Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: I(O)(=O)(=O)=O.[F:6][C:7]1[CH:20]=[CH:19][C:10]([C:11]([NH:13][CH:14]([CH2:17][OH:18])[CH:15]=[CH2:16])=[O:12])=[C:9]([C:21]([F:24])([F:23])[F:22])[CH:8]=1.C1(C)C=CC=CC=1.C(OCC)(=[O:34])C>C(#N)C.O>[F:6][C:7]1[CH:20]=[CH:19][C:10]([C:11]([NH:13][CH:14]([CH:15]=[CH2:16])[C:17]([OH:34])=[O:18])=[O:12])=[C:9]([C:21]([F:22])([F:23])[F:24])[CH:8]=1
Reactant: CCOC(C)=O
Reactant: C=CC(CO)NC(=O)c1ccc(F)cc1C(F)(F)F
Agent: [O-][I+3]([O-])([O-])O
Solvent: Cc1ccccc1
Solvent: CC#N
Solvent: O
Product: C=CC(NC(=O)c1ccc(F)cc1C(F)(F)F)C(=O)O
Temperature: 25 °C
Reaction time: 15 h

Procedure:
At RT, 51.5 g (226 mmol) of periodic acid and 9.9 g (99 mmol) of CrO3 were dissolved in acetonitrile/water. Furthermore, 25 g (90.3 mmol) of 4-fluoro-N-(1-hydroxymethylallyl)-2-trifluoromethylbenzamide were dissolved in acetonitrile/water and the NalO4/CrO3 solution which had been prepared earlier was added dropwise at 0-5° C. over a period of 3 h. The mixture was then stirred at RT for 15 h. 400 ml of 6% strength Na2HPO4 solution were then added dropwise, toluene and ethyl acetate were added and the phases were separated. The aqueous phase was re-extracted with ethyl acetate. The combined organic phases were washed, dried and concentrated. This gave 24.1 g (92% of theory) of the title compound.
Reaction SMILES: [I-].[CH3:2][C:3]1[CH:29]=[CH:28][C:6]([CH2:7][CH2:8][P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=[CH:5][CH:4]=1.ICCC1C=CC(C)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Li]CCCC.[O:64]1[C:68]2[CH:69]=[CH:70][C:71]([CH:73]=O)=[CH:72][C:67]=2[O:66][CH2:65]1>>[C:3]1([CH3:2])[CH:4]=[CH:5][C:6]([CH2:7][CH:8]=[CH:73][C:71]2[CH:70]=[CH:69][C:68]3[O:64][CH2:65][O:66][C:67]=3[CH:72]=2)=[CH:28][CH:29]=1
Reactant: O=Cc1ccc2c(c1)OCO2
Reactant: Cc1ccc(CC[P+](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: Cc1ccc(CCI)cc1
Agent: [I-]
Agent: [Li]CCCC
Product: Cc1ccc(CC=Cc2ccc3c(c2)OCO3)cc1
Yield: 40 %

Procedure:
Starting from p-methylphenethyltriphenylphosphonium iodide, which has been synthesized from 1-(2-iodoethyl)-4-methylbenzene and PPh3, (2.54 g, 5.00 mmol, 1.0 equiv.), n-BuLi (1.6 M in hexanes, 3.1 mL, 5.00 mmol, 1.0 equiv.) and benzo[d][1,3]dioxole-5-carbaldehyde (0.98 g, 6.50 mmol, 1.3 equiv.), 0.50 g (40%) of the title compound as a light yellow oil was obtained after purification by flash chromatography on SiO2 (cyclohexane/EtOAc 997:3).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH2:9][CH2:10][NH:11][C:12]([C:14]23[CH2:23][CH:18]4[CH2:19][CH:20]([CH2:22][C:16]([C:24]5[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=5)([CH2:17]4)[CH2:15]2)[CH2:21]3)=[O:13])[CH:5]=[CH:6][C:7]=1[OH:8]>C(OC(=O)C(C)C)(=O)C(C)C.OS(O)(=O)=O>[Cl:30][C:27]1[CH:26]=[CH:25][C:24]([C:16]23[CH2:17][CH:18]4[CH2:19][CH:20]([CH2:21][C:14]([C:12]([NH:11][CH2:10][CH2:9][C:4]5[CH:5]=[CH:6][C:7]([OH:8])=[C:2]([O:1][C:12](=[O:13])[CH:14]([CH3:21])[CH3:15])[CH:3]=5)=[O:13])([CH2:23]4)[CH2:15]2)[CH2:22]3)=[CH:29][CH:28]=1
Reactant: O=C(NCCc1ccc(O)c(O)c1)C12CC3CC(C1)CC(c1ccc(Cl)cc1)(C3)C2
Agent: CC(C)C(=O)OC(=O)C(C)C
Agent: O=S(=O)(O)O
Product: CC(C)C(=O)Oc1cc(CCNC(=O)C23CC4CC(C2)CC(c2ccc(Cl)cc2)(C4)C3)ccc1O
Temperature: 25 °C
Reaction time: 72 h

