Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: I[CH2:2][C:3]([O:5][CH2:6][C:7]1[C:8](=[O:28])[N:9]2[C:21](=[CH:22][C:23]=1[C:24](=[O:27])[CH2:25][CH3:26])[C:12]1=[N:13][C:14]3[C:19]([CH:20]=[C:11]1[CH2:10]2)=[CH:18][CH:17]=[CH:16][CH:15]=3)=[O:4].[NH:29]([CH3:31])[CH3:30].C(Cl)[Cl:33]>>[ClH:33].[CH3:30][N:29]([CH2:2][C:3]([O:5][CH2:6][C:7]1[C:8](=[O:28])[N:9]2[C:21](=[CH:22][C:23]=1[C:24](=[O:27])[CH2:25][CH3:26])[C:12]1=[N:13][C:14]3[C:19]([CH:20]=[C:11]1[CH2:10]2)=[CH:18][CH:17]=[CH:16][CH:15]=3)=[O:4])[CH3:31]
Reactant: CCC(=O)c1cc2n(c(=O)c1COC(=O)CI)Cc1cc3ccccc3nc1-2
Reactant: CNC
Reactant: ClCCl
Product: CCC(=O)c1cc2n(c(=O)c1COC(=O)CN(C)C)Cc1cc3ccccc3nc1-2
Product: Cl

Procedure:
A suspension of 8-[[(iodoacetyl)oxy]methyl]-7-(1-oxopropyl)indolizino[1,2-b]quinolin-9(11H)-one (48.8 mg, 0.098 mmol) in dry CH2Cl2 (5.0 mL) was covered by an atmosphere of (CH3)2NH (balloon). Within a few min the solid had dissolved and after 5 min the reaction was stripped to dryness. The residue was dissolved in CH2Cl2, washed first with 5% aqueous NaHCO3 and then with H2O, and dried over Na2SO4. The solvent was removed in vacuo, and the residue was suspended in H2O (20 mL) to which was added 1N HCl (100 μL) to dissolve most of the solid. After filtration, lyophilization gave the title compound. 1H NMR (CDCl3 /MeOH-d4) d 8.47 (s, 1H), 8.23 (d, J=8.3 Hz, 1H), 7.98 (d, J=7.5 Hz, 1H), 7.87 (m, 1H), 7.71 (m, 1H), 7.44 (s, 1H), 5.38 (s, 2H), 5.35 (s, 2H), 3.95 (s, 2H), 3.05 (s, 6H), 3.02 (q, J=7.1 Hz, 2H), 1.27 (t, J=7.1 Hz, 3H). Anal. Calcd for C23H23N3O4.HCl.7/4 H2O: C, 58.35; H, 5.86; N, 8.88. Found: C, 58.26; H, 5.51; N, 8.68.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][C:7]([O:11][S:12]([C:15]([F:18])([F:17])[F:16])(=[O:14])=[O:13])=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.N1C=CC=CC=1.[Br:25]Br>C(Cl)(Cl)(Cl)Cl>[Br:25][C:3]1[CH:2]=[N:1][C:10]2[C:5]([CH:4]=1)=[CH:6][C:7]([O:11][S:12]([C:15]([F:18])([F:16])[F:17])(=[O:13])=[O:14])=[CH:8][CH:9]=2
Reactant: BrBr
Reactant: O=S(=O)(Oc1ccc2ncccc2c1)C(F)(F)F
Solvent: ClC(Cl)(Cl)Cl
Solvent: c1ccncc1
Product: O=S(=O)(Oc1ccc2ncc(Br)cc2c1)C(F)(F)F
Temperature: 25 °C
Yield: 26.1 %

