Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[CH2:15][CH:2]1[CH2:3][O:4][C:5]1[C:14]2[CH2:13][CH:12]=[CH:11][CH2:10][C:9]=2[CH:8]=[CH:7][CH:6]=1.ClC1C=CC=C(C(OO)=[O:24])C=1>C(Cl)Cl>[O:24]1[CH:12]2[CH:11]1[CH2:10][C:9]1[CH:8]=[CH:7][CH:6]=[C:5]([O:4][CH2:3][CH:2]3[O:1][CH2:15]3)[C:14]=1[CH2:13]2
Reactant: C1=CCc2c(cccc2OCC2CO2)C1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: c1cc2c(c(OCC3CO3)c1)CC1OC1C2
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a well-stirred solution of 7 g. (0.03 m.) of 1-(2,3-epoxy-propoxy)-5,8-dihydro-naphthalene (prepared as described in application Ser. No. 768,176, filed Oct. 16, 1968, issued Oct. 13, 1970, as U.S. Pat. No. 3,534,085) in 60 ml. of CH2Cl2, 7.1 g. (0.03 m.) of 85% m-chloroperbenzoic acid in 100 ml. CH2Cl2 is added dropwise at such a rate that the temperature is maintained between 25° to 30° C. The mixture is stirred overnight at room temperature. The resulting precipitate (m-chlorobenzoic acid) is filtered off and the CH2Cl2 extract is washed successively with sat. NaHCO3 solution, and water. After drying (MgSO4), the solution is evaporated in vacuo to give 7.2 g. (95%) of oil which solidifies. A sample recrystallized from ether gives white needles, m.p. 85°-87°; λ Nujolmax 1330-1350 cm-1 (epoxy), τ CDCl3 absence of vinyl protons 4.0-4.2 region.
Reaction SMILES: [N:1]1([CH2:6][CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]([C:17]3[C:18]4[CH:42]=[CH:41][C:40]([O:43]CC5C=CC=CC=5)=[CH:39][C:19]=4[S:20][C:21]=3[C:22]3[CH:27]=[CH:26][C:25]([O:28][Si](C(C)C)(C(C)C)C(C)C)=[CH:24][CH:23]=3)=O)=[CH:11][CH:10]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH4+:51].[OH-]>C(Cl)(Cl)Cl>[OH:43][C:40]1[CH:41]=[CH:42][C:18]2[C:17]([CH2:15][C:12]3[CH:11]=[CH:10][C:9]([O:8][CH2:7][CH2:6][N:1]4[CH2:2][CH2:3][CH2:4][CH2:5]4)=[CH:14][CH:13]=3)=[C:21]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH2:2][CH2:3][CH2:4][C:5]#[N:51])=[CH:24][CH:23]=3)[S:20][C:19]=2[CH:39]=1
Reactant: [NH4+]
Reactant: CC(C)[Si](Oc1ccc(-c2sc3cc(OCc4ccccc4)ccc3c2C(=O)c2ccc(OCCN3CCCC3)cc2)cc1)(C(C)C)C(C)C
Agent: [OH-]
Solvent: ClC(Cl)Cl
Product: N#CCCCOc1ccc(-c2sc3cc(O)ccc3c2Cc2ccc(OCCN3CCCC3)cc2)cc1

Procedure:
By essentially following the proceedure described in Example 14, Part D, the title compound was prepared as a foam starting from 6-benzyloxy-2-(4-triisopropylsilyloxyphenyl)benzo[b]thiophene-3-yl 4-[2-(1-pyrrolidinyl)ethoxy]phenyl ketone (Part B) in quantitative yield following MPLC (SiO2; 0.5% in CHCl3 sat'd with NH4OH).
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[CH:17][CH:18]=[C:13]3[CH:12]=[C:11]2[C:19](OS(C2C=CC(C)=CC=2)(=O)=O)=[CH:20][CH:21]([CH3:23])[CH3:22])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:35]1([CH3:44])[CH:40]=[CH:39][CH:38]=[C:37](B(O)O)[CH:36]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[CH:17][CH:18]=[C:13]3[CH:12]=[C:11]2[C:19]([C:37]2[CH:36]=[C:35]([CH3:44])[CH:40]=[CH:39][CH:38]=2)=[CH:20][CH:21]([CH3:23])[CH3:22])(=[O:8])=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: Cc1cccc(B(O)O)c1
Reactant: Cc1ccc(S(=O)(=O)OC(=CC(C)C)c2cc3cccnc3n2S(=O)(=O)c2ccccc2)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: Cc1cccc(C(=CC(C)C)c2cc3cccnc3n2S(=O)(=O)c2ccccc2)c1
Temperature: 25 °C
Yield: 118.8 %

