Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl-].[CH3:2][O:3][CH2:4][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[CH:24](/[CH:29]1[CH2:34][CH2:33][C:32](=O)[CH2:31][CH2:30]1)=[CH:25]\[CH2:26][CH2:27][CH3:28].O>COC(C)(C)C.O1CCCC1>[CH3:2][O:3][CH:4]=[C:32]1[CH2:33][CH2:34][CH:29](/[CH:24]=[CH:25]/[CH2:26][CH2:27][CH3:28])[CH2:30][CH2:31]1
Reactant: COC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CCC/C=C/C1CCC(=O)CC1
Agent: [Cl-]
Solvent: O
Solvent: COC(C)(C)C
Solvent: C1CCOC1
Product: CCC/C=C/C1CCC(=COC)CC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
7 g of methoxymethyl-triphenylphosphonium chloride were suspended in 35 ml of t-butyl methyl ether and the suspension was treated at -20° C. with 2.43 g of potassium t-butylate. The mixture was stirred for a further 1 hour at room temperature, then treated dropwise at -20° C. with a solution of 2 g of 4-(1E-pentenyl)cyclohexanone in 18 ml of tetrahydrofuran and the mixture was stirred for a further 1 hour at room temperature. The reaction mixture was subsequently treated with water and extracted three times with 50 ml of diethyl ether each time. The extracts were washed with water and the wash-water was back-extracted with diethyl ether. The organic phases were dried over magnesium sulphate and freed from solvent. The residue was dissolved in ethyl acetate and the solution was diluted with petroleum ether, freed from precipitated triphenylphosphine oxide by filtration and the filtrate was concentrated. This procedure for the separation of triphenylphosphine oxide was repeated twice and the crude product of 1-(methoxymethylene)-4-(1E-pentenyl)cyclohexane obtained was processed without additional purification.
Reaction SMILES: Br[C:2]1[C:3](=[O:14])[C:4]([CH3:13])([CH3:12])[O:5][C:6]=1[C:7]1[N:8]=[CH:9][S:10][CH:11]=1.CC1(C)C(C)(C)OB([C:23]2[CH:40]=[CH:39][C:26]([O:27][CH2:28][C:29]3[CH:38]=[CH:37][C:36]4[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=4)[N:30]=3)=[CH:25][CH:24]=2)O1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:12][C:4]1([CH3:13])[C:3](=[O:14])[C:2]([C:23]2[CH:24]=[CH:25][C:26]([O:27][CH2:28][C:29]3[CH:38]=[CH:37][C:36]4[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=4)[N:30]=3)=[CH:39][CH:40]=2)=[C:6]([C:7]2[N:8]=[CH:9][S:10][CH:11]=2)[O:5]1
Reactant: CC1(C)OC(c2cscn2)=C(Br)C1=O
Reactant: CC1(C)OB(c2ccc(OCc3ccc4ccccc4n3)cc2)OC1(C)C
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: O
Solvent: Cc1ccccc1
Product: CC1(C)OC(c2cscn2)=C(c2ccc(OCc3ccc4ccccc4n3)cc2)C1=O
Yield: 18.9 %

