Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([CH:3]1[CH:29]=[C:28]([CH3:30])[CH2:27][CH:26]([CH3:31])[CH2:25][CH:24]([O:32][CH3:33])[CH:23]2[O:34][C:19]([OH:38])([CH:20]([CH3:37])[CH2:21][CH:22]2[O:35][CH3:36])[C:18](=[O:39])[C:17](=[O:40])[N:16]2[CH:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[C:10](=[O:41])[O:9][CH:8]([C:42]([CH3:60])=[CH:43][CH:44]2[CH2:49][CH2:48][CH:47]([O:50][Si](C(C)(C)C)(C)C)[CH:46]([O:58][CH3:59])[CH2:45]2)[CH:7]([CH3:61])[CH:6]([O:62][Si:63]([C:66]([CH3:69])([CH3:68])[CH3:67])([CH3:65])[CH3:64])[CH2:5][C:4]1=[O:70])[CH3:2].F>C(#N)C.C(OCC)(=O)C>[CH2:1]([CH:3]1[CH:29]=[C:28]([CH3:30])[CH2:27][CH:26]([CH3:31])[CH2:25][CH:24]([O:32][CH3:33])[CH:23]2[O:34][C:19]([OH:38])([CH:20]([CH3:37])[CH2:21][CH:22]2[O:35][CH3:36])[C:18](=[O:39])[C:17](=[O:40])[N:16]2[CH:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[C:10](=[O:41])[O:9][CH:8]([C:42]([CH3:60])=[CH:43][CH:44]2[CH2:49][CH2:48][CH:47]([OH:50])[CH:46]([O:58][CH3:59])[CH2:45]2)[CH:7]([CH3:61])[CH:6]([O:62][Si:63]([C:66]([CH3:67])([CH3:68])[CH3:69])([CH3:65])[CH3:64])[CH2:5][C:4]1=[O:70])[CH3:2]
Reactant: CCC1C=C(C)CC(C)CC(OC)C2OC(O)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C)=CC3CCC(O[Si](C)(C)C(C)(C)C)C(OC)C3)C(C)C(O[Si](C)(C)C(C)(C)C)CC1=O)C(C)CC2OC
Agent: F
Solvent: CCOC(C)=O
Solvent: CC#N
Product: CCC1C=C(C)CC(C)CC(OC)C2OC(O)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C)=CC3CCC(O)C(OC)C3)C(C)C(O[Si](C)(C)C(C)(C)C)CC1=O)C(C)CC2OC
Temperature: 25 °C
Reaction time: 4 h
Yield: 58.4 %

Procedure:
To a solution of 17-ethyl-1-hydroxy-14-(tert-butyldimethylsiloxy)-12-[2'-(4"-(tert-butyldimethylsiloxy)-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9 ]octacos-18-ene-2,3,10,16-tetraone (2.91 g) in acetonitrile (15 ml) was added a solution of 2% hydrogen fluoride in aqueous acetonitrile (2 ml), and the mixture stirred at room temperature. After 4 hours, the solution was diluted with ethyl acetate, extracted with saturated sodium bicarbonate solution and the organic phase dried over magnesium sulfate. Purification of the concentrate by flash chromatography on silica gel (ethyl acetate:hexane (1:1)+1% methanol) gave the title compound (1.51 g). (1H NMR was consistent with the desired structure).
Reaction SMILES: [NH:1]([C:16]([O:18][CH2:19][CH:20]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26]2[C:21]1=[CH:22][CH:23]=[CH:24][CH:25]=2)=[O:17])[C@@H:2]([C:13]([OH:15])=O)[CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1.[NH2:33][C@H:34]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:35][O:36][C:37]([CH3:40])([CH3:39])[CH3:38].Cl.C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>CN(C)C=O.C(N1CCOCC1)C>[NH:1]([C:16]([O:18][CH2:19][CH:20]1[C:21]2[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:27]2[C:32]1=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:17])[C@@H:2]([C:13]([NH:33][C@H:34]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:35][O:36][C:37]([CH3:40])([CH3:38])[CH3:39])=[O:15])[CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1
Reactant: CC(C)(C)OC[C@H](N)C(=O)OC(C)(C)C
Reactant: O=C(N[C@H](Cc1c[nH]c2ccccc12)C(=O)O)OCC1c2ccccc2-c2ccccc21
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CCN1CCOCC1
Agent: Cl
Solvent: CN(C)C=O
Product: CC(C)(C)OC[C@H](NC(=O)[C@@H](Cc1c[nH]c2ccccc12)NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)OC(C)(C)C

