Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1[C:6]([CH2:7][CH2:8][CH2:9]C(O)=O)=[CH:5][CH:4]=[C:3]([N:13]([CH2:17][CH2:18][Cl:19])[CH2:14][CH2:15][Cl:16])[CH:2]=1.C([N:22](CC)CC)C.ClC(OCC)=O.[N-]=[N+]=[N-].[Na+]>CC(C)=O.O>[Cl:16][CH2:15][CH2:14][N:13]([C:3]1[CH:4]=[CH:5][C:6]([CH2:7][CH2:8][CH2:9][NH2:22])=[CH:1][CH:2]=1)[CH2:17][CH2:18][Cl:19]
Reactant: CCN(CC)CC
Reactant: O=C(O)CCCc1ccc(N(CCCl)CCCl)cc1
Agent: CCOC(=O)Cl
Agent: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: O
Solvent: CC(C)=O
Product: NCCCc1ccc(N(CCCl)CCCl)cc1
Temperature: 100 °C
Reaction time: 1 h
Yield: 77.1 %

Procedure:
Chlorambucil (0.30 g; 0.99 mmol) was suspended in 2 ml of acetone. The resultant mixture was stirred under a nitrogen gas atmosphere and ice-cooling, to which 0.17 ml (1.22 mmol; 1.2 equivalents) of triethylamine and 0.11 ml (1.22 mmol; 1.2 equivalents) of ethyl chloroformate were added successively. Twenty minutes later, a solution of 0.13 g (2.0 mmol; 2.0 equivalents) of sodium azide in 2 ml of water was added dropwise. The resulting mixture was stirred, as was, for 1 hour, to which ice was added to terminate the reaction. The thus-obtained mixture was extracted three times with 20 ml portions of benzene. The benzene layers were combined, dried over sodium sulfate and then heated under reflux for 1 hour. The reaction mixture was concentrated under reduced pressure. The residue was added with 9 ml of 8N hydrochloric acid, followed by heating for 15 minutes at 100° C. The resulting mixture was concentrated under reduced pressure and the residue was diluted with water. The thus-obtained mixture was adjusted to pH 12 with concentrated aqueous ammonia, followed by extraction with ethyl acetate. The extract was dried and concentrated, whereby 0.21 g of the title compound was obtained as a crude yellow oil of high viscosity. This reaction product was provided for use in the next reaction without purification.
Reaction SMILES: [CH3:1][C:2]1([CH3:14])[CH2:11][CH2:10][C:9]([CH3:13])([CH3:12])[C:8]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]1=2.[N+:15]([C:18]1[CH:26]=[CH:25][CH:24]=[CH:23][C:19]=1[C:20](Cl)=[O:21])([O-:17])=[O:16].[Al+3].[Cl-].[Cl-].[Cl-].O>ClCCl>[CH3:12][C:9]1([CH3:13])[CH2:10][CH2:11][C:2]([CH3:14])([CH3:1])[C:3]2[CH:4]=[C:5]([C:20]([C:19]3[CH:23]=[CH:24][CH:25]=[CH:26][C:18]=3[N+:15]([O-:17])=[O:16])=[O:21])[CH:6]=[CH:7][C:8]1=2
Reactant: CC1(C)CCC(C)(C)c2ccccc21
Reactant: O=C(Cl)c1ccccc1[N+](=O)[O-]
Agent: [Al+3]
Agent: [Cl-]
Solvent: O
Solvent: ClCCl
Product: CC1(C)CCC(C)(C)c2cc(C(=O)c3ccccc3[N+](=O)[O-])ccc21
Yield: 44 %

