Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH-].[Na+].[CH2:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([OH:14])=[CH:11][CH:12]=2)[CH2:7][C:6]1=[O:15])[CH3:4].[Na].[C:17]1([C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:20][O:19]1)=[O:18]>CO>[CH2:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][CH2:20][C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:26]=3[C:17]([OH:19])=[O:18])=[CH:11][CH:12]=2)[CH2:7][C:6]1=[O:15])[CH3:4]
Reactant: O=C1OCc2ccccc21
Reactant: CCN1C(=O)Cc2cc(O)ccc21
Agent: [Na+]
Agent: [Na]
Agent: [OH-]
Solvent: CO
Product: CCN1C(=O)Cc2cc(OCc3ccccc3C(=O)O)ccc21
Reaction time: 0.33 h
Yield: 24 %

Procedure:
To a solution of 2.24 g. (54.3 mmoles) of sodium hydroxide in 450 ml. of methanol was added 9.63 g. (54.3 mmoles) of 1-ethyl-5-hydroxyoxindole and the resulting solution concentrated in vacuo to dryness at 65° C. The residual sodium salt was mixed with 10.7 g. (79.8 mmoles) of phthalide and the mixture heated one hour at 185° C. An additional 4.0 g. (29.9 mmoles) of phthalide was added and the heating continued at 220° C. for 20 minutes. The reaction was cooled, the solids washed with diethyl ether and the remaining solids partitioned between 1N hydrochloric acid and diethyl ether. The organic phase was separated and extracted with a saturated sodium bicarbonate solution. The bicarbonate solution was separated, acidified with 4N hydrochloric acid and extracted with diethyl ether. The ether layer was separated, dried over magnesium sulfate and concentrated to give a solid. Recrystallization from methanol gave 4.0 g. (24% yield) of the desired product, m.p. 180° -181° C.
Reaction SMILES: [OH:1][CH2:2][CH2:3][C:4]1[CH:46]=[CH:45][CH:44]=[CH:43][C:5]=1[O:6][CH2:7][CH2:8][O:9][CH:10]1[CH:15]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][CH2:25][O:26][CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[O:34][CH3:35])=[CH:18][CH:17]=2)[CH2:14][CH2:13][N:12]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:11]1.[N:47]1([C:52](N2C=CN=C2)=[O:53])[CH:51]=[CH:50][N:49]=[CH:48]1>C(#N)C.COC(C)(C)C>[N:47]1([C:52]([O:1][CH2:2][CH2:3][C:4]2[CH:46]=[CH:45][CH:44]=[CH:43][C:5]=2[O:6][CH2:7][CH2:8][O:9][CH:10]2[CH:15]([C:16]3[CH:17]=[CH:18][C:19]([O:22][CH2:23][CH2:24][CH2:25][O:26][CH2:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=4[O:34][CH3:35])=[CH:20][CH:21]=3)[CH2:14][CH2:13][N:12]([C:36]([O:38][C:39]([CH3:41])([CH3:42])[CH3:40])=[O:37])[CH2:11]2)=[O:53])[CH:51]=[CH:50][N:49]=[CH:48]1
Reactant: COc1ccccc1COCCCOc1ccc(C2CCN(C(=O)OC(C)(C)C)CC2OCCOc2ccccc2CCO)cc1
Reactant: O=C(n1ccnc1)n1ccnc1
Solvent: CC#N
Solvent: COC(C)(C)C
Product: COc1ccccc1COCCCOc1ccc(C2CCN(C(=O)OC(C)(C)C)CC2OCCOc2ccccc2CCOC(=O)n2ccnc2)cc1
Temperature: 25 °C