Procedure:
To a mixture of trifluoromethanesulfonic acid quinolin-6-yl ester (3.88 g, 14 mmol) and pyridine (2.26 mL, 28 mmol) in CCl4 (50 mL) was added bromine (0.86 mL, 16.8 mmol) dropwise. The mixture was heated to reflux for 2 hrs and cooled to room temperature. The liquid in the flask was decanted and washed with NaHCO3 and water. The dark solid on the bottom of the flask was treated with NaHCO3 and dichloromethane. The combined organic layers were washed with water again and dried before being evaporated to dryness. The crude product was purified by flash column chromatography eluting with petroleum ether/ethyl acetate (10/1˜1/1) to give 1.3 g of trifluoromethanesulfonic acid 3-bromo-quinolin-6-yl ester: 1H NMR (300 MHz, CDCl3) δ: 7.62 (m, 1H), 7.68 (d, 1H), 8.20 (d, 1H), 8.36 (m, 1H), 8.98 (d, 1H); MS (m/z) 356 [M+H]+.
Reaction SMILES: [N:1]1[CH:5]=[N:4][N:3]([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=2[OH:12])[N:2]=1.[OH-].[Na+].I[CH3:16]>CN(C)C=O.O.C(OCC)(=O)C>[CH3:16][N:1]1[CH:5]=[N:4][N:3]([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=2[OH:12])[NH:2]1
Reactant: Oc1ccccc1-n1ncnn1
Reactant: CI
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CN1C=NN(c2ccccc2O)N1
Temperature: 25 °C
Reaction time: 15 h
Yield: 65.2 %

Procedure:
2-(Tetrazol-3-yl)phenol (32.8 g, 202.3 mmol) is dissolved in dimethylformamide (100 mL) and water (25 mL) and cooled in ice. Sodium hydroxide (8.49 g, 212.3 mmol) in water (20 mL) is added and the solution is warmed to ambient temperature. After thirty minutes, iodomethane (31.58 g, 222.5 mmol) is added neat. The solution is stirred for 15 hours then diluted with ethyl acetate (300 mL) and water (500 mL). The aqueous layer is washed three times with ethyl acetate (300 mL) and the organic layers are combined, washed three times with water (1 L), once with brine (1.2 L), dried over magnesium sulfate, filtered and concentrated in vacuo. The solid is purified by flash column chromatography (80% hexane:20% ethyl acetate gradient to 50% hexane:50% ethyl acetate as an eluent) to give 23.5 g of 2-(1-methyltetrazol-3-yl)phenol (66%).
Reaction SMILES: C1(P(=O)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.C([S:43][CH:44]([CH2:73][N:74]1[CH2:79][CH2:78][O:77][CH2:76][CH2:75]1)[CH2:45][NH:46][C:47]([C:49]1[NH:50][C:51]2[C:56]([CH:57]=1)=[CH:55][C:54]([O:58][C:59]([F:62])([F:61])[F:60])=[CH:53][C:52]=2[N:63]([CH3:72])[S:64]([C:67]1[S:68][CH:69]=[CH:70][CH:71]=1)(=[O:66])=[O:65])=O)C1C=CC=CC=1.CSC>ClCCl.O>[CH3:72][N:63]([C:52]1[CH:53]=[C:54]([O:58][C:59]([F:62])([F:60])[F:61])[CH:55]=[C:56]2[C:51]=1[NH:50][C:49]([C:47]1[S:43][CH:44]([CH2:73][N:74]3[CH2:79][CH2:78][O:77][CH2:76][CH2:75]3)[CH2:45][N:46]=1)=[CH:57]2)[S:64]([C:67]1[S:68][CH:69]=[CH:70][CH:71]=1)(=[O:65])=[O:66]
Reactant: CN(c1cc(OC(F)(F)F)cc2cc(C(=O)NCC(CN3CCOCC3)SCc3ccccc3)[nH]c12)S(=O)(=O)c1cccs1
Agent: O=P(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Solvent: ClCCl
Solvent: O
Solvent: CSC
Product: CN(c1cc(OC(F)(F)F)cc2cc(C3=NCC(CN4CCOCC4)S3)[nH]c12)S(=O)(=O)c1cccs1
Reaction time: 0.17 h
Yield: 44.7 %

