Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C@@H:1]12[CH2:6][C@@H:5]1[C:4](=[O:7])[O:3][C:2]2=[O:8].[CH3:9][C:10]([OH:13])([CH3:12])[CH3:11]>>[C:10]([O:13][C:4]([C@H:5]1[CH2:6][C@H:1]1[C:2]([OH:8])=[O:3])=[O:7])([CH3:12])([CH3:11])[CH3:9]
Reactant: O=C1OC(=O)[C@@H]2C[C@H]12
Reactant: CC(C)(C)O
Product: CC(C)(C)OC(=O)[C@H]1C[C@H]1C(=O)O
Temperature: 110 °C
Reaction time: 60 h

Procedure:
A mixture of rel-(1R,5S)-3-oxabicyclo[3.1.0]hexane-2,4-dione (1.1 g) and 2-methyl-2-propanol (10 ml) was stirred at 110° C. for 2.5 days. The reaction mixture was concentrated under reduced pressure to obtain rel-(1R,2S)-2-(tert-butoxycarbonyl)cyclopropanecarboxylic acid (1.8 g).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[CH:4][C:3]=1[O:11][CH3:12].[C:13](OC(=O)C)(=[O:15])[CH3:14]>[Fe]>[Br:1][C:2]1[CH:7]=[C:6]([NH:8][C:13](=[O:15])[CH3:14])[CH:5]=[CH:4][C:3]=1[O:11][CH3:12]
Reactant: CC(=O)OC(C)=O
Reactant: COc1ccc([N+](=O)[O-])cc1Br
Agent: [Fe]
Product: COc1ccc(NC(C)=O)cc1Br

Procedure:
By the reaction in the same manner as in Example 33-(i) using 2-bromo-4-nitroanisole (5.41 g), iron powder (6.49 g) and acetic anhydride (4.4 ml), the title compound (4.87 g) was obtained as a colorless powder crystals.
Reaction SMILES: [CH:1]1[N:5]=[CH:4][N:3]([C:6](N2C=NC=C2)=[O:7])[CH:2]=1.[C:13]([O:17][C:18](=[O:23])[NH:19][CH2:20][CH2:21][OH:22])([CH3:16])([CH3:15])[CH3:14]>C(Cl)Cl>[N:3]1([C:6]([O:22][CH2:21][CH2:20][NH:19][C:18]([O:17][C:13]([CH3:16])([CH3:14])[CH3:15])=[O:23])=[O:7])[CH:2]=[CH:1][N:5]=[CH:4]1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: CC(C)(C)OC(=O)NCCO
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NCCOC(=O)n1ccnc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of CDI (218 mg, 1.30 mmol) in DCM (4 mL) was added a solution of tert-butyl(2-hydroxyethyl)carbamate (0.22 mL, 1.37 mmol) in DCM (1 mL). After stirring at rt for 1 h, the reaction mixture was used directly in DCM for the next step.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)[CH:6]=[CH:7][CH:8]=1)#[N:2].[H-].[Na+].C1(C)C=CC(S(O[CH2:28][C@H:29]([O:38][C:39](=[O:46])[C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH2:30][CH2:31][C:32]2[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=2)(=O)=O)=CC=1.O>CN(C)C=O>[N:34]1[CH:35]=[CH:36][CH:37]=[C:32]([CH2:31][CH2:30][C@@H:29]([O:38][C:39](=[O:46])[C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH2:28][O:15][C:12]2[CH:13]=[CH:14][C:9]([C:5]3[CH:6]=[CH:7][CH:8]=[C:3]([C:1]#[N:2])[CH:4]=3)=[CH:10][CH:11]=2)[CH:33]=1
Reactant: Cc1ccc(S(=O)(=O)OC[C@@H](CCc2cccnc2)OC(=O)c2ccccc2)cc1
Reactant: N#Cc1cccc(-c2ccc(O)cc2)c1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: N#Cc1cccc(-c2ccc(OC[C@@H](CCc3cccnc3)OC(=O)c3ccccc3)cc2)c1
Reaction time: 0.5 h
Yield: 75 %

