Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: FC(F)(F)S(O)(=O)=O.[CH3:9][N:10]([CH3:39])[C:11]1([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH2:16][CH2:15][C:14]([C:17]2[NH:18][C:19]3[C:24]([C:25]=2[CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=2)=[CH:23][CH:22]=[CH:21][CH:20]=3)=[CH:13][CH2:12]1.[OH-].[Na+]>C(Cl)Cl>[CH3:39][N:10]([CH3:9])[C:11]1([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH2:16][CH2:15][CH:14]([C:17]2[NH:18][C:19]3[C:24]([C:25]=2[CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=2)=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:13][CH2:12]1
Reactant: CN(C)C1(c2ccccc2)CC=C(c2[nH]c3ccccc3c2Cc2ccccn2)CC1
Agent: O=S(=O)(O)C(F)(F)F
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Product: CN(C)C1(c2ccccc2)CCC(c2[nH]c3ccccc3c2Cc2ccccn2)CC1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
(±)-Dimethyl-[1-phenyl-4-(3-pyridin-2-ylmethyl-1H-indol-2-yl)cyclohex-3-enyl]amine Trifluoromethanesulfonic acid (3.95 g, 2.30 ml, 26 mmol) was added to a solution of Ind-49 (2.17 g 10.4 mmol) and Ket-10 (2.70 g, 12.5 mmol) in anhydrous methylene chloride (80 ml), while cooling with ice. The reaction mixture was stirred at room temperature for 2 d and 0.5 M sodium hydroxide solution (50 ml) was then added and the mixture was stirred at room temperature for 2 h. The phases were separated, the aqueous phase was extracted with methylene chloride (3×30 ml) and the combined organic phases were dried with sodium sulfate and concentrated i. vac. The crude product (6.45 g) was purified by flash chromatography (400 g, 20×7.6 cm) with chloroform/methanol (9:1).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7](Cl)=[CH:6][CH:5]=1)([O-:3])=[O:2].C([NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=O>>[CH:17]1[CH:18]=[CH:19][C:14]([NH:13][C:7]2[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=2)=[CH:15][CH:16]=1
Reactant: O=CNc1ccccc1
Reactant: O=[N+]([O-])c1ccc(Cl)cc1
Product: O=[N+]([O-])c1ccc(Nc2ccccc2)cc1

Procedure:
combining in a reaction zone paranitrochlorobenzene and a molar excess of formanilide at condensation temperature for forming 4-nitrodiphenylamine and
Reaction SMILES: Br[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:17]=[N:18][CH:19]=[CH:20][CH:21]=2)(=[O:15])=[O:14])[CH:11]=[C:10]([CH:22]=[O:23])[CH:9]=1.O.[CH3:25][N:26](C)C=O>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:22]([C:10]1[CH:9]=[C:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[C:25]#[N:26])[N:12]([S:13]([C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)(=[O:15])=[O:14])[CH:11]=1)=[O:23]
Reactant: CN(C)C=O
Reactant: O=Cc1cc(-c2ccccc2Br)n(S(=O)(=O)c2cccnc2)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [C-]#N
Agent: [Zn+2]
Solvent: O
Product: N#Cc1ccccc1-c1cc(C=O)cn1S(=O)(=O)c1cccnc1
Yield: 63 %

