Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:17]=[CH:16][C:5]2[N:6]=[C:7]([O:9][CH:10]3[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]3)[S:8][C:4]=2[CH:3]=1.Br[C:19]1[S:20][C:21]([CH3:24])=[N:22][N:23]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[Br:1][C:2]1[CH:17]=[CH:16][C:5]2[N:6]=[C:7]([O:9][CH:10]3[CH2:11][CH2:12][N:13]([C:19]4[S:20][C:21]([CH3:24])=[N:22][N:23]=4)[CH2:14][CH2:15]3)[S:8][C:4]=2[CH:3]=1
Reactant: Cc1nnc(Br)s1
Reactant: Brc1ccc2nc(OC3CCNCC3)sc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1nnc(N2CCC(Oc3nc4ccc(Br)cc4s3)CC2)s1
Temperature: 110 °C
Reaction time: 8 h
Yield: 57.7 %

Procedure:
To a solution of 6-bromo-2-(piperidin-4-yloxy)benzo[d]thiazole (Compound 1B, 600 mg, 1.916 mmol) and 2-bromo-5-methyl-1,3,4-thiadiazole (480 mg, 2.68 mmol) in DMF (15 mL) was added potassium carbonate (794 mg, 5.75 mmol). The reaction mixture was stirred at 110° C. overnight. The reaction mixture was cooled to rt, diluted with water (20 mL), and extracted with EtOAc (3×10 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated. The residue was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 100% EtOAc) to afford 6-bromo-2-(1-(5-methyl-1,3,4-thiadiazol-2-yl)piperidin-4-yloxy)benzo[d]thiazole (455 mg, 1.106 mmol, 58% yield) as a yellow solid. 1H NMR (500 MHz, chloroform-d) δ ppm 7.78 (1H, d, J=1.9 Hz), 7.50-7.56 (1H, m), 7.45-7.50 (1H, m), 5.40-5.52 (1H, m), 3.77-3.88 (2H, m), 3.54-3.66 (2H, m), 2.61 (3H, s), 2.19-2.29 (2H, m), 2.07-2.17 (2H, m). LCMS (m/z)=412 (M+H)+.
Reaction SMILES: [CH3:1][O-:2].[Na+].[Na].[CH2:5]([O:12][C:13]1[C:18](I)=[C:17]([CH3:20])[N:16]=[C:15]([CH3:21])[C:14]=1[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[NH4+].[Cl-]>[Cu]I.CO>[CH2:5]([O:12][C:13]1[C:18]([O:2][CH3:1])=[C:17]([CH3:20])[N:16]=[C:15]([CH3:21])[C:14]=1[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: C[O-]
Reactant: CCCCCCCc1c(C)nc(C)c(I)c1OCc1ccccc1
Agent: [Cu]I
Agent: [Cl-]
Agent: [NH4+]
Solvent: CO
Product: CCCCCCCc1c(C)nc(C)c(OC)c1OCc1ccccc1
Temperature: 110 °C

Procedure:
To a solution of sodium methoxide prepared from sodium (5.0 mg, 0.23 mmol) and MeOH (1 mL) were added the iodo derivative 19 (27 mg, 0.06 mmol) and CuI (1.66 mg, 0.009 mmol). The reaction mixture was heated at 110° C. for 18 h and cooled, and 1 M aqueous NH4Cl was added. The mixture was extracted with portions of ethyl ether. The combined organic phase was dried over anhydrous MgSO4 and concentrated under diminished pressure to afford a crude residue. Elution with ethyl acetate gave 4-(benzyloxy)-3-heptyl-5-methoxy-2,6-dimethylpyridine (20) as a light yellow oil: yield 19 mg (71%); silica gel TLC Rf 0.3 (1:1 hexane/ethyl acetate); 1H NMR (CDCl3) δ 0.60-0.89 (m, 3H), 1.26-1.30 (m, 10H), 2.48 (s, 3H), 2.60-2.62 (m, 2H) 2.74 (s, 3H), 3.70 (s, 3H). 4.95 (s, 2H), 7.38-7.42 (m, 4H) and 7.53-7.56 (m, 1H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([S:8][C:9]2[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][C:10]=2[CH2:11]Br)[CH:5]=[CH:6][CH:7]=1.[C-:20]#[N:21]>C(O)C>[Br:1][C:2]1[CH:3]=[C:4]([S:8][C:9]2[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][C:10]=2[CH2:11][C:20]#[N:21])[CH:5]=[CH:6][CH:7]=1
Reactant: [C-]#N
Reactant: O=[N+]([O-])c1ccc(Sc2cccc(Br)c2)c(CBr)c1
Solvent: CCO
Product: N#CCc1cc([N+](=O)[O-])ccc1Sc1cccc(Br)c1

