Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]([CH3:46])=[CH:3][CH2:4][CH2:5][C@@:6]1([CH3:45])[O:11][C:10]2[C:12]([CH2:40][CH:41]=[C:42]([CH3:44])[CH3:43])=[C:13]3[O:25][C@@:24]45[C:26]6([CH2:33]/[CH:34]=[C:35](/[C:37]([OH:39])=[O:38])\[CH3:36])[O:29][C:30]([CH3:32])([CH3:31])[CH:23]4[CH2:22][C@H:21]([C:27]6=[O:28])[CH:20]=[C:19]5[C:17](=[O:18])[C:14]3=[C:15]([OH:16])[C:9]=2[CH:8]=[CH:7]1.CC(C)=CCC[C@]1(C)OC2C(CC=C(C)C)=C3O[C@@]45C6(C/C=C(/C(O)=O)\CO)OC(C)(C)C4C[C@H](C6=O)C=C5C(=O)C3=C(O)C=2C=C1>>[CH3:1][C:2]([CH3:46])=[CH:3][CH2:4][CH2:5][C@@:6]1([CH3:45])[O:11][C:10]2[C:12]([CH2:40][CH:41]=[C:42]([CH3:43])[CH3:44])=[C:13]3[O:25][C@@:24]45[C@@:26]6([CH2:33]/[CH:34]=[C:35](\[C:37]([OH:39])=[O:38])/[CH3:36])[O:29][C:30]([CH3:31])([CH3:32])[C@@H:23]4[CH2:22][C@H:21]([C:27]6=[O:28])[CH:20]=[C:19]5[C:17](=[O:18])[C:14]3=[C:15]([OH:16])[C:9]=2[CH:8]=[CH:7]1
Reactant: CC(C)=CCC[C@]1(C)C=Cc2c(O)c3c(c(CC=C(C)C)c2O1)O[C@]12C(=C[C@@H]4CC1C(C)(C)OC2(C/C=C(\C)C(=O)O)C4=O)C3=O
Agent: CC(C)=CCC[C@@]1(C)C=Cc2c(O)c3c(c(CC=C(C)C)c2O1)O[C@]12C(=C[C@@H]4CC1C(C)(C)OC2(C/C=C(\CO)C(=O)O)C4=O)C3=O
Product: CC(C)=CCC[C@]1(C)C=Cc2c(O)c3c(c(CC=C(C)C)c2O1)O[C@]12C(=C[C@@H]4C[C@H]1C(C)(C)O[C@@]2(C/C=C(/C)C(=O)O)C4=O)C3=O

Procedure:
Gambogic acid (GA, CAS No. 2752-65-0) which was previously isolated as an inseparable stereomeric mixture of C-2 epimers, were separated into two epimers (gambogic acid and epigambogic acid, referred to as 1 and 2) according to the present invention. In the HPLC analysis, GA presented as one peak (m/z 628) on C18 column (Alltima C18, 5μ, 4.6×250 mm) eluted with CH3CN/0.1% acetic acid (90:10). When the fraction corresponding to the single peak was then subject to C8 column (Alltima C8, 5μ, 4.6×250 mm), eluted with CH3CN/0.1% acetic acid (75:25), two completely separated peaks appear. These two peaks were isolated by HPLC under the same analytical condition with each injection of 20 μL acetone solution of gambogic acid (35 mg/mL), yielding 1 (12 mg) and 2 (10 mg). The two peaks being two C-2 epimers of GA was clearly confirmed by extensive spectroscopic analysis and direct comparison of NMR and HPLC data with those of the known R-epimer. In addition, two similar pairs of C-2 epimeric xanthones were also isolated from this plant by the same method. They were identified to be isogambogic acid, epiisogambogic acid, 30-hydroxygambogic acid, and 30-hydroxyepigambogic acid by extensive spectroscopic and chromatographic analysis including HRMS, 2D NMR, and HPLC techniques. All of these epimers except gambogic acid (R-epimer which had been reported by American scientists using single crystal X-ray diffraction) were isolated and separated for the first time, and 30-hydroxygambogic acid and 30-hydroxyepigambogic acid were previously unknown compounds.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=[O:7])=[CH:4][N:3]=1.[OH:11]O>C(O)(=O)C>[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=[O:7])=[CH:4][N+:3]=1[O-:11]
Reactant: OO
Reactant: NC(=O)c1ccc(N)nc1
Solvent: CC(=O)O
Product: NC(=O)c1ccc(N)[n+]([O-])c1
Temperature: 100 °C