Procedure:
Solid 3'-cyanobiphenyl-4-ol (0.20 g, Example 36b)) was added to a suspension of sodium hydride (60%, 0.049 g) in dimethylformamide (5 ml) and the resulting solution stirred for 30 minutes. Solid (2R)-2-benzoyloxy-4-(3-pyridyl)-1-butyl para-toluenesulfonate (0.43 g) was then added and the mixture stirred at 60° C. for 2 hours. The mixture was cooled, poured into water (50 ml) and extracted with ethyl acetate. The combined organic extracts were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue obtained was purified by column chromatography over silica eluting with diethyl ether to give the sub-title compound as an oil (0.34 g).
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[CH:5][CH:4]=[N:3]1.[Cl:7][S:8](O)(=[O:10])=[O:9]>>[CH3:1][N:2]1[CH:6]=[C:5]([S:8]([Cl:7])(=[O:10])=[O:9])[CH:4]=[N:3]1
Reactant: Cn1cccn1
Reactant: O=S(=O)(O)Cl
Product: Cn1cc(S(=O)(=O)Cl)cn1
Temperature: 0 °C

Procedure:
Add 1-methyl-1H-pyrazole (100 g, 1.18 mol) dropwise to chlorosulfonic acid (325 mL, 4.84 mol) stirring at 0° C. under nitrogen atmosphere. Heat reaction mixture at 110° C. for 3 hr. Cool to room temperature, then pour carefully into crushed ice with stirring. Recover the resulting white solid by vacuum filtration, wash with water, and dry under vacuum. Use the resulting material (72.2 g, 33%) without further purification.
Reaction SMILES: [C:1]([C:3]1[C:8]([NH:9][C:10]2[S:14][N:13]=[C:12]([CH3:15])[CH:11]=2)=[CH:7][C:6]([NH:16][C@H:17]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=2)[C:18]([NH2:20])=[O:19])=[C:5]([F:28])[CH:4]=1)#[N:2].[OH-].[Na+].OO.CC(O)=[O:35]>CCO.CS(C)=O>[NH2:20][C:18](=[O:19])[C@H:17]([NH:16][C:6]1[C:5]([F:28])=[CH:4][C:3]([C:1]([NH2:2])=[O:35])=[C:8]([NH:9][C:10]2[S:14][N:13]=[C:12]([CH3:15])[CH:11]=2)[CH:7]=1)[CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1
Reactant: Cc1cc(Nc2cc(N[C@H](Cc3ccccn3)C(N)=O)c(F)cc2C#N)sn1
Reactant: CC(=O)O
Agent: OO
Agent: [Na+]
Agent: [OH-]
Solvent: CS(C)=O
Solvent: CCO
Product: Cc1cc(Nc2cc(N[C@H](Cc3ccccn3)C(N)=O)c(F)cc2C(N)=O)sn1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a solution of (R)-2-(4-cyano-2-fluoro-5-(3-methylisothiazol-5-ylamino)phenylamino)-3-(pyridin-2-yl)propanamide (53 mg, 0.133 mmol) in EtOH (1 mL) and DMSO (0.5 mL), aq. 1N NaOH (0.5 mL, 0.50 mmol) and aq. H2O2 (50%, 0.5 mL) were added. The mixture was stirred at room temperature for 15 min. HOAc (0.5 mL) was added. The mixture was purified by HPLC to give the titled compound (16 mg). MS 415.1 (M+H); UV 214.4, 278.0, 302.6 nm.
Reaction SMILES: Cl.[CH2:2]([NH2:10])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[S-:11][C:12]#[N:13].[NH4+]>BrC1C=CC=CC=1.O>[CH2:2]([NH:10][C:12]([NH2:13])=[S:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: N#C[S-]
Reactant: NCCc1ccccc1
Agent: Cl
Agent: [NH4+]
Solvent: O
Solvent: Brc1ccccc1
Product: NC(=S)NCCc1ccccc1
Temperature: 25 °C
Yield: 89 %

