Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]1([C:6]2[CH:11]=[CH:10][C:9]([CH:12]=[C:13]([N+]([O-])=O)[CH3:14])=[CH:8][CH:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.Cl.C[OH:20]>O.[Fe]>[N:1]1([C:6]2[CH:11]=[CH:10][C:9]([CH2:12][C:13](=[O:20])[CH3:14])=[CH:8][CH:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: CO
Reactant: CC(=Cc1ccc(-n2ccnc2)cc1)[N+](=O)[O-]
Agent: [Fe]
Agent: Cl
Solvent: O
Product: CC(=O)Cc1ccc(-n2ccnc2)cc1

Procedure:
A mixture of 1-[4-(1H-imidazol-1-yl)phenyl]-2-nitropropene prepared above, iron powder (94.7 grams), and hydrated iron (III) chloride (1.2 grams) in 50 ml of methanol and 170 ml of water is heated to reflux and treated dropwise with 85 ml of 12 N hydrochloric acid over four hours. After heating under reflux for one additional hour, the reaction mixture is cooled, and filtered. The filtrate is made basic with 40% ammonium hydroxide solution and the entire mixture is extracted thoroughly with ethyl acetate. The ethyl acetate is treated with charcoal, dried (magnesium sulfate) and concentrated on the rotary evaporator to give a dark yellow oil. This material is chromatographed on a Waters Prep 500A, using silica gel and eluting with 2% methanol in chloroform. The main fraction contains 1-[-4-(1H-imidazol-1-yl)-phenyl]-2-propanone.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][C:12]([C:14]([OH:16])=O)=[CH:13][C:8]=2[N:7]=[C:6]1[NH:17][C:18]1[S:19][C:20]2[CH:26]=[C:25]([O:27][C:28]([F:31])([F:30])[F:29])[CH:24]=[CH:23][C:21]=2[N:22]=1.[CH3:32][O:33][CH2:34][CH2:35][NH2:36].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:32][O:33][CH2:34][CH2:35][NH:36][C:14]([C:12]1[CH:11]=[CH:10][C:9]2[N:5]([CH2:4][CH2:3][O:2][CH3:1])[C:6]([NH:17][C:18]3[S:19][C:20]4[CH:26]=[C:25]([O:27][C:28]([F:31])([F:30])[F:29])[CH:24]=[CH:23][C:21]=4[N:22]=3)=[N:7][C:8]=2[CH:13]=1)=[O:16]
Reactant: COCCN
Reactant: COCCn1c(Nc2nc3ccc(OC(F)(F)F)cc3s2)nc2cc(C(=O)O)ccc21
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COCCNC(=O)c1ccc2c(c1)nc(Nc1nc3ccc(OC(F)(F)F)cc3s1)n2CCOC
Yield: 37.3 %

Procedure:
1-(2-Methoxy-ethyl)-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-methoxy-ethyl)-amide (42.0 mg) was prepared by following General Procedure F starting from 1-(2-methoxy-ethyl)-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (100.0 mg), 2-methoxy-ethylamine (26.0 mg), HBTU (130.0 mg) and DIEA (0.1 mL) in DMF (1.0 mL). LCMS: m/z 511; and 1H NMR (DMSO-d6, 400 MHz): δ 8.47 (1H, br. s), 8.08 (1H, br. s), 7.93 (1H, br. s), 7.74-7.72 (1H, br. m), 7.51 (1H, m), 7.37-7.35 (1H, m), 4.35 (2H, br. s), 3.73-3.72 (2H, br. t), 3.53-3.43 (4H, m), 3.29 (3H, s), 3.24 (3H, s), 2 —NH proton signals were not observed.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:12]([S:13]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([OH:22])[CH:17]=2)(=[O:15])=[O:14])[CH:11]=[C:10]([CH2:23][N:24]([CH3:32])[C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH:9]=1.O[CH2:34][C:35]1([C:38]([NH:40][CH3:41])=[O:39])[CH2:37][CH2:36]1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:12]([S:13]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH2:34][C:35]3([C:38](=[O:39])[NH:40][CH3:41])[CH2:37][CH2:36]3)[CH:17]=2)(=[O:14])=[O:15])[CH:11]=[C:10]([CH2:23][N:24]([CH3:32])[C:25](=[O:31])[O:26][C:27]([CH3:28])([CH3:29])[CH3:30])[CH:9]=1
Reactant: CNC(=O)C1(CO)CC1
Reactant: CN(Cc1cc(-c2ccccc2F)n(S(=O)(=O)c2cccc(O)c2)c1)C(=O)OC(C)(C)C
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CNC(=O)C1(COc2cccc(S(=O)(=O)n3cc(CN(C)C(=O)OC(C)(C)C)cc3-c3ccccc3F)c2)CC1
Reaction time: 16 h

