Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][CH:12]([C:17]([OH:19])=O)[CH2:13][CH:14]([CH3:16])[CH3:15])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.C(Cl)(=O)OCC.[NH2:33][C:34]1[S:35][CH:36]=[N:37][N:38]=1>C(Cl)(Cl)Cl>[CH2:1]([O:8][C:9]([NH:11][CH:12]([C:17]([NH:33][C:34]1[S:35][CH:36]=[N:37][N:38]=1)=[O:19])[CH2:13][CH:14]([CH3:16])[CH3:15])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Nc1nncs1
Reactant: CC(C)CC(NC(=O)OCc1ccccc1)C(=O)O
Agent: CCOC(=O)Cl
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: CC(C)CC(NC(=O)OCc1ccccc1)C(=O)Nc1nncs1
Reaction time: 2 h
Yield: 71.4 %

Procedure:
9.6 g of N-benzyloxycarbonyl-DL-leucine and 3.7 g of triethylamine were dissolved in 150 ml of chloroform, to which was added dropwise 3.9 g of ethyl chlorocarbonate under sodium chloride-ice cooling conditions. The solution was stirred for 2 hours, to which was then added 3.7 g of 2-amino-1,3,4-thiadiazole, followed by stirring for further 24 hours. The reaction solution was washed with water, and after drying, the solvent was removed by distillation to obtain 9.0 g (yield: 71%) of 2-(N-benzyloxycarbonyl-DL-leucylamino)-1,3,4-thiadiazole as white crystals having a melting point of 118°-120° C.
Reaction SMILES: Br[CH2:2][C:3]1[C:8]([CH2:9][CH3:10])=[CH:7][N:6]=[CH:5][C:4]=1[CH2:11][CH3:12].[CH3:13][C:14]1[N:19]=[C:18]([SH:20])[N:17]=[C:16]([OH:21])[CH:15]=1.C(N(CC)CC)C.CCOCC>C(O)C>[CH2:11]([C:4]1[CH:5]=[N:6][CH:7]=[C:8]([CH2:9][CH3:10])[C:3]=1[CH2:2][S:20][C:18]1[N:17]=[C:16]([OH:21])[CH:15]=[C:14]([CH3:13])[N:19]=1)[CH3:12]
Reactant: Cc1cc(O)nc(S)n1
Reactant: CCc1cncc(CC)c1CBr
Solvent: CCO
Solvent: CCN(CC)CC
Solvent: CCOCC
Product: CCc1cncc(CC)c1CSc1nc(C)cc(O)n1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a mixture of crude 4-(bromomethyl)-3,5-diethylpyridine (2.07 g, 9.07 mmol) and 6-methyl-2-sulfanylpyrimidin-4-ol (0.838 g, 5.89 mmol) in anhydrous ethanol (50 mL) at 0° C. was added triethylamine (3.21 g, 4.42 mL 31.75 mmol), and the reaction mixture was allowed to stir at room temperature overnight. The solvent was evaporated to provide a crude residue. Ether was added to precipitate the triethylamine hydrobromide salt. The solid was filtered and washed with ether several times. The combined ether layers were evaporated, and the crude residue was purified by Combiflash using 0-10% MeOH in dichloromethane to provide 2-{[(3,5-diethylpyridin-4-yl)methyl]sulfanyl}-6-methylpyrimidin-4-ol as a white solid; 1H NMR (400 MHz, DMSO-d6): δ 1.23 (t, 6H), 1.40 (t, 3H), 2.64 (q, 4H), 4.44 (q, 2H), 8.36 (s, 2H); M+1 290.4.
Reaction SMILES: [CH2:1]([OH:19])[CH2:2][O:3][CH2:4][CH2:5][O:6][CH2:7][CH2:8][O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][O:15][CH2:16][CH2:17][OH:18].[C:20](Cl)([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.O>C(#N)C.N1C=CC=CC=1>[C:21]1([C:20]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[O:18][CH2:17][CH2:16][O:15][CH2:14][CH2:13][O:12][CH2:11][CH2:10][O:9][CH2:8][CH2:7][O:6][CH2:5][CH2:4][O:3][CH2:2][CH2:1][OH:19])[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: OCCOCCOCCOCCOCCOCCO
Solvent: O
Solvent: c1ccncc1
Solvent: CC#N
Product: OCCOCCOCCOCCOCCOCCOC(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 66.7 %

