Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC([N:8]1[C@H:12]([CH2:13][N:14]([C:24]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[O:25])[CH2:15][CH2:16][C:17](OC(C)(C)C)=[O:18])[CH2:11][CH2:10][C@@H:9]1[CH2:34][CH:35]=[CH2:36])=O)(C)(C)C.CN1CCOCC1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>Cl>[CH2:27]([O:26][C:24]([N:14]1[CH2:15][CH2:16][C:17](=[O:18])[N:8]2[C@@H:9]([CH2:34][CH:35]=[CH2:36])[CH2:10][CH2:11][C@H:12]2[CH2:13]1)=[O:25])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
Reactant: C=CC[C@H]1CC[C@@H](CN(CCC(=O)OC(C)(C)C)C(=O)OCc2ccccc2)N1C(=O)OC(C)(C)C
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN1CCOCC1
Product: C=CC[C@H]1CC[C@H]2CN(C(=O)OCc3ccccc3)CCC(=O)N12
Temperature: 25 °C
Reaction time: 16 h
Yield: 83.8 %

Procedure:
A solution of (2R,5S)-2-allyl-5-{[benzyloxycarbonyl-(2-tert-butoxycarbonyl-ethyl)-amino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester (875 mg, 1.74 mmol) in hydrogen chloride solution (4 M in 1,4-dioxane) was stirred for 21/2 h at room temperature, then concentrated in vacuo. The residue was taken up in N,N-dimethylformamide (10 mL), then 4-methylmorpholine (528 mg, 5.23 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (993 mg, 2.61 mmol) were added. The reaction mixture was stirred for 16 h at room temperature, then partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, filtered, and evaporated. Chromatography (SiO2; heptane-ethyl acetate gradient) afforded the title compound (479 mg, 84%). Colourless gum, MS: 329.4 (M+H)+.
Reaction SMILES: F[C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.[CH3:10][S:11]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[OH:20])(=[O:13])=[O:12].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C(OCC)(=O)C>[CH3:10][S:11]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[O:20][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1)(=[O:12])=[O:13]
Reactant: CS(=O)(=O)c1ccccc1O
Reactant: O=Cc1ccc(F)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CS(=O)(=O)c1ccccc1Oc1ccc(C=O)cc1
Temperature: 100 °C
Yield: 53.3 %

Procedure:
4-Fluorobenzaldehyde (0.690 mL, 6.4 mmol) and 2-(methylsulfonyl)phenol (1.2 g, 7.0 mmol) were dissolved in N,N-dimethylformamide (15 mL), and potassium carbonate (0.85 g, 6.1 mmol) was added. The mixture was heated at 100° C. for 4 days. The reaction was diluted with ethyl acetate and extracted with water three times. The combined aqueous layers were extracted with ethyl acetate twice. The combined organic layers were dried over sodium sulfate, filtered, and evaporated on the rotovap. The residue was chromatographed on silica gel using a 20–40% ethyl acetate in hexanes. The major component was collected to give a solid (0.942 g, 53%). 1H NMR (400 MHz, CDCl3): δ 9.97 (s, 1H), 8.12 (dd, J=8.0 Hz, J′=1.6 Hz, 1H), 7.92 (dd, J=6.6 Hz, J′=2.1 Hz, 2H), 7.64 (m, 1H), 7.38 (td, J=7.9 Hz, J′=1.0 Hz, 1H), 7.18 (dd, J=6.7 Hz, J′=1.9 Hz, 2H), 7.07 (dd, J=8.8.2 Hz, J′=1.0 Hz, 1H), 3.28 (s, 3H); LCMS found for C14H13O4S (M+H)+: m/z=277.0.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]3[CH:13]=[C:14]([C:16]([O:18][CH3:19])=[O:17])[S:15][C:10]=3[CH:9]=2)=[CH:4][CH:3]=1.C(OC(=O)C)(=O)C.[C:27]1(=O)[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1.P(=O)(O)(O)O>C(O)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[NH:12][C:11]3[CH:13]=[C:14]([C:16]([O:18][CH3:19])=[O:17])[S:15][C:10]=3[C:9]=2[C:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH:28]=2)=[CH:6][CH:7]=1
Reactant: COC(=O)c1cc2[nH]c(-c3ccc(Cl)cc3)cc2s1
Reactant: O=C1CCCCC1
Agent: O=P(O)(O)O
Solvent: CC(=O)OC(C)=O
Solvent: CC(=O)O
Product: COC(=O)c1cc2[nH]c(-c3ccc(Cl)cc3)c(C3=CCCCC3)c2s1
Temperature: 80 °C
Yield: 91 %