Procedure:
tert-Butyl ((5-(2-fluorophenyl)-1-((3-hydroxyphenyl)sulfonyl)-1H-pyrrol-3-yl)methyl)(methyl)carbamate 1h (100 mg, 0.22 mmol), 1-(hydroxymethyl)-N-methyl cyclopropanecarboxamide 5c (47 mg, 0.33 mmol), diisopropyl azodicarboxylate (150 mg, 0.65 mmol) and triphenylphosphine (171 mg, 0.65 mmol) were added to 3 mL of dichloromethane, and then the reaction solution was stirred for 16 h. The reaction solution was concentrated under reduced pressure, and the resulting residue was purified by thin layer chromatography with elution system B to obtain the title compound tert-butyl ((5-(2-fluorophenyl)-1-((3-((1-(methylcarbamoyl)cyclopropyl)methoxy)phenyl)sulfonyl)-1H-pyrrol-3-yl)methyl)(methyl)carbamate 5d (100 mg, a yellow oil) in 81% yield.
Reaction SMILES: COC(=O)CC[C:6]1(C)[CH2:15][CH2:14][CH2:13][CH2:12][C:7]21OCCO2.CO[C:20](=O)[CH2:21][CH2:22][C:23]1([CH2:33][CH2:34][CH3:35])[CH2:32][CH2:31][CH2:30][CH2:29][C:24]21[O:28]CCO2.O=[C:38]1[CH2:43][CH2:42][CH2:41][CH2:40][C:39]1(CCC)CC(O)=O>>[C:38]1([C:20]([C:6]2[CH:7]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[CH:21][CH2:22][C:23]2([CH2:33][CH2:34][CH3:35])[CH2:32][CH2:31][CH2:30][CH2:29][C:24]2=[O:28])[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1
Reactant: CCCC1(CCC(=O)OC)CCCCC12OCCO2
Reactant: COC(=O)CCC1(C)CCCCC12OCCO2
Reactant: CCCC1(CC(=O)O)CCCCC1=O
Product: CCCC1(CC=C(c2ccccc2)c2ccccc2)CCCCC1=O

Procedure:
Again in the same manner but replacing 6-methyl-1,4-dioxaspiro[4.5]decane-6-propionic acid methyl ester with an equivalent amount of 6-propyl-1,4-dioxaspiro[4.5]decane6-propionic acid methyl ester, described in Example 7, 2-oxo-1-propylcyclohexaneacetic acid, νmaxCHCl3 1775, 1710 cm-1, is obtained via the respective intermediates, α,α-diphenyl-6-propyl-1,6-dioxaspiro[4.5]decane-6-propanol, νmaxCHCl3 3620, 3480, 1175, 1130, 1110, 1062 cm-1, and 2-(3,3-diphenylallyl)-2-propylcyclohexanone, nmr (CDCl3) δ 0.85 (m, 3H), 6.0 (t, 1H), 7.3 (m, 10H).
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][C:11]2([CH2:22][CH2:21][C:20]3[C:15](=[CH:16][CH:17]=[C:18]([Cl:23])[CH:19]=3)[O:14]2)[CH2:10][CH2:9]1)C1C=CC=CC=1.ClC(OC(Cl)C)=O>C1(C)C=CC=CC=1>[ClH:23].[Cl:23][C:18]1[CH:19]=[C:20]2[C:15](=[CH:16][CH:17]=1)[O:14][C:11]1([CH2:10][CH2:9][NH:8][CH2:13][CH2:12]1)[CH2:22][CH2:21]2
Reactant: Clc1ccc2c(c1)CCC1(CCN(Cc3ccccc3)CC1)O2
Agent: CC(Cl)OC(=O)Cl
Solvent: Cc1ccccc1
Product: Cl
Product: Clc1ccc2c(c1)CCC1(CCNCC1)O2
Yield: 84.6 %