Procedure:
A suspension of 5-(2-bromophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carbaldehyde (102 mg), zinc cyanide (61.0 mg) and tetrakis(triphenylphosphine)palladium (60.0 mg) in N,N-dimethylformamide (2 mL) was heated (100 W, 4 min 30 sec) using a microwave focused chemical synthesis reactor manufactured by CEM, water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=4:1→2:1) to give the title compound as a pale-yellow oil (yield 97.4 mg, 63%).
Reaction SMILES: [Si:1]([CH2:17][CH2:18][CH2:19][NH:20][CH2:21][CH2:22][NH2:23])([O:12][CH2:13]COC)([O:7][CH2:8]COC)[O:2][CH2:3]COC.[Si](CCCN)(OCC)(OCC)OCC.[Si](CCCN)(OCCOC)(OCCOC)OCCOC.[Si](CCCOCCCN)(OCC)(OCC)OCC.[Si](COCCN)(OCC)(OCC)OCC.[Si](CCCOCCN)(OCC)(OCC)OCC>>[Si:1]([CH2:17][CH2:18][CH2:19][NH:20][CH2:21][CH2:22][NH2:23])([O:7][CH3:8])([O:12][CH3:13])[O:2][CH3:3]
Reactant: COCCO[Si](CCCNCCN)(OCCOC)OCCOC
Agent: CCO[Si](CCCN)(OCC)OCC
Agent: CCO[Si](CCCOCCCN)(OCC)OCC
Agent: CCO[Si](CCCOCCN)(OCC)OCC
Product: CO[Si](CCCNCCN)(OC)OC

Procedure:
(CH3OCH2CH2O)3Si(CH2)3NH(CH2)2NH2 ; (C2H5O)3Si(CH2)3NH2 ; (CH3OCH2CH2O)3Si(CH2)3NH2 ; (C2H5O)3Si(CH2)3O(CH2)3NH2 ; (C2H5O)2C6H5Si(CH2)3O(CH2)3NH2 ; (C2H5O)3SiCH2O(CH2)2NH2 ; (C2H5O)3Si(CH2)3O(CH2)2NH2 ; and (C2H5O)2CH3Si(CH2)3NH2.
Reaction SMILES: [F:1][C:2]1[C:13]([CH3:14])=[CH:12][CH:11]=[CH:10][C:3]=1[C:4](N(OC)C)=[O:5].[CH3:15][O:16][C:17]1[CH:22]=[C:21]([O:23][CH3:24])[CH:20]=[CH:19][C:18]=1[Mg]Br>>[CH3:15][O:16][C:17]1[CH:22]=[C:21]([O:23][CH3:24])[CH:20]=[CH:19][C:18]=1[C:4]([C:3]1[CH:10]=[CH:11][CH:12]=[C:13]([CH3:14])[C:2]=1[F:1])=[O:5]
Reactant: CON(C)C(=O)c1cccc(C)c1F
Reactant: COc1ccc([Mg]Br)c(OC)c1
Product: COc1ccc(C(=O)c2cccc(C)c2F)c(OC)c1

Procedure:
Prepared according to Method A step B from 2-fluoro-3-methyl-N-methoxy-N-methyl-benzamide (2.84 g, 14.4 mmol) and 2,4-dimethoxyphenylmagnesium bromide (26 mL, 0.5 M in THF) to give 1.13 g of the title compound as a white solid.
Reaction SMILES: [C:1]1(=[O:8])[CH2:6][CH2:5][CH2:4][C:3](=[O:7])[CH2:2]1.[CH3:9][C:10]([CH3:15])([CH2:13]O)[CH2:11][OH:12]>C1(C)C=CC=CC=1>[CH3:9][C:10]1([CH3:15])[CH2:11][O:12][C:3]2([CH2:4][CH2:5][CH2:6][C:1](=[O:8])[CH2:2]2)[O:7][CH2:13]1
Reactant: CC(C)(CO)CO
Reactant: O=C1CCCC(=O)C1
Solvent: Cc1ccccc1
Product: CC1(C)COC2(CCCC(=O)C2)OC1