Procedure:
A suspension of toluene-4-sulfonic acid-1-(1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methyl-but-1-enyl ester (3.0 g, 6.04 mmol), m-tolylboronic acid (2.05 g, 15.1 mmol), bis(triphenylphosphine)palladium(II) dichloride (0.5 g, 0.71 mmol) in dioxane (30 mL) and an aqueous sodium carbonate solution (2N, 15 mL) was heated in a microwave at ˜90° C. for 2 h. The reaction mixture was cooled to 25° C., diluted with ethyl acetate (300 mL), washed with a saturated aqueous sodium bicarbonate solution and saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Silica gel column chromatography (300-400 mesh, 9% ethyl acetate/petroleum ether) afforded 1-benzenesulfonyl-2-(3-methyl-1-m-tolyl-but-1-enyl)-1H-pyrrolo[2,3-b]pyridine (2.99 g, crude) as a white solid, which was used in the next step without further purification: 1H NMR (300 MHz, CDCl3) δ ppm 8.49 (dd, 1H, J1=4.8 Hz, J2=0.9 Hz), 7.89 (dd, 1H, J1=7.8 Hz, J2=1.5 Hz), 7.61 (dd, 2H, J1=8.4 Hz, J2=1.5 Hz), 7.43-7.01 (m, 7H), 6.89 (s, 1H), 6.52 (s, 1H), 6.11 (d, 1H, J=10.2 Hz), 2.73-2.60 (m, 1H), 2.17 (s, 3H), 1.12 (dd, 6H, J1=9.3 Hz, J2=6.6 Hz).
Reaction SMILES: [Cl:1][C:2]1[C:3]([CH3:12])=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5](O)([CH3:7])[CH3:6].C1(C)C=CC=CC=1.C(O)(=O)C(O)=O>O>[CH3:12][C:3]1[C:4]([C:5]([CH3:7])=[CH2:6])=[CH:9][CH:10]=[CH:11][C:2]=1[Cl:1]
Reactant: Cc1c(Cl)cccc1C(C)(C)O
Agent: O=C(O)C(=O)O
Solvent: O
Solvent: Cc1ccccc1
Product: C=C(C)c1cccc(Cl)c1C
Yield: 53.4 %

Procedure:
190 g of 3-chloro-2-methyl-alpha,alpha-dimethylbenzyl alcohol are refluxed with 1.5 l of toluene and 370 g of oxalic acid under a water separator until no more water separates off. The oxalic acid is filtered off under suction and the filtrate is washed with sodium bicarbonate solution, dried over sodium sulfate and evaporated down. Fractional distillation of the residue gives 91.5 g of the desired compound, which is listed in Table 1 as Example 2.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].[CH2:14]([NH2:18])[CH:15]([CH3:17])[CH3:16].C(N(CC)CC)C>O1CCCC1>[CH2:14]([NH:18][C:6](=[O:7])[C:5]1[CH:9]=[CH:10][C:2]([Cl:1])=[C:3]([N+:11]([O-:13])=[O:12])[CH:4]=1)[CH:15]([CH3:17])[CH3:16]
Reactant: O=C(Cl)c1ccc(Cl)c([N+](=O)[O-])c1
Reactant: CC(C)CN
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(C)CNC(=O)c1ccc(Cl)c([N+](=O)[O-])c1