Procedure:
A solution of 1′-benzyl-6-chloro-3,4-dihydrospiro[chromene-2,4′-piperidine] (1.63 g, 5.0 mmol) and 1-chloroethyl chloroformate (1.07 g, 7.5 mmol) in toluene (5 ml) was heated with reflux overnight. The solvent was removed i. vacuo, the oily residue dissolved in methanol (10 ml) and heated with reflux overnight. The solvent was removed in vacuo, and the residue treated with diethyl ether (50 ml). The white precipitate was collected by filtration, washed with diethyl ether and dried to afford the subtitle compound as white powder (0.58 g, 49%).
Reaction SMILES: [Cl:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([C:12]2[CH2:13][CH2:14][O:15][C:16]3[CH:22]=[CH:21][C:20]([C:23]4[CH:28]=[CH:27][C:26]([O:29][CH2:30][CH3:31])=[CH:25][CH:24]=4)=[CH:19][C:17]=3[CH:18]=2)=[O:11])=[CH:5][CH:4]=1.[CH3:32][N:33]([CH3:40])[CH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1.C(OCC)(=O)C>CN(C=O)C>[Cl-:1].[CH2:30]([O:29][C:26]1[CH:27]=[CH:28][C:23]([C:20]2[CH:21]=[CH:22][C:16]3[O:15][CH2:14][CH2:13][C:12]([C:10]([NH:9][C:6]4[CH:5]=[CH:4][C:3]([CH2:2][N+:33]([CH3:40])([CH3:32])[CH:34]5[CH2:39][CH2:38][O:37][CH2:36][CH2:35]5)=[CH:8][CH:7]=4)=[O:11])=[CH:18][C:17]=3[CH:19]=2)=[CH:24][CH:25]=1)[CH3:31]
Reactant: CCOc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(CCl)cc2)CCO3)cc1
Reactant: CN(C)C1CCOCC1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCOc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(C[N+](C)(C)C4CCOCC4)cc2)CCO3)cc1
Product: [Cl-]
Reaction time: 14 h
Yield: 41.8 %

Procedure:
To a solution of N-(4-chloromethylphenyl)-7-(4-ethoxyphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (2.38 g) in DMF (20 ml) was added N,N-dimethyl-N-tetrahydropyran-4-ylamine (1.42 g) at room temperature, and the mixture was stirred for 14 hours. To the reaction mixture was added ethyl acetate (100 ml) to precipitate crystals, which were collected by filtration. The crystal was washed with ethyl acetate to give crude product as pale yellow crystals, which were recrystallized from ethanol to give as N-(4-(((7-(4-ethoxyphenyl)-2,3-dihydro-1-benzoxepin-4-yl)carbonyl)amino)benzyl)-N,N-dimethyl-N-(4-tetrahydropyranyl)ammonium chloride (Compound 250) (1.29 g) colorless crystals.
Reaction SMILES: C(=O)([O-])[O-:2].[K+].[K+].[C:7]([C:15]1[CH:24]=[CH:23][C:18]2[N:19]=[CH:20][S:21](=O)[C:17]=2[CH:16]=1)(=[O:14])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.Cl[CH2:26][CH2:27][O:28][C:29]1[CH:34]=[CH:33][C:32]([CH2:35][CH:36]([O:41][CH2:42][CH3:43])[C:37]([O:39][CH3:40])=[O:38])=[CH:31][CH:30]=1>CN(C)C=O>[C:7]([C:15]1[CH:24]=[CH:23][C:18]2[N:19]([CH2:26][CH2:27][O:28][C:29]3[CH:34]=[CH:33][C:32]([CH2:35][CH:36]([O:41][CH2:42][CH3:43])[C:37]([O:39][CH3:40])=[O:38])=[CH:31][CH:30]=3)[C:20](=[O:2])[S:21][C:17]=2[CH:16]=1)(=[O:14])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: O=C([O-])[O-]
Reactant: O=C(c1ccccc1)c1ccc2c(c1)S(=O)C=N2
Reactant: CCOC(Cc1ccc(OCCCl)cc1)C(=O)OC
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(Cc1ccc(OCCn2c(=O)sc3cc(C(=O)c4ccccc4)ccc32)cc1)C(=O)OC
Temperature: 100 °C