Procedure:
125 g (630 mmole) 3,3-dimethyl-1,5-dioxa-spiro[5,5] undecan-8-one, which was obtained by the azeotropic acetylation of cyclohexane-1,3-dione with 2,2-dimethylpropane-1,3-diol in toluene as a solvent using p-toluenesulphonic acid as a catalyst, and 59 g (630 mmole) dimethylammonium methylene chloride were stirred at room temperature in 400 ml of dry acetonitrile. After adding 1 ml acetyl chloride the mixture was stirred for a further 3 hours at room temperature, whereupon a clear colourless solution was obtained. 800 ml of dry ether were then added drop-wise to the reaction mixture, whereupon the hydrochloride crystallised out. 158 g of (18) were obtained (98% theoretical).
Reaction SMILES: [CH3:1][C:2]1[CH2:22][S:21][C@@H:5]2[C@H:6]([NH:9][C:10]([C@H:12]([NH2:20])[C:13]3[CH:14]=[CH:15][C:16]([OH:19])=[CH:17][CH:18]=3)=[O:11])[C:7](=[O:8])[N:4]2[C:3]=1[C:23]([OH:25])=[O:24].CN(C=[O:30])C>CN(C=O)C>[CH3:1][C:2]1[CH2:22][S:21][C@@H:5]2[C@H:6]([NH:9][C:10]([C@H:12]([NH2:20])[C:13]3[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=3)=[O:11])[C:7](=[O:8])[N:4]2[C:3]=1[C:23]([OH:25])=[O:24].[OH2:30]
Reactant: CN(C)C=O
Agent: CC1=C(C(=O)O)N2C(=O)[C@@H](NC(=O)[C@H](N)c3ccc(O)cc3)[C@H]2SC1
Product: O

Procedure:
400 ml of dichloromethane and 45.3 ml (327 mmol) of triethylamine were added to 35.0 g of 7-ADCA (163 mmol) and 41.5 ml (327 mmol) of trimethylchlorosilane were added dropwise over a few minutes without cooling while the temperature raised to 38° C. After refluxing for one hour at 38° to 40° C. the reaction mixture was cooled to -30° C. and then 82.2 g of cefadroxil-DMF solvate were obtained by following the same additional steps B and C of Example 3 for a yield of 98.8%. The structure was confirmed by IR and PMR spectra, indicating a high purity of the obtained product. Using the same process of Step D of Example 3, the cefadroxil-DMF solvate was converted into 41.5 g of cefadroxil-monohydrate. The structure was confirmed by IR and PMR spectra which indicated a high purity of the said product. According to a Karl Fisher test, the moisture content seemed to be 5.5%. From the mother liquor, an additional 23 g of DMF solvate could be obtained for an overall yield of 89.5% of cefadroxil monohydrate based on the starting 7-ADCA.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([CH3:14])=[N:12][NH:11][C:10](=O)[C:9]=2[C:16]2[C:21]([F:22])=[CH:20][C:19]([Cl:23])=[CH:18][N:17]=2)=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:26])=O>>[Cl:26][C:10]1[N:11]=[N:12][C:13]([CH3:14])=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[C:9]=1[C:16]1[C:21]([F:22])=[CH:20][C:19]([Cl:23])=[CH:18][N:17]=1
Reactant: Cc1n[nH]c(=O)c(-c2ncc(Cl)cc2F)c1-c1ccc(Cl)cc1
Reactant: O=P(Cl)(Cl)Cl
Product: Cc1nnc(Cl)c(-c2ncc(Cl)cc2F)c1-c1ccc(Cl)cc1
Temperature: 110 °C
Reaction time: 1.5 h
Yield: 69.7 %