Procedure:
25 g of hexaethyleneglycol was dissolved in a mixture of 100 mL of acetonitrile and 30 mL of pyridine, to which 12.5 g of trityl chloride was added at 0° C., and then the solution was stirred overnight at room temperature. The reaction solution was mixed with iced water and subjected to extraction with ethyl acetate, and then the organic layer washed with water and concentrated under reduced pressure after drying. The residue was purified with silica gel column chromatography to obtain 15.7 g of the objective compound.
Reaction SMILES: [I:1]I.[NH2:3][C:4]1[CH:14]=[CH:13][C:12]([Br:15])=[C:6]2[C:7]([NH:9][C:10](=[O:11])[C:5]=12)=[O:8].S([O-])([O-])(=O)=S.[Na+].[Na+]>C(O)C.S([O-])([O-])(=O)=O.[Ag+2]>[NH2:3][C:4]1[C:14]([I:1])=[CH:13][C:12]([Br:15])=[C:6]2[C:7]([NH:9][C:10](=[O:11])[C:5]=12)=[O:8]
Reactant: II
Reactant: Nc1ccc(Br)c2c1C(=O)NC2=O
Agent: [Ag+2]
Agent: O=S(=O)([O-])[O-]
Agent: O=S([O-])([O-])=S
Solvent: CCO
Product: Nc1c(I)cc(Br)c2c1C(=O)NC2=O
Temperature: 25 °C
Reaction time: 23 h
Yield: 94.5 %

Procedure:
Iodine (6.29 g, 24.8 mmol) was dissolved in ethanol (225 mL), and the solution was added with silver sulfate (3.87 g, 12.4 mmol) and 3-amino-6-bromophthalimide (3.00 g, 12.4 mmol), followed by stirring at room temperature for 23 hours. The reaction mixture was added with 10% aqueous sodium thiosulfate solution and extracted with ethyl acetate. The organic layer was washed with 0.5 mol/L hydrochloric acid and saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, the residue was purified by slurry using hexane and methanol to obtain 3-amino-4-iodo-6-bromophthalimide (4.3 g. yield 96%).
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][C:7]([O:10][CH:11]2[CH2:16][CH2:15][O:14][C:12]2=O)=[C:6](C(OC)=O)[CH:5]=1)(=[O:3])[CH3:2].[Cl-].[Na+]>C1CCN2C(=NCCC2)CC1.CN(C)C=O>[C:1]([C:4]1[CH:5]=[CH:6][C:7]2[O:10][C:11]3([C:12](=[O:14])[C:8]=2[CH:9]=1)[CH2:16][CH2:15]3)(=[O:3])[CH3:2]
Reactant: COC(=O)c1cc(C(C)=O)ccc1OC1CCOC1=O
Agent: [Cl-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: C1CCC2=NCCCN2CC1
Product: CC(=O)c1ccc2c(c1)C(=O)C1(CC1)O2
Yield: 56.5 %