Procedure:
6-Aminonicotinamide, 50 g, was dissolved in warm glacial acetic acid, 500 ml. To this clear solution 30% hydrogen peroxide, 80 ml was slowly added with agitation. The mixture was then heated to 100° C. for 5 hours. The light brownish solution thus formed was evaporated to a syrupy residue which crystallized on cooling in an ice water bath. The crystals were washed with acetone and dried. The yield of practically pure 6-aminonicotinamide-1-oxide was 51.6 g. This product had a mobility (Rf) of 0.48 on thin-layer chromatogram using a solvent system of benzene:methanol, 1:1.
Reaction SMILES: [CH2:1]([NH:5][C:6]1[C:14]2[N:13]=[CH:12][N:11]([C:15]3[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[CH:17][CH:16]=3)[C:10]=2[CH:9]=[C:8]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:7]=1)[CH:2]([CH3:4])[CH3:3].CN(C(ON1N=NC2[CH:41]=[CH:42][CH:43]=[N:44]C1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>C1COCC1>[CH:43]1([NH:44][C:19](=[O:21])[C:18]2[CH:17]=[CH:16][C:15]([N:11]3[C:10]4[CH:9]=[C:8]([C:24]5[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=5)[CH:7]=[C:6]([NH:5][CH2:1][CH:2]([CH3:3])[CH3:4])[C:14]=4[N:13]=[CH:12]3)=[CH:23][CH:22]=2)[CH2:41][CH2:42]1
Reactant: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Reactant: CC(C)CNc1cc(-c2ccccc2)cc2c1ncn2-c1ccc(C(=O)O)cc1
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: CC(C)CNc1cc(-c2ccccc2)cc2c1ncn2-c1ccc(C(=O)NC2CC2)cc1
Temperature: 23 °C
Reaction time: 20 h
Yield: 84.7 %

Procedure:
To a solution of 44 mg (114 μmol) 4-[4-(isobutylamino)-6-phenyl-1H-benzimidazol-1-yl]benzoic acid which was prepared according to intermediate example 4-2 in 2.8 mL THF were added 47.7 mg HATU, 22 μL N,N-diisopropylethylamine and the mixture was stirred at 23° C. for 20 hours. The solvent was removed and the residue purified by chromatography to give 41.0 mg (85%) of the title compound.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[OH:11])[C:7](=[O:12])[CH2:6][CH2:5]2.[N-:13]=[N+]=[N-].[Na+].O>C(Cl)(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[OH:11])[C:7](=[O:12])[NH:13][CH2:6][CH2:5]2
Reactant: [N-]=[N+]=[N-]
Reactant: O=C1CCc2cc(F)c(O)cc21
Agent: [Na+]
Solvent: O
Solvent: ClC(Cl)Cl
Product: O=C1NCCc2cc(F)c(O)cc21
Reaction time: 3 h