Procedure:
Compound 1 was dissolved in iso-butyric anhydride with a catalytic amount of 98% H2SO4 and stirred under N2 for 3 days at room temperature. The solution was then concentrated under a vacuum and filtered to give the product Compound 5, with a melting point of 126-128° C. 1H NMR (500 MHz, CDCl3) δ 1.29-1.33 (d, d, 6H, 2CH3), 1.74 (m, 2H, Admant-H), 1.81-1.88 (m, 8H, Admant-H), 1.94 (s, 2H, Admant-H), 2.26 (m, 2H, Admant-H), 2.74-2.81 (m, 2H, 2COCH), 2.82-2.85 (t, J=7.5 Hz, 2H, CH2), 3.50-3.54 (q, 2H, NCH2), 5.68 (s, 1H, NH), 6.99 (s, 1H, Ar—H), 7.05-7.07 (d, d, 1H, H—Ar), 7.11-7.13 (d, J=10 Hz, 1H, Ar—H), 7.30 (s, 4H, Ar—H); 13C NMR (500 MHz, CDCl3) δ 18.9, 28.8, 34.0, 35.0, 35.5, 36.5, 38.3, 40.3, 41.7, 42.0, 44.4, 123.5, 123.9, 126.4, 126.7, 128.3, 131.5, 137.7, 140.9, 142.2, 148.4, 174.4, 174.5, 177.4; MS m/z (relative intensity) 566.22 (MH+, 50), 567.22 (10), 567.22 (15).
Reaction SMILES: NC1C=CC(OCCCN(C)C2N=C(C3C(C4C=C(NC(=O)C5C(F)=CC=CC=5F)C=CC=4)=NN4C=CC=CC=34)C=CN=2)=C(F)C=1.[F:47][C:48]1[CH:53]=[C:52]([N+:54]([O-])=O)[CH:51]=[CH:50][C:49]=1[O:57][CH2:58][CH2:59][N:60]1[CH2:65][CH2:64][CH2:63][CH2:62][CH2:61]1>>[F:47][C:48]1[CH:53]=[C:52]([CH:51]=[CH:50][C:49]=1[O:57][CH2:58][CH2:59][N:60]1[CH2:65][CH2:64][CH2:63][CH2:62][CH2:61]1)[NH2:54]
Reactant: O=[N+]([O-])c1ccc(OCCN2CCCCC2)c(F)c1
Agent: CN(CCCOc1ccc(N)cc1F)c1nccc(-c2c(-c3cccc(NC(=O)c4c(F)cccc4F)c3)nn3ccccc23)n1
Product: Nc1ccc(OCCN2CCCCC2)c(F)c1

Procedure:
In a manner analogous to Example 125, 0.57 g of the title compound was prepared from 1-{2-[(2-fluoro-4-nitrophenyl)oxy]ethyl}piperidine as a brown oil: 1H NMR (CDCl3, 400 MHz) δ 1.44-1.46 (m, 2H), 1.57-1.63 (m, 4H), 2.50-2.57 (m, 4H), 2.74 (t, 2H, J=6.2 Hz), 3.50 (brs, 2H), 4.08 (t, 2H, J=6.2 Hz), 6.35 (ddd, 1H, J=8.6, 2.5, and 1.5 Hz), 6.45 (dd, 1H, J=12.7 and 2.8 Hz), and 6.81 (t, 1H, J=8.8 Hz).
Reaction SMILES: [N:1]1([C:7]2[N:12]=[CH:11][NH:10][C:9](=[O:13])[CH:8]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[F:14][C:15]1[CH:22]=[CH:21][CH:20]=[C:17]([CH:18]=O)[C:16]=1[OH:23]>>[F:14][C:15]1[C:16]([OH:23])=[C:17]([CH:20]=[CH:21][CH:22]=1)[CH2:18][N:4]1[CH2:5][CH2:6][N:1]([C:7]2[N:12]=[CH:11][NH:10][C:9](=[O:13])[CH:8]=2)[CH2:2][CH2:3]1
Reactant: O=c1cc(N2CCNCC2)nc[nH]1
Reactant: O=Cc1cccc(F)c1O
Product: O=c1cc(N2CCN(Cc3cccc(F)c3O)CC2)nc[nH]1