Procedure:
0.3 g of 5-(4-chlorophenyl)-4-(5-chloro-3-fluoro-2-pyridyl)-6-methyl-2H-pyridazin-3-one and 10 g of phosphorus oxychloride were mixed. The mixture was stirred for 1.5 hours on an oil bath of 110° C. The reaction mixture was allowed to cool to room temperature, the, concentrated under reduced pressure. To the resultant residue were added ethyl acetate and ice-cooled sodium bicarbonate water. The mixture was stirred for about 5 minutes at room temperature, then, liquid-separated. The organic layer was washed with brine, and dried over anhydrous magnesium sulfate, then, concentrated under reduced pressure. 0.3 g of the resultant residue was subjected to silica gel column chromatography, to obtain 0.22 g of 3-chloro-5-(4-chlorophenyl)-4-(5-chloro-3-fluoro-2-pyridyl)-6-methylpyridazine (hereinafter, described as compound (14) of the present invention.).
Reaction SMILES: C[O:2][C:3]1[CH:8]=[C:7]([OH:9])[CH:6]=[CH:5][C:4]=1[C:10]1[CH:18]=[C:17]2[C:13]([C:14]([C:19]3[NH:23][C:22]4[CH:24]=[CH:25][CH:26]=[CH:27][C:21]=4[N:20]=3)=[N:15][NH:16]2)=[CH:12][CH:11]=1>[Cl-].[NH+]1C=CC=CC=1>[NH:23]1[C:22]2[CH:24]=[CH:25][CH:26]=[CH:27][C:21]=2[N:20]=[C:19]1[C:14]1[C:13]2[C:17](=[CH:18][C:10]([C:4]3[CH:5]=[CH:6][C:7]([OH:9])=[CH:8][C:3]=3[OH:2])=[CH:11][CH:12]=2)[NH:16][N:15]=1
Reactant: COc1cc(O)ccc1-c1ccc2c(-c3nc4ccccc4[nH]3)n[nH]c2c1
Agent: [Cl-]
Agent: c1cc[nH+]cc1
Product: Oc1ccc(-c2ccc3c(-c4nc5ccccc5[nH]4)n[nH]c3c2)c(O)c1
Yield: 59 %

Procedure:
6-(2-methoxy-4-hydroxyphenyl)-3-1H-benzoimidazol-2-yl-1H-indazole, prepared in example 24(d), (46 mg, 0.13 mmol) was heated in pyridinium chloride (0.5 g) at 180° C. for 2 h. The reaction was allowed to cool, and was quenched with sat. NaHCO3 (15 mL) and extracted with EtOAc (2×20 mL). Organics were dried (Na2SO4) and concentrated in vacuo. Purification by silica gel chromatography (60% THF/hexanes) gave 26 mg (59%) of the title compound as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 13.49 (s, 1H), 12.94 (s, 1H), 9.49 (s, 1H), 9.39 (s, 1H), 8.43 (d, 1H, J=8.4 Hz), 7.71–7.74 (m, 2H), 7.50 (d, 1H, J=6.9 Hz), 7.43 (dd, 1H, J=8.4, 1.2 Hz), 7.16–7.23 (m, 3H), 6.45 (d, 1H, J=2.1 Hz), 6.35 (dd, 1H, J=8.4, 2.1 Hz). MS (ES) [m+H]/z calc'd 343. found 343. [m−H]/z calc'd 341. found 341.
Reaction SMILES: Cl[CH2:2][C:3]([N:5]1[CH2:9][C:8](=[O:10])[N:7]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[C:12]=2[CH3:18])[CH2:6]1)=[O:4].[NH:19]1[C:23]2=[N:24][CH:25]=[CH:26][CH:27]=[C:22]2[CH:21]=[N:20]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.C(OCC)(=O)C>[Cl:17][C:13]1[C:12]([CH3:18])=[C:11]([N:7]2[C:8](=[O:10])[CH2:9][N:5]([C:3](=[O:4])[CH2:2][N:20]3[CH:21]=[C:22]4[C:23]([N:24]=[CH:25][CH:26]=[CH:27]4)=[N:19]3)[CH2:6]2)[CH:16]=[CH:15][CH:14]=1
Reactant: c1cnc2[nH]ncc2c1
Reactant: Cc1c(Cl)cccc1N1CN(C(=O)CCl)CC1=O
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Cc1c(Cl)cccc1N1CN(C(=O)Cn2cc3cccnc3n2)CC1=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 1-(2-Chloro-acetyl)-3-(3-chloro-2-methyl-phenyl)-imidazolidin-4-one (230 mg, 0.8 mmol, 1 eq), 1H-Pyrazolo[3,4-b]pyridine (96 mg, 0.8 mmol, 1 eq), Cesium carbonate (653 mg, 2.0 mmol, 2.5 eq) in DMF (6 ml) was stirred at room temperature overnight. It was diluted with ethyl acetate, washed with water and purified with HPLC to give the desired product. LCMS observed for (M+H)+: 370.1
Reaction SMILES: [FH:1].[NH:2]([C:6]1[C:23](=[O:24])[C@@H:22]2O[CH:21]2[C@@:20]2([CH3:26])[C:7]=1[CH:8]=[CH:9][C@@H:10]1[C@@H:19]2[CH2:18][CH2:17][C@@:15]2([CH3:16])[C@H:11]1[CH2:12][CH2:13][C:14]2=[O:27])[C:3]([CH3:5])=[O:4].F.O1CCCC1.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.C(Cl)(Cl)Cl>[C:3]([NH:2][C:6]1[C:23](=[O:24])[C:22]([F:1])=[CH:21][C@@:20]2([CH3:26])[C:7]=1[CH:8]=[CH:9][C@@H:10]1[C@@H:19]2[CH2:18][CH2:17][C@@:15]2([CH3:16])[C@H:11]1[CH2:12][CH2:13][C:14]2=[O:27])(=[O:4])[CH3:5]
Reactant: F
Reactant: CC(=O)NC1=C2C=C[C@H]3[C@@H]4CCC(=O)[C@@]4(C)CC[C@@H]3[C@@]2(C)C2O[C@H]2C1=O
Agent: *CC*
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClC(Cl)Cl
Solvent: C1CCOC1
Product: CC(=O)NC1=C2C=C[C@@H]3[C@H](CC[C@]4(C)C(=O)CC[C@@H]34)[C@@]2(C)C=C(F)C1=O
Temperature: -60 °C
Yield: 70 %