Procedure:
5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene (10.0 g, 53.2 mmol) and o-nitrobenzoic acid chloride (9.4 g, 50.5 mmol) were dissolved in dichloromethane (50 ml), and the mixture was added with AlCl3 (14.3 g) portionwise and then heated under reflux for 1 hour and 30 minutes. The reaction mixture was poured into water and extracted with dichloromethane and dried, and then the solvent was evaporated to give a crude product (21.59 g). This product was purified by silica gel column chromatography (AcOEt:n-hexane=1:10) to give (5,5,8,8-tetramethyl-5,6,7,8- tetrahydro-2-naphthyl) carbonyl-2-nitrobenzene (Compound 37, 7.5 g, 42%). This product was further recrystallized from n-hexane.
Reaction SMILES: [ClH:1].[C:2]([O:5][CH:6]([CH2:27][NH:28]C)[CH2:7][O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])(=[O:4])[CH3:3]>CCCCCC>[ClH:1].[C:2]([O:5][CH:6]([CH2:27][NH2:28])[CH2:7][O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])(=[O:4])[CH3:3]
Reactant: CCCCCCCCCCCCCCCCCCOCC(CNC)OC(C)=O
Agent: Cl
Solvent: CCCCCC
Product: CCCCCCCCCCCCCCCCCCOCC(CN)OC(C)=O

Procedure:
2 a) (±)-3-methylamino-1-octadecyloxy-2-propyl acetate hydrochloride; m.p. 109°-113° C. from n-hexane; yield 61%.
Reaction SMILES: [CH3:1][P:2](Cl)([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)=[O:3].[CH3:11][O:12][C:13](=[O:23])[C@@H:14]([CH3:22])[NH:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21].C(N(CC)CC)C>ClCCl.CN(C)C1C=CN=CC=1>[CH3:11][O:12][C:13](=[O:23])[C@@H:14]([CH3:22])[N:15]([P@@:2]([CH3:1])([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)=[O:3])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]
Reactant: CCCCCCN[C@H](C)C(=O)OC
Reactant: CP(=O)(Cl)c1ccccc1
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCCCCN([C@H](C)C(=O)OC)[P@](C)(=O)c1ccccc1
Temperature: 0 °C
Reaction time: 16 h

Procedure:
Methylphenyl-phosphinic chloride (1.05 g, 6 mmol) is dissolved in dichloromethane (50 mL) and cooled to 0° C. To this is added a solution of N-hexyl-D-alanine methyl ester (1 g, 5.34 mmol) and triethylamine (2.1 mL, 15 mmol) in dichloromethane (10 mL). A catalytic amount of 4-dimethylaminopyridine is added and reaction is stirred for 16 hours, washed with water and brine, dried over sodium sulfate, and concentrated. The crude product is purified by silica gel flash chromatography (100% ethyl acetate) to give N-((R)-methylphenylphosphinyl)-N-hexyl-D-alanine methyl ester as an oil.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:10])=[O:9])=[CH:4][CH:3]=1.[BrH:11].BrBr.O>C(O)(=O)C>[Br:11][CH2:10][C:8]([C:5]1[CH:6]=[CH:7][C:2]([CH3:1])=[CH:3][CH:4]=1)=[O:9]
Reactant: Br
Reactant: CC(=O)c1ccc(C)cc1
Agent: BrBr
Solvent: CC(=O)O
Solvent: O
Product: Cc1ccc(C(=O)CBr)cc1
Temperature: 30 °C
Reaction time: 5 h
Yield: 65 %

Procedure:
To a stirring solution of 20 g (150 mmol) of 4-methylacetophenone in 100 mL of glacial acetic acid was added catalytic amount of HBr (0.5 mL) followed by 21.40 g (134 mmol) of bromine dissolved in acetic acid (30 mL) dropwise at 10-15° C. The reaction mixture was stirred at 25-35° C. for 5 hrs, then poured into water (100 mL). The solid that separated was filtered to give the required product (20 g, 65%).
Reaction SMILES: O.[C:2]1([C:8]([CH:10]=[O:11])=[O:9])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:12]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)([CH3:15])([CH3:14])[CH3:13]>ClC(Cl)C.[Ti](Cl)(Cl)(Cl)Cl>[C:12]([C:16]1[CH:21]=[CH:20][C:19]([CH:10]([OH:11])[C:8](=[O:9])[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:18][CH:17]=1)([CH3:15])([CH3:14])[CH3:13]
Reactant: O=CC(=O)c1ccccc1
Reactant: CC(C)(C)c1ccccc1
Agent: Cl[Ti](Cl)(Cl)Cl
Solvent: O
Solvent: CC(Cl)Cl
Product: CC(C)(C)c1ccc(C(O)C(=O)c2ccccc2)cc1