Procedure:
6-[4-(3-Fluoro-2-hydroxy-benzyl)-piperazin-1-yl]-3H -pyrimidin-4-one was prepared using Procedure B from 6-piperazin-1-yl-3H-pyrimidin-4-one (Intermediate 4) and 3-fluorosalicylaldehyde (available from Aldrich). 1H NMR (400 MHz, CDCl3) δ 2.62-2.66 (m, 4H), 3.58-3.65 (m, 4H), 3.79 (s, 2H), 5.40 (s, 1H), 6.71-6.76 (m, 2H), 6.99-7.03 (m, 1H), 7.84 (s, 1H), 11.85 (br s, 1H). Mass spectrum (ES) MH+=305.
Reaction SMILES: [F-].[K+].[F:3][C:4]([F:19])([F:18])[C:5]1[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[C:6]=1[C:7]([OH:9])=[O:8].Br[CH2:21][C:22](CBr)=[O:23].[C:26]([NH:34][C@H:35]([C:39]([NH:41][C@H:42]([C:44]([NH:46][C@H:47]([C:52]([OH:54])=[O:53])[CH2:48][CH2:49][CH2:50][CH3:51])=[O:45])[CH3:43])=[O:40])[CH:36]([CH3:38])[CH3:37])(=[O:33])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>CN(C=O)C>[CH3:21][C:22]([O:8][C:7](=[O:9])[C:6]1[C:5]([C:4]([F:18])([F:19])[F:3])=[CH:13][CH:12]=[CH:11][C:10]=1[C:14]([F:15])([F:17])[F:16])=[O:23].[C:26]([NH:34][C@H:35]([C:39]([NH:41][C@H:42]([C:44]([NH:46][C@H:47]([C:52]([OH:54])=[O:53])[CH2:48][CH2:49][CH2:50][CH3:51])=[O:45])[CH3:43])=[O:40])[CH:36]([CH3:37])[CH3:38])(=[O:33])[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1
Reactant: O=C(O)c1c(C(F)(F)F)cccc1C(F)(F)F
Reactant: O=C(CBr)CBr
Agent: CCCC[C@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)c1ccccc1)C(C)C)C(=O)O
Agent: [F-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(=O)OC(=O)c1c(C(F)(F)F)cccc1C(F)(F)F
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
A mixture of potassium fluoride (0.1 mmol, 6 mg) and 2,6-bis(trifluoromethyl)benzoic acid (0.066 mmol, 17 mg) in dry DMF (500 μl) was stirred over molecular sieves at room temperature for 5 minutes. A solution of N-benzoyl-L-valyl-L-alanyl-L-norleucine bromomethyl ketone (0.033 mmol), 16 mg) in dry DMF (500 μl) was added and the reaction mixture stirred for 1 hour. The reaction mixture was passed through a short silica plug and washed with 5% methanol in dichloromethane. Solvent was removed under vacuum and the residue purified using prep. HPLC. Freeze drying afforded (6.4 mg) as a white lyophilisate. Electrospray MS m/z 660 [MH+ ]. ##STR6##
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:19])[CH2:11][N:10]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:9]2)=[CH:4][CH:3]=1.[CH3:20][N:21](C)C=O>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:20]([C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:19])[CH2:11][N:10]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:9]2)=[CH:4][CH:3]=1)#[N:21]
Reactant: CN(C)C=O
Reactant: CC(C)(C)OC(=O)N1CC(O)(c2ccc(Br)cc2)C1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [C-]#N
Agent: [Zn+2]
Product: CC(C)(C)OC(=O)N1CC(O)(c2ccc(C#N)cc2)C1
Temperature: 100 °C
Reaction time: 15 h

