Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CO[C:3]([C:5]1[N:6]=[CH:7][C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[C:10]([O:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH:9]=2)=[O:4].[NH2:23][CH2:24][CH2:25][CH2:26][C:27]([OH:29])=[O:28].CO.Cl>C[O-].[Na+].O>[OH:15][C:14]1[C:13]2[C:8](=[CH:9][C:10]([O:16][C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)=[CH:11][CH:12]=2)[CH:7]=[N:6][C:5]=1[C:3]([NH:23][CH2:24][CH2:25][CH2:26][C:27]([OH:29])=[O:28])=[O:4]
Reactant: NCCCC(=O)O
Reactant: COC(=O)c1ncc2cc(Oc3ccccc3)ccc2c1O
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Solvent: O
Product: O=C(O)CCCNC(=O)c1ncc2cc(Oc3ccccc3)ccc2c1O
Yield: 94.1 %

Procedure:
A mixture of 4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid methyl ester (100 mg, 0.34 mmol) and 4-aminobutyric acid (525 mg, 5.1 mmol) in 0.5 N NaOMe in MeOH solution (6.8 mL, 3.4 mmol) was heated to reflux overnight. Reaction mixture was diluted with water (100 mL) and acidified by 1 N HCl solution to pH=3-4. Precipitate was collected and rinsed with water. It was dried in vacuo to provide the title compound (117 mg, 0.32 mmol) in 94% yield. LC-MS ESI−: 365.05 (M−1)−.
Reaction SMILES: [CH:1]([S:4][C:5]1[C:10]([CH2:11]O)=[CH:9][CH:8]=[CH:7][N:6]=1)([CH3:3])[CH3:2].O=S(Cl)[Cl:15]>CC#N>[Cl:15][CH2:11][C:10]1[C:5]([S:4][CH:1]([CH3:3])[CH3:2])=[N:6][CH:7]=[CH:8][CH:9]=1
Reactant: O=S(Cl)Cl
Reactant: CC(C)Sc1ncccc1CO
Solvent: CC#N
Product: CC(C)Sc1ncccc1CCl
Temperature: 25 °C
Reaction time: 2 h
Yield: 92.1 %

Procedure:
(2-Isopropylsulfanyl-pyridin-3-yl)-methanol (3.0 g, 16.37 mmol) obtained in Step B was dissolved in CH3CN (20 mL), and SOCl2(2.39 mL, 32.74 mmol) was added thereto dropwise at 0° C. The mixture was stirred at room temperature for 2 hours. After the termination of the reaction, the reactant was concentrated under reduced pressure. After the addition of EtOAc, the organic layer was washed with water, dried with MgSO4, filtrated and concentrated under reduced pressure to obtain the title compound (3.04 g, 92%).
Reaction SMILES: Cl.[NH2:2][OH:3].[Br:4][CH2:5][C:6](=O)[C:7]([CH3:10])([CH3:9])[CH3:8].C(O)C>O>[Br:4][CH2:5][C:6](=[N:2][OH:3])[C:7]([CH3:10])([CH3:9])[CH3:8]
Reactant: NO
Reactant: CC(C)(C)C(=O)CBr
Agent: Cl
Solvent: CCO
Solvent: O
Product: CC(C)(C)C(CBr)=NO
Temperature: 25 °C
Reaction time: 16 h
Yield: 56.4 %