Procedure:
To a solution ob 17.1 g (40 mmol) of Fmoc-D-Trp-OH, 10.12 g of H-Ser(tBu)-OtBu.HCl and 5.4 g of HOBt in 100 ml of dimethylformamide, 5.2 ml of N-ethylmorpholine are added at 0° C. with stirring, followed by 8.8 g of DCC. After allowing to stir for 1 hour at 0° C. and 3 hours at room temperature, the precipitate is filtered off with suction and the filtrate is concentrated in vacuo. The residue is dissolved in ethyl acetate and washed successively with water, saturated NaHCO3 solution and water, dried over Na2SO4 and concentrated in vacuo. The solution of the resulting oil in 70 ml of diethyl ether is dropper with stirring into 700 ml of petroleum ether. The precipitate is filtered off with suction and dried.
Reaction SMILES: [H-].[Na+].[C:3]1([CH2:9][CH2:10][OH:11])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[NH2:12][C:13]1[N:14]=[C:15]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:16]([C:23]2[CH:24]=[CH:25][C:26](=[O:32])[N:27]([CH:29]([CH3:31])[CH3:30])[N:28]=2)=[N:17][C:18]=1S(C)(=O)=O.Cl>C(Cl)(Cl)Cl>[NH2:12][C:13]1[N:14]=[C:15]([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[C:16]([C:23]2[CH:24]=[CH:25][C:26](=[O:32])[N:27]([CH:29]([CH3:31])[CH3:30])[N:28]=2)=[N:17][C:18]=1[O:11][CH2:10][CH2:9][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: CC(C)n1nc(-c2nc(S(C)(=O)=O)c(N)nc2-c2ccccc2)ccc1=O
Reactant: OCCc1ccccc1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: CC(C)n1nc(-c2nc(OCCc3ccccc3)c(N)nc2-c2ccccc2)ccc1=O
Temperature: 27.5 °C
Reaction time: 0.5 h

Procedure:
To a suspension of NaH (60% in oil suspension) (31.1 mg) in 1,2-dimethyl-2-imidazolidinone (0.6 ml) was added 2-phenylethanol (0.094 ml) and the mixture was stirred at 25-30° C. for 30 minutes. 6-[5-Amino-6-(methylsulfonyl)-3-phenyl-2-pyrazinyl]-2-isopropyl-3(2H)-pyridazinone (150 mg) was added and the mixture was heated at 100-105° C. for 15 hours. To the mixture was added 0.1N HCl (3 ml) and an aqueous layer was removed by decantation to give a residue. The residue was dissolved in CHCl3, dried over MgSO4, concentrated under reduced pressure and purified by column chromatography on silica gel. By elution with a mixture of n-hexane and EtOAc (60:40 v/v) was obtained 6-[5-amino-3-phenyl-6-(2-phenylethoxy)-2-pyrazinyl]-2-isopropyl-3(2H)-pyridazinone as a solid (9 mg). By elution with a mixture of MeOH and EtOAc (1:99 v/v) was obtained 6-(5-amino-6-oxo-3-phenyl-1,6-dihydro-2-pyrazinyl)-2-isopropyl-3(2H)-pyridazinone as a solid (89 mg).
Reaction SMILES: B(Br)(Br)Br.C[O:6][C:7]1[CH:8]=[C:9]2[C:13](=[N:14][CH:15]=1)[NH:12][CH:11]=[CH:10]2.O>C(Cl)Cl>[OH:6][C:7]1[CH:8]=[C:9]2[C:13](=[N:14][CH:15]=1)[NH:12][CH:11]=[CH:10]2
Reactant: COc1cnc2[nH]ccc2c1
Agent: BrB(Br)Br
Solvent: O
Solvent: ClCCl
Product: Oc1cnc2[nH]ccc2c1
Temperature: -30 °C
Reaction time: 8 h
Yield: 70.6 %