Procedure:
A solution of 0.100 g of tert-butyl 3-{2-[2-(2-hydroxyethyl)phenoxy]ethoxy}-4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}piperidine-1-carboxylate (Example 26c) and 0.049 g of diimidazol-1-ylmethanone in 4 ml of acetonitrile is stirred at reflux over 5 hours. The reaction mixture is cooled at room temperature, diluted with tert-butyl methyl ether, washed with 1N HCl and 0.5N NaOH, dried over sodium sulphate and concentrated by evaporation. The crude title compound is obtained as a yellow oil from the residue. Rf=0.41 (2:1 EtOAc-heptane); Rt=5.61.
Reaction SMILES: CN([C:4](=[O:13])[CH2:5][C:6]1[N:7]([CH3:12])[N:8]=[C:9]([CH3:11])[CH:10]=1)N.Cl.[O:15]1CCOCC1>>[CH3:12][N:7]1[C:6]([CH2:5][C:4]([OH:13])=[O:15])=[CH:10][C:9]([CH3:11])=[N:8]1
Reactant: C1COCCO1
Reactant: Cc1cc(CC(=O)N(C)N)n(C)n1
Agent: Cl
Product: Cc1cc(CC(=O)O)n(C)n1

Procedure:
To a solution of (2,5-dimethyl-2H-pyrazol-3-yl)-acetic acid N-methyl-hydrazide (9.1 g, 41 mmol) in dioxane (50 mL) aqueous sodium hydroxide solution was added (5 N, 50 mL) and the and the resulting mixture was heated under reflux for 4 h. After addition of hydrochloric acid (5 N, 50 mL), all volatiles were evaporated. The residue was extracted with refluxing ethanol (150 mL) and the solvent was evaporated. Residual volatiles were azeotropically removed by coevaporation with toluene to afford (2,5-dimethyl-2H-pyrazol-3-yl)-acetic acid as a viscous oil. It was dissolved in ethanol (100 ml), p-toluene sulfonic acid (2.0 g, catalytic) was added and the resulting mixture was heated under reflux for 16 h. After evaporation of the solvent, the residue was extracted with ethyl acetate and water. The organic phase was dried over sodium sulfate, concentrated and chromatographed (SiO2, heptanes:ethyl acetate=100:0 to 40:60) to afford the title compound as a colorless oil (7.6 g, 100%). 1H-NMR (400 MHz, CDCl3): δ=1.22 (t, J=7 Hz, 3H), 2.22 (s, 3H), 3.61 (s, 2H), 3.75 (s, 2H), 4.18 (q, J=7 Hz, 2H), 5.95 (s, 1H).
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[CH3:10][C:11](C)=[O:12]>CS(C)=O.O1CCCC1>[C:4]1([C:1](=[O:3])[CH2:2][C:11](=[O:12])[CH3:10])[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: CC(=O)c1ccccc1
Reactant: CC(C)=O
Solvent: CS(C)=O
Solvent: C1CCOC1
Product: CC(=O)CC(=O)c1ccccc1

Procedure:
The procedure of Example 1 is repeated, using in place of acetophenone 17.4 g of acetone and increasing the amount of solvent from 100 g to 150 g of dimethyl sulfoxide/tetrahydrofuran.
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([C:8]([CH3:11])([CH3:10])[CH3:9])[CH:5]=[C:4]([Br:12])[CH:3]=1.[CH2:13]=[C:14](B(O)O)[CH3:15].C([O-])([O-])=O.[K+].[K+].O>O1CCOCC1.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>[Br:12][C:4]1[CH:3]=[C:2]([C:14]([CH3:15])=[CH2:13])[CH:7]=[C:6]([C:8]([CH3:11])([CH3:10])[CH3:9])[CH:5]=1
Reactant: C=C(C)B(O)O
Reactant: CC(C)(C)c1cc(Br)cc(Br)c1
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: [K+]
Solvent: O
Solvent: C1COCCO1
Product: C=C(C)c1cc(Br)cc(C(C)(C)C)c1
Temperature: 90 °C
Reaction time: 8 h