Procedure:
2.16 G. 2-(3'-bromophenylthio)-5-nitrobenzyl bromide is refluxed in 50 cc. ethanol and 2.4 g. of cyanide ion exchange resin for 1/2 hour. The mixture is filtered hot and the resin washed with ethyl acetate. The combined organic filtrates are evaporated to dryness to yield 1.85 g. of crude residue which is chromatographed on silica gel. Elution with benzene affords 800 mg. of the desired compound.
Reaction SMILES: [OH:1][CH2:2][C:3]#[C:4][C:5]1[CH:14]=[C:13]2[C:8]([CH:9]=[C:10]([C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)[C:11](=[O:15])[O:12]2)=[CH:7][CH:6]=1>C1COCC1>[OH:1][CH2:2][CH2:3][CH2:4][C:5]1[CH:14]=[C:13]2[C:8]([CH:9]=[C:10]([C:16]3[CH:17]=[CH:18][C:19]([O:22][CH3:23])=[CH:20][CH:21]=3)[C:11](=[O:15])[O:12]2)=[CH:7][CH:6]=1
Reactant: COc1ccc(-c2cc3ccc(C#CCO)cc3oc2=O)cc1
Solvent: C1CCOC1
Product: COc1ccc(-c2cc3ccc(CCCO)cc3oc2=O)cc1

Procedure:
7-(3-Hydroxyprop-1-ynyl)-3-(4-methoxyphenyl)chromen-2-one is hydrogenated to completion in THF on palladium/active carbon catalyst. The catalyst is filtered off, the solvent is removed in vacuo, and the crude product is recrystallised from toluene/heptane (1:1), giving 7-(3-hydroxypropyl)-3-(4-methoxyphenyl)chromen-2-one as colourless solid.
Reaction SMILES: Cl.[NH2:2][CH:3]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]([F:26])([F:25])[CH:22]([F:24])[F:23])[CH:15]=1)[CH:4]([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([F:12])[N:7]=1)[OH:5].[F:27][C:28]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[C:31]([C:38](O)=[O:39])=[CH:30][CH:29]=1.Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>C(#N)C.O>[F:27][C:28]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[C:31]([C:38]([NH:2][CH:3]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]([F:25])([F:26])[CH:22]([F:23])[F:24])[CH:15]=2)[CH:4]([C:6]2[CH:11]=[CH:10][CH:9]=[C:8]([F:12])[N:7]=2)[OH:5])=[O:39])=[CH:30][CH:29]=1
Reactant: NC(Cc1cccc(OC(F)(F)C(F)F)c1)C(O)c1cccc(F)n1
Reactant: O=C(O)c1ccc(F)c2ccccc12
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: CC#N
Solvent: O
Product: O=C(NC(Cc1cccc(OC(F)(F)C(F)F)c1)C(O)c1cccc(F)n1)c1ccc(F)c2ccccc12
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of (1RS,2RS)-2-amino-1-(6-fluoropyridin-2-yl)-3-[3-(1,1,2,2-tetrafluoroethoxy)phenyl]propan-1-ol hydrochloride (300 mg, 0.75 mmol) in acetonitrile (20 ml) were added 4-fluoronaphthalenecarboxylic acid (141 mg, 0.75 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (216 mg, 1.13 mmol), 1-hydroxybenzotriazole hydrate (115 mg, 0.75 mmol) and triethylamine (1.03 ml, 0.75 mmol), and the mixture was stirred overnight at room temperature. The reaction solution was diluted with water (100 ml) and extracted with ethyl acetate (100 ml×2). The extract was washed successively with water and saturated brine, dried (anhydrous magnesium sulfate) and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1-ethyl acetate). Recrystallization from ethyl acetate-hexane gave the objective substance (306 mg, 76%).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=2)[CH2:9][CH2:10][NH:11][CH3:12])=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:29]2[CH:30]=[N:31][NH:32][CH:33]=2)O1>>[Cl:20][C:16]1[CH:15]=[C:14]([CH:19]=[CH:18][CH:17]=1)[O:13][CH:8]([C:5]1[CH:6]=[CH:7][C:2]([C:29]2[CH:30]=[N:31][NH:32][CH:33]=2)=[CH:3][CH:4]=1)[CH2:9][CH2:10][NH:11][CH3:12]
Reactant: CC1(C)OB(c2cn[nH]c2)OC1(C)C
Reactant: CNCCC(Oc1cccc(Cl)c1)c1ccc(Br)cc1
Product: CNCCC(Oc1cccc(Cl)c1)c1ccc(-c2cn[nH]c2)cc1