Procedure:
Into a 500-mL round-bottom flask, purged and maintained with an inert atmosphere of nitrogen, was placed a mixture of tert-butyl 3-(4-bromophenyl)-3-hydroxyazetidine-1-carboxylate (compound 43.1, 16.3 g, 49.7 mmol) in N,N-dimethylformamide (250 mL), zinc cyanide (8.7 g, 75 mmol) and Pd(PPh3)4 (5.77 g, 5.00 mmol). The resulting mixture was stirred for 15 h at 100° C., then cooled to room temperature. The reaction was quenched with saturated aqueous FeSO4 (500 mL) and stirred vigorously. The mixture was filtered through Celite® and the layers from the filtrate were separated. The aqueous phase was extracted with ethyl acetate (300 mL) and the combined organic layers were washed with brine (2×100 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with ethyl acetate/petroleum ether (1/100-1/3) as the eluent to yield 14 g (crude) of the title compound as a white solid.
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][CH:9]=[CH:8][C:3]=1[CH2:4][CH2:5][CH:6]=[O:7].[O:12]=[C:13]([C:20]1[CH:25]=[CH:24][C:23]([Br:26])=[CH:22][CH:21]=1)/[CH:14]=[CH:15]/[C:16]([O:18][CH3:19])=[O:17]>C(Cl)(Cl)Cl>[CH2:4]([C@H:5]1[C@@H:15]([C:16]([O:18][CH3:19])=[O:17])[CH:14]=[C:13]([C:20]2[CH:21]=[CH:22][C:23]([Br:26])=[CH:24][CH:25]=2)[O:12][C:6]1=[O:7])[C:3]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:2]=1
Reactant: O=CCCc1ccccc1Cl
Reactant: COC(=O)/C=C/C(=O)c1ccc(Br)cc1
Solvent: ClC(Cl)Cl
Product: COC(=O)[C@H]1C=C(c2ccc(Br)cc2)OC(=O)[C@H]1Cc1ccccc1
Yield: 80 %

Procedure:
Prepared according to the general procedure from 2-chloro-hydrocinnamaldehyde and (E)-methyl 4-oxo-4-(4-bromophenyl)but-2-enoate using 0.5 mol % 1 as the catalyst in 80% yield as a 6:1 mixture of diastereomers (white solid). [α]D20 (c 1.23, CHCl3)=+112.1; mp=139-141° C.; 1H NMR (400 MHz, CDCl3) δ 7.53-7.47 (m, 4H), 7.35-7.25 (m, 5H), 7.19-7.17 (m, 2H), 5.81 (d, 1H, J=7.1 Hz), 5.74* (d, 1H, J=5.6 Hz), 4.23 (q, 2H, J=7.0 Hz), 4.13* (q, 2H, J=7.2 Hz), 3.55 (dd, 1H, J=14.4, 4.7 Hz), 3.40-3.35* (m, 1H), 3.27-3.24* (m. 1H), 3.25 (dd, 1H, J=7.1, 5.8 Hz), 3.14* (dd, 1H, J=13.8, 5.7 Hz), 3.03-2.97 (m, 1H), 2.91* (dd, 1H, J=13.8, 8.8 Hz), 2.77 (dd, 1H, J=14.3, 10.0 Hz), 1.30 (t, 3H, J=7.0 Hz), 1.24* (t, 3H, J=7.2 Hz); 13C NMR (100 MHz, CDCl3) δ 170.2, 168.7, 151.7, 138.1, 131.9, 130.9, 1294, 129.2, 129.0, 127.4, 127.1, 126.5, 124.0, 98.7, 96.7, 66.1, 62.1, 61.9, 42.8, 42.2, 41.5, 40.7, 35.5, 33.3, 15.5, 14.3, 14.2; IR (thin film) ν 3087, 3027, 2980, 1778, 1731, 1489, 1455, 1176, 1069, 1009 cm−1; HRMS (ESI) calcd for C21H19BrO4 [M+Na]+ 437.0358, found 437.0359; 99% ee (3S,4S)-isomer as determined by HPLC (AD-H, 9:1 hexanes/i-PrOH), tr (3S,4S)=57.6 min, tr (3R,4R)=25.4 min.
Reaction SMILES: C([O:4][C@H:5]1[CH2:10][C:9]([CH3:12])([CH3:11])[C:8]([C:13]#[CH:14])=[C:7]([CH3:15])[CH2:6]1)(=O)C.[OH-].[K+].O.C(O)(=O)C>CO>[C:13]([C:8]1[C:9]([CH3:11])([CH3:12])[CH2:10][C@H:5]([OH:4])[CH2:6][C:7]=1[CH3:15])#[CH:14]
Reactant: C#CC1=C(C)C[C@@H](OC(C)=O)CC1(C)C
Agent: [K+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: CO
Solvent: O
Product: C#CC1=C(C)C[C@@H](O)CC1(C)C
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 99.8 %