Procedure:
To a solution of 1,3-dibromo-5-(tert-butyl)benzene (2.92 g, 10 mmol) in dioxane (20 mL) was added Pd(PPh3)4 (3.0 g, 2.6 mmol), prop-1-en-2-ylboronic acid (1.0 g, 12 mmol), K2CO3 (2.8 g, 20 mmol) and H2O (1 mL) under N2. The resulting mixture was stirred at 90° C. overnight, concentrated and purified by CC (hexane) to give compound P24a (2.5 g, 100%; 80% by GC/MS) as a liquid.
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH2:10][OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:19][S:20](Cl)(=[O:22])=[O:21].C(=O)(O)[O-].[Na+]>C1COCC1>[CH3:19][S:20]([O:11][CH2:10][CH2:9][O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)(=[O:22])=[O:21]
Reactant: CS(=O)(=O)Cl
Reactant: OCCOCc1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CS(=O)(=O)OCCOCc1ccccc1
Reaction time: 3 h
Yield: 96.4 %

Procedure:
2-Benzyloxyethanol (85.0 g) and triethylamine (73.5 g) were dissolved in THF (500 mL) and methanesulfonyl chloride (76.8 g) was added dropwise at from 0° C. to 10° C. The mixture was stirred for 3 hr. 10% Aqueous sodium bicarbonate (300 mL) was poured into the reaction mixture, the mixture was partitioned and combined with an extract of the aqueous layer with MTBE (300 mL), and the mixture was washed with 10% aqueous sodium bicarbonate and saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated to give 2-benzyloxyethyl methanesulfonate (124.0 g). The 2-benzyloxyethyl methanesulfonate (124.0 g) was dissolved in acetone (500 mL), and sodium iodide (130.0 g) was added. The mixture was stirred at from 50° C. to 60° C. for 3 hr. The reaction mixture was filtered and the solvent was evaporated. Water (300 mL) was added, and the mixture was extracted twice with toluene (300 mL). The toluene layer was washed successively with aqueous sodium hydrogen sulfite solution, water and brine and dried over anhydrous magnesium sulfate. The solvent was evaporated to give the title compound (127.0 g).
Reaction SMILES: [O:1]=[CH:2][C@H:3]([C@@H:5]([C@@H:7]([C@H:9]([CH3:11])[OH:10])[OH:8])[OH:6])[OH:4].C(O[C:16](=[O:18])[CH3:17])(=O)C>N1C=CC=CC=1>[C:2]([O:4][C@@H:3]([C@@H:5]([C@@H:7]([C@H:9]([CH3:11])[O:10][C:16](=[O:18])[CH3:17])[O:8][C:9](=[O:10])[CH3:11])[O:6][C:5](=[O:6])[CH3:7])[CH:2]=[O:1])(=[O:1])[CH3:3]
Reactant: C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C=O
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: CC(=O)O[C@H]([C@H](OC(C)=O)[C@H](C)OC(C)=O)[C@@H](C=O)OC(C)=O
Temperature: 25 °C
Reaction time: 36 h

Procedure:
To a suspension of 10 grams of L-fucose in 50 milliliters of pyridine is slowly added 50 milliliters of acetic anhydride. The mixture is stirred for 1 to 2 days at room temperature and then poured into a separatory funnel containing ice water. The resulting mixture is extracted 3 to 4 times with 50 milliliter portions of chloroform. The organic extracts are washed with water, aqueous sodium bicarbonate, and dried over magnesium sulfate. The mixture is filtered and the solvent removed under reduced pressure to give a residue of crude fucose tetraacetate. The crude tetraacetate is co-evaporated several times with toluene to remove any remaining pyridine or acetic acid. The fucose tetraacetate is then treated with 32% hydrogen bromide and acetic acid for 2 hours, and the mixture is then worked up similarly to that just described for the tetraacetate, i.e., chloroform extraction from an ice water mixture. The resultant crude product is 2,3,4-tri-O-acetyl-L-fucopyranosyl bromide.
Reaction SMILES: [N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][C:2]=1[NH:10][C:11]([N:13]1[CH:17]=[CH:16]N=C1)=[S:12].[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23](CCN)=[CH:22][CH:21]=1.C(OCC)(=O)C>CN(C)C=O>[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:16][CH2:17][NH:13][C:11]([NH:10][C:2]2[NH:1][C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[N:3]=2)=[S:12])=[CH:22][CH:21]=1
Reactant: S=C(Nc1nc2ccccc2[nH]1)n1ccnc1
Reactant: COc1ccc(CCN)cc1
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COc1ccc(CCNC(=S)Nc2nc3ccccc3[nH]2)cc1
Temperature: 25 °C
Yield: 67.4 %

