Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][S:5]([O:8][CH2:9][C:10]([CH3:26])([CH3:25])[C@@H:11]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20](OC)=[CH:19][CH:18]=1)[C:12]([OH:14])=[O:13])(=[O:7])=[O:6].[CH:27]1([O:33][C:34]([O:36][CH:37](Cl)[CH3:38])=[O:35])[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Ag+2]>[Cl:1][CH2:2][CH2:3][CH2:4][S:5]([O:8][CH2:9][C:10]([CH3:25])([CH3:26])[C@@H:11]([O:15][CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[C:12]([O:14][CH2:38][CH2:37][O:36][C:34]([O:33][CH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)=[O:35])=[O:13])(=[O:6])=[O:7]
Reactant: COc1ccc(CO[C@@H](C(=O)O)C(C)(C)COS(=O)(=O)CCCCl)cc1
Reactant: CC(Cl)OC(=O)OC1CCCCC1
Agent: [Ag+2]
Agent: O=C([O-])[O-]
Solvent: Cc1ccccc1
Product: CC(C)(COS(=O)(=O)CCCCl)[C@@H](OCc1ccccc1)C(=O)OCCOC(=O)OC1CCCCC1
Yield: 74.7 %

Procedure:
Following the general procedure for the preparation of acyloxyalkyl/alkoxycarbonyloxyalkyl carboxylic esters from carboxylic acids of Description 22, (2R)-4-[(3-chloropropyl)sulfonyloxy]-3,3-dimethyl-2-(phenylmethoxy)butanoic acid (11) (0.4 g, 1.0 mmol) dissolved in 5 mL of anhydrous toluene was reacted with 0.67 g (4.0 mmol) of 1-chloroethyl cyclohexyloxyformate in the presence of 0.55 g (2.0 mmol) of silver carbonate (Ag2CO3). After work-up, the crude product was purified by silica gel column chromatography using a mixture of ethyl acetate (EtOAc) and hexane (Hxn) (EtOAc/Hxn=1:4) as eluent to provide 0.41 g (71% yield) of the title compound (43a). Rf=0.40 (EtOAc/Hxn=1:4). 1H NMR (400 MHz, CDCl3, both diastereomers): δ=1.06-1.08 (m, 6H), 1.25-1.58 (br. m, 9H), 1.73-1.78 (br. m, 2H), 1.88-1.95 (br. m, 2H), 2.24-2.31 (m, 2H), 3.20-3.25 (m, 2H), 3.63-3.66 (m, 2H), 3.84-3.85 (2s, 1H), 3.94-3.97 (2d, J=9.2, 8.8 Hz, 1H), 4.19-4.23 (2d, J=9.2, 8.8 Hz, 1H), 4.33-4.38 (2d, J=11.2, 11.6 Hz, 1H), 4.55-4.70 (m, 2H), 6.81-6.87 (m, 1H), 7.31-7.37 (m, 5H) ppm. MS (ESI) m/z 571.05 (M+Na)+. The analytical data was consistent with the proposed structure.
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[CH2:4][CH2:5][OH:6].[H-].[Na+].[S:13](Cl)(=[O:16])(=[O:15])[NH2:14]>CN(C=O)C>[S:13](=[O:16])(=[O:15])([O:6][CH2:5][CH2:4][C:3]1[CH:7]=[CH:8][CH:9]=[CH:10][C:2]=1[CH3:1])[NH2:14]
Reactant: Cc1ccccc1CCO
Reactant: NS(=O)(=O)Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1ccccc1CCOS(N)(=O)=O
Yield: 43 %