Procedure:
To a solution of 5-fluoro-6-hydroxyindan-1-one ((90), 10.5 g, 63.3 mmol) in chloroform (600 ml) was added NaN3 (12.3 g, 190 mmol), followed by dropwise addition of methanasulfonic acid (33 ml, 506 mmol). Resulting mixture was stirred for 3 hr. The reaction mixture was poured into cold water and extracted with chloroform (3×). Organic extracts were combined and washed with H2O and sat. NaCl, then dried over Na2SO4. Concentration in vacuo gave a mixture of required product and reversed lactam. Purification of crude product on silica eluting with 30-60% EtOAc/Hexane offered the title compound as a off-white solid (5.3 g, 46%). MS (ES) m/z 180.0.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH:9]([C:11]2[CH:19]=[CH:18][CH:17]=[CH:16][C:12]=2[C:13]([OH:15])=[O:14])[OH:10])=[CH:4][CH:3]=1>CO.[Pd]>[C:5]1([CH2:8][N:1]([CH2:9][C:11]2[CH:12]=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:2]2[CH:3]=[CH:4][C:5]([CH2:8][CH:9]([C:11]3[CH:19]=[CH:18][CH:17]=[CH:16][C:12]=3[C:13]([OH:15])=[O:14])[OH:10])=[CH:6][CH:7]=2)[CH:6]=[CH:7][CH:2]=[CH:3][CH:4]=1
Reactant: Nc1ccc(CC(O)c2ccccc2C(=O)O)cc1
Agent: [Pd]
Solvent: CO
Product: O=C(O)c1ccccc1C(O)Cc1ccc(N(Cc2ccccc2)Cc2ccccc2)cc1
Reaction time: 1.5 h
Yield: 59.5 %

Procedure:
Compound VII (32 mg), obtained in Example 10, was dissolved in methanol (2 ml). Pd/C (10 mg) was added and the reaction mixture flushed with hydrogen and stirred for about 1.5 hours until all spotting material was gone, as determined by TLC in CH2Cl2 :ethylacetate (1:1), yielding 16.2 mg (86 percent yield) of Compound 5b.
Reaction SMILES: [CH3:1][CH2:2][O:3][C:4]1[CH:9]=[C:8]2[NH:10][CH:11]=[C:12]([C:15]#[N:16])[C:13](=O)[C:7]2=[CH:6][C:5]=1[NH:17][C:18]([CH3:20])=[O:19].[Cl:21]Cl>>[CH3:1][CH2:2][O:3][C:4]1[CH:9]=[C:8]2[N:10]=[CH:11][C:12]([C:15]#[N:16])=[C:13]([Cl:21])[C:7]2=[CH:6][C:5]=1[NH:17][C:18]([CH3:20])=[O:19]
Reactant: ClCl
Reactant: CCOc1cc2[nH]cc(C#N)c(=O)c2cc1NC(C)=O
Product: CCOc1cc2ncc(C#N)c(Cl)c2cc1NC(C)=O

Procedure:
3-Cyano-7-ethoxy-4-hydroxy-6-N-acetylquinoline 6 was reacted with a chlorine-substituting reagent to yield 4-Chloro-3-cyano-7-ethoxy-6-N-acetylquinoline 7 followed by condensation with 3-chloro-4-fluoroaniline optionally in the presence of acid to yield N-[4-(3-Chloro-4-fluoro-phenylamino)-3-cyano-7-ethoxy-quinolin-6-yl]-acetamide 8.
Reaction SMILES: [NH:1]1[C:11](=[O:12])[C:10]2[NH:9][C:7](=[O:8])[NH:6][C:5]=2[NH:4][C:2]1=[O:3].C12C(=O)NC(=O)NC=1NC(N2)=O.N.[Cl:26]([OH:30])(=[O:29])(=[O:28])=[O:27]>>[NH:1]1[C:11](=[O:12])[C:10]2[NH:9][C:7](=[O:8])[NH:6][C:5]=2[NH:4][C:2]1=[O:3].[Cl:26]([O-:30])(=[O:29])(=[O:28])=[O:27]
Reactant: [O-][Cl+3]([O-])([O-])O
Agent: N
Agent: O=c1[nH]c(=O)c2[nH]c(=O)[nH]c2[nH]1
Product: [O-][Cl+3]([O-])([O-])[O-]