Procedure:
A mixture of α-[(4-acetyl-2-methoxycarbonylphenyl)oxy]-γ-butyrolactone (2.8 g), 1,8-diazabicyclo[5,4,0]-7-undecene (0.056 g), sodium chloride (0.6 g) and N,N-dimethylformamide (28 ml) was heated at 150°-155° C. for 4 hours. The solvent was removed in vacuo and the resulting residue was dissolved in ethyl acetate. The ethyl acetate solution was washed with water and dried. The residue obtained by removal of the solvent in vacuo was chromatographed on silica gel. The fraction eluted with dichloromethane was crystallized from ethanol to give 5-acetylspiro[benzo[b]furan-2(3H), 1'-cyclopropane]-3-one (1.15 g) as colorless crystals.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]([F:12])([F:11])[F:10])=[CH:4][C:3]=1[C:13]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=1)=O.[F:22][C:23]([F:31])([F:30])[C:24](=[O:29])[CH2:25][C:26](=O)[CH3:27].C(O)(C)C>CCCCCCC.C(OCC)(=O)C>[Cl:21][C:17]1[CH:16]=[C:15]([C:13]2[C:3]3[C:2](=[CH:7][CH:6]=[C:5]([O:8][C:9]([F:12])([F:11])[F:10])[CH:4]=3)[N:1]=[C:26]([CH3:27])[C:25]=2[C:24](=[O:29])[C:23]([F:31])([F:30])[F:22])[CH:20]=[CH:19][CH:18]=1
Reactant: CC(=O)CC(=O)C(F)(F)F
Reactant: Nc1ccc(OC(F)(F)F)cc1C(=O)c1cccc(Cl)c1
Solvent: CC(C)O
Solvent: CCOC(C)=O
Solvent: CCCCCCC
Product: Cc1nc2ccc(OC(F)(F)F)cc2c(-c2cccc(Cl)c2)c1C(=O)C(F)(F)F
Reaction time: 60 h
Yield: 58 %

Procedure:
The title compound was prepared from (2-Amino-5-trifluoromethoxy-phenyl)-(3-chloro-phenyl)-methanone [example A7] and 1,1,1-trifluoro-2,4-pentanedione according to the procedure of example 1, except that the solvent was isopropanol, the reaction time was of 60 h and heptane/ethyl acetate (1:2) was used. Yield: 58%; MS: m/z=433 (M).
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C:12]([CH3:17])([CH3:16])[C:13]([OH:15])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC.[NH2:49][C:50]1[S:51][C:52]([O:58][C:59]2[CH:66]=[CH:65][C:62]([C:63]#[N:64])=[CH:61][CH:60]=2)=[C:53]([CH:55]2[CH2:57][CH2:56]2)[N:54]=1>CN(C=O)C>[CH2:1]([O:8][C:9](=[O:10])[NH:11][C:12]([C:13](=[O:15])[NH:49][C:50]1[S:51][C:52]([O:58][C:59]2[CH:66]=[CH:65][C:62]([C:63]#[N:64])=[CH:61][CH:60]=2)=[C:53]([CH:55]2[CH2:57][CH2:56]2)[N:54]=1)([CH3:17])[CH3:16])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: N#Cc1ccc(Oc2sc(N)nc2C2CC2)cc1
Reactant: CC(C)(NC(=O)OCc1ccccc1)C(=O)O
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CC(C)(NC(=O)OCc1ccccc1)C(=O)Nc1nc(C2CC2)c(Oc2ccc(C#N)cc2)s1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A mixture of 2-Benzyloxycarbonylamino-2-methyl-propionic acid (360 mg, 1.52 mmol), HBTU (576 mg, 1.52 mmol) and Et3N (0.21 mL, 1.5 mmol) in DMF (4 mL) was stirred at room temperature for 30 min. To this was added a solution of 4-(2-Amino-4-cyclopropyl-thiazol-5-yloxy)-benzonitrile (260 mg, 1.01 mmol) in DMF (4 mL). The mixture was heated at 85° C. for 18 h and partitioned between EtOAc and 3M HCl. The organic extract was dried over MgSO4, concentrated and chromatographed to give the title compound. m/z 477.1 (MH+).
Reaction SMILES: [OH:1][CH:2]([C@@H:13]1[CH2:17][CH2:16][CH2:15][N:14]1[C:18](=[O:34])[C@@H:19]1[CH2:23][CH2:22][CH2:21][N:20]1[C:24](=[O:33])[CH2:25][S:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][CH:6]=1.CS(C)=O.C1C=CC=CC=1>C(N(CC)CC)C>[CH3:12][O:11][C:8]1[CH:7]=[CH:6][C:5]([O:4][CH2:3][C:2]([C@@H:13]2[CH2:17][CH2:16][CH2:15][N:14]2[C:18](=[O:34])[C@@H:19]2[CH2:23][CH2:22][CH2:21][N:20]2[C:24](=[O:33])[CH2:25][S:26][C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)=[O:1])=[CH:10][CH:9]=1
Reactant: COc1ccc(OCC(O)[C@@H]2CCCN2C(=O)[C@@H]2CCCN2C(=O)CSc2ccccc2)cc1
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Solvent: c1ccccc1
Product: COc1ccc(OCC(=O)[C@@H]2CCCN2C(=O)[C@@H]2CCCN2C(=O)CSc2ccccc2)cc1
Yield: 82.6 %

