Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: N(C(OCC)=O)=NC(OCC)=O.[CH3:13][CH:14]([OH:16])[CH3:15].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[N:37]1[C:41](=[O:42])[C:40]2=[CH:43][CH:44]=[CH:45][CH:46]=[C:39]2[C:38]1=[O:47]>C1COCC1>[CH:14]([O:16][N:37]1[C:41](=[O:42])[C:40]2[C:39](=[CH:46][CH:45]=[CH:44][CH:43]=2)[C:38]1=[O:47])([CH3:15])[CH3:13]
Reactant: O=C1c2ccccc2C(=O)N1O
Reactant: CC(C)O
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)ON1C(=O)c2ccccc2C1=O
Temperature: 25 °C
Reaction time: 20 h
Yield: 86.8 %

Procedure:
Diethyl azodicarboxylate (14.5 mL, 73.56 mmol) was added dropwise at 0° C. to a stirred suspension of propan-2-ol (4.7 mL, 61.30 mmol), triphenylphosphine (19.30 g, 73.56 mmol), and N-hydroxyphthalimide (10.00 g, 61.30 mmol) in THF (50 mL). The mixture was stirred at room temperature for 20 h and evaporated to dryness. The product was purified by flash column chromatography using gradient elution from petroleum ether/EtOAc (9:1) to petroleum ether/EtOAc (5:1) to yield 2-isopropoxy-isoindole-1,3-dione (LIX, 10.92 g, 87%). 400 MHz 1H NMR (DMSO-d6, ppm): 7.86 (4H, s), 4.44 (1H, septet, J=6.2 Hz), 1.28 (6H, d, J=6.2 Hz).
Reaction SMILES: [Si:1]([O:8][CH2:9][C:10]1[CH:34]=[CH:33][C:13]([CH2:14][O:15]C(C2C=CC(CO[Si](C(C)(C)C)(C)C)=CC=2)=C)=[CH:12][CH:11]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Si](OCC(OC(C1C=CC=C(CO[Si](C(C)(C)C)(C)C)C=1)=C)C1C=CC=CC=1)(C(C)(C)C)(C)C.C(OC(C1C=CC=C(COC(=O)C)C=1)=C)C1C=CC=CC=1.OCC1C=CC(C(OC)=O)=CC=1.[Si](Cl)(C(C)(C)C)(C)C.[H-].[Al+3].[Li+].[H-].[H-].[H-]>>[Si:1]([O:8][CH2:9][C:10]1[CH:34]=[CH:33][C:13]([CH2:14][OH:15])=[CH:12][CH:11]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: C=C(OCc1ccc(CO[Si](C)(C)C(C)(C)C)cc1)c1ccc(CO[Si](C)(C)C(C)(C)C)cc1
Agent: C=C(OC(CO[Si](C)(C)C(C)(C)C)c1ccccc1)c1cccc(CO[Si](C)(C)C(C)(C)C)c1
Agent: C=C(OCc1ccccc1)c1cccc(COC(C)=O)c1
Agent: CC(C)(C)[Si](C)(C)Cl
Product: CC(C)(C)[Si](C)(C)OCc1ccc(CO)cc1