Procedure:
To a solution of triphenylphosphine oxide (670 mg) in dichloromethane (15 mL) was added trifluoromethanesulfonic anhydride (340 mg) under ice-cooling, and the mixture was stirred for 10 min. A solution of N-[2-(benzylthio)-3-morpholinopropyl]-7-[methyl(2-thienylsulfonyl)amino]-5-(trifluoromethoxy)-1H-indole-2-carboxamide (400 mg) and dimethylsulfide (40 mg) in dichloromethane (15 mL) was added dropwise to the reaction mixture under ice-cooling, and the mixture was stirred for 2 hr under ice-cooling. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4), and concentrated. The obtained residue was subjected to basic silica gel column chromatography, and eluted with hexane-ethyl acetate (4:1-2:1, volume ratio). The obtained compound was further purified by preparative HPLC to give the title compound (150 mg, yield 44%) as white crystals. The crystals were recrystallized from ethyl acetate-hexane to give colorless prism crystals. melting point 165-166° C.
Reaction SMILES: [C:1]([OH:5])(=[O:4])[CH:2]=[CH2:3].[CH3:6][C:7]([CH2:9]C([NH:13][C:14]([CH:16]=[CH2:17])=[O:15])(C)C)=[O:8]>O>[C:14]([NH2:13])(=[O:15])[CH:16]=[CH2:17].[CH3:6][C:7]([CH3:9])=[O:8].[CH3:6][C:7]([CH3:9])=[O:8].[C:1]([OH:5])(=[O:4])[CH:2]=[CH2:3]
Reactant: C=CC(=O)NC(C)(C)CC(C)=O
Agent: C=CC(=O)O
Solvent: O
Product: C=CC(N)=O
Product: CC(C)=O

Procedure:
By analysis it was found that the copolymer comprised 1.1% of water, 2.85 m.eq. of COOH/g of product, and 6.43-6.52% of nitrogen, from which it could be derived that the copolymer comprised 38.1 mole % of acrylic acid and 61.9 mole % of diacetone-acrylamide.
Reaction SMILES: C(C1C=CC=CC=1)(CC)C.[Na].[CH3:12][CH:13](O)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C=CC1C=CC=CC=1.[C:29]1([CH2:35][CH2:36][C:37]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)(C)[CH2:38]C)[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>CO>[C:14]1([CH2:13][CH2:12][CH:35]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:36][CH:37]([C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=2)[CH3:38])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: CC(O)c1ccccc1
Reactant: CCC(C)(CCc1ccccc1)c1ccccc1
Agent: CCC(C)c1ccccc1
Agent: [Na]
Solvent: C=Cc1ccccc1
Solvent: CO
Product: CC(CC(CCc1ccccc1)c1ccccc1)c1ccccc1
Temperature: 135 °C
Yield: 460 %