Procedure:
Boron tribromide (0.506 μl, 5.35 mmol) in methylene chloride (1 ml) was added to a solution of 5-methoxy-7-azaindole (0.36 g, 2.43 mmol) in methylene chloride (25 ml) cooled at −30° C. The mixture was left to warm up to ambient temperature and was stirred overnight. The mixture was poured onto ice and water and the pH of the aqueous phase was adjusted to 6. The organic phase was separated and the aqueous phase was further extracted with ethyl acetate. The organic phases were combined, washed with brine, dried over magnesium sulphate and evaporated. The residue was purified by column chromatography eluting with increasingly polar mixtures of methylene chloride and methanol to give 5-hydroxy-7-azaindole (0.23 g, 71%).
Reaction SMILES: [CH:1]([OH:3])=O.C(OC(=O)C)(=O)C.[OH:11][NH:12][CH2:13][CH2:14][CH2:15][P:16](=[O:19])([OH:18])[OH:17].[CH2:20]([CH2:22][NH2:23])[OH:21]>C(O)C>[CH2:20]([CH2:22][NH2:23])[OH:21].[CH:1]([N:12]([CH2:13][CH2:14][CH2:15][P:16](=[O:17])([OH:19])[OH:18])[OH:11])=[O:3]
Reactant: O=P(O)(O)CCCNO
Reactant: O=CO
Solvent: NCCO
Solvent: CC(=O)OC(C)=O
Solvent: CCO
Product: O=CN(O)CCCP(=O)(O)O
Reaction time: 0.5 h

Procedure:
Formic acid (1.0 ml.) was added dropwise to acetic anhydride (1.2 ml.) at ambient temperature with stirring. The stirring was continued at the same temperature for 30 minutes and then 3-(N-hydroxyamino)propylphosphonic acid (1.51 g.) was added to the mixture. The reaction mixture was stirred at ambient temperature for 1.5 hours and concentrated under reduced pressure to give an oily residue, which was dissolved in ethanol (20 ml.). To the aqueous solution was added ethanolamine (0.61 g.) to precipitate an oil, which was separated by decantation and crystallized with ethanol (20 ml.) to give crystals. The crystals were separated by filtration, washed with ethanol and dried to give crystalline monoethanolamine salt of 3-(N-formyl-N-hydroxyamino)propylphosphonic acid (1.75 g.), a part (1.5 g.) of which was recrystallized from 90% aqueous ethanol to give the purified object compound (1.15 g). M.p. 139°-142° C.
Reaction SMILES: [SH:1][C:2]1[NH:3][CH:4]=[C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[N:6]=1.[C:12]([O-])([O-])=O.[K+].[K+].CI>CN(C=O)C>[CH3:12][S:1][C:2]1[NH:3][CH:4]=[C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[N:6]=1
Reactant: CCOC(=O)c1c[nH]c(S)n1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CN(C)C=O
Product: CCOC(=O)c1c[nH]c(SC)n1
Reaction time: 18 h

