Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:10]=[C:9]([I:11])[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17].[O:20]1[CH2:23][CH:22]([N:24]2[CH2:29][CH2:28][N:27]([C:30]3[CH:36]=[CH:35][C:33]([NH2:34])=[CH:32][CH:31]=3)[CH2:26][CH2:25]2)[CH2:21]1.C(N(CC)CC)C>C(O)(C)C>[I:11][C:9]1[N:8]=[C:7]2[C:3]([N:4]=[CH:5][N:6]2[CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])=[C:2]([NH:34][C:33]2[CH:32]=[CH:31][C:30]([N:27]3[CH2:28][CH2:29][N:24]([CH:22]4[CH2:23][O:20][CH2:21]4)[CH2:25][CH2:26]3)=[CH:36][CH:35]=2)[N:10]=1
Reactant: Nc1ccc(N2CCN(C3COC3)CC2)cc1
Reactant: C[Si](C)(C)CCOCn1cnc2c(Cl)nc(I)nc21
Solvent: CCN(CC)CC
Solvent: CC(C)O
Product: C[Si](C)(C)CCOCn1cnc2c(Nc3ccc(N4CCN(C5COC5)CC4)cc3)nc(I)nc21
Temperature: 80 °C
Reaction time: 4 h
Yield: 59.9 %

Procedure:
A mixture of 117b (2.05 g, 5.0 mmol), 117e (1.17 g, 5.0 mmol), and triethylamine (1.01 g, 10 mmol) in i-propanol (30 mL) was stirred at 80° C. for 4 h. It was then filtered and the filtrate was evaporated in vacuo. The residue was purified by silica-gel column chromatography eluting with 30:1 dichloromethane/methanol to afford 117f (1.82 g, 60%) as a yellow solid. MS-ESI: [M+H]+ 608.1
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[CH:10][C:5]([CH:6]=[CH:7][C:8]#[N:9])=[CH:4][CH:3]=1.[OH-:12].[Na+]>O>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH:6]=[CH:7][C:8]([NH2:9])=[O:12])=[CH:10][CH:11]=1
Reactant: [OH-]
Reactant: N#CC=Cc1ccc(N)cc1
Agent: [Na+]
Solvent: O
Product: NC(=O)C=Cc1ccc(N)cc1
Temperature: 20 °C

Procedure:
72 parts of 4-amino-cinnamonitrile are gradually added to 85 parts of 66° Be sulphuric acid diluted by 15 parts of water. The temperature rises of itself to 100°-105° C. It is maintained up to the end of the addition, then heated for 50 minutes at 100°-105° C., cooled to 20° C. and run on to 100 parts of water and 200 parts of ice. The product is neutralised by adding 170 parts of a 35° Be solution of sodium hydroxide, the temperature being maintained at 10°-20° C. and the solid is then filtered off and dried. 56 parts of 4-amino-cinnamamide are thus obtained. It is recrystallised from 400 parts of monochlorobenzene, M.p. 200° C.
Reaction SMILES: [CH2:1]([OH:4])[CH2:2][OH:3].CC(C)=O.[C:9](Cl)(=[O:21])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]>N1C=CC=CC=1>[OH:3][CH2:2][CH2:1][O:4][C:9](=[O:21])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]
Reactant: CCCCCCCCCCCC(=O)Cl
Reactant: OCCO
Solvent: CC(C)=O
Solvent: c1ccncc1
Product: CCCCCCCCCCCC(=O)OCCO
Temperature: 25 °C
Reaction time: 2 h
Yield: 95.4 %