Procedure:
A solution (0.2 M) of methyl 5-(4-chlorophenyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate in acetic acid was treated with acetic anhydride (2.5 eq.), cyclohexanone (10 eq.) and 85% phosphoric acid (2.1 eq.). The mixture was heated at 80° C. for 3.5 days. After cooling down it was poured into ice cold ammonium hydroxide. The product was extracted with AcOEt and the combined organic layers were washed sequentially with aqueous HCl (1 N), aqueous NaHCO, (saturated solution) and brine then dried and concentrated. The crude was purified by flash chromatography on silica gel (1:9 to 1:4 AcOEt/petroleum ether) affording the title compound (91%) as a solid.
Reaction SMILES: [OH:1][C@@H:2]1[CH2:21][CH2:20][C@@:19]2([CH3:22])[C@@H:4]([CH2:5][CH2:6][C@@H:7]3[C@@H:18]2[C:17](=[O:23])[CH2:16][C@@:15]2([CH3:24])[C@H:8]3[CH2:9][CH2:10][C@@H:11]2[C:12](=[O:14])[CH3:13])[CH2:3]1.[C:25](OC(=O)C)(=[O:27])[CH3:26].O>N1C=CC=CC=1>[C:25]([O:1][C@@H:2]1[CH2:21][CH2:20][C@@:19]2([CH3:22])[C@@H:4]([CH2:5][CH2:6][C@@H:7]3[C@@H:18]2[C:17](=[O:23])[CH2:16][C@@:15]2([CH3:24])[C@H:8]3[CH2:9][CH2:10][C@@H:11]2[C:12](=[O:14])[CH3:13])[CH2:3]1)(=[O:27])[CH3:26]
Reactant: CC(=O)OC(C)=O
Reactant: CC(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@H](O)CC[C@]4(C)[C@H]3C(=O)C[C@]12C
Solvent: c1ccncc1
Solvent: O
Product: CC(=O)O[C@@H]1CC[C@@]2(C)[C@@H](CC[C@H]3[C@@H]4CC[C@H](C(C)=O)[C@@]4(C)CC(=O)[C@@H]32)C1
Reaction time: 8 h

Procedure:
A solution of 3α-hydroxy-5α-pregnane-11,20-dione (1 g) in pyridine (ca 5 ml) was treated with acetic anhydride (2.5 ml) and allowed to stand overnight. The reaction mixture was poured into water and the solid collected by filtration and dried to give the title compound m.p. 150°-151°.
Reaction SMILES: F[C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([F:9])[N:3]=1.[NH2:10][CH2:11][C:12]1([C:18]#[N:19])[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.C(N(CC)CC)C>CS(C)=O>[F:8][C:7]1[C:2]([NH:19][CH2:18][C:12]2([C:11]#[N:10])[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)=[N:3][C:4]([F:9])=[CH:5][CH:6]=1
Reactant: N#CC1(CN)CCOCC1
Reactant: Fc1ccc(F)c(F)n1
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Product: N#CC1(CNc2nc(F)ccc2F)CCOCC1
Temperature: 105 °C
Yield: 48.3 %

