Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]=[CH:2][C@@H:3]([C@H:5]([C@@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])[OH:4].C(O)[C@H]1O[C@H]([O:20][CH2:21][C@H:22]2[O:27][C@H:26]([O:28][C@@H:29]([C@H:34]([OH:39])[C@@H:35]([OH:38])[CH:36]=[O:37])[C@H:30]([OH:33])[CH2:31][OH:32])[C@H:25]([OH:40])[C@@H:24]([OH:41])[C@@H:23]2[OH:42])[C@H](O)[C@@H](O)[C@@H]1O.[CH2:47]([OH:69])[C@H:48]1[O:53][C@H:52]([O:54][C@H:55]2[C@H:60]([OH:61])[C@@H:59]([OH:62])[C@H:58]([OH:63])[O:57][C@@H:56]2[CH2:64][OH:65])[C@H:51]([OH:66])[C@@H:50]([OH:67])[C@@H:49]1[OH:68]>>[CH2:21]([OH:20])[C@H:22]1[O:27][C@H:26]([O:28][C@H:29]2[C@H:34]([OH:39])[C@@H:35]([OH:38])[C@H:36]([OH:37])[O:33][C@@H:30]2[CH2:31][OH:32])[C@H:25]([OH:40])[C@@H:24]([OH:41])[C@@H:23]1[OH:42].[O:1]=[CH:2][C@@H:3]([C@H:5]([C@@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])[OH:4].[CH2:47]([OH:69])[C@H:48]1[O:53][C@H:52]([O:54][C@H:55]2[C@H:60]([OH:61])[C@@H:59]([OH:62])[C@@H:58]([O:63][C@H:23]3[C@H:24]([OH:41])[C@@H:25]([OH:40])[C@@H:26]([O:28][C@H:29]4[C@H:34]([OH:39])[C@@H:35]([OH:38])[C@@H:36]([OH:37])[O:33][C@@H:30]4[CH2:31][OH:32])[O:27][C@@H:22]3[CH2:21][OH:20])[O:57][C@@H:56]2[CH2:64][OH:65])[C@H:51]([OH:66])[C@@H:50]([OH:67])[C@@H:49]1[OH:68]
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O[C@H]1O[C@H](CO[C@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)[C@@H](O)[C@H](O)[C@H]1O)[C@H](O)CO
Agent: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Agent: OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O
Product: OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@@H](O[C@H]3[C@H](O)[C@@H](O)[C@@H](O[C@H]4[C@H](O)[C@@H](O)[C@@H](O)O[C@@H]4CO)O[C@@H]3CO)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O

Procedure:
As evident from the results in Table 23, it was revealed that, after the enzymatic action, glucose and α-isomaltosylglucose alias 62-O-α-glucosylmaltose or panose were mainly formed maltose as a substrate; and maltose and α-isomaltosylglucose alias 63-O-α-glucosylmaltotriose were mainly formed along with small amounts of glucose, maltotetraose, α-isomaltosylglucose alias 62-O-α-glucosylmaltose or panose, and a product X. Also, it was revealed that maltotriose and the product X were mainly formed from maltotetraose as a substrate along with small amounts of maltose, maltopentaose, α-isomaltosylglucose alias 63-O-α-glucosylmaltotriose; and a product Y; and that maltotetraose and the product Y were mainly formed from maltopentaose as a substrate along with small amounts of maltotriose, maltohexaose, and the products X and Z. The product X as a main product from maltotetraose as a substrate and the product Y as a main product from maltopentaose as a substrate were respectively isolated and purified as follows: The products X and Y were respectively purified on HPLC using “YMC PACK ODS-A R355-15S-15 12A”, a separatory HPLC column commercialized by YMC Co., Ltd., Tokyo, Japan, to isolate the product X having a purity of at least 99.9% from the reaction product from maltotetraose in a yield of about 8.3%, d.s.b., and the product Y having a purity of at least 99.9% from the reaction product from maltopentaose in a yield of about 11.5%, d.s.b.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:8])=[N:6][CH:7]=1.[Br:9]Br.C(OCC)(=O)C.O>C(O)(=O)C>[Br:9][C:4]1[C:5]([OH:8])=[N:6][CH:7]=[C:2]([Cl:1])[CH:3]=1
Reactant: Oc1ccc(Cl)cn1
Reactant: BrBr
Solvent: O
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: Oc1ncc(Cl)cc1Br
Temperature: 25 °C
Reaction time: 48 h