Procedure:
183.8 g of (R)-4-ethynyl-3,5,5-trimethyl-3-cyclohexen-1-yl acetate (prepared according to Example 10) were dissolved in 1 l of methanol. The solution was cooled to 0° C. and treated portionwise within 15 minutes with 74.2 g of potassium hydroxide in such a manner that the temperature did not exceed 11° C. The mixture was stirred at 4°-8° C. for a further 15 minutes and then at room temperature for 30 minutes. The reaction mixture was subsequently poured into 2 l of water and 26.5 g of glacial acetic acid. The mixture was extracted three times with 500 ml of methylene chloride each time. The organic phases were washed with 500 ml of saturated sodium chloride solution, and with 600 ml of saturated sodium bicarbonate solution dried over sodium sulphate and filtered. The filtrate was concentrated almost completely in a rotary evaporator under a water-jet vacuum at 30° C. bath temperature. The residual oil was dissolved in 300 ml of pentane and the solution was evaporated completely in a rotary evaporator under a water-jet vacuum at 30° C. bath temperature. The oil obtained was dried at room temperature for 30 minutes in a high vacuum, whereby spontaneous crystalization (strongly exothermic) took place. There were thus obtained 146 g of (R)-4-ethynyl-3,5,5-trimethyl-3-cyclohexen-1-ol (purity 98%, chemical yield 98.8%) as colourless crystals having a pale violet hue; Rf value (diisopropyl ether) 0.40.
Reaction SMILES: BrCC(CC)CCCC.CC(CC(C)(C)C)CCO.[Li].ClC([O-])=O.[CH2:25]([CH:27]([CH2:46][CH2:47][CH2:48][CH3:49])[CH2:28][CH:29]([O:38]C(N1C=NC=N1)=O)[CH2:30][CH:31]([CH3:37])[CH2:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH3:26]>O1CCCC1.[Cu]>[CH2:25]([CH:27]([CH2:46][CH2:47][CH2:48][CH3:49])[CH2:28][CH:29]([OH:38])[CH2:30][CH:31]([CH3:37])[CH2:32][C:33]([CH3:34])([CH3:36])[CH3:35])[CH3:26]
Reactant: CCCCC(CC)CC(CC(C)CC(C)(C)C)OC(=O)n1cncn1
Agent: [Cu]
Agent: CC(CCO)CC(C)(C)C
Agent: CCCCC(CC)CBr
Solvent: C1CCOC1
Product: CCCCC(CC)CC(O)CC(C)CC(C)(C)C

Procedure:
8-Ethyl-2,2,4-trimethyl-6-dodecanol (b.p. 86°-90° at 0.15 mm of mercury pressure) was prepared by reacting 1-bromo-2-ethylhexane and 3,5,5-trimethylhexanol with lithium in tetrahydrofuran at 0° to -10° according to the general method of Pearce, Richards and Scilly (J. Chem. Soc., Perkin I, 1655, 1972). This compound was converted, by way of the chloroformate, into 1-[8-ethyl-2,2,4-trimethyl-6-dodecyloxycarbonyl]-1,2,4-triazole of formula: ##STR16## The compound was evaluated as an extractant for copper by the procedure of Example 1 and the results are presented in Table 2.
Reaction SMILES: [CH3:1][C:2]1[C:10]([CH3:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[CH3:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([CH:20]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[CH2:21][NH2:22])=[CH:16][CH:15]=1>>[CH3:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([CH:20]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[CH2:21][NH:22][C:4](=[O:6])[C:3]2[CH:7]=[CH:8][CH:9]=[C:10]([CH3:11])[C:2]=2[CH3:1])=[CH:16][CH:15]=1
Reactant: Cc1cccc(C(=O)O)c1C
Reactant: COc1ccc(C(CN)N2CCOCC2)cc1
Product: COc1ccc(C(CNC(=O)c2cccc(C)c2C)N2CCOCC2)cc1