Procedure:
A multi-faceted process for preparing uric acid of varying degrees of purity includes a first phase wherein uric acid of approximately 80-90% purity is prepared by dissolving fecal matter containing uric acid in a dilute alkali solution and then separating any undissolved solid residue therefrom. An ammonium salt is added to the solution to precipitate ammonium urate, which is readily convertible by conventional means to uric acid of 80-90% purity. Uric acid of even greater purity is prepared in the second phase by dissolving a relatively impure uric acid product, such as the above ammonium urate, in a second dilute alkali solution. Urate salt is then precipitated by gradually adjusting the pH of the second alkali solution with a dilute mineral acid to a pH of about 10.5. The urate salt is subsequently separated and converted to uric acid by suspending it in hot dilute mineral acid, the resultant uric acid having a purity of approximately 99%. The third phase of the present invention comprises preparing ultra pure crystalline uric acid by dissolving a relatively pure uric acid product, such as that obtained from the second phase, or an impure uric acid product, in a hot perchloric acid solution. Immediately upon dissolution of the uric acid, the hot perchloric acid solution is gradually cooled to form perchlorate salt crystals which contain uric acid. The perchlorate salt crystals are separated and then redissolved in a second hot perchloric acid solution which is thereupon immediately gradually cooled to again form perchlorate salt crystals containing uric acid. This second batch of perchlorate salt crystals is separated from the solution and then suspended in warm water to dissolve the perchloric acid and precipitate uric acid crystals. The resultant uric acid crystals are then separated and have a purity of approximately 99.9%.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].Cl.[C:8]([N:16]1[CH2:22][CH2:21][N:20]([CH2:23][CH2:24][CH2:25][CH:26]([C:34]2[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=2)[C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)[CH2:19][CH2:18][N:17]1[C:41](=O)[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)(=O)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>CCOCC>[F:33][C:30]1[CH:31]=[CH:32][C:27]([CH:26]([C:34]2[CH:35]=[CH:36][C:37]([F:40])=[CH:38][CH:39]=2)[CH2:25][CH2:24][CH2:23][N:20]2[CH2:21][CH2:22][N:16]([CH2:8][C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[N:17]([CH2:41][C:42]3[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=3)[CH2:18][CH2:19]2)=[CH:28][CH:29]=1
Reactant: O=C(c1ccccc1)N1CCN(CCCC(c2ccc(F)cc2)c2ccc(F)cc2)CCN1C(=O)c1ccccc1
Agent: Cl
Agent: [Al+3]
Agent: [H-]
Solvent: CCOCC
Product: Fc1ccc(C(CCCN2CCN(Cc3ccccc3)N(Cc3ccccc3)CC2)c2ccc(F)cc2)cc1
Yield: 82.6 %

Procedure:
To lithium aluminum hydride (21 g) in ether (150 ml) was added 1,2-dibenzoyl-5-[4,4-bis(4-fluorophenyl)butyl]hexahydro-1H-1,2,5-triazepine hydrochloride (34.4 g) slowly in small portions. The mixture was stirred and heated under reflux with protection from moisture for 22 hours. The reaction was quenched with 10% sodium hydroxide and water. The resulting hydroxides were collected on a filter and washed well with ether. The filtrate and washings were evaporated to a syrup, wt. 30.4 g. The syrup was dissolved in acetone and the solution was decolorized (Nuchar). The solution was concentrated and a solution of fumaric acid (6.7 g) in acetone (800 ml) was added. The resulting solution was boiled down until crystallization occurred. After cooling, the crude product was collected on a filter and washed with acetone; wt. 32.9 g. Recrystallization from methanol-ether gave 25.3 g (68%) of pure titled product as the fumarate salt (1:1), mp=184°-185°.
Reaction SMILES: [CH:1]1[CH:6]=[C:5]2[C:7]3[C:14]([C:15]([OH:17])=O)=[CH:13][CH:12]=[CH:11][C:8]=3[C:9](=[O:10])[C:4]2=[CH:3][CH:2]=1.S(Cl)([Cl:20])=O>>[CH:11]1[C:8]2[C:9](=[O:10])[C:4]3[C:5](=[CH:6][CH:1]=[CH:2][CH:3]=3)[C:7]=2[C:14]([C:15]([Cl:20])=[O:17])=[CH:13][CH:12]=1
Reactant: O=C(O)c1cccc2c1-c1ccccc1C2=O
Reactant: O=S(Cl)Cl
Product: O=C(Cl)c1cccc2c1-c1ccccc1C2=O