Procedure:
To a solution of anhydrous hydrogen fluoride (6 g) in tetrahydrofuran (11.8 g) and chloroform (6 ml) contained in a screw-capped polyethylene bottle chilled to about -60° C. was added a solution of 4-acetamino-1,2α-epoxy-androsta-4,6-diene-3,17-dione (3.554 g, 10 mmol) in chloroform (30 ml) likewise chilled to about -60° C. The hydrogen fluoride-tetrahydrofuran reagent was immersed in an acetone-dry ice bath while the steroid was being added. Additional chloroform (6 ml) was used to aid the transfer of the epoxide. Subsequently the reaction mixture was maintained at -30° C. for 4 h and then added gradually to a well agitated mixture of an aqueous solution of potassium carbonate, chloroform and ice. The organic layer was separated, the alkaline aqueous layer back-extracted twice with chloroform and the combined organic layers were evaporated to dryness. The residue was submitted to flash chromatography with ethyl acetate-ethanol to give pure 4-acetylamino-2-fluoroandrosta-1,4,6-triene-3,17-dione in 70% yield (2.502 g).
Reaction SMILES: [CH3:1][Sn](C)(C)C.[OH:6][C:7]1[C:16]2[C:11](=[C:12]([NH2:17])[CH:13]=[CH:14][CH:15]=2)[C:10](Br)=[CH:9][N:8]=1>>[OH:6][C:7]1[C:16]2[C:11](=[C:12]([NH2:17])[CH:13]=[CH:14][CH:15]=2)[C:10]([CH3:1])=[CH:9][N:8]=1
Reactant: C[Sn](C)(C)C
Reactant: Nc1cccc2c(O)ncc(Br)c12
Product: Cc1cnc(O)c2cccc(N)c12

