Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6](=[O:21])[NH:7][C:8]1[CH:13]=[C:12]([O:14][CH3:15])[C:11]([C:16]([F:19])([F:18])[F:17])=[CH:10][C:9]=1[NH2:20])([CH3:4])([CH3:3])[CH3:2].C([O:26][C:27](=O)[CH2:28][C:29]([C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([C:37]2[O:41][N:40]=[C:39]([CH3:42])[CH:38]=2)[CH:32]=1)=[O:30])(C)(C)C>>[C:1]([O:5][C:6](=[O:21])[NH:7][C:8]1[CH:13]=[C:12]([O:14][CH3:15])[C:11]([C:16]([F:19])([F:18])[F:17])=[CH:10][C:9]=1[NH:20][C:27](=[O:26])[CH2:28][C:29]([C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([C:37]2[O:41][N:40]=[C:39]([CH3:42])[CH:38]=2)[CH:32]=1)=[O:30])([CH3:4])([CH3:2])[CH3:3]
Reactant: COc1cc(NC(=O)OC(C)(C)C)c(N)cc1C(F)(F)F
Reactant: Cc1cc(-c2cccc(C(=O)CC(=O)OC(C)(C)C)c2)on1
Product: COc1cc(NC(=O)OC(C)(C)C)c(NC(=O)CC(=O)c2cccc(-c3cc(C)no3)c2)cc1C(F)(F)F

Procedure:
The title compound was prepared from (2-amino-5-methoxy-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example J9) (306 mg. 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as an off-white solid (301 mg).
Reaction SMILES: [O:1]1[CH2:6]COCC1.Cl.[CH:8]([C:11]([NH:13][CH:14]1[CH2:19][CH2:18][CH:17]([CH2:20][NH:21]C(=O)OC(C)(C)C)[CH2:16][CH2:15]1)=O)(C)C.[CH3:29]COCC>>[NH2:21][CH2:20][CH:17]1[CH2:16][CH2:15][CH:14]([N:13]([CH:11]([CH3:8])[CH3:29])[CH:6]=[O:1])[CH2:19][CH2:18]1
Reactant: C1COCCO1
Reactant: CCOCC
Reactant: CC(C)C(=O)NC1CCC(CNC(=O)OC(C)(C)C)CC1
Agent: Cl
Product: CC(C)N(C=O)C1CCC(CN)CC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 100 %

Procedure:
Dioxane containing HCl was added (10 ml of 4N HCl solution) to a solution of tert-butyl N-[4-(isopropylformylamino)-cyclohexyl]methylcarbamate dissolved in 10 ml Et2O, stirred at room temperature for 2 hours and the solvent removed under reduced pressure to obtain N-[4-(aminomethyl)cyclohexyl]-N-isopropylformamide: 100% yield, 199 (ESMS, MH+); 1H NMR (CD3OD) δ 8.16 (s, 1H), 4.16 & 3.57 (two m, 1H), 3.70 (m, 1H), 2.79 (m, 2H), 1.36 (m, 6H), 1.91-1.06 (m, 9H).
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]=[CH:4][C:3]=1[CH3:25].CC1(C)C(C)(C)OB([C:34]2[CH:35]=[C:36]([C:40]3([C:43]([O:45][CH3:46])=[O:44])[CH2:42][CH2:41]3)[CH:37]=[CH:38][CH:39]=2)O1.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:38]5[CH:37]=[C:36]([C:40]6([C:43]([O:45][CH3:46])=[O:44])[CH2:42][CH2:41]6)[CH:35]=[CH:34][CH:39]=5)[C:3]([CH3:25])=[CH:4][CH:5]=4)=[O:10])[CH2:13][CH2:12]3)=[CH:15][C:16]=2[O:20]1
Reactant: Cc1ccc(NC(=O)C2(c3ccc4c(c3)OC(F)(F)O4)CC2)nc1Cl
Reactant: COC(=O)C1(c2cccc(B3OC(C)(C)C(C)(C)O3)c2)CC1
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: COC(=O)C1(c2cccc(-c3nc(NC(=O)C4(c5ccc6c(c5)OC(F)(F)O6)CC4)ccc3C)c2)CC1
Temperature: 120 °C