Procedure:
A mixture of 2.65 g (0.019 mole) of 2-methylphenethyl alcohol in 10 ml DMF was added dropwise to a suspension of sodium hydride (1.1 g, 60% in oil; 0.08 mole) in 35 ml DMF at 0°-5° C. The suspension was stirred for 20 min under argon after which sulfamoyl chloride (2.86 g, 0.02 mole) was added portion wise at 0°-5° C. After stirring for 20 min the resultant suspension was poured into ice and extracted twice with Et2O. The combined organic phases were washed with saturated brine, dried over potassium carbonate and concentrated in vacuo to a syrup which was purified by preparative HPLC with hexane/EtOAc (1:1, v/v) as the eluant to give 1.76 g (43%) of the title compound as a solid, mp 50°-52° C.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:29]=[C:30]([N:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)[CH:31]=1)[C:5]([NH:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([O:18][C:19]2[CH:24]=[CH:23][N:22]=[C:21](S(C)(=O)=O)[N:20]=2)=[CH:10][CH:9]=1)=[O:6].[NH:38]1[CH2:43][CH2:42][CH2:41][CH:40]([OH:44])[CH2:39]1>>[F:1][C:2]1[CH:3]=[C:4]([CH:29]=[C:30]([N:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)[CH:31]=1)[C:5]([NH:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([O:18][C:19]2[CH:24]=[CH:23][N:22]=[C:21]([N:38]3[CH2:43][CH2:42][CH2:41][CH:40]([OH:44])[CH2:39]3)[N:20]=2)=[CH:10][CH:9]=1)=[O:6]
Reactant: OC1CCCNC1
Reactant: CS(=O)(=O)c1nccc(Oc2ccc(NC(=O)c3cc(F)cc(N4CCOCC4)c3)c3ccccc23)n1
Product: O=C(Nc1ccc(Oc2ccnc(N3CCCC(O)C3)n2)c2ccccc12)c1cc(F)cc(N2CCOCC2)c1

Procedure:
Compound is prepared from 3-fluoro-N-(4-{[2-(methylsulfonyl)pyrimidin-4-yl]oxy}-1-naphthyl)-5-morpholin-4-ylbenzamide and piperidin-3-ol according to conditions described in general procedure C. Mp: 180-181° C.; 1H NMR (400 MHz, DMSO-d6) δ 1.26-1.31 (m, 2 H), 1.54 (s, 2 H), 1.81-1.83 (m, 2 H), 2.70-2.82 (m, 2 H), 3.27 (t, J=4.4 Hz, 4 H), 3.36 (s, 2 H), 3.77 (t, J=4.8 Hz, 4 H), 4.22 (bs, 1 H), 4.82 (s, 1 H), 6.16 (d, J=5.1Hz, 1 H), 7.03-7.06 (m, 1 H), 7.26 (d, J=8.4 Hz, 1 H), 7.43 (d, J=8.0 Hz, 1 H), 7.50 (s, 1 H), 7.55-7.63 (m, 3 H), 7.84-7.87 (m, 1 H), 7.99-8.01 (m, 1 H), 8.25 (d, J=5.8 Hz, 1 H), 10.49 (s, 1 H).
Reaction SMILES: [H-].[Na+].[Na+].[I-].C[C:6]1([CH3:13])[O:10][CH:9]([CH2:11][OH:12])[CH2:8][O:7]1.S(C1C=CC(C)=CC=1)(O[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]/[CH:26]=[CH:27]\[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]CC)(=O)=O>CN(C=O)C.O>[CH2:6]([O:7][CH2:8][CH:9]([CH2:11][OH:12])[OH:10])[CH2:13][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]/[CH:24]=[CH:25]\[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33]
Reactant: CCCCCCCC/C=C\CCCCCCCCOS(=O)(=O)c1ccc(C)cc1
Reactant: CC1(C)OCC(CO)O1
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCCCCCCC/C=C\CCCCCCCCOCC(O)CO
Reaction time: 72 h