Procedure:
The following steps are suitable for synthesizing some charge transport materials of this invention involving a linking reaction as described in the following. In the first step, diphenic acid or its derivative is dissolved in large access of concentrated sulfuric acid and the solution is heated at approximately 70° C. for about 10 minutes. The product, 9-fluorenone-4-carboxylic acid or its derivative, is isolated. In the second step, 9-fluorenone-4-carboxylic acid or its derivative is chlorinated with thionyl chloride to form 9-fluorenone-4-carbonyl chloride or its derivative. Then, 9-fluorenone-4-carbonyl chloride or its derivative reacts with a diol, a dithiol, a diamine, a hydroxylamine, a hydroxythiol, or a thioamine in the presence of triethylamine. Non-limiting examples of suitable dithiol are 4,4′-thiobisbenzenethiol, 1,4-benzenedithiol, 1,3-benzenedithiol, sulfonyl-bis(benzenethiol), 2,5-dimecapto-1,3,4-thiadiazole, 1,2-ethanedithiol, 1,3-propanedithiol, 1,4-butanedithiol, 1,5-pentanedithiol, and 1,6-hexanedithiol. Non-limiting examples of suitable diols are 2,2′-bi-7-naphtol, 1,4-dihydroxybenzene, 1,3-dihydroxybenzene, 10,10-bis(4-hydroxyphenyl)anthrone, 4,4′-sulfonyldiphenol, bisphenol, 4,4′-(9-fluorenylidene)diphenol, 1,10-decanediol, 1,5-pentanediol, diethylene glycol, 4.4′-(9-fluorenylidene)-bis(2-phenoxyethanol), bis(2-hydroxyethyl) terephthalate, bis[4-(2-hydroxyethoxy)phenyl] sulfone, hydroquinone-bis (2-hydroxyethyl)ether, and bis(2-hydroxyethyl) piperazine. Non-limiting examples of suitable diamine are diaminoarenes, and diaminoalkanes. Non-limiting examples of suitable hydroxylamine are p-aminophenol and fluoresceinamine. Non-limiting examples of suitable hydroxythiol are monothiohydroquinone and 4-mercapto-1-butanol. Non-limiting example of suitable thioamine is p-aminobenzenethiol. The intermediate product is isolated and dried. Then, the intermediate product is reacted with malononitrile in the presence of piperidine to form the dimeric electron transport material, which can be purified and dried.
Reaction SMILES: C[O:2][C:3](=[O:31])[C@H:4]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[C:24](=[O:30])[N:25]([CH3:29])[CH:26]=[CH:27][CH:28]=2)=[CH:19][CH:18]=1)[NH:5][C:6]([C:8]1[C:13]([CH3:14])=[CH:12][CH:11]=[CH:10][C:9]=1[Cl:15])=[O:7].[OH-].[Na+]>C(O)C>[Cl:15][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]([CH3:14])[C:8]=1[C:6]([NH:5][C@H:4]([C:3]([OH:31])=[O:2])[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[C:24](=[O:30])[N:25]([CH3:29])[CH:26]=[CH:27][CH:28]=2)=[CH:19][CH:18]=1)=[O:7]
Reactant: COC(=O)[C@H](Cc1ccc(-c2cccn(C)c2=O)cc1)NC(=O)c1c(C)cccc1Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: Cc1cccc(Cl)c1C(=O)N[C@@H](Cc1ccc(-c2cccn(C)c2=O)cc1)C(=O)O
Temperature: 50 °C
Reaction time: 2 h
Yield: 70.9 %