Procedure:
(2S)-2-[1-Hydroxy-2-(4-methoxyphenoxy)ethyl]-1-{N-[(phenylthio)acetyl]-L-prolyl}pyrrolidine (620 mg) was treated in the same manner as in Example 47-D) using DMSO (10 ml), benzene (5 ml), triethylamine (0.90 ml), and sulfur trioxide-pyridine complex (960 mg) to give 510 mg of the title compound.
Reaction SMILES: [OH:1][CH2:2][CH:3]1[O:8][CH2:7][CH2:6][NH:5][CH2:4]1.O1CCCNCC1.[C:16]([OH:23])(=[O:22])/[CH:17]=[CH:18]/[C:19]([OH:21])=[O:20]>CO>[C:16]([OH:23])(=[O:22])/[CH:17]=[CH:18]/[C:19]([OH:21])=[O:20].[OH:1][CH2:2][C@@H:3]1[O:8][CH2:7][CH2:6][NH:5][CH2:4]1
Reactant: OCC1CNCCO1
Agent: C1CNCCOC1
Agent: O=C(O)/C=C/C(=O)O
Solvent: CO
Product: OC[C@H]1CNCCO1
Temperature: 10 °C
Reaction time: 0.5 h

Procedure:
To a mixture of 2-hydroxymethylmorpholine and 1,4-oxazepane compound (20.0 g, 2-hydroxymethylmorpholine:1,4-oxazepane compound=75.8:24.2) synthesized in Example 5 were added methanol (100 ml) and fumaric acid (17.5 g, 0.151 mol) and the mixture was stirred for 30 min. Methanol was evaporated under reduced pressure. To the residue was added 2-propanol (50 ml) and the mixture was subjected twice to azeotropic distillation with dehydrating. To the residue after azeotropic distillation with dehydrating was added ethyl acetate (100 ml) at 40° C., and the mixture was cooled to 10° C. After crystallization, the mixture was cooled to 0° C. and stirred for 1 hr. The crystals were collected by filtration, washed withed twice with ethyl acetate (25 ml) and dried (1 mmHg, 40° C.) to give (R)-2-hydroxymethylmorpholine fumarate (14.8 g) (2-hydroxymethylmorpholine:fumaric acid=1:1, yield from (S)-epichlorohydrin: 42.2%). The obtained (R)-2-hydroxymethylmorpholine fumarate was analyzed by HPLC to find an optical purity of 99% ee.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:18])[CH:4]=[C:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]1.O>CO.[Pd]>[CH3:1][O:2][C:3](=[O:18])[CH2:4][CH:5]1[CH2:6][CH2:7][N:8]([C:11]([O:13][C:14]([CH3:16])([CH3:15])[CH3:17])=[O:12])[CH2:9][CH2:10]1
Reactant: COC(=O)C=C1CCN(C(=O)OC(C)(C)C)CC1
Agent: [Pd]
Solvent: CO
Solvent: O
Product: COC(=O)CC1CCN(C(=O)OC(C)(C)C)CC1
Reaction time: 4 h
Yield: 99.9 %

