Example 15, step A (using pyridine instead of triethylamine), the title compound was obtained.
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[C@@H]2CO)[C@H:5]([OH:20])[C@@H:4]([OH:21])[C@@H:3]1[OH:22].N([CH2:28][CH2:29][OH:30])CCO.ClC(Cl)(Cl)C(O)=[O:34]>>[CH2:29]([OH:30])[C@H:28]1[O:34][C@H:9]([O:8][C@H:6]2[O:7][C@H:2]([CH2:1][OH:23])[C@@H:3]([OH:22])[C@H:4]([OH:21])[C@H:5]2[OH:20])[C@H:14]([OH:15])[C@@H:13]([OH:16])[C@@H:12]1[OH:17]
Reactant: OCCNCCO
Reactant: O=C(O)C(Cl)(Cl)Cl
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
Product: OC[C@H]1O[C@H](O[C@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)[C@H](O)[C@@H](O)[C@@H]1O

Procedure:
Transformed E. coli ATCC35467/pCJ121, ATCC35467/pCJ122 and ATCC35467/pCJ123 were cultured on an LB-Ap medium until the early resting stage. The cells were recovered by centrifuigation and washed twice with an appropriate volume of 20 mM diethanolamine solution. The washed cells were suspended in an appropriate volume of 20 mM diethanolamine solution and crushed by ultrasonicater. The crushed cells were centrifuged and the supematant obtained therefrom was used as enzymatic liquid. The supematant was reacted with 20% maltose solution containing 20 mM diethanolamine, pH 8.5 to 9.0 at 35° C. 1.0% trichloroacetic acid was added to the reaction solution, and centrifugation and HPLC were conducted for analysis. One unit of enzyme activity was defined as a quantity of enzyme when it produced 1 μl of trehalose per minute. The results are shown in Table 5 below.