Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C@@H:2]1[O:10][CH2:9][C@H:7]([OH:8])[C@H:5]([OH:6])[C@H:3]1[OH:4].C[O-].[Na+].[N+:14]([CH3:17])([O-:16])=[O:15]>CO>[N+:14]([CH2:17][C@H:2]([C@@H:3]([C@H:5]([C@H:7]([CH2:9][OH:10])[OH:8])[OH:6])[OH:4])[OH:1])([O-:16])=[O:15]
Reactant: O[C@@H]1[C@@H](O)[C@@H](O)CO[C@H]1O
Reactant: C[N+](=O)[O-]
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: O=[N+]([O-])C[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)CO
Reaction time: 20 h

Procedure:
A suspension of commercial α-L-arabinose (100 g.) in absolute methanol (200 ml.) and dry nitromethane (360 ml.), in a 3-necked, 2-liter flask fitted with an efficient mechanical stirrer and a calcium chloride drying tube, was treated with a 1.3 N methanolic sodium methoxide solution (700 ml.). After 20 hr. of vigorous stirring, the precipitated sodium aci-nitro alcohols were collected by filtration and washed with a small volume of cold methanol followed by cold petroleum ether (60°-80°). The moist, highly hygroscopic salts were immediately dissolved in 800 ml. of iced water and the solution deionized either by passage over a column containing 800 ml. of Dowex® 50W-X8 (H+) resin or by three successive treatments with 300 ml. of fresh resin. The effluent and washings (total volume 2.5-3.0 liters for the column treatment and 1.5-2.0 liters for the batch treatment) were then evaporated at reduced pressure to a semi-crystalline mass which was further concentrated with several portions of absolute ethanol to remove residual water. The resulting crystalline mass was filtered with the aid of cold ethanol and the filtrate reprocessed to provide two additional crops of crystals. The crude product (70 g.) was separated by fractional crystallization from ethanol into the less soluble 1-deoxy-1-nitro-L-mannitol (30 g.) and the more soluble 1-deoxy-1-nitro-L-glucitol (25 g.). Two additional recrystallizations of samples of the nitro alcohols provided 1-deoxy-1-nitro-L-glucitol, m.p. 106°-107°, [α]D +7.44° (c 3.2, water), compared to m.p. 107°-108°, [α]D +9.5° (c 6.7, water); and 1-deoxy-1-nitro-L-mannitol, m.p. 133°-134°, [α]D +6.67° (c 5.4, water), compared to m.p. 133°-134°, [α]D +7.0° (c 6.2, water).
Reaction SMILES: [F:1][C:2]([F:14])([F:13])[O:3][C:4]1[CH:12]=[CH:11][CH:10]=[CH:9][C:5]=1[C:6](O)=O.S(Cl)(Cl)=O.CN(C)[CH:21]=[O:22].[C:24]1([OH:30])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>ClCCl>[F:1][C:2]([F:14])([F:13])[O:3][C:4]1[CH:12]=[CH:11][CH:10]=[CH:9][C:5]=1[C:6]1[CH:25]=[CH:26][CH:27]=[CH:28][C:29]=1[C:24]([O:22][C:21]1[CH:11]=[CH:12][CH:4]=[CH:5][CH:6]=1)=[O:30]
Reactant: CN(C)C=O
Reactant: O=C(O)c1ccccc1OC(F)(F)F
Reactant: Oc1ccccc1
Solvent: ClCCl
Solvent: O=S(Cl)Cl
Product: O=C(Oc1ccccc1)c1ccccc1-c1ccccc1OC(F)(F)F