Procedure:
Prepared analogously to Example 24b from 4-chloro-3-nitro-benzoylchloride, isobutylamine and triethylamine in tetrahydrofuran.
Reaction SMILES: [OH:1][C@H:2]1[CH2:19][C@@:18]2([CH3:20])[C@@H:5]([CH2:6][CH2:7][C@@H:8]3[C@@H:17]2[C@H:16]([NH:21][CH2:22][CH2:23][CH:24]([CH3:26])[CH3:25])[CH2:15][C@@:13]2([CH3:14])[C@H:9]3[CH2:10][CH2:11][C@@H:12]2[C:27]([O:29][CH3:30])=[O:28])[CH2:4][C@@H:3]1[OH:31].S(=O)(=O)(O)O.[CH2:37](O)[CH2:38]C>>[OH:1][C@H:2]1[CH2:19][C@@:18]2([CH3:20])[C@@H:5]([CH2:6][CH2:7][C@@H:8]3[C@@H:17]2[C@H:16]([NH:21][CH2:22][CH2:23][CH:24]([CH3:26])[CH3:25])[CH2:15][C@@:13]2([CH3:14])[C@H:9]3[CH2:10][CH2:11][C@@H:12]2[C:27]([O:29][CH2:30][CH2:37][CH3:38])=[O:28])[CH2:4][C@@H:3]1[OH:31]
Reactant: CCCO
Reactant: COC(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@H](O)[C@@H](O)C[C@]4(C)[C@H]3[C@H](NCCC(C)C)C[C@]12C
Agent: O=S(=O)(O)O
Product: CCCOC(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@H](O)[C@@H](O)C[C@]4(C)[C@H]3[C@H](NCCC(C)C)C[C@]12C

Procedure:
A solution of methyl 2β,3α-dihydroxy-11α-(3-methylbutylamino)-5α-androstane-17β-carboxylate (437 mg) in propan-1-ol (30 ml) was heated at 100° C. with conc. sulphuric acid (0.2 ml) for 40 h. The cooled mixture was concentrated by evaporation and the residue diluted with water (150 ml) and brought to pH 10 by the addition of 0.88 ammonia solution. The suspension was extracted with ethyl acetate (3×) and the extracts washed with brine, dried and evaporated to give a solid. This was crystallised from ethyl acetate to give the title compound (70 mg), m.p. 140°-142° C., [α]D +17.2°.
Reaction SMILES: [Mg].[O:2]([CH2:10][CH2:11][C:12]#[C:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]I)[Si:3]([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4].C(Br)C.[CH2:23]1[O:26][CH:24]1[CH3:25]>C1COCC1>[O:2]([CH2:10][CH2:11][C:12]#[C:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:23][CH:24]([OH:26])[CH3:25])[Si:3]([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4]
Reactant: CC1CO1
Reactant: CC(C)(C)[Si](C)(C)OCCC#CCCCCCI
Agent: [Mg]
Solvent: CCBr
Solvent: C1CCOC1
Product: CC(O)CCCCCCC#CCCO[Si](C)(C)C(C)(C)C
Reaction time: 0.5 h
Yield: 45.9 %

Procedure:
To magnesium powder (830 mg, 35 mmol) and 18 (8.7 g, 23 mmol) in 40 mL of dry THF under nitrogen was added ethyl bromide (0.1 mL,=1.3 mmol). Grignard formation was maintained by refluxing for 3 hr. After the iodide (18) was consumed, 2.2 g (11.5 mmol) of cuprous iodide was added. The mixture was cooled in an ice-bath and stirred for 30 min. Propylene oxide (2.7 g, 46 mmol) diluted in 10 mL of dry THF was added dropwise, the reaction stirred for 30 min at 23° C. and then quenched with saturated aqueous ammonium chloride (100 mL). The ether extract (3×75 mL) of the aqueous mixture was washed with brine (3×75 mL). The isolated product was purified by chromatography9 on 180 g (20 cm×4.5 cm I.D. column) of silica gel (20% EtOAc in hexane) to give 3.3 g (46% yield) of 19.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([CH2:8][OH:9])[CH:5]=[CH:4][CH:3]=1.Cl[C:11]([CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])=O>O1CCOCC1>[OH:9][CH2:8][C:6]1[N:7]2[C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:11][N:1]=[C:2]2[CH:3]=[CH:4][CH:5]=1
Reactant: Nc1cccc(CO)n1
Reactant: CCOC(=O)CC(=O)Cl
Solvent: C1COCCO1
Product: CCOC(=O)c1cnc2cccc(CO)n12