Procedure:
To 2,3,6-Trifluoropyridine (0.6 g, 4.5 mmol) in DMSO (5 ml) at room temperature was added 4-(aminomethyl)tetrahydro-2H-pyran-4-carbonitrile (Intermediate R, 1.01 g, 7.23 mmol) and triethylamine (1.57 ml, 11.24 mmol) sequentially. The light brown mixture was heated at 105° C. in a sealed glass bomb for 18 hours. After cooled to room temperature the reaction mixture was extracted with EtOAc (40 ml), washed with saturated NaHCO3 solution and brine, dried over sodium sulfate and concentrated in vacuo to give a light brown liquid. This crude material was purified by silica gel chromatography using a 12 g column, eluting with 5%-20% ethyl acetate in hexane to afford 550 mg (48.2% yield) of the desired product. LCMS (m/z): 254.1 [M+H]+; retention time=0.743 min. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.69-1.95 (m, 4 H) 3.60-3.82 (m, 4 H) 4.00 (ddd, J=12.13, 4.30, 1.96 Hz, 2 H) 5.02 (br. S., 1 H) 6.12 (td, J=5.58, 2.54 Hz, 1 H) 7.19-7.33 (m, 1 H).
Reaction SMILES: [CH3:1][C:2]1[C:7]([C:8]([CH:10](C(OCC)=O)[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[O:9])=[C:6]([F:21])[C:5]([F:22])=[C:4]([F:23])[C:3]=1[F:24].C1(C)C=CC(S(O)(=O)=O)=CC=1>O>[CH3:1][C:2]1[C:7]([C:8]([CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])=[O:9])=[C:6]([F:21])[C:5]([F:22])=[C:4]([F:23])[C:3]=1[F:24]
Reactant: CCOC(=O)C(C(=O)OCC)C(=O)c1c(C)c(F)c(F)c(F)c1F
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Product: CCOC(=O)CC(=O)c1c(C)c(F)c(F)c(F)c1F
Yield: 70.8 %