Procedure:
From 2,3-dimethylbenzoic acid and 2-(4-methoxy-phenyl)-2-morpholin-4-yl-ethylamine.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1B(O)O)(=[O:3])[CH3:2].C(=O)([O-])[O-].[Na+].[Na+].Br[C:20]1[S:21][CH:22]=[C:23]([C:25]([N:27]2[CH:36]3[CH:31]([CH2:32][CH2:33][CH2:34][CH2:35]3)[CH2:30][CH2:29][CH2:28]2)=[O:26])[N:24]=1>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:27]1([C:25]([C:23]2[N:24]=[C:20]([C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[C:1](=[O:3])[CH3:2])[S:21][CH:22]=2)=[O:26])[CH:36]2[CH:31]([CH2:32][CH2:33][CH2:34][CH2:35]2)[CH2:30][CH2:29][CH2:28]1
Reactant: O=C(c1csc(Br)n1)N1CCCC2CCCCC21
Reactant: CC(=O)c1ccccc1B(O)O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Product: CC(=O)c1ccccc1-c1nc(C(=O)N2CCCC3CCCCC32)cs1
Temperature: 25 °C
Yield: 72.4 %

Procedure:
In a Microwave process tube, tetrakis(triphenylphosphine)palladium (5 mg, 0.004 mmol) was added to a degassed (nitrogen) mixture of 2-acetylphenylboronic acid (Aldrich; 38 mg, 0.15 mmol) and sodium carbonate (2 M in water, 0.2 mL, 0.4 mmol), and (2-bromo-thiazol-4-yl)-(octahydro-qunolin-1-yl)-methanone (from Step 1; 50 mg, 0.15 mmol) in DME (dry, 1.5 mL). The tube was submitted to 150 W Microwave Irradiation at 160° C. for 5 minutes. The reaction mixture was cooled to room temperature, filtered through celite and silica plug, and extracted with EtOAc and water three times. The organic layers were combined, concentrated and purified by C-18 reversed phase HPLC with a gradient of 10-100% Acetonitrile/Water to give 1-{2-[4-(octahydro-quinoline-1-carbonyl)-thiazol-2-yl]-phenyl}-ethanone (40 mg, 70%).
Reaction SMILES: C([O-])([O-])=O.[K+].[K+].[CH3:7][CH:8]([CH3:24])[C:9]([NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH:18]2[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]2)[CH:13]=1)=[O:10].Cl[CH2:26][CH2:27][CH2:28][C:29]([C:31]1[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=1)=[O:30]>>[CH3:38][O:37][C:34]1[CH:35]=[CH:36][C:31]([C:29](=[O:30])[CH2:28][CH2:27][CH2:26][N:21]2[CH2:22][CH2:23][CH:18]([C:14]3[CH:13]=[C:12]([NH:11][C:9](=[O:10])[CH:8]([CH3:24])[CH3:7])[CH:17]=[CH:16][CH:15]=3)[CH2:19][CH2:20]2)=[CH:32][CH:33]=1
Reactant: CC(C)C(=O)Nc1cccc(C2CCNCC2)c1
Reactant: COc1ccc(C(=O)CCCCl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: COc1ccc(C(=O)CCCN2CCC(c3cccc(NC(=O)C(C)C)c3)CC2)cc1

Procedure:
Prepared by Procedure K (KI) and Scheme E (K2CO3) using 2-methyl-N-[3-(4-piperidinyl)phenyl]propanamide and 4-chloro-1-(4-methoxyphenyl)-1-butanone: ESMS m/e:423.2 (M+H)+.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[NH:12][C:11](=[O:16])[CH2:10][CH2:9]2.[Cl:17][C:18]1[CH:19]=[C:20]([SH:25])[CH:21]=[CH:22][C:23]=1[Cl:24]>>[Cl:17][C:18]1[CH:19]=[C:20]([S:25][CH2:2][CH2:3][CH2:4][O:5][C:6]2[CH:7]=[C:8]3[C:13](=[CH:14][CH:15]=2)[NH:12][C:11](=[O:16])[CH2:10][CH2:9]3)[CH:21]=[CH:22][C:23]=1[Cl:24]
Reactant: Sc1ccc(Cl)c(Cl)c1
Reactant: O=C1CCc2cc(OCCCBr)ccc2N1
Product: O=C1CCc2cc(OCCCSc3ccc(Cl)c(Cl)c3)ccc2N1