Procedure:
A mixture of 4-bromo-2,2-dimethyl-5-(thiazol-4-yl)furan-3(2H)-one (0.1 g, 0.37 mmol), 2-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)methyl)quinoline (0.164 g, 0.454 mmol), and Cs2CO3 (0.673 g, 2.06 mmol) in toluene (1 mL) and water (1 mL) was degassed and Pd(dppf)Cl2 (0.067 g, 0.082 mmol) was added under an inert atmosphere, and degassed once more. Then the reaction was refluxed for 2 h and was filtered through a pad of Celite®, the filtrate was diluted with EtOAc (10 mL), washed with water (5 mL), brine (5 mL), dried over Na2SO4, filtered and concentrated in vacuo to obtain the crude product. The crude material was purified via silica gel column chromatography to afford 2,2-dimethyl-4-(4-(quinolin-2-ylmethoxy)phenyl)-5-(thiazol-4-yl)furan-3(2H)-one (30 mg, 18%) as a solid. 1H NMR (500 MHz, d6-DMSO): δ 9.17 (s, 1H), 8.43 (d, J=8.5 Hz, 1H), 8.30 (s, 1H), 8.02-7.98 (m, 2H), 7.80 (t, J=8.2 Hz, 1H), 7.70 (d, J=8.2 Hz, 1H), 7.62 (t, J=8.5 Hz, 1H), 7.24 (d, J=7.5 Hz, 2H), 7.08 (d, J=7.4 Hz, 2H), 5.38 (s, 2H), 1.42 (s, 6H). MS: [M+H]: m/z=429.1. HPLC: 97.9% (RT-2.36 min), Column: Acquity BEH-C-18, 50×2.1 mm, 1.7 um. Mobile Phase: 0.025% TFA in Water (A), ACN (B), Flow rate: 0.5 ml/min (Gradient).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([Cl:12])[N:10]=2)[N:5]=[CH:4][C:3]=1[C:13]([O:15][CH2:16][CH3:17])=[O:14].[NH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]([CH3:29])([CH3:28])[C:26]#[N:27])=[CH:21][CH:20]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>C(O)(C)(C)C>[Cl:12][C:9]1[N:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[CH:4][C:3]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[C:2]2[NH:18][C:19]1[CH:20]=[CH:21][C:22]([C:25]([C:26]#[N:27])([CH3:29])[CH3:28])=[CH:23][CH:24]=1
Reactant: CC(C)(C#N)c1ccc(N)cc1
Reactant: CCOC(=O)c1cnc2ccc(Cl)nc2c1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CC(C)(C)O
Product: CCOC(=O)c1cnc2ccc(Cl)nc2c1Nc1ccc(C(C)(C)C#N)cc1
Yield: 86.9 %

Procedure:
Ethyl 4,6-dichloro-1,5-naphthyridine-3-carboxylate (6.4 g, 23.6 mmol) and 2-(4-aminophenyl)-2-methylpropionitrile (5.6 g, 35 mmol) were dissolved in tert-butanol (200 mL), to the system added potassium carbonate (16.4 g, 119 mmol), and the reaction mixture was stirred under reflux for 2 h. After confirming a disappearance of the raw materials by a thin layer chromatography plate (ethyl acetate:petroleum ether=1:3), the reaction mixture was suction filtered, the filtrate was concentrated under reduced pressure, and the resulting residue was washed with diethyl ether to give 8.1 g of a pale yellow solid.
Reaction SMILES: [CH3:1][C:2](C)([O-])C.[K+].[CH3:7][Si:8]([CH3:44])([C:38]([CH3:43])([CH3:42])[CH:39]([CH3:41])[CH3:40])[O:9][C@H:10]1[CH2:27][C@H:26]([O:28][Si:29]([CH2:34][CH3:35])([CH2:32][CH3:33])[CH2:30][CH3:31])[C@@:25]2([CH3:36])[C:12](=[CH:13][CH:14]=[C:15]3[C@@H:24]2[CH2:23][CH2:22][C@@:20]2([CH3:21])[C@H:16]3[CH2:17][CH2:18][C:19]2=O)[CH2:11]1.C(O)(=O)C>[Br-].C([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)C.C1(C)C=CC=CC=1>[CH3:44][Si:8]([CH3:7])([O:9][C@H:10]1[CH2:27][C@H:26]([O:28][Si:29]([CH2:30][CH3:31])([CH2:32][CH3:33])[CH2:34][CH3:35])[C@@:25]2([CH3:36])[C:12](=[CH:13][CH:14]=[C:15]3[C@@H:24]2[CH2:23][CH2:22][C@@:20]2([CH3:21])[C@H:16]3[CH2:17][CH2:18]/[C:19]/2=[CH:1]/[CH3:2])[CH2:11]1)[C:38]([CH3:43])([CH3:42])[CH:39]([CH3:40])[CH3:41]
Reactant: CC[Si](CC)(CC)O[C@H]1C[C@H](O[Si](C)(C)C(C)(C)C(C)C)CC2=CC=C3[C@H](CC[C@]4(C)C(=O)CC[C@@H]34)[C@]21C
Reactant: CC(C)(C)[O-]
Agent: CC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Agent: [K+]
Solvent: CC(=O)O
Solvent: Cc1ccccc1
Product: C/C=C1/CC[C@H]2C3=CC=C4C[C@@H](O[Si](C)(C)C(C)(C)C(C)C)C[C@H](O[Si](CC)(CC)CC)[C@]4(C)[C@H]3CC[C@]12C
Temperature: 25 °C
Reaction time: 2 h
Yield: 92.2 %