Procedure:
tert-Butyl 4-(2-methoxy-2-oxoethylidene)piperidine-1-carboxylate (3.6 g, 14 mmol) and 10% Pd/C moistened with water (0.8 g) was mixed in MeOH (75 mL) and stirred under H2 (1 atm) for 4 h. The mixture was filtered through Celite and concentrated to give the title compound (3.6 g, 99%).
Reaction SMILES: [CH3:1][C:2]([CH3:29])=[CH:3][CH2:4][C:5]1[C:6]([OH:28])=[CH:7][C:8]2[O:27][C:15]3[CH:16]=[C:17]([OH:26])[C:18]([OH:25])=[C:19]([CH2:20][CH:21]=[C:22]([CH3:24])[CH3:23])[C:14]=3[C:12](=[O:13])[C:9]=2[C:10]=1[OH:11].[C-:30]#N.[Na+]>CS(C)=O>[CH3:1][C:2]([CH3:29])=[CH:3][CH2:4][C:5]1[C:10]([OH:11])=[C:9]2[C:12]([C:14]3[C:15]([O:27][C:8]2=[CH:7][C:6]=1[OH:28])=[CH:16][C:17]([OH:26])=[C:18]([O:25][CH3:30])[C:19]=3[CH2:20][CH:21]=[C:22]([CH3:23])[CH3:24])=[O:13]
Reactant: CC(C)=CCc1c(O)cc2oc3cc(O)c(O)c(CC=C(C)C)c3c(=O)c2c1O
Reactant: [C-]#N
Agent: [Na+]
Solvent: CS(C)=O
Product: COc1c(O)cc2oc3cc(O)c(CC=C(C)C)c(O)c3c(=O)c2c1CC=C(C)C
Temperature: 195 °C
Reaction time: 6 h
Yield: 64 %

Procedure:
γ-Mangostin from 3,6,7-trimethyl-γ-mangostin: To a solution of 3,6,7-trimethyl-γ-mangostin (0.5 g, 1.14 mmol) in DMSO (LR, 20 mL) was added sodium cyanide (1.0 g, 20.5 mmol) at RT and the mixture was stirred at 190-200° C. for 6 h. The reaction mixture was allowed to ambient temperature and poured into ice cold water and extracted with a mixture of ethyl acetate and THF (1:1, 5×100 mL). The combined organic layer was washed with aqueous potassium permanganate (10%), water, brine and dried over sodium sulfate. The solution was filtered and the solvent evaporated under vacuum and the residue was chromatographed over silica gel column using chloroform-methanol mixture (95:5) as eluents to give α-mangostin (300 mg, 64%). The α-mangostin was then converted to γ-mangostin using the inventive demethylation procedure as described in example 12.
Reaction SMILES: [C:1]([O:5][C:6]([CH2:8][N:9]1[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[N:13]([CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)[CH2:12][CH:11]([NH:26][C:27]([NH:29][C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([O:38]CC3C=CC=CC=3)=[O:37])[CH:31]=2)=[O:28])[C:10]1=[O:46])=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(O)C.[C].[Pd]>[C:1]([O:5][C:6]([CH2:8][N:9]1[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[N:13]([CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)[CH2:12][CH:11]([NH:26][C:27](=[O:28])[NH:29][C:30]2[CH:31]=[C:32]([CH:33]=[CH:34][CH:35]=2)[C:36]([OH:38])=[O:37])[C:10]1=[O:46])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)CN1C(=O)C(NC(=O)Nc2cccc(C(=O)OCc3ccccc3)c2)CN(C2CCCCC2)c2ccccc21
Agent: [Pd]
Solvent: CCO
Product: CC(C)(C)OC(=O)CN1C(=O)C(NC(=O)Nc2cccc(C(=O)O)c2)CN(C2CCCCC2)c2ccccc21
Temperature: 25 °C
Reaction time: 3 h
Yield: 54.7 %