Procedure:
A solution of 69.5 g (1.0 m) of hydroxylamine hydrochloride in 100 ml of water is chilled in an ice bath as 90 g (0.5 m) of 1-bromo-3,3-dimethyl-2-butanone is added. After addition of 100 ml of 95% ethanol, the mixture is stirred for 16 hours and allowed to warm to room temperature. The resulting white slurry is filtered, and the solid is washed with water and dried to give 55 g of the desired compound, m. 111°-112° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]([CH2:13]O)=[CH:9][C:4]=1[C:5]([O:7][CH3:8])=[O:6].C(N(CC)C(C)C)(C)C.CS([Cl:28])(=O)=O>ClCCl>[CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]([CH2:13][Cl:28])=[CH:9][C:4]=1[C:5]([O:7][CH3:8])=[O:6]
Reactant: CS(=O)(=O)Cl
Reactant: COC(=O)c1cc(CO)ccc1OC
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: COC(=O)c1cc(CCl)ccc1OC
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Combine methyl 2-methoxy-5-hydroxymethylbenzoate (1.34 g, 6.8 mmol) and N,N-diisopropylethylamine (1.4 mL) in dichloromethane (25 mL). Cool in a ice-bath. Add dropwise, methanesulfonyl chloride (0.56 mL). After 30 minutes, warm to ambient temperature. After 2 hours, dilute with dichloromethane and extract with 1 M hydrochloric acid solution and 5% sodium bicarbonate solution. Dry the organic layer over Na2SO4, filter, and concentrate in vacuo to give methyl 2-methoxy-5-chloromethylbenzoate: Rf=0.64 (silica gel, 1/1 ethyl acetate/hexane).
Reaction SMILES: [Cl-].COC1N=C(OC)N=C([N+:12]2([CH3:18])[CH2:17][CH2:16]OC[CH2:13]2)N=1.[C:19]([OH:30])(=O)[C:20]1[CH:28]=[CH:27][C:23]([C:24]([OH:26])=O)=[CH:22][CH:21]=1.[CH3:31][N:32]([CH3:45])[C:33]1[C:42]2[C:37](=[CH:38][CH:39]=[C:40]([NH2:43])[CH:41]=2)[N:36]=[C:35]([CH3:44])[CH:34]=1>CN(C)C=O.C(#N)C.C(OC(C)C)(C)C>[CH3:18][N:12]([CH3:13])[C:17]1[C:16]2[C:37](=[CH:38][CH:39]=[C:40]([NH:43][C:24](=[O:26])[C:23]3[CH:22]=[CH:21][C:20]([C:19]([NH:43][C:40]4[CH:41]=[C:42]5[C:37](=[CH:38][CH:39]=4)[N:36]=[C:35]([CH3:44])[CH:34]=[C:33]5[N:32]([CH3:45])[CH3:31])=[O:30])=[CH:28][CH:27]=3)[CH:41]=2)[N:36]=[C:35]([CH3:44])[CH:34]=1
Reactant: COc1nc(OC)nc([N+]2(C)CCOCC2)n1
Reactant: O=C(O)c1ccc(C(=O)O)cc1
Reactant: Cc1cc(N(C)C)c2cc(N)ccc2n1
Agent: [Cl-]
Solvent: CC#N
Solvent: CC(C)OC(C)C
Solvent: CN(C)C=O
Product: Cc1cc(N(C)C)c2cc(NC(=O)c3ccc(C(=O)Nc4ccc5nc(C)cc(N(C)C)c5c4)cc3)ccc2n1
Temperature: 20 °C
Reaction time: 12 h
Yield: 99.7 %

Procedure:
4-(4,6-Dimethoxy-1,3,5-triazine-2-yl)-4-methylmorpholinium chloride (177 mg) is added to a solution of 48 mg (0.29 mmol) of terephthalic acid and 128 mg (0.64 mmol) of 4-dimethylamino-6-aminoquinaldine in 6 mL of dimethylformamide, at a temperature in the region of 20° C. The mixture obtained is stirred at a temperature in the region of 20° C. for about 12 hours. The reaction mixture is successively taken up in 2 mL of acetonitrile and 2 mL of diisopropyl ether, and the precipitate thus obtained is slowly filtered on a 6 mL BOND-ELUT cartridge filled with sintered material. The insoluble matter obtained is washed with diisopropyl ether and then dried under argon. 154 mg of N,N′-bis(4-dimethylamino-2-methylquinolin-6-yl)-terephthalamide are thus obtained in the form of a beige powder of whose characteristics are the following:
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][C:5]2[N:8]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH:19]4[CH2:21][CH2:20]4)=[CH:13][CH:12]=3)[O:10][C:4]=2[CH:3]=1.[CH3:22][C@H:23]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[C:24]#[CH:25].C(N(CC)CC)C.O>CN(C=O)C.[Cu]I>[CH:19]1([CH2:18][O:17][C:14]2[CH:15]=[CH:16][C:11]([C:9]3[O:10][C:4]4[CH:3]=[C:2]([C:25]#[C:24][C@@H:23]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH3:22])[N:7]=[CH:6][C:5]=4[N:8]=3)=[CH:12][CH:13]=2)[CH2:21][CH2:20]1
Reactant: Clc1cc2oc(-c3ccc(OCC4CC4)cc3)nc2cn1
Reactant: C#C[C@H](C)NC(=O)OC(C)(C)C
Agent: [Cu]I
Solvent: O
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: C[C@@H](C#Cc1cc2oc(-c3ccc(OCC4CC4)cc3)nc2cn1)NC(=O)OC(C)(C)C
Temperature: 100 °C
Reaction time: 2 h
Yield: 13.1 %