Procedure:
A 2-L three-necked flask equipped with a mechanical stirrer and an Ar-inlet tube was charged with 90.0 g (242 mmol) of ethyl triphenylphosphonium bromide and 480 mL of toluene. To the suspension, 27.2g (242 mmol) of potassium t-butoxide was added. After stirring at room temperature for 2 hr, the orange-red mixture was cooled with an ice-water bath. Then, 96.8 g (173 mmol) of (1α,3β)-3-[[dimethyl(1,1,2-trimethylpropyl)silyl]oxy]-1-[(triethylsilyl)oxy]androsta-5,7-dien-17-one was added with the aid of 30 mL of toluene. The mixture was stirred at room temperature overnight, and the reaction was quenched by the addition of 3.96 mL of acetic acid (69 mmol). After stirring for an additional hour, the suspension was filtered through a Celite pad. The filter cake was washed with 2×130 mL of toluene. The combined filtrate and washes were concentrated, and the residual toluene was removed by co-evaporation with 180 mL of methanol followed by drying under high vacuum. The residue was then dissolved in a mixture of 350 mL of hexane and 350 mL of 95% methanol. The hexane layer was washed with 180 mL of 95% methanol. The combined methanol layers were extracted with 2×150 mL of hexane. The combined hexane solutions were dried over sodium sulfate (Na2SO4), and concentrated. The residual hexane was removed by co-evaporation with 30 mL of methanol. The resulting solid residue was suspended in 175 mL of methanol, and the suspension was stirred for 1 hr to obtain a powdery material. After the suspension was stored in a refrigerator overnight, the precipitate was filtered and washed with 2×175 mL of 95% methanol. Drying under high vacuum gave 91.1 g (92.9% yield) of (1α,3β,17Z)-dimethyl[[1-[(triethylsilyl)oxy]pregna-5,7,17(20)-trien-3-yl]oxy](1,1,2-trimethylpropyl)silane as an off-white solid.
Reaction SMILES: [C:1]1([CH3:10])[CH:6]=[CH:5][C:4]([N:7]=[N+]=[N-])=[CH:3][CH:2]=1.[CH3:11][C:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH:13]=1>>[CH3:11][C:12]12[N:7]([C:4]3[CH:5]=[CH:6][C:1]([CH3:10])=[CH:2][CH:3]=3)[CH:17]1[CH2:16][CH2:15][CH2:14][CH2:13]2
Reactant: CC1=CCCCC1
Reactant: Cc1ccc(N=[N+]=[N-])cc1
Product: Cc1ccc(N2C3CCCCC32C)cc1