Procedure:
Phenylglyoxal monohydrate (304 mg, 2 mM) and tert-butylbenzene (0.62 ml, 4 mM) were dissolved in dichloroethane (2 ml), titanium tetrachloride (0.33 ml, 3 mM) was added, and reacted at room temperature for 2.5 hours. Using the same procedure as in Example 1, 4'-tert-butylbenzoin was obtained as crystal (216.9 mg, 40.5% yield).
Reaction SMILES: S(=O)(=O)(O)O.[O:6]1[CH2:11][CH2:10][CH2:9][CH2:8][CH:7]1[O:12]CC#CCCCCl.[C-]#N.[K+].[OH-].[K+].[CH2:25]([OH:27])[CH3:26]>O>[OH:27][CH2:25][C:26]#[C:11][CH2:10][CH2:9][CH2:8][C:7]([OH:12])=[O:6]
Reactant: CCO
Reactant: ClCCCC#CCOC1CCCCO1
Agent: O=S(=O)(O)O
Agent: [C-]#N
Agent: [K+]
Solvent: O
Product: O=C(O)CCCC#CCO

Procedure:
By following the procedure of A. I. Rachlin, et al., cited above, 6-chloro-2-hexyn-1-ol is prepared by condensing propargyl alcohol tetrahydropyran-2-yl ether and the dihaloalkane of formula VIII, 1-bromo-3-chloropropane, to give 1-[(tetrahydropyran-2-yl)oxy]-6-chloro-2-hexyne, which is then converted to the desired compound followed by hydrolysis in the presence of sulfuric acid. The 6-chloro-2-hexyn-1-ol (280 g) is dissolved in ethanol (2.8 l) then water (560 ml) and potassium cyanide (290 g) is added and the mixture stirred and refluxed for 20 hr. Potassium hydroxide (768 g) and water (500 ml) are added and the stirred mixture kept at reflux for an additional 20 hr. Methanol is evaporated and the water phase is acidified with concentrated HCl and extracted with ether for 2 days in a continuous liquid-liquid extractor. The ether extract is dried (Na2SO4) and concentrated to give the title compound, nmr (CDCl3) δ 4.22 (m, 2 H), 7.41 (broad, 2H).
Reaction SMILES: [C:1]([CH:10]1C(=O)O[C:13](C)([CH3:17])[O:12][C:11]1=[O:19])(=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]>C(O)C>[O:9]=[C:1]([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])[CH2:10][C:11]([O:12][CH2:13][CH3:17])=[O:19]
Reactant: CCCCCCCC(=O)C1C(=O)OC(C)(C)OC1=O
Solvent: CCO
Product: CCCCCCCC(=O)CC(=O)OCC
Yield: 90 %

Procedure:
The resulting 5-octanoyl-2,2-dimethyl-1,3-dioxane-4,6-dione was allowed to reflux in ethanol for 2 hours, and then concentrated under reduced pressure. The resulting residue was purified using silica gel chromatography (developing solvent: n-hexane/ethyl acetate=8/2) to obtain ethyl 3-oxodecanoate shown by the formula below.
Reaction SMILES: [OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4](O)[CH:3]=1.[NH3:13]>>[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]([NH2:13])[CH:3]=1
Reactant: N
Reactant: Oc1cc(O)c2ccccc2c1
Product: Nc1cc(O)c2ccccc2c1
Temperature: 135 °C
Reaction time: 14 h