Procedure:
5-Chloro-2-pyridinol (5.18 g, 40 mmol) was dissolved in glacial acetic acid (50 ml) and bromine (7.51 g, 2.41 ml, 47 mmol) added. The mixture was stirred at room temperature for 48 hours. Ethyl acetate and water were added and the organic layer washed with water (×3), dried (MgSO4) and evaporated. The residue was triturated with diethyl ether and the buff solid filtered and dried (5.59 g).
Reaction SMILES: [C:1]([CH:4]([N:14]1[CH2:17][CH:16]([NH:18][C:19](=[O:43])[C:20]([C:23]2[CH:28]=[CH:27][C:26]([O:29][CH2:30][CH2:31][CH:32]([C:40]([OH:42])=[O:41])[NH:33]C(=O)C(F)(F)F)=[CH:25][CH:24]=2)=[N:21][OH:22])[C:15]1=[O:44])[C:5]1[CH:10]=[C:9]([Br:11])[C:8]([OH:12])=[C:7]([Br:13])[CH:6]=1)([OH:3])=[O:2].[OH-].[Na+].Cl>O>[C:1]([CH:4]([N:14]1[CH2:17][CH:16]([NH:18][C:19](=[O:43])[C:20]([C:23]2[CH:24]=[CH:25][C:26]([O:29][CH2:30][CH2:31][CH:32]([NH2:33])[C:40]([OH:42])=[O:41])=[CH:27][CH:28]=2)=[N:21][OH:22])[C:15]1=[O:44])[C:5]1[CH:10]=[C:9]([Br:11])[C:8]([OH:12])=[C:7]([Br:13])[CH:6]=1)([OH:3])=[O:2]
Reactant: O=C(NC1CN(C(C(=O)O)c2cc(Br)c(O)c(Br)c2)C1=O)C(=NO)c1ccc(OCCC(NC(=O)C(F)(F)F)C(=O)O)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: NC(CCOc1ccc(C(=NO)C(=O)NC2CN(C(C(=O)O)c3cc(Br)c(O)c(Br)c3)C2=O)cc1)C(=O)O
Reaction time: 0.5 h
Yield: 9.2 %

Procedure:
1-(α-Carboxy-3,5-dibromo-4-hydroxybenzyl)-3-[2-[4-{3-carboxy-3-(2,2,2-trifluoroacetamido)propoxy}phenyl]-2-hydroxyiminoacetamido]-2-azetidinone (0.50 g.) was suspended in water (3 ml.), and 1N-sodium hydroxide aqueous solution (3 ml) was added to said suspension, and then the solution was stirred for 30 minutes. The reaction mixture was adjusted to pH 3 with 10% hydrochloric acid under ice-cooling. The precipitated crystals were collected by filtration, and the crystals were dissolved in a small amount of a sodium bicarbonate aqueous solution, and then the solution was treated with activated carbon. After the treatment, the solution was adjusted to pH 4 with 10% hydrochloric acid under ice-cooling, and the precipitate was collected by filtration to give 1-(α-carboxy-3,5-dibromo-4-hydroxybenzyl)-3-[2-{4-(3-amino-3-carboxypropoxy)phenyl}-2-hydroxyiminoacetamido]-2-azetidinone (40 mg.). Furthermore, the same compound (60 mg.) was recovered from the mother liquor. Total yield was 100 mg. Mp 190° to 194° C. (dec.).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[C:11]([CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[CH2:29]([O:28][C:26](=[O:27])[CH2:25][O:15][C:12]1[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:10][C:11]=1[CH2:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH3:30]
Reactant: Oc1ccc(OCc2ccccc2)cc1CCc1ccccc1
Reactant: CCOC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CCOC(=O)COc1ccc(OCc2ccccc2)cc1CCc1ccccc1
Temperature: 55 °C