Procedure:
To a mixture of NaH (4.8 g, 120 mmol) and NaI (0.2 g) in dry DMF (20 mL) was added solketal (5.0 mL, 40 mmol) dropwise over a 30 min period. Once the effervescence had stopped, oleyl tosylate (Compound 13) (16.9 g, 40 mmol) was added and the reaction mixture was left for 3 days at 50° C. Then, H2O (10 mL) was added and the mixture was extracted with diethyl ether (2×100 mL), the combined organic phases were dried (MgSO4) and evaporated to dryness. The residue was taken up in THF (150 mL), 2M HCl was added until the solution turned turbid and the reaction was left to stir for 16 hours. The mixture was concentrated and subjected to silica-gel column chromatography [eluent: ethyl acetate/hexane, 50/50, v/v] to give 1-O-oleyl-rac-glycerol (Compound 20) as an oil.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:10]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[S:17][CH2:18][CH2:19][CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][N:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[O:34][CH3:35])[CH2:24][CH2:23]2)[C:9]([N+:36]([O-:38])=[O:37])=[C:8]([CH3:39])[NH:7][C:6]=1[NH2:40])=[O:4].FC(F)(F)S(O)(=O)=[O:44].ClC1C=CC=C(C(OO)=O)C=1.C(=O)(O)[O-].[Na+]>ClCCl>[CH3:1][O:2][C:3]([C:5]1[CH:10]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[S:17]([CH2:18][CH2:19][CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][N:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[O:34][CH3:35])[CH2:24][CH2:23]2)=[O:44])[C:9]([N+:36]([O-:38])=[O:37])=[C:8]([CH3:39])[NH:7][C:6]=1[NH2:40])=[O:4]
Reactant: COC(=O)C1=C(N)NC(C)=C([N+](=O)[O-])C1c1ccccc1SCCCCN1CCN(c2ccccc2OC)CC1
Reactant: O=S(=O)(O)C(F)(F)F
Agent: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: COC(=O)C1=C(N)NC(C)=C([N+](=O)[O-])C1c1ccccc1S(=O)CCCCN1CCN(c2ccccc2OC)CC1
Temperature: -10 °C
Reaction time: 2 h

Procedure:
To a 4-neck 500 ml round-bottom flask fitted with an addition funnel, thermometer and mechanical stirrer under a nitrogen atmosphere, was added 5.00 g of 2-amino-1,4-dihydro-4-(2-{4-[4-(2-methoxyphenyl)-1-piperazinyl]-butylthio}phenyl)-6-methyl-5-nitro-3-pyridinecarboxylic acid methyl ester and 120 ml of dichloromethane, followed by 1.73 ml of trifluoromethanesulfonic acid. The reaction mixture was cooled to -10° C. with an ice/acetone bath, and 1.88 g of 80% m-chloroperbenzoic acid in 120 ml of dichloromethane was added dropwise, maintaining -5° to -10° C. The reaction was stirred for an additional 2 hr. at -10° C. after the addition was complete. The reaction mixture was poured into conc. sodium bicarbonate, and the reaction flask was rinsed with acetone. The organic layer was separated, dried over magnesium sulfate, filtered and concentrated to an orange oil. The product (Ex. No. 2, Table 1) was isolated after column chromatography on silica gel, eluting with 20% methanol in ethyl acetate as an orange foam, 2.8 g. 1H-NMR (CDCl3) δ 1.84-2.05(m,2H); 2.03-2.05(m,2H); 2.36(s,3H); 2.55(t,2H,J=7 Hz); 2.71(br s,4H); 3.00-3.18(br s,6H); 3.61(s,3H); 3.85(s,3H); 5.76(s,1H); 6.70(br s,2H); 6.83-7.03(m,4H); 7.28-7.41(m,4H); 7.82-7.86(m,1H). Mass spectrum: 584 (M+1).
Reaction SMILES: [CH3:1][CH:2]([CH3:19])[C:3]([O:5][C@H:6]([C@H:9]1[O:18][C@@H:12]2[O:13][C:14]([CH3:17])(C)[O:15][C@@H:11]2[CH2:10]1)[CH2:7][CH3:8])=[O:4].[C:20]([O:23]C(=O)C)(=[O:22])[CH3:21].C(O)(=O)C.S(=O)(=O)(O)O>C(Cl)Cl>[CH3:19][CH:2]([CH3:1])[C:3]([O:5][C@H:6]([C@@H:9]1[CH2:10][C@@H:11]([O:15][C:14](=[O:13])[CH3:17])[C@@H:12]([O:23][C:20](=[O:22])[CH3:21])[O:18]1)[CH2:7][CH3:8])=[O:4]
Reactant: CC(=O)OC(C)=O
Reactant: CC[C@H](OC(=O)C(C)C)[C@@H]1C[C@H]2OC(C)(C)O[C@H]2O1
Agent: O=S(=O)(O)O
Solvent: CC(=O)O
Solvent: ClCCl
Product: CC[C@H](OC(=O)C(C)C)[C@@H]1C[C@@H](OC(C)=O)[C@@H](OC(C)=O)O1
Temperature: 25 °C
Reaction time: 8 h
Yield: 19.2 %