Procedure:
[3-(4-Bromo-phenyl)-3-(3-chloro-phenoxy)-propyl]-methyl-amine was reacted with 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole following the procedure set out in Example 1 to give the title compound. LC/MS: (PS-B3) Rt 2.80 [M+H]+ 342.26. 1H NMR (Me-d3-OD) δ 2.19-2.30 (1H, m), 2.30-2.45 (1H, m), 2.72 (3H, s), 3.10-3.28 (2H, m), 5.40-5.47 (1H, m), 6.80-6.88 (1H, d), 6.88-6.94 (1H, d), 6.96 (1H, s), 7.15-7.20 (1H, t), 7.38-7.45 (2H, d), 7.57-7.65 (2H, d), 7.98 (2H, s).
Reaction SMILES: [F:1][C:2]([F:29])([F:28])[C:3]1[CH:4]=[C:5]([CH:21]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:23]=1)[CH2:6][N:7]([CH2:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1Br)[C:8](=[O:11])[O:9][CH3:10].C(=O)([O-])[O-].[K+].[K+].[CH3:36][O:37][C:38]1[CH:43]=[CH:42][C:41]([CH3:44])=[CH:40][C:39]=1B(O)O.CC(C)=O.O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC(C)=O.CCCCCC>[CH3:10][O:9][C:8](=[O:11])[N:7]([CH2:6][C:5]1[CH:4]=[C:3]([C:2]([F:29])([F:28])[F:1])[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=1)[CH2:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1[C:39]1[CH:40]=[C:41]([CH3:44])[CH:42]=[CH:43][C:38]=1[O:37][CH3:36]
Reactant: COc1ccc(C)cc1B(O)O
Reactant: COC(=O)N(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)Cc1cc(F)ccc1Br
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: CCCCCC
Solvent: O
Solvent: CC(C)=O
Product: COC(=O)N(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)Cc1cc(F)ccc1-c1cc(C)ccc1OC

Procedure:
A mixture of the Methyl [3,5-bis(trifluoromethyl)benzyl](2-bromo-5-fluorobenzyl)carbamate from Step B (0.02 g, 0.04 mmol), potassium carbonate (0.011 g, 0.08 mmol), 2-methoxy-5-methyl phenyl boronic acid (0.008 g, 0.05 mmol) and catalytic amount of palladium acetate (1 mg) in 4:1 acetone/water (2.5 ml) was heated to and maintained at reflux for 1 h. TLC analysis (acetone/hexane=5:95) showed no starting material. The solvent was removed under reduced pressure and the residue was extracted with methylene chloride (3×10 ml). The combined organic layers were washed with brine and dried over sodium sulfate. The title compound was obtained by preparative thin layer chromatography using acetone:hexane (5:95) as the eluant. 1H NMR (CDCl3, 500 MHz) δ 7.75 (s, 1H), 7.50 (s, 1H), 7.38 (s, 1H), 7.20 (m, 2H), 7.04 (m, 2H), 6.84 (s, 1H), 6.80 (m, 1H), 4.18-4.60 (m, 4H), 3.80 (s, 3H), 3.68 (s, 3H), 2.32 (s, 3H). LC-MS (M+1) 530.4 (4.43 min).
Reaction SMILES: FC(F)(F)C(O)=O.[CH:8]1([N:11]2[CH2:16][CH2:15][CH:14]([N:17]([CH2:27][C:28]3[CH:33]=[C:32]([C:34]4[CH:61]=[CH:60][C:37]5[N:38](C(C6C=CC=CC=6)(C6C=CC=CC=6)C6C=CC=CC=6)[N:39]=[N:40][C:36]=5[CH:35]=4)[CH:31]=[CH:30][C:29]=3[F:62])[C:18](=[O:26])[C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[CH2:13][CH2:12]2)[CH2:10][CH2:9]1.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl>[NH:38]1[C:37]2[CH:60]=[CH:61][C:34]([C:32]3[CH:31]=[CH:30][C:29]([F:62])=[C:28]([CH:33]=3)[CH2:27][N:17]([CH:14]3[CH2:13][CH2:12][N:11]([CH:8]4[CH2:10][CH2:9]4)[CH2:16][CH2:15]3)[C:18](=[O:26])[C:19]3[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=3)=[CH:35][C:36]=2[N:40]=[N:39]1
Reactant: O=C(c1ccc(F)cc1)N(Cc1cc(-c2ccc3c(c2)nnn3C(c2ccccc2)(c2ccccc2)c2ccccc2)ccc1F)C1CCN(C2CC2)CC1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C(c1ccc(F)cc1)N(Cc1cc(-c2ccc3[nH]nnc3c2)ccc1F)C1CCN(C2CC2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 97.2 %