Procedure:
A solution of 1,3-dihydroxynaphthalene (1, 50 g, 0.312 mol) in liquid ammonia (200 mL) at −78° C. was sealed in a 1 L steel bomb containing a glass liner. The reaction mixture was warmed to 135±10° C. and 1300 psi for 14 h with vigorous stirring. The vessel was allowed to cool to 60° C., and the ammonia was released slowly. The remaining traces of ammonia were removed by co-evaporation with THF (2×150 mL) under a stream of argon at 60° C. The intermediate 4-hydroxy-2-naphthylamine (2) was not isolated but was immediately converted to the di-tert-butyloxycarbonyl protected compound 3. A solution of di-tert-butyl dicarbonate (175 g, 0.801 mol) in dry THF (300 mL) and N,N-diisopropylethylamine (140 mL, 0.803 mol) were sequentially added to the bomb. The bomb was re-sealed, and the contents were warmed at 100 ° C. with stirring for 4 h. The bomb was cooled to room temperature, opened, and the residue partitioned between saturated aqueous NaCl (800 mL) and ethyl acetate (500 mL). The aqueous phase was extracted with ethyl acetate (200 mL×2). The combined organic layers were dried (magnesium sulfate), filtered, and concentrated under reduced pressure. Chromatography on silica gel (1:8 to 1:4 ethyl acetate/hexane) and recrystallization with ethyl acetate/ethanol/hexane provided pure 77.41 g (69%) of the title compound (3). 1H NMR (CDCl3, 400 MHz) 8.14 (d, 1H, J=8.1 Hz), 7.66 (d, 1H, J=8.1 Hz), 7.43 (dd, 1H, J=6.8, 8.2 Hz), 7.35 (dd, 1H, J=6.8, 8.2 Hz), 7.22 (d, 1H, J=1.8 Hz), 7.15 (br, 1H, NH), 6.69 (s, 1H), 1.59 (s, 9H), 1.37 (s, 9H); 13C NMR (CDCl3) 153.71, 152.9, 136.11, 135.20, 128.12, 128.01, 126.81, 126.03, 123.61, 107.94, 102.95, 82.98, 82.10, 28.93, 27.69; MS m/z 382.52 (M+Na)+.
Reaction SMILES: [CH3:1][C:2]([C:5]1[O:9][N:8]=[C:7]([NH:10][C:11](=[O:20])[N:12]([CH2:14][CH:15](OC)[O:16]C)[CH3:13])[CH:6]=1)([CH3:4])[CH3:3].Cl>O>[CH3:1][C:2]([C:5]1[O:9][N:8]=[C:7]([N:10]2[CH:15]([OH:16])[CH2:14][N:12]([CH3:13])[C:11]2=[O:20])[CH:6]=1)([CH3:4])[CH3:3]
Reactant: COC(CN(C)C(=O)Nc1cc(C(C)(C)C)on1)OC
Agent: Cl
Solvent: O
Product: CN1CC(O)N(c2cc(C(C)(C)C)on2)C1=O
Yield: 87.1 %

Procedure:
A round bottom flask was charged with 2.6 grams of the 3-[5-(1,1-dimethylethyl)-3-isoxazoly]-1-methyl-(2,2-dimethoxyethyl)urea (prepared above), 150 milliliters of water and 1.5 milliliters of concentrated hydrochloric acid (HCl). The resulting mixture was heated until one phase formed, and crystals coated out on the sides of the flask and cooled; and the scrapings of the crystals and the solution were filtered. The crystalline precipitate was washed twice with separate portions of H2O, and then air dried to yield 1.9 grams of white crystals of 3-[5-(1,1-dimethylethyl-3-isoxazolyl]-1-methyl-4-hydroxy-2-imidazolidinone. M.P. 173°-177° C., IR spectra (mull.) bands at 3400, 3140, 1700, and 1590 cm-1.
Reaction SMILES: [CH3:1][C:2]1[CH:6]=[C:5]([NH2:7])[O:4][N:3]=1.N1C=CC=CC=1.Cl[C:15]([O:17][CH2:18][C:19]([Cl:22])([Cl:21])[Cl:20])=[O:16].O>O1CCCC1>[CH3:1][C:2]1[CH:6]=[C:5]([NH:7][C:15](=[O:16])[O:17][CH2:18][C:19]([Cl:22])([Cl:21])[Cl:20])[O:4][N:3]=1
Reactant: O=C(Cl)OCC(Cl)(Cl)Cl
Reactant: Cc1cc(N)on1
Solvent: C1CCOC1
Solvent: c1ccncc1
Solvent: O
Product: Cc1cc(NC(=O)OCC(Cl)(Cl)Cl)on1
Temperature: 25 °C
Reaction time: 3 h
Yield: 25.7 %