Procedure:
Prepared analogous to Example 122 from 6-(3-bromopropoxy)-3,4-dihydro-carbostyril (m.p. 111°-118° C.) and 3,4-dichloro-thiophenol.
Reaction SMILES: Br[C:2]1[N:7]2[N:8]=[C:9]([CH2:22][CH3:23])[C:10]([N:11]([CH2:18][CH:19]3[CH2:21][CH2:20]3)[CH2:12][CH:13]3[CH2:17][CH2:16][O:15][CH2:14]3)=[C:6]2[CH:5]=[CH:4][CH:3]=1.[CH3:24][O:25][C:26]1[CH:31]=[C:30]([O:32][CH3:33])[CH:29]=[C:28]([CH3:34])[C:27]=1OB(O)O.O.O.O.O.O.O.O.O.[OH-].[Ba+2].[OH-].C(OCC)(=O)C>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:19]1([CH2:18][N:11]([C:10]2[C:9]([CH2:22][CH3:23])=[N:8][N:7]3[C:2]([C:27]4[C:28]([CH3:34])=[CH:29][C:30]([O:32][CH3:33])=[CH:31][C:26]=4[O:25][CH3:24])=[CH:3][CH:4]=[CH:5][C:6]=23)[CH2:12][CH:13]2[CH2:17][CH2:16][O:15][CH2:14]2)[CH2:21][CH2:20]1
Reactant: COc1cc(C)c(OB(O)O)c(OC)c1
Reactant: CCc1nn2c(Br)cccc2c1N(CC1CC1)CC1CCOC1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Ba+2]
Agent: [OH-]
Solvent: O
Solvent: COCCOC
Solvent: CCOC(C)=O
Product: CCc1nn2c(-c3c(C)cc(OC)cc3OC)cccc2c1N(CC1CC1)CC1CCOC1
Temperature: 80 °C
Reaction time: 1 h
Yield: 49.4 %

Procedure:
After dissolving N-(7-bromo-2-ethylpyrazolo[1,5-a]pyridin-3-yl)-N-cyclopropylmethyl-N-tetrahydro-3-furanylmethylamine (150 mg) in 1,2-dimethoxyethane (20 mL) and water (10 mL), 2,4-dimethoxy-6-methylphenylboric acid (155 mg), tetrakis(triphenylphosphine)palladium (0) complex (92 mg) and barium hydroxide octahydrate (250 mg) were added and the mixture was heated and stirred at 80° C. for 1 hour. Water was added to the reaction mixture, extraction was performed with ethyl acetate, the organic layer was washed with brine, dried over anhydrous magnesium sulfate and filtered, and the solvent was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography, and the title compound (88 mg) was obtained from the n-hexane:ethyl acetate (6:1) fraction as a yellow oil.
Reaction SMILES: O(C([C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[CH:12]=[C:11]([C:16]([OH:18])=[O:17])[CH:10]=[CH:9]2)(C)C)O.[OH:19]C(C1C=C2C(=CC=1)C=C(C(O)=O)C=C2)(C)C.OO.Cl(O)(=O)(=O)=O>C(#N)C>[OH:19][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[CH:12]=[C:11]([C:16]([OH:18])=[O:17])[CH:10]=[CH:9]2
Reactant: CC(C)(O)c1ccc2cc(C(=O)O)ccc2c1
Reactant: CC(C)(OO)c1ccc2cc(C(=O)O)ccc2c1
Agent: OO
Agent: [O-][Cl+3]([O-])([O-])O
Solvent: CC#N
Product: O=C(O)c1ccc2cc(O)ccc2c1

Procedure:
The thus obtained white microcrystals consisting of 6-(2-hydroperoxy-2-propyl)naphthalene-2-carboxylic acid and 6-(2-hydroxy-2-propyl)naphthalene-2-carboxylic acid were reacted in acetonitrile at 50° C. for 30 minutes in the presence of hydrogen peroxide and perchloric acid. Thus, the two compounds were subjected to acid decomposition to form 6-hydroxynaphthalene-2-carboxylic acid almost quantitatively.
Reaction SMILES: [CH2:1]([N:3]([CH2:22][CH3:23])[CH2:4][CH2:5][NH:6][C:7]([C:9]1[C:10]([SH:21])=[N:11][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[N:13][CH:14]=1)=[O:8])[CH3:2].II>>[CH2:22]([N:3]([CH2:1][CH3:2])[CH2:4][CH2:5][N:6]1[C:7](=[O:8])[C:9]2[C:10](=[N:11][C:12]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)=[N:13][CH:14]=2)[S:21]1)[CH3:23]
Reactant: CCN(CC)CCNC(=O)c1cnc(-c2ccccc2)nc1S
Agent: II
Product: CCN(CC)CCn1sc2nc(-c3ccccc3)ncc2c1=O
Yield: 68.5 %