Procedure:
A one-liter glass flask equipped with a stirrer, a dropping funnel with a gas introduction conduit, a reflux condenser with a calcium chloride tube, and a thermometer was charged with 268 grams (2.0 moles) of purified secondary butylbenzene, 4.0 grams (0.17 mole) of metallic sodium and 2.4 grams (0.02 moles) of α-phenethyl alcohol while introducing argon gas through the gas introduction conduit, and the resulting mixture was heated to 135° C. Then 69 grams (0.66 mole) of purified styrene and 20 grams (0.15 mole) of secondary butylbenzene were dropped thereto over 2 hours while maintaining the temperature of the reaction system at 135° C. After dropwise addition was completed, the reaction mixture was stirred while heating for 1 hour and then cooled to room temperature. An excess of metallic sodium was decomposed by dropping methanol in small portions while stirring. Introduction of argon gas was stopped, and the contents were transferred to a separating funnel and then washed with water. The aqueous laer was removed, and the remaining oily layer was analyzed by gas chromatography. This gas chromatographic analysis showed that 40.7 grams (0.17 mole) of 1,3-dipenyl-3-methylpentane and 31.4 grams (0.092 mole) of 1,3,5-triphenyl-5-methylpentane were formed. The total yield (per styrene) was 54 mole %.
Reaction SMILES: [O:1]=[C:2]([C:7]1[CH:12]=[C:11]([F:13])[C:10]([F:14])=[C:9]([F:15])[C:8]=1[F:16])[CH2:3][C:4]([O-])=O.CC(OC(C)=O)=O.[CH:24]([O:31]CC)([O:28][CH2:29][CH3:30])OCC.[NH2:34][C:35]1([CH2:39][CH2:40][OH:41])[CH2:38][CH2:37][CH2:36]1>C1(C)C=CC=CC=1>[OH:41][CH2:40][CH2:39][C:35]1([NH:34][CH:4]=[C:3]([C:2](=[O:1])[C:7]2[CH:12]=[C:11]([F:13])[C:10]([F:14])=[C:9]([F:15])[C:8]=2[F:16])[C:24]([O:28][CH2:29][CH3:30])=[O:31])[CH2:38][CH2:37][CH2:36]1
Reactant: CCOC(OCC)OCC
Reactant: NC1(CCO)CCC1
Reactant: O=C([O-])CC(=O)c1cc(F)c(F)c(F)c1F
Solvent: CC(=O)OC(C)=O
Solvent: Cc1ccccc1
Product: CCOC(=O)C(=CNC1(CCO)CCC1)C(=O)c1cc(F)c(F)c(F)c1F
Temperature: 25 °C
Reaction time: 2 h
Yield: 61 %

Procedure:
A stirred solution of 3-oxo-3-(2,3,4,5-tetrafluorophenyl)propionate (3.67 g, 13.9 mmol), Ac2O (7.89 mL, 83.5 mmol) and triethyl orthoformate (4.63 mL, 27.8 mmol) was heated at 120° C. for 3 hours. The mixture was concentrated in vacuo and dried under high vacuum. 1-amino-1-(2-hydroxyethyl)cyclobutane (1.60 g, 13.9 mmol) in anhydrous toluene (20 mL) was added slowly at 0° C. to a solution of the mixture in anhydrous toluene (50 mL). The resulting mixture was stirred at room temperature for 2 hours, and the solvent was removed by evaporation. Flash chromatography (AcOEt:Hexane=1:1) of the residue gave the title compound as a pale yellow solid (3.30 g, 61%). 1H-NMR (400 MHz, CDCl3) δ 0.96 (0.6H, t, J=7.3 Hz), 1.09 (2.4H, t, J=7.3 Hz), 1.85-2.03 (12H, m), 2.06-2.13 (2H, m), 2.20-2.30 (2H, m), 2.32-2.43 (2H, m), 3.82-3.88 (2H, m), 4.02 (0.4H, q, J=7.3 Hz), 4.07 (1.6H, q, J=7.3 Hz), 6.94-7.03 (0.2H, m), 7.05-7.13 (0.8H, m), 8.23-8.30 (1H, m), 10.05-10.17 (0.2H, m), 11.36-11.50 (0.8H, m).
Reaction SMILES: [Li+].CCC[CH2-].Cl[P:7](=[O:14])([O:11][CH2:12][CH3:13])[O:8][CH2:9][CH3:10].[CH2:15]1[CH2:19][O:18]CC1>>[P:7]([O:18][CH:19]=[CH2:15])([O:11][CH2:12][CH3:13])([O:8][CH2:9][CH3:10])=[O:14]
Reactant: CCOP(=O)(Cl)OCC
Reactant: C1CCOC1
Agent: [CH2-]CCC
Agent: [Li+]
Product: C=COP(=O)(OCC)OCC
Temperature: 0 °C
Reaction time: 15 h