Procedure:
To a mixture of ethyl 2-mercapto-4-imidazole carboxylate (II) (49.82 g, 289 mmol) and K2CO3 (79.92 g, 579 mmol) in DMF (1500 mL) was added MeI (18.55 mL, 298 mmol) at room temperature, with stirring. After 18 hrs, it was filtered. The filtrate was concentrated under high vacuum to remove DMF. The residue was then filtered through a silica gel pad with EtOAc, and concentrated. PhMe (200 mL) was then added, followed by addition of Hexanes (1000 mL), precipitating III (50.5 g, 94%) as a yellow solid. 1H NMR (CDCl3, 400 MHz): 7.69 (s, 1H), 4.35 (q, J=7.1 Hz, 2H), 2.67 (s, 3H), 1.35 (t, J=7.1 Hz, 3H).
Reaction SMILES: [C:1]1([CH:7]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:8](Cl)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:17]([NH2:22])[CH2:18][CH2:19][C:20]#[CH:21]>>[CH2:17]([NH:22][C:8](=[O:9])[CH:7]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[CH2:18][CH2:19][C:20]#[CH:21]
Reactant: C#CCCCN
Reactant: O=C(Cl)C(c1ccccc1)c1ccccc1
Product: C#CCCCNC(=O)C(c1ccccc1)c1ccccc1

Procedure:
The title compound, white solid, m.p. 90° C. and MS: m/e=278.2 (M+H+) was prepared in accordance with the general method of example 1 from diphenylacetyl chloride and pent-4-ynyl-amine.
Reaction SMILES: C[C:2](C)([O-:4])C.[K+].C(=O)(OC)OC.[Cl:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[C:15]=1[CH:21]([OH:25])[C:22]([NH2:24])=[O:23].Cl>O.C(O)(C)(C)C>[Cl:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[C:15]=1[CH:21]1[O:25][C:2](=[O:4])[NH:24][C:22]1=[O:23]
Reactant: NC(=O)C(O)c1c(Cl)cccc1Cl
Reactant: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: CC(C)(C)O
Solvent: COC(=O)OC
Solvent: O
Product: O=C1NC(=O)C(c2c(Cl)cccc2Cl)O1
Temperature: 25 °C

Procedure:
Potassium tert-butoxide (5.16 g., 0.046 mole) was dissolved in 60 ml. of tert-butanol. Dimethyl carbonate (4.14 g., 0.046 mole) and then 2-(2,6-dichlorophenyl)-2-hydroxyacetamide (5 g., 0.023 mole) were added. The suspension was heated at reflux for 2 hours and cooled to room temperature. Hydrochloric acid (46 ml. of 1 N) and then 100 ml. of water were added, and the mixture extracted with three portions of methylene chloride. The combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated to dryness. Recrystallization of the residue from toluene gave purified 5-(2,6-dichlorophenyl)oxazolidine-2,4-dione (3.15 g., 50%; m.p. 151°-153° C.), ir (KBr) 1818, 1739, 1724, 1434, 1377 cm-1.
Reaction SMILES: [CH3:1][C:2]([CH2:4][C:5]([OH:7])=[O:6])=[O:3].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[O:26]1CC[CH2:28][CH2:27]1>>[CH3:28][C:27]([CH2:1][C:2]([CH2:4][C:5]([OH:7])=[O:6])=[O:3])=[O:26]
Reactant: CC(=O)CC(=O)O
Reactant: C1CCOC1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Product: CC(=O)CC(=O)CC(=O)O
Yield: 85.2 %

Procedure:
A solution of the diacetate from stage (c) (7 g) in tetrahydrofuran (150 ml) was treated with tetra-n-butylammonium fluoride (1.4 g) at room temperature for 18 h. Tlc (ether/light petroleum, 6:1) showed one major product with traces of slow moving products due to partial deacetylation. The mixture was concentrated, taken up in dry pyridine (50 ml) and treated acetic anhydride (7 ml) at room temperature for 3 h. Tlc ether/light petroleum (7:1) showed only one product. The reaction mixture was concentrated and was eluted from short column of silica gel (50 g) with ether/light petroleum (1:1) to give a crystalline product (4.3 g, 85.2%) identical with the product from Route 1, m.p. 133°-134° [α]D20 +116.3° (c 1.0, CHCl3).
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH2:11][O:12]C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[N:6]=1.O1CCOCC1>Cl>[CH3:1][O:2][CH2:3][CH2:4][C:5]1[N:6]=[C:7]([CH2:11][OH:12])[CH:8]=[CH:9][CH:10]=1
Reactant: COCCc1cccc(COC(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Agent: Cl
Solvent: C1COCCO1
Product: COCCc1cccc(CO)n1