Procedure:
To a suspension of N-[(2-chloro-6-methylphenyl)carbonyl]-4-(1-methyl-2-oxo-3-pyridinyl)-L-phenylalanine methyl ester (118 mg, 0.269 mmol) in ethanol (6 mL) was added 1N aqueous sodium hydroxide solution (4 mL) at room temperature. The resulting solution was heated to 50° C. and stirred for 2 h. Then, the ethanol was removed under vacuum and the residue was diluted with water (25 mL). The aqueous solution was washed with diethyl ether (25 mL) to remove any neutral impurities. The aqueous layer was acidified with 1.0 N HCl and the product was extracted into ethyl acetate (2×25 mL). The combined organic extracts were washed with brine solution (50 mL) and were dried over anhydrous magnesium sulfate. Filtration of the drying agent and concentration afforded 81 mg (71% yield) of N-[(2-chloro-6-methylphenyl)carbonyl]-4-(1-methyl-2-oxo-3-pyridinyl)-L-phenylalanine as a white solid: mp 204-210° C. FAB-HRMS m/e calcd for C23H21ClN2O4 (M+H) 425.1268. found 425.1267.
Reaction SMILES: [F:1][C:2]1([F:26])[C:9]2([OH:13])[C:10]([F:12])([F:11])[C:5]3(F)[C:6]([F:21])([F:20])[C:7]([OH:19])([C:16]([F:18])([F:17])[C:3]1([OH:25])[C:4]3([F:24])[F:23])[C:8]2([F:15])[F:14].[OH:27]C12CC3(O)CC(O)(CC(O)(C3)C1)C2>>[OH:25][C:3]12[C:16]([F:17])([F:18])[C:7]3([OH:19])[C:6]([F:20])([F:21])[C:5]([OH:27])([C:10]([F:11])([F:12])[C:9]([OH:13])([C:8]3([F:14])[F:15])[C:2]1([F:26])[F:1])[C:4]2([F:23])[F:24]
Reactant: OC12C(F)(F)C3(O)C(F)(F)C(O)(C1(F)F)C(F)(F)C(F)(C2(F)F)C3(F)F
Reactant: OC12CC3(O)CC(O)(C1)CC(O)(C2)C3
Product: OC12C(F)(F)C3(O)C(F)(F)C(O)(C1(F)F)C(F)(F)C(O)(C2(F)F)C3(F)F

Procedure:
By changing 1,3,5-trihydroxyadamantane in Example 9 to 1,3,5,7-tetrahydroxyadamantane, reactions are carried out in the same manner as in Examples 9-1 to 9-3 to obtain 1,3,5,7-tetrahydroxy(perfluoroadamantane).
Reaction SMILES: C([NH:20][S:21](=[O:46])(=[O:45])[O:22][CH2:23][C@@H:24]1[C@@H:31]2[C@@H:27]([O:28]C(C)(C)[O:30]2)[C@H:26]([N:34]2[CH:42]=[N:41][C:40]3[C:35]2=[N:36][CH:37]=[N:38][C:39]=3[CH2:43][CH3:44])[O:25]1)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>C(O)(C(F)(F)F)=O.O>[S:21](=[O:46])(=[O:45])([O:22][CH2:23][C@@H:24]1[C@@H:31]([OH:30])[C@@H:27]([OH:28])[C@H:26]([N:34]2[CH:42]=[N:41][C:40]3[C:35]2=[N:36][CH:37]=[N:38][C:39]=3[CH2:43][CH3:44])[O:25]1)[NH2:20]
Reactant: CCc1ncnc2c1ncn2[C@@H]1O[C@H](COS(=O)(=O)NC(c2ccccc2)(c2ccccc2)c2ccccc2)[C@H]2OC(C)(C)O[C@H]21
Solvent: O=C(O)C(F)(F)F
Solvent: O
Product: CCc1ncnc2c1ncn2[C@@H]1O[C@H](COS(N)(=O)=O)[C@@H](O)[C@H]1O
Yield: 84.7 %