Procedure:
To diethyl 6-methyl-2,3,4,5-tetrafluorobenzoylmalonate (8 g) are added water (20 ml) and p-toluenesulfonic acid (80 mg) and the mixture is refluxed for 2.5 hours. After cooling, the resultant is extracted with diethyl ether, and the extract is dried over magnesium sulfate and concentrated to give ethyl 6-methyl-2,3,4,5-tetrafluorobenzoylacetate (4.5 g).
Reaction SMILES: [OH:1][C@H:2]1[C@H:6]2[O:7][CH2:8][C@:3]1([CH2:25][OH:26])[O:4][C@H:5]2[N:9]1[CH:17]=[N:16][C:15]2[C:14](=[O:18])[NH:13][C:12]([NH:19][C:20](=[O:24])[CH:21]([CH3:23])[CH3:22])=[N:11][C:10]1=2.[CH3:27][O:28][C:29]1[CH:50]=[CH:49][C:32]([C:33](Cl)([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[C:34]2[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=2)=[CH:31][CH:30]=1>N1C=CC=CC=1>[CH3:41][O:40][C:37]1[CH:36]=[CH:35][C:34]([C:33]([O:26][CH2:25][C@@:3]23[C@@H:2]([OH:1])[C@@H:6]([O:7][CH2:8]2)[C@H:5]([N:9]2[CH:17]=[N:16][C:15]4[C:14](=[O:18])[NH:13][C:12]([NH:19][C:20](=[O:24])[CH:21]([CH3:22])[CH3:23])=[N:11][C:10]2=4)[O:4]3)([C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=2)[C:32]2[CH:49]=[CH:50][C:29]([O:28][CH3:27])=[CH:30][CH:31]=2)=[CH:39][CH:38]=1
Reactant: COc1ccc(C(Cl)(c2ccccc2)c2ccc(OC)cc2)cc1
Reactant: CC(C)C(=O)Nc1nc2c(ncn2[C@@H]2O[C@@]3(CO)CO[C@@H]2[C@@H]3O)c(=O)[nH]1
Solvent: c1ccncc1
Product: COc1ccc(C(OC[C@@]23CO[C@@H]([C@H](n4cnc5c(=O)[nH]c(NC(=O)C(C)C)nc54)O2)[C@@H]3O)(c2ccccc2)c2ccc(OC)cc2)cc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A mixture of compound 51 (440 mg, 1.21 mmol) and 4,4′-dimethoxytrityl chloride (573 mg, 1.69 mmol) was dissolved in anhydrous pyridine (7 cm3) and was stirred at room temperature for 4 h. The mixture was evaporated under reduced pressure to give an oil. Extraction was performed in a system of dichloromethane/water (1:1, v/v, 40 cm3). The organic phase was separated and concentrated to give a solution in a minimal volume of dichloromethane containing 0.5% of pyridine (v/v) which was applied to a silica gel column equilibrated by the same solvent. The product was eluted in gradient concentrations of methanol (0.6-2%, v/v) in dichloromethane containing 0.5% of pyridine (v/v) to give compound 52 as a white solid material (695 mg, 86%). δH (CDCl3) 12.17 (1H, br s, NHCO), 10.09 (1H, br s, NH), 7.87 (1H, s, 8-H), 7.42-6.72 (13H, m, DMT), 5.69 (1H, s, 1′-H), 4.59 (1H, s, 2′-H), 4.50 (1H, s, 3′-H), 3.98 (1H, d, J 8.1, 1″-Ha), 3.69-3.39 (9H, m, DMT, 5′-H, 1″-Hb), 2.72 (1H, m, CHCO), 1.17 (6H, d, J 6.8, CH3CH). (CDCl3) 179.8 (COCH), 158.8, 144.5, 135.6, 135.5, 130.1, 128.1, 127.7, 126.9, 113.2 (DMT), 155.8, 147.9, 147.5, 137.0, 120.8 (guanine), 87.6, 86.4, 86.1 (C-1′, C-4′, DMT), 79.7 (C-3′), 72.6, 71.4 (C-2′, C-5′), 59.8 (C-1″), 55.2 (DMT), 36.1 (COCH), 19.1, 18.8 (CH3CH). FAB-MS m/z 668 [M+H]+.
Reaction SMILES: [Si]([N:8]1[C@@H:11]([S:12][C:13]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C@H:10]([CH2:32][OH:33])[C:9]1=[O:34])(C(C)(C)C)(C)C.[N-]=[N+]=[N-].[Na+]>CN(P(N(C)C)(N(C)C)=O)C>[OH:33][CH2:32][C@H:10]1[C@H:11]([S:12][C:13]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[NH:8][C:9]1=[O:34]
Reactant: CC(C)(C)[Si](C)(C)N1C(=O)[C@@H](CO)[C@@H]1SC(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Product: O=C1N[C@@H](SC(c2ccccc2)(c2ccccc2)c2ccccc2)[C@@H]1CO
Temperature: 25 °C
Reaction time: 4.5 h

Procedure:
To a solution of trans 1-t-Butyldimethylsilyl-3-hydroxymethyl-4-triphenylmethylthio-2-azetidinone (9.3 g, 19 mmol) in HMPA-10% H2O (40 ml) was added sodium azide (1.5 g, 23 mmol) and the mixture stirred at room temperature for 4.5 h, followed by partition between water and a mixture of ether (60 ml) and petroleum ether (40 ml). The organic phase was washed with water several times, dried and concentrated to give an oil which crystallized from CH2Cl2 -ether to give the title compound as a solid, mp 160°-162° C., Hmr (CDCl3) δ: 7.4 (15H, m), 4.48 (1H, d, J=2.3, 4-H), 3.75 (2H, m) and 3.22 ppm (1H, m).
Reaction SMILES: [CH3:1][N:2]([CH3:21])[CH2:3][CH2:4][CH2:5][NH:6][C:7]1[CH:17]=[CH:16][C:10]([C:11]([N:13]([CH3:15])[CH3:14])=[O:12])=[CH:9][C:8]=1[N+:18]([O-])=O>C(O)C.[C].[Pd]>[NH2:18][C:8]1[CH:9]=[C:10]([CH:16]=[CH:17][C:7]=1[NH:6][CH2:5][CH2:4][CH2:3][N:2]([CH3:1])[CH3:21])[C:11]([N:13]([CH3:15])[CH3:14])=[O:12]
Reactant: CN(C)CCCNc1ccc(C(=O)N(C)C)cc1[N+](=O)[O-]
Agent: [Pd]
Solvent: CCO
Product: CN(C)CCCNc1ccc(C(=O)N(C)C)cc1N
Temperature: 25 °C
Reaction time: 13 h
Yield: 102.3 %