Procedure:
Phenethylamine hydrochloride (257 grams, 1.63 moles) and ammonium thiocyanate (123.6 grams, 1.63 moles) were heated to 160° C. in 340 ml bromobenzene under nitrogen. After heating for 90 minutes, the mixture was cooled to room temperature and then to 5° C. This procedure was repeated with a further batch of 257 grams of phenethylamine hydrochloride. The combined solids obtained in the above reaction were stirred in 1.5 l water and filtered. Recrystallization from isopropyl alcohol yielded 261.5 grams (45%) N-phenethylthiourea, m.p. 132°-134°.
Reaction SMILES: [CH2:1]([O:3][C:4]([CH2:6][CH2:7][C:8]1[C:9]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[N:10][N:11]([CH2:13][C:14]2[CH:15]=[C:16]([CH:20]=[CH:21][CH:22]=2)[C:17](O)=[O:18])[CH:12]=1)=[O:5])[CH3:2].[F:29][C:30]([F:40])([F:39])[C:31]1[CH:38]=[CH:37][C:34]([CH2:35][NH2:36])=[CH:33][CH:32]=1.O.ON1C2C=CC=CC=2N=N1.CCN=C=NCCCN(C)C>O.CN(C)C=O>[C:23]1([C:9]2[C:8]([CH2:7][CH2:6][C:4]([O:3][CH2:1][CH3:2])=[O:5])=[CH:12][N:11]([CH2:13][C:14]3[CH:22]=[CH:21][CH:20]=[C:16]([C:17]([NH:36][CH2:35][C:34]4[CH:37]=[CH:38][C:31]([C:30]([F:39])([F:40])[F:29])=[CH:32][CH:33]=4)=[O:18])[CH:15]=3)[N:10]=2)[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1
Reactant: NCc1ccc(C(F)(F)F)cc1
Reactant: CCOC(=O)CCc1cn(Cc2cccc(C(=O)O)c2)nc1-c1ccccc1
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)CCc1cn(Cc2cccc(C(=O)NCc3ccc(C(F)(F)F)cc3)c2)nc1-c1ccccc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 90.8 %

Procedure:
A mixture of 3-[4-(2-ethoxycarbonylethyl)-3-phenyl-1H-pyrazol-1-ylmethyl]benzoic acid (700 mg), 4-trifluoromethylbenzylamine (390 mg), 1-hydroxybenzotriazole monohydrate (340 mg), WSC (430 mg), and N,N-dimethylformamide (30 ml) was stirred at room temperature for 18 hours. The reaction mixture was poured into water, which was extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried (MgSO4), and concentrated. The residue was subjected to silica gel column chromatography, and ethyl 3-[3-phenyl-1-[3-(4-trifluoromethylbenzylaminocarbonyl)benzyl]-1H-pyrazol-4-yl]propionate (900 mg, yield: 91%) was obtained as an oily substance from the fraction eluted with acetone-hexane (1:2, volume ratio).
Reaction SMILES: Cl[S:2]([C:5]1[S:9][C:8]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][CH2:17][CH3:18])=[CH:12][CH:11]=2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].[NH2:19][C:20]1[O:24][N:23]=[C:22]([CH3:25])[C:21]=1[Br:26]>CO.C(Cl)(Cl)Cl>[Br:26][C:21]1[C:22]([CH3:25])=[N:23][O:24][C:20]=1[NH:19][S:2]([C:5]1[S:9][C:8]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][CH2:17][CH3:18])=[CH:12][CH:11]=2)=[CH:7][CH:6]=1)(=[O:4])=[O:3]
Reactant: Cc1noc(N)c1Br
Reactant: CCCc1ccc(-c2ccc(S(=O)(=O)Cl)s2)cc1
Solvent: ClC(Cl)Cl
Solvent: CO
Product: CCCc1ccc(-c2ccc(S(=O)(=O)Nc3onc(C)c3Br)s2)cc1

Procedure:
N-(4-bromo-3-methyl-5-isoxazolyl)-5-(4-propylphenyl)thiophene-2-sulfonamide was prepared in the same manner as described in Example 2. Reaction of 5-chlorosulfonyl-2-(4-propylphenyl)thiophene (260 mg, 0.87 mmol) with 5-amino-4-bromo-3-methylisoxazole (161 mg, 0.91 mmol) yielded after flash chromatography using 10% MeOH/CHCl3 a brown solid (76.1 mg) which was further purified using preparative HPLC to give the pure sulfonamide as a tan colored oil.
Reaction SMILES: [C:1]([CH2:7][C:8]#[N:9])(=O)[C:2]([CH3:5])([CH3:4])[CH3:3].[C:10]([NH:13][NH2:14])([NH2:12])=[NH:11].[ClH:15]>CO.C(O)(=O)C>[ClH:15].[NH2:9][C:8]1[N:13]([C:10]([NH2:12])=[NH:11])[N:14]=[C:1]([C:2]([CH3:5])([CH3:4])[CH3:3])[CH:7]=1
Reactant: CC(C)(C)C(=O)CC#N
Reactant: N=C(N)NN
Agent: Cl
Solvent: CC(=O)O
Solvent: CO
Product: CC(C)(C)c1cc(N)n(C(=N)N)n1
Yield: 33.8 %