Procedure:
The title product is prepared by the reaction of the title compound from Example 3 with ethyl a-chloroformylacetate by the method of Example 4 or in dioxane by the procedure of W. W. Paudley; R. A. VanDahm; Y. N. Park, J. Heterocyclic Chem., 1972, (9), 81-85.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([C:9]#[CH:10])[CH:5]=[C:6]([CH3:8])[CH:7]=1.I[C:12]1[CH:18]=[C:17]([N+:19]([O-:21])=[O:20])[CH:16]=[CH:15][C:13]=1[NH2:14]>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>[CH3:1][C:2]1[CH:3]=[C:4]([C:9]#[C:10][C:12]2[CH:18]=[C:17]([N+:19]([O-:21])=[O:20])[CH:16]=[CH:15][C:13]=2[NH2:14])[CH:5]=[C:6]([CH3:8])[CH:7]=1
Reactant: Nc1ccc([N+](=O)[O-])cc1I
Reactant: C#Cc1cc(C)cc(C)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Product: Cc1cc(C)cc(C#Cc2cc([N+](=O)[O-])ccc2N)c1
Temperature: 25 °C

Procedure:
To a solution of 3,5-dimethylphenylethyne (156 mg in 7 mL of dry, nitrogen saturated triethylamine) was added 2-iodo-4-nitroaniline (264 mg, prepared essentially as described in: Toth, I. Helv. Chim. Acta, 1971, 54, 1486.) followed by tetrakis(triphenylphosphine)palladium (23 mg) and cuprous bromide (10 mg) and the mixture heated to reflux on an oil bath. After 2 hours the mixture was cooled to room temperature, concentrated in vacuo and purified by flash chromatography on silica gel (hexane:methylene chloride:ethyl acetate, 15:8:1) to give the title compound (256 mg).
Reaction SMILES: [NH2:1][CH2:2][C:3]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([NH:15][C:16]([C:18]1([C:21]3[CH:29]=[CH:28][C:24]4[O:25][CH2:26][O:27][C:23]=4[CH:22]=3)[CH2:20][CH2:19]1)=[O:17])=[CH:10][CH:9]=2)([CH3:5])[CH3:4].N1C=CC=CC=1.[C:36](OC(=O)C)(=[O:38])[CH3:37].O>ClCCl>[C:36]([NH:1][CH2:2][C:3]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([NH:15][C:16]([C:18]1([C:21]3[CH:29]=[CH:28][C:24]4[O:25][CH2:26][O:27][C:23]=4[CH:22]=3)[CH2:20][CH2:19]1)=[O:17])=[CH:10][CH:9]=2)([CH3:4])[CH3:5])(=[O:38])[CH3:37]
Reactant: CC(C)(CN)c1cc2cc(NC(=O)C3(c4ccc5c(c4)OCO5)CC3)ccc2[nH]1
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Solvent: ClCCl
Solvent: O
Product: CC(=O)NCC(C)(C)c1cc2cc(NC(=O)C3(c4ccc5c(c4)OCO5)CC3)ccc2[nH]1
Reaction time: 2 h
Yield: 72.6 %