Procedure:
4-Benzyloxy-2-phenethylphenol (1,77 mmol) was dissolved in anhydrous DMF (4 mL), followed by the addition of ethyl bromoacetate (0.29 mL, 2.65 mmol), and cesium carbonate (0.75 g, 2.30 mmol). The mixture was then heated for 18 h (55° C.). The reaction mixture was then cooled and concentrated in vacuo. The crude residue was partitioned between ethyl acetate (70 mL) and water (40 mL). The organic layer was washed with brine, dried (Na2SO4), and removed in vacuo to give the desired product.
Reaction SMILES: [NH2:1][C@@H:2]([CH2:15][CH2:16][CH3:17])[C:3]([O:12][CH2:13][CH3:14])([O:9][CH2:10][CH3:11])[C:4]([O:6][CH2:7][CH3:8])=[O:5].[C:18](Cl)([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19].O>C1COCC1>[CH2:21]([O:20][C:18]([NH:1][C@@H:2]([CH2:15][CH2:16][CH3:17])[C:3]([O:9][CH2:10][CH3:11])([O:12][CH2:13][CH3:14])[C:4]([O:6][CH2:7][CH3:8])=[O:5])=[O:19])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: CCC[C@H](N)C(OCC)(OCC)C(=O)OCC
Reactant: O=C(Cl)OCc1ccccc1
Solvent: O
Solvent: C1CCOC1
Product: CCC[C@H](NC(=O)OCc1ccccc1)C(OCC)(OCC)C(=O)OCC

Procedure:
To (S)-ethyl 3-amino-2,2-diethoxyhexanoate (prepared analogously to examples 1, 10, 11 and 15) (1000 mg, 4 mmol) in THF (20 mL) at ambient temperature was added K2OC3 (829 mg, 6 mmol), followed by CbzCl (628 μL, 4.4 mmol). After 20 h water was added and the aqueous layer was extracted with Et2O. The combined organic layers were dried and the solvent was removed under reduced pressure. Column chromatography (silicagel, cyclohexane:EtOAc 10:1→5:1) gave 1000 mg of the carbamate.
Reaction SMILES: [CH2:1]([N:3]1[C:12]2[C:7](=[C:8]([F:33])[C:9]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=3)=[C:10]([O:13][CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=3)[CH:11]=2)[C:6](=[O:34])[C:5]([C:35](O)=[O:36])=[CH:4]1)[CH3:2].ClC(OCC(C)C)=O.CC(C[AlH]CC(C)C)C>O1CCCC1.C1(C)C=CC=CC=1>[CH2:1]([N:3]1[C:12]2[C:7](=[C:8]([F:33])[C:9]([O:23][CH2:24][C:25]3[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=3)=[C:10]([O:13][CH2:14][C:15]3[CH:16]=[CH:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=3)[CH:11]=2)[C:6](=[O:34])[C:5]([CH2:35][OH:36])=[CH:4]1)[CH3:2]
Reactant: CCn1cc(C(=O)O)c(=O)c2c(F)c(OCc3ccc(OC)cc3)c(OCc3ccc(OC)cc3)cc21
Agent: CC(C)COC(=O)Cl
Agent: CC(C)C[AlH]CC(C)C
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: CCn1cc(CO)c(=O)c2c(F)c(OCc3ccc(OC)cc3)c(OCc3ccc(OC)cc3)cc21
Temperature: 25 °C
Reaction time: 1 h
Yield: 59.1 %

Procedure:
To a suspension of 1-ethyl-5-fluoro-6,7-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (20 g, 39.4 mmol) in Tetrahydrofuran (THF) (100 mL) was added TEA (6.04 mL, 43.3 mmol) and isobutyl chloroformate (5.69 mL, 43.3 mmol). The resulting mixture was stirred at r.t. for 1 h. Then the mixture was cooled down to −78° C. and a solution of DIBAL-H (52.5 mL, 79 mmol) in toluene (1.5 M) was added. The mixture was stirred at the same temperature for 2 h, LCMS indicated completion of the reaction. The reaction was quenched with sat. NH4Cl (aq.), and was warmed up to r.t., concentrated, diluted with sat. NH4Cl and extracted with dichloromethane. The organic mixture was filtered through Celite to remove gummy precipitate. The combined organic solution was then washed with brine, dried over sodium sulfate, filtered and the filtrate was concentrated in vacuo to afford 1-ethyl-5-fluoro-3-(hydroxymethyl)-6,7-bis((4-methoxybenzyl)oxy)quinolin-4(1H)-one (11.5 g, 23.30 mmol, 59.1% yield) as a yellow solid, which was used in the next oxidation step without further purification. LCMS: (M+H)+: 494.2
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:9](=O)[CH3:10])[CH:5]=[N:6][C:7]=1[Cl:8].[CH:12]1([NH2:15])[CH2:14][CH2:13]1>>[Br:1][C:2]1[CH:3]=[C:4]([CH:9]([NH:15][CH:12]2[CH2:14][CH2:13]2)[CH3:10])[CH:5]=[N:6][C:7]=1[Cl:8]
Reactant: CC(=O)c1cnc(Cl)c(Br)c1
Reactant: NC1CC1
Product: CC(NC1CC1)c1cnc(Cl)c(Br)c1