Procedure:
To a solution of 3-methyl-5-aminoisoxazole (1.00 g, 10.2 mmol) and pyridine (0.97 ml, 12.2 mmol) in tetrahydrofuran (34 ml) was added 2,2,2-trichloroethyl chloroformate (1.69 ml, 12.2 mmol) under ice-cooling, and the mixture was stirred at room temperature for 3 hours and half. Water was poured to the reaction mixture, and the resulting solution was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=7:3) to give 718 mg (26%) of the desired product as a solid.
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=1)=O.[CH3:12][O:13][C:14](=[O:22])[C:15]1[CH:20]=[CH:19][C:18]([NH2:21])=[N:17][CH:16]=1>O1CCOCC1>[CH3:12][O:13][C:14]([C:15]1[CH:20]=[CH:19][C:18]2[N:17]([CH:2]=[C:3]([C:5]3[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=3)[N:21]=2)[CH:16]=1)=[O:22]
Reactant: O=C(CBr)c1ccc(F)cc1
Reactant: COC(=O)c1ccc(N)nc1
Solvent: C1COCCO1
Product: COC(=O)c1ccc2nc(-c3ccc(F)cc3)cn2c1

Procedure:
2-Bromo-1-(4-fluoro-phenyl)-ethanone (1.135 g, 5.23 mmol) and 6-amino-nicotinic acid methyl ester (795.7 mg, 5.23 mmol) were heated under reflux in 50 ml dioxane for 8.5 hours. After cooling the solid was filtered and dried. Yield: 1.36 g, 96%. MS (mass spectrum): M+H+=271.06.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH2:11][CH2:10][CH2:9]2)=[C:4]([N+:18]([O-])=O)[CH:3]=1.C(O)C>C1C=CC=CC=1.[Pt]>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH2:11][CH2:10][CH2:9]2)=[C:4]([NH2:18])[CH:3]=1
Reactant: O=[N+]([O-])c1cc(Br)ccc1N1CCCc2ccccc21
Agent: [Pt]
Solvent: CCO
Solvent: c1ccccc1
Product: Nc1cc(Br)ccc1N1CCCc2ccccc21
Reaction time: 6.5 h
Yield: 99.9 %

Procedure:
1-(4-Bromo-2-nitrophenyl)-1,2,3,4-tetrahydroquinoline (11.6 g, 0.035 mole) was dissolved in benzene (125 ml), and ethanol added (75 ml), followed by 1% platinum-on-charcoal (0.40 g). The mixture was shaken under an initial pressure of 56 psi for 6.5 hours. The mixture was filtered and the filtrate was evaporated at 50° C. under vacuum to provide 10.6 g (100%) of product, as a gum.
Reaction SMILES: ON=C(C#N)C1C=CC=CC=1.OC1C=CC(S(ON=C(C2SC=CC=2)C#N)(=O)=O)=CC=1.C([O:35][C:36]1[CH:41]=[CH:40][C:39]([S:42]([O:45][N:46]=[C:47]([C:54]#[N:55])[C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)(=[O:44])=[O:43])=[CH:38][CH:37]=1)(=O)C.[OH-].[Na+]>>[OH:35][C:36]1[CH:41]=[CH:40][C:39]([S:42]([O:45][N:46]=[C:47]([C:54]#[N:55])[C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)(=[O:44])=[O:43])=[CH:38][CH:37]=1
Reactant: CC(=O)Oc1ccc(S(=O)(=O)ON=C(C#N)c2ccccc2)cc1
Agent: N#CC(=NO)c1ccccc1
Agent: N#CC(=NOS(=O)(=O)c1ccc(O)cc1)c1cccs1
Agent: [Na+]
Product: N#CC(=NOS(=O)(=O)c1ccc(O)cc1)c1ccccc1