Procedure:
p-Tolyl azide (0.100 g, 0.751 mmol), 1-methyl-cyclohexene (4.055 g, 42.2 mol), and [(Me,EtTCPh)Fe(NCCH3)2](PF6)2 (0.0104 g, 0.0075 mmol) were used in the General Catalytic Reaction described above yielding 0.059 g, 39%. 1H NMR (CDCl3, 499.74 MHz): δ 7.02 (d, J=7.5 Hz, 2H), 6.75 (d, J=6.5 Hz, 2H), 2.28 (s, 3H), 2.15 (m, 1H), 2.02 (m, 1H), 1.99 (m, 2H), 1.64 (m, 1H), 1.55 (m, 2H), 1.35 (m, 1H), 1.25 (m, 1H), 0.99 (s, 3H) 13C NMR (CDCl3, 125.66 MHz): δ 148.74, 130.52, 129.27, 120.49, 44.17, 41.60, 32.41, 24.62, 21.16, 20.85, 20.81, 20.65. GC/MS (m/z): 201.1. DART HR MS (m/z): [M+H]+202.1594 (found). C15H22N, 202.1596 (calcd).
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[C:13]([O:17][C:18]([NH:20][CH2:21][C:22]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23])=[O:19])([CH3:16])([CH3:15])[CH3:14].[C:32]1(=[O:36])[CH2:35][CH2:34][CH2:33]1.C(O)(=O)C>O1CCCC1.O.CCCCCC>[C:13]([O:17][C:18]([NH:20][CH:21]([C:32]1([OH:36])[CH2:35][CH2:34][CH2:33]1)[C:22]([O:24][CH2:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)=[O:23])=[O:19])([CH3:16])([CH3:14])[CH3:15]
Reactant: O=C1CCC1
Reactant: CC(C)(C)OC(=O)NCC(=O)OCc1ccccc1
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: CC(C)NC(C)C
Solvent: O
Product: CC(C)(C)OC(=O)NC(C(=O)OCc1ccccc1)C1(O)CCC1
Temperature: -40 °C
Reaction time: 0.33 h
Yield: 77.5 %

Procedure:
A solution of diisopropylamine (9.7 ml, 70 mmoles) in 150 ml of dry tetrahydrofuran at -40° C. under argon was treated with 39 ml (64.5 mmoles) of 1.71N n-butyllithium is hexane and the pale yellow solution stirred at -40° C. for 20 minutes. The solution was cooled to -78° C., and a solution of 7.95 g (30 mmoles) of N-(t-butoxycarbonyl)glycine, benzyl ester in 30 ml of dry tetrahydrofuran was dripped in over 5 minutes, resulting in a dark yellow solution, and, after 20 minutes, a slight turbidity. After 0.5 hours, a solution of 2.42 g (2.0 ml, 34.5 mmoles) of cyclobutanone in 30 ml of tetrahydrofuran was added. The resulting yellow turbid mixture was stirred at -78° C. for 15 minutes, then placed in a 0° C. ice bath for 2 hours. At an internal temperature of -25° C. (1 hour), the solution became clear, and at -15° C. turned dark purple. It was stirred at 0° C. for 0.5 hours, then treated with 3.96 g (66 mmoles) of glacial acetic acid in 15 ml of tetrahydrofuran, giving a turbid, light yellow mixture. This was poured into 500 ml of cold water and extracted twice with ethyl acetate. The extracts were washed with 2% potassium bisulfate, 5% sodium bicarbonate, and brine, dried (sodium sulfate) and evaporated to a thick oil. Chromatography on 800 ml of LPS-1 in hexane:ethyl acetate (2:1) and combination of the product fractions (Rf=0.29) gave 7.8 g of product as an oil.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:28]([F:31])([F:30])[F:29])=[C:6]([CH:27]=1)[CH2:7][N:8]1[CH2:13][CH2:12][NH:11][C:10]2[N:14]=[CH:15][C:16]([C:18]3[CH:26]=[CH:25][C:21]([C:22](O)=[O:23])=[CH:20][CH:19]=3)=[CH:17][C:9]1=2.[NH2:32][CH2:33][C:34]1[C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[CH:37]=[CH:36][CH:35]=1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:28]([F:31])([F:30])[F:29])=[C:6]([CH:27]=1)[CH2:7][N:8]1[CH2:13][CH2:12][NH:11][C:10]2[N:14]=[CH:15][C:16]([C:18]3[CH:26]=[CH:25][C:21]([C:22]([NH:32][CH2:33][C:34]4[C:43]5[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=5)[CH:37]=[CH:36][CH:35]=4)=[O:23])=[CH:20][CH:19]=3)=[CH:17][C:9]1=2
Reactant: NCc1cccc2ccccc12
Reactant: O=C(O)c1ccc(-c2cnc3c(c2)N(Cc2cc(Cl)ccc2C(F)(F)F)CCN3)cc1
Product: O=C(NCc1cccc2ccccc12)c1ccc(-c2cnc3c(c2)N(Cc2cc(Cl)ccc2C(F)(F)F)CCN3)cc1