Procedure:
α-[4-(tert-Butyldimethylsilyloxymethyl)-benzyloxy][4-(tert-butyldimethylsilyloxymethyl)styrene] and α-[(tert-Butyldimethylsilyloxymethyl)-benzyloxy][3-(tert-butyldimethylsilyloxymethyl)styrene]. (Formula II, R1 =tert-butyldimethylsilyloxymethylphenyl, R2 =4-tert-butyldimethylsilyloxymethylbenzyl). Methyl 4-(hydroxymethyl)benzoate was treated with tert-butyldimethylsilyl chloride using the general procedure described in Journal of the American Chemical Society, 1972, 94, 6190. The resulting product was reduced with lithium aluminium hydride to afford 4-(tert-butyldimethylsilyloxymethyl)benzyl alcohol. This alcohol was converted into the required compound using Method C. 1H NMR (CCl4) δ 0.08 (12H, s), 0.91 (18H, s), 4.22 (1H, d, J 2 Hz), 4.68 (5H, br s), 4.90 (2H, s), 7.1-7.6 (8H, m); MS (CH4) 483 (M+ -CH3, 52%), 133 100%).
Reaction SMILES: [C:1]1([CH3:45])[CH:6]=[CH:5][C:4]([S:7]([NH:10][C@@H:11]([CH2:15][NH:16][C:17]([C:19]2[CH:44]=[C:22]3[C:23](=[O:43])[N:24]([CH2:28][CH2:29][CH:30]4[CH2:35][CH2:34][N:33](C(OC(C)(C)C)=O)[CH2:32][CH2:31]4)[CH2:25][CH2:26][CH2:27][N:21]3[N:20]=2)=[O:18])[C:12]([OH:14])=[O:13])(=[O:9])=[O:8])=[CH:3][CH:2]=1>C(Cl)Cl>[C:1]1([CH3:45])[CH:6]=[CH:5][C:4]([S:7]([NH:10][C@@H:11]([CH2:15][NH:16][C:17]([C:19]2[CH:44]=[C:22]3[C:23](=[O:43])[N:24]([CH2:28][CH2:29][CH:30]4[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]4)[CH2:25][CH2:26][CH2:27][N:21]3[N:20]=2)=[O:18])[C:12]([OH:14])=[O:13])(=[O:8])=[O:9])=[CH:3][CH:2]=1
Reactant: Cc1ccc(S(=O)(=O)N[C@@H](CNC(=O)c2cc3n(n2)CCCN(CCC2CCN(C(=O)OC(C)(C)C)CC2)C3=O)C(=O)O)cc1
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)N[C@@H](CNC(=O)c2cc3n(n2)CCCN(CCC2CCNCC2)C3=O)C(=O)O)cc1
Temperature: 25 °C
Reaction time: 0.03 h

Procedure:
15-1 (7.42 g, 11.48 mmol) was placed in a 1L round bottom flask equipped with a magnetic stir bar. Methylene chloride was added and the reaction mixture was cooled to 0°-5°. Hydrogen chloride was bubbled through the suspension with stirring. After about 2 min. the solid went into solution, and soon afterward a second precipitate formed. After bubbling gas through the suspension for an additional 5 min. the reaction flask was warmed to room temperature. After 30 min. the contents of the reaction flask were concentrated. The resulting white solid was the hydrochloride salt of 15-2 and by HPLC analysis was of >99% purity.
Reaction SMILES: C([S:8][C:9]([CH3:16])([CH2:13][CH2:14][CH3:15])[CH2:10][CH2:11][OH:12])C1C=CC=CC=1.N.CCO.Cl>CCOCC>[SH:8][C:9]([CH3:16])([CH2:13][CH2:14][CH3:15])[CH2:10][CH2:11][OH:12]
Reactant: CCCC(C)(CCO)SCc1ccccc1
Agent: Cl
Agent: N
Solvent: CCOCC
Solvent: CCO
Product: CCCC(C)(S)CCO
Temperature: 25 °C
Yield: 112.6 %

Procedure:
At a temperature of −78° C. to a solution of 16.0 g (67.1 mmol) of (rac)-3-benzylsulfanyl-3-methyl-hexan-1-ol of step (c) in 200 ml of Et2O was added from a cylinder about 200 ml of NH3 Then pieces of Na (ca. 4.0 g) were added until the reaction mixture remained blue for more than 20 min. The blue colored mixture was allowed to warm up to room temperature overnight and EtOH was added until the blue color disappeared. The mixture was then acidified with about 2.7 M of HCl, and extracted three times with 150 ml of Et2O. The combined organic layers were dried over Na2SO4 and concentrated in vacuo. Distillation of the crude product at reduced pressure (40 mbar/130° C.) gave 11.2 g (73%) of (rac)-3-mercapto-3-methyl-hexan-1-ol in form of a colorless oil.
Reaction SMILES: [N:1]([C@H:4]1[C@@H:9]([CH3:10])[CH2:8][N:7]([C:11]2[CH:16]=[CH:15][N:14]=[CH:13][C:12]=2[N:17]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:6][C@H:5]1[NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])=[N+]=[N-].O.CP(C)C>C1COCC1>[NH2:1][C@H:4]1[C@@H:9]([CH3:10])[CH2:8][N:7]([C:11]2[CH:16]=[CH:15][N:14]=[CH:13][C:12]=2[N:17]([C:25]([O:27][C:28]([CH3:30])([CH3:29])[CH3:31])=[O:26])[C:18]([O:20][C:21]([CH3:22])([CH3:23])[CH3:24])=[O:19])[CH2:6][C@H:5]1[NH:32][C:33]([O:35][C:36]([CH3:37])([CH3:39])[CH3:38])=[O:34]
Reactant: C[C@H]1CN(c2ccncc2N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)C[C@@H](NC(=O)OC(C)(C)C)[C@H]1N=[N+]=[N-]
Agent: CP(C)C
Solvent: C1CCOC1
Solvent: O
Product: C[C@H]1CN(c2ccncc2N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)C[C@@H](NC(=O)OC(C)(C)C)[C@H]1N
Temperature: 50 °C
Reaction time: 15 h
Yield: 104.9 %