Procedure:
A solution of 1-[(2-benzimidazolyl)thiocarbamoyl]imidazole (1.22 g, 5.0 mmol) and 2-(4-methoxyphenyl)ethylamine (0.77 g, 5.0 mmol) in N,N-dimethylformamide (20 mL) was stirred at 90° C. for 1 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, 1N aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the resultant solid was purified by chromatography on silica gel to provide 1.1 g (67%) of the titled product as a white solid:
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH:4]1[C:12]2[C:7](=[C:8]([NH:15][C:16](=[O:21])[C:17]([CH3:20])([CH3:19])[CH3:18])[C:9]([CH3:14])=[CH:10][C:11]=2[CH3:13])[NH:6][CH2:5]1.I[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30].CCOC(C)=O>CN(C=O)C>[CH2:23]([N:6]1[C:7]2[C:12](=[C:11]([CH3:13])[CH:10]=[C:9]([CH3:14])[C:8]=2[NH:15][C:16](=[O:21])[C:17]([CH3:18])([CH3:20])[CH3:19])[CH:4]([CH2:3][CH2:2][OH:1])[CH2:5]1)[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30]
Reactant: CCCCCCCCI
Reactant: Cc1cc(C)c2c(c1NC(=O)C(C)(C)C)NCC2CCO
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCCCCCCCN1CC(CCO)c2c(C)cc(C)c(NC(=O)C(C)(C)C)c21
Temperature: 70 °C
Reaction time: 10 h
Yield: 13.5 %