Procedure:
A mixture composed of 10 g (48.5 mmol) of 2-(trifluoromethoxy)benzoic acid, 50 ml of thionyl chloride and a drop of dimethylformamide is heated under reflux for 1.5 hours. After cooling and concentrating the reaction mixture under vacuum, a residue is obtained which is stirred for 2 hours at 100° C. in the presence of 4.75 g (50 mmol) of phenol. After cooling, the reaction medium is taken up in dichloromethane, washed with a saturated NaHCO3 solution and then with water, dried over Na2SO4 and concentrated.
Reaction SMILES: O.O.O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[C:22]([O:26][C:27]([N:29]([C:31]1[CH:36]=[C:35]([CH2:37][O:38][Si](C(C)(C)C)(C)C)[CH:34]=[CH:33][N:32]=1)[CH3:30])=[O:28])([CH3:25])([CH3:24])[CH3:23].C(OCC)(=O)C.O>O1CCCC1>[C:22]([O:26][C:27]([N:29]([C:31]1[CH:36]=[C:35]([CH2:37][OH:38])[CH:34]=[CH:33][N:32]=1)[CH3:30])=[O:28])([CH3:25])([CH3:23])[CH3:24]
Reactant: CN(C(=O)OC(C)(C)C)c1cc(CO[Si](C)(C)C(C)(C)C)ccn1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: O
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CN(C(=O)OC(C)(C)C)c1cc(CO)ccn1
Reaction time: 0.25 h
Yield: 50 %

Procedure:
A solution of tetra-n-butylammonium fluoride trihydrate(1.3 g, 4.2 mmol) in tetrahydrofuran (20 mL) was added to a solution of 2-(N-tert-butoxycarbonyl-N-methylamino)-4-(tert-butyldimethylsilyloxymethyl)pyridine (Reference compound No. 6-1, 1.4 g, 3.7 mmol) in tetrahydrofuran (20 mL) for 5 minutes at room temperature, and the mixture was stirred for 15 minutes. Ethyl acetate (50 mL) and water (100 mL) were added to the reaction mixture, the whole was separated, and then the aqueous layer was extracted with ethyl acetate (50 mL). These organic layers were combined, then it was washed with brine (100 mL) and dried over anhydrous magnesium sulfate. The organic layer was evaporated under reduced pressure, then the resulting residue was purified by silica gel column chromatography to give 450 mg of the title reference compound as a reddish brown oil. (Yield 50%)
Reaction SMILES: [CH3:1][S:2][C:3]1[S:7][N:6]=[C:5]([C:8]([F:11])([F:10])[F:9])[C:4]=1C(O)=O>N1C2C(=CC=CC=2)C=CC=1.CCOCC>[CH3:1][S:2][C:3]1[S:7][N:6]=[C:5]([C:8]([F:11])([F:9])[F:10])[CH:4]=1
Reactant: CSc1snc(C(F)(F)F)c1C(=O)O
Solvent: CCOCC
Solvent: c1ccc2ncccc2c1
Product: CSc1cc(C(F)(F)F)ns1
Temperature: 170 °C

Procedure:
5-Methylthio-3-(trifluoromethyl)isothiazole-4-carboxylic acid (9.4 g, 39 mmol) was dissolved in 15 mL of quinoline and 0.6 g (4.2 mmol) of cuprous oxide was added. The mixture was heated at 170° C. for about 30 min and then allowed to cool. It was then diluted with ether and the resulting solution was washed with 100 mL of 2N hydrochloric acid, dried over sodium bicarbonate, filtered, and distilled to obtain 6.55 g (85 percent of theory) of the title compound as a colorless liquid boiling at 126°-127° C. at 84 mm Hg (11 kPa (kiloPascals)) pressure.
Reaction SMILES: O1[C:5]2([CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][C:12]=3[OH:18])[CH2:7][CH2:6]2)[O:4]CC1.O.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>CC(C)=O>[OH:18][C:12]1[CH:13]=[C:14]([OH:17])[CH:15]=[CH:16][C:11]=1[CH:8]1[CH2:7][CH2:6][C:5](=[O:4])[CH2:10][CH2:9]1
Reactant: Oc1ccc(C2CCC3(CC2)OCCO3)c(O)c1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: c1cc[nH+]cc1
Solvent: CC(C)=O
Solvent: O
Product: O=C1CCC(c2ccc(O)cc2O)CC1
Yield: 99.8 %