Procedure:
To a solution of 6-chloro-2-(4-(cyclopropylmethoxy)phenyl) [1,3]oxazolo[4,5-c]pyridine (700 mg), tert-butyl (2S)-but-3-yn-2-ylcarbamate (1.13 g) and triethylamine (0.649 g) in DMF (10 mL) were added bistriphenylphosphinedichloropalladium(II) (163 mg) and copper(I) iodide (88.7 mg), and the mixture was stirred at 100° C. for 2 hr under an argon atmosphere. The reaction mixture was allowed to cool to room temperature, water was added thereto, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and subjected to silica gel column chromatography (NH, ethyl acetate). The solvent was evaporated under reduced pressure, and the obtained solid was washed with ethyl acetate to give the title compound (132 mg).
Reaction SMILES: Cl.[NH2:2][OH:3].[OH-].[Na+].[CH:6]([C:8]1[N:17]=[C:16]([NH:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]3[O:26][CH2:27][O:28][C:22]=3[CH:21]=2)[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([Cl:29])[CH:14]=2)[N:9]=1)=O>C(O)C>[OH:3][N:2]=[CH:6][C:8]1[N:17]=[C:16]([NH:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]3[O:26][CH2:27][O:28][C:22]=3[CH:21]=2)[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([Cl:29])[CH:14]=2)[N:9]=1
Reactant: O=Cc1nc(NCc2ccc3c(c2)OCO3)c2cc(Cl)ccc2n1
Reactant: NO
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: ON=Cc1nc(NCc2ccc3c(c2)OCO3)c2cc(Cl)ccc2n1
Temperature: 60 °C
Reaction time: 0.5 h
Yield: 95.7 %

Procedure:
0.60 g of hydroxylamine hydrochloride and 3.0 ml of a 1N aqueous solution of sodium hydroxide were added to a solution of 1.00 g (2.93 mmol) of 2-formyl4-(3,4-methylenedioxybenzyl)amino-6-chloroquinazoline in 30 ml of ethanol. The obtained mixture was stirred at 60° C. for 30 minutes and cooled by allowing to stand. The crystal thus precipitated was recovered by filtration, washed with ethanol and n-hexane and air-dried to give 1.00 g of the title compound as a white crystal.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([OH:22])=[O:21])=[CH:16][N:15]=2)[C@H:10]([CH3:23])[CH2:9]1)=O)(C)(C)C.S(=O)(=O)(O)O.[OH-].[Na+].[CH3:31]O>>[CH3:31][O:22][C:20](=[O:21])[C:17]1[CH:18]=[CH:19][C:14]([N:11]2[CH2:12][CH2:13][NH:8][CH2:9][C@H:10]2[CH3:23])=[N:15][CH:16]=1
Reactant: C[C@@H]1CN(C(=O)OC(C)(C)C)CCN1c1ccc(C(=O)O)cn1
Reactant: CO
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Product: COC(=O)c1ccc(N2CCNC[C@H]2C)nc1
Temperature: 64 °C
Reaction time: 8 h