Procedure:
To 20 ml of dimethylformamide add potassium carbonate (0.01044 mol) and then 6-benzoylbenzothiazolinone (0.00453 mol). Heat at 100° C. for 1 hour. Add the compound obtained in Step B (0.00348 mol) and heat at 150° C. for 16 hours. Evaporate off the dimethylformamide. Take up the residue in 50 ml of water and then extract with 50 ml of dichloromethane twice. The organic phase is dried over MgSO4 and then evaporated. The residue is recrystallised from methanol and yields the title compound in the form of a solid.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][O:4][C:5]1[CH:6]=[CH:7][C:8]2[O:12][CH:11]=[CH:10][C:9]=2[CH:13]=1.[Li]CCCC.[CH2:19]([Sn:23](Cl)([CH2:28][CH2:29][CH2:30][CH3:31])[CH2:24][CH2:25][CH2:26][CH3:27])[CH2:20][CH2:21][CH3:22]>>[CH2:28]([Sn:23]([CH2:19][CH2:20][CH2:21][CH3:22])([CH2:24][CH2:25][CH2:26][CH3:27])[C:11]1[O:12][C:8]2[CH:7]=[CH:6][C:5]([O:4][CH2:3][CH2:2][Cl:1])=[CH:13][C:9]=2[CH:10]=1)[CH2:29][CH2:30][CH3:31]
Reactant: CCCC[Sn](Cl)(CCCC)CCCC
Reactant: ClCCOc1ccc2occc2c1
Agent: [Li]CCCC
Product: CCCC[Sn](CCCC)(CCCC)c1cc2cc(OCCCl)ccc2o1

Procedure:
Treatment of 5-(2-chloroethoxy)-1-benzofuran with n-BuLi for 16 h followed by the addition of tributyltin chloride at −50° C. gave tributyl (5-(2-chloroethoxy)benzofuran-2-yl)stannane upon warming to room temperature.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[OH-].[Na+].Cl[C:12]1[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][C:13]=1[C:14]#[N:15].O>CS(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:12]2[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][C:13]=2[C:14]#[N:15])=[CH:4][CH:3]=1
Reactant: N#Cc1cc([N+](=O)[O-])ccc1Cl
Reactant: Oc1ccc(Cl)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CS(C)=O
Solvent: O
Product: N#Cc1cc([N+](=O)[O-])ccc1Oc1ccc(Cl)cc1
Temperature: 60 °C
Yield: 92.3 %

Procedure:
To a solution of 3.95 g (0.0307 moles) of 4-chlorophenol dissolved in 150 ml of DMSO was added 1.23 g (0.0307 moles) of NaOH. The slurry was heated at 60° C. for 15 minutes and 5.04 g (0.0276 moles) of 2-chloro-5-nitrobenzonitrile was added and the mixture was heated at 75° C. for 3 hrs. The reaction mixture was cooled and poured into water. The product was collected by filtration, washed well with water and dried, to produce 7.0 g of the product (92% yield). Recrystallization from ethanol afforded purified 2-(4-chlorophenoxy)-5-nitrobenzonitrile, mp 163°-164° C.
Reaction SMILES: [CH3:1][C:2]1[N:3]=[C:4]([NH:10][C:11]([C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)=[O:12])[S:5][C:6]=1[C:7]([OH:9])=O.CN1CCOCC1.ClC1N=C(OC)N=C(OC)N=1.[CH2:37]([NH2:44])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>O1CCCC1>[CH2:37]([NH:44][C:7]([C:6]1[S:5][C:4]([NH:10][C:11](=[O:12])[C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)=[N:3][C:2]=1[CH3:1])=[O:9])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1
Reactant: NCc1ccccc1
Reactant: Cc1nc(NC(=O)c2ccncc2)sc1C(=O)O
Agent: COc1nc(Cl)nc(OC)n1
Solvent: CN1CCOCC1
Solvent: C1CCOC1
Product: Cc1nc(NC(=O)c2ccncc2)sc1C(=O)NCc1ccccc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 45 %