Procedure:
A solution of 2-(2-methoxyethyl)-6-(triphenylmethoxy)methylpyridine (1.08 g, 2.64 mmol) in 4-M HCl in dioxan (10 mL, 40.0 mmol) was stirred for 4 h and concentrated in vacuo. The residue was partitioned between dichloromethane (15 mL) and saturated NaHCO3 solution (15 mL), the aqueous phase was extracted with dichloromethane (10 mL) and the combined organic phase was dried (MgSO4) and concentrated in vacuo to give 6-(2-methoxyethyl)pyridine-2-methanol. A solution of this product in dichloromethane (40 mL) at 0° C. was treated with triphenylphosphine (830 mg, 3.16 mmol) followed portion wise by carbon tetrabromide (1.31 g, 3.96 mmol), stirred for 1 h, concentrated in vacuo and purified by chromatography [SiO2; isohexane:EtOAc (4:1)] to give the title compound (303 mg, 50%) as a yellow oil; NMR δH (400 MHz, CDCl3) 7.60 (1H, t, J 7.5 Hz), 7.28 (1H, d, J 7.5 Hz), 7.13 (1H, d, J 7.5 Hz), 4.53 (2H, s), 3.76 (2H, t, J 6.5 Hz), 3.35 (3H, s) and 3.05 (2H, t, J 6.5 Hz).
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[C:3]([CH2:10][CH3:11])=[CH:4][C:5](OCC)=[O:6].[H-].C([Al+]CC(C)C)C(C)C.S(=O)(=O)(O)O>O1CCCC1>[F:1][C:2]([F:13])([F:12])[C:3]([CH2:10][CH3:11])=[CH:4][CH2:5][OH:6]
Reactant: CCOC(=O)C=C(CC)C(F)(F)F
Agent: CC(C)C[Al+]CC(C)C
Agent: O=S(=O)(O)O
Agent: [H-]
Solvent: C1CCOC1
Product: CCC(=CCO)C(F)(F)F
Reaction time: 2 h

Procedure:
To a solution of 10 g of a mixture of (E) and (Z) isomers of ethyl 3-trifluoromethyl-2-pentenoate in 100 ml of tetrahydrofuran was added dropwise 100 ml of diisobutylaluminum hydride (1.02M solution in hexane) under ice-cooling, and then stirred at the same temperature for 2 hours. To the reaction mixture was added diluted sulfuric acid and then extracted with t-butyl methyl ether. The organic layer was dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure to obtain crude 3-trifluoromethyl-2-penten-1-ol as a mixture of (E) and (Z) isomers.
Reaction SMILES: [C:1]([C:3]1[N:4]=[C:5]([O:13][CH2:14][C@@H:15]2[CH2:19][CH2:18][CH2:17][N:16]2[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C:6]2[C:11]([CH:12]=1)=[CH:10][CH:9]=[CH:8][CH:7]=2)#[N:2].CN1C(=O)CCC1.[NH:34]([C:36](OCC)=[O:37])[NH2:35]>CCOC(C)=O>[O:37]=[C:36]1[NH:34][N:35]=[C:1]([C:3]2[N:4]=[C:5]([O:13][CH2:14][C@@H:15]3[CH2:19][CH2:18][CH2:17][N:16]3[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C:6]3[C:11]([CH:12]=2)=[CH:10][CH:9]=[CH:8][CH:7]=3)[NH:2]1
Reactant: CCOC(=O)NN
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1COc1nc(C#N)cc2ccccc12
Solvent: CCOC(C)=O
Solvent: CN1CCCC1=O
Product: CC(C)(C)OC(=O)N1CCC[C@H]1COc1nc(-c2n[nH]c(=O)[nH]2)cc2ccccc12
Temperature: 175 °C