Procedure:
14.6 g (0.1 mole) of α-hydroxyiminobenzyl cynide (1c) are reacted with 23.46 g (0.1 mole) of 4-acetoxybenzenesulfonyl chloride (3a) in accordance with a procedure analogous to that of Example 3c. The resultant α-(4-acetoxybenzenesulfonyloxyimino)benzyl cyanide melts at 142°-143° C. 6 g of this compound are hydrolysed with a solution of NaOH in accordance with a procedure analogous to that of Example 3d, affording the title compound which, after recrystalisation from toluene, melts at 148° C.
Reaction SMILES: [CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@H:19]([C:23]([N:25]([CH3:38])[C@@H:26]([C@@H:34]([CH3:37])[CH2:35][CH3:36])[C@H:27]([O:32][CH3:33])[CH2:28][C:29](O)=[O:30])=[O:24])[CH:20]([CH3:22])[CH3:21])=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.Cl.[CH3:40][O:41][C@@H:42]([C@@H:60]1[CH2:64][CH2:63][CH2:62][NH:61]1)[C@@H:43]([CH3:59])[C:44]([NH:46][C@H:47]([C:55]([O:57][CH3:58])=[O:56])[CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)=[S:45].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>ClCCl>[CH:10]1[C:11]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@H:19]([C:23]([N:25]([CH3:38])[C@@H:26]([C@@H:34]([CH3:37])[CH2:35][CH3:36])[C@H:27]([O:32][CH3:33])[CH2:28][C:29]([N:61]3[CH2:62][CH2:63][CH2:64][C@H:60]3[C@H:42]([O:41][CH3:40])[C@@H:43]([CH3:59])[C:44]([NH:46][C@H:47]([C:55]([O:57][CH3:58])=[O:56])[CH2:48][C:49]3[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=3)=[S:45])=[O:30])=[O:24])[CH:20]([CH3:22])[CH3:21])=[O:17])[C:13]3[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=3)[C:6]=2[CH:7]=[CH:8][CH:9]=1
Reactant: CC[C@H](C)[C@@H]([C@@H](CC(=O)O)OC)N(C)C(=O)[C@@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(C)C
Reactant: COC(=O)[C@H](Cc1ccccc1)NC(=S)[C@H](C)[C@@H](OC)[C@@H]1CCCN1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=S)N[C@@H](Cc1ccccc1)C(=O)OC)OC)N(C)C(=O)[C@@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(C)C

Procedure:
According to general procedure D, from #@5 (260 mg, 0.648 mmol, 1 eq.), #39 (340 mg, ≦0.629 mmol, 1 eq.), dichloromethane (10 mL, 0.065 M), HATU (296 mg, 0.778 mmol, 1.2 eq.) and diisopropylethylamine (339 μL, 1.94 mmol, 3 eq.) was synthesized the crude desired material, which was purified by silica gel chromatography (Gradient: 0% to 40% acetone in heptane) to give #76 (466 mg, 83% over two steps) as a solid. LC-MS: m/z 871.5 [M+H+], 893.5 [M+Na+], retention time=1.10 minutes; HPLC (Protocol C): retention time=9.249 minutes (purity >99%); 1H NMR (400 MHz, DMSO-d6), presumed to be a mixture of rotamers, characteristic signals: δ [10.19 (br d, J=7.4 Hz) and 10.49 (br d, J=7.8 Hz), total 1H], 7.89 (br d, J=7.4 Hz, 2H), 7.68-7.75 (m, 2H), 7.54-7.60 (m, 1H), 7.41 (br dd, J=7.4, 7.4 Hz, 2H), 7.28-7.36 (m, 2H), 7.15-7.28 (m, 5H), [5.20 (ddd, J=10.9, 7.3, 4.4 Hz) and 5.34-5.43 (m), total 1H], 3.65 and 3.69 (2 s, total 3H), 3.24 and 3.25 (2 s, total 3H), 3.17 (br s, 3H), 2.93 and 2.98 (2 br s, total 3H), [1.15 (d, J=6.6 Hz) and 1.18 (d, J=6.6 Hz), total 3H].
Reaction SMILES: Br[C:2]1[S:6][C:5]([C:7]2[N:11]3[CH:12]=[C:13]([C:16]4[C:17]([C:40]5[CH:45]=[CH:44][C:43]([F:46])=[CH:42][CH:41]=5)=[N:18][N:19]([C:21]([C:34]5[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=5)([C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=5)[C:22]5[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=5)[CH:20]=4)[CH:14]=[CH:15][C:10]3=[N:9][CH:8]=2)=[CH:4][CH:3]=1.C([Sn](CCCC)(CCCC)[C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][N:53]=1)CCC>>[F:46][C:43]1[CH:44]=[CH:45][C:40]([C:17]2[C:16]([C:13]3[CH:14]=[CH:15][C:10]4[N:11]([C:7]([C:5]5[S:6][C:2]([C:52]6[CH:57]=[CH:56][CH:55]=[CH:54][N:53]=6)=[CH:3][CH:4]=5)=[CH:8][N:9]=4)[CH:12]=3)=[CH:20][N:19]([C:21]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[N:18]=2)=[CH:41][CH:42]=1
Reactant: Fc1ccc(-c2nn(C(c3ccccc3)(c3ccccc3)c3ccccc3)cc2-c2ccc3ncc(-c4ccc(Br)s4)n3c2)cc1
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccccn1
Product: Fc1ccc(-c2nn(C(c3ccccc3)(c3ccccc3)c3ccccc3)cc2-c2ccc3ncc(-c4ccc(-c5ccccn5)s4)n3c2)cc1