Procedure:
5% Palladium carbon (300 mg) was added to a solution of 1-(1-tert-butoxycarbonylmethyl-2-oxo-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl)-3-(3-benzyloxycarbonylphenyl)urea (960 mg) in ethanol (50 ml), the mixture was stirred at room temperature for 3 hours under hydrogen atmosphere. The reaction mixture was filtrated through a pad of Celite, and the filtrate was concentrated under reduced pressure. Isopropyl alcohol was added to the residue for crystallization, collected by filtrated, to thereby obtain 450 mg of the titled compound.
Reaction SMILES: [Br:1][C:2]1[C:3](Cl)=[C:4]([N+:9]([O-:11])=[O:10])[C:5]([NH2:8])=[N:6][CH:7]=1.[N:13]1[CH:18]=[CH:17][C:16]([CH2:19][N:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)=[CH:15][CH:14]=1.C(N(C(C)C)CC)(C)C>C(O)(C)C>[Br:1][C:2]1[C:3]([N:23]2[CH2:24][CH2:25][N:20]([CH2:19][C:16]3[CH:15]=[CH:14][N:13]=[CH:18][CH:17]=3)[CH2:21][CH2:22]2)=[C:4]([N+:9]([O-:11])=[O:10])[C:5]([NH2:8])=[N:6][CH:7]=1
Reactant: Nc1ncc(Br)c(Cl)c1[N+](=O)[O-]
Reactant: c1cc(CN2CCNCC2)ccn1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(C)O
Product: Nc1ncc(Br)c(N2CCN(Cc3ccncc3)CC2)c1[N+](=O)[O-]
Temperature: 45 °C

Procedure:
To a mixture of 5-bromo-4-chloro-3-nitro-pyridin-2-ylamine (0.126 g, 0.50 mmol) and isopropanol (9 ml) was added 1-[(4-pyridyl)-methyl]-piperazine (0.097 g, 0.55 mmol) followed by diisopropylethylamine (0.10 ml, 0.57 mmol). The reaction mixture was heated at 45° C. for 20 h, then allowed to cool to room temperature. The precipitate was collected by filtration and washed with isopropanol and diethyl ether. The title compound was thus obtained as an orange solid (0.080 g). The filtrate was concentrated in vacuo, and purification of the residue on a isolute silica column using 1 to 5% methanol in ethyl acetate as eluant gave an additional 0.055 g of the product (total yield: 68%); 1H-NMR (500 MHz, DMSO-d6) 2.53 (br s, 4H, piperazine N(CH2)2), 3.08 (br s, 4H, piperazine N(CH2)2), 3.57 (s, 2H, NCH2), 6.97 (s, 2H, NH2), 7.34 (d, J=5.88 Hz, 2H), and 8.51 (d, J=4.48 Hz, 2H) (pyrid-4-yl protons), 8.16 (s, 1H, 6-H); LC (Method B)-MS (ESI, m/z): Rt=2.00 min—393, 395 [(M+H)+, Br isotopic pattern].
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].CC(O)C.[CH2:17]([NH2:33])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32]>O>[CH2:17]([NH:33][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])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32]
Reactant: CCCCCCCCCCCCCCCCN
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Solvent: O
Solvent: CC(C)O
Product: CCCCCCCCCCCCCCCCNC1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O
Reaction time: 8 h