Procedure:
To a mixture of 4-methyl-2-[(pyridine-4-carbonyl)amino]thiazole-5-carboxylic acid (0.40 g, 1.50 mmol) and 4-methylmorpholine (0.25 mL, 2.20 mmol) in tetrahydrofuran (50 mL) was added 2-chloro-4,6-dimethoxy-1,3,5-triazine (0.32 g, 1.80 mmol). The resulting mixture was stirred at ambient temperature for 4 h, and then benzylamine (0.2 mL, 1.80 mmol) was added. The reaction mixture was stirred at room temperature for 47 h and then concentrated. Purification of the residue by column chromatography afforded the title compound in 45% yield (0.24 g); m.p. 171-172° C.; 1H NMR (DMSO-d6, 300 MHz) δ 13.15 (s, 1H), 8.78-8.63 (m, 3H), 7.94 (dd, J=1.5, 4.5 Hz, 2H), 7.32-7.17 (m, 5H), 4.38 (d, J=6.0 Hz, 2H), 2.51 (s, 3H); 13C NMR (DMSO-d6, 75 MHz) δ 162.0, 150.9, 140.0, 139.5, 128.7, 127.7, 127.2, 122.2, 114.3, 43.1, 17.1; MS (ES+) m/z 353.3 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:37])=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][N:15]([CH2:31][C@@H:32]([OH:36])[C:33]([OH:35])=[O:34])[NH:16][C:17]([C:19]3[NH:23][C:22](=[O:24])[N:21]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[N:20]=3)=[O:18])=[CH:10][CH:9]=2)[CH:7]=1.[C:38]([O:43][CH2:44]Cl)(=[O:42])[CH2:39][CH2:40][CH3:41].[Na+].[I-].CC1C=CC=C(C)N=1>CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:37])=[C:6]([C:8]2[CH:9]=[CH:10][C:11]([CH2:14][N:15]([CH2:31][C@@H:32]([OH:36])[C:33]([O:35][CH2:44][O:43][C:38](=[O:42])[CH2:39][CH2:40][CH3:41])=[O:34])[NH:16][C:17]([C:19]3[NH:23][C:22](=[O:24])[N:21]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[N:20]=3)=[O:18])=[CH:12][CH:13]=2)[CH:7]=1
Reactant: O=C(NN(Cc1ccc(-c2cc(Cl)ccc2F)cc1)C[C@@H](O)C(=O)O)c1nn(-c2ccccc2)c(=O)[nH]1
Reactant: CCCC(=O)OCCl
Agent: [I-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Solvent: Cc1cccc(C)n1
Product: CCCC(=O)OCOC(=O)[C@H](O)CN(Cc1ccc(-c2cc(Cl)ccc2F)cc1)NC(=O)c1nn(-c2ccccc2)c(=O)[nH]1
Temperature: 25 °C
Reaction time: 8 h
Yield: 10 %

Procedure:
To a solution of (R)-3-[N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(5-oxo-1-phenyl-4,5-dihydro-1H-[1,2,4]triazole-3-carbonyl)hydrazino]-2-hydroxypropionic acid (200 mg, 335 μmol) in dry DMF (6 mL) was added chloromethyl butyrate (68 mg, 503 mmol), NaI (101 mg, 670 mmol), and 2,6-dimethylpyridine (143 mg, 1.3 mmol) in portions at room temperature. The resulting mixture was stirred at room temperature for 8 hours. Water (12 mL) was added and the mixture was extracted with EtOAc (3×20 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography (PE:EtOAc=3:1) to yield the title compound as a white solid (21 mg). LC-MS: 625.9 [M+H]+. 1H NMR (DMSO-d6, 400 MHz) δ 0.84 (t, J=7.4 Hz, 3H), 1.45-1.56 (m, 2H), 2.29 (t, J=7.3 Hz, 2H), 3.31-3.17 (m, 2H), 4.18-4.35 (m, 2H), 4.35 (t, J=5.3 Hz, 1H), 5.68-5.79 (m, 2H), 7.28 (t, J=7.4 Hz, 1H), 7.34-7.40 (m, 1H), 7.43-7.55 (m, 7H), 7.58 (dd, J=6.8, 2.6 Hz, 1H), 7.90 (d, J=7.6 Hz, 2H), 9.98 (s, 1H), 12.76 (s, 1H).
Reaction SMILES: C1(CC[CH:9]([OH:11])C)C=CC=CC=1.[CH2:12]1[CH:17]2C3[NH+:20]([O-:21])[CH:15]([CH2:16]2)[CH2:14][CH:13]1C3.C(O)(=[O:24])C.CC(OC(/N=N/C(OC(C)C)=O)=O)C.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl>[N+:20]([C:15]1[CH:14]=[CH:13][C:12]([CH2:9][OH:11])=[CH:17][CH:16]=1)([O-:21])=[O:24]
Reactant: CC(=O)O
Reactant: [O-][NH+]1C2CC3CC(C2)C1C3
Reactant: CC(O)CCc1ccccc1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Product: O=[N+]([O-])c1ccc(CO)cc1
Reaction time: 8 h