Procedure:
To a crude reaction mixture containing (S)-tert-butyl 2-(((3-cyanoisoquinolin-1-yl)oxy)methyl)pyrrolidine-1-carboxylate (0.562 g) was added NMP (2 mL) followed by ethyl hydrazinecarboxylate (0.663 g, 6.36 mmol). The reaction mixture was heated at 175° C. overnight and was subsequently cooled, diluted with EtOAc, and washed with brine. The organic layer was separated, dried over Na2SO4, and concentrated to give the title compound, which was used directly in the next step.
Reaction SMILES: Cl[CH2:2][C:3]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[O:5][N:4]=1.[I-:14].[Na+]>CC(C)=O.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[I:14][CH2:2][C:3]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[O:5][N:4]=1
Reactant: [I-]
Reactant: ClCc1noc(-c2ccccn2)n1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Na+]
Solvent: CC(C)=O
Product: ICc1noc(-c2ccccn2)n1

Procedure:
Step-2: The 2-(3-chloromethyl-[1,2,4]-oxadiazole-5-yl)-pyridine (0.550 g, 2.8 mmol) was dissolved in acetone (20 ml). To the clear solution, sodium iodide (0.843 g, 5.62 mmol) and tetra-n-butyl-ammonium iodide (0.259 g, 0.70 mmol) were added. The reaction mixture was refluxed for 2 hr. It was quenched by addition of water (20 ml) and extracted with ethyl acetate (2×25 ml). The combined organic layer was dried over Na2SO4 and evaporated under vacuum to yield 2-(3-Iodomethyl-[1,2,4]oxadiazole-5-yl)-pyridine in 90% (0.750 g) yield. MS: m/z: 288.1 (M+1).
Reaction SMILES: [Cl:1][C:2]1[C:14]([Cl:15])=[CH:13][CH:12]=[C:11]2[C:3]=1[C:4]1[CH2:5][CH2:6][CH2:7][C:8](=[O:26])[C:9]=1[N:10]2[S:16]([C:19]1[CH:25]=[CH:24][C:22]([CH3:23])=[CH:21][CH:20]=1)(=[O:18])=[O:17].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[F:37]NS(C1C=CC=CC=1)(=O)=O>C1COCC1>[Cl:1][C:2]1[C:14]([Cl:15])=[CH:13][CH:12]=[C:11]2[C:3]=1[C:4]1[CH2:5][CH2:6][CH:7]([F:37])[C:8](=[O:26])[C:9]=1[N:10]2[S:16]([C:19]1[CH:20]=[CH:21][C:22]([CH3:23])=[CH:24][CH:25]=1)(=[O:18])=[O:17]
Reactant: O=S(=O)(NF)c1ccccc1
Reactant: Cc1ccc(S(=O)(=O)n2c3c(c4c(Cl)c(Cl)ccc42)CCCC3=O)cc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: Cc1ccc(S(=O)(=O)n2c3c(c4c(Cl)c(Cl)ccc42)CCC(F)C3=O)cc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 33.5 %