Procedure:
N-[3-(2—Hydroxyethyl)-4,6-dimethylindolin-7-yl]-2,2-dimethyl-propanamide (1.6 g) was dissolved in DMF (15 ml) and 1-iodooctane (3.9 g) and K2 CO3 (2.3 g) were added, which was followed by stirring at 70° C for 10 hr. AcOEt (200 ml) was added, and the mixture was washed with water and dried over anhydrous sodium sulfate. AcOEt was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: benzene/AcOEt=5/1−1/2) to give 300 mg of the title compound.
Reaction SMILES: [C:1]([C:3]1[S:7][C:6]([C:8]([OH:10])=O)=[CH:5][CH:4]=1)#[CH:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:35][CH2:36][C:37]1[N:38]=[CH:39][N:40]([C:42]2[CH:47]=[CH:46][C:45]([N:48]3[CH:53]=[CH:52][CH:51]=[CH:50][C:49]3=[O:54])=[CH:44][CH:43]=2)[CH:41]=1>CN(C=O)C>[C:1]([C:3]1[S:7][C:6]([C:8]([NH:35][CH2:36][C:37]2[N:38]=[CH:39][N:40]([C:42]3[CH:43]=[CH:44][C:45]([N:48]4[CH:53]=[CH:52][CH:51]=[CH:50][C:49]4=[O:54])=[CH:46][CH:47]=3)[CH:41]=2)=[O:10])=[CH:5][CH:4]=1)#[CH:2]
Reactant: NCc1cn(-c2ccc(-n3ccccc3=O)cc2)cn1
Reactant: C#Cc1ccc(C(=O)O)s1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Product: C#Cc1ccc(C(=O)NCc2cn(-c3ccc(-n4ccccc4=O)cc3)cn2)s1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of 5-ethynyl-thiophene-2-carboxylic acid (83 mg, 0.54 mmol) and TEA (0.15. mL, 1.1 mmol) in DMF (4 mL), HATU (228 mg, 0.60 mmol) was added. After being stirred at room temperature for 30 min, a solution of 1-(4-(4-(aminomethyl)-1H-imidazol-1-yl)phenyl)pyridin-2(1H)-one prepared above (145 mg, 0.54 mmol) and TEA (0.15 mL, 1.1 mmol) in DMF (8 mL) was added. The mixture was stirred at room temperature overnight. It was then purified by HPLC to give the title compound (65 mg). MS 401 (M+H).
Reaction SMILES: [C:1]([O:5][CH2:6][CH:7]1[CH2:12][N:11]([S:13]([CH3:16])(=[O:15])=[O:14])[CH:10]([CH2:17][OH:18])[CH2:9][CH2:8]1)([CH3:4])([CH3:3])[CH3:2].ClC(Cl)(Cl)C(=N)O[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.FC(F)(F)S(O)(=O)=O.C(=O)(O)[O-].[Na+]>ClCCl.C1CCCCC1>[CH2:23]([O:18][CH2:17][CH:10]1[CH2:9][CH2:8][CH:7]([CH2:6][O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:12][N:11]1[S:13]([CH3:16])(=[O:15])=[O:14])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: CC(C)(C)OCC1CCC(CO)N(S(C)(=O)=O)C1
Reactant: N=C(OCc1ccccc1)C(Cl)(Cl)Cl
Agent: O=C([O-])O
Agent: O=S(=O)(O)C(F)(F)F
Agent: [Na+]
Solvent: C1CCCCC1
Solvent: ClCCl
Product: CC(C)(C)OCC1CCC(COCc2ccccc2)N(S(C)(=O)=O)C1
Temperature: 25 °C
Reaction time: 1 h
Yield: 97.2 %

Procedure:
(6-ring): To a solution of (2RS,5RS)-(5-tert-butoxymethyl-1-methanesulfonyl -piperidin-2-yl)-methanol (2.80 g) in dichloromethane (20 ml) and cyclohexane (30 ml) was added benzyl 2,2,2-trichloroacetimidate (3.03 g) and trifluoromethanesulphonic acid (0.2 ml). The reaction mixture was stirred 1 h at room temperature, poured onto a saturated sodium bicarbonate solution and extracted with EtOAc. The organic phase was washed with brine, dried over magnesium sulphate and concentrated. The residue was chromatographed on silica gel using EtOAc/hexane 1:3 and 1:2 as eluents to obtain (2RS,5RS)-2-benzyloxymethyl-5-tert-butoxymethyl-1-methanesulfonyl-piperidine (3,6 g) as a syrup, MS: 369 (M+).
Reaction SMILES: [CH3:1][C:2]1[S:3][C:4]2[C:13]3[CH:12]([CH2:14][CH2:15][NH:16][C:17](=[O:19])[CH3:18])[CH2:11][CH2:10][C:9]=3[CH:8]=[CH:7][C:5]=2[N:6]=1>CCCCCC.C(O)C>[CH3:1][C:2]1[S:3][C:4]2[C:13]3[C@H:12]([CH2:14][CH2:15][NH:16][C:17](=[O:19])[CH3:18])[CH2:11][CH2:10][C:9]=3[CH:8]=[CH:7][C:5]=2[N:6]=1
Reactant: CC(=O)NCCC1CCc2ccc3nc(C)sc3c21
Solvent: CCO
Solvent: CCCCCC
Product: CC(=O)NCC[C@@H]1CCc2ccc3nc(C)sc3c21
Yield: 50.4 %