Procedure:
A solution of 4-phenylbutan-2-ol (97.7 mg, 0.651 mmol), Nor-AZADO (0.90 mg, 6.51 μmol, 1 mol %) and acetic acid (37 μl, 0.651 mmol) in dichloromethane (0.65 ml) was added with DIAD (128 μl, 0.651 mmol, 1 equivalent), and the mixture was stirred for 8 hours under reflux by heating. The reaction mixture was added with saturated aqueous sodium carbonate (2 ml), and the mixture was extracted with dichloromethane. The organic layer was dried over sodium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the objective compound (95.1 mg; yield, 99%). The spectrum data were found to be the same as those obtained in Example 5, (b).
Reaction SMILES: [H-].[Na+].[OH:3][C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=1.[CH3:14][O:15][CH2:16]Cl>CN(C=O)C.O>[CH3:14][O:15][CH2:16][O:3][C:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=1
Reactant: COCCl
Reactant: Oc1ccc2ccccc2c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: COCOc1ccc2ccccc2c1
Temperature: 25 °C
Reaction time: 4 h
Yield: 96.1 %

Procedure:
To a suspension of 5.0 g of NaH (208.33 mmol) in 150 mL of DMF under argon flow were added 20.0 g of solid 2-hydroxynaphthalene (138.7 mmol) at a temperature of 0° C., by small portions. The suspension was kept under stirring for 4 h at room temperature, 17.8 g of methoxymethyl chloride (221.2 mmol) were added slowly, and the reaction mixture was stirred for 10 additional hours. The reaction was carefully diluted with 1 L of water and the organic part was extracted with 3 times 50 mL of CH2Cl2. The combined organic extracts were washed twice with 500 mL of water, brine and dried over MgSO4. The solution was evaporated, dried in vacuum at a temperature of 80° C. to give 25.1 g of colorless oily product (133.3 mmol) that was used without further purification.
Reaction SMILES: F[C:2]1[C:7](F)=[CH:6][C:5]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][C:10]=2[N:15]([CH2:32][CH2:33][S:34]([CH3:37])(=[O:36])=[O:35])C(=O)C2C=C(C(F)(F)F)N=C(C(F)(F)F)C=2)=[C:4]([O:38][CH3:39])C=1.COC1C(B(O)O)=CC=C[N:43]=1>C(Cl)Cl.CO>[CH3:37][S:34]([CH2:33][CH2:32][NH:15][C:10]1[CH:11]=[N:12][CH:13]=[CH:14][C:9]=1[C:5]1[C:4]([O:38][CH3:39])=[N:43][CH:2]=[CH:7][CH:6]=1)(=[O:36])=[O:35]
Reactant: COc1ncccc1B(O)O
Reactant: COc1cc(F)c(F)cc1-c1ccncc1N(CCS(C)(=O)=O)C(=O)c1cc(C(F)(F)F)nc(C(F)(F)F)c1
Solvent: CO
Solvent: ClCCl
Product: COc1ncccc1-c1ccncc1NCCS(C)(=O)=O