Procedure:
Under cooling with ice, ethylene glycol (434 mg) was dissolved into acetone (20 ml), and pyridine (632 mg) was added thereto and then lauroyl chloride (1532 mg) was added dropwise thereto. The temperature of the solution was warmed to room temperature, and it was stirred for 2 hours. The mixture was evaporated. To the residue was added water, and the solution was extracted with ethyl acetate. The organic layer was washed with water (three times), dried over magnesium sulfate and evaporated. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=4:1) to give the title compound (1.63 g) having the following physical data.
Reaction SMILES: [C:1]([O:5][C:6](=[O:25])[NH:7][C:8]1[CH:13]=[C:12]([N:14]([CH2:16][CH:17]([CH3:19])[CH3:18])[CH3:15])[C:11]([C:20]#[N:21])=[CH:10][C:9]=1[N+:22]([O-])=O)([CH3:4])([CH3:3])[CH3:2].O.O.Cl[Sn]Cl>>[C:1]([O:5][C:6](=[O:25])[NH:7][C:8]1[CH:13]=[C:12]([N:14]([CH2:16][CH:17]([CH3:18])[CH3:19])[CH3:15])[C:11]([C:20]#[N:21])=[CH:10][C:9]=1[NH2:22])([CH3:3])([CH3:4])[CH3:2]
Reactant: CC(C)CN(C)c1cc(NC(=O)OC(C)(C)C)c([N+](=O)[O-])cc1C#N
Agent: Cl[Sn]Cl
Solvent: O
Product: CC(C)CN(C)c1cc(NC(=O)OC(C)(C)C)c(N)cc1C#N

Procedure:
The title compound was prepared from [4-cyano-5-(isobutyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C29) (1.76 g, 5.05 mmol) by reduction with SnCl2.2H2O according to the general procedure J (method b). Obtained as a light brown solid (1.55 g, 96%).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:13]2[N:17]([C:18]3[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=3)[N:16]=[C:15]([C:24]3[CH:32]=[CH:31][CH:30]=[C:29]4[C:25]=3[CH2:26][NH:27][C:28]4=[O:33])[CH:14]=2)[CH:5]=[C:6]([O:8][C:9]([F:12])([F:11])[F:10])[CH:7]=1.O.O.O.O.O.O.O.[N+]([O-])([O-])=[O:42].[Mg+2].[N+]([O-])([O-])=O.[Mn]([O-])(=O)(=O)=O.[K+]>CC(C)=O.C(#N)C>[F:1][C:2]1[CH:3]=[C:4]([C:13]2[N:17]([C:18]3[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=3)[N:16]=[C:15]([C:24]3[CH:32]=[CH:31][CH:30]=[C:29]4[C:25]=3[C:26](=[O:42])[NH:27][C:28]4=[O:33])[CH:14]=2)[CH:5]=[C:6]([O:8][C:9]([F:10])([F:11])[F:12])[CH:7]=1
Reactant: O=C1NCc2c1cccc2-c1cc(-c2cc(F)cc(OC(F)(F)F)c2)n(-c2cccnc2)n1
Reactant: O=[N+]([O-])[O-]
Agent: O=[Mn](=O)(=O)[O-]
Agent: [K+]
Agent: [Mg+2]
Solvent: O
Solvent: CC#N
Solvent: CC(C)=O
Product: O=C1NC(=O)c2c1cccc2-c1cc(-c2cc(F)cc(OC(F)(F)F)c2)n(-c2cccnc2)n1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
40 mg (0.09 mmol) of the compound from example 7 are absorbed in 1 ml acetone and mixed with 1 ml water, 74 mg (0.29 mmol) magnesium nitrate hexahydrate and 32 mg (0.20 mmol) potassium permanganate. The reaction mixture is stirred for 24 hours at room temperature, diluted with 5 ml acetonitrile and filtered through a Millipore filter. The filtrate is extracted twice with dichloromethane and the combined organic phases washed with a saturated sodium chloride solution, dried using sodium sulfate, filtered and evaporated under vacuum until dryness. The residue is recrystallized from acetonitrile. This produces 14 mg (25% of theoretical yield, 75% purity) of the title compound.
Reaction SMILES: Cl[C:2]1[CH:12]=[C:11]([N+:13]([O-:15])=[O:14])[CH:10]=[CH:9][C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[NH:49]1[CH2:54][CH2:53][O:52][CH2:51][CH2:50]1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.COCCOC>[N:49]1([C:2]2[CH:12]=[C:11]([N+:13]([O-:15])=[O:14])[CH:10]=[CH:9][C:3]=2[C:4]([O:6][CH2:7][CH3:8])=[O:5])[CH2:54][CH2:53][O:52][CH2:51][CH2:50]1
Reactant: CCOC(=O)c1ccc([N+](=O)[O-])cc1Cl
Reactant: C1COCCN1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=P([O-])([O-])[O-]
Solvent: COCCOC
Solvent: O
Product: CCOC(=O)c1ccc([N+](=O)[O-])cc1N1CCOCC1