Procedure:
To a mixture of (R)-4-(5-carboxy-pyridin-2-yl)-3-methyl-piperazine-1-carboxylic acid tert-butyl ester (50 g, 0.156 mol) and methanol (500 mL) was slowly added concentrated sulfuric acid (37 mL). The reaction mixture was warmed to 64° C., stirred at 64° C. overnight, cooled to RT and then ice water (800 mL) was added followed by 50% aqueous sodium hydroxide (60 mL). The reaction mixture was extracted with ethyl acetate (3×800 mL). Combined organic layers were dried over sodium sulfate and evaporated to give the title intermediate as an oil. HPLC Method A: Retention time 3.50 and 3.72 min.
Reaction SMILES: [OH:1][CH2:2][C:3](CO)(COCC(CO)(CO)CO)CO.C(OCC(CO)(COCC(CO)(CO)CO)CO)(=O)C.[C:38]([O:41][CH2:42][C:43]([CH2:59][OH:60])([CH2:49][O:50][CH2:51][C:52]([CH2:57][OH:58])([CH2:55][OH:56])[CH2:53][OH:54])[CH2:44][O:45][C:46](=[O:48])[CH3:47])(=[O:40])[CH3:39]>>[C:38]([O:41][CH2:42][C:43]([CH2:59][OH:60])([CH2:49][O:50][CH2:51][C:52]([CH2:55][OH:56])([CH2:57][OH:58])[CH2:53][O:54][C:2](=[O:1])[CH3:3])[CH2:44][O:45][C:46](=[O:48])[CH3:47])(=[O:40])[CH3:39]
Reactant: CC(=O)OCC(CO)(COCC(CO)(CO)CO)COC(C)=O
Reactant: OCC(CO)(CO)COCC(CO)(CO)CO
Agent: CC(=O)OCC(CO)(CO)COCC(CO)(CO)CO
Product: CC(=O)OCC(CO)(CO)COCC(CO)(COC(C)=O)COC(C)=O

Procedure:
In each of Runs 1 to 4 shown in Table 1 below, a mixture having a melting point of 70° to 92° C. and composed of dipentaerythritol, dipentaerythritol monoacetate, dipentaerythritol diacetate and dipentaerythritol triacetate was produced by melting the materials together.
Reaction SMILES: [CH:1]1([CH:7]([NH:24][C:25]2[CH:33]=[CH:32][C:28]([C:29](O)=[O:30])=[CH:27][CH:26]=2)[C:8]2[C:9]([CH2:22][CH3:23])=[N:10][N:11]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH2:20][CH3:21])[CH:14]=3)[CH:12]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.[NH2:56][CH2:57][CH:58]([CH3:63])[C:59]([O:61][CH3:62])=[O:60]>CN(C)C=O.O>[CH:1]1([CH:7]([NH:24][C:25]2[CH:33]=[CH:32][C:28]([C:29]([NH:56][CH2:57][CH:58]([CH3:63])[C:59]([O:61][CH3:62])=[O:60])=[O:30])=[CH:27][CH:26]=2)[C:8]2[C:9]([CH2:22][CH3:23])=[N:10][N:11]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH2:20][CH3:21])[CH:14]=3)[CH:12]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: CCOc1cccc(-n2cc(C(Nc3ccc(C(=O)O)cc3)C3CCCCC3)c(CC)n2)c1
Reactant: COC(=O)C(C)CN
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: O
Product: CCOc1cccc(-n2cc(C(Nc3ccc(C(=O)NCC(C)C(=O)OC)cc3)C3CCCCC3)c(CC)n2)c1
Reaction time: 8 h
Yield: 13.6 %

Procedure:
4-({Cyclohexyl[1-(3-ethoxyphenyl)-3-ethyl-1H-pyrazol-4-yl]methyl}amino)benzoic acid (0.18 g) synthesized in the above-mentioned (2) was dissolved in N,N-dimethylformamide (3 mL), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.11 g), 1-hydroxybenzotriazole.monohydrate (0.09 g) and methyl 3-amino-2-methylpropanoate (0.07 g) were added at room temperature, and the mixture was stirred overnight. Water was added to the reaction mixture, and the mixture was extracted with diethyl ether. The extract was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:1, volume ratio) to give methyl 3-({[4-({cyclohexyl[1-(3-ethoxyphenyl)-3-ethyl-1H-pyrazol-4-yl]methyl}amino)phenyl]carbonyl}amino)-2-methylpropanoate (0.03 g) as a yellow oil. This was dissolved in ethanol (2.0 mL), 1N aqueous sodium hydroxide solution (0.5 mL) was added at room temperature, and the mixture was stirred at room temperature for 0.5 hr. Ethanol was evaporated under reduced pressure, and 1N hydrochloric acid (0.5 mL) was added to the residue. The precipitate was washed with water to give the title object compound (0.02 g, 9%) as a colorless solid.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[OH:8].C(N(CC)CC)C.[C:16]1([CH3:26])[CH:21]=[CH:20][C:19]([S:22](Cl)(=[O:24])=[O:23])=[CH:18][CH:17]=1>CC(C)=O>[OH:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[NH:1][S:22]([C:19]1[CH:20]=[CH:21][C:16]([CH3:26])=[CH:17][CH:18]=1)(=[O:24])=[O:23]
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: Nc1ccccc1O
Solvent: CCN(CC)CC
Solvent: CC(C)=O
Product: Cc1ccc(S(=O)(=O)Nc2ccccc2O)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 49.4 %