Procedure:
A flask equipped with magnetic stirrer was charged with 4-(1,4-dioxaspiro[4.5]dec-8yl)-1,3-benzenediol (11.3 g, 45.2 mmol), acetone (250 ml) and water (50 ml). To the stirred solution was added pyridinium p-toluenesulfonate (1.14 g, 4.52 mmol) in one portion and the reaction mixture was then heated under reflux for 8 hr. After allowing the reaction mixture to cool to room temperature, most of the acetone was removed in vacuo and the remaining mixture was partitioned between ethyl acetate (200 ml) and water (50 ml). The aqueous layer was extracted with ethyl acetate (3×50 ml) and the combined organic layers were washed with brine (30 ml), dried (MgSO4), filtered and concentrated under reduced pressure to afford an off-white powder. After washing the powder with dichloromethane (100 ml) and removal of excess solvent under reduced pressure, the title compound (9.30 g, 100%) was obtained as an off-white powder. m/z (ES+) 207 (M+H+).
Reaction SMILES: Cl.[Br:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][C:8]([OH:10])=[O:9].[CH3:11]O>>[CH3:11][CH:7]([CH2:6][CH2:5][CH2:4][CH2:3][Br:2])[C:8]([OH:10])=[O:9].[Br:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][C:8]([O:10][CH3:11])=[O:9]
Reactant: O=C(O)CCCCCBr
Reactant: CO
Agent: Cl
Product: CC(CCCCBr)C(=O)O
Product: COC(=O)CCCCCBr
Reaction time: 3 h
Yield: 90 %

Procedure:
Hydrogen chloride (gas) was added to a solution of 5.01 g (25.7 mmol) of 6-bromocaproic acid in 250 ml of methanol via vigorous bubbling for 2-3 minutes. The mixture was stirred at 15°-25° C. for 3 hours and then concentrated to afford 4.84 g of the product as a yellow oil (90%):
Reaction SMILES: Cl[C:2]([O:4][CH:5]1[CH2:9][CH2:8][CH2:7][CH2:6]1)=[O:3].[NH2:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][CH:15]=[C:14]2[CH2:20][C:21]1[CH:30]=[CH:29][C:24]([C:25]([O:27][CH3:28])=[O:26])=[CH:23][C:22]=1[O:31][CH3:32].CN1CCOCC1>ClCCl>[CH:5]1([O:4][C:2]([NH:10][C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[NH:16][CH:15]=[C:14]3[CH2:20][C:21]2[CH:30]=[CH:29][C:24]([C:25]([O:27][CH3:28])=[O:26])=[CH:23][C:22]=2[O:31][CH3:32])=[O:3])[CH2:9][CH2:8][CH2:7][CH2:6]1
Reactant: COC(=O)c1ccc(Cc2c[nH]c3ccc(N)cc23)c(OC)c1
Reactant: O=C(Cl)OC1CCCC1
Solvent: ClCCl
Solvent: CN1CCOCC1
Product: COC(=O)c1ccc(Cc2c[nH]c3ccc(NC(=O)OC4CCCC4)cc23)c(OC)c1
Reaction time: 0.5 h
Yield: 89 %