Procedure:
To a stirred solution of [(1S)-1-[(3aR,5S,6aR)-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-5-yl]propyl] 2-methylpropanoate (compound 42a, 470 mg, 1.73 mmol), acetic anhydride (0.81 mL, 8.64 mmol) and acetic acid (0.51 mL, 8.64 mmol) in DCM (10 mL) was added concentrated sulfuric acid (18.4 μL, 0.17 mmol). The resulting mixture was stirred at room temperature overnight. The resulting mixture was concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 0-20% EtOAc in petroleum ether) to afford 105 mg of [(1S)-1-[(2S,4R,5R)-4,5-diacetoxytetrahydrofuran-2-yl]propyl] 2-methylpropanoate (compound 42b).
Reaction SMILES: [Cl:1][C:2]1[C:3]2[CH:10]=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Br:11]N1C(=O)CCC1=O.CO>CN(C=O)C>[Br:11][C:10]1[C:3]2[C:2]([Cl:1])=[N:7][CH:6]=[N:5][C:4]=2[NH:8][CH:9]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: Clc1ncnc2[nH]ccc12
Solvent: CN(C)C=O
Solvent: CO
Product: Clc1ncnc2[nH]cc(Br)c12
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a solution of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (4-1) (1.53 g, 10.0 mmol) in DMF (20 mL) was added N-bromosuccinimide (1.78 g, 10.0 mmol) in DMF (10 mL) dropwise at 0° C. The reaction mixture was stirred at 0° C. for 30 min and then at room temperature for 1 h. Methanol (25 mL) was added, and the reaction mixture was stirred for an additional 1 h. The solvent was evaporated and the residue was crystallized from methanol to give the title compound as white solid.
Reaction SMILES: C[Mg]Br.[CH3:4]I.[CH3:6][C:7]1[CH:8]=[C:9]([CH:16]=[CH:17][CH:18]=1)[O:10][CH2:11][CH2:12][C:13](=[O:15])[CH3:14]>CCOCC>[CH3:14][C:13]([OH:15])([CH2:12][CH2:11][O:10][C:9]1[CH:16]=[CH:17][CH:18]=[C:7]([CH3:6])[CH:8]=1)[CH3:4]
Reactant: CI
Reactant: CC(=O)CCOc1cccc(C)c1
Agent: C[Mg]Br
Solvent: CCOCC
Product: Cc1cccc(OCCC(C)(C)O)c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of methyl magnesium bromide in ether (50 mL), prepared from Mg (572 mg, 23.56 mmol) and MeI (3.34 g, 23.56 mmol), was added 4-(3-methylphenoxy)-2-butanone (2.1 g, 11.78 mmol) in 10 mL ether. The solution was stirred at room temperature for 30 minutes, after which quenched with water and dil. Hydrochloric acid. The organic layer was separated, dried over sodium sulfate, filtered through a silica plug. Colorless syrup 1.91 g (83%).
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[CH:10]=[CH:9][N:8]([S:11]([C:14]3[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=3)(=[O:13])=[O:12])[C:6]=2[N:7]=1.[NH2:22][C:23]1[CH:31]=[C:30]([F:32])[C:29]([F:33])=[CH:28][C:24]=1[C:25]([NH2:27])=[O:26]>>[Cl:1][C:2]1[N:3]=[C:4]([NH:22][C:23]2[CH:31]=[C:30]([F:32])[C:29]([F:33])=[CH:28][C:24]=2[C:25]([NH2:27])=[O:26])[C:5]2[CH:10]=[CH:9][N:8]([S:11]([C:14]3[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=3)(=[O:13])=[O:12])[C:6]=2[N:7]=1
Reactant: Cc1ccc(S(=O)(=O)n2ccc3c(Cl)nc(Cl)nc32)cc1
Reactant: NC(=O)c1cc(F)c(F)cc1N
Product: Cc1ccc(S(=O)(=O)n2ccc3c(Nc4cc(F)c(F)cc4C(N)=O)nc(Cl)nc32)cc1