Procedure:
150 mg of 3-(5-bromo-2-thienyl)-6-[3-(4-fluorophenyl)-1-trityl-1H-4-pyrazolyl]imidazo[1,2-a]pyridine obtained in Example 4 and 0.13 mL of 2-(tri-n-butylstannyl)pyridine were reacted in the same manner as in Example 21, to give 137 mg of the title compound as a yellow amorphous.
Reaction SMILES: CC1[C@H]2C(C)(C)[C@H](C2)CC=1.B.S(C)C.[CH:15]1([C:20]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:21])[CH2:19][CH:18]=[CH:17][CH2:16]1.C1C[O:33]CC1>>[OH:33][CH:17]1[CH2:18][CH2:19][CH:15]([C:20]([O:22][CH2:23][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)=[O:21])[CH2:16]1
Reactant: O=C(OCc1ccccc1)C1CC=CC1
Reactant: C1CCOC1
Agent: B
Agent: CC1=CC[C@H]2C[C@@H]1C2(C)C
Solvent: CSC
Product: O=C(OCc1ccccc1)C1CCC(O)C1
Temperature: 0 °C
Reaction time: 4 h
Yield: 37 %

Procedure:
A solution of (−)-α-pinene (5.80 g, 42.6 mmol) in THF (10 mL) was cooled to 0° C. and a solution of borane-Me2S (10N, 1.5 mL, 15 mmol) was added. The mixture was stirred for 4 h at 0° C. and benzyl cyclopent-3-enecarboxylate (3.5 g, 17 mmol) was added. The reaction mixture was allowed to warm to ambient temperature and stirred overnight. The mixture was cooled to 0° C. again and quenched with water (2 mL) and aqueous NaOH (3N, 15 mL). Then 30% hydrogen peroxide (20 mL) was added dropwise. The mixture was stirred for 1 h at 0° C. and diluted with water (20 mL) and EtOAc (50 mL). The two layers were separated and the aqueous phase was extracted with EtOAc (50 mL×3). The combined organic phases were washed with brine (200 mL×3), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by flash column chromatography on silica gel (EtOAc/hexane=1:4) to afford benzyl 3-hydroxycyclopentanecarboxylate (1.4 g, 37% yield).
Reaction SMILES: ClC1C=C(C=CC=1)C(OO)=[O:6].[OH:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:20]=[N:21][C:22]([N:25]3[C:33]4[C:28](=[CH:29][CH:30]=[C:31]([C:34]([N:36]5[CH2:41][CH2:40][O:39][CH2:38][CH2:37]5)=[O:35])[CH:32]=4)[C:27]([S:42][CH3:43])=[CH:26]3)=[N:23][CH:24]=2)=[CH:15][CH:14]=1>ClCCl.CN(C=O)C.ClCCl>[OH:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[N:23][C:22]([N:25]3[C:33]4[C:28](=[CH:29][CH:30]=[C:31]([C:34]([N:36]5[CH2:41][CH2:40][O:39][CH2:38][CH2:37]5)=[O:35])[CH:32]=4)[C:27]([S:42]([CH3:43])=[O:6])=[CH:26]3)=[N:21][CH:20]=2)=[CH:15][CH:14]=1
Reactant: CSc1cn(-c2ncc(-c3ccc(O)cc3)cn2)c2cc(C(=O)N3CCOCC3)ccc12
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CS(=O)c1cn(-c2ncc(-c3ccc(O)cc3)cn2)c2cc(C(=O)N3CCOCC3)ccc12
Reaction time: 1 h