Procedure:
Cyclopentyl chloroformate was added to a stirred solution of the amino ester (A) (0.15 g.) and N-methylmorpholine (0.27 g.) in dichloromethane (3 ml.) at 0°-5° C., under an atmosphere of nitrogen. The mixture was stirred for 30 minutes at 0°-5° C., the cooling bath removed, and stirring continued for 1 hour. The mixture was then poured into 1M hydrochloric acid (15 ml.), and extracted with ethyl-acetate. The combined extracts were dried (MgSO4) and evaporated. The residual oil was purified by flash chromatography on silica gel (50 ml.), eluting with 3:7 v/v ethyl acetate:hexane, to give the title compound (0.18 g., 89%) as a colorless oil; NMR: 1.66(m, 6H), 1.82(m,2H), 3.83(s,3H, CO.OCH3), 3.92(s,3H, OCH3), 3.97(s,2H, CH2.Ar), 5.04(m,1H, --CHO--), 7.09(m, 3H), 7.22(d,1H), 7.42(dd,1H), 7.48(d,1H), 7.57(br,1H), 9.18(br,1H, CONH), 10.57(s,1H, H1 -indole).
Reaction SMILES: [Li+].CC([N-]C(C)C)C.C(C1C=CC=CC=1)C.[CH2:17]([O:19][C:20]([CH:22]1[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]1)=[O:21])[CH3:18].Cl[CH2:36][O:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>C1COCC1>[CH2:17]([O:19][C:20]([C:22]1([CH2:36][O:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:33])([CH3:32])[CH3:34])=[O:29])[CH2:24][CH2:23]1)=[O:21])[CH3:18]
Reactant: ClCOCc1ccccc1
Reactant: CCOC(=O)C1CCN(C(=O)OC(C)(C)C)CC1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCc1ccccc1
Product: CCOC(=O)C1(COCc2ccccc2)CCN(C(=O)OC(C)(C)C)CC1
Reaction time: 2 h
Yield: 78.9 %

Procedure:
To a pre-cooled THF solution under an argon atmosphere was added at −5° C. LDA (2 M, in THF/hepatane/ethylbenzene, 17.5 ml) and then dropwise a solution of piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester (5 g) in THF, keeping the temperature at about −7° C. The mixture was stirred 2 hours between −10 and −5° C. then treated slowly and dropwise with benzyl chlormethyl ether (5.47 g) at −5° C. The mixture was stirred 1 hour at 0° C. and 48 h at RT. The solvent was evaporated off, the residue partitioned between AcOEt and water. The layers were separated, the organic layer washed with brine, dried over sodium sulphate and concentrated in vacuo. The residue purified by flash chromatography (AcOEt/heptane, gradient from 0 to 5%) to give the desired 4-Benzyloxymethyl-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester (5.79 g) as a light brown oil. MS (ESI): 378.4 (MH+).
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[Na].[C:7]([C:9](=[N:18][OH:19])[C:10]1[C:15]([Cl:16])=C[CH:13]=[CH:12][C:11]=1[Cl:17])#[N:8].[CH3:20]C(C)=O>>[CH3:20][O:19][N:18]=[C:9]([C:7]#[N:8])[C:10]1[CH:15]([Cl:16])[C:1](=[S:2](=[O:4])=[O:3])[CH:13]=[CH:12][C:11]=1[Cl:17]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)=O
Reactant: N#CC(=NO)c1c(Cl)cccc1Cl
Agent: [Na]
Product: CON=C(C#N)C1=C(Cl)C=CC(=S(=O)=O)C1Cl
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A 3.3 g (0.028 mol) sample of methylsulfonyl chloride was added slowly to a slurry of 6.5 g (0.027 mol) of the sodium salt of alpha-cyano-2,6-dichlorobenzaldoxime in 60 ml acetone. The reaction was exothermic. After the addition was completed, the reaction mixture was stirred at about 25° C. for 1 hour, filtered and evaporated under reduced pressure to give a tan oil which crystallized to give the product. Recrystallization from ether/hexane gave the product as white crystals, m.p. 81-82. Nuclear magnetic resonance analysis showed the product to be approximately a 60:40 mixture of the syn- and anti-isomers. Elemental analysis for the product is tabulated in Table I as Compound No 3.
Reaction SMILES: [C:1]1([O:7][S:8](=[O:11])(=[O:10])[NH2:9])[CH:6]=[CH:5]C=[CH:3][CH:2]=1.[CH:12](C1(O)CC1)(C)C>>[CH:6]([C:1]1([O:7][S:8](=[O:10])(=[O:11])[NH2:9])[CH2:2][CH2:3]1)([CH3:5])[CH3:12]
Reactant: CC(C)C1(O)CC1
Reactant: NS(=O)(=O)Oc1ccccc1
Product: CC(C)C1(OS(N)(=O)=O)CC1