Procedure:
Trifluoroacetic acid (TFA, 1 mL) was added to a solution of N-(1-cyclopropyl-piperidin-4-yl)-4-fluoro-N-[2-fluoro-5-(1-trityl-1H-benzotriazol-5-yl)-benzyl]-benzamide (14 mg, 0.019 mmol) in 1 mL of dichloromethane and the resulting mixture stirred at ambient temperature overnight and then the mixture was neutralized by careful addition of 1M sodium carbonate. The layers were separated, the aqueous phase was extracted with dichloromethane, and the combined organic phases were dried over magnesium sulfate, filtered, and the volatiles were removed in vacuo to leave the crude product. Chromatography (elution with methanol/dichloromethane) provided 9 mg of the title compound. LC/MS: Retention time, 2.22 min; (M+H)=488.
Reaction SMILES: [OH:1][C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.[I-].C[N+]1C=CN([C:19](=[O:28])[N:20]([CH3:27])[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)C=1.C(N(CC)CC)C>C(#N)C>[CH:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH:11]=[C:2]([O:1][C:19](=[O:28])[N:20]([CH3:27])[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[N:3]=1
Reactant: Oc1cc2ccccc2cn1
Reactant: CN(C(=O)n1cc[n+](C)c1)c1ccccc1
Agent: [I-]
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CN(C(=O)Oc1cc2ccccc2cn1)c1ccccc1
Yield: 98.2 %

Procedure:
A solution of 3-hydroxyisoquinoline (0.44 g, 3.00 mmol), 1-methyl-3-(methyl-phenyl-carbamoyl)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitrile (15 ml) was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (SiO2, ethyl acetate:heptane (50:50)) yielding the title compound (0.82 g, 99% yield) as a white solid.
Reaction SMILES: Br[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[N:5][C:6](Br)=[CH:7][CH:8]=2)[N:3]=1.CC1(C)C(C)(C)OB([C:21]2[CH:22]=[C:23]([C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:24]=[C:25]([CH:31]=2)[C:26]([O:28][CH2:29][CH3:30])=[O:27])O1.[F-].[Cs+]>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:3]1[C:4]2[C:9](=[CH:8][CH:7]=[C:6]([C:21]3[CH:31]=[C:25]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH:24]=[C:23]([CH:22]=3)[C:32]([O:34][CH2:35][CH3:36])=[O:33])[N:5]=2)[CH:10]=[CH:11][C:2]=1[C:21]1[CH:31]=[C:25]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH:24]=[C:23]([CH:22]=1)[C:32]([O:34][CH2:35][CH3:36])=[O:33]
Reactant: CCOC(=O)c1cc(B2OC(C)(C)C(C)(C)O2)cc(C(=O)OCC)c1
Reactant: Brc1ccc2ccc(Br)nc2n1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cs+]
Agent: [F-]
Product: CCOC(=O)c1cc(C(=O)OCC)cc(-c2ccc3ccc(-c4cc(C(=O)OCC)cc(C(=O)OCC)c4)nc3n2)c1
Yield: 70 %