Procedure:
The title compound was prepared in analogy to example 72, from (4-iodo-pyridin-3-yl)-(2-methanesulfonyl-ethyl)-amine (example 158, intermediate b) and 2-methoxypyridine-3-boronic acid (CAS RN 163105-90-6) and using a gradient of CH2Cl2:methanol (100:0 to 85:15) for the chromatographic purification. Brown solid (89%). MS (ESI): m/z=308.11 [M+H]+.
Reaction SMILES: [CH:1]1[C:2]([C:10]([O:12][CH3:13])=[O:11])=[CH:3][N:4]2[C:9]=1[CH2:8][CH2:7][CH2:6][CH2:5]2.I[CH2:15][C:16]#[N:17].OO>O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Fe+2].CS(C)=O>[C:16]([CH2:15][C:3]1[N:4]2[C:9]([CH2:8][CH2:7][CH2:6][CH2:5]2)=[CH:1][C:2]=1[C:10]([O:12][CH3:13])=[O:11])#[N:17]
Reactant: N#CCI
Reactant: COC(=O)c1cc2n(c1)CCCC2
Agent: [Fe+2]
Agent: O=S(=O)([O-])[O-]
Agent: OO
Solvent: O
Solvent: CS(C)=O
Product: COC(=O)c1cc2n(c1CC#N)CCCC2
Yield: 78.4 %

Procedure:
A 500-mL three-neck round-bottomed flask equipped with an addition funnel, thermometer and charged with methyl 5,6,7,8-tetrahydroindolizine-2-carboxylate 101d (6.70 g, 37.4 mmol), iodoacetonitrile (12.5 g, 74.9 mmol), iron (II) sulfate heptahydrate (5.20 g, 18.7 mmol) and dimethyl sulfoxide (250 mL). Hydrogen peroxide (35%, 18.2 g, 187 mmol) was added dropwise to the mixture in 1 h through a syringe pump at room temperature using a water bath. Iron (II) sulfate heptahydrate (2 to 3 equivalent) was added to the reaction mixture in portions to keep the temperature between 25° C. to 35° C., until the color of the reaction mixture is deep red. If TLCs show the reaction not completed, then more hydrogen peroxide (2-3 equivalent) and more iron (II) sulfate heptahydrate (1-2 equivalent) were added in the same manner until the reaction is completed. After that time, the reaction mixture was partitioned between aqueous saturated sodium bicarbonate solution (200 mL) and ethyl acetate (400 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with saturated Sodium thiosulfate solution (50 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography to afford a 78% yield (6.40 g) of 101e as a yellow oil: 1H NMR (500 MHz, CDCl3) δ 6.23 (s, 1H), 4.23 (s, 2H), 3.94 (t, 2H, J=6.5 Hz), 3.81 (s, 3H), 2.74 (t, 2H, J=6.5 Hz), 2.00 (m, 2H), 1.83 (m, 2H); (APCI+) m/z 219.3 (M+H)
Reaction SMILES: C([O-])=O.[NH4+].[CH3:5][O:6][CH2:7][CH2:8][O:9][C:10]1[C:15]([N:16]2[N:20]=[CH:19][CH:18]=[N:17]2)=[CH:14][C:13]([N+:21]([O-])=O)=[CH:12][N:11]=1>[Pd].CO.C(OCC)(=O)C>[CH3:5][O:6][CH2:7][CH2:8][O:9][C:10]1[N:11]=[CH:12][C:13]([NH2:21])=[CH:14][C:15]=1[N:16]1[N:20]=[CH:19][CH:18]=[N:17]1
Reactant: COCCOc1ncc([N+](=O)[O-])cc1-n1nccn1
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CCOC(C)=O
Solvent: CO
Product: COCCOc1ncc(N)cc1-n1nccn1
Yield: 94.6 %