Procedure:
Sulfamic acid 1-isopropyl-cyclopropyl ester was synthesized according to the method presented in the synthesis of sulfamic acid phenyl ester in Example 1 with the exception of utilizing 1-isopropylcyclopropanol (synthesized by methods reported in Synthesis 1991, 234.) to obtain sulfamic acid 1-isopropyl-cyclopropyl ester.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:30])[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[NH:16][CH2:17][CH:18]2[CH2:23][CH2:22][N:21]([C:24]3[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=3)[CH2:20][CH2:19]2)=[N:6][CH:7]=1.[CH2:31]=O>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:30])[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[N:16]([CH3:31])[CH2:17][CH:18]2[CH2:19][CH2:20][N:21]([C:24]3[CH:25]=[CH:26][N:27]=[CH:28][CH:29]=3)[CH2:22][CH2:23]2)=[N:6][CH:7]=1
Reactant: C=O
Reactant: O=C(Nc1ccc(Cl)cn1)c1ccccc1NCC1CCN(c2ccncc2)CC1
Product: CN(CC1CCN(c2ccncc2)CC1)c1ccccc1C(=O)Nc1ccc(Cl)cn1

Procedure:
Using a similar procedure to that described in Example 27, N-(5-chloropyridin-2-yl)-2-[1-(4-pyridinyl)piperidin-4-ylmethyl]aminobenzamide (100 mg, 0.237 mmol) and paraformaldehyde (20 mg, 0.238 mmol) afforded, after purification by column chromatography (SiO2: 2 to 4% [2 N ammonia in methanol]:chloroform), 25 mg (24%) of the title compound.
Reaction SMILES: [NH2:1][CH:2]1[C:25](=[O:26])[N:4]2[C:5]([C:22]([OH:24])=[O:23])=[C:6]([CH:9]([S:16][C:17]3[NH:21][N:20]=[N:19][N:18]=3)[CH2:10][CH2:11][S:12](=[O:15])(=[O:14])[NH2:13])[CH2:7][S:8][C@H:3]12.CN(C)C=O.[F:32][C:33]([F:42])([F:41])[CH2:34][S:35]([CH2:37][C:38](O)=[O:39])=[O:36]>C(N(CC)CC)C>[F:32][C:33]([F:42])([F:41])[CH2:34][S:35]([CH2:37][C:38]([NH:1][CH:2]1[C:25](=[O:26])[N:4]2[C:5]([C:22]([OH:24])=[O:23])=[C:6]([CH:9]([S:16][C:17]3[NH:18][N:19]=[N:20][N:21]=3)[CH2:10][CH2:11][S:12](=[O:14])(=[O:15])[NH2:13])[CH2:7][S:8][C@H:3]12)=[O:39])=[O:36]
Reactant: NC1C(=O)N2C(C(=O)O)=C(C(CCS(N)(=O)=O)Sc3nnn[nH]3)CS[C@H]12
Reactant: O=C(O)CS(=O)CC(F)(F)F
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: NS(=O)(=O)CCC(Sc1nnn[nH]1)C1=C(C(=O)O)N2C(=O)C(NC(=O)CS(=O)CC(F)(F)F)[C@H]2SC1