Procedure:
10% of palladium-carbon (0.56 g) was added to a solution containing 4-{[3-(dimethylamino)propyl]amino}-N,N-dimethyl-3-nitrobenzamide (2.82 g) in ethanol (20 ml) and the mixture was stirred for 13 hours under a hydrogen gas atmosphere at room temperature. After the catalyst was removed out by filtration, the filtrate was concentrated, thereby yielding the entitled compound (2.59 g) as dark red solid.
Reaction SMILES: O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1.C(N(CC)C(C)C)(C)C.[CH:25]1[CH:30]=[CH:29][C:28]([CH2:31][C:32]2[CH:37]=[CH:36][C:35]([NH2:38])=[CH:34][CH:33]=2)=[CH:27][CH:26]=1.[C:39]([O:43][C:44]([NH:46][CH2:47][C:48](O)=[O:49])=[O:45])([CH3:42])([CH3:41])[CH3:40]>ClCCl>[CH2:31]([C:32]1[CH:33]=[CH:34][C:35]([NH:38][C:48](=[O:49])[CH2:47][NH:46][C:44]([O:43][C:39]([CH3:41])([CH3:40])[CH3:42])=[O:45])=[CH:36][CH:37]=1)[C:28]1[CH:27]=[CH:26][CH:25]=[CH:30][CH:29]=1
Reactant: Nc1ccc(Cc2ccccc2)cc1
Reactant: CC(C)(C)OC(=O)NCC(=O)O
Agent: O=C1OCCN1P(=O)(Cl)N1CCOC1=O
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NCC(=O)Nc1ccc(Cc2ccccc2)cc1
Reaction time: 17.5 h
Yield: 83.9 %

Procedure:
Bis(2-oxo-3-oxazolidinyl)phosphinic chloride (1.90 g) and N,N-diisopropylethyl-amine (1.5 mL) were added to a solution of 4-aminodiphenylmethane (0.52 g) and N-tert-butoxycarbonylglycine (0.50 g) in dichloromethane (30 mL) at 0° C. After stiriing at 0° C. for 10 min and at room temperature for 17.5 hr, the solvent was removed in vacuo. The residue was diluted with 1 N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with water, saturated sodium hydrogen carbonate, and brine, dried over anhydrous sodium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1, v/v) to afford the title compound (0.81 g) as a colorless powder: 1H NMR (400 MHz, CDCl3) δ 1.47 (s, 9H), 3.90 (d, 2H), 3.94 (s, 2H), 7.12-7.21 (m, 5H), 7.28 (d, 2H), 7.41 (d, 2H).
Reaction SMILES: [O:1]=[C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=2)[CH2:5][CH2:4][N:3]1[CH2:13][C:14]([O:16]C(C)(C)C)=[O:15].Cl>CCOC(C)=O>[O:1]=[C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=2)[CH2:5][CH2:4][N:3]1[CH2:13][C:14]([OH:16])=[O:15]
Reactant: CC(C)(C)OC(=O)CN1CCN(c2ccccn2)C1=O
Agent: Cl
Solvent: CCOC(C)=O
Product: O=C(O)CN1CCN(c2ccccn2)C1=O

Procedure:
A solution of tert-butyl (2-oxo-3-pyridin-2-ylimidazolidin-1-yl)acetate from Step B (150 mg, 0.54 mmol) in EtOAc (10 mL) at 0° C. was saturated with HCl (g). The mixture was stood at 0° C. for a total of 30 min, then concentrated in vacuo to give the title compound. MS: m/z=222 (M+1).
Reaction SMILES: [OH:1][C:2]1[C:3]([CH:9]=[O:10])=[N:4][C:5]([CH3:8])=[CH:6][CH:7]=1.[C:11]1([Mg]Br)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.O>O1CCCC1>[OH:10][CH:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:3]1[C:2]([OH:1])=[CH:7][CH:6]=[C:5]([CH3:8])[N:4]=1
Reactant: Br[Mg]c1ccccc1
Reactant: Cc1ccc(O)c(C=O)n1
Solvent: O
Solvent: C1CCOC1
Product: Cc1ccc(O)c(C(O)c2ccccc2)n1
Temperature: 25 °C
Reaction time: 1 h
Yield: 100 %