Procedure:
1-(5-Bromo-6-chloropyridin-3-yl)ethanone and cyclopropylamine were treated in the similar manner to Reference Example 6(6) to give N-[1-(5-bromo-6-chloropyridin-3-yl)ethyl]cyclopropylamine [REx(113-2)] as a pale yellow oil.
Reaction SMILES: [Na].[Cl-].[NH2:3][C:4]([NH2:6])=[NH2+:5].[CH2:7]([N:14]1[C:22](=[O:23])[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]1[CH2:24][C:25](OCC)=[O:26])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>C(O)C>[CH2:7]([N:14]1[C:22](=[O:23])[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]1[CH2:24][C:25]([NH:5][C:4]([NH2:6])=[NH:3])=[O:26])[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: NC(N)=[NH2+]
Reactant: CCOC(=O)CC1c2ccccc2C(=O)N1Cc1ccccc1
Agent: [Cl-]
Agent: [Na]
Solvent: CCO
Product: N=C(N)NC(=O)CC1c2ccccc2C(=O)N1Cc1ccccc1
Temperature: 20 °C
Reaction time: 1 h
Yield: 57.6 %

Procedure:
0.22 g of sodium is added to 20 cm3 of absolute ethanol under an inert atmosphere. After the sodium has totally disappeared, 0.94 g of guanidinium chloride is added. The reaction mixture is stirred under an inert atmosphere at a temperature in the region of 20° C. for 1 hour, followed by addition of a solution of 2 g of ethyl (2-benzyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetate in 5 cm3 of absolute ethanol. The reaction mixture is stirred at a temperature in the region of 20° C. for 18 hours and is then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue is taken up in a mixture of 10 cm3 of water and 30 cm3 of diethyl ether and is then stirred at a temperature in the region of 0° C. for 15 minutes. The precipitate obtained is filtered off, washed with twice 10 cm3 of ice-cold water and then dried in a desiccator under reduced pressure (2 kPa) at a temperature in the region of 20° C. 1.2 g of N-[(2-benzyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetyl]guanidine are thus obtained in the form of a white powder melting at 222-225° C. Infrared spectrum (KBr) 3488; 3410; 3344; 1662; 1621; 1521; 1382 and 704 cm−1.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:9])=[C:6]([CH3:8])[CH:7]=1.C([Li])(C)(C)C.[CH2:15]([C@@H:17]1[O:19][CH2:18]1)[Cl:16]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[Cl:16][CH2:15][C@H:17]([OH:19])[CH2:18][C:2]1[CH:3]=[CH:4][C:5]([Cl:9])=[C:6]([CH3:8])[CH:7]=1
Reactant: ClC[C@H]1CO1
Reactant: Cc1cc(Br)ccc1Cl
Agent: [Li]C(C)(C)C
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: Cc1cc(C[C@@H](O)CCl)ccc1Cl
Reaction time: 0.5 h
Yield: 44.8 %