Procedure:
Racemic N-[2-(2-methyl-7,8-dihydro-6H-indeno[5,4-d][1,3]thiazol-8-yl)ethyl]acetamide (1.00 g) was fractionated by high performance liquid chromatography (instrument: Prep LC 2000 (manufactured by Nihon Waters K.K.), column: CHIRALPAK AD (50 mmID×500 mL, manufactured by Daicel Chemical Industries, Ltd.), mobile phase: hexane/ethanol=90/10, flow rate: 80 mL/min, column temperature: 30° C., sample concentration: 10 mg/mL (hexane/ethanol=90/10), injection weight: 500 mg×2). A fraction containing an optically active compound having a shorter retention time under the above-mentioned high performance liquid chromatography conditions was concentrated to give the title compound (504 mg, 99.9% ee). Enantiomer excess (ee) was measured by high performance liquid chromatography (column: CHIRALPAK AD (4.6 mmID×250 mL, manufactured by Daicel Chemical Industries, Ltd.), mobile phase: hexane/ethanol=90/10, flow rate: 1.0 mL/min, column temperature: 30° C., sample concentration: 0.25 mg/mL (hexane/ethanol=90/10), injection volume: 10 μL).
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@@H:10]([CH2:11]OS(C2C=CC(C)=CC=2)(=O)=O)[O:9][CH:8]=[CH:7][CH2:6]1)(=[O:3])[CH3:2].[N-:23]=[N+:24]=[N-:25].[Na+].CCOCC>CN(C)P(N(C)C)(N(C)C)=O>[C:1]([O:4][C@@H:5]1[C@@H:10]([CH2:11][N:23]=[N+:24]=[N-:25])[O:9][CH:8]=[CH:7][CH2:6]1)(=[O:3])[CH3:2]
Reactant: [N-]=[N+]=[N-]
Reactant: CC(=O)O[C@H]1CC=CO[C@@H]1COS(=O)(=O)c1ccc(C)cc1
Agent: [Na+]
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Solvent: CCOCC
Product: CC(=O)O[C@H]1CC=CO[C@@H]1CN=[N+]=[N-]
Reaction time: 24 h
Yield: 60.2 %

Procedure:
4-O-Acetyl-3-deoxy-6-O-tosyl-D-glucal (550 mg.) and sodium azide (550 mg.) were dissolved in hexamethylphosphoramide (50 ml.) and the mixture was stirred at 25° for 24 hours. The reaction mixture was poured into ether and extracted with water and the ether extract was dried (MgSO4) and evaporated and the product was chromatographed on a silica gel column (58 × 2.5 cm) using 7% acetone in hexane as the eluent to give 4-O-acetyl-6-azido-3,6-dideoxy-D-glucal (200 mg.) as a colorless oil, (Found: C, 48.84; H, 5.33; N,21.49. C8H11N3O3 requires: C, 48.72; H, 5.62; N, 21.31%), [α]D26 = 158.8° (CH3OH), νmax (film) 2100, 1720, 1660, 1220, 1050 cm.-1, δ(CDCl3) 2.09 (3H, s, OAc), 4.72 (1H, ddd, H = 6Hz, J = 4.5Hz, J = 3Hz, H2) and 6.39 ppm (1H, ddd, J = 2Hz, J = H1. )
Reaction SMILES: [CH3:1][N:2]([CH3:7])[C:3](=[O:6])[CH:4]=[CH2:5].Br[C:9]1[CH:10]=[CH:11][C:12]([O:29][CH2:30][CH3:31])=[C:13]([C:15]2[NH:16][C:17](=[O:28])[C:18]3[N:23]([CH3:24])[N:22]=[C:21]([CH2:25][CH2:26][CH3:27])[C:19]=3[N:20]=2)[CH:14]=1>>[CH3:1][N:2]([CH3:7])[C:3](=[O:6])/[CH:4]=[CH:5]/[C:9]1[CH:10]=[CH:11][C:12]([O:29][CH2:30][CH3:31])=[C:13]([C:15]2[NH:16][C:17](=[O:28])[C:18]3[N:23]([CH3:24])[N:22]=[C:21]([CH2:25][CH2:26][CH3:27])[C:19]=3[N:20]=2)[CH:14]=1
Reactant: C=CC(=O)N(C)C
Reactant: CCCc1nn(C)c2c(=O)[nH]c(-c3cc(Br)ccc3OCC)nc12
Product: CCCc1nn(C)c2c(=O)[nH]c(-c3cc(/C=C/C(=O)N(C)C)ccc3OCC)nc12