Procedure:
10 ml of N-butyllithium solution (2.1 M solution in hexane) were added dropwise to 50 ml of abs. THF under an argon atmosphere at 0° C. The solution was stirred for 30 minutes at 0° C. and for 15 hours at room temperature, then added to 3.01 ml diethyl chlorophosphonate (20 mmol) at −76° C. and stirred for 1 h at 0° C., then for 16 hours at room temperature. A white solid was filtered off, and the solvent was removed on a rotary evaporator. The slightly yellowish crude product was purified by column chromatography on silica gel (PE:EE=4:1). 2.2 g (60% of th.) of the title compound were obtained as a yellowish liquid.
Reaction SMILES: [CH3:1][C:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][CH:8]=2)[O:4][N:3]=1.[H][H]>[Pt](=O)=O.C(O)C>[NH2:3][C:2]([CH3:1])=[CH:6][C:5]([C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:14])([F:15])[F:16])=[CH:9][CH:8]=1)=[O:4]
Reactant: [H][H]
Reactant: Cc1cc(-c2ccc(C(F)(F)F)cc2)on1
Agent: O=[Pt]=O
Solvent: CCO
Product: CC(N)=CC(=O)c1ccc(C(F)(F)F)cc1

Procedure:
3-Methyl-5-[4-(trifluoromethyl)phenyl]isoxazole (1.8 g, 7.92 mmol) is introduced into 20 ml of ethanol, platinum(IV) oxide catalyst (180 mg) is added, and the mixture is then hydrogenated under atmospheric pressure hydrogen for 12 h. The catalyst is filtered off, and the filtrate is concentrated. 1.72 g (94% of theory) of the title compound are obtained as a white solid.
Reaction SMILES: [C:1](OC)(=[O:6])[CH2:2][C:3]([CH3:5])=O.[H-].[Na+].C([Li])CCC.[C:16]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)(=[O:22])[CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]>CCCCCC.O1CCCC1>[CH2:17]([C:16]1([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[O:22][C:1](=[O:6])[CH:2]=[CH:3][CH2:5]1)[CH2:18][CH2:19][CH2:20][CH3:21]
Reactant: COC(=O)CC(C)=O
Reactant: CCCCCC(=O)c1ccccc1
Agent: [H-]
Agent: [Li]CCCC
Agent: [Na+]
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CCCCCC1(c2ccccc2)CC=CC(=O)O1

Procedure:
The title compound was prepared as described in General Method 1 using 10 mmol of methyl acetoacetate, 11 mmol of NaH 60% dispersion in oil, 10.5 mmol of 1.6M n-butyl lithium in hexane, 10 mmol of hexanophenone and 28 mL of tetrahydrofuran. Upon concentrating the reaction a solid precipitated out which was triturated with ether and filtered (m.p. 123°-124° C.). 1H NMR (CDCl3) δ 0.83 (t, 3 H), 1.1-1.4 (m, 6 H), 1.9-2.0 (m, 2 H), 2.90 (d, 1 H), 2.92 (d, 1 H), 3.25 (d, 1 H), 3.35 (d, 1 H), 7.2-7.5 (m, 5 H).
Reaction SMILES: [C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C@@H:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C@H:17]([O:24][C:25]3[CH:26]=[CH:27][C:28]4[N:29]([C:31]([N:34]5[CH2:39][CH2:38][CH2:37][CH2:36][C@@H:35]5[CH3:40])=[N:32][N:33]=4)[CH:30]=3)[CH2:16][CH2:15]2)=[O:12])[N:7]([C:41]2[CH:42]=[C:43]([CH:50]=[CH:51][CH:52]=2)[CH2:44][O:45]S(C)(=O)=O)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.Cl.[F:63][CH:64]1[CH2:69][CH2:68][NH:67][CH2:66][CH2:65]1.C1C[O:73]CC1>>[CH:44]([OH:45])=[O:73].[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C@@H:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C@H:17]([O:24][C:25]3[CH:26]=[CH:27][C:28]4[N:29]([C:31]([N:34]5[CH2:39][CH2:38][CH2:37][CH2:36][C@@H:35]5[CH3:40])=[N:32][N:33]=4)[CH:30]=3)[CH2:16][CH2:15]2)=[O:12])[N:7]([C:41]2[CH:52]=[CH:51][CH:50]=[C:43]([CH2:44][N:67]3[CH2:68][CH2:69][CH:64]([F:63])[CH2:65][CH2:66]3)[CH:42]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: FC1CCNCC1
Reactant: C1CCOC1
Reactant: C[C@H]1CCCCN1c1nnc2ccc(O[C@@H]3CC[C@H](NC(=O)Nc4cc(C(C)(C)C)nn4-c4cccc(COS(C)(=O)=O)c4)c4ccccc43)cn12
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Product: C[C@H]1CCCCN1c1nnc2ccc(O[C@@H]3CC[C@H](NC(=O)Nc4cc(C(C)(C)C)nn4-c4cccc(CN5CCC(F)CC5)c4)c4ccccc43)cn12
Product: O=CO
Temperature: 50 °C
Reaction time: 24 h
Yield: 16 %