Procedure:
A solution of [(3aR,4R,6R,6aR)-6-(6-ethyl-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methyl tritylsulfamate (149.0 mg, 0.23 mmol) in TFA/water (5.0 mL, 9:1) was stirred for 30 minutes, concentrated to dryness, dissolved in methanol and concentrated again. The residue was purified by prep HPLC to yield the title compound (70 mg, 84%).
Reaction SMILES: C([O:8][C:9]1[CH:30]=[CH:29][C:12]([CH2:13][C:14]2[N:18]3[N:19]=[C:20]([C:23]4[CH:24]=[N:25][N:26]([CH3:28])[CH:27]=4)[CH:21]=[CH:22][C:17]3=[N:16][CH:15]=2)=[CH:11][CH:10]=1)C1C=CC=CC=1>[Pd].C(O)C>[CH3:28][N:26]1[CH:27]=[C:23]([C:20]2[CH:21]=[CH:22][C:17]3[N:18]([C:14]([CH2:13][C:12]4[CH:11]=[CH:10][C:9]([OH:8])=[CH:30][CH:29]=4)=[CH:15][N:16]=3)[N:19]=2)[CH:24]=[N:25]1
Reactant: Cn1cc(-c2ccc3ncc(Cc4ccc(OCc5ccccc5)cc4)n3n2)cn1
Agent: [Pd]
Solvent: CCO
Product: Cn1cc(-c2ccc3ncc(Cc4ccc(O)cc4)n3n2)cn1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
10% Palladium on carbon (49 mg) was added to a solution of 3-(4-benzyloxy-benzyl)-6-(1-methyl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazine (Stage 5.1, 214 mg, 0.46 mmol) in ethanol and the resulting mixture was stirred under an atmosphere of hydrogen at rt for 24 h. The RM was filtered through Celite and concentrated in vacuo. Purification by HPLC afforded the title compound as a white solid (tR 0.8 min (conditions 2), MH+=306, 1H-NMR in CD3OD: 8.4 (s, 1H), 8.2 (d, 1H), 8.1 (s, 1H), 8.0 (d, 1H), 7.7 (s, 1H), 7.2 (d, 2H), 6.8 (d, 2H), 4.3 (s, 2H), 4.0 (s, 3H)).
Reaction SMILES: [C:1]([S@:5]([N:7]=[C:8]([C:10]1[N:11]=[CH:12][C:13]2[N:18](C(OCC)=O)[CH:17]=[CH:16][C:14]=2[N:15]=1)[CH3:9])=[O:6])([CH3:4])([CH3:3])[CH3:2].CCC(C)[BH-](C(C)CC)C(C)CC.[Li+]>C1COCC1>[N:15]1[C:14]2[CH:16]=[CH:17][NH:18][C:13]=2[CH:12]=[N:11][C:10]=1[CH:8]([NH:7][S@@:5]([C:1]([CH3:2])([CH3:4])[CH3:3])=[O:6])[CH3:9]
Reactant: CCOC(=O)n1ccc2nc(C(C)=N[S@](=O)C(C)(C)C)ncc21
Agent: CCC(C)[BH-](C(C)CC)C(C)CC
Agent: [Li+]
Solvent: C1CCOC1
Product: CC(N[S@](=O)C(C)(C)C)c1ncc2[nH]ccc2n1
Temperature: 25 °C
Reaction time: 16 h
Yield: 87.8 %