Procedure:
To a solution of N-(2-(1-amino-2-methylpropan-2-yl)-1H-indol-5-yl)-1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (21 mg, 0.054 mmol) in dichloromethane (1 mL) was added pyridine (14 μL, 0.16 mmol) followed by acetic anhydride (6.0 μL, 0.059 mmol). The mixture was stirred for 2 h. Water was added and the mixture was extracted with dichloromethane, evaporated, coevaporated with toluene (3×) and purified by silica gel chromatography (60-100% ethylacetate in hexane) to give N-(2-(1-acetamido-2-methylpropan-2-yl)-1H-indol-5-yl)-1-(benzo[d][1,3]-dioxol-5-yl)cyclopropanecarboxamide (17 mg, 73%). 1H NMR (400 MHz, DMSO) δ 10.79 (s, 1H), 8.39 (s, 1H), 7.66 (t, J=6.2 Hz, 1H), 7.56 (d, J=1.7 Hz, 1H), 7.18-7.14 (m, 1H), 7.02-6.89 (m, 4H), 6.08 (d, J=1.5 Hz, 1H), 6.03 (s, 2H), 3.31 (d, J=6.2 Hz, 2H), 1.80 (s, 3H), 1.41-1.38 (m, 2H), 1.26 (s, 6H), 1.04-1.01 (m, 2H).
Reaction SMILES: I[C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=1.[CH3:13][C:14]1([CH3:21])[CH2:17][CH:16]([C:18](Cl)=[O:19])[CH2:15]1>O1CCCC1.Cl.[Cu]I>[CH2:9]([O:8][C:6](=[O:7])[C:5]1[CH:11]=[CH:12][C:2]([C:18]([CH:16]2[CH2:17][C:14]([CH3:21])([CH3:13])[CH2:15]2)=[O:19])=[CH:3][CH:4]=1)[CH3:10]
Reactant: CCOC(=O)c1ccc(I)cc1
Reactant: CC1(C)CC(C(=O)Cl)C1
Agent: [Cu]I
Agent: Cl
Solvent: C1CCOC1
Product: CCOC(=O)c1ccc(C(=O)C2CC(C)(C)C2)cc1
Temperature: -40 °C
Reaction time: 0.67 h
Yield: 104.1 %

Procedure:
Ethyl 4-iodobenzoate (600 mg, 2.17 mmol) was dissolved in tetrahydrofuran (6.0 mL) and brought to −40° C. Isopropylmagnesium chloride lithium chloride complex solution (1.0 M in tetrahydrofuran, 0.365 mL, 2.17 mmol) was added dropwise and the yellow-red solution was stirred at −40° C. for 40 min. CuI (124 mg, 0.65 mmol) was added in one portion and the mixture was then stirred at −15° C. for 20 min to dissolve all the solids. The yellow solution was then brought back to −40° C. and 3,3-dimethylcyclobutanecarbonyl chloride (Intermediate 22) (450 mg, 3.07 mmol) was added dropwise. The color changed from slightly green to yellow, then red, then yellow. The mixture was warmed to 0° C. over 2 h in the same bath. The mixture was diluted with 1 N HCl and extracted with ethyl acetate (3 times). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo. The crude material was partially purified by silica gel flash chromatography (ethyl acetate/heptane) to give impure 4-(3,3-dimethyl-cyclobutanecarbonyl)-benzoic acid ethyl ester (588 mg). 1H NMR (400 MHz, CDCl3) δ 8.11 (d, J=8.4 Hz, 2 H) 7.94 (d, J=8.4 Hz, 2 H) 4.38-4.48 (m, 2 H) 3.90 (quin, J=8.8 Hz, 1 H) 2.16-2.29 (m, 2 H) 2.04-2.13 (m, 2 H) 1.42 (t, J=7.2 Hz, 3 H) 1.28 (s, 3 H) 1.09 (s, 3 H); MS (M+1): 261.4.
Reaction SMILES: [C:1]([N:5]1[C:9]([CH2:10][CH2:11][CH:12]=O)=[CH:8][C:7]([CH2:14][CH2:15][CH3:16])=[N:6]1)([CH3:4])([CH3:3])[CH3:2].[CH3:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([N:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)=[CH:21][CH:20]=1.CCN(C(C)C)C(C)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>>[C:1]([N:5]1[C:9]([CH2:10][CH2:11][CH2:12][N:28]2[CH2:27][CH2:26][N:25]([C:22]3[CH:21]=[CH:20][C:19]([O:18][CH3:17])=[CH:24][CH:23]=3)[CH2:30][CH2:29]2)=[CH:8][C:7]([CH2:14][CH2:15][CH3:16])=[N:6]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CCCc1cc(CCC=O)n(C(C)(C)C)n1
Reactant: COc1ccc(N2CCNCC2)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Product: CCCc1cc(CCCN2CCN(c3ccc(OC)cc3)CC2)n(C(C)(C)C)n1