Procedure:
A suspension of 4.17 g. (0.01 mol.) of 7-amino-3-[1-(2-sulfamoylethyl)tetrazol-5-ylthiomethyl]-3-cephem-4-carboxylic acid in 50 ml. of dry dimethylformamide is treated with 2 ml. of triethylamine and the mixture is stirred for 15 minutes at 25°. A slight excess of 0.01 mol. of the activated ester of 2,2,2-trifluoroethylsulfinylacetic acid is added to the mixture and it is stirred an additional hour. The reaction mixture is evaporated to dryness and water and ethyl acetate are added to the residue. The layers are separated, ethyl acetate is added to the aqueous phase and it is acidified to pH 2.5 by addition of 6N hydrochloric acid. The mixture is filtered, the layers are separated and the aqueous phase is extracted with ethyl acetate. The extract is washed with water, dried (MgSO4) and evaporated to dryness to give the title compound.
Reaction SMILES: [CH3:1][C:2]1([C:7]2[N:8]=[C:9]([CH2:12][N:13]3[CH:17]=[CH:16][C:15]([NH2:18])=[N:14]3)[S:10][CH:11]=2)[O:6]CCO1.[CH3:19][N:20]([CH3:35])[C:21]1[CH:22]=[C:23]([C:27]2[O:31][CH:30]=[N:29][C:28]=2[C:32](O)=[O:33])[CH:24]=[CH:25][CH:26]=1>>[C:2]([C:7]1[N:8]=[C:9]([CH2:12][N:13]2[CH:17]=[CH:16][C:15]([NH:18][C:32]([C:28]3[N:29]=[CH:30][O:31][C:27]=3[C:23]3[CH:24]=[CH:25][CH:26]=[C:21]([N:20]([CH3:35])[CH3:19])[CH:22]=3)=[O:33])=[N:14]2)[S:10][CH:11]=1)(=[O:6])[CH3:1]
Reactant: CN(C)c1cccc(-c2ocnc2C(=O)O)c1
Reactant: CC1(c2csc(Cn3ccc(N)n3)n2)OCCO1
Product: CC(=O)c1csc(Cn2ccc(NC(=O)c3ncoc3-c3cccc(N(C)C)c3)n2)n1

Procedure:
Following general procedure B followed by C, starting from 1-[4-(2-methyl-[1,3]dioxolan-2-yl)-thiazol-2-ylmethyl]-1H-pyrazol-3-ylamine and 5-(3-dimethylamino-phenyl)-oxazole-4-carboxylic acid. LC-MS-conditions 05: tR=0.68 min; [M+H]+=437.04.
Reaction SMILES: Cl.[CH3:2][O:3][C:4]1[CH:5]=[C:6]([C:12]2([CH2:22][CH2:23][CH2:24][N:25]([CH3:35])[CH:26](C)[CH2:27]C3C=CC=CC=3)[S:17](=O)(=O)[CH2:16][CH2:15][CH2:14][S:13]2(=O)=O)[CH:7]=[CH:8][C:9]=1[O:10][CH3:11].[CH3:36][O:37][C:38]1[CH:39]=[C:40]([CH:65]=[CH:66][C:67]=1[O:68][CH3:69])[CH2:41]CN(C)CCCCC1(C2C=CC(OC)=CC=2OC)SCCCS1>CC(C)=O.C(OCC)(=O)C>[CH3:2][O:3][C:4]1[CH:5]=[C:6]([C:12]2([CH2:22][CH2:23][CH2:24][N:25]([CH2:26][CH2:27][CH2:41][C:40]3[CH:65]=[CH:66][C:67]([O:68][CH3:69])=[C:38]([O:37][CH3:36])[CH:39]=3)[CH3:35])[S:13][CH2:14][CH2:15][CH2:16][S:17]2)[CH:7]=[CH:8][C:9]=1[O:10][CH3:11]
Reactant: COc1ccc(C2(CCCCN(C)CCc3ccc(OC)c(OC)c3)SCCCS2)c(OC)c1
Reactant: COc1ccc(C2(CCCN(C)C(C)Cc3ccccc3)S(=O)(=O)CCCS2(=O)=O)cc1OC
Agent: Cl
Solvent: CC(C)=O
Solvent: CCOC(C)=O
Product: COc1ccc(CCCN(C)CCCC2(c3ccc(OC)c(OC)c3)SCCCS2)cc1OC