Procedure:
The title compound was prepared from N,N-dimethylacrylamide and 5-(5-bromo-2-ethoxyphenyl)-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one following the procedure of Example 69 and was obtained, following crystallisation from ethyl acetate-hexane, as colourless crystals (38%), m.p. 219-221° C. Found: C,64.15; H,6.46; N,16.96. C22H27N5O3 requires C,64.53; H,6.65; N,17.10%.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]([C:11]2([C:14]3[CH:24]=[CH:23][C:17]4[O:18][C:19]([F:22])([F:21])[O:20][C:16]=4[CH:15]=3)[CH2:13][CH2:12]2)=[O:10])[CH:5]=[C:4]([CH3:25])[C:3]=1[CH3:26].[CH3:27][O:28][C:29]1[C:34](B(O)O)=[CH:33][C:32]([CH3:38])=[CH:31][N:30]=1.C([O-])([O-])=O.[Na+].[Na+]>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>[F:21][C:19]1([F:22])[O:18][C:17]2[CH:23]=[CH:24][C:14]([C:11]3([C:9]([NH:8][C:6]4[N:7]=[C:2]([C:34]5[C:29]([O:28][CH3:27])=[N:30][CH:31]=[C:32]([CH3:38])[CH:33]=5)[C:3]([CH3:26])=[C:4]([CH3:25])[CH:5]=4)=[O:10])[CH2:13][CH2:12]3)=[CH:15][C:16]=2[O:20]1
Reactant: COc1ncc(C)cc1B(O)O
Reactant: Cc1cc(NC(=O)C2(c3ccc4c(c3)OC(F)(F)O4)CC2)nc(Cl)c1C
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: COc1ncc(C)cc1-c1nc(NC(=O)C2(c3ccc4c(c3)OC(F)(F)O4)CC2)cc(C)c1C
Temperature: 120 °C
Yield: 57 %

Procedure:
To a mixture of N-(6-chloro-4,5-dimethylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (114 mg, 0.3 mmol) and 2-methoxy-5-methylpyridin-3-ylboronic acid (75 mg, 0.45 mmol) in DME (3 mL) and Na2CO3 (2M, 0.3 mL, 0.6 mmol) was added Pd(PPh3)4 (17 mg, 0.015 mmol). The mixture was heated in microwave oven at 120° C. for 30 min. The reaction was re-partitioned between EtOAc and H2O and the aqueous layer was extracted with EtOAc twice. The combined organic layers were washed with brine and dried over MgSO4. After the removal of solvent, the residue was purified by column chromatography (0-20% EtOAc-Hexane) to yield 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(2′-methoxy-3,4,5′-trimethyl-2,3′-bipyridin-6-yl)cyclopropanecarboxamide (80 mg, 57%). 1H NMR (400 MHz, CDCl3) 8.02 (s, 1H), 7.99 (d, J=1.6 Hz, 1H), 7.59 (s, 1H), 7.31 (d, J=2.1 Hz, 1H), 7.20-7.16 (m, 2H), 7.04 (d, J=8.1 Hz, 1H), 3.85 (s, 3H), 2.33 (s, 3H), 2.26 (s, 3H), 1.95 (s, 3H), 1.73 (dd, J=3.8, 6.9 Hz, 2H), 1.14 (dd, J=3.9, 7.0 Hz, 2H). Retention time: 2.02 min; ESI-MS m/z calc. 467.5. found 468.2 (M+H)+.
Reaction SMILES: [C:1]1([C:7]2[CH2:8][CH2:9][N:10]([CH2:13][CH2:14][CH2:15][CH2:16][N:17]([C:23]3[CH:31]=[C:30]([N+:32]([O-:34])=[O:33])[CH:29]=[CH:28][C:24]=3[C:25]([OH:27])=O)[C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:11][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N:35]1C=CC=CC=1.[OH-].[NH4+]>C(#N)C.O>[C:1]1([C:7]2[CH2:8][CH2:9][N:10]([CH2:13][CH2:14][CH2:15][CH2:16][N:17]([C:23]3[CH:31]=[C:30]([N+:32]([O-:34])=[O:33])[CH:29]=[CH:28][C:24]=3[C:25]([NH2:35])=[O:27])[C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:11][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CCOC(=O)N(CCCCN1CC=C(c2ccccc2)CC1)c1cc([N+](=O)[O-])ccc1C(=O)O
Reactant: c1ccncc1
Agent: [NH4+]
Agent: [OH-]
Solvent: CC#N
Solvent: O
Product: CCOC(=O)N(CCCCN1CC=C(c2ccccc2)CC1)c1cc([N+](=O)[O-])ccc1C(N)=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 39.3 %