Procedure:
4-{1-[5-chloro-2-(trifluoromethyl)benzyl]-1,2,3,4-tetrahydropyrido[2,3-b]pyrazin-7-yl}benzoic acid was reacted with 1-(aminomethyl)naphthalene as in General Procedure 10 to give the title compound. LCMS: m/z=586.95 (M+H+); retention time=1.01 minutes.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[C:12]([N:14]1[CH2:18][CH2:17][CH2:16][CH2:15]1)=[O:13])[N:8]=[CH:7][N:6]=[C:5]2[NH:19][CH:20]([C:26]1[N:30](C(OC(C)(C)C)=O)[C:29]2[CH:38]=[CH:39][C:40]([Cl:42])=[CH:41][C:28]=2[N:27]=1)[CH2:21][CH2:22][C:23](O)=[O:24].[NH:43]1[CH2:48][CH2:47][O:46][CH2:45][CH2:44]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.FC(F)(F)C(O)=O>C(#N)C.O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[C:12]([N:14]1[CH2:18][CH2:17][CH2:16][CH2:15]1)=[O:13])[N:8]=[CH:7][N:6]=[C:5]2[NH:19][CH:20]([C:26]1[NH:30][C:29]2[CH:38]=[CH:39][C:40]([Cl:42])=[CH:41][C:28]=2[N:27]=1)[CH2:21][CH2:22][C:23]([N:43]1[CH2:48][CH2:47][O:46][CH2:45][CH2:44]1)=[O:24]
Reactant: C1COCCN1
Reactant: CC(C)(C)OC(=O)n1c(C(CCC(=O)O)Nc2ncnc3cc(C(=O)N4CCCC4)c(Cl)cc23)nc2cc(Cl)ccc21
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CC#N
Solvent: C1CCOC1
Solvent: O=C(O)C(F)(F)F
Product: O=C(CCC(Nc1ncnc2cc(C(=O)N3CCCC3)c(Cl)cc12)c1nc2cc(Cl)ccc2[nH]1)N1CCOCC1

Procedure:
Prepared analogously to Example 61 from 6-chloro-4-[1-(1-tert.-butyloxycarbonyl-5-chloro-1H-benzimidazol-2-yl)-3-hydroxycarbonyl-propyl-amino]-7-(pyrrolidin-1-yl-carbonyl)-quinazoline and morpholine with TBTU in acetonitrile/tetrahydrofuran and subsequent reaction with trifluoroacetic acid.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3](/[C:7](/[C:16]2[S:17][CH:18]=[CH:19][CH:20]=2)=[CH:8]\[CH2:9][CH2:10][CH2:11][CH2:12][C:13](O)=[O:14])[CH:2]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>O1CCCC1>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3](/[C:7](/[C:16]2[S:17][CH:18]=[CH:19][CH:20]=2)=[CH:8]\[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][OH:14])[CH:2]=1
Reactant: O=C(O)CCCC/C=C(\c1cccnc1)c1cccs1
Agent: O=C([O-])[C@H](O)[C@@H](O)C(=O)[O-]
Agent: [Al+3]
Agent: [H-]
Solvent: C1CCOC1
Product: OCCCCC/C=C(\c1cccnc1)c1cccs1
Temperature: 50 °C
Yield: 54.9 %

Procedure:
(E)-7-(3-Pyridyl)-7-(2-thienyl)-6-heptenoic acid (0.4 g, 1.4 mmoles) was dissolved in dry tetrahydrofuran (20 ml) and lithium aluminum hydride (0.1 g, 2.6 mmoles) was added to the solution. The mixture was stirred at 50° C. for an hour, followed by addition of a saturated aqueous Rochelle salt solution (10 ml). The organic alyer was separated and the precipitate was washed with tetrahydrofuran (20 ml). The tetrahydrofuran solutions were combined, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography using ethyl acetate as the eluent to give (E)-7-(3-pyridyl)-7-(2-thienyl)-6-hepten-1-ol (0.21 g, 52%) (Compound I-17).
Reaction SMILES: S(=O)(=O)(O)O.[CH3:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([CH3:15])=[O:14])=[CH:9][CH:8]=1.[N+:16]([O-])([OH:18])=[O:17]>>[CH3:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([CH3:15])=[O:14])=[CH:9][C:8]=1[N+:16]([O-:18])=[O:17]
Reactant: CC(=O)c1ccc(C)cc1
Reactant: O=[N+]([O-])O
Agent: O=S(=O)(O)O
Product: CC(=O)c1ccc(C)c([N+](=O)[O-])c1
Reaction time: 0.5 h