Procedure:
A flask with a stirrer was charged with 10.9 g of 2-aminophenol, 10.1 g of triethylamine and 100 ml of acetone, and a solution of 19.1 g of p-toluenesulfonyl chloride in 50 ml of acetone was dropwise added with cooling with ice over 30 minutes. After completion of the addition, the reaction mixture was stirred at room temperature for 2 hours and then poured into 500 ml of ice water. A precipitated crystal was recovered by filtration and washed with water. The obtained crystal was recrystallized from ethyl acetate/n-hexane mixed solvents, to give 13.0 g of an end product. Melting point 140.0° C.
Reaction SMILES: [CH2:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH:12]=[N:11][C:10]=2Br)[CH2:5][CH2:4]1)[CH3:2].C([Li])(C)(C)C.CN(C)[CH:27]=[O:28].[Cl-].[NH4+]>O1CCCC1>[CH2:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH:12]=[N:11][C:10]=2[CH2:27][OH:28])[CH2:5][CH2:4]1)[CH3:2]
Reactant: CN(C)C=O
Reactant: CCC1CCN(c2c(Br)ncc3ccccc23)CC1
Agent: [Cl-]
Agent: [Li]C(C)(C)C
Agent: [NH4+]
Solvent: C1CCOC1
Product: CCC1CCN(c2c(CO)ncc3ccccc23)CC1
Temperature: 25 °C
Yield: 52.7 %

Procedure:
A solution of 4-(4-ethylpiperidin-1-yl)-3-bromoisoquinoline (1.03 g) in tetrahydrofuran (20 ml) was cooled to −78° C., followed by the dropwise addition of 1.7M tert-butyllithium (3 ml). Fifteen minutes later, N,N-dimethylformamide (0.5 ml) was added thereto and the temperature of the reaction solution was raised to room temperature. To the reaction solution was added an aqueous solution of ammonium chloride, and the mixture was extracted with ethyl acetate, followed by washing with water and brine, drying and evaporating. The resulting residue was dissolved in methanol (15 ml), and reacted with sodium borohydride (0.4 g). The solvent was removed, the resulting residue was extracted with ethyl acetate extraction, followed by washing with water and brine, drying and evaporating. The resulting residue was purified by silica gel column chromatography (methylene chloride/methanol system), to give 4-(4-ethylpiperidin-1-yl)-3-hydroxymethylisoquinoline (0.46 g, 52.7%) as a pale yellow oil.
Reaction SMILES: Cl[C:2]1[C:3]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:7][CH:6]=2.CCN(C(C)C)C(C)C.[CH2:32]([NH:36][CH3:37])[CH:33]([CH3:35])[CH3:34]>CS(C)=O.O>[F:22][C:19]1[CH:20]=[CH:21][C:16]([C:3]2[C:2]([N:36]([CH2:32][CH:33]([CH3:35])[CH3:34])[CH3:37])=[N:11][C:10]3[C:5](=[CH:6][CH:7]=[C:8]([C:12]([O:14][CH3:15])=[O:13])[CH:9]=3)[N:4]=2)=[CH:17][CH:18]=1
Reactant: COC(=O)c1ccc2nc(-c3ccc(F)cc3)c(Cl)nc2c1
Reactant: CNCC(C)C
Solvent: O
Solvent: CS(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)c1ccc2nc(-c3ccc(F)cc3)c(N(C)CC(C)C)nc2c1
Temperature: 70 °C
Reaction time: 8 h
Yield: 68 %