Procedure:
A solution of 1.26 g of pivaloylacetonitrile and 1.37 g of aminoguanidine hydrochloride in 15 ml of methanol and 15 ml of acetic acid was heated under reflux for 5 hours. The solvents were removed by distillation under reduced pressure, and the resulting residue was purified by silica gel chromatography (eluent: chloroform/methanol=5/1) and then recrystallized from ethanol-ether to obtain 0.74 g of 5-amino-3-(1,1-dimethylethyl)-1H-pyrazole-1-carboxamidine hydrochloride having the following physico-chemical properties:
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][C:5]2[S:10]C(C(F)(F)F)C(C(OCC)=O)=[CH:7][C:6]=2[CH:20]=1.[OH-:21].[Na+]>C1COCC1.C(O)C>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([SH:10])=[C:6]([CH:20]=1)[CH:7]=[O:21]
Reactant: CCOC(=O)C1=Cc2cc(C)ccc2SC1C(F)(F)F
Reactant: [OH-]
Agent: [Na+]
Solvent: CCO
Solvent: C1CCOC1
Product: Cc1ccc(S)c(C=O)c1
Temperature: 25 °C
Reaction time: 88 h
Yield: 51.1 %

Procedure:
The ester from Step 2 (0.55 g 1.8 mmol) was dissolved in THF (1.5 mL) and ethanol (1.5 mL), treated with 2.5 N sodium hydroxide (1.5 mL, 3.8 mmol), and stirred at room temperature for 88 hours. The reaction mixture was concentrated in vacuo, acidified with 3 N HCl, filtered, and recrystallized from diethyl ether/petroleum ether to yield the title compound as a yellow solid (0.14 g, 28%): mp 180.8-184.2° C. 1H NMR (acetone-d6/300 MHz) 7.95 (s, 1H), 7.42 (s, 1H), 7.31 (d, 1H, J=8.1 Hz), 7.25 (d, 1H, J=8.1 Hz), 4.94 (q, 1H, J=8.7 Hz), 2.34 (s, 3H). FABLRMS m/z 281 (M+Li). EIHRMS m/z 274.0250 (M+, Calc'd 274.0275). Anal. Calc'd for C12H9F3O2S: C, 52.55; H, 3.31. Found: C, 52.54; H, 3.35.
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]([N:12]3[C@@H:21]4[C@@H:16]([C:17]5[CH:25]=[CH:24][C:23]([C:26]([OH:28])=O)=[CH:22][C:18]=5[CH2:19][CH2:20]4)[CH2:15][CH2:14][CH2:13]3)=[O:11])=[CH:9][C:4]=2[N:3]=[CH:2]1.[CH3:29][NH2:30]>>[CH3:29][NH:30][C:26]([C:23]1[CH:24]=[CH:25][C:17]2[C@@H:16]3[C@H:21]([CH2:20][CH2:19][C:18]=2[CH:22]=1)[N:12]([C:10]([C:8]1[CH:7]=[CH:6][C:5]2[NH:1][CH:2]=[N:3][C:4]=2[CH:9]=1)=[O:11])[CH2:13][CH2:14][CH2:15]3)=[O:28]
Reactant: O=C(O)c1ccc2c(c1)CC[C@H]1[C@@H]2CCCN1C(=O)c1ccc2[nH]cnc2c1
Reactant: CN
Product: CNC(=O)c1ccc2c(c1)CC[C@H]1[C@@H]2CCCN1C(=O)c1ccc2[nH]cnc2c1
Yield: 75 %