Procedure:
162 mg (83%) of target compound was obtained by using a method same as in Example 1 by using 3-(1-tert-butyl-3-propyl-1H-pyrazol-5-yl)propanal (100 mg, 0.450 mmol), 1-(4-methoxyphenyl)piperazine (87 mg, 0.450 mmol), DIPEA (0.118 mL, 0.675 mmol) and NaBH(OAc)3 (286 mg, 1.350 mmol).
Reaction SMILES: C([O-])([O-])=O.[Na+].[Na+].[CH:7]([C:9]1[CH:14]=[CH:13][C:12](B(O)O)=[CH:11][CH:10]=1)=[O:8].Cl[C:19]1[N:24]=[CH:23][C:22]([CH2:25][CH3:26])=[CH:21][N:20]=1>C(O)C.C1(C)C=CC=CC=1.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[CH2:25]([C:22]1[CH:21]=[N:20][C:19]([C:12]2[CH:13]=[CH:14][C:9]([CH:7]=[O:8])=[CH:10][CH:11]=2)=[N:24][CH:23]=1)[CH3:26]
Reactant: O=Cc1ccc(B(O)O)cc1
Reactant: CCc1cnc(Cl)nc1
Agent: Cl[Pd]Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Solvent: CCO
Product: CCc1cnc(-c2ccc(C=O)cc2)nc1
Temperature: 25 °C
Yield: 76.3 %

Procedure:
A suspension of saturated aq. Na2CO3 (10 mL) and 4-formylphenylboronic acid (1.80 g, 12.0 mmol) in ethanol (5 mL) was added to a solution of 2-chloro-5-ethylpyrimidine (1.20 mL, 10.0 mmol) and [1,4-bis(diphenylphosphino)butane]palladium(II) dichloride (0.300 g, 0.5 mmol) in toluene (20 mL). The reaction mixture was heated to reflux for 5 h, cooled to room temperature, diluted with ethyl acetate, washed with sat. aq. NaHCO3 and brine, dried with Na2SO4, and concentrated in vacuo. Purification by medium pressure liquid chromatography (SiO2, 3:1 hexanes/ethyl acetate) gave 1.62 g (76%) of the title compound. MS 213 (M+H)+.
Reaction SMILES: [F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]([OH:12])[O:5][C:6]2=[O:7].[C:13](=O)([O-])[O-].[K+].[K+].CI>CC(C)=O>[F:1][C:2]1[C:3]([CH:4]=[O:12])=[C:8]([CH:9]=[CH:10][CH:11]=1)[C:6]([O:5][CH3:13])=[O:7]
Reactant: O=C1OC(O)c2c(F)cccc21
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CC(C)=O
Product: COC(=O)c1cccc(F)c1C=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 95.3 %

Procedure:
A stirred mixture containing 7.36 g 4-fluoro-3-hydroxyphthalide, 18.15 g potassium carbonate and 11 mL methyl iodide in 125 mL acetone is heated at reflux for two hours. After stirring overnight at room temperature, the mixture is filtered and concentrated. The residue is dispersed in 200 mL ether, filtered and the filtrate concentrated to give 7.6 g residue which is used directly without further purification. The nmr spectrum of this material is consistent with that expected for the desired product.
Reaction SMILES: [C:1]1(B(O)O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.Br[C:15]1[S:19][C:18]([S:20]([N:23]2[CH:27]=[CH:26][CH:25]=[CH:24]2)(=[O:22])=[O:21])=[CH:17][CH:16]=1>>[C:1]1([C:15]2[S:19][C:18]([S:20]([N:23]3[CH:27]=[CH:26][CH:25]=[CH:24]3)(=[O:21])=[O:22])=[CH:17][CH:16]=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: O=S(=O)(c1ccc(Br)s1)n1cccc1
Reactant: OB(O)c1cccc2ccccc12
Product: O=S(=O)(c1ccc(-c2cccc3ccccc23)s1)n1cccc1
Yield: 87 %