Procedure:
To a solution of methyl 3-chloro-2-(4-fluorophenyl)quinoxaline-6-carboxylate (100 mg, 0.32 mmol) in DMSO (3 mL) was added DIEA (81.5 mg, 0.63 mmol) and isobutyl(methyl)amine (41 mg, 0.47 mmol), and the reaction was stirred overnight at 70° C. in an oil bath. The reaction mixture was cooled to room temperature, diluted with water (50 mL), and extracted with ethyl acetate (3×20 mL). The organic layers were combined, dried over magnesium sulfate, and concentrated in vacuo to give the residue, which was purified via silica gel column chromatography (1% ethyl acetate in petroleum ether) to afford methyl 2-(4-fluorophenyl)-3-(isobutyl(methyl)amino)quinoxaline-6-carboxylate as a light yellow solid (80 mg, 69%).
Reaction SMILES: [CH2:1]([CH2:3][NH2:4])[OH:2].C(N(CC)CC)C.[N+:12]([C:15]1[CH:20]=[CH:19][C:18]([S:21](Cl)(=[O:23])=[O:22])=[CH:17][CH:16]=1)([O-:14])=[O:13]>ClCCl.CCOC(C)=O>[OH:2][CH2:1][CH2:3][NH:4][S:21]([C:18]1[CH:17]=[CH:16][C:15]([N+:12]([O-:14])=[O:13])=[CH:20][CH:19]=1)(=[O:22])=[O:23]
Reactant: NCCO
Reactant: O=[N+]([O-])c1ccc(S(=O)(=O)Cl)cc1
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=[N+]([O-])c1ccc(S(=O)(=O)NCCO)cc1
Yield: 55.8 %

Procedure:
To a solution of ethanolamine (0.68 g, 11 mmol) and triethylamine (1.10 g, 10.9 mmol) in dichloromethane (20 mL) was added 4-nitrobenzenesulfonyl chloride (2.20 g, 9.9 mmol) portionwise with stirring. The resulting clear yellow solution was stirred at room temperature for 15 min. The clear yellow solution was diluted with equal volume of EtOAc and washed with water and then with 5% HCl. The organic phase was evaporated to dryness to give 1.36 g of light yellow crystalline solid which was dried and used without further purification. δH (200 MHz, DMSO-d6) 2.90 [2H, m, NHCH2CH2OH], 3.36 [2H, m, NHCH2CH2OH], 4.75 [1H, t, OH], 8.00 [1H, m, NH], 8.02 and 8.38 [2×2H, q (A2B2), 2×Nosyl CH].
Reaction SMILES: C([O:8][C:9]1[CH:10]=[CH:11][C:12]2[N:16]=[N:15][N:14]([CH:17]([CH3:22])[C:18]([O:20][CH3:21])=[O:19])[C:13]=2[CH:23]=1)C1C=CC=CC=1.[H][H]>C(COC)OC.CO.[Pd]>[OH:8][C:9]1[CH:10]=[CH:11][C:12]2[N:16]=[N:15][N:14]([CH:17]([CH3:22])[C:18]([O:20][CH3:21])=[O:19])[C:13]=2[CH:23]=1
Reactant: [H][H]
Reactant: COC(=O)C(C)n1nnc2ccc(OCc3ccccc3)cc21
Agent: [Pd]
Solvent: CO
Solvent: COCCOC
Product: COC(=O)C(C)n1nnc2ccc(O)cc21

Procedure:
A solution of methyl 6-(benzyloxy)-α-methyl-1H-benzotriazole-1-acetate (31 g, 0.1 mole) in dimethoxyethane and methanol is shaken with 10% palladium on carbon catalyst (8 g, 50% water wet) under 24 -33 psig of hydrogen in a Parr apparatus until approximately 0.1 mole of H2 is absorbed (21/2 hours). The reaction mixture is filtered and the filtrate is concentrated in vacuo to give the title compound as an off-white solid, 21.7 g, mp 132.5°-134.5° C., identified by NMR and elemental analyses.
Reaction SMILES: [C:1]1([C:7]2[N:8]=[CH:9][N:10]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:11]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Li])CCC.CCCCCC.[Br:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43]Br>O1CCCC1.O>[Br:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][C:9]1[N:10]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:11]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[N:8]=1
Reactant: C[Si](C)(C)CCOCn1cnc(-c2ccccc2)c1-c1ccccc1
Reactant: BrCCCCCCBr
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Solvent: O
Product: C[Si](C)(C)CCOCn1c(CCCCCCBr)nc(-c2ccccc2)c1-c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 385.5 %