Procedure:
N-(6-Chloro-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (93 mg, 0.26 mmol) was dissolved in 1,2-dimethoxyethane (2.5 mL) in a reaction tube. Methyl 1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclopropanecarboxylate (100 mg, 0.33 mmol), aqueous 2 M sodium carbonate (0.25 mL), and (Ph3P)4Pd (15 mg, 0.013 mmol) were added and the reaction mixture was heated at 120° C. for 20 minutes in the microwave. The resulting material was cooled to room temperature, filtered, and evaporated under reduced pressure. The residue was purified by prep LC-MS to yield methyl 1-(3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)phenyl)cyclopropanecarboxylate, which was used in the next step without further purification.
Reaction SMILES: [CH2:1]1[O:27][C:4]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[F:26])([C:5]2[CH:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:6]=2[CH2:12]SC2C=CC=CC=2)[O:3][CH2:2]1.C[I:29]>>[CH2:1]1[O:27][C:4]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[F:26])([C:5]2[CH:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:6]=2[CH2:12][I:29])[O:3][CH2:2]1
Reactant: Fc1ccccc1C1(c2cc(Cl)ccc2CSc2ccccc2)OCCO1
Reactant: CI
Product: Fc1ccccc1C1(c2cc(Cl)ccc2CI)OCCO1

Procedure:
The starting material is obtained as follows: The solution of 10 g of 5-chloro-2'-fluoro-2-phenylmercaptomethyl-benzophenone ethylene ketal (Example 2) in 50 ml of methyl iodide is refluxed under nitrogen for 5 days. It is evaporated and the formed methyl phenyl thioether distilled off at 60°/0.1 mm Hg, to yield the 5-chloro-2'-fluoro-2-iodomethyl-benzophenone ethylene ketal.
Reaction SMILES: [S:1]([O-])([O-])(=O)=[S:2].[Na+].[Na+].O.Br[CH2:10][CH2:11][N:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14]([CH3:21])=[CH:13]1>C(O)C>[CH3:21][C:14]1[C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[N:12]([CH2:11][CH2:10][S:1][S:2][CH2:10][CH2:11][N:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]([CH3:21])=[CH:13]2)[CH:13]=1
Reactant: Cc1cn(CCBr)c2ccccc12
Reactant: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: Cc1cn(CCSSCCn2cc(C)c3ccccc32)c2ccccc12

Procedure:
A solution of 10.4 g. of sodium thiosulfate in 60 ml. of water and 100 ml. of ethanol is poured onto 8.6 g. of 1-(2-bromoethyl)-3-methylindole. The reactionmixture is stirred and heated at reflux for 3.5 hr., allowed to cool, and evaporated to dryness. The solid residue is dissolved in boiling isopropanol, dried with a hydrated alkali-aluminum silicate ("Molecular Sieves"), and filtered. Chilling of the filtrate causes 6.4 g. of the sodium indolyethyl thiosulfate derivative to precipitate. This material is collected by filtration and washed with ether. The isolated intermediate is heated at reflux with a solution of sodium hydroxide (9 g. of NaOH, 60 ml. of water, 140 ml. of ethanol) for 3 hr. Ethanol is removed under reduced pressure, the aqueous residue diluted with water and extracted with three portions of ether. Combined ether extracts are washed with water, saturated brine solution, and dried over magnesium sulfate. The filtrate is evaporated, to yield bis-[2-(3-methylindole-1-yl)ethyl]disulfide.
Reaction SMILES: [F:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].N1C=CC=CC=1.Cl[S:20]([C:23]1[CH:31]=[CH:30][C:26]([C:27]([OH:29])=[O:28])=[CH:25][CH:24]=1)(=[O:22])=[O:21].[OH-].[Na+]>ClCCl>[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][S:20]([C:23]2[CH:24]=[CH:25][C:26]([C:27]([OH:29])=[O:28])=[CH:30][CH:31]=2)(=[O:22])=[O:21])=[CH:4][C:3]=1[C:9]([F:10])([F:11])[F:12]
Reactant: Nc1ccc(F)c(C(F)(F)F)c1
Reactant: O=C(O)c1ccc(S(=O)(=O)Cl)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: c1ccncc1
Product: O=C(O)c1ccc(S(=O)(=O)Nc2ccc(F)c(C(F)(F)F)c2)cc1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
10 g (55.8 mmol) of 4-fluoro-3-trifluoromethylaniline and 6 ml (74.3 mmol) of pyridine are dissolved in 250 ml of dichloromethane. The mixture is cooled with ice water and, under agitation and exclusion of moisture, 12.7 g (57.6 mmol) of 4-chlorosulfonylbenzoic acid is added in incremental portions. The mixture is stirred overnight; the slurry is combined with 75 ml of 2N sodium hydroxide solution, and the organic phase is separated. The alkaline solution is washed with dichloromethane and then adjusted to pH 2 with hydrochloric acid. The product is taken up in ethyl acetate. The solution is washed with water, dried over sodium sulfate and concentrated to dryness. The title compounds melts at 243-°245° C. after crystallization from ethanol.
Reaction SMILES: [Si:1]([O:8][CH2:9][CH2:10][O:11][CH2:12][N:13]1[C:20]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:19][C:17](=[O:18])[NH:16][C:14]1=[S:15])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Li]N1C(C)(C)CCCC1(C)C.[I:38]I.C(=O)(O)[O-].[Na+]>O1CCCC1.C(Cl)(Cl)Cl.C(O)(=O)C>[Si:1]([O:8][CH2:9][CH2:10][O:11][CH2:12][N:13]1[C:20]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)=[C:19]([I:38])[C:17](=[O:18])[NH:16][C:14]1=[S:15])([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]
Reactant: II
Reactant: CC(C)(C)[Si](C)(C)OCCOCn1c(-c2ccccc2)cc(=O)[nH]c1=S
Agent: O=C([O-])O
Agent: [Li]N1C(C)(C)CCCC1(C)C
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClC(Cl)Cl
Solvent: C1CCOC1
Product: CC(C)(C)[Si](C)(C)OCCOCn1c(-c2ccccc2)c(I)c(=O)[nH]c1=S
Temperature: -70 °C
Yield: 23.6 %