Procedure:
N-[5-(1-napthyl)thiophene-2-sulfonyl]pyrrole was prepared in the same manner as described in Example 32C from 1-napthaleneboronic acid (353 mg, 2.05 mmol) and N-(5-bromothiophene-2-sulfonyl)pyrrole (600 mg, 2.05 mmol). Purification by column chromatography using 2% ethyl acetate/hexanes gave the pure sulfonamide in 87% yield as a pale yellow clear oil.
Reaction SMILES: [C:1]([CH2:6][CH:7]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([O:3][CH2:4][CH3:5])=[O:2].[CH2:27]([O:34][C:35]1[CH:42]=[CH:41][C:38]([CH:39]=O)=[CH:37][CH:36]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.CCOC(C)=O>C1COCC1>[CH2:27]([O:34][C:35]1[CH:42]=[CH:41][C:38](/[CH:39]=[C:6](\[CH3:7])/[C:1]([O:3][CH2:4][CH3:5])=[O:2])=[CH:37][CH:36]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
Reactant: O=Cc1ccc(OCc2ccccc2)cc1
Reactant: CCOC(=O)CC=P(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CCOC(=O)/C(C)=C/c1ccc(OCc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of (carbethoxyethylidene)triphenylphosphorane (5.50 g, 15.2 mmol) (commercially available from Aldrich, catalog #377708) in THF (25 mL) was added 4-(benzyloxy)benzaldehyde (12.1) (2.93 g, 13.8 mmol) (commercially available from Lancaster, catalog #6285) in THF (10 mL) under nitrogen at −78° C. The reaction was allowed to slowly warm to room temperature and stirred for 2 hours. EtOAc (100 mL) was added, and the mixture was washed with brine (30×2 mL). The organic layer was dried over MgSO4. The solvent was removed by evaporation. The crude product was purified by passing through a short silica gel column, eluting with hexane/EtOAc (85/15) to give the title compound. 1H NMR (CDCl3) δ 7.65 (s, 1H), 7.46-7.35 (m, 7H), 7.01 (d, 2H), 5.11(s, 2H), 4.28 (q, 2H), 2.14 (s, 3H), 1.36 (t, 3H).
Reaction SMILES: [CH3:1][C:2]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH2:14][CH2:15][O:16][C@@H:17]2[CH2:22][CH2:21][CH2:20][C@H:19]([O:23][CH2:24][C:25]3[N:26]=[C:27]([C:31]4[CH:32]=[C:33]([CH3:37])[CH:34]=[CH:35][CH:36]=4)[O:28][C:29]=3[CH3:30])[CH2:18]2)[C:3]=1[C:4]([O:6]CC)=[O:5].[OH-].[Na+]>CO.Cl.C(OCC)(=O)C>[CH3:1][C:2]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH2:14][CH2:15][O:16][C@@H:17]2[CH2:22][CH2:21][CH2:20][C@H:19]([O:23][CH2:24][C:25]3[N:26]=[C:27]([C:31]4[CH:32]=[C:33]([CH3:37])[CH:34]=[CH:35][CH:36]=4)[O:28][C:29]=3[CH3:30])[CH2:18]2)[C:3]=1[C:4]([OH:6])=[O:5]
Reactant: CCOC(=O)c1c(C)cccc1OCCO[C@@H]1CCC[C@H](OCc2nc(-c3cccc(C)c3)oc2C)C1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: CCOC(C)=O
Product: Cc1cccc(-c2nc(CO[C@H]3CCC[C@@H](OCCOc4cccc(C)c4C(=O)O)C3)c(C)o2)c1
Temperature: 80 °C
Reaction time: 12 h