Procedure:
A 2 L two neck round bottom flask equipped with condenser was charged with D(+) glucose (60 g, 0.333 moles), 2-propanol (900 mL), hexadecylamine (81 g, 0.334 moles) and deionized water (300 mL). The reaction was stirred and heated to 50°-55° celsius for 1 hour to obtain a homogeneous solution. The reaction was then allowed to run overnight at room temperature. The reaction precipitated out after 2-3 hours.
Reaction SMILES: [CH3:1][S:2][C:3]1[N:25]=[C:6]2[N:7]=[C:8]([C:17]3[CH:24]=[CH:23][C:20]([CH:21]=O)=[CH:19][CH:18]=3)[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[CH:10][N:5]2[N:4]=1.[NH:26]1[CH2:29][CH:28]([C:30]2[NH:34][N:33]=[C:32]([C:35]3[CH:40]=[CH:39][CH:38]=[C:37]([CH3:41])[N:36]=3)[N:31]=2)[CH2:27]1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CN1C(=O)CCC1.CC(O)=O>[CH3:41][C:37]1[N:36]=[C:35]([C:32]2[NH:33][N:34]=[C:30]([CH:28]3[CH2:27][N:26]([CH2:21][C:20]4[CH:23]=[CH:24][C:17]([C:8]5[C:9]([C:11]6[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=6)=[CH:10][N:5]6[N:4]=[C:3]([S:2][CH3:1])[N:25]=[C:6]6[N:7]=5)=[CH:18][CH:19]=4)[CH2:29]3)[N:31]=2)[CH:40]=[CH:39][CH:38]=1
Reactant: Cc1cccc(-c2n[nH]c(C3CNC3)n2)n1
Reactant: CSc1nc2nc(-c3ccc(C=O)cc3)c(-c3ccccc3)cn2n1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: CC(=O)O
Solvent: CN1CCCC1=O
Product: CSc1nc2nc(-c3ccc(CN4CC(c5n[nH]c(-c6cccc(C)n6)n5)C4)cc3)c(-c3ccccc3)cn2n1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 4-(2-methylsulfanyl-6-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-5-yl)benzaldehyde (200 mg, 0.548 mmol), 2-(5-Azetidine-3-yl-[1,2,4]triazole-3-yl)-6-methylpyridine×2HCl (174 mg, 60% pure), triethylamine (0.168 mL), AcOH (0.075 mL) and NMP (4.6 mL) were stirred overnight at room temperature. Sodium triacetoxyborohydride (279 mg) and the mixture stirred for 3 h. The reaction was partitioned between CH2Cl2 and water, the organic phase separated, dried and concentrated in vacuo. The residue was purified by preparative HPLC to give the title compound (78 mg) as a white solid.
Reaction SMILES: [CH2:1]([O:11][C:12]1[CH:20]=[CH:19][C:15]([C:16]([OH:18])=O)=[CH:14][CH:13]=1)/[CH:2]=[C:3](/[CH2:5][CH2:6][CH:7]=[C:8]([CH3:10])[CH3:9])\[CH3:4].C1(P(Cl)(C2C=CC=CC=2)=O)C=CC=CC=1.[NH2:36][CH2:37][CH2:38][NH:39][C:40]1[CH:41]=[N:42][C:43]([O:46][CH3:47])=[CH:44][CH:45]=1>C(Cl)(Cl)Cl.C(N(CC)CC)C>[CH2:1]([O:11][C:12]1[CH:13]=[CH:14][C:15]([C:16]([NH:36][CH2:37][CH2:38][NH:39][C:40]2[CH:41]=[N:42][C:43]([O:46][CH3:47])=[CH:44][CH:45]=2)=[O:18])=[CH:19][CH:20]=1)/[CH:2]=[C:3](/[CH2:5][CH2:6][CH:7]=[C:8]([CH3:9])[CH3:10])\[CH3:4]
Reactant: CC(C)=CCC/C(C)=C/COc1ccc(C(=O)O)cc1
Reactant: COc1ccc(NCCN)cn1
Agent: O=P(Cl)(c1ccccc1)c1ccccc1
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: COc1ccc(NCCNC(=O)c2ccc(OC/C=C(\C)CCC=C(C)C)cc2)cn1
Reaction time: 1 h
Yield: 25.9 %