Procedure:
3-Hydroxy-6-methyl-pyridine-2-carbaldehyde (350 mg) was dissolved in tetrahydrofuran (13 ml) to prepare a solution which was brought to −78° C. Phenylmagnesium bromide (7.4 ml) was slowly added dropwise thereto, and the mixture was stirred at room temperature for one hr. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was then washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by thin layer chromatography using chloroform-acetone to give 2-(hydroxyphenyl-methyl)-6-methyl-pyridin-3-ol (553 mg, yield 100%).
Reaction SMILES: [CH2:1]([O:11][C:12]1[CH:13]=[N:14][C:15]([C:18]2[CH:23]=[CH:22][C:21](Br)=[CH:20][CH:19]=2)=[N:16][CH:17]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[OH-:25].[Na+].OO.C(Cl)(Cl)Cl>O1CCCC1>[CH2:1]([O:11][C:12]1[CH:13]=[N:14][C:15]([C:18]2[CH:23]=[CH:22][C:21](/[CH:3]=[CH:4]/[CH2:5][CH2:6][CH2:7][CH:8]([O:25][C:1](=[O:11])[CH3:2])[CH3:9])=[CH:20][CH:19]=2)=[N:16][CH:17]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: [OH-]
Reactant: CCCCCCCCCCOc1cnc(-c2ccc(Br)cc2)nc1
Agent: OO
Agent: [Na+]
Solvent: C1CCOC1
Solvent: ClC(Cl)Cl
Product: CCCCCCCCCCOc1cnc(-c2ccc(/C=C/CCCC(C)OC(C)=O)cc2)nc1
Temperature: 25 °C
Reaction time: 6 h
Yield: 163.9 %

Procedure:
Apart from the above, inner atmosphere of a four-necked flask equipped with a stirring device, a reflux condenser and a thermometer was replaced with nitrogen gas, and then the flask was charged with 6.6 g (17 mmol) of 5-decyloxy-2-(4-bromophenyl)-pyrimidine, 0.23 g (0.2 mmol) of tetrakis-triphenylphosphine-palladium, 2.4 g (60 mmol) of sodium hydroxide and 60 ml of tetrahydrofuran. Subsequently, 50 ml of a solution prepared by dissolving 20 mmol of the above-obtained E-6-acetoxy-1-heptenylcatecholborane in tetrahydrofuran was dropwise added thereto at room temperature. Then, the whole mixture was heated under reflux with stirring for 6 hours. After cooling the reaction mixture to room temperature, 5 ml of 10% aqueous solution of sodium hydroxide and 2 ml of 30% aqueous solution of hydrogen peroxide were added, and the resulting mixture was stirred for one hour. The mixture was extracted with ether, and the organic layer was twice washed with each 20 ml portion of saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate. The solvent was distilled off, and the residue was purified by silica gel column chromatography to obtain 6.5 g (yield 81%) of (+)-5-decyloxy-2-{4-(6-acetoxy-1-trans-heptenyl)-phenyl}-pyrimidine, [α]D20 =+0.9 (c=1.0, CHCl3).
Reaction SMILES: [C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]([N:11]2[CH2:16][CH:15]([C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=3)[CH2:14][CH:13]([C:28]([OH:30])=O)[CH2:12]2)=[O:10])[CH2:5][CH2:4]1)#[N:2].O[N:32]=[C:33]([NH2:37])[CH:34]([CH3:36])[CH3:35]>>[CH3:35][CH:34]([C:33]1[N:37]=[C:28]([CH:13]2[CH2:14][CH:15]([C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]([F:25])([F:27])[F:26])=[CH:19][CH:18]=3)[CH2:16][N:11]([C:9]([N:6]3[CH2:7][CH2:8][CH:3]([C:1]#[N:2])[CH2:4][CH2:5]3)=[O:10])[CH2:12]2)[O:30][N:32]=1)[CH3:36]
Reactant: N#CC1CCN(C(=O)N2CC(C(=O)O)CC(c3ccc(OC(F)(F)F)cc3)C2)CC1
Reactant: CC(C)C(N)=NO
Product: CC(C)c1noc(C2CC(c3ccc(OC(F)(F)F)cc3)CN(C(=O)N3CCC(C#N)CC3)C2)n1