Procedure:
To a solution of di-tert-butyl (4-{(3R,4S,5S)-4-azido-3-[(tert-butoxycarbonyl)amino]-5-methylpiperidin-1-yl}pyridin-3-yl)imidodicarbonate (1.337 g, 2.441 mmol) in THF (20 mL), water (1.00 mL, 55.5 mmol) was added, followed by trimethylphosphine (383 mg, 5.03 mmol). The mixture was stirred at 50° C. for 15 h. The mixture was then concentrated under reduced pressure. The residue was diluted with EtOAc, washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give the sub-title compound as a white foamy solid (1.336 g, 105%). LCMS calc. for C26H44N5O6 (M+H)+: m/z=522.3. Found: 522.3.
Reaction SMILES: [CH2:1]([C:3]1[O:4][CH:5]=[CH:6][C:7](=[O:10])[C:8]=1[OH:9])[CH3:2].[OH-].[Na+].[CH2:13](Cl)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>CO>[CH2:13]([O:9][C:8]1[C:7](=[O:10])[CH:6]=[CH:5][O:4][C:3]=1[CH2:1][CH3:2])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: CCc1occc(=O)c1O
Reactant: ClCc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CCc1occc(=O)c1OCc1ccccc1
Temperature: 25 °C
Yield: 59.9 %

Procedure:
To a suspension of 2-ethyl-3-hydroxy-4-pyrone (70 g, 0.5 mol) in methanol (650 ml) and sodium hydroxide solution (24 g, 0.6 mol of sodium hydroxide dissolved in 80 ml distilled water) was added benzyl chloride (90 ml, 0.75 mol) with stirring at room temperature. The reaction mixture was refluxed for 24 hours and then cooled. The solvent was removed by rotary evaporation and the residue was extracted into dichloromethane (500 ml). The organic layer was washed with 5% w/v sodium hydroxide solution (3×600 ml) and water (2×600 ml), dried over anhydrous sodium sulphate, filtered and rotary evaporated to give an oil. This oil was crystallized from diethylether in liquid nitrogen and the product recrystallized from diethylether to give the title compound (69 g, 65%) as colourless crystals, m.p. 33°-34° C.
Reaction SMILES: Cl[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([N+:10]([O-:12])=[O:11])[CH:3]=1.C[O-].[Na+].C(N(CC)CC)C.[CH3:23][C@H:24]1[CH2:29][NH:28][CH2:27][C@@H:26]([CH3:30])[NH:25]1>CC(O)=O.CC(P(C(C)(C)C)C1C(C2[C-]=CC=CC=2)=CC=CC=1)(C)C.[Pd]>[CH3:23][C@H:24]1[NH:25][C@@H:26]([CH3:30])[CH2:27][N:28]([C:2]2[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([N+:10]([O-:12])=[O:11])[CH:3]=2)[CH2:29]1
Reactant: C[C@@H]1CNC[C@H](C)N1
Reactant: N#Cc1ccc(Cl)cc1[N+](=O)[O-]
Agent: [Pd]
Agent: CC(C)(C)P(c1ccccc1-c1[c-]cccc1)C(C)(C)C
Agent: C[O-]
Solvent: CCN(CC)CC
Solvent: CC(=O)O
Product: C[C@@H]1CN(c2ccc(C#N)c([N+](=O)[O-])c2)C[C@H](C)N1
Temperature: 85 °C
Reaction time: 16 h