Procedure:
After cooling 35 ml of tetradydrofuran to -70° C., 2.1 g (15 mmol) of 2,2,6,6-tetramethylpiperidine and 15 mmol of n-butyl lithium were successively added thereto to obtain a lithium tetramethylpiperidide solution. Separately, 2.04 g (15 mmol) of 1-[(2-t-butyldimethylsilyloxyethoxy)methyl]-6-phenylthiouracil was dissolved in 20 ml of tetrahydrofuran and added dropwise to the said lithium tetramethylpiperidide solution to react for an hour at -70° C. Then, a solution of 3.81 g (15 mmol) of iodine in 20 ml of tetrahydrofuran was further added to the reaction solution while maintaining the reaction temperature at -70° C. to react for an hour. After the completion of the reaction, the reaction solution was added to 0.8 ml of acetic acid, allowed to warm to room temperature and distributed between a chloroform layer and a saturated aqueous solution of sodium bicarbonate. The chloroform layer was concentrated to dryness. The residue was crystallized from petroleum ether to obtain 1.835 g of 1-[(2-t-butyldimethylsilyloxyethoxy)methyl]-5-iodo-6-phenylthiouracil (Yield: 62.8%).
Reaction SMILES: [CH3:1][CH:2]([C:7]1[CH:8]=[C:9]([OH:25])[C:10]2[CH:11]([C:19]3[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=3)[CH2:12][C:13]([CH3:18])([CH3:17])[O:14][C:15]=2[CH:16]=1)[CH2:3][CH2:4][CH2:5][CH3:6].[C:26]1([CH2:32][CH2:33][Br:34])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>CC(C)=O>[Br-:34].[C:26]1([CH2:32][CH2:33][N+:22]2[CH:21]=[CH:20][C:19]([CH:11]3[C:10]4[C:15](=[CH:16][C:7]([CH:2]([CH2:3][CH2:4][CH2:5][CH3:6])[CH3:1])=[CH:8][C:9]=4[OH:25])[O:14][C:13]([CH3:18])([CH3:17])[CH2:12]3)=[CH:24][CH:23]=2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: BrCCc1ccccc1
Reactant: CCCCC(C)c1cc(O)c2c(c1)OC(C)(C)CC2c1ccncc1
Solvent: CC(C)=O
Product: CCCCC(C)c1cc(O)c2c(c1)OC(C)(C)CC2c1cc[n+](CCc2ccccc2)cc1
Product: [Br-]
Yield: 86 %