Procedure:
The title compound is prepared from cis-4-(1H-benzoimidazole-5-carbonyl)-1,2,3,4,4a,5,6,10b-octahydro-benzo[f]quinoline-8-carboxylic acid and methylamine (2 mol/L in tetrahydrofuran) following a procedure analogous to that described in Example 1. Yield: 75% of theory; LC (method 1): tR=1.91 min; Mass spectrum (ESI+): m/z=389 [M+H]+.
Reaction SMILES: [CH2:1]([N:8]1[CH2:12][CH2:11][C@@H:10]([N:13]=[CH:14][C:15]2[CH:28]=[CH:27][C:18]3[N:19]([CH2:25][CH3:26])[C:20](=[O:24])[N:21]([CH2:22][CH3:23])[C:17]=3[CH:16]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[CH3:33][N:34]([CH3:37])C=O>>[CH2:1]([N:8]1[CH2:12][CH2:11][C@@H:10]([N:13]2[C:14]([C:15]3[CH:28]=[CH:27][C:18]4[N:19]([CH2:25][CH3:26])[C:20](=[O:24])[N:21]([CH2:22][CH3:23])[C:17]=4[CH:16]=3)=[C:37]([C:4]3[CH:3]=[C:2]([CH3:1])[CH:7]=[CH:6][CH:5]=3)[N:34]=[CH:33]2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCn1c(=O)n(CC)c2cc(C=N[C@@H]3CCN(Cc4ccccc4)C3)ccc21
Reactant: CN(C)C=O
Agent: O=C([O-])[O-]
Product: CCn1c(=O)n(CC)c2cc(-c3c(-c4cccc(C)c4)ncn3[C@@H]3CCN(Cc4ccccc4)C3)ccc21
Reaction time: 40 h

Procedure:
To a flask charged with 5-[((3R)-1-Benzyl-pyrrolidin-3-ylimino)-methyl]-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one was added a stir bar and 4-methylphenyl-toylsulfonomethylisocyanide (326 mg, 1.15 mmoles) (Joseph Sisko, Mark Mellinger, Peter W. Sheldrake, and Neil H. Baine, Organic Synthesis, Vol. 77, 198–205 (1999); Joseph Sisko, Mark Mellinger, Peter W. Sheldrake, and Neil H. Baine, Tetrahedron Letters, Vol. 37, No. 45, 8113–8116, (1996); U.S. Pat. No. 5,756,499; prepared in an analogous manner starting with 3-methylbenzylaldehyde). N,N-dimethylformamide (2 mL, 0.58 M) was added and within 5 minutes a light yellow solution was obtained. To this stirred solution was added MP-carbonate (498 mg, 1.37 mmoles) (Argonaut Tech); the flask was sealed with a plastic cap and the mixture was stirred for 40 hours. The mixture was filtered into a separatory funnel with ethyl acetate. The ethyl acetate layer was extracted with 3 N HCl (3 times). The aqueous extracts were made basic to approximately pH 9.5 with solid potassium carbonate. The basic mixture was extracted with ethyl acetate (3 times). These ethyl acetate extracts were washed with water (2 times), dried with sodium sulfate, filtered and the filtrate was concentrated to give a yellow oil. This oil was purified by flash chromatography (95:5 ethyl acetate/methyl alcohol) to give 240 mg of the named compound as a light yellow foam/gum.
Reaction SMILES: [CH:1]12[CH2:6][CH:5]1[CH2:4][N:3]([C:7]1[N:12]=[C:11]([NH:13][CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([Cl:23])[CH:16]=3)[C:10]([C:24]([OH:26])=O)=[CH:9][N:8]=1)[CH2:2]2.[CH2:27]([NH2:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C1COCC1>[CH2:27]([NH:34][C:24]([C:10]1[C:11]([NH:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([Cl:23])[CH:16]=2)=[N:12][C:7]([N:3]2[CH2:4][CH:5]3[CH:1]([CH2:6]3)[CH2:2]2)=[N:8][CH:9]=1)=[O:26])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
Reactant: COc1ccc(CNc2nc(N3CC4CC4C3)ncc2C(=O)O)cc1Cl
Reactant: NCc1ccccc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccc(CNc2nc(N3CC4CC4C3)ncc2C(=O)NCc2ccccc2)cc1Cl
Temperature: 25 °C
Reaction time: 8 h

Procedure:
In THF (50 mL) were dissolved 2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)pyrimidine-5-carboxylic acid (16 g, 42.8 mmol), benzylamine (5.0 g, 47 mmol), HATU (17.9 g, 47 mmol) and DIEA (11 g, 85.6 mmol). The reaction mixture was stirred at ambient temperature overnight and concentrated, followed by addition of DCM (500 mL). After the completion of the reaction, water (500 mL×4) was added to the reaction mixture for extraction. The organic phase was concentrated. The crude product was purified by silica gel column chromatography to give N-benzyl-2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)pyrimidine-5-formamide as the product (50 mg, 24% yield).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:25]=[CH:24][CH:23]=[CH:22][C:11]=3[C:12]=2[C:13](=[O:21])[C:14]2[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=2)=[CH:4][CH:3]=1.[CH2:26]([N:28]([CH2:33][CH3:34])[CH2:29][CH2:30][CH2:31]Cl)[CH3:27]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:25]=[CH:24][CH:23]=[CH:22][C:11]=3[C:12]=2[C:13](=[O:21])[C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:31][CH2:30][CH2:29][N:28]([CH2:33][CH3:34])[CH2:26][CH3:27])=[CH:16][CH:15]=2)=[CH:4][CH:3]=1
Reactant: O=C(c1ccc(O)cc1)c1c(-c2ccc(Cl)cc2)oc2ccccc12
Reactant: CCN(CC)CCCCl
Product: CCN(CC)CCCOc1ccc(C(=O)c2c(-c3ccc(Cl)cc3)oc3ccccc23)cc1