Procedure:
A mixture of 4-chloro-2-nitrobenzonitrile (Tetrahedron 1994, 50, 5515-5126) (650 mg, 3.56 mmol), sodium methoxide (270 mg, 5.00 mmol) and acetato-(2′-di-tert-butylphosphino-1,1′-biphenyl-2-yl)palladium (II) (115 mg, 0.25 mmol) was treated with triethylamine (0.25 ml, 1.79 mmol) followed by cis-2,6-dimethylpiperazine (488 mg, 4.27 mmol) and the mixture heated to 85° C. under an inert atmosphere over 30 minutes. The mixture was then kept at this temperature for 16 hours. The mixture was then filtered through kieselguhr, washing with toluene (50 ml) and the filtrate reduced in vacuo. The residue was then purified using an SCX ion exchange cartridge (Varian bond-elute) eluting with methanol followed by 2M ammonia in methanol to afford a dark residue which was purified by mass directed autoprep BPLC to afford the title compound as the formic acid salt. MS (ES+) m/e 261 [M+H]+.
Reaction SMILES: [OH:1][CH2:2][C:3]1[N:8]=[C:7]([C:9](=[O:16])[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:6]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:5][CH:4]=1.N1C=CN=C1.[Si:30](Cl)([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31]>CN(C)C=O>[C:9]([C:7]1[C:6]([O:17][CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[CH:5][CH:4]=[C:3]([CH2:2][O:1][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])[N:8]=1)(=[O:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: O=C(c1ccccc1)c1nc(CO)ccc1OCc1ccccc1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)OCc1ccc(OCc2ccccc2)c(C(=O)c2ccccc2)n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 89.5 %

Procedure:
116 g of 6-hydroxymethyl-2-benzoyl-3-benzyloxypyridine was dissolved in 450 ml of N,N-dimethylformamide. 100 g of imidazole and 85 g of tert-butyldimethylsilyl chloride was added thereto, followed by stirring at room temperature overnight. The solvent was removed, water was added thereto and the mixture was extracted with ethyl acetate. Further, the organic phase was washed with dilute hydrochloric acid, water, an aqueous saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate and evaporated. The residue was dried, to give 141 g of the target compound.
Reaction SMILES: [CH2:1]([NH:8][C:9]1[CH:15]=[CH:14][C:13]([C:16]2[O:17][C:18]3[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=3[N:20]=2)=[CH:12][C:10]=1[NH2:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:25](=O)[CH3:26].OOS([O-])=O.[K+].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[O:17]1[C:18]2[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=2[N:20]=[C:16]1[C:13]1[CH:14]=[CH:15][C:9]2[N:8]([CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[C:25]([CH3:26])=[N:11][C:10]=2[CH:12]=1
Reactant: Nc1cc(-c2nc3ccccc3o2)ccc1NCc1ccccc1
Reactant: CC=O
Agent: O=C([O-])[O-]
Agent: O=S([O-])OO
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1nc2cc(-c3nc4ccccc4o3)ccc2n1Cc1ccccc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 40.8 %

Procedure:
To a solution of 2-(2-benzylaminoanilin-5-yl)benzoxazole (see Working Example 17-2) (80.0 mg, 0.254 mmol) in dimethylformamide (2 mL) was added an aqueous solution of acetaldehyde (approx. 90%, 47.7 μL, 0.761 mmol) and oxone (102 mg, 0.165 mmol), and this was stirred at room temperature for 3 hours. After the reaction was complete, aqueous potassium carbonate solution was added, and this was extracted with ethyl acetate. The organic layer obtained was dried over anhydrous sodium sulfate, filtered, and concentrated to give an oil that was purified by silica gel column chromatography to yield the title compound (35.2 mg, 41% yield) as light brown crystals.
Reaction SMILES: FC(F)(F)[C:3](O)=[O:4].F[C:9]1[C:14]([C:15]#[N:16])=[C:13]([CH3:17])[C:12]([C@@H:18]2[O:23][CH2:22][C@H:21]3[CH2:24][NH:25][CH2:26][CH2:27][N:20]3[CH2:19]2)=[CH:11][CH:10]=1.C(=O)([O-])[O-].[Na+].[Na+]>CO>[CH3:3][O:4][C:9]1[C:14]([C:15]#[N:16])=[C:13]([CH3:17])[C:12]([C@@H:18]2[O:23][CH2:22][C@H:21]3[CH2:24][NH:25][CH2:26][CH2:27][N:20]3[CH2:19]2)=[CH:11][CH:10]=1
Reactant: Cc1c([C@H]2CN3CCNC[C@@H]3CO2)ccc(F)c1C#N
Reactant: O=C(O)C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CO
Product: COc1ccc([C@H]2CN3CCNC[C@@H]3CO2)c(C)c1C#N
Temperature: 150 °C