Procedure:
2-(3,4-Dimethoxyphenyl)-N-methyl-N-(-methylphenethyl)-m-dithiane-2-propylamine-1,1,3,3-tetraoxide hydrochloride of melting point 185°-187° C. (from acetone/ethyl acetate), starting from 2-(3,4-dimethoxyphenyl)-N-methyl-N-(α-methylphenethyl)-m-dithiane-2-propylamine (prepared as described in Example 6).
Reaction SMILES: O=[C:2]1[NH:8][C:7]2[CH:9]=[CH:10][CH:11]=[CH:12][C:6]=2[NH:5][C:4](=[O:13])[CH2:3]1.[CH2:14](I)[C:15]([CH3:18])([CH3:17])[CH3:16].[C:20]([O-:23])([O-])=O.[Cs+].[Cs+].O>CS(C)=O.CCOC(C)=O>[O:13]=[C:4]1[N:5]([CH2:14][C:15]([CH3:18])([CH3:17])[CH3:16])[C:6]2[CH:12]=[CH:11][CH:10]=[CH:9][C:7]=2[N:8]([CH2:2][C:15]([CH3:17])([CH3:16])[CH3:14])[C:20](=[O:23])[CH2:3]1
Reactant: O=C([O-])[O-]
Reactant: CC(C)(C)CI
Reactant: O=C1CC(=O)Nc2ccccc2N1
Agent: [Cs+]
Solvent: O
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: CC(C)(C)CN1C(=O)CC(=O)N(CC(C)(C)C)c2ccccc21
Temperature: 75 °C
Reaction time: 6 h

Procedure:
To a stirred suspension of the product from Example 8-P, Step A (1.0 eq., 17.08 g) in DMSO (500 mL) at room temperature was added neopentyl iodide (43.01 g, 2.24 eq., Aldrich) and Cs2CO3 (72.65 g, 2.3 eq., Aldrich). The resulting mixture was heated to 75° C. for 30 minutes, then additional Cs2CO3 (31.59 g, 1.0 eq.) was added and the mixture rapidly stirred at 75° C. for 6 hours. The mixture was allowed to cool and H2O (500 mL) and EtOAc (1000 mL) were added. The phases were partitioned and the organic phase washed with H2O (1×500 mL), 1 M aq. HCl (2×500 mL), and brine (1×500 mL). Then, the organic phase was dried over MgSO4, filtered, concentrated, and purified by flash chromatography eluting with hexanes/EtOAc (3:2 gradient to 2:3) to provide 2,4-dioxo-1,5-bis-(2,2-dimethylpropyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine as a white solid.
Reaction SMILES: [OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([CH:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]2)[C:3]1=[O:20].C(N(CC)CC)C.[CH3:28][S:29](Cl)(=[O:31])=[O:30]>C1COCC1>[CH3:28][S:29]([O:1][C@@H:2]1[CH2:6][CH2:5][N:4]([CH:7]2[CH2:8][CH2:9][N:10]([C:13]([O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[O:14])[CH2:11][CH2:12]2)[C:3]1=[O:20])(=[O:31])=[O:30]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)(C)OC(=O)N1CCC(N2CC[C@@H](O)C2=O)CC1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1CCC(N2CC[C@@H](OS(C)(=O)=O)C2=O)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 97.6 %