Procedure:
100 mg (about 0.153 mmol) of the compound from Example 108A and 31 mg (0.306 mmol) of N′-hydroxy-2-methylpropanimidamide were reacted according to the General Method 2. Yield: 60 mg (80% of theory)
Reaction SMILES: ClC1C=C(C=CC=1)C(OO)=[O:6].[C:12]([C@@H:14]([NH:32][C:33]([C@@H:35]1[CH2:40][CH2:39][CH2:38][CH2:37][N:36]1[C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])=[O:34])[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[CH:27]=[CH:26][C:25]([C:28]#[N:29])=[C:24]([S:30][CH3:31])[CH:23]=2)=[CH:18][CH:17]=1)#[N:13]>C(Cl)Cl>[C:12]([C@@H:14]([NH:32][C:33]([C@@H:35]1[CH2:40][CH2:39][CH2:38][CH2:37][N:36]1[C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])=[O:34])[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[CH:27]=[CH:26][C:25]([C:28]#[N:29])=[C:24]([S:30]([CH3:31])=[O:6])[CH:23]=2)=[CH:18][CH:17]=1)#[N:13]
Reactant: CSc1cc(-c2ccc(C[C@@H](C#N)NC(=O)[C@@H]3CCCCN3C(=O)OC(C)(C)C)cc2)ccc1C#N
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: CS(=O)c1cc(-c2ccc(C[C@@H](C#N)NC(=O)[C@@H]3CCCCN3C(=O)OC(C)(C)C)cc2)ccc1C#N
Temperature: 25 °C
Reaction time: 2 h
Yield: 55.4 %

Procedure:
3-Chloroperoxybenzoic acid (0.137 g) was added to a solution of (S)-tert-butyl 2-((S)-1-cyano-2-(4′-cyano-3′-(methylthio)biphenyl-4-yl)ethylcarbamoyl)piperidine-1-carboxylate (0.140 g) in DCM (20 mL) at 0° C. and the mixture was stirred for 2 h then allowed to warm to RT. The mixture was washed with saturated sodium bicarbonate solution, sodium metabisulfite solution, water and brine then dried over sodium sulfate and evaporated. Purification by flash silica chromatography eluting with 30-50% ethyl acetate in isohexane afforded a colourless solid (0.08 g).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[S:10][C:9](Br)=[N:8][C:7]=1[C:12]([F:15])([F:14])[F:13])=[O:5])[CH3:2].C([Sn](CCCC)(CCCC)[C:21]1[N:26]=[CH:25][CH:24]=[CH:23][N:22]=1)CCC.[F-].[K+].CCOC(C)=O>O1CCOCC1.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>[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([C:21]2[N:26]=[CH:25][CH:24]=[CH:23][N:22]=2)=[N:8][C:7]=1[C:12]([F:15])([F:14])[F:13])=[O:5])[CH3:2]
Reactant: CCOC(=O)c1sc(Br)nc1C(F)(F)F
Reactant: CCCC[Sn](CCCC)(CCCC)c1ncccn1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [F-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: CCOC(=O)c1sc(-c2ncccn2)nc1C(F)(F)F
Temperature: 110 °C
Reaction time: 1 h