Procedure:
Reaction of 2-(4-chlorophenyl)-3-(4-hydroxybenzoyl)-benzofuran with 3-diethylaminopropyl chloride according to the procedure of Example 1 gives the title compound.
Reaction SMILES: CS(O[CH:6]([CH3:29])[CH2:7][CH2:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([N:15]2[CH:23]=[C:22]3[C:17]([CH:18]=[C:19]([O:24][CH2:25][CH:26]4[CH2:28][CH2:27]4)[CH:20]=[CH:21]3)=[N:16]2)[CH2:11][CH2:10]1)(=O)=O.[N-:30]=[N+:31]=[N-:32].[Na+]>CN(C=O)C>[N:30]([CH:6]([CH3:29])[CH2:7][CH2:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([N:15]2[CH:23]=[C:22]3[C:17]([CH:18]=[C:19]([O:24][CH2:25][CH:26]4[CH2:28][CH2:27]4)[CH:20]=[CH:21]3)=[N:16]2)[CH2:11][CH2:10]1)=[N+:31]=[N-:32]
Reactant: CC(CC[C@H]1CC[C@H](n2cc3ccc(OCC4CC4)cc3n2)CC1)OS(C)(=O)=O
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(CC[C@H]1CC[C@H](n2cc3ccc(OCC4CC4)cc3n2)CC1)N=[N+]=[N-]
Temperature: 80 °C
Reaction time: 2 h

Procedure:
A mixture of 3-{trans-4-[6-(cyclopropylmethoxy)-2H-indazol-2-yl]cyclohexyl}-1-methylpropyl methanesulfonate (2.95 g), sodium azide (1.37 g) and DMF (100 mL) was stirred at 80° C. for 2 hr. The reaction mixture was allowed to cool to room temperature, and concentrated under reduced pressure. The residue was diluted with ethyl acetate and water, and the organic layer was separated. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane/ethyl acetate) to give the title compound (2.50 g).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([O:24][CH3:25])[C:5]([O:22][CH3:23])=[C:6]([CH:8]([NH:10][C:11]2[CH:16]=[C:15](F)[CH:14]=[CH:13][C:12]=2[S:18]([CH3:21])(=[O:20])=[O:19])[CH3:9])[CH:7]=1.[CH3:26][N:27]([CH3:34])[CH:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1.C(N(CC)C(C)C)(C)C>C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4]([O:24][CH3:25])[C:5]([O:22][CH3:23])=[C:6]([CH:8]([NH:10][C:11]2[CH:16]=[C:15]([N:31]3[CH2:32][CH2:33][CH:28]([N:27]([CH3:34])[CH3:26])[CH2:29][CH2:30]3)[CH:14]=[CH:13][C:12]=2[S:18]([CH3:21])(=[O:20])=[O:19])[CH3:9])[CH:7]=1
Reactant: CN(C)C1CCNCC1
Reactant: COc1cc(Cl)cc(C(C)Nc2cc(F)ccc2S(C)(=O)=O)c1OC
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: COc1cc(Cl)cc(C(C)Nc2cc(N3CCC(N(C)C)CC3)ccc2S(C)(=O)=O)c1OC
Yield: 19.4 %

Procedure:
N-(1-(5-Chloro-2,3-dimethoxyphenyl)ethyl)-5-fluoro-2-(methylsulfonyl)benzenamine (100.0 mg, 0.26 mmol), N,N-dimethylpiperidin-4-amine (66.0 mg, 0.51 mmol), N,N-diisopropylethylamine (133.0 mg, 1.03 mmol) were stirred at 100° C. in dry acetonitrile (3 mL) for 16 h. The solvent was evaporated and the residue