Procedure:
7-(2-Hexyl)-2,2-dimethyl-4-(4-pyridyl) chroman-5-ol (5.45 g, 0.016 mole) and 2-phenylethyl bromide (3.70 g, 0.020 mole) were dissolved in acetone (120 ml) and the solution was refluxed for 4 days. The solution was then allowed to cool and the resulting precipitate was filtered, washed with acetone and dried to yield 1-(2-phenylethyl)-4-[7-(2-hexyl)-2,2-dimethyl-5-hydroxychroman-4-yl] pyridinium bromide (7.22 g, 88%) as colourless microcrystals, m.p. 232°-235°C.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[C:8]([O:12][C:13](=[O:28])[N:14]([C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=1)[C:15](=[O:20])[CH2:16][CH2:17][C:18]#[CH:19])([CH3:11])([CH3:10])[CH3:9]>>[C:8]([O:12][C:13](=[O:28])[N:14]([C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=1)[C:15](=[O:20])[CH2:16][CH2:17][C:18]#[C:19][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1)([CH3:11])([CH3:9])[CH3:10].[C:8]([O:12][C:13](=[O:28])[N:14]([C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=1)[C:15](=[O:20])[C:16]#[C:17][CH2:18][CH2:19][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1)([CH3:9])([CH3:10])[CH3:11]
Reactant: Brc1ccccn1
Reactant: C#CCCC(=O)N(C(=O)OC(C)(C)C)c1cccc(F)c1
Product: CC(C)(C)OC(=O)N(C(=O)C#CCCc1ccccn1)c1cccc(F)c1
Product: CC(C)(C)OC(=O)N(C(=O)CCC#Cc1ccccn1)c1cccc(F)c1
Yield: 120.9 %

Procedure:
The title compound was prepared in accordance with the general method of Example 1, from 2-bromo-pyridine (137 mg, 0.86 mmol) and (3-fluoro-phenyl)-pent-4-ynoyl-carbamic acid tert-butyl ester (250 mg, 0.86 mmol). Reaction time: 3 hours. The crude residue was purified by flash chromatography (cyclohexane/AcOEt 4:1) to yield 190 mg (0.52 mmol, 60%) of (3-fluoro-phenyl)-(5-pyridin-2-yl-pent-ynoyl)-carbamic acid tert-butyl ester as a white solid.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH:3]([CH2:7][NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH2:2]1.[CH3:16][S:17](Cl)(=[O:19])=[O:18].C(N(CC)CC)C>ClCCl>[CH3:16][S:17]([N:1]1[CH2:6][CH2:5][CH2:4][CH:3]([CH2:7][NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:14])[CH3:13])[CH2:2]1)(=[O:19])=[O:18]
Reactant: CC(C)(C)OC(=O)NCC1CCCNC1
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)NCC1CCCN(S(C)(=O)=O)C1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
tert-Butyl piperidin-3-ylmethylcarbamate (500 mg) was dissolved in anhydrous dichloromethane (10 mL), and methanesulfonyl chloride (0.181 mL) was added followed by the addition of triethylamine (1.3 mL). The reaction mixture was stirred at room temperature overnight. The organic solvent was removed under vacuum. The residue was purified with flash column chromatography on silica gel eluting with 0-70% ethyl acetate in hexane to give the title compound.
Reaction SMILES: [SH:1][C:2]([CH3:18])([CH3:17])[CH2:3][NH:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[NH:11][CH2:12][C:13]([CH3:16])([SH:15])[CH3:14].[H-].[Na+].[CH3:21]I>O1CCCC1>[CH3:21][S:1][C:2]([CH3:18])([CH3:17])[CH2:3][NH:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[NH:11][CH2:12][C:13]([SH:15])([CH3:16])[CH3:14]
Reactant: CC(C)(S)CNc1ccccc1NCC(C)(C)S
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CSC(C)(C)CNc1ccccc1NCC(C)(C)S
Reaction time: 1 h
Yield: 79.1 %