Procedure:
Using General Protocol II and starting with 2,4-dichloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidine (3.0 g, 8.8 mmol) and 2-amino-4,5-difluorobenzamide (4.15 g, 23.9 mmol), 2-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-4,5-difluorobenzamide was isolated as a white solid (1.80 g, 43% Yield); 1H NMR (400 MHz, DMSO-d6) δ ppm 2.34 (s, 3H), 6.67 (d, J=4.03 Hz, 1 H), 7.46 (d, J=8.61 Hz, 2 H), 7.76 (d, J=4.03 Hz, 1 H), 7.92-8.01 (m, 4 H), 8.35 9s, 1 H), 8.55 (dd, J=13.55, 7.69 Hz, 1 H), 12.50 (s, 1 H).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([N:10]2[CH2:15][CH2:14][C@@:13]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)([CH2:16][CH2:17][CH2:18][OH:19])[O:12][C:11]2=[O:27])[CH3:9])=[CH:4][CH:3]=1.[CH3:28][O:29][C:30]1[N:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1>>[F:26][C:23]1[CH:24]=[CH:25][C:20]([C@:13]2([CH2:16][CH2:17][CH2:18][OH:19])[O:12][C:11](=[O:27])[N:10]([C@H:8]([C:5]3[CH:6]=[CH:7][C:2]([C:33]4[CH:34]=[N:35][C:30]([O:29][CH3:28])=[CH:31][CH:32]=4)=[CH:3][CH:4]=3)[CH3:9])[CH2:15][CH2:14]2)=[CH:21][CH:22]=1
Reactant: C[C@@H](c1ccc(Br)cc1)N1CC[C@](CCCO)(c2ccc(F)cc2)OC1=O
Reactant: COc1ccc(B(O)O)cn1
Product: COc1ccc(-c2ccc([C@H](C)N3CC[C@](CCCO)(c4ccc(F)cc4)OC3=O)cc2)cn1

Procedure:
The title compound was prepared from (R)-3-((S)-1-(4-bromophenyl)ethyl)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-1,3-oxazinan-2-one and 6-methoxypyridine-3-boronic acid following a procedure analogous to that described in Example 1 Step 2. LC-MS Method 2 tR=1.3 min, m/z=487.1; 1H NMR (CD3OD) 1.25-1.37 (m, 1H), 1.55 (d, 3H), 1.61 (m, 1H), 1.95 (m, 2H), 2.17-2.28 (m, 1H), 2.36 (m, 1H), 2.48 (m, 1H), 3.12 (m, 1H), 3.48 (m, 2H), 3.94 (s, 3H), 5.58 (m, 1H), 6.86 (d, 1H), 7.07 (m, 4H), 7.35 (m, 4H), 7.86 (dd, 1H), 8.28 (s, 1H).
Reaction SMILES: [C:1]([NH:4][C:5]1[C:6]([I:20])=[C:7]([C:11]([I:19])=[C:12]([NH:15][C:16](=[O:18])[CH3:17])[C:13]=1[I:14])[C:8](Cl)=[O:9])(=[O:3])[CH3:2].Cl.[CH2:22]([O:24][C:25](=[O:35])[C@H:26]([CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[NH2:27])[CH3:23]>>[CH2:22]([O:24][C:25](=[O:35])[C@H:26]([CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[NH:27][C:8](=[O:9])[C:7]1[C:6]([I:20])=[C:5]([NH:4][C:1](=[O:3])[CH3:2])[C:13]([I:14])=[C:12]([NH:15][C:16](=[O:18])[CH3:17])[C:11]=1[I:19])[CH3:23]
Reactant: CCOC(=O)[C@@H](N)Cc1ccccc1
Reactant: CC(=O)Nc1c(I)c(NC(C)=O)c(I)c(C(=O)Cl)c1I
Agent: Cl
Product: CCOC(=O)[C@H](Cc1ccccc1)NC(=O)c1c(I)c(NC(C)=O)c(I)c(NC(C)=O)c1I