Procedure:
According to the method of Example 106, Step A, a methylation reaction with tetramethyltin was performed by using Intermediate 138 to obtain the title compound.
Reaction SMILES: [CH3:1][C:2]1([CH3:25])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:14]=[CH:13][C:12]([C@H:15]([NH:17]C(=O)OC(C)(C)C)[CH3:16])=[CH:11][CH:10]=2)[O:3]1.[ClH:26]>C(Cl)Cl.O1CCOCC1>[ClH:26].[CH3:8][C:6]1([CH3:7])[C:2]([CH3:1])([CH3:25])[O:3][B:4]([C:9]2[CH:10]=[CH:11][C:12]([C@H:15]([NH2:17])[CH3:16])=[CH:13][CH:14]=2)[O:5]1
Reactant: C[C@@H](NC(=O)OC(C)(C)C)c1ccc(B2OC(C)(C)C(C)(C)O2)cc1
Agent: Cl
Solvent: ClCCl
Solvent: C1COCCO1
Product: C[C@@H](N)c1ccc(B2OC(C)(C)C(C)(C)O2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
(R)-tert-butyl 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethylcarbamate (727 mg, 2.09 mmol) was dissolved in CH2Cl2 (4 mL) and a solution of HCl in dioxane (4M, 4 mL). The mixture was stirred at room temperature for overnight. LCMS indicated the reaction was complete. The reaction solution was concentrated in vacuo to afford the title compound as a white solid (1.00 g).
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:9]=[CH:8][C:7]([Br:10])=[CH:6][CH:5]=1)=[O:3].[CH2:11](O)[CH2:12][OH:13]>C1C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>[Br:10][C:7]1[CH:8]=[CH:9][C:4]([C:2]2([CH3:1])[O:13][CH2:12][CH2:11][O:3]2)=[CH:5][CH:6]=1
Reactant: CC(=O)c1ccc(Br)cc1
Reactant: OCCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: c1ccccc1
Product: CC1(c2ccc(Br)cc2)OCCO1
Temperature: 25 °C
Yield: 94.6 %

Procedure:
A mixture of 4-bromoacetophenone (1 Scheme 19, 20.0 g, 0.1 mol) and ethylene glycol (12.5 g, 0.2 mol) and p-toluenesulfonic acid (200 mg) in benzene (400 mL) was refluxed in a Dean Stark apparatus for 6 h. The reaction mixture was cooled to room temperature, and the solution was extracted with H2O/ethyl acetate. The organic layer was washed with brine, dried (Na2SO4), and concentrated to give a colorless oil (23 g, 96%); 1H NMR (300 MHz, CDCl3) δ 1.63 (s, 3 H), 3.76 (m, 2 H), 4.04 (m, 2 H), 7.37 (d, J=8.40 Hz, 2 H), 7.47 (d, J=8.40 Hz, 2 H); 13C NMR (75 MHz, CDCl3) 27.6, 64.5 (2C), 108.4, 121.9, 127.2 (2C), 131.4 (2C), 142.5
Reaction SMILES: [CH3:1][C:2]1[N:3]=[CH:4][O:5][C:6]=1[C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][N:8]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Cl:27]C(Cl)(Cl)C(Cl)(Cl)Cl>C1COCC1>[Cl:27][C:4]1[O:5][C:6]([C:7]2[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:14])[F:15])=[CH:9][N:8]=2)=[C:2]([CH3:1])[N:3]=1
Reactant: ClC(Cl)(Cl)C(Cl)(Cl)Cl
Reactant: Cc1ncoc1-c1ccc(C(F)(F)F)cn1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: Cc1nc(Cl)oc1-c1ccc(C(F)(F)F)cn1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A solution of Example 34D (3.37 g, 14.8 mmol) in THF (50 mL) was cooled to −78° C., followed by addition of LiHMDS (1M in THF, 16.3 ml, 16.3 mmol). After 0.5 hr at −78° C., hexachloroethane (3.50 g, 14.8 mmol) was added in one portion. The reaction was allowed to stir overnight with gradual warming to room temperature. The reaction was quenched with water and extracted with EtOAc. The combined organic extract was washed with water and brine, and then filtered through celite filter aid. The filtrate was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was dissolved in minimal toluene and place on silica gel (Analogix® 25×115 column) and eluted with 2 column lengths of hexanes, then 5% to 50% EtOAc/hexanes. The result was 2.20 g (57%) of the title compound as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 8.88 (m, 1H), 8.00-7.93 (m, 1H), 7.72-7.66 (m, 1H), 2.63 (s, 3H). MS (DCI+) m/z 263 (M+H).
Reaction SMILES: CC(C)CCN.[N:7]1[CH:8]=[CH:9][N:10]2[CH:15]=[CH:14][C:13]([CH2:16][NH:17][C:18](=[O:28])[NH:19][C:20]3[S:21][C:22]([C:25]([OH:27])=O)=[CH:23][N:24]=3)=[CH:12][C:11]=12.[N+:29]([C:32]1C=[CH:39][C:35](C(O)=O)=[CH:34][CH:33]=1)([O-])=O>>[N:7]1[CH:8]=[CH:9][N:10]2[CH:15]=[CH:14][C:13]([CH2:16][NH:17][C:18]([NH:19][C:20]3[S:21][C:22]([C:25]([N:29]4[CH2:32][CH2:33][CH2:34][CH2:35][CH2:39]4)=[O:27])=[CH:23][N:24]=3)=[O:28])=[CH:12][C:11]=12
Reactant: O=C(NCc1ccn2ccnc2c1)Nc1ncc(C(=O)O)s1
Reactant: O=C(O)c1ccc([N+](=O)[O-])cc1
Agent: CC(C)CCN
Product: O=C(NCc1ccn2ccnc2c1)Nc1ncc(C(=O)N2CCCCC2)s1