Procedure:
1,2-Bis (2-Mercapto-2-methylpropylamino)benzene (0.47 g, 1.69×10-3 mol), and 0.09 g (1.85×10-3 mol, 110 M%) sodium hydride were dissolved in 25 ml tetrahydrofuran. Methyl iodide (0.080 ml, 1.27×10-3 mol, 75 M%) was added, and the mixture was stirred under nitrogen for 1 hour. The excess hydride was destroyed by the slow addition of 10 ml 0.5 M HCl. The mixture was shaken with a mixture of 100 ml ether and 100 ml 0.5 N HCl. The aqueous layer was extracted with an additional 50 ml portion of ether, and the combined ether layers were washed with 100 ml saturated NaCl. The ether layer was then dried over anhydrous Na2SO4. Rotary evaporation yielded 0.30 g (94% yield) of 1-[2-methylthio-2 -methylpropylamino]-2-(2-mercapto-2-methylpropylamino)benzene as a yellow oil. Isolation was performed by radial chromatograph on a 1 mm silica plate, using petroleum ether: ethyl acetate-80:20 as the eluting solvent to give yielding a mixture of the 1-[2-methylthio-2-methylpropyl- amino]-2-(2-mercapto-2-methylpropylamino)benzene, S,S'-dimethyl, and the dithiol starting material.
Reaction SMILES: [CH3:1][C:2]1[CH:23]=[CH:22][CH:21]=[CH:20][C:3]=1[CH2:4][NH:5][C:6]([N:8]1[C:16](=[O:17])[C:15]2[C:10](=[N:11][C:12]([Cl:19])=[CH:13][C:14]=2[CH3:18])[NH:9]1)=[O:7].[CH3:24]C(C)([O-])C.[K+].IC.C(N(CC)CC)C>C1COCC1>[CH3:1][C:2]1[CH:23]=[CH:22][CH:21]=[CH:20][C:3]=1[CH2:4][NH:5][C:6]([N:8]1[C:16](=[O:17])[C:15]2[C:10](=[N:11][C:12]([Cl:19])=[CH:13][C:14]=2[CH3:18])[N:9]1[CH3:24])=[O:7]
Reactant: Cc1ccccc1CNC(=O)n1[nH]c2nc(Cl)cc(C)c2c1=O
Reactant: CC(C)(C)[O-]
Agent: [K+]
Solvent: CCN(CC)CC
Solvent: CI
Solvent: C1CCOC1
Product: Cc1ccccc1CNC(=O)n1c(=O)c2c(C)cc(Cl)nc2n1C
Temperature: 60 °C
Reaction time: 4 h

Procedure:
99.89 mg (0.3 mmol) of 6-chloro-4-methyl-3-oxo-1,3-dihydropyrazolo[3,4-b]pyridine-2-carboxylic acid 2-methylbenzylamide and 37.3 mg (0.33 mmol) of potassium tert-butoxide were stirred in 10 ml of THF at room temperature for 10 minutes. Addition of 20.7 μl of iodomethane was followed by stirring at room temperature for 2 h and at 60° C. for 4 h. Then 30 μl of iodomethane and 50 μl of triethylamine were added, and stirring was continued at 60° C. for 7 h, the mixture was concentrated and mixed with water and ethyl acetate, and the organic phase was separated off, concentrated and purified by preparative HPLC (PR18, acetonitrile/water 0.1% TFA). Yield: 18 mg (17%), M+H+: 345.08.
Reaction SMILES: [N+:1]([O-])([O:3]C(=O)C)=[O:2].[O:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[S:17][CH2:18][CH2:19][N:20]1[CH2:25][CH2:24][N:23]([CH2:26][C:27]([NH:29][C:30]2[C:35]([CH:36]([CH3:38])[CH3:37])=[CH:34][CH:33]=[C:32]([OH:39])[C:31]=2[CH:40]([CH3:42])[CH3:41])=[O:28])[CH2:22][CH2:21]1.C(=O)(O)[O-].[Na+]>C(#N)C.O>[O:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[S:17][CH2:18][CH2:19][N:20]1[CH2:25][CH2:24][N:23]([CH2:26][C:27]([NH:29][C:30]2[C:35]([CH:36]([CH3:37])[CH3:38])=[CH:34][C:33]([N+:1]([O-:3])=[O:2])=[C:32]([OH:39])[C:31]=2[CH:40]([CH3:42])[CH3:41])=[O:28])[CH2:22][CH2:21]1
Reactant: CC(C)c1ccc(O)c(C(C)C)c1NC(=O)CN1CCN(CCSc2nc3ccccc3o2)CC1
Reactant: CC(=O)O[N+](=O)[O-]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC#N
Solvent: O
Product: CC(C)c1cc([N+](=O)[O-])c(O)c(C(C)C)c1NC(=O)CN1CCN(CCSc2nc3ccccc3o2)CC1
Reaction time: 0.17 h
Yield: 50.4 %