Procedure:
To a solution of Intermediate 167b (0.19 mmol) in THF (2 mL) was added DIPEA (260 μL, 1.5 mmol) and 4-fluoropiperidine hydrochloride (104 mg, 0.75 mmol) and the reaction stirred at 50° C. for 24 h. The crude reaction mixture was cooled and partitioned between EtOAc and water. The aqueous phase was extracted with EtOAc (×3) and the combined organic layers were washed with brine, dried (MgSO4) and concentrated in vacuo. The resulting residue was purified by FCC on silica, using a gradient of 0-10% (2M NH3 in MeOH) in DCM, followed by MDAP (Method 7) purification, to give the title compound (25 mg, 16%). LCMS (Method 5): Rt 3.68 min, m/z 734 [MH+]. 1H NMR (400 MHz, d6-DMSO): 0.86 (3H, d, J=6.2 Hz), 1.23 (9H, s), 1.42-1.50 (2H, m), 1.58-1.70 (4H, m), 1.70-1.92 (6H, m), 1.95-2.12 (2H, m), 2.23-2.31 (2H, m), 2.86 (1H, ddd, J=12.7, 9.0, 3.9 Hz), 3.11 (1H, dt, J=12.2, 4.3 Hz), 3.24-3.30 (2H, m), 3.48 (2H, s), 4.60 (1H, dsp, J=48.9, 3.5 Hz), 4.77 (1H, td, J=8.4, 5.7 Hz), 5.47 (1H, t, J=4.2 Hz), 6.28 (1H, s), 6.98 (1H, d, J=8.6 Hz), 7.14 (1H, dd, J=9.8, 2.1 Hz), 7.20-7.25 (2H, m), 7.25-7.34 (3H, m), 7.35-7.38 (2H, m), 7.40 (1H, t, J=7.7 Hz), 7.59 (1H, d, J=10.0 Hz), 7.62 (1H, d, J=1.8 Hz), 8.05 (1H, s), 8.10 (1.8H, s).
Reaction SMILES: [NH:1]1[CH:5]=[C:4]([C:6]2[CH:11]=[C:10]([C:12]([NH2:14])=[O:13])[CH:9]=[CH:8][N:7]=2)[N:3]=[CH:2]1.[CH2:15]([O:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[CH2:24][CH2:25]OS(C)(=O)=O)[CH3:16].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH2:15]([O:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[CH2:24][CH2:25][N:1]1[CH:5]=[C:4]([C:6]2[CH:11]=[C:10]([C:12]([NH2:14])=[O:13])[CH:9]=[CH:8][N:7]=2)[N:3]=[CH:2]1)[CH3:16]
Reactant: NC(=O)c1ccnc(-c2c[nH]cn2)c1
Reactant: CCOc1ccccc1CCOS(C)(=O)=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOc1ccccc1CCn1cnc(-c2cc(C(N)=O)ccn2)c1
Temperature: 70 °C
Reaction time: 8 h
Yield: 53 %