Procedure:
To a 250 mL Schlenk flask, 2,7-dibromo-1,8-naphthyridine (2.00 g, 6.94 mmol), diethyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isophthalate (6.06 g, 17.40 mmol, this compound was synthesized according to literature method: J. Natera, L. Otero, L. Sereno, F. Fungo, N.-S. Wang, Y.-M. Tsai, T.-Y. Hwu, K.-T. Wong, Macromolecules 2007, 40, 4456-4463), CsF (4.00 g) and Pd(PPh3)4 (200 mg) were added. The flask was connected to a Schlenk line and evacuated of air then refilled with nitrogen. 140 mL of 1,2-dimethoxyethane (DME) was degassed (two hours) and added to the flask through a canula. The flask was equipped with a water condenser and refluxed under nitrogen for 3 days. The solvent was removed on a rotary evaporator. 100 mL of H2O was added and then extracted with CHCl3. The organic phase was dried with MgSO4. After removal of the CHCl3 solvent, the crude product was purified by column chromatography (silica, ethyl acetate/hexane, 20% and then 50%) to give a yellow solid product with a yield of 70% (2.77 g) based on 2,7-dibromo-1,8-naphthyridine. 1H NMR (300 MHz, DMSO-d6): δ 1.42 (t, 12H), 4.46 (q, 8H), 8.43 (d, 2H), 8.60 (s, 2H), 8.69 (d, 2H), 9.07 (s, 4H).
Reaction SMILES: [H-].[Na+].[CH3:3][C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([Cl:12])[CH:7]=1)=[O:5].[C:13](OCC)(=[O:19])[C:14]([O:16][CH2:17][CH3:18])=[O:15].Cl>CN(C=O)C.CC(=O)OCC>[CH2:17]([O:16][C:14](=[O:15])[C:13](=[O:19])[CH2:3][C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([Cl:12])[CH:7]=1)=[O:5])[CH3:18]
Reactant: CCOC(=O)C(=O)OCC
Reactant: CC(=O)c1cccc(Cl)c1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCOC(=O)C(=O)CC(=O)c1cccc(Cl)c1
Temperature: 80 °C
Reaction time: 1 h
Yield: 67.2 %