Procedure:
Acetyl nitrate (145 mg, 0.75 mmol) was added to a solution of 2-[4-[2-(benzoxazol-2-ylthio)ethyl]piperazin-1-yl]-N-(2,6-diisopropyl-3-hydroxyphenyl)acetamide (107 mg, 0.22 mmol) in acetonitrile (3 ml) with ice cooling followed by stirring for 10 minutes. The reaction solution was diluted with water, made alkaline by adding an aqueous solution of sodium bicarbonate thereto and extracted with chloroform twice. The organic layer was washed with a saturated sodium chloride solution and dried over anhydrous sodium sulfate and the solvent was evaporated therefrom. The residue was purified by a preparative thin layer chromatography (developing solvent, chloroform:methanol=20:1) and the resulting crude crystals were recrystallized from chloroform-ethyl acetate-hexane to provide 60 mg (yield 51%) of the desired compound as yellow powdery crystals.
Reaction SMILES: [C:1]1([CH:8]=[CH:7][CH:6]=[C:4]([OH:5])[CH:3]=1)[OH:2].[CH:9]1(O)[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1>>[CH:9]1([C:6]2[CH:7]=[CH:8][C:1]([OH:2])=[CH:3][C:4]=2[OH:5])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1
Reactant: Oc1cccc(O)c1
Reactant: OC1CCCCC1
Product: Oc1ccc(C2CCCCC2)c(O)c1
Temperature: 125 °C
Yield: 44.2 %

Procedure:
Resorcinol (2.2 g, 20 mmol) and cyclohexanol (6.33 ml, 6 g, 60 mmol) were suspended in 85% polyphosphoric acid (8 ml). The mixture was heated to 125° C. for 24 hours, after which time TLC appeared to show complete consumption of the starting materials. On cooling the mixture was partitioned between water (50 ml) and diethyl ether (50 ml). The aqueous layer was discarded, and the organic portion extracted with sodium hydroxide solution (2×50 ml, 2M). The base extract was washed with ether (3×50 ml), and then acidified with aqueous hydrochloric acid (120 ml, 2M). The organic components were then extracted into diethyl ether (2×50 ml), dried (magnesium sulfate), filtered and the solvent removed under reduced pressure. The resulting brown oil was then chromatographed on silica gel, eluting with ethyl acetate/petroleum ether (bp 60-80° C.) 1:2 to give the desired product as an off-white solid (1.7 g, 44%).
Reaction SMILES: [OH:1][C@@H:2]1[C@H:11]2[C:6]([CH:7]=[CH:8][C@H:9]([CH3:29])[C@@H:10]2[CH2:12][CH2:13][C@H:14]2[O:19][C:18](=[O:20])[CH2:17][C@H:16]([O:21][Si](C(C)(C)C)(C)C)[CH2:15]2)=[CH:5][CH2:4][CH2:3]1.[CH2:30]([C:32]([CH2:38][CH3:39])([CH2:36][CH3:37])[C:33](Cl)=[O:34])[CH3:31]>>[CH2:30]([C:32]([CH2:38][CH3:39])([CH2:36][CH3:37])[C:33]([O:1][C@@H:2]1[C@H:11]2[C:6]([CH:7]=[CH:8][C@H:9]([CH3:29])[C@@H:10]2[CH2:12][CH2:13][C@H:14]2[O:19][C:18](=[O:20])[CH2:17][C@H:16]([OH:21])[CH2:15]2)=[CH:5][CH2:4][CH2:3]1)=[O:34])[CH3:31]
Reactant: C[C@H]1C=CC2=CCC[C@H](O)[C@@H]2[C@H]1CC[C@@H]1C[C@@H](O[Si](C)(C)C(C)(C)C)CC(=O)O1
Reactant: CCC(CC)(CC)C(=O)Cl
Product: CCC(CC)(CC)C(=O)O[C@H]1CCC=C2C=C[C@H](C)[C@H](CC[C@@H]3C[C@@H](O)CC(=O)O3)[C@H]21
Yield: 61.6 %