Procedure:
The solution of 1.0 g (4.9 mmol) 5-bromo-2-chlorotoluene in 10 mL toluene was cooled down to −70° C. and treated dropwise with 3.6 mL (5.4 mmol; 1.5M solution in toluene) tert-butyllithium. After 30 min. 0.42 mL (5.3 mmol) (R)-(−)-epichlorohydrin was added and the temperature was allowed to rise to 0° C. After 1 h the reaction mixture was diluted with ethyl acetate and extracted with 10% aqueous sodium bicarbonate solution followed by brine. The organic layer was dried over magnesium sulfate, filtered and evaporated and the residue was purified by column chromatography on silica gel with n-hexane:ethyl acetate (1:1) as eluant to give the title compound as a colorless oil (44.8%).
Reaction SMILES: [Br:1][C:2]1[C:3]([F:12])=[C:4]2[C:10]([NH2:11])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[CH3:13][O:14][C:15]1[N:20]=[C:19]([C:21](O)=[O:22])[CH:18]=[CH:17][CH:16]=1.O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1.C(N(CC)CC)C.[Li+].[OH-]>C(Cl)Cl.O>[Br:1][C:2]1[C:3]([F:12])=[C:4]2[C:10]([NH:11][C:21](=[O:22])[C:19]3[CH:18]=[CH:17][CH:16]=[C:15]([O:14][CH3:13])[N:20]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1
Reactant: COc1cccc(C(=O)O)n1
Reactant: Nc1c[nH]c2ncc(Br)c(F)c12
Agent: O=C1OCCN1P(=O)(Cl)N1CCOC1=O
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1cccc(C(=O)Nc2c[nH]c3ncc(Br)c(F)c23)n1
Temperature: 25 °C
Reaction time: 1 h
Yield: 72.2 %

Procedure:
A solution of 5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-amine (200 mg, 0.869 mmol, Example 1, Step H) in CH2Cl2 (10 mL) was treated with 6-methoxypicolinic acid (160 mg, 1.04 mmol), bis(2-oxooxazolidin-3-yl)phosphinic chloride (332 mg, 1.30 mmol) and triethylamine (440 mg, 4.35 mmol). The reaction was stirred at room temperature for 1 hour, and then 2M aqueous LiOH (3 mL) was added. The reaction was stirred for 1 hour, and then water was added (10 mL). The solid, which separated, was filtered and washed with CH2Cl2 (10 mL). The filtered cake was dried to yield N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-6-methoxypicolinamide (229 mg, 72% yield). 1H NMR (400 MHz, (CD3)2SO) δ 12.17 (s, 1H), 12.25 (s, 1H), 8.40 (d, 1H), 7.96 (dd, 1H), 7.92 (dd. 1H), 7.74 (dd. 1H), 7.11 (dd, 1H), 4.05 (s, 3H); LCMS (APCI+) m/z 365, 366.9 (M+H)+, Retention time=3.75 minutes (Method 2).
Reaction SMILES: C([O:5][C:6]1[CH:11]=[C:10]([C:12]2[CH:29]=[CH:28][C:15]([CH2:16][NH:17][C:18](=[O:27])[C:19]3[C:24]([Cl:25])=[CH:23][CH:22]=[CH:21][C:20]=3[Cl:26])=[CH:14][CH:13]=2)[CH:9]=[CH:8][N:7]=1)(C)(C)C>C(O)=O>[Cl:26][C:20]1[CH:21]=[CH:22][CH:23]=[C:24]([Cl:25])[C:19]=1[C:18]([NH:17][CH2:16][C:15]1[CH:28]=[CH:29][C:12]([C:10]2[CH:9]=[CH:8][NH:7][C:6](=[O:5])[CH:11]=2)=[CH:13][CH:14]=1)=[O:27]
Reactant: CC(C)(C)Oc1cc(-c2ccc(CNC(=O)c3c(Cl)cccc3Cl)cc2)ccn1
Solvent: O=CO
Product: O=C(NCc1ccc(-c2cc[nH]c(=O)c2)cc1)c1c(Cl)cccc1Cl
Temperature: 40 °C
Reaction time: 3 h
Yield: 75.5 %