Procedure:
Part A. To a solution of 4,5-diphenyl-1-[(trimethylsilyl)ethoxymethyl]-1H-imidazole (2.5 g, 0. 00734 mol) (B. Lipshutz, B. Huff, W. Hazen, Tetrahedron Letters, 29, 3411-14, 1988), in dry tetrahydrofuran (50 mL) cooled to -78° under a nitrogen atmosphere, n-butyl lithium in hexane (2.5M, 0.00734 mol) was added slowly. The reaction mixture was stirred for 1 hour and 1,6-dibromohexane (2.68 g, 0.0011 mol) was added rapidly, stirred for 1/2 hour and was allowed to warm to ambient temperature and stirred for 2 additional hours. The reaction mixture was poured into water and extracted with ethyl acetate (2×50 mL). The combined organic layer was washed with water, brine, dried over magnesium sulfate and concentrated to give a viscous oil. The product was purified by flash chromatography on silica gel (250 mL) eluting with hexane:ethyl acetate (70:30 v:v) to give 6-bromo-1-(4,5-diphenyl-1-[(trimethylsilyl)ethoxymethyl]imidazol-2-yl)hexane as an oil (2.18 g, 0.00424 mol). 1H NMR (CDCl3) δ 7.53-7.16(m,10H), 5.10(s,2H), 3.48(t,2H), 3.34(t,2H), 2.90(t,2H), 1.99-1.5 (m,8H), 0.875(t,2H), 0.008(s,9H).
Reaction SMILES: [N:1]1([CH2:6][C:7]2[CH:8]=[CH:9][C:10]3[N:14]=[N:13][N:12]([OH:15])[C:11]=3[CH:16]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.[H-].[Na+].[H][H].Cl[CH2:22][CH2:23][O:24][CH3:25].COCCOCCN(CCOCCOC)CCOCCOC>O.CS(C)=O.CN(C)C=O>[N:1]1([CH2:6][C:7]2[CH:8]=[CH:9][C:10]3[N:14]=[N:13][N:12]([O:15][CH2:22][CH2:23][O:24][CH3:25])[C:11]=3[CH:16]=2)[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: COCCCl
Reactant: [H][H]
Reactant: On1nnc2ccc(Cn3ccnc3)cc21
Agent: COCCOCCN(CCOCCOC)CCOCCOC
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Solvent: CS(C)=O
Product: COCCOn1nnc2ccc(Cn3ccnc3)cc21
Yield: 46.7 %

Procedure:
To a stirred and heated (50° C.) mixture of 2.81 parts of 6-(1H-imidazol-1-ylmethyl)-1H-benzotriazol-1-ol and 22.5 parts of N,N-dimethylformamide were added 0.69 parts of a sodium hydride dispersion. The reaction mixture was stirred until hydrogen evolution had ceased. 1.28 Parts of 1-chloro-2-methoxyethane were added at room temperature and stirring was continued for a while. 22 Parts of dimethyl sulfoxide and 0.04 parts of 2-(2-methoxyethoxy)-N,N-bis[2-(2-methoxyethoxy)ethyl]ethanamine were added. The reaction mixture was stirred overnight at 50° C. and then poured into water. The product was extracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from a mixture of ethyl acetate and 2,2'-oxybispropane (1:3 by volume). The product was filtered off, washed with a mixture of ethyl acetate and 2,2'-oxybispropane (1:3 by volume) and 2,2'-oxybispropane and dried in vacuo at 50° C., yielding 1.66 parts (46.7%) of 6-(1H-imidazol-1-ylmethyl)-1-(2-methoxyethoxy)-1H-benzotriazole; mp. 77.0° C. (compound 220).