Procedure:
Following the procedure of example 13, 60 g (75%) of the product was synthesized from 63.2 g (0.1 Mol) 3,5-diacetamido-2,4,6-triiodobenzoyl chloride and 33.5 g (0.15 Mol) L-phenylalanine ethyl ester hydrochloride.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:26]=[CH:27][C:28]=1[O:29][CH3:30])/[CH:6]=[CH:7]/[C:8]1[N:16]([CH3:17])[C:15]2[C:14](=[O:18])[N:13]([CH2:19][CH2:20][CH3:21])[C:12](=[O:22])[N:11]([CH2:23][CH2:24][CH3:25])[C:10]=2[N:9]=1>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:26]=[CH:27][C:28]=1[O:29][CH3:30])/[CH:6]=[CH:7]\[C:8]1[N:16]([CH3:17])[C:15]2[C:14](=[O:18])[N:13]([CH2:19][CH2:20][CH3:21])[C:12](=[O:22])[N:11]([CH2:23][CH2:24][CH3:25])[C:10]=2[N:9]=1
Reactant: CCCn1c(=O)c2c(nc(/C=C/c3ccc(OC)c(OC)c3)n2C)n(CCC)c1=O
Solvent: CO
Product: CCCn1c(=O)c2c(nc(/C=C\c3ccc(OC)c(OC)c3)n2C)n(CCC)c1=O
Yield: 56.6 %

Procedure:
Compound 1 (1.00 g, 2.42 mmol) obtained in Reference Example 1 was dissolved in 1.6 L of methanol, and the solution was irradiated with sunlight for 5 hours. After evaporation under reduced pressure, the residue was purified by high performance liquid chromatography (column: YMC Pack ODS-A, SH-365-10, S-10; 30 mm.O slashed.×500 mm, flow rate: 90 ml/min, detection: UV 246 nm) to give 565 mg (yield 57%) of Compound 186 as white needles.
Reaction SMILES: [C:1]([CH:5]1[CH2:17][C:16]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]([CH2:18][CH2:19][N:20]3[CH2:24][CH2:23][CH2:22][CH2:21]3)[C:8]=2[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].OO.[Mn]([O-])(=O)(=O)=[O:28].[K+]>CO.O>[C:1]([CH:5]1[CH2:17][C:16]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]([CH2:18][CH2:19][N+:20]3([O-:28])[CH2:21][CH2:22][CH2:23][CH2:24]3)[C:8]=2[CH2:7][CH2:6]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: O=[Mn](=O)(=O)[O-]
Reactant: CC(C)(C)C1CCc2c(c3ccccc3n2CCN2CCCC2)C1
Agent: OO
Agent: [K+]
Solvent: O
Solvent: CO
Product: CC(C)(C)C1CCc2c(c3ccccc3n2CC[N+]2([O-])CCCC2)C1
Temperature: 0 °C
Reaction time: 72 h

Procedure:
The product of Example 1 as free base (22.25g) in methanol (300 ml) was cooled to 0° (ice/water bath). Aqueous 30% w/v hydrogen peroxide (31.4g) was added dropwise over about 15 minutes, with cooling and stirring. The mixture was kept at ambient temperature for 3 days, and the excess hydrogen peroxide was then decomposed with a trace of potassium permanganate. The mixture was evaporated to dryness and the residue was dissolved in hot isopropanol (40 ml). Water (500 ml) was added with stirring and the mixture was refrigerated overnight, yielding a precipitate which was dissolved in hot water, filtered, and cooled, yielding a precipitate of 14.5g of 1-[2-(3-tert-butyl-1,2,3,4-tetrahydrocarbazole-9-yl) ethyl]pyrrolidine-N-oxide quarter-hydrate, m.p. 163-5°C.
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH2:3][C@H:2]1[CH2:6][N:7]1[CH2:11][CH2:10][CH2:9][CH2:8]1.CN1CCOCC1.[Cl:19][C:20]1[CH:37]=[CH:36][C:23]2[NH:24][C:25]([C:27]3[CH:35]=[CH:34][C:30]([C:31](Cl)=[O:32])=[CH:29][CH:28]=3)=[N:26][C:22]=2[CH:21]=1>ClCCl>[Cl:19][C:20]1[CH:37]=[CH:36][C:23]2[NH:24][C:25]([C:27]3[CH:28]=[CH:29][C:30]([C:31]([N:1]4[CH2:5][CH2:4][CH2:3][CH:2]4[CH2:6][N:7]4[CH2:11][CH2:10][CH2:9][CH2:8]4)=[O:32])=[CH:34][CH:35]=3)=[N:26][C:22]=2[CH:21]=1
Reactant: O=C(Cl)c1ccc(-c2nc3cc(Cl)ccc3[nH]2)cc1
Reactant: C1CN[C@H](CN2CCCC2)C1
Solvent: CN1CCOCC1
Solvent: ClCCl
Product: O=C(c1ccc(-c2nc3cc(Cl)ccc3[nH]2)cc1)N1CCCC1CN1CCCC1