Procedure:
The title compound was prepared as described in Example 1A, substituting piperidine for 3-methylbutan-1-amine and 2-(3-(imidazo[1,2-a]pyridin-7-ylmethyl)ureido)thiazole-5-carboxylic acid for 4-nitrobenzoic acid. 1H NMR (300 MHz, DMSO-d6) ppm 10.91 (s, 1H), 8.49 (d, J=7.1 Hz, 1H), 7.89 (s, 1H), 7.62 (s, 1H), 7.52 (d, J=0.8 Hz, 1H), 7.39 (s, 1H), 7.11-7.18 (m, 1H), 6.83 (dd, J=6.9, 1.4 Hz, 1H), 4.39 (d, J=6.0 Hz, 2H), 3.54-3.61 (m, 4H), 1.47-1.67 (m, 6H); MS (ESI(+)) m/e 385 (M+H)+.
Reaction SMILES: CS[C:3]1[NH:12][C:11](=[O:13])[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[N:4]=1.Cl.[CH3:15][O:16][C:17]1[CH:18]=[C:19]([N:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)[CH:20]=[CH:21][CH:22]=1.C(N(CC)CC)C>C(O)CC(C)C>[CH3:15][O:16][C:17]1[CH:18]=[C:19]([N:23]2[CH2:28][CH2:27][N:26]([C:3]3[NH:12][C:11](=[O:13])[C:10]4[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=4[N:4]=3)[CH2:25][CH2:24]2)[CH:20]=[CH:21][CH:22]=1
Reactant: CSc1nc2c(c(=O)[nH]1)CCCC2
Reactant: COc1cccc(N2CCNCC2)c1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CC(C)CCO
Product: COc1cccc(N2CCN(c3nc4c(c(=O)[nH]3)CCCC4)CC2)c1

Procedure:
2-Methylsulfanyl-5,6,7,8-tetrahydro-3H-quinazolin-4-one (100 mg; 0.51 mmol), 1-(3-methoxyphenyl)piperazine hydrochloride (116.5 mg; 0.51 mmol) and triethylamine (141.3 μl; 1.02 mmol) are reacted in isoamyl alcohol (1 ml) in accordance with the procedure for Example 1 (reaction time 4 h) and worked up; yield: 79 mg (45%), crystals;
Reaction SMILES: [CH3:1][N:2]1[CH:11]2[C:6]([CH3:17])([C:7]3[CH:15]=[CH:14][C:13]([SH:16])=[CH:12][C:8]=3[CH2:9][CH2:10]2)[CH2:5][CH2:4][C:3]1=[O:18].C(=O)([O-])[O-].[K+].[K+].Cl[C:26]1[S:27][C:28]2[CH:34]=[CH:33][CH:32]=[C:31]([O:35][CH3:36])[C:29]=2[N:30]=1.CN(C)C=O>C(OCC)(=O)C>[CH3:1][N:2]1[C@H:11]2[C@@:6]([CH3:17])([C:7]3[CH:15]=[CH:14][C:13]([S:16][C:26]4[S:27][C:28]5[CH:34]=[CH:33][CH:32]=[C:31]([O:35][CH3:36])[C:29]=5[N:30]=4)=[CH:12][C:8]=3[CH2:9][CH2:10]2)[CH2:5][CH2:4][C:3]1=[O:18]
Reactant: CN1C(=O)CCC2(C)c3ccc(S)cc3CCC12
Reactant: COc1cccc2sc(Cl)nc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COc1cccc2sc(Sc3ccc4c(c3)CC[C@H]3N(C)C(=O)CC[C@]43C)nc12
Yield: 66.3 %