Procedure:
Sodium hydride (60% oil dispersion, 1.24 g, 31.1 mmol) was added in portions to a solution of 3-chloroacetophenone (4.0 g, 25.9 mmol) and diethyl oxalate (4.54 g, 31.1 mmol) in DMF (32 mL) at 0° C. The mixture was stirred at r.t for 1 h and was then heated at 80° C. for 0.5 h. After cooling, the mixture was treated with 3N HCl and then diluted with EA. The organic layer was washed with water and saturated brine, dried (Na2SO4), filtered and concentrated. The resulting residue was then purified by column chromatography using 0-10% EA in hex to afford the title compound (4.43g, 67%). 1H NMR: 15.12 (br s, 1H), 7.98 (s, 1H), 7.88 (d, 1H), 7.58 (d, 1H), 7.47 (t, 1H), 7.05 (s, 1H), 4.39 (m, 2H), 1.41 (m, 3H).
Reaction SMILES: [Br-].[CH2:2]([C:8]1[C:9]([C:22]2C=CC=CC=2[P+](C)(C2C=CC=CC=2)C2C=CC=CC=2)=[CH:10][C:11]2[C:12]([CH3:21])([CH3:20])[CH2:13][CH2:14][C:15]([CH3:19])([CH3:18])[C:16]=2[CH:17]=1)[CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].C([Li])CCC.[CH:47]([C:49]1[S:53][C:52]([C:54]([O:56][CH3:57])=[O:55])=[CH:51][CH:50]=1)=O.C(OCC)(=O)C.CCCCCC>C1COCC1.CCCCCC.[Cl-].[NH4+]>[CH2:2]([C:8]1[C:9](/[CH:22]=[CH:47]/[C:49]2[S:53][C:52]([C:54]([O:56][CH3:57])=[O:55])=[CH:51][CH:50]=2)=[CH:10][C:11]2[C:12]([CH3:21])([CH3:20])[CH2:13][CH2:14][C:15]([CH3:19])([CH3:18])[C:16]=2[CH:17]=1)[CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]
Reactant: COC(=O)c1ccc(C=O)s1
Reactant: CCCCCCc1cc2c(cc1-c1ccccc1[P+](C)(c1ccccc1)c1ccccc1)C(C)(C)CCC2(C)C
Agent: [Br-]
Agent: [Cl-]
Agent: [Li]CCCC
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CCCCCCc1cc2c(cc1/C=C/c1ccc(C(=O)OC)s1)C(C)(C)CCC2(C)C
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
A suspension of 1.917 g of (3-hexyl-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-methyl triphenylphosphonium bromide (From Example 7.1) in 40 ml THF was cooled to −78° C. and treated with 1.91 ml of butyllithium 1.6 M in hexane. The mixture was allowed to warm to room temperature for 30 min. then was cooled back to −78° C. A solution of 495 mg of methyl 5-formylthiophene-2-carboxylate in 10 ml THF was added. The mixture was kept at −78° C. for 30 min. then was allowed to warm to room temperature for 30 min. The reaction mixture was diluted with 50 ml of a saturated ammonium chloride solution and extracted with 3 portions of 50 ml of ethyl acetate. The combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo, giving a yellow solid. Flash chromatography (SiO2, 3% ethyl acetate/hexane) gave 1.2 g of a mixture (E/Z) of the desired product. Chromatography on a medium pressure liquid chromatography system (3% ethyl acetate/hexane) provided 1.12 g of the title product without trace of the Z isomer. 1H NMR (CDCl3): 7.69 (d, J=4.5 Hz, 1H), 7.48 (s, 1H), 7.30 (d, J=15.6 Hz, 1H), 7.09 (s, 1H), 7.05 (d, J=4.9 Hz, 1H), 7.04 (d, J=15.6 Hz, 1H), 3.89 (s, 3H), 2.67 (t, J=8.3 Hz, 2H), 1.68 (s, 4H), 1.2-1.5 (m, 8H), 1.32 (s, 6H), 1.28 (s, 6H), 0.90 (t, J=7.0 Hz, 3H).
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Cl[C:34]1[CH:39]=[CH:38][N+:37]([O-:40])=[CH:36][CH:35]=1>COCCOC.C([O-])([O-])=O.[K+].[K+].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:1][C:2]([F:13])([F:12])[C:3]1[CH:8]=[CH:7][C:6]([C:34]2[CH:39]=[CH:38][N+:37]([O-:40])=[CH:36][CH:35]=2)=[CH:5][CH:4]=1
Reactant: [O-][n+]1ccc(Cl)cc1
Reactant: OB(O)c1ccc(C(F)(F)F)cc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: COCCOC
Product: [O-][n+]1ccc(-c2ccc(C(F)(F)F)cc2)cc1
Yield: 25.2 %

Procedure:
A solution of 4-(trifluoromethyl)phenylboronic acid (1.78 g, 9.37 mmol) in DME (10 mL) and aqueous K2CO3 (12 mL, 1.8 M) was degassed with argon for 20 minutes. Triphenylphosphine (797 mg, 3.04 mmol), palladium(II)acetate (174 mg, 0.775 mmol), and 4-chloropyridine 1-oxide (1.00 g, 7.72 mmol) were added sequentially, and the mixture was heated to reflux under an argon atmosphere. After stirring at reflux for 14 h, the mixture was allowed to cool and then filtered. The filtrate was diluted with H2O (25 mL) and extracted with EtOAc (3×25 mL). The organics were dried over Na2SO4, filtered and concentrated to dryness. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH, 95:5) gave the title compound (465 mg, 25%) as white crystals: 1H NMR (500 MHz, CDCl3) δ 8.29 (d, J=7.2 Hz, 2H), 7.75 (d, J=8.3 Hz, 2H), 7.69 (d, J=8.2 Hz, 2H), 7.52 (d, J=7.2 Hz, 2H); ESI MS m/z 240 [M+H]+.
Reaction SMILES: Cl[C:2]1[CH2:6][CH2:5][CH2:4][C:3]=1[CH:7]=O.[CH2:9]([O:11][C:12](=[O:22])[CH2:13][NH:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH3:10]>C1(C)C=CC=CC=1>[CH2:15]([N:14]1[C:13]([C:12]([O:11][CH2:9][CH3:10])=[O:22])=[CH:7][C:3]2[CH2:4][CH2:5][CH2:6][C:2]1=2)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: CCOC(=O)CNCc1ccccc1
Reactant: O=CC1=C(Cl)CCC1
Solvent: Cc1ccccc1
Product: CCOC(=O)c1cc2c(n1Cc1ccccc1)CCC2