Procedure:
m-Chloroperoxybenzoic acid (134 mg, 0.5022 mmol, 0.8 eq) was added at 0° C. to a stirred solution of 86a) (280 mg, 0.6278 mmol, 1.0 eq) in dichloromethane/DMF (10:1; 22 mL) and the solution was stirred for 1 h at this temperature. The reaction mixture was then diluted with dichloromethane (20 mL), washed with saturated sodium hydrogen carbonate solution and brine, and dried over anhydrous sodium sulfate. The solvents were removed under vacuum and the residue was purified by preparative TLC using ethyl acetate as eluent. White solid. Yield: 65 mg (21% of theory)
Reaction SMILES: OS(O)(=O)=O.[CH2:6]([OH:19])[CH2:7][C:8]#[C:9][CH2:10][C:11]#[C:12][CH2:13][CH2:14][CH2:15][CH:16]([OH:18])[CH3:17].[OH2:20]>CC(C)=O.[O-2].[O-2].[O-2].[Cr+6]>[O:18]=[C:16]([CH3:17])[CH2:15][CH2:14][CH2:13][C:12]#[C:11][CH2:10][C:9]#[C:8][CH2:7][C:6]([OH:20])=[O:19]
Reactant: O
Reactant: CC(O)CCCC#CCC#CCCO
Agent: [Cr+6]
Agent: O=S(=O)(O)O
Agent: [O-2]
Solvent: CC(C)=O
Product: CC(=O)CCCC#CCC#CCC(=O)O
Yield: 40 %

Procedure:
Chromium trioxide (12.0 g, 120 mmol) was dissolved in 120 mL of 3.5M H2SO4 (420 mmol) and cooled to -5°. A solution of diol 11 (4.30 g, 22.2 mmol) in acetone (250 mL) was added dropwise over 4 hr. When the addition was complete, the mixture was warmed to 20° over 45 min, then poured into water (400 mL), and extracted with ether (4×150 mL). The combined ether extracts were washed with brine (3×50 mL), dried (MgSO4), and concentrated in vacuo. The crude product was flash chromatographed9 (hexane:EtOAc:AcOH, 75:75:1), yielding 1.83 g (40% yield) of a highly unstable yellow oil.
Reaction SMILES: [CH:1]1[N:9]2[C:4]([NH:5][NH:6][C:7]3[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=32)=[N:3][N:2]=1.[C:14]1([CH2:20][C:21](Cl)=[O:22])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>>[C:14]1([CH2:20][C:21]([N:5]2[C:4]3=[N:3][N:2]=[CH:1][N:9]3[C:8]3[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=3[N:6]2[C:21](=[O:22])[CH2:20][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:22])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: O=C(Cl)Cc1ccccc1
Reactant: c1ccc2c(c1)NNc1nncn1-2
Product: O=C(Cc1ccccc1)N1c2ccccc2-n2cnnc2N1C(=O)Cc1ccccc1
Yield: 63.9 %

Procedure:
5 g (0.028 mole) of 4,5-dihydro-s-triazolo[3,4-c]benzo-as-triazine are reacted with 9.8 g (0.064 mole) of phenylacetyl chloride as described in Example 12. 7.33 g (64%) of the title compound are obtained; m.p.: 150°-151° C.