Procedure:
A mixture of 2-(1H-imidazol-4-yl)pyridine-4-carboxamide (200 mg, 1.06 mmol, PREPARATION 7), methanesulfonic acid 2-(2-ethoxy-phenyl)-ethyl ester (311 mg, 1.28 mmol) and K2CO3 (294 mg, 2.13 mmol) in DMF (10 mL) was stirred overnight at 70° C., LC/MS showed the reaction was completed, purified by FCC (DCM/MeOH=20/1) to give the title compound (189 mg, 53%) as a yellow solid. [M+H] Calc'd for C19H20N4O2, 337. Found, 337.
Reaction SMILES: [CH:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[CH2:1]([OH:8])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[C:1]([O:8][CH2:1][CH2:2][CH2:7][CH2:6][CH2:5][CH3:4])(=[O:8])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: O=Cc1ccccc1
Solvent: Cc1ccccc1
Product: CCCCCCO
Product: CCCCCCOC(=O)CCCCC
Yield: 60 %

Procedure:
When a toluene solution of benzyl alcohol and 0.1% complex 2′ was refluxed for 24 hrs in an open system, benzyl benzoate was formed in 70% yield, accompanied by a small amount of benzaldehyde (4%) (Table 24, entry 1). Refluxing 1-hexanol with 0.1% 2 in toluene (115° C.) or neat (157° C.) for 24 hrs resulted in formation of 60-70% of hexyl hexanoate, accompanied by 2.5-10% hexanal (Table 24, entries 2 and 3). Complex 6′ was slightly less catalytically active than 2 (Table 24, entry 7). The PNN complex 4′ exhibited significantly higher catalytic activity than that of the PNP complexes 2′ and 6′; benzyl alcohol, 1-hexanol and 1-butanol were dehydrogenated to the corresponding esters in over 90% yield after heating with 0.1% 4′ in toluene (Table 24, entry 4-6).
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)=[CH2:3].OO.C(Cl)(C1C=CC=CC=1)(C)C.C([O:31][O:32]C(C1C=CC=CC=1)(C)C)(C1C=CC=CC=1)(C)C>>[O-:31][OH:32].[C:4]1([CH:2]([CH3:3])[CH3:1])[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: C=C(C)c1ccccc1
Reactant: CC(C)(OOC(C)(C)c1ccccc1)c1ccccc1
Agent: CC(C)(Cl)c1ccccc1
Agent: OO
Product: CC(C)c1ccccc1
Product: [O-]O
Temperature: 30 °C
Reaction time: 0.58 h
Yield: 5 %

Procedure:
Into a 250 ml round bottom flask equipped with a magnetic stirrer, condenser, thermometer and addition funnel were added 59.0 grams (B 0.05 m) α-methylstyrene and 9.8 grams (0.2 m) of 70% H2O2. The flask was immersed in a 25° C. water bath and the temperature allowed to come to 23° C. Then with rapid stirring, 6.2 grams (0.14 m) of cumyl chloride were added over 5 minutes. The reaction mixture was stirred vigorously for 35 minutes at 25° C.±2° C., the reaction temperature raised to 30° C. and stirred 1 hour at 30° C.±2° C., the reaction temperature raised to 35° C. and the reaction mixture stirred an additional hour at 35° C.±2° C., the reaction temperature raised to 40° C. and the reaction mixture stirred 1 hour at 40° C.± 2° C. At this point there was essentially no dicumyl peroxide formed and about 5% cumene hydroperoxide formed. The reaction mixture was allowed to stand at room temperature over the weekend and then stirred an additional 2 hours at room temperature. The gas chromatography scans indicated there was still less than 1% dicumyl peroxide present and about 5% cumene hydroperoxide present. The reaction mixture was stirred with 15% NaOH, the organic layer separated and discarded in the organic waste bottle since it contained essentially no dicumyl peroxide.
Reaction SMILES: C([O:3][C:4]([C:6]1(C(OCC)=O)[CH2:10][C:9]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=2[NH2:18])=[CH:8][N:7]1C(=O)C)=[O:5])C.Br>>[Cl:17][C:14]1[CH:13]=[C:12]2[C:11](=[CH:16][CH:15]=1)[C:9]([CH2:10][C@@H:6]([C:4]([OH:3])=[O:5])[NH2:7])=[CH:8][NH:18]2
Reactant: CCOC(=O)C1(C(=O)OCC)CC(c2ccc(Cl)cc2N)=CN1C(C)=O
Agent: Br
Product: N[C@@H](Cc1c[nH]c2cc(Cl)ccc12)C(=O)O
Yield: 91.1 %