Procedure:
46.7 g (0.358 mol) of 2-chloro-1-formylcyclopent-1-ene are dissolved in 400 ml of toluene. 138 g (0.716 mol) of N-benzylglycine ethyl ester are added. The mixture is refluxed for one hour, the ester of reaction being separated off via a water separator. After cooling, any precipitate formed is filtered off with suction and the toluene solution is washed with water, dried and concentrated. The residue is taken up in 300 ml of ethanol, 600 ml of 2N hydrochloric acid are added and the mixture is extracted 3x with petroleum ether. The petroleum ether phase is washed with 2×175 ml of ethanol/2N hydrochloric acid 1:2 and then with 100 ml of saturated NaHCO3 solution, the organic phase is dried over MgSO4, stirred with active charcoal and filtered with suction, and the filtrate is evaporated in vacuo.
Reaction SMILES: [BH2:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[NH2:9].[C:10]([C:14]1[CH:19]=[CH:18][C:17]([S:20](Cl)(=[O:22])=[O:21])=[CH:16][CH:15]=1)([CH3:13])([CH3:12])[CH3:11]>C(=O)=O>[BH2:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[NH:9][S:20]([C:17]1[CH:18]=[CH:19][C:14]([C:10]([CH3:13])([CH3:12])[CH3:11])=[CH:15][CH:16]=1)(=[O:22])=[O:21]
Reactant: Bc1cc(Cl)ccc1N
Reactant: CC(C)(C)c1ccc(S(=O)(=O)Cl)cc1
Agent: O=C=O
Product: Bc1cc(Cl)ccc1NS(=O)(=O)c1ccc(C(C)(C)C)cc1
Reaction time: 4 h
Yield: 49 %

Procedure:
A 100 mL round-bottom flask was charged with 2-boranyl-4-chloro-phenylamine (1.1 g, 7.9 mmol) and 4-tert-butyl benzenesulfonyl chloride (2.7 g, 11.6 mmol). The flask was evacuated and purged with nitrogen, followed by the addition of pyridine (20 mL). The homogeneous light purple solution was stirred 4 hours, and then poured onto a rapidly stirring cold slurry of 6 M HCl (66 mL) (formed by placing the acidic solution in acetonic dry ice). The resultant precipitated sulfonamide was filtered, washed thoroughly with 10% HCl, and dried in vacuo to afford purplish solid. The crude product was purified by flash chromatograph to yield 1.3 g of product as colorless solid: MS (ES) M+H expected 336.5, found 336.5.
Reaction SMILES: [CH:1]([C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:13][CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[CH:10][CH:11]=2)[CH:6]=[C:5]([C:21]([O:23][CH3:24])=[O:22])[CH:4]=1)=[CH2:2].[OH-:25].[Na+].OO.Cl>C1COCC1.O>[OH:25][CH:1]([C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:13][CH2:14][C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)=[CH:10][CH:11]=2)[CH:6]=[C:5]([C:21]([O:23][CH3:24])=[O:22])[CH:4]=1)[CH3:2]
Reactant: [OH-]
Reactant: C=Cc1cc(C(=O)OC)cc2cc(OCc3ccccc3)ccc12
Agent: Cl
Agent: OO
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: COC(=O)c1cc(C(C)O)c2ccc(OCc3ccccc3)cc2c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of 0.3 g (0.9 mmol) of 1-vinyl-3-carbomethoxy-6benzyloxynaphthalene and 0.9 ml (0.9 mmol) of 1.0M BH3.THF complex in 15 ml of THF is stirred at 25° C. for 2 hours. To this is added 1 ml of H2O, 1 ml of 1N NaOH and 1 ml of 30% H2O2 which is then stirred at 25° C. for 2 hours. The mixture is acidified to pH ~1 using 1N HCl and extracted with ethyl acetate. The organics are dried (MgSO4) and concentrated in vacuo. Purification by flash silica gel chromatography using 15% ethyl acetate in hexanes as an eluent affords 0.08 g of 1-hydroxyethyl-3-carbomethoxy-6-benzyloxynaphthalene in the form a yellow oil which is used directly in the next step.