Procedure:
A microwave vial was charged with 6-fluoro-2-methyl-3-[(3S,9aR)-octahydropyrazino[2,1-c][1,4]oxazin-3-yl]benzonitrile trifluoroacetate (110 mg, 0.290 mmol), sodium carbonate (30 mg, 0.290 mmol), and methanol (2 mL). The mixture was heated to 150° C. in a microwave apparatus for 2 h, then cooled to ambient temperature, filtered and concentrated to provide the title compound which was used without further purification. LC-MS (IE, m/z): 288 [M+1]+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[N:9][C:8]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[C:7]2[C:18]1[CH:19]=[C:20](N)[CH:21]=[CH:22][CH:23]=1.[Cl:25][C:26]1[CH:27]=[C:28]([CH:31]=[CH:32][C:33]=1[Cl:34])[CH:29]=[O:30]>>[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[N:9][C:8]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[C:7]2[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([O:30][CH2:29][C:28]2[CH:31]=[CH:32][C:33]([Cl:34])=[C:26]([Cl:25])[CH:27]=2)[CH:19]=1
Reactant: Nc1cccc(-c2c(-c3ccccc3)nnc3c(Cl)cccc23)c1
Reactant: O=Cc1ccc(Cl)c(Cl)c1
Product: Clc1ccc(COc2cccc(-c3c(-c4ccccc4)nnc4c(Cl)cccc34)c2)cc1Cl

Procedure:
The title compound was prepared from 3-(8-chloro-3-phenyl-cinnolin-4-yl)-phenylamine and 3,4-dichlorobenzaldehyde according to the procedure of Step 5 Example 6. MS (ES) m/z 491.1.
Reaction SMILES: [CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:24]([CH2:25][CH2:26][CH3:27])[CH2:23][CH2:22][C:21]([C:28]([NH:30][C:31]4[CH:32]=[N:33][C:34]([S:37][CH2:38][C:39]5[N:40]([CH2:44][CH2:45][CH3:46])[CH:41]=[CH:42][N:43]=5)=[CH:35][CH:36]=4)=[O:29])=[CH:20][C:19]=3[CH:47]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4].ClC1C=CC=C(C(OO)=[O:56])C=1.S([O-])([O-])(=O)=S.[Na+].[Na+]>C(Cl)Cl>[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:24]([CH2:25][CH2:26][CH3:27])[CH2:23][CH2:22][C:21]([C:28]([NH:30][C:31]4[CH:32]=[N:33][C:34]([S:37]([CH2:38][C:39]5[N:40]([CH2:44][CH2:45][CH3:46])[CH:41]=[CH:42][N:43]=5)=[O:56])=[CH:35][CH:36]=4)=[O:29])=[CH:20][C:19]=3[CH:47]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(SCc4nccn4CCC)nc2)CCN3CCC)cc1
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: ClCCl
Product: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(S(=O)Cc4nccn4CCC)nc2)CCN3CCC)cc1
Reaction time: 0.25 h
Yield: 44.6 %