Procedure:
To a mixture of ethyl 2-chloro-4-nitrobenzoate (1.5 g), palladium acetate (73.3 mg), 2-(dicyclohexylphosphino)biphenyl (229 mg), tripotassium phosphate (1.94 g) and morpholine (0.57 mL) was added 1,2-dimethoxyethane (23 mL), and the mixture was stirred with heating under reflux for 8 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated. The obtained residue was purified by column chromatography (ethyl acetate:hexane) to give ethyl 2-(morpholin-4-yl)-4-nitrobenzoate (220 mg). The obtained ethyl 2-(morpholin-4-yl)-4-nitrobenzoate (220 mg) and 1-(2,4-dimethylphenyl)piperazine (149 mg) were dissolved in ethanol (3.5 mL), 1N aqueous sodium hydroxide solution (1.1 mL) was added, and the mixture was stirred at 50° C. To the reaction mixture was added 1N hydrochloric acid (1.1 mL), 1-(2,4-dimethylphenyl)piperazine (149 mg) and 4-(4,6-dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrate (DMT-MM) (218 mg) were added, and the mixture was stirred at room temperature overnight. To the reaction mixture was added saturated brine, and the mixture was extracted with ethyl acetate. The solvent was evaporated from the organic layer, the obtained residue was purified by silica gel column chromatography to give [4-(2,4-dimethylphenyl)piperazin-1-yl][2-(morpholin-4-yl)-4-nitrophenyl]methanone (206 mg). Then, to a solution of ethanol (3 mL) and water (1 mL) were added ammonium chloride (294 mg) and iron (211 mg), and the obtained [4-(2,4-dimethylphenyl)piperazin-1-yl][2-(morpholin-4-yl)-4-nitrophenyl]methanone (206 mg) was added while stirring at 60° C.-70° C. After completion of the reaction, the insoluble material was collected by filtration, and the filtrate was concentrated. To the obtained residue was added aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The solvent was evaporated from the organic layer to give the title compound (188 mg).
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[CH:8][C:7]([O:11][CH2:12][CH2:13][CH3:14])=[CH:6][CH:5]=2.[CH2:15]([O:17]C1C=C2C(=CC=1)NC(C)=C2C=O)C>>[CH3:1][C:2]1[NH:3][C:4]2[C:9]([C:10]=1[CH:15]=[O:17])=[CH:8][C:7]([O:11][CH2:12][CH2:13][CH3:14])=[CH:6][CH:5]=2
Reactant: CCCOc1ccc2[nH]c(C)cc2c1
Reactant: CCOc1ccc2[nH]c(C)c(C=O)c2c1
Product: CCCOc1ccc2[nH]c(C)c(C=O)c2c1
Reaction time: 1 h

Procedure:
This compound was prepared from 408b (263 mg, 1.39 mmol) in a manner similar to that for 409a except for after the drop-wise addition of substituted indole, the solution was stirred for 1 h. A cream-colored powder was obtained (228 mg, 75%): mp 156-158° C. TLC Rf 0.52 (75% EtOAc/hexanes). 1H NMR (600 MHz, d6-DMSO) δ 11.85 (s, 1H), 10.00 (s, 1H), 7.55 (d, 1H, J=2.46 Hz), 7.27-7.25 (d, 1H, J=8.7 Hz), 6.79-6.77 (dd, 1H, J1=8.7 Hz, J2=2.52 Hz), 3.92-3.90 (t, 2H, J=6.54 Hz), 2.64 (s, 3H), 1.77-1.71 (sex, 2H, J=7.38 Hz), 1.00-0.98 (t, 3H, J=7.38 Hz). NMR (150 MHz, d6-DMSO) δ 184.0, 154.9, 148.5, 130.0, 126.4, 113.6, 112.26, 112.04, 103.2, 69.3, 22.2, 11.5, 10.5. Elemental analysis calculated for C13H15NO2: C, 71.87; H, 6.96; N, 6.45. Found: C, 71.74; H, 6.81; N, 6.42.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:9][C:10](=[O:17])[C:11](=[CH:15][CH:16]=2)[C:12]([OH:14])=[O:13])=[CH:4][CH:3]=1.C(N(CC)CC)C.Cl[Si](C)(C)C.[CH3:30][S:31](Cl)(=[O:33])=[O:32]>ClCCl>[CH3:30][S:31]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[NH:9][C:10](=[O:17])[C:11](=[CH:15][CH:16]=2)[C:12]([OH:14])=[O:13])=[CH:6][CH:7]=1)(=[O:33])=[O:32]
Reactant: Nc1ccc(-c2ccc(C(=O)O)c(=O)[nH]2)cc1
Reactant: CS(=O)(=O)Cl
Agent: C[Si](C)(C)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)Nc1ccc(-c2ccc(C(=O)O)c(=O)[nH]2)cc1

Procedure:
A suspension of 23.02 g (0.1 mol) of 6-(4-aminophenyl)-1,2-dihydro-2-oxonicotinic acid, 1 L of dichloromethane, and 42.0 ml (0.303 mol) of triethylamine is stirred at 0°-5° and 42.17 ml (0.33 mol) of chlorotrimethylsilane is added. The ice bath is removed and the mixture is stirred at room temperature for 1 hr. The hazy solution is cooled to 10° and 23.8 ml (0.31 mol) of methanesulfonyl chloride is added. The resulting solution is stirred at room temperature for 24 hours and the dichloromethane is evaporated under reduced pressure and 500 ml of water is added to the residue. The mixture is cooled to 10° and the solid is filtered, washed with water, acetonitrile, and ether, and dried to give 29.9 of 6-[4-(methylsulfonylamino)phenyl]-1,2-dihydro-2-oxonicotinic acid; mp>320°.
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][C:15](O)=O)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O.[NH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[SH:32].[OH-].[NH4+]>O>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][C:15]2[S:32][C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=3[N:25]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Nc1ccccc1S
Reactant: O=C(O)CC1CCN(Cc2ccccc2)CC1
Agent: [NH4+]
Agent: [OH-]
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: c1ccc(CN2CCC(Cc3nc4ccccc4s3)CC2)cc1
Temperature: 120 °C
Reaction time: 18 h
Yield: 86.3 %

Procedure:
A mixture of 1.2 g of (1-benzyl-piperidin-4-yl)acetic acid.TFA, (from EXAMPLE 163, Step C) and 433 mg of 2-aminothiophenol was treated with 10 mL of polyphosphoric acid. After stirring at 120° C. for 18 h, the syrup was poured onto ice and H2O, maintaining the temperature of the aqueous mixture below 10° C. The resulting dark brown solution was made basic with ammonium hydroxide. The aqueous mixture was extracted with EtOAc (3×). The combined organic extracts were washed with sat'd NaCl and dried over MgSO4. Concentration afforded 962 mg of the title compound as a oil.
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1[C:10]([NH:12][C@H:13]([C:24]([O:26]C)=[O:25])[CH2:14][C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[NH:17][CH:16]=1)=[O:11].[OH-].[Na+]>CO>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1[C:10]([NH:12][C@H:13]([C:24]([OH:26])=[O:25])[CH2:14][C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[NH:17][CH:16]=1)=[O:11]
Reactant: COC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)c1cc2ccccc2o1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(N[C@@H](Cc1c[nH]c2ccccc12)C(=O)O)c1cc2ccccc2o1
Yield: 68.7 %

Procedure:
The same procedures as in Example 64 were carried out from the compound obtained in Example 18 (5.6 g), 1 mol/L of an aqueous sodium hydroxide solution (23 mL), and methanol (230 mL), to give the captioned compound (3.7 g, 69%) as crystals.
Reaction SMILES: [F:1][C:2]([F:21])([F:20])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:11]=[C:12]([C:15](OCC)=[O:16])[S:13][CH:14]=2)=[CH:6][CH:5]=1.O.[NH2:23][NH2:24]>CO>[F:1][C:2]([F:21])([F:20])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:11]=[C:12]([C:15]([NH:23][NH2:24])=[O:16])[S:13][CH:14]=2)=[CH:6][CH:5]=1
Reactant: CCOC(=O)c1nc(-c2ccc(OC(F)(F)F)cc2)cs1
Reactant: NN
Solvent: O
Solvent: CO
Product: NNC(=O)c1nc(-c2ccc(OC(F)(F)F)cc2)cs1
Temperature: 25 °C
Reaction time: 16 h
Yield: 100.5 %

Procedure:
To a solution of ethyl 4-(4-(trifluoromethoxy)phenyl)thiazole-2-carboxylate (10.0 g, 31.5 mmol) in MeOH (80 mL) was added hydrazine hydrate (1.95 g, 33.1 mmol; 85%) dropwise over 15 minutes, and the resulting mixture was stirred for a further 16 h at RT. The mixture was then concentrated under reduced pressure to half volume, and H2O (30 mL) was added. A white solid precipitated, was filtered, washed with H2O (3×30 mL) and dried to afford the title compound as a white solid (9.6 g, 100%). MS (ES+) C11H8F3N3O2S requires: 303. found: 304[M+H]+.
Reaction SMILES: [O-:1][S:2]([O-:4])=[O:3].[Na+:5].[Na+].Cl[CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>O>[O:10]([CH2:9][CH2:8][S:2]([O-:4])(=[O:1])=[O:3])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[Na+:5]
Reactant: O=S([O-])[O-]
Reactant: ClCCOc1ccccc1
Agent: [Na+]
Solvent: O
Product: O=S(=O)([O-])CCOc1ccccc1
Temperature: 120 °C
Reaction time: 24 h
Yield: 87 %

Procedure:
To a solution of Na2SO3 (12.9 g, 102.3 mmol) in 100 mL of water is added β-chlorophenetole (15.3 g, 97.4 mmol), and the mixture is stirred at 120° C. for 24 h. Cooling the mixture affords white precipitates, which are collected by filtration and dried in vacuo. The product is obtained as a white solid in 87% yield. The structure is confirmed by 1H-NMR spectrum (DMSO-d6). δ [ppm]: 2.88 (t, 2H), 4.18 (t, 2H), 6.88-6.93 (m, 3H), 7.24-7.29 (m, 2H).
Reaction SMILES: [CH2:1]([O:17][CH2:18][CH:19]([CH2:29][OH:30])[O:20][CH2:21][CH2:22][CH2:23][CH2:24][CH:25]([OH:28])CO)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].C(O)(=O)C>C(O)(C)C.O.C(O)C.C[N+](CC(NN)=O)(C)C.[Cl-]>[CH2:1]([O:17][CH2:18][CH:19]([CH2:29][OH:30])[O:20][CH2:21][CH2:22][CH2:23][CH2:24][CH:25]=[O:28])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: CCCCCCCCCCCCCCCCOCC(CO)OCCCCC(O)CO
Agent: C[N+](C)(C)CC(=O)NN
Agent: [Cl-]
Solvent: CCO
Solvent: CC(=O)O
Solvent: O
Product: CCCCCCCCCCCCCCCCOCC(CO)OCCCCC=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 27 %

Procedure:
As depicted in Scheme III, 1-Hexadecyl-2-(5′,6′-dihydroxy-hexanyl)-glycerol (7.84 grams) was dissolved in isopropanol (50 ml) and water (12 ml). NaIO4 (9 grams) was added and the reaction mixture was stirred at room temperature for 3 hours. Water (50 ml) was added and the reaction mixture extracted with chloroform (3×50 ml), dried over anhydrous Na2SO4, filtered and the solvent removed under reduced pressure yielding 5.56 grams. The crude product was dissolved in ethanol (60 ml) and glacial acetic acid (2.3 grams). Girard's reagent T (5.6 grams) was added and the reaction mixture was refluxed for 2 hours. The reaction mixture was cooled in ice-bath, alkaline solution (2.3 grams in 45 ml water) was added and the mixture was extracted with ether (3×25 ml). The etheral phase was washed with water and the water combined with the alkaline phase. The aqueous phase was acidified with concentrated HCl (4.4 ml) and extracted with ether (3×25 ml). Washing with water, saturated aqueous sodium bicarbonate (3×25 ml), water (2×25 ml), drying over anhydrous Na2SO4 and removal of the solvent under reduced pressure gave 1.95 grams (0.0049 mol) of 1-Hexadecyl-2-(5′-oxo-pentanyl)-glycerol (26.9% yield).
Reaction SMILES: FC(F)(F)S(O[C:7]1[CH:8]=[N:9][C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[CH:12][C:11]=2[C:17]([O:19][CH3:20])=[O:18])(=O)=O.[CH2:23](B(O)O)[CH2:24][CH2:25][CH2:26][CH2:27][CH3:28].C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.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>[CH2:23]([C:7]1[CH:8]=[N:9][C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[CH:12][C:11]=2[C:17]([O:19][CH3:20])=[O:18])[CH2:24][CH2:25][CH2:26][CH2:27][CH3:28]
Reactant: CCCCCCB(O)O
Reactant: COC(=O)c1cccc2cc(OS(=O)(=O)C(F)(F)F)cnc12
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: [Cs+]
Solvent: Cc1ccccc1
Product: CCCCCCc1cnc2c(C(=O)OC)cccc2c1
Temperature: 95 °C
Yield: 41 %

Procedure:
Methyl 3-(((trifluoromethyl)sulfonyl)oxy)quinoline-8-carboxylate (538 mg, 1.6 mmol), hexylboronic acid (415 mg, 3.2 mmol) and Cs2CO3 (779 mg, 2.4 mmol) were suspended in toluene (30 mL). The mixture was purged with nitrogen then tetrakis(triphenylphosphine)palladium (0) (55 mg, 0.05 mmol) was added. The reaction was sealed and heated at 95° C. for 16 h. The mixture was cooled and filtered through celite, rinsing with excess CH2Cl2. The filtrate was concentrated in vacuo. The resulting oil was purified on 40 g silica gel (19:1 CH2Cl2/methyl t-butyl ether) to afford 178 mg (41%) of methyl 3-hexylquinoline-8-carboxylate.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]3[N:15]4[CH2:16][CH2:17][S:18][C:19]([CH2:22][O:23][Si](C(C)(C)C)(C)C)([CH3:21])[CH2:20][C:14]4=[N:13][N:12]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[C:31]([C:33]1[CH:38]=[CH:37][N:36]=[CH:35][C:34]=1B1OC(C)(C)C(C)(C)O1)#[N:32].C(=O)([O-])[O-].[K+].[K+].C(=O)([O-])O.[Na+]>C(COC)OC.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>[OH:23][CH2:22][C:19]1([CH3:21])[S:18][CH2:17][CH2:16][N:15]2[C:11]([C:8]3([C:5]4[CH:4]=[CH:3][C:2]([C:38]5[CH:37]=[N:36][CH:35]=[CH:34][C:33]=5[C:31]#[N:32])=[CH:7][CH:6]=4)[CH2:10][CH2:9]3)=[N:12][N:13]=[C:14]2[CH2:20]1
Reactant: CC1(C)OB(c2cnccc2C#N)OC1(C)C
Reactant: CC1(CO[Si](C)(C)C(C)(C)C)Cc2nnc(C3(c4ccc(Br)cc4)CC3)n2CCS1
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: O=C([O-])[O-]
Solvent: O
Solvent: COCCOC
Product: CC1(CO)Cc2nnc(C3(c4ccc(-c5cnccc5C#N)cc4)CC3)n2CCS1
Temperature: 25 °C
Reaction time: 16 h
Yield: 26.1 %

Procedure:
A solution of the compound (508 mg, 1.0 mmol) obtained in Example 16-4), 4-cyanopyridine-3-boronic acid pinacol ester (366 mg, 1.5 mmol), tetrakis(triphenylphosphine)palladium(0) (231 mg, 0.2 mmol), and potassium carbonate (276 mg, 2 mmol) in dimethoxyethane (4 mL) and water (1 mL) was stirred at 130° C. for 1.5 h under microwave irradiation. The reaction mixture was cooled to room temperature, saturated aqueous sodium hydrogencarbonate was added to the reaction mixture, the mixture was extracted with dichloromethane, and the organic layer was washed with saturated sodium chloride solution and dried with anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was partially purified by silica gel chromatography (Isco Combiflash, 40 g, methanol:ethyl acetate=0:100 to 20:80, gradient). This partially purified product was dissolved in a solution of 4 M hydrochloric acid (1,4-dioxane solution, 1 mL) in methanol (4 mL), and the mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated under reduced pressure, saturated aqueous sodium hydrogencarbonate was added to the residue, the mixture was extracted with dichloromethane, and the organic layer was washed with saturated sodium chloride solution and dried with anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel chromatography (Isco Combiflash, 12 g, methanol:ethyl acetate=0:100 to 40:60, gradient) to obtain the title compound (109 mg, 26%) as a colorless solid.
Reaction SMILES: CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[CH3:23][C:24]1([CH3:53])[O:28][C@@H:27]([C@@H:29]([CH2:49][CH:50]=[CH2:51])[C:30]([NH:32][C@H:33]([C:38]([NH:40][C@@H:41]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH3:42])=[O:39])[C:34]([CH3:37])([CH3:36])[CH3:35])=[O:31])[C:26](=[O:52])[O:25]1.Br[C:55]1[CH:60]=[CH:59][C:58]([O:61][C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)=[C:57]([F:68])[CH:56]=1.C(N1CCOCC1)C>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:53][C:24]1([CH3:23])[O:28][C@@H:27]([C@@H:29]([CH2:49]/[CH:50]=[CH:51]/[C:55]2[CH:60]=[CH:59][C:58]([O:61][C:62]3[CH:63]=[CH:64][CH:65]=[CH:66][CH:67]=3)=[C:57]([F:68])[CH:56]=2)[C:30]([NH:32][C@H:33]([C:38]([NH:40][C@@H:41]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH3:42])=[O:39])[C:34]([CH3:35])([CH3:36])[CH3:37])=[O:31])[C:26](=[O:52])[O:25]1
Reactant: C=CC[C@@H](C(=O)N[C@H](C(=O)N[C@H](C)c1ccccc1)C(C)(C)C)[C@@H]1OC(C)(C)OC1=O
Reactant: Fc1cc(Br)ccc1Oc1ccccc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CCN1CCOCC1
Solvent: CC#N
Product: C[C@@H](NC(=O)[C@@H](NC(=O)[C@H](C/C=C/c1ccc(Oc2ccccc2)c(F)c1)[C@@H]1OC(C)(C)OC1=O)C(C)(C)C)c1ccccc1
Yield: 22.7 %

Procedure:
A mixture of palladium acetate (17 mg, 0.075 mmol) and tri-(2-methylphenyl)phosphine (46 mg, 0.15 mmol) in anhydrous acetonitrile (2 mL) was sonicated at room temperature for 1 min until a creamy-coloured suspension formed. This suspension was added via Pasteur pipette to a stirred solution of (2R)-2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]-N-[(1S)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]pent-4-enamide (650 mg, 1.5 mmol), 1-bromo-3-fluoro-4-phenoxybenzene (Preparation 10)(587 mg, 2.26 mmol), and N-ethylmorpholine (348 μL, 3.0 mmol) in anhydrous acetonitrile (2.5 mL) under nitrogen. The mixture was purged with nitrogen, then heated at reflux for 16 h. After being cooled, the mixture was poured into ethyl acetate (100 mL) and washed with 5% aqueous citric acid (30 mL), saturated aqueous sodium chloride (50 mL), dried (NaSO4), and concentrated under reduced pressure. The residue was purified by flash chromatography (gradient elution with dichloromethane:ether) to give mainly (2R, 5E)-2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]-N-[(1S)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]-5-(3-fluoro-4-phenoxyphenyl)pent-4-enamide as a pale yellow foam (210 mg, 22%). 1H nmr suggested that alkene isomers were also present. The mixture of alkenes was taken onto the next step (see b, below).