Procedure:
To 250 ml of cold (-20° C.) concentrated sulfuric acid is added with stirring 4-methylacetophenone (40 g, 300 mmoles). When the first addition is complete, a mixture of 25.5 ml (36.3 g, 300 mmoles) of 70% nitric acid and 300 g of 20% fuming sulfuric acid is added dropwise over 40 minutes. The temperature remains below -15° C. The mixture is stirred for an additional 30 minutes and then poured onto ice. The solids are filtered, washed with water and then with hexane. The solids are dissolved in dichloromethane and washed with 10% sodium bicarbonate solution and finally with saturated sodium chloride solution. The organic phase is dried, charcoaled, concentrated and diluted with hexane, whereupon the product, 4-methyl-3-nitroacetophenone, crystallizes, m.p. 61°-62° C.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.[C:7]([C:11]1[CH:12]=[C:13]([CH2:22][CH2:23][C:24]([OH:26])=[O:25])[CH:14]=[C:15]([C:18]([CH3:21])([CH3:20])[CH3:19])[C:16]=1[OH:17])([CH3:10])([CH3:9])[CH3:8].[CH2:27]([N:34]([CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)O)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(N(CC)CC)C>>[C:7]([C:11]1[CH:12]=[C:13]([CH:14]=[C:15]([C:18]([CH3:19])([CH3:20])[CH3:21])[C:16]=1[OH:17])[CH2:22][CH2:23][C:24]([O:26][N:34]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[O:25])([CH3:10])([CH3:8])[CH3:9]
Reactant: CC(C)(C)c1cc(CCC(=O)O)cc(C(C)(C)C)c1O
Reactant: ON(Cc1ccccc1)Cc1ccccc1
Agent: O=C(Cl)C(=O)Cl
Solvent: CCN(CC)CC
Product: CC(C)(C)c1cc(CCC(=O)ON(Cc2ccccc2)Cc2ccccc2)cc(C(C)(C)C)c1O
Yield: 76.5 %

Procedure:
The procedure of Example II is followed using 3.17 g (25 mmol) of oxalyl chloride, 6.96 g (25 mmol) of 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propanoic acid, 5.33 g (25 mmol) of N,N-dibenzylhydroxylamine, and 2.53 g (25 mmol) of triethylamine. The residue is recrystallized from petroleum ether to give 9.06 g (77%) of a white solid: mp 93°-95.5° C.
Reaction SMILES: C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[K+].[K+].Br[C:27]1[C:28]([F:36])=[C:29]([CH:33]=[CH:34][CH:35]=1)[C:30]([NH2:32])=[O:31].[CH3:37][C:38]([Si:41]([CH3:54])([CH3:53])[O:42][CH2:43][C:44]1[CH:45]=[C:46](B(O)O)[CH:47]=[CH:48][CH:49]=1)([CH3:40])[CH3:39]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:40][C:38]([Si:41]([CH3:54])([CH3:53])[O:42][CH2:43][C:44]1[CH:45]=[C:46]([C:27]2[CH:35]=[CH:34][CH:33]=[C:29]([C:30]([NH2:32])=[O:31])[C:28]=2[F:36])[CH:47]=[CH:48][CH:49]=1)([CH3:37])[CH3:39]
Reactant: NC(=O)c1cccc(Br)c1F
Reactant: CC(C)(C)[Si](C)(C)OCc1cccc(B(O)O)c1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Product: CC(C)(C)[Si](C)(C)OCc1cccc(-c2cccc(C(N)=O)c2F)c1
Temperature: 80 °C
Yield: 63 %