Procedure:
7-[4-(2-butoxyethoxy)phenyl]-1-propyl-N-[6-[[(1-propylimidazol-2-yl)methyl]sulfanyl]-3-pyridinyl]-2,3-dihydro-1-benzazepine-4-carboxamide (0.70 g) was dissolved in methylene chloride (21 ml), and a solution of m-chloroperbenzoic acid (0.28 g) in methylene chloride (14 ml) was added dropwise to the solution at −78° C. The mixture was stirred for 15 minutes, and an aqueous solution of saturated sodium thiosulfate was added to the mixture. The mixture was extracted with ethyl acetate, washed with saturated brine, and dried over magnesium sulfate. The solvent was removed under reduced pressure, and the obtained residue was purified by silica gel column chromatography, to give 7-[4-(2-butoxyethoxy)phenyl]-1-propyl-N-[6-[[(1-propylimidazol-2-yl)methyl]sulfinyl]-3-pyridinyl]-2,3-dihydro-1-benzazepine-4-carboxamide (Compound 291) (0.32 g).
Reaction SMILES: [C:1]([O:5][CH2:6][CH:7]1[O:9][CH2:8]1)(=[O:4])[CH2:2][CH3:3].[CH2:10]([O:14][CH2:15][CH:16]=[CH2:17])[CH:11]1[O:13][CH2:12]1>>[C:1]([O:5][CH2:6][CH:7]1[O:9][CH2:8]1)(=[O:4])[CH2:2][CH2:3][CH3:10].[CH2:10]([O:14][CH2:15][CH:16]=[CH2:17])[CH:11]1[O:13][CH2:12]1
Reactant: CCC(=O)OCC1CO1
Agent: C=CCOCC1CO1
Product: CCCC(=O)OCC1CO1

Procedure:
Copolymers of glycidyl propionate and allyl glycidyl ether and a copolymer of glycidyl butyrate and allyl glycidyl ether were prepared in the same way as in Example 4.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[N:6][NH:7][CH:8]=1)([O-:3])=[O:2].[N:9]1[CH:14]=[CH:13][C:12]([CH2:15]O)=[CH:11][CH:10]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>C1COCC1>[N+:1]([C:4]1[CH:5]=[N:6][N:7]([CH2:15][C:12]2[CH:13]=[CH:14][N:9]=[CH:10][CH:11]=2)[CH:8]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1cn[nH]c1
Reactant: OCc1ccncc1
Agent: CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: O=[N+]([O-])c1cnn(Cc2ccncc2)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 64.7 %

Procedure:
To a stirred solution of 4-nitro-1H-pyrazole (211 mg, 1.87 mmol), pyridine-4-methanol (0.28 mL, 2.56 mmol), and triphenylphosphine (538 mg, 2.05 mmol) in THF (10 mL) under nitrogen is added di-t-butyl azodicarboxylate (472 mg, 2.05 mmol) over 3 min. The reaction mixture was stirred for 16 h at room temperature. The mixture is concentrated and is purified by flash column chromatography using a gradient of 0-3% methanol in CH2Cl2 to afford the title compound as a yellow oil (247 mg, 65%).
Reaction SMILES: O[C:2]([C:14]1[CH:19]=[CH:18][C:17]([N:20]([CH3:30])[S:21]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)(=[O:23])=[O:22])=[CH:16][CH:15]=1)([C:5]1[N:6]([CH2:10][CH2:11][O:12][CH3:13])[CH:7]=[CH:8][CH:9]=1)[CH2:3][CH3:4].C([SiH](CC)CC)C.B(F)(F)F.CCOCC>>[CH3:13][O:12][CH2:11][CH2:10][N:6]1[CH:7]=[CH:8][CH:9]=[C:5]1[CH:2]([C:14]1[CH:19]=[CH:18][C:17]([N:20]([CH3:30])[S:21]([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)(=[O:22])=[O:23])=[CH:16][CH:15]=1)[CH2:3][CH3:4]
Reactant: CCC(O)(c1ccc(N(C)S(=O)(=O)c2ccccc2)cc1)c1cccn1CCOC
Agent: CC[SiH](CC)CC
Agent: FB(F)F
Solvent: CCOCC
Product: CCC(c1ccc(N(C)S(=O)(=O)c2ccccc2)cc1)c1cccn1CCOC

Procedure:
The title compound was prepared from N-(4-{1-hydroxy-1-[1-(2-methoxyethyl)-1H-pyrrol-2-yl]-propyl}-phenyl)-N-methyl-benzenesulfonamide (Example 2) using triethylsilane and boron trifluoride diethyl etherate as described in Example 88 of co-pending application Ser. No. 10/354,922, entitled “Arylsulfonamidobenzylic Compounds” and provided below as Preparative Example B.
Reaction SMILES: [CH3:1][C:2]1([CH3:14])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[N:11][NH:12][CH:13]=2)[O:3]1.Br[CH:16]([CH3:18])[CH3:17].C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C>[CH:16]([N:12]1[CH:13]=[C:9]([B:4]2[O:5][C:6]([CH3:7])([CH3:8])[C:2]([CH3:14])([CH3:1])[O:3]2)[CH:10]=[N:11]1)([CH3:18])[CH3:17]
Reactant: CC(C)Br
Reactant: CC1(C)OB(c2cn[nH]c2)OC1(C)C
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC#N
Product: CC(C)n1cc(B2OC(C)(C)C(C)(C)O2)cn1