Procedure:
A mixture of 60 g (0.16 mol) of the compound of Example 11, and 450 ml. of 2 N aqueous HBr was heated under N2 at 95° for 30 hours. The solution was concentrated in vacuo and the residual salt was taken up in 300 ml of water. The solution was brought to pH 5.5 with 4N NaOH and the mixture was chilled in an icebath for 1 hour. The precipitate was collected, washed with cold water and dried to give 34.8 g of product. Crystallization from glacial acetic acid (360 ml.) afforded, after drying at 100°/0.2 mmHg, 30.8 g (82%) of white crystals, m.p. 280° (dec.) (lit. m.p. 285°-286°), which was identical with an authentic sample.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]([O:8][CH2:9][CH3:10])=[O:7].[Al+3].[Cl-].[Cl-].[Cl-].[C:15](Cl)(=[O:17])[CH3:16].CO>ClCCCl.ClCCl>[C:15]([C:4]1[CH:3]=[C:2]([C:6]([O:8][CH2:9][CH3:10])=[O:7])[NH:1][CH:5]=1)(=[O:17])[CH3:16]
Reactant: CC(=O)Cl
Reactant: CCOC(=O)c1ccc[nH]1
Agent: [Al+3]
Agent: [Cl-]
Solvent: CO
Solvent: ClCCl
Solvent: ClCCCl
Product: CCOC(=O)c1cc(C(C)=O)c[nH]1
Temperature: 25 °C
Reaction time: 1 h
Yield: 76.7 %

Procedure:
In a two-neck round bottom flask with an argon inlet, 4.0 g of ethyl pyrrole 2-carboxylate (28.8 mmol) is dissolved in 100 ml of 1,2-dichloroethane. Subsequently, 8.0 g of AlCl3 is added slowly. A solution of 4.4 ml of acetyl chloride (62 mmol) in 50 ml of 1,2-dichloroethane was then added dropwise over a period of 15 min. After stirring the reaction mixture at room temperature for one hour, it is carefully poured onto 200 g of crushed ice. After hydrolysis, the mixture is transferred into a separatory funnel and the organic phase is separated off. The aqueous phase is extracted with dichloromethane (2×200 ml), and the combined organic phases are washed with a saturated solution of aqueous sodium bicarbonate (1×100 ml) and with water (1×100 ml) before being dried over magnesium sulfate. The solvent is then removed under vacuum. Chromatographic workup (silica gel; 1% methanol in dichloromethane as eluent) yielded the product as a pale brown powder (4.0 g, 76% yield). 1H NMR (δ ppm, CDCl3): 10.41 (s, br, 1H, NH); 7.51 (dd, J=3.34, 1.62 Hz, 1H, α-pyrrolic); 7.28 (dd, J=1.62, 2.31 Hz, 1H, β-pyrrolic); 4.29 (q, J=7.12 Hz, 2H, CO2Et); 2.39 (s, 3H, Me); 1.31 (t, J=7.12 H, 3H, CO2Et). 13C NMR (δ ppm, CDCl3): 193.55; 161.07; 127.00; 126.54; 124.04; 114.86; 60.83; 27.13; 14.15. Exact mass calculated for C9H12NO3 (M+H)=182.081718, found=182.081495.