Procedure:
A 15 mL round bottom flask was charged with (+)-(4aR)-10bR)-4-methyl-8-mercapto-10b-methyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolin-3-one (100 mg, 0.38 mmol), potassium carbonate (158 mg, 1.14 mmol), 2-chloro-4-methoxybenzothiazole (92 mg, 0.46 mmol) and 1.5 mL of anhydrous dimethylformamide, fitted with a reflux condenser, and the stirred mixture was heated at 60°, under nitrogen, for 18 h. The mixture was cooled, diluted with ethyl acetate (75 mL) and washed with brine (4×25 mL). The combined organic extracts were dried over sodium sulfate, concentrated, and purified by silica gel chromatography (ethyl acetate eluent) to give 107 mg (66%) of the title compound as an off white solid. mp 200°-205°. FDMS: m/e=424. α[D]589 =+60.56 (c=0.96, chloroform).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][CH:4]=1.[CH2:11]=[CH: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][CH2:26][CH2:27][CH3:28]>>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][C:4]=1[CH:27]([CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH3:11])[CH3:28]
Reactant: C=CCCCCCCCCCCCCCCCC
Reactant: COc1ccc(OC)cc1
Product: CCCCCCCCCCCCCCCCC(C)c1cc(OC)ccc1OC
Yield: 52.8 %

Procedure:
33.5 g of p-dimethoxy benzene, 68.0 g of 1-octadecene and 7.7 g of dry silica alumina were heated at 225°-240° C. for 6 hours. After being allowed to cool, the reaction mixture was extracted with ethyl acetate and filtered. The solvent was distilled off under reduced pressure and the residue was distilled under reduced pressure to give 50.0 g of 2-sec-octadecylhydroquinone dimethyl ether having b.p. 220°-223° C./2.5 mmHg.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:10][C@H:9]2[NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:4][CH:3]=1.[CH2:19]([C:26]1[CH:27]=[C:28]([CH:32]=[CH:33][CH:34]=1)[C:29](O)=[O:30])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1>C(#N)C.O.C(N(CC)CC)C>[CH2:19]([C:26]1[CH:27]=[C:28]([C:29]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([C@@H:8]3[CH2:10][C@H:9]3[NH:11][C:12](=[O:18])[O:13][C:14]([CH3:15])([CH3:17])[CH3:16])=[CH:4][CH:3]=2)=[O:30])[CH:32]=[CH:33][CH:34]=1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: CC(C)(C)OC(=O)N[C@@H]1C[C@H]1c1ccc(N)cc1
Reactant: O=C(O)c1cccc(Cc2ccccc2)c1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: CC#N
Solvent: O
Product: CC(C)(C)OC(=O)N[C@@H]1C[C@H]1c1ccc(NC(=O)c2cccc(Cc3ccccc3)c2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 70.7 %

Procedure:
To a solution of tert-butyl [trans-2-(4-aminophenyl)cyclopropyl]carbamate (100 mg) described in a document (J. Am. Chem. Soc., 2010, 132, 6827.) in acetonitrile (4 mL) were added 3-benzylbenzoic acid (103 mg) described in a document (J. Org. Chem. 2001, 66, 2874.), N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (93 mg), 1-hydroxybenzotriazole (65.3 mg) and triethylamine (140 μL). The mixture was stirred at room temperature overnight and water was added. The mixture was extracted with ethyl acetate, and the extract was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was recrystallized (hexane/ethyl acetate) to give the title compound (126 mg).