Procedure:
4-geranyloxybenzoic acid(3.48 g) was dissolved in chloroform(50 ml) and triethylamine(3.52 ml), and then diphenylphosphinic chloride(2.42 ml) was added thereto while being cooled with ice. After being stirred for 1 hour, the mixture, with 3-(2-aminoethylamino)-6-methoxypyridine(2.12 g) added thereto, was stirred for 3 hours at room temperature. The reaction mixture was washed with saturated sodium hydrogencarbonate aqueous solution and saturated brine successively, dried over sodium sulfate anhydride, and then concentrated under a vacuum. The residue was purified by silica gel column chromatography (chloroform:methanol=20:1). The resulting solid was recrystallized from n-hexane/ethyl acetate, thereby yielding 1.39 g of the aimed compound.
Reaction SMILES: C[O-].[Na+].[SH:4][CH2:5][CH2:6][CH2:7][OH:8].[BH4-].[Na+].CS(O[CH2:16][CH:17]([O:38][CH3:39])[CH2:18][O:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1)(=O)=O.Cl>O1CCCC1.CO>[OH:8][CH2:7][CH2:6][CH2:5][S:4][CH2:16][CH:17]([O:38][CH3:39])[CH2:18][O:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1
Reactant: COC(COCCCCCCCCCCCCC1CCCCC1)COS(C)(=O)=O
Reactant: OCCCS
Agent: C[O-]
Agent: Cl
Agent: [BH4-]
Solvent: C1CCOC1
Solvent: CO
Product: COC(COCCCCCCCCCCCCC1CCCCC1)CSCCCO
Yield: 99 %

Procedure:
To 90 ml of a methanol solution of sodium methoxide (1 M solution) are added 8.82 g of 3-mercaptopropanol and 1.5 g of sodium borohydride, to which a solution of 10.4 g of 2-methoxy-3-(12-cyclohexyldodecyloxy)propyl methanesulfonate in 120 ml of tetrahydrofuran is added dropwise at room temperature with stirring under nitrogen streams. The reaction mixture, after being stirred at room temperature overnight, is acidified with hydrochloric acid. The methanol is distilled off under reduced pressure and the residue is extracted with hexane. The extract layer is washed with water, dried and concentrated to leave 10.2 g of crude 2-methoxy-3-(12-cyclohexyldodecyloxy)propyl 3-hydroxypropyl sulfide. The crude sulfide is dissolved in 250 ml of dichlromethane, to which 10.0 g of m-chloroperbenzoic acid is added little by little at room temperature with stirring. After 3 hour-stirring at room temperature, the undissolved substances are removed by filtration and the filtrate is washed with an aqueous sodium hydrogensulfite solution, an aqueous sodium bicarbonate solution and water, and dried. The solvent is then distilled off under reduced pressure to leave a residue which in turn is purified by silica gel column chromatography, thereby yielding 8.9 g of the captioned compound.
Reaction SMILES: P(Cl)(Cl)(Cl)(Cl)[Cl:2].[N:7]1[CH:12]=[CH:11][CH:10]=[C:9]([S:13]([OH:16])(=O)=[O:14])[CH:8]=1>C1(C)C=CC=CC=1>[N:7]1[CH:12]=[CH:11][CH:10]=[C:9]([S:13]([Cl:2])(=[O:16])=[O:14])[CH:8]=1
Reactant: ClP(Cl)(Cl)(Cl)Cl
Reactant: O=S(=O)(O)c1cccnc1
Solvent: Cc1ccccc1
Product: O=S(=O)(Cl)c1cccnc1
Temperature: 25 °C
Yield: 62.6 %

Procedure:
Phosphorus pentachloride (1.57 g, 7.5 mmol) was added to a stirred solution of pyridine-3-sulfonic acid (1.00 g, 6.3 mmol) in toluene (5 mL). The mixture was heated at reflux for 16 hours and then cooled to room temperature. The mixture was filtered through celite, and the celite was washed with benzene (2×10 mL). The combined filtrates were concentrated under reduced pressure to give crude pyridine-3-sulfonyl chloride (0.70 g, 100%), which was used directly in the next step without further purification.