Procedure:
To a solution of 5,6-dichloro-9-tosyl-2,3,4,9-tetrahydro-1H-carbazol-1-one (300 mg, 0.7 mmol) in anhydrous THF (10 mL), cooled to −78° C., LiHMDS (1.47 mL, 1.4 mmol, 1M solution in THF) was added slowly. The reaction mixture was slowly warmed to 0° C. and stirred for an additional 30 min. while maintaining the temperature at 0° C. The reaction mixture was then cooled to −78° C. and N-fluoro benzene sulfonamide (0.22 g, 0.9 mmol), dissolved in THF (3 mL), was added dropwise. The reaction mixture was slowly warmed to 0° C. and stirred for 15 min during which time the reaction was complete. The reaction was quenched with saturated NH4Cl and extracted with EtOAc (3×25 mL). The combined organic extracts were dried over Na2SO4 and concentrated under reduced pressure to give the crude compound which was purified by column chromatography [EtOAc-hexane (1:9) as eluant] to give the title compound (100 mg, 32%). 1H NMR (500 MHz, CDCl3, δ in ppm) 8.27 (d, J=9.5 Hz, 1H), 8.07 (d, J=8.5 Hz, 2H), 7.59 (d, J=9.5 Hz, 1H), 7.35 (d, J=8.5 Hz, 2H), 5.30-5.13 (m, 1H), 3.71-3.66 (m, 1H), 3.35-3.28 (m, 1H), 2.58-2.55 (m, 1H), 2.43 (s, 3H), 2.40-2.38 (m, 1H)
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[OH:11])[C:6]#[N:7].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[O:31]1[CH2:36][CH2:35][CH:34](O)[CH2:33][CH2:32]1.CC(OC(/N=N/C(OC(C)(C)C)=O)=O)(C)C>O1CCCC1.O.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[O:11][CH:34]1[CH2:35][CH2:36][O:31][CH2:32][CH2:33]1)[C:6]#[N:7]
Reactant: COc1cc(C#N)ccc1O
Reactant: OC1CCOCC1
Agent: CC(C)(C)OC(=O)/N=N/C(=O)OC(C)(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: O
Solvent: CCOC(C)=O
Product: COc1cc(C#N)ccc1OC1CCOCC1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
8 g 3-Methoxy-4-hydroxy-benzonitrile, 28.1 g triphenylphosphine and 5.48 g tetrahydro-4H-pyran-4-ol was suspended in 1 L tetrahydrofuran at 0° C. before 24.7 g di-tert-butylazodicarboxylate (DBAD) was added over 30 min. The reaction was warmed to ambient temperature and stirred for 2 d. After this time, the reaction was diluted with water and ethyl acetate. The organic phase was separated and then it was washed with 1N sodium hydroxide, water and saturated sodium chloride, dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. The residue was purified on silica gel chromatography (SiO2: heptane/ethyl acetate 8:2 to 7:3) to provide the title compound.
Reaction SMILES: Cl.[NH2:2][C:3]1[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=2)([OH:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1.Br[CH2:21][CH2:22][CH2:23]Br>C(O)C>[Cl:19][C:15]1[CH:14]=[C:13]([C:11]2([OH:12])[C:10]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=3[N:4]3[CH2:21][CH2:22][CH2:23][N:2]=[C:3]23)[CH:18]=[CH:17][CH:16]=1
Reactant: NC1=Nc2ccccc2C1(O)c1cccc(Cl)c1
Reactant: BrCCCBr
Agent: Cl
Solvent: CCO
Product: OC1(c2cccc(Cl)c2)C2=NCCCN2c2ccccc21

Procedure:
2-Amino-3-(m-chlorophenyl)-3H-indol-3-ol hydrochloride (2.3 g) is converted to its oily base then heated under reflux in ethanol (10 ml) with 1,3-dibromopropane (1.55 g) for 20 hours. On cooling the title compound is obtained as its hydrobromide, m.p. 270°-273°C (decomp.).
Reaction SMILES: [C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7]([O-:10])(=[O:9])=[O:8])=[CH:3][CH:2]=1.C([O:16][C:17]1[CH:22]=[CH:21][C:20]([S+:23]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[CH:19][CH:18]=1)(C)(C)C>O.C1(C)C=CC(S(O)(=O)=O)=CC=1.CO>[C:1]1([CH3:11])[CH:2]=[CH:3][C:4]([S:7]([O-:10])(=[O:8])=[O:9])=[CH:5][CH:6]=1.[OH:16][C:17]1[CH:22]=[CH:21][C:20]([S+:23]([C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[CH:19][CH:18]=1
Reactant: CC(C)(C)Oc1ccc([S+](c2ccccc2)c2ccccc2)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Solvent: CO
Solvent: O
Product: Oc1ccc([S+](c2ccccc2)c2ccccc2)cc1
Temperature: 80 °C
Reaction time: 5 h
Yield: 108 %