Procedure:
Using the procedure of Example 20, 3.3 g (0.01 mol) of 4-mercapto-2-phenyl-pyrimidine-5-carboxylic acid (2-diethylamino-ethyl)-amide (from Preparation 36) and 2.54 g (0.01 mol) of iodine were reacted to give 2.25 g of the title compound after recrystallization from isopropanol, mp 106°-107° C.
Reaction SMILES: C1C=CC=CC=1.C(N(CC)CC)C.[CH3:14][N:15]1[C:19]([OH:20])=[C:18]([C:21](=[O:30])[C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=2[Cl:29])[C:17]([CH3:31])=[N:16]1.[C:32](Cl)(=[O:35])[O:33][CH3:34]>O>[CH3:14][N:15]1[C:19]([O:20][C:32]([O:33][CH3:34])=[O:35])=[C:18]([C:21](=[O:30])[C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=2[Cl:29])[C:17]([CH3:31])=[N:16]1
Reactant: COC(=O)Cl
Reactant: Cc1nn(C)c(O)c1C(=O)c1ccc(Cl)cc1Cl
Solvent: c1ccccc1
Solvent: O
Solvent: CCN(CC)CC
Product: COC(=O)Oc1c(C(=O)c2ccc(Cl)cc2Cl)c(C)nn1C
Reaction time: 12 h
Yield: 92 %

Procedure:
In a mixture of 20 ml. of dry benzene and 0.28 g. of triethylamine is dissolved 0.72 g. of 1,3-dimethyl-4-(2,4-dichlorobenzoyl)-5-hydroxypyrazole and then 0.26 g. of methyl chlorocarbonate is added dropwise at room temperature with stirring. After completion of the dropwise addition, the mixture is stirred at room temperature for 1 hour. After completion of the reaction, the reaction mixture is allowed to stand for 12 hours and then 30 ml. of water is added thereto. Then, a benzene layer is separated and an aqueous layer is extracted with benzene. The benzene layer and the benzene extract are combined and the mixture is washed with water and dried over anhydrous sodium sulfate. Then, the solvent is distilled off from the benzene solution and the resulting residue is recrystallized from a small amount of n-hexane to give 0.77 g. of the desired product as white crystals melting at 86°-88° C. Yield 92%.
Reaction SMILES: CI.[C:3]([O-:6])([O-])=O.[K+].[K+].[Br:9][C:10]1[CH:15]=[C:14]([F:16])[C:13](O)=[C:12]([F:18])[CH:11]=1.C(OCC)(=O)C>CN(C=O)C>[Br:9][C:10]1[CH:15]=[C:14]([F:16])[C:13]([O:6][CH3:3])=[C:12]([F:18])[CH:11]=1
Reactant: O=C([O-])[O-]
Reactant: Oc1c(F)cc(Br)cc1F
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CI
Solvent: CN(C)C=O
Product: COc1c(F)cc(Br)cc1F
Temperature: 25 °C
Reaction time: 24 h
Yield: 66.6 %

Procedure:
Methyl iodide (580 μL, 10.06 mmol) and K2CO3 (2.80 g, 20.12 mmol) were added to a solution of 4-bromo-2,6-difluorophenol (1.05 g, 5.03 mmol) in DMF (10 mL) and stirred at rt under Ar for 24 h. Upon completion, ethyl acetate was added and the reaction was washed with 1% HCl (2×20 mL), brine (1×), dried over MgSO4 and concentrated in vacuo. The residue was purified by flash chromatography (hexane) to afford 4-bromo-2,6-difluoroanisole (747 mg, 67%) as a white solid. See, for example, Chambers, R. D.; et al. J. Fluorine Chem. 2000, 102, 169–174, which is incorporated by reference in its entirety. 1H NMR (CDCl3, 400 MHz) 67.06 (m, 2H), 3.97 (q, 3H, J=1.1 Hz). 13C NMR (CDCl3, 100 MHz) δ 155.8, 136.3, 116.2, 113.8, 61.9. LREIMS found for C7H5F2OBr (M+) 223.0.