Procedure:
10% Pd/C (200 mg) and ammonium formate (200 mg) were added to an MeOH/ethyl acetate (5 ml/5 ml) solution containing 2-(2-methoxyethoxy)-5-nitro-3-(2H-1,2,3-triazol-2-yl)pyridine (286 mg) obtained in the 1st step, followed by reflux for 1 hour. Insoluble matter was removed using Celite and the solvent was distilled away under reduced pressure. The obtained residue was purified by silica gel chromatography (n-hexane:ethyl acetate=1:0 to 1:5) and a white solid of 6-(2-methoxyethoxy)-5-(2H-1,2,3-triazol-2-yl)pyridin-3-amine (240 mg) was thus obtained.
Reaction SMILES: C([O:4][C@@H:5]1[C@@H:10]([O:11]C(=O)C)[C@@H:9]([O:15]C(=O)C)[C@@H:8]([CH2:19][O:20]C(=O)C)[O:7][C@H:6]1[O:24][C:25]1[C:29]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH2:38][CH2:39][C:40](O)=[O:41])=[CH:33][CH:32]=2)=[C:28]([CH:43]([CH3:45])[CH3:44])[NH:27][N:26]=1)(=O)C.[NH2:46][C:47]([CH3:58])([CH3:57])[C:48]([N:50]1[CH2:55][CH2:54][N:53]([CH3:56])[CH2:52][CH2:51]1)=[O:49].NC(C)(C)C(N)=O>>[C@@H:6]1([O:24][C:25]2[C:29]([CH2:30][C:31]3[CH:36]=[CH:35][C:34]([O:37][CH2:38][CH2:39][C:40](=[O:41])[NH:46][C:47]([C:48]([N:50]4[CH2:55][CH2:54][N:53]([CH3:56])[CH2:52][CH2:51]4)=[O:49])([CH3:58])[CH3:57])=[CH:33][CH:32]=3)=[C:28]([CH:43]([CH3:45])[CH3:44])[NH:27][N:26]=2)[O:7][C@H:8]([CH2:19][OH:20])[C@H:9]([OH:15])[C@H:10]([OH:11])[C@H:5]1[OH:4]
Reactant: CN1CCN(C(=O)C(C)(C)N)CC1
Reactant: CC(=O)OC[C@H]1O[C@@H](Oc2n[nH]c(C(C)C)c2Cc2ccc(OCCC(=O)O)cc2)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@H]1OC(C)=O
Agent: CC(C)(N)C(N)=O
Product: CC(C)c1[nH]nc(O[C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2O)c1Cc1ccc(OCCC(=O)NC(C)(C)C(=O)N2CCN(C)CC2)cc1

Procedure:
The title compound was prepared in a similar manner to that described in Example 78 using 3-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyloxy)-4-{[4-(2-carboxyethoxy)phenyl]methyl}-5-isopropyl-1H-pyrazole and 1-(2-amino-2-methylpropionyl)-4-methylpiperazine instead of 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-4-{[4-(2-carboxyethoxy)-2-methylphenyl]methyl}-5-isopropyl-1H-pyrazole and 2-amino-2-methylpropionamide, respectively.
Reaction SMILES: [O:1]=[C:2]1[O:8][C@H:7]([C@H:9]([CH2:11][OH:12])[OH:10])[C:5]([OH:6])=[C:3]1[OH:4].[O:13]1[CH:15]([CH2:16][CH2:17][CH2:18][CH3:19])[CH2:14]1>CN(C=O)C>[OH:13][CH:15]([CH2:16][CH2:17][CH2:18][CH3:19])[CH2:14][O:6][C:5]1[C@@H:7]([C@H:9]([CH2:11][OH:12])[OH:10])[O:8][C:2](=[O:1])[C:3]=1[OH:4]
Reactant: CCCCC1CO1
Reactant: O=C1O[C@H]([C@@H](O)CO)C(O)=C1O
Solvent: CN(C)C=O
Product: CCCCC(O)COC1=C(O)C(=O)O[C@@H]1[C@@H](O)CO
Temperature: 80 °C
Reaction time: 24 h
Yield: 24.6 %

Procedure:
Under an argon atmosphere, 30 ml of DMF was added to L-ascorbic acid (5.00 g), and further, 1,2-epoxyhexane (3.45 g) was added thereto. The mixture was heated up to 80° C. and stirred for 24 hours, then, extracted with ethyl acetate. The extracted liquid was dried over anhydrous sodium sulfate, then, concentrated under reduced pressure. Thereafter, 7.56 g of the resultant residue was subjected to silica gel column chromatography. Elution was performed with chloroform/methanol/water(volume ratio:20/3/0.3), and concentration was performed under reduced pressure to obtain 3-O-(2-hydroxyhexyl) ascorbic acid (1.93 g).