Procedure:
To a stirring solution of (S)-(+)-1-(2-pyrrolidinylmethyl)pyrrolidine (11.0 mmol) and n-methylmorpholine (1.0 mmol) in dichloromethane (0.10M), slowly add the product from 4-(5-Chloro-1H-benzoimidazol-2-yl)-benzoyl chloride (1.0 mmol) diluted in dichloromethane. Stir reaction at room temperature for two hours. After this time wash the reaction with saturated aqueous sodium bicarbonate while extracting with 10% isopropanol/dichloromethane. Concentrate the organics in vacuo. Purify via radial chromatography eluting with 2M ammonia in methanol and dichloromethane. MS (m/e): 409.3 (M+1)
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[O:3][C:4]1[CH:9]=[CH:8][C:7]([NH2:10])=[CH:6][CH:5]=1.C(O[CH:16]1[CH2:20][CH2:19][CH:18](OCC)O1)C>C(O)(=O)C>[F:1][C:2]([F:11])([F:12])[O:3][C:4]1[CH:5]=[CH:6][C:7]([N:10]2[CH:16]=[CH:20][CH:19]=[CH:18]2)=[CH:8][CH:9]=1
Reactant: CCOC1CCC(OCC)O1
Reactant: Nc1ccc(OC(F)(F)F)cc1
Solvent: CC(=O)O
Product: FC(F)(F)Oc1ccc(-n2cccc2)cc1
Yield: 81 %

Procedure:
The compound was prepared according to Colotta et al. J. Med. Chem. 2006, 49, 6015. A solution of 4-trifluoromethoxyphenyl amine (500 milligrams (mg), 2.82 millimoles (mmol), 1.00 equivalent (eq)) and 2,5-diethoxy tetrahydrofuran (452 mg, 2.82 mmol, 1.00 eq) in glacial acetic acid (20 milliliters (mL)) was heated at 90° C. for 1 hour (h) before being dried onto silica gel. The residue was then slurried in refluxing hexane, filtered hot, and concentrated to dryness affording the desired intermediate (519 mg, 81%).
Reaction SMILES: [CH3:1][C:2]([O:14][Si](C)(C)C)([CH3:13])[C:3]#[C:4][C:5]([C:7]1[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=1)=[O:6].CC1C=CC(S(O)(=O)=O)=CC=1>C(Cl)Cl.O>[OH:14][C:2]([CH3:13])([CH3:1])[C:3]#[C:4][C:5]([C:7]1[CH:8]=[CH:9][N:10]=[CH:11][CH:12]=1)=[O:6]
Reactant: CC(C)(C#CC(=O)c1ccncc1)O[Si](C)(C)C
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: ClCCl
Solvent: O
Product: CC(C)(O)C#CC(=O)c1ccncc1
Reaction time: 1 h
Yield: 72.1 %