Procedure:
Pd(OAc)2 (123.6 mg, 0.55 mmol), PPh3 (557.5 mg, 2.2 mmol), K2CO3 (3.8 g, 27.5 mmol) and 3-bromo-2-fluorobenzamide (4.0 g, 18.4 mmol) were suspended in 1,4-dioxane (30 mL). After the mixture was heated to 80° C. for 15 min, [3-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)phenyl]boronic acid (5.9 g, 22.0 mmol) was added. Then the reaction mixture was stirred over night at 100° C. After cooling to room temperature, the solvent was removed under reduced pressure. The residue was dissolved in CH2Cl2 (50 mL), then was washed with water (20 mL), brine (20 mL), and dried over Na2SO4. After the solvent was removed, the crude product was purified on an Al2O3 column chomatography, eluting with CH2Cl2/CH3OH (300:1). 3′-({[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}methyl)-2-fluoro-3-biphenylcarboxamide, was obtained (4.1 g, yield: 63%). 1H NMR (400 MHz, CDCl3) δ 0.12 (s, 6H), 0.95 (s, 9H), 4.81 (s, 2H), 7.25-8.12 (m, 7H).
Reaction SMILES: [I:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=O)[CH2:9][CH2:10][CH2:11][CH2:12][N:13]1[CH2:18][CH2:17][CH:16]([C:19]2[CH:20]=[C:21]([NH:25][C:26](=[O:30])[CH:27]([CH3:29])[CH3:28])[CH:22]=[CH:23][CH:24]=2)[CH2:15][CH2:14]1.[C:32]1([NH:38]N)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>>[I:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[NH:38][C:32]2[C:37]([C:9]=1[CH2:10][CH2:11][CH2:12][N:13]1[CH2:18][CH2:17][CH:16]([C:19]3[CH:20]=[C:21]([NH:25][C:26](=[O:30])[CH:27]([CH3:29])[CH3:28])[CH:22]=[CH:23][CH:24]=3)[CH2:15][CH2:14]1)=[CH:36][CH:35]=[CH:34][CH:33]=2
Reactant: CC(C)C(=O)Nc1cccc(C2CCN(CCCCC(=O)c3ccccc3I)CC2)c1
Reactant: NNc1ccccc1
Product: CC(C)C(=O)Nc1cccc(C2CCN(CCCc3c(-c4ccccc4I)[nH]c4ccccc34)CC2)c1

Procedure:
Prepared by Procedure E and Scheme M using N-(3-{1-[5-(2-iodophenyl)-5-oxopentyl]-4-piperidinyl}phenyl)-2-methylpropanamide and phenylhydrazine: ESMS m/e: 606.1 (M+H)+.
Reaction SMILES: [NH2:1][C@@H:2]([CH:12]([CH3:14])[CH3:13])[CH2:3][NH:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[C:15](OCC)(=[O:21])[C:16](OCC)=[O:17]>CCO>[CH3:13][CH:12]([C@H:2]1[CH2:3][N:4]([CH2:5][C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:16](=[O:17])[C:15](=[O:21])[NH:1]1)[CH3:14]
Reactant: CCOC(=O)C(=O)OCC
Reactant: CC(C)[C@H](N)CNCc1ccccc1
Solvent: CCO
Product: CC(C)[C@H]1CN(Cc2ccccc2)C(=O)C(=O)N1
Temperature: 25 °C
Yield: 74 %