Procedure:
A mixture of 25 g of (4-tert-butyloxyphenyl)diphenylsulfonium p-toluenesulfonate, 0.5 g of p-toluenesulfonic acid monohydrate, and 75 g of methanol was stirred at 80° C. for 5 hours. The reaction solution was cooled to room temperature and concentrated in vacuum, to which 100 g of methylene chloride and 50 g of deionized water were added. The organic layer was separated, washed with water, and concentrated in vacuum. To the concentrate, 100 g of MIBK was added. This was concentrated in vacuum again, obtaining 24 g of the target compound, (4-hydroxyphenyl)diphenylsulfonium p-toluenesulfonate as oily matter. Yield 96%.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([C:44]1[CH:49]=[CH:48][C:47]([O:50][CH2:51][CH3:52])=[CH:46][CH:45]=1)[C:9]1[N:14]2[N:15]=[CH:16][CH:17]=[C:13]2[N:12]=[C:11]([NH:18][C@H:19]2[CH2:24][CH2:23][CH2:22][N:21]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:20]2)[C:10]=1[CH2:32][CH:33](O)[CH2:34][O:35][Si:36]([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:38])[CH3:37])=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]([C:44]1[CH:49]=[CH:48][C:47]([O:50][CH2:51][CH3:52])=[CH:46][CH:45]=1)[C:9]1[N:14]2[C:13](=[CH:17][CH:16]=[N:15]2)[N:12]=[C:11]2[C:10]=1[CH:32]=[C:33]([CH2:34][O:35][Si:36]([C:39]([CH3:40])([CH3:41])[CH3:42])([CH3:37])[CH3:38])[N:18]2[C@H:19]1[CH2:24][CH2:23][CH2:22][N:21]([C:25]([O:27][C:28]([CH3:29])([CH3:30])[CH3:31])=[O:26])[CH2:20]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]
Reactant: CCOc1ccc(N(C(=O)OC(C)(C)C)c2c(CC(O)CO[Si](C)(C)C(C)(C)C)c(N[C@H]3CCCN(C(=O)OC(C)(C)C)C3)nc3ccnn23)cc1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Product: CCOc1ccc(N(C(=O)OC(C)(C)C)c2c3cc(CO[Si](C)(C)C(C)(C)C)n([C@H]4CCCN(C(=O)OC(C)(C)C)C4)c3nc3ccnn23)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 40.6 %

Procedure:
To a methylene chloride (1 mL) solution containing tert-butyl (S)-3-{7-[tert-butoxycarbonyl-(4-ethoxyphenyl)amino]-6-[3-(tert-butyldimethylsilanyloxy)-2-hydroxypropyl]pyrazolo[1,5-a]pyrimidin-5-ylamino}piperidine-1-carboxylate (28.6 mg, 0.0495 mmol), Dess-Martin periodinane (25.2 mg, 0.0594 mmol) was added at 0° C., and the mixture was allowed to warm to room temperature and stirred for 3 hr. After the reaction, the reaction solution was concentrated, and the residue was purified with PTLC (30% ethyl acetate-hexane) to obtain the title compound (14.5 mg).
Reaction SMILES: C([O:3][C:4](=O)[CH2:5][N:6]1[CH:11]=[C:10]([CH3:12])[CH:9]=[CH:8][C:7]1=[O:13])C.O.[NH2:16][NH2:17]>C(O)C>[CH3:12][C:10]1[CH:9]=[CH:8][C:7](=[O:13])[N:6]([CH2:5][C:4]([NH:16][NH2:17])=[O:3])[CH:11]=1
Reactant: NN
Reactant: CCOC(=O)Cn1cc(C)ccc1=O
Solvent: O
Solvent: CCO
Product: Cc1ccc(=O)n(CC(=O)NN)c1
Yield: 92 %

Procedure:
As described for example 112a, (5-methyl-2-oxo-2H-pyridin-1-yl)-acetic acid ethyl ester in ethanol was reacted with hydrazine hydrate (1.2 equivalents) at rt for 16 h. The mixture was concentrated and crystallized from ethanol/diisopropylether and the compound was obtained as a white solid (yield: 92%). MS: m/e=204.1 [M+Na]+.