Procedure:
A mixture of 2-bromo-4-trifluoromethyl-thiazole-5-carboxylic acid ethyl ester (303 mg), 2-tributylstannanyl-pyrimidine (553 mg) and dichlorobis(triphenylphosphine)-palladium (II) (70 mg) in dioxane (5 mL) is heated at 110° C. in a sealed tube overnight. After the reaction mixture is cooled, a potassium fluoride solution and EtOAc are added and the mixture is stirred for 1 h and filtered. The organic layer is separated and aqueous layer is extracted with EtOAc once. The combined extracts are concentrated and the residue is purified by chromatography (silica gel, 4:1 Hexane and EtOAc) to give the title compound.
Reaction SMILES: [OH:1][CH:2]([CH3:15])[CH2:3][CH2:4][C:5]([O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:6].C(N(CC)CC)C.[C:23](Cl)(=[O:25])[CH3:24]>C(Cl)Cl>[C:23]([O:1][CH:2]([CH3:15])[CH2:3][CH2:4][C:5]([O:7][CH2:8][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)=[O:6])(=[O:25])[CH3:24]
Reactant: CC(=O)Cl
Reactant: CC(O)CCC(=O)OCc1ccccc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(=O)OC(C)CCC(=O)OCc1ccccc1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
63 g (302.5 mmol) of benzyl 4-hydroxypentanoate and 46.4 ml (332.8 mmol) of triethylamine are charged under nitrogen at room temperature to 300 ml of CH2Cl2. The mixture is cooled to 0° C. and 21.5 ml (302.5 mmol) of acetyl chloride are added dropwise at 0°-5° C. When the dropwise addition is complete, the ice bath is removed and stirring is continued overnight at room temperature. The reaction mixture is mixed with ice-water and the organic phase is separated and washed twice with water. The aqueous phases are extracted twice with CH2Cl2. The organic phases are combined, dried over MgSO4, filtered and concentrated by evaporation. Distillation of the residue gives benzyl 4-acetoxypentanoate as a colourless oil of b.p. 126°-127° C./2.10-2 torr.
Reaction SMILES: [Br:1][C:2]1[C:3]([NH:16][C@H:17]([CH:20]([CH3:22])[CH3:21])[CH2:18][OH:19])=[N:4][C:5]([NH:8][C:9]2[NH:13][C:12]([S:14][CH3:15])=[N:11][N:10]=2)=[N:6][CH:7]=1.C([O-])(O)=[O:24].[Na+].OOS([O-])=O.[K+]>CO.O.O>[Br:1][C:2]1[C:3]([NH:16][C@H:17]([CH:20]([CH3:22])[CH3:21])[CH2:18][OH:19])=[N:4][C:5]([NH:8][C:9]2[NH:13][C:12]([S:14]([CH3:15])=[O:24])=[N:11][N:10]=2)=[N:6][CH:7]=1
Reactant: CSc1nnc(Nc2ncc(Br)c(N[C@@H](CO)C(C)C)n2)[nH]1
Reactant: O=C([O-])O
Agent: O=S([O-])OO
Agent: [K+]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CC(C)[C@H](CO)Nc1nc(Nc2nnc(S(C)=O)[nH]2)ncc1Br
Temperature: 25 °C
Reaction time: 2 h

Procedure:
At 0° C., 159 mg (0.41 mmol) of (R)-2-[5-bromo-2-(5-methylsulfanyl-4H-[1,2,4]triazol-3-ylamino)-pyrimidin-4-ylamino]-3-methyl-butan-1-ol in 4 ml of MeOH/water (4:1) is mixed with 80 mg (0.95 mmol) of NaHCO3 and 98 mg (0.95 mmol) of oxone. The reaction mixture is stirred for 2 hours at room temperature, then another 50 mg (0.5 mmol) of oxone is added, and it is stirred for 1 hour at 30° C. The batch is diluted with water and extracted with ethyl acetate. The organic phase is concentrated by evaporation and purified by chromatography (methylene chloride-(methylene chloride/ethanol: 9/1); Flashmaster II). After the recrystallization, 45 mg (0.11 mmol, 27% of theory) of the product (R)-2-[5-bromo-2-(5-methanesulfinyl-4H-[1,2,4]triazol-3-ylamino)-pyrimidin-4-ylamino]-3-methyl-butan-1-ol is obtained.