Procedure:
[(2S)-2-Amino-3-methylbutyl](phenylmethyl)amine (Katritzky, A. R. Tetrahedron: Asymmetry 2002, 13, 933-938) (2.57 g, 13.4 mmol) was dissolved in 100 mL of EtOH with stirring. Diethyl oxalate (1.82 mL, 13.4 mmol) was added via syringe. The mixture was heated to reflux for 3.5 days and subsequently cooled to rt. The mixture was concentrated in vacuo. Purification by flash chromatography afforded the title compound of step A (2.43 g, 9.87 mmol, 74%). 1H NMR (400 MHz, DMSO-d6) δ 8.74 (br. s, 1H), 7.38-7.24 (m, 5H), 4.54 (AB, ΔνAB=88.7 Hz, JAB=14.7 Hz, 2H), 3.48 (dd, J=13.2, 4.2 Hz, 1H), 3.31 (dd, J=13.2, 6.2 Hz, 1H), 3.17 (m, 1H), 1.61 (m, 1H), 0.82 (d, J=6.8 Hz, 3H), 0.63 (d, J=6.8 Hz, 3H).
Reaction SMILES: C([N:4]1[C:8]([CH3:9])=[C:7]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:6]([O:17][C@@H:18]2[O:44][C@H:43]([CH2:45][O:46][C:47](=[O:52])[C:48]([CH3:51])([CH3:50])[CH3:49])[C@@H:35]([O:36][C:37](=[O:42])[C:38]([CH3:41])([CH3:40])[CH3:39])[C@H:27]([O:28][C:29](=[O:34])[C:30]([CH3:33])([CH3:32])[CH3:31])[C@H:19]2[O:20][C:21](=[O:26])[C:22]([CH3:25])([CH3:24])[CH3:23])=[N:5]1)(=O)C.C(=O)(O)[O-].[K+]>CO>[CH2:10]([C:7]1[C:6]([O:17][C@@H:18]2[O:44][C@H:43]([CH2:45][O:46][C:47](=[O:52])[C:48]([CH3:51])([CH3:50])[CH3:49])[C@@H:35]([O:36][C:37](=[O:42])[C:38]([CH3:39])([CH3:40])[CH3:41])[C@H:27]([O:28][C:29](=[O:34])[C:30]([CH3:33])([CH3:32])[CH3:31])[C@H:19]2[O:20][C:21](=[O:26])[C:22]([CH3:23])([CH3:24])[CH3:25])=[N:5][NH:4][C:8]=1[CH3:9])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: CC(=O)n1nc(O[C@@H]2O[C@H](COC(=O)C(C)(C)C)[C@@H](OC(=O)C(C)(C)C)[C@H](OC(=O)C(C)(C)C)[C@H]2OC(=O)C(C)(C)C)c(Cc2ccccc2)c1C
Agent: O=C([O-])O
Agent: [K+]
Solvent: CO
Product: Cc1[nH]nc(O[C@@H]2O[C@H](COC(=O)C(C)(C)C)[C@@H](OC(=O)C(C)(C)C)[C@H](OC(=O)C(C)(C)C)[C@H]2OC(=O)C(C)(C)C)c1Cc1ccccc1
Temperature: 25 °C
Yield: 95.5 %

Procedure:
To a solution of 1-acetyl-4-benzyl-5-methyl-3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1H-pyrazole (1.00 g) in methanol (10 mL) was added potassium bicarbonate (0.058 g) under stirring at room temperature. The reaction mixture was stirred at room temperature for 16 hours. After the precipitation of the crystals by the addition of a solution of glacial acetic acid (0.034 g) in water (20 mL) at room temperature, the mixture was stirred for 2 hours. After the suspension was stirred under ice-cooling for 1 hour, the crystals were collected by filtration. The obtained crystals were washed with a mixed solution of 2-propanol and n-heptane, and dried under reduced pressure to give 4-benzyl-5-methyl-3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1H-pyrazole (0.90 g).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N+:10]([O-])=O)=[C:7]([OH:9])[CH:8]=1>[Pd].C(OCC)(=O)C.C(O)C>[NH2:10][C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][C:7]=1[OH:9]
Reactant: COc1ccc([N+](=O)[O-])c(O)c1
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CCO
Product: COc1ccc(N)c(O)c1
Temperature: 25 °C
Reaction time: 3.5 h
Yield: 98.1 %

Procedure:
Subsequently, a mixture of 5-methoxy-2-nitrophenol (7.47 g) and 10% Pd/C (1.87 g) was prepared in an ethyl acetate/ethanol (100 mL, 1:1 v/v) mixture. The resulting slurry was stirred under an H2 atmosphere for 3.5 h at room temperature. Hydrogen was subsequently purged from the reaction flask and the reaction mixture was filtered through Celite. After washing the celite pad with additional solvent, volatiles in the resultant filtrate were removed in vacuo to give 2-amino-5-methoxyphenol (6.03 g, 98%).