Procedure:
To (R)-ethyl 2-(1-(tert-butylsulfinylimino)ethyl)-5H-pyrrolo[3,2-d]pyrimidine-5-carboxylate (259.0 mg, 0.77 mmol) in anhydrous THF (5 mL) at 0° C. was added dropwise L-selectride (1.0 mol/L) in THF (1.2 mL). The resultant orange reaction mixture was warmed to RT and stirred under N2 for 16 h. The solvent was removed in vacuo and the crude was partitioned between EtOAc and water. The organic layer was washed with sat'd. aq. NaHCO3, water and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The crude was purified by SiO2 chromatography eluted with a mixture of EtOAc containing 1% TEA and MeOH to afford 180.0 mg (87.8%) of (R)—N-(1-(5H-pyrrolo[3,2-d]pyrimidin-2-yl)ethyl)-2-methylpropane-2-sulfinamide as racemic mixture. MS (ESI) m/z: 267 [M+1]+.
Reaction SMILES: FC(F)(F)C(O)=O.[NH2:8][CH2:9][CH2:10][C:11]1[N:16]=[C:15]([C:17]2[S:18][C:19]3[CH:27]=[CH:26][CH:25]=[CH:24][C:20]=3[C:21](=[O:23])[N:22]=2)[CH:14]=[CH:13][CH:12]=1.C(=O)([O-])[O-].[K+].[K+].[C:34]1([N:40]=[C:41]=[O:42])[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>C(#N)C>[O:23]=[C:21]1[C:20]2[CH:24]=[CH:25][CH:26]=[CH:27][C:19]=2[S:18][C:17]([C:15]2[N:16]=[C:11]([CH2:10][CH2:9][NH:8][C:41]([NH:40][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)=[O:42])[CH:12]=[CH:13][CH:14]=2)=[N:22]1
Reactant: NCCc1cccc(-c2nc(=O)c3ccccc3s2)n1
Reactant: O=C=Nc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O=C(O)C(F)(F)F
Solvent: CC#N
Product: O=C(NCCc1cccc(-c2nc(=O)c3ccccc3s2)n1)Nc1ccccc1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 17.4 %

Procedure:
A mixture of 2-[6-(2-aminoethyl)-2-pyridyl]-4H-1,3-benzothiazine-4-one trifluoroacetic acid salt (0.40 g, 1.0 mmol), potassium carbonate (0.41 g, 3.0 mmol) and acetonitrile (15 ml) was stirred at room temperature for 20 minutes. Successively phenyl isocyanate (0.47 g, 4.0 mmol) was added to the mixture, and the mixture was refluxed for 4 hrs. After cooling, the precipitates were collected by filtration and dissolved in chlorobenzene and water. The organic layer was dried over magnesium sulfate. The solvent was evaporated, and the residue was recrystallized from hexane-chlorobenzene to give the titled compound (0.07 g, 17%) as pale yellow crystals.
Reaction SMILES: [CH3:1][S:2][C:3]1[CH:4]=[C:5]([C:9](=[N:16][O:17][CH2:18][C:19]2[N:24]=[C:23]([N:25]3C(=O)C4C(=CC=CC=4)C3=O)[CH:22]=[CH:21][CH:20]=2)[C:10]2[N:14]([CH3:15])[N:13]=[N:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1.O.NN>C1COCC1>[CH3:1][S:2][C:3]1[CH:4]=[C:5]([C:9](=[N:16][O:17][CH2:18][C:19]2[N:24]=[C:23]([NH2:25])[CH:22]=[CH:21][CH:20]=2)[C:10]2[N:14]([CH3:15])[N:13]=[N:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1
Reactant: CSc1cccc(C(=NOCc2cccc(N3C(=O)c4ccccc4C3=O)n2)c2nnnn2C)c1
Agent: NN
Solvent: O
Solvent: C1CCOC1
Product: CSc1cccc(C(=NOCc2cccc(N)n2)c2nnnn2C)c1
Temperature: 25 °C
Reaction time: 4 h
Yield: 77 %

Procedure:
To a stirred solution of 2-(6-{[({[3-(methylsulfanyl)phenyl](1-methyl-1H-tetrazol-5-yl)methylene}amino)oxy]methyl}pyridin-2-yl)-1H-isoindole-1,3(2H)-dione (2.79 g, 5.75 mmol) in dry THF (70 mL) was added hydrazine hydrate (1.44 g, 28.7 mmol). The reaction mixture was stirred at room temperature for 4 h, then insolubles were removed by filtration and washed with dichloromethane. The filtrates were combined and concentrated in vacuo. The residue was dissolved in dichloromethane (100 mL), washed with water (50 mL), and the organic layer was dried over MgSO4 and concentrated in vacuo to afford 6-{[({[3-(methylsulfanyl)phenyl](1-methyl-1H-tetrazol-5-yl)methylene}amino)oxy]methyl}pyridin-2-amine as a white solid [1.63 g, yield 77%; HPLC/MS: m/z=356 (M+H); logP(HCOOH)=1.42].