Procedure:
A procedure similar to that described in Example 6, above, was followed, but using 1.26 g (3.0 mmol) of (4R,6R)-6-{2-[(1S,2S,8S,8aR)-1,2,6,7,8,8a-hexahydro-8-hydroxy-2-methyl-1-naphthyl]ethyl}tetrahydro-4-t-butyl-dimethylsilyloxy-2H-pyran-2-one [prepared as described in Japanese Patent Kokai Application No. Sho 59-175450] and 2.22 g (13.6 mmol) of 2,2-diethylbutyryl chloride, to provide 800 mg of the title compound.
Reaction SMILES: C(O[CH:4](OCC)[CH2:5][N:6]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[CH:19]=1)S(C1C=CC(C)=CC=1)(=O)=O)C.O1CCOCC1.Cl>O>[CH3:25][O:24][C:20]1[CH:19]=[C:18]2[C:23]([CH:4]=[CH:5][N:6]=[CH:17]2)=[CH:22][CH:21]=1
Reactant: CCOC(CN(Cc1cccc(OC)c1)S(=O)(=O)c1ccc(C)cc1)OCC
Agent: Cl
Solvent: C1COCCO1
Solvent: O
Product: COc1ccc2ccncc2c1
Yield: 102.4 %

Procedure:
To a 2 liter round bottom flask equipped with a magnetic stir bar, condenser and nitrogen inlet is added (75 g, 0.184 mole) of N-(2,2-diethoxyethyl)-N-[(3-methoxyphenyl)methyl]-4-methyl-benzenesulfonamide, 1.0 liter of dioxane and 200 ml of 6N HCl. This slurry is stirred and heated at reflux under nitrogen for 18 hours. The reaction solution is then slowly poured into 1 liter of H2O and stirred for an additional 30 minutes then extracted with ether (2×500 ml). The pH of the aqueous layer is adjusted to 8 with ammonium hydroxide, the product is extracted with dichloromethane. The combined organics extracts are dried over MgSO4, filtered and evaporated to yield 30 g of an oil. The crude product is purified by chromatography with 12.0% acetone in dichloromethane to provide the product (19.7 g) in a 67% yield.
Reaction SMILES: [CH2:1]([N:14]1[CH2:19][C:18]([CH3:21])([CH3:20])[NH:17][C:16]([CH3:23])([CH3:22])[C:15]1=[O:24])[CH2:2][N:3]1[CH2:8][C:7]([CH3:10])([CH3:9])[NH:6][C:5]([CH3:12])([CH3:11])[C:4]1=[O:13].NC(C)(C)CNCCN.C[C:35](C)([OH:38])[C:36]#N.[C:40](OC(=O)C)(=[O:42])[CH3:41]>S(=O)(=O)(O)O.C(Cl)Cl>[CH2:2]([N:3]1[CH2:8][C:7]([CH3:9])([CH3:10])[N:6]([C:35](=[O:38])[CH3:36])[C:5]([CH3:12])([CH3:11])[C:4]1=[O:13])[CH2:1][N:14]1[CH2:19][C:18]([CH3:21])([CH3:20])[N:17]([C:40](=[O:42])[CH3:41])[C:16]([CH3:23])([CH3:22])[C:15]1=[O:24]
Reactant: CC(C)(O)C#N
Reactant: CC1(C)CN(CCN2CC(C)(C)NC(C)(C)C2=O)C(=O)C(C)(C)N1
Reactant: CC(=O)OC(C)=O
Agent: CC(C)(N)CNCCN
Agent: O=S(=O)(O)O
Solvent: ClCCl
Product: CC(=O)N1C(C)(C)CN(CCN2CC(C)(C)N(C(C)=O)C(C)(C)C2=O)C(=O)C1(C)C
Temperature: 130 °C

Procedure:
31.5 grams (0.1 mole) of 1,1'-ethylenebis(3,3,5,5-tetra- methyl-2-piperazinone), prepared according to Example 6,E of U.S. Pat. No. 4,190,571 from N,N'-(2-amino-2-methylpropyl)-e thylenediamine and acetone cyanohydrin, is dissolved in 102 grams (1.0 mole) of acetic anhydride. After three drops of concentrated sulfuric acid are added to the solution, the mixture is heated for four hours at 130° C. and then cooled to room temperature. Methylene chloride (200 ml.) is added to extract the product into an organic layer which is then washed successively with water and with saturated sodium bicarbonate solution and is finally dried over anhydrous magnesium sulfate. The solvent is removed in vacuo and the residual product is recrystallized from toluene to give 30.4 grams of the above-named product as a white solid, melting at 180°-183° C. (sintering at 170° C.).