Procedure:
N-[4-(2-tert-Butoxy-pyridin-4-yl)-benzyl]-2,6-dichloro-benzamide was dissolved in 30 mL dichloromethone and 12 mL of 98% formic acid. The mixture was stirred at 40° C. for three hours after which the volatile components were evaporated under vacuum. The residue was triturated with ethyl acetate, filtered, washed with ethyl acetate and dried giving 2,6-dichloro-N-[4-(2-oxo-1,2-dihydro-pyridin-4-yl)-benzyl]-benzamide (4.34 g, 75.5% yield over two steps) as white powder. C19H14Cl2N2O2; MS m/z: 373 (MH+) 1H NMR (DMSO-d6): δ 11.56 (s, 1H), δ 9.21 (t, J=5.6 Hz, 1H), δ 7.67 (d, J=8.0 Hz, 2H), δ 7.46 (m, 6H), δ 6.57 (d, J=1.2 Hz, 1H), δ 6.49 (dd, J=6.8 Hz, F=1.6 Hz, 1H), δ 4.50 (d, J=6.0 Hz, 2H.
Reaction SMILES: [O:1]([C:8]1[CH:13]=[CH:12][C:11]([NH:14][CH2:15][C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:22][S:23](Cl)(=[O:25])=[O:24].C(=O)([O-])[O-].[K+].[K+]>ClCCl>[O:1]([C:8]1[CH:13]=[CH:12][C:11]([N:14]([CH2:15][C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)[S:23]([CH3:22])(=[O:25])=[O:24])=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CS(=O)(=O)Cl
Reactant: c1ccc(Oc2ccc(NCc3cccnc3)cc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Product: CS(=O)(=O)N(Cc1cccnc1)c1ccc(Oc2ccccc2)cc1
Temperature: 25 °C

Procedure:
A 5.5 g. portion of 3-(4-phenoxyphenylaminomethyl)pyridine was dissolved in dichloromethane, and reacted with 1.7 ml. of methanesulfonyl chloride in the presence of 3 g. of potassium carbonate. The mixture was stirred at ambient temperature for several days. It was diluted with dichloromethane, extracted with water, dried over magnesium sulfate, and evaporated under vacuum. The residue was triturated in diethyl ether and petroleum ether, filtered and dried to obtain 6.4 g. of the desired product, m.p. 139°-140°.
Reaction SMILES: C([Si]([O:8][CH2:9][CH2:10][C@H:11]1[C@H:15]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[Cl:22])[O:14][C:13]([CH3:24])([CH3:23])[O:12]1)(C)C)(C)(C)C.C([Si](OCC[C@@H]1[C@@H](C2C=CC=CC=2Cl)OC(C)(C)O1)(C)C)(C)(C)C>>[Cl:22][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[C@@H:15]1[O:14][C:13]([CH3:23])([CH3:24])[O:12][C@H:11]1[CH2:10][CH2:9][OH:8]
Reactant: CC1(C)O[C@@H](CCO[Si](C)(C)C(C)(C)C)[C@H](c2ccccc2Cl)O1
Agent: CC1(C)O[C@H](c2ccccc2Cl)[C@@H](CCO[Si](C)(C)C(C)(C)C)O1
Product: CC1(C)O[C@@H](CCO)[C@H](c2ccccc2Cl)O1
Yield: 80 %

Procedure:
The substantially same method as described in Example 352 was conducted, except that tert-butyl(2-((4S,5S)-5-(2-chlorophenyl)-2,2-dimethyl-1,3-dioxolan-4-yl)ethoxy)dimethylsilane (Preparation example 355) was used instead of that tert-butyl(2-((4R,5R)-5-(2-chlorophenyl)-2,2-dimethyl-1,3-dioxolan-4-yl)ethoxy)dimethyl silane (Preparation example 351), to obtain the title compound (0.3 g, 80˜95%).
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH:12]=[O:13])[CH:8]=2)[N:3]=1.[BH4-].[Na+]>C1COCC1>[CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH2:12][OH:13])[CH:8]=2)[N:3]=1
Reactant: Cc1ccc2cc(C=O)ccc2n1
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Cc1ccc2cc(CO)ccc2n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 105.1 %

Procedure:
To a stirred solution of 2-methylquinoline-6-carbaldehyde (1.00 g, 5.8 mmol) in THF (60 mL) in a 100 mL round-bottomed flask equipped with a magnetic stirrer was added NaBH4 (0.221 g, 5.8 mmol) and the mixture was stirred overnight at RT then cooled in an ice bath before quenching by addition of a 1 N aq. HCl solution (10 mL). After stirring for 15 min at RT, the mixture was basified to pH=9 with a 2 N aq. NaOH solution. THF was then removed at 40° C. under vacuum and the solution was extracted with CH2Cl2 (200 mL), washed with brine (20 mL), dried over Na2SO4, filtered and concentrated under vacuum to give (2-methylquinolin-6-yl)methanol SLA 47080A as a yellow oil (1.056 g, quant.).
Reaction SMILES: [CH3:1][O-:2].[Na+].F[C:5]1[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[CH:7][C:6]=1[O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>CO>[CH2:16]([O:15][C:6]1[CH:7]=[C:8]([C:11]([F:14])([F:13])[F:12])[CH:9]=[CH:10][C:5]=1[O:2][CH3:1])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: Fc1ccc(C(F)(F)F)cc1OCc1ccccc1
Reactant: C[O-]
Agent: [Na+]
Solvent: CO
Product: COc1ccc(C(F)(F)F)cc1OCc1ccccc1