Procedure:
(R)-tert-Butyl 4-(3-hydroxy-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (20.5 g, 72.1 mmol) was dissolved in THF (500 mL) and triethylamine (20.1 mL, 144 mmol) and methanesulfonyl chloride (6.74 mL, 86.5 mmol) were added to the reaction and stirred at ambient temperature for 1 hour. The reaction was partitioned between saturated aqueous NaHCO3 and EtOAc, dried over Na2SO4, filtered and concentrated. The residue was purified over silica gel to afford (R)-tert-butyl 4-(3-(methylsulfonyloxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (Preparation D; 25.5 g, 70.4 mmol, 98% yield) as a white solid. 1H NMR CDCl3 5.2 ppm (t, 1H), 4.3 ppm (m, 2H), 4.1 ppm (m, 1H), 3.4 ppm (m, 1H), 3.3 ppm (m, 1H), 3.3 ppm (s, 3H), 2.8 ppm (m, 2H), 2.6 ppm (m, 1H), 2.3 ppm (m, 1H), 1.7 ppm (m, 2H, 1.6 ppm (m, 2H), 1.5 ppm (s, 9H).
Reaction SMILES: [NH2:1][C:2]1[CH:22]=[C:21]([CH3:23])[CH:20]=[CH:19][C:3]=1[O:4][C:5]1[C:14]2[C:9](=[CH:10][C:11]([O:17][CH3:18])=[C:12]([O:15][CH3:16])[CH:13]=2)[N:8]=[CH:7][CH:6]=1.[C:24]1(B(O)O)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C(N(CC)CC)C.CN(C)C=O.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH3:16][O:15][C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][C:11]=1[O:17][CH3:18])[N:8]=[CH:7][CH:6]=[C:5]2[O:4][C:3]1[CH:19]=[CH:20][C:21]([CH3:23])=[CH:22][C:2]=1[NH:1][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: OB(O)c1ccccc1
Reactant: COc1cc2nccc(Oc3ccc(C)cc3N)c2cc1OC
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COc1cc2nccc(Oc3ccc(C)cc3Nc3ccccc3)c2cc1OC
Temperature: 25 °C
Reaction time: 8 h
Yield: 77.2 %

Procedure:
4-(2-Amino-4-methylphenoxy)-6,7-dimethoxyquinoline (52 mg) was dissolved in triethylamine/N,N-dimethylformamide (0.5 ml/2.5 ml), and phenylboronic acid (100 mg) and copper acetate (250 mg) were added to the solution which was then stirred at room temperature overnight. The reaction solution was filtered, and the solvent was removed therefrom by distillation under the reduced pressure. Water was added to the residue, and the mixture was extracted with ethyl acetate. Next, the ethyl acetate layer was then washed with water and saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed therefrom by distillation under the reduced pressure, and the residue was purified by thin layer chromatography using acetone-chloroform to give the title compound (50 mg, yield 76%).
Reaction SMILES: Cl[C:2]1[N:7]2[N:8]=[CH:9][C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:6]2[N:5]=[CH:4][C:3]=1[C:16]([N:18]1[CH2:23][CH2:22][CH:21]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:20][CH2:19]1)=[O:17].[CH3:30][N:31]1[C:39]2[C:34](=[CH:35][C:36]([NH2:40])=[CH:37][CH:38]=2)[CH:33]=[CH:32]1>>[CH2:14]([O:13][C:11]([C:10]1[CH:9]=[N:8][N:7]2[C:2]([NH:40][C:36]3[CH:35]=[C:34]4[C:39](=[CH:38][CH:37]=3)[N:31]([CH3:30])[CH:32]=[CH:33]4)=[C:3]([C:16]([N:18]3[CH2:23][CH2:22][CH:21]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[CH2:20][CH2:19]3)=[O:17])[CH:4]=[N:5][C:6]=12)=[O:12])[CH3:15]
Reactant: CCOC(=O)c1cnn2c(Cl)c(C(=O)N3CCC(c4ccccc4)CC3)cnc12
Reactant: Cn1ccc2cc(N)ccc21
Product: CCOC(=O)c1cnn2c(Nc3ccc4c(ccn4C)c3)c(C(=O)N3CCC(c4ccccc4)CC3)cnc12
Yield: 89.8 %

Procedure:
In the same manner as in Example 19, step 5 and using 7-chloro-3-ethoxycarbonyl-6-(4-phenylpiperidine-1-carbonyl)pyrazolo[1,5-a]pyrimidine (0.15 g, 0.36 mmol) obtained in Example 19, step 4 and 1-methyl-5-aminoindole (0.072 g, 0.49 mmol), the title compound (0.169 g, 90%) was obtained.