Procedure:
To a stirred solution of 4-methyl-1-(pyridin-4-yl)-4-(trimethylsilyloxy)pent-2-yn-1-one (3.0 g, 11.0 mmol) in DCM (60 mL) was added PTSA (2.62 g, 13.0 mmol) at RT and the reaction mixture was stirred for 1 h. The reaction mixture was diluted with water (10 mL), the organic layer was washed with a saturated NaHCO3 solution, water, dried over Na2SO4, filtered and then concentrated in vacuo to afford 4-hydroxy-4-methyl-1-(pyridin-4-yl)pent-2-yn-1-one (1.5 g, 69%) as an oil.
Reaction SMILES: Br[C:2]([CH3:7])([CH3:6])[C:3]([OH:5])=[O:4].[Al+3].[Cl-].[Cl-].[Cl-].Cl.O.[CH:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>>[CH3:6][C:2]([CH3:7])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:3]([OH:5])=[O:4]
Reactant: CC(C)(Br)C(=O)O
Reactant: c1ccccc1
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: O
Product: CC(C)(C(=O)O)c1ccccc1
Temperature: 5 °C

Procedure:
Molten alpha-bromoisobutyric acid, 328 g, 2 moles, was added to a 5-L flask equipped with a reflux condenser and large magnetic stirrer. Anhydrous benzene 2000 mL, was added to the flask, followed by fresh anhydrous AlCl3, 900 g, 6.75 moles, in small portions. The solution was then slowly heated to the reflux temperature and at this time the exit of the reflux condenser was connected to a flowing-water HBr trap. The mixture was heated a total of 24 hours without interruption. The reaction mixture was then cooled to ca. 5° C. and treated with 2 L of 50/50 (by volume) conc. HCl/H2O to decompose the catalyst complex. The benzene layer was then separated, washed once with ice-cold H2O (1200 mL) and twice with dilute aqueous sodium hydroxide. The aqueous sodium hydroxide extracts were combined, heated to 80° C. to drive out any physically trapped benzene and decolorized with activated charcoal. After filtration through diatomaceous earth filter aid ("Celite") the aqueous basic filtrate was neutralized slowly with conc. HCl. The precipitated acid was filtered, washed with a minimum amount of ice-cold water, and dried in a vacuum oven at 25°-30° C. The crude yield was 209 g (65%), and the melting point at this stage was 75.5°-77° C. The crude acid was recrystallized from n-heptane (450 mL for ca. 200 g acid). The final yield was 180 g of mp=76°-78°.
Reaction SMILES: C1([CH:7]2[C:12](=S(=O)=O)[CH:11]=[CH:10][CH:9]=[C:8]2[C:16](=[CH2:21])[C:17]([O:19][CH3:20])=[O:18])C=CC=CC=1.[CH2:22]([SnH:26]([CH2:31][CH2:32][CH2:33][CH3:34])[CH2:27][CH2:28][CH2:29][CH3:30])[CH2:23][CH2:24][CH3:25].N(C(C)(C)C#N)=NC(C)(C)C#N>C1CCCCC1>[C:8]1([C:16](=[CH:21][Sn:26]([CH2:27][CH2:28][CH2:29][CH3:30])([CH2:31][CH2:32][CH2:33][CH3:34])[CH2:22][CH2:23][CH2:24][CH3:25])[C:17]([O:19][CH3:20])=[O:18])[CH:7]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: CCCC[SnH](CCCC)CCCC
Reactant: C=C(C(=O)OC)C1=CC=CC(=S(=O)=O)C1c1ccccc1
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: C1CCCCC1
Product: CCCC[Sn](C=C(C(=O)OC)c1ccccc1)(CCCC)CCCC
Temperature: 25 °C

Procedure:
Combine 2-phenyl-3-sulfonlyphenyl-propenoic acid, methyl ester (41.0 g, 136 mmol) and tri-n-butyltin hydride (79.0 g, 271 mmol) in cyclohexane (900 mL). Add 2,2'-azobisisobutyronitrile (AIBN) (0.7 g, 4.3 mmol) and heat to reflux for 3 hours. Cool to ambient temperature and evaporate in vacuo. Chromatograph on silica gel eluting with 20% ethyl acetate/hexane. Evaporate the product containing fractions and chromatograph on silica gel eluting sequentially with 5% ethyl acetate/hexane and 10% ethyl acetate/hexane to give the title compound and a clear oil.