Procedure:
A mixture of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.05 g, 0.2 mmol), 2-Bromopropane (36 uL, 0.39 mmol, Aldrich, Cat. No. 239909), and cesium carbonate (250 mg, 0.77 mmol) in acetonitrile (1 mL) was stirred at 90° C. for 2 h. After cooling it was quenched with water. The product was extracted with ethyl acetate. The extract was washed with water twice, brine once; dried over Na2SO4. After filtration the filtrate was concentrated to yield 53 mg of the product which was directly used in the next step reaction without further purification.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9](=O)[NH:10][CH2:11][CH2:12][N:13]=2)=[C:4]([O:15][CH3:16])[CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>C(OCC)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:9][NH:10][CH2:11][CH2:12][NH:13]2)=[C:4]([O:15][CH3:16])[CH:3]=1
Reactant: COc1cc(F)ccc1C1=NCCNC1=O
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: CCOCC
Product: COc1cc(F)ccc1C1CNCCN1
Temperature: 0 °C
Yield: 99 %

Procedure:
5,6-Dihydro-3-(4-fluoro-2-methoxyphenyl)pyrazinone was added to the solution of lithium aluminium hydride (0.46 g, 12 mmol) in diethyl ether (25 ml) and refluxed for 6 hr. Water (0.48 ml), 15% sodium hydroxide solution (0.48 ml) and again water (1.21 ml) were added to the ice-cooled solution and the precipitate was filtered and washed with dichloromethane. Combined organic layer was evaporated to give 2-(4-fluoro-2-methoxyphenyl)piperazine (0.83 g, 99%).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:13])[CH:4]=[CH:5][NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[C:14](#[N:16])[CH3:15]>CC([O-])=O.CC([O-])=O.[Cu+2].CC(OC)(C)C.CCOC(C)=O>[CH3:1][O:2][C:3]([C:4]1[C:14]([CH3:15])=[N:16][N:6]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:5]=1)=[O:13]
Reactant: CC#N
Reactant: COC(=O)C=CNc1ccccc1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: COC(C)(C)C
Solvent: CCOC(C)=O
Product: COC(=O)c1cn(-c2ccccc2)nc1C

Procedure:
According to AVV A, 3-phenylamino acrylic acid methylester (197) (177.2 mg, 1.0 mmol, 1.0 equiv.) was stirred with Cu(OAc)2 (544.9 mg, 3.0 mmol, 3.0 equiv.) into acetonitrile (3.0 ml, 57.1 mmol, 57.1 equiv.) for 22 hours at 110° C. The greenish solid obtained as raw product (242.4 mg) was purified by means of column chromatography (silica gel (50 g), pentane/MTBE 95:5→0:100, then MTBE/EtOAc 100:0→0:100), whereby the desired product was obtained in the form of a yellowish solid (35.1 mg, 0.16 mmol, 16%).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:15]1[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][NH2:23])=[CH:17][CH:16]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].CC(O)=O>C(Cl)Cl>[C:18]1([CH2:21][CH2:22][NH:23][CH:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]2)[CH:19]=[CH:20][CH:15]=[CH:16][CH:17]=1
Reactant: NCCc1ccccc1
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCC(NCCc2ccccc2)CC1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of tert-butyl-4-oxo-1-piperidinecarboxylate in methylene chloride was added 2-phenethylamine, NaBH(OAc)3 and HOAc. The mixture was stirred at ambient temperature for 16 hours and quenched by addition of H2O. The aqueous layer was neutralized with NaHCO3 and extracted with CH2Cl2. The combined organic layer was washed with saturated NaHCO3 and brine and dried over MgSO4. Evaporation of solvent gave an off-white solid. This material was used without further purification. ESI-MS 305 (M+H); HPLC A: 2.54 min.