Procedure:
A solution of sodium methoxide in methanol (25% wt, 20 ml) and the product from step (i) (1.20 g) was heated at 100° C. for 3 h. The mixture was quenched with water (100 ml) and the solid was filtered and dried, yield 1.28 g.
Reaction SMILES: [CH2:1](Br)[CH:2]=[CH2:3].C1C=CC=CC=1.[CH:11]12[CH2:21][CH:16]3[CH2:17][CH:18]([CH2:20][CH:13]([NH:14][CH2:15]3)[CH2:12]1)[CH2:19]2.C(OC(=O)C)(=O)C>C(O)(=O)C>[CH2:1]([N:14]1[CH2:15][CH:16]2[CH2:21][CH:11]3[CH2:19][CH:18]([CH2:20][CH:13]1[CH2:12]3)[CH2:17]2)[CH:2]=[CH2:3]
Reactant: C=CCBr
Reactant: C1NC2CC3CC1CC(C3)C2
Solvent: CC(=O)OC(C)=O
Solvent: c1ccccc1
Solvent: CC(=O)O
Product: C=CCN1CC2CC3CC(C2)CC1C3
Temperature: 0 °C

Procedure:
To a well stirred solution of 1.2 gm. (0.01 mole) of allyl bromide in 50 ml. of benzene, a solution of 1.5 gm. (0.01 mole) of 4-azatricyclo[4.3.1.13,8 ]undecane in 50 ml. of benzene is added dropwise. The mixture is refluxed 1 hr., cooled, and 1 gm. of acetic anhydride is added. The mixture is refluxed an additional 2 hrs., cooled, poured into ice water and acidified with acetic acid. The layers are separated and the aqueous layer is extracted with ether. The acidic aqueous layer is made basic with NaOH, and extracted with chloroform. The chloroform extract is washed with water, dried over magnesium sulfate, filtered and the solvent evaporated to give 4-allyl- 4-azatricyclo[4.3.1.13,8 ]undecane.
Reaction SMILES: [N:1]([CH2:4][CH2:5][O:6][CH2:7][CH2:8][O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][NH:15][S:16]([C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([CH:25]2[C:34]3[C:29](=[C:30]([Cl:36])[CH:31]=[C:32]([Cl:35])[CH:33]=3)[CH2:28][N:27]([CH2:37][CH3:38])[CH2:26]2)[CH:20]=1)(=[O:18])=[O:17])=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1COCC1>O>[NH2:1][CH2:4][CH2:5][O:6][CH2:7][CH2:8][O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][NH:15][S:16]([C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([CH:25]2[C:34]3[C:29](=[C:30]([Cl:36])[CH:31]=[C:32]([Cl:35])[CH:33]=3)[CH2:28][N:27]([CH2:37][CH3:38])[CH2:26]2)[CH:20]=1)(=[O:18])=[O:17]
Reactant: CCN1Cc2c(Cl)cc(Cl)cc2C(c2cccc(S(=O)(=O)NCCOCCOCCOCCN=[N+]=[N-])c2)C1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: O
Product: CCN1Cc2c(Cl)cc(Cl)cc2C(c2cccc(S(=O)(=O)NCCOCCOCCOCCN)c2)C1

Procedure:
Into a 100-mL round-bottom flask, was placed N-(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethyl)-3-(6,8-dichloro-2-ethyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide (400 mg, 0.68 mmol, 1.00 equiv), triphenylphosphine (400 mg, 2.20 equiv), THF (10 mL) and water (1 mL) and the reaction was stirred overnight at room temperature. The resulting mixture was concentrated under vacuum and applied onto a preparative thin-layer chromatography (TLC) plate, eluting with DCM:methanol (5:1). This resulted in 350 mg (73%) of N-(2-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)ethyl)-3-(6,8-dichloro-2-ethyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide as yellow oil.