Procedure:
Unpurified ethyl (1R,3S)-2-methyl-6-{2-[3-(5-methyl-2-m-tolyloxazol-4-ylmethoxy)cyclohexyloxy]ethoxy}benzoate are dissolved in 3 ml of methanol, and 0.25 ml of a 5 N sodium hydroxide solution are added. The mixture is stirred at 60° C. for 8 h and at 80° C. for 12 h. After cooling, the mixture is taken up in 2N HCl/ethyl acetate, the organic phase is dried over sodium sulfate and the solvent is removed under reduced pressure. The residue is purified by RP-HPLC. This gives (1R,3S)-2-methyl-6-{2-[3-(5-methyl-2-m-tolyloxazol-4-ylmethoxy)cyclohexyloxy]ethoxy)benzoic acid as a colorless oil. C28H33NO6 (479.58), MS (ESI). 480 (M+H+).
Reaction SMILES: [C:1]1([C:7]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[N:8]2[CH:12]=[C:11]([CH2:13][CH2:14][C:15]#[C:16][CH2:17][CH2:18][CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)[N:10]=[CH:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.N1C2C(=CC=CC=2)C=CC=1>C(OCC)(=O)C.[Pd].CC([O-])=O.CC([O-])=O.[Pb+2]>[C:31]1([C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[N:8]2[CH:12]=[C:11]([CH2:13][CH2:14]/[CH:15]=[CH:16]\[CH2:17][CH2:18][CH:19]3[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]3)[N:10]=[CH:9]2)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1
Reactant: C(#CCCC1CCCCC1)CCc1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
Agent: [Pd]
Agent: CC(=O)[O-]
Agent: [Pb+2]
Solvent: CCOC(C)=O
Solvent: c1ccc2ncccc2c1
Product: C(=C\CCC1CCCCC1)\CCc1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
Temperature: 25 °C
Reaction time: 48 h
Yield: 101.6 %

Procedure:
1-[1-Triphenylmethyl-1H-imidazol-4-yl]-6-cyclohexyl-3-hexyne (6.8 g, 0.014 mol) was dissolved in dry ethyl acetate (100 ml). Lindlar catalyst (5%, 1.8 g Pd on CaCO3 poisoned with lead) and 15 mgs of quinoline were added. H2 was added to the reaction flask via a balloon. The reaction flask was evacuated and then refilled with H2 gas from the balloon 3 times. The reaction was left to stir at room temperature under the presence of H2 (1 atm) for 48 hours. The H2 gas was removed and the reaction mixture filtered through a pad of celite with ethyl acetate, the ethyl acetate was removed in vacuo to afford 6.75 g of 1-[1-triphenylmethyl-1H-imidazol-4-yl]-6-cyclohexyl-cis-3-hexene.
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([CH2:10][CH2:11][CH2:12][C:13](O)=[O:14])=[N:2]1.[H-].C([Al+]C(C)(C)C)(C)(C)C.S(=O)(=O)(O)O>C1(C)C=CC=CC=1>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([CH2:10][CH2:11][CH2:12][CH2:13][OH:14])=[N:2]1
Reactant: O=C(O)CCCc1nsc2ccccc12
Agent: CC(C)(C)[Al+]C(C)(C)C
Agent: O=S(=O)(O)O
Agent: [H-]
Solvent: Cc1ccccc1
Product: OCCCCc1nsc2ccccc12
Temperature: -10 °C
Reaction time: 2 h
Yield: 32.7 %

Procedure:
4-(1,2-Benzisothiazol-3-yl)butyric acid (C. Branca et al, Phytochemistry 14, 1975, 2545) (17 g) was dissolved in dry toluene (500 ml) and cooled to -10° C. Di-tert-butyl aluminium hydride (120 ml of an 1 M solution in toluene) was added dropwise at -10° C. followed by stirring for 2 h at room temperature. Dilute sulfuric acid (2 M, is 300 ml) was added, the phases separated, the aqeous phase extracted with ether, and the combined organic phases dried over magnesium sulfate. Removal of solvents in vacuo left a viscous oil which was purified by column chromatography (silica gel, eluent: ether). 4-(1,2-Benzisothiazol-3-yl)-1-butanol (5.2 g) was obtained as an oil.