Procedure:
A mixture of 2-[N-{4-(4-phenyl-1,2,3,6-tetrahydropyridin-1-yl)butyl}-N-ethoxycarbonylamino]-4-nitrobenzoic acid (1.53 g), N,N'-disuccinimidoyl carbonate (924 mg) and pyridine (285 mg) in dry acetonitrile (20 ml) was stirred for 3 hours at room temperature. Then, to the mixture was added 28% ammonium hydroxide (1.4 ml) on an ice-bath. After 1 hour, the reaction mixture was diluted with water, and extracted with chloroform. The extract was washed with brine, dried over magnesium sulfate, and evaporated. The residue was chromatographed on silica gel (30 g). Elution with a mixed solvent of chloroform and methanol (50:1 V/V) gave 2-[N-{4-(4-phenyl-1,2,3,6-tetrahydropyridin-1-yl)butyl}-N-ethoxycarbonylamino]-4-nitrobenzamide (600 mg) as caramel.
Reaction SMILES: [CH2:1]1[CH2:11][CH2:10]N2[C:4](=NCCC2)[CH2:3][CH2:2]1.[CH2:12]([OH:18])[CH2:13][CH2:14][CH2:15]CC.CCCCCCCCCC>CCCCCC>[CH2:12]([OH:18])[CH2:13][CH2:14][CH2:15][CH2:10][CH2:11][CH2:1][CH2:2][CH2:3][CH3:4]
Reactant: CCCCCCO
Reactant: C1CCC2=NCCCN2CC1
Solvent: CCCCCC
Solvent: CCCCCCCCCC
Product: CCCCCCCCCCO
Reaction time: 1 h

Procedure:
In an inert atmosphere, 26.8 mmol each of DBU (95 ppm H2O) and 1-hexanol (26 ppm H2O) were charged into a flame-dried flask. N-Decane (2 mL, undried) was added and was found to be miscible at room temperature; only one homogeneous liquid phase was observed. CO2 (H2O<5 ppm) was slowly bubbled through the decane/1-hexanol/DBU mixture at 1 bar overnight. The resultant mixture appeared split into two separate liquids. Argon was then bubbled through the two-phase liquid mixture for 1 h at 35° C. After 1 h, the two liquids had merged into one liquid. A schematic representation of this reversible reaction appears in FIG. 4. Similar experiments were performed with hexane in place of decane and with several alcohols (1-propanol, 1-butanol, 1-hexanol, 1-octanol, and 1-decanol) in place of 1-hexanol; similar results were obtained except that with 1-decanol, no phase split was observed even after the treatment with CO2. Miscibility data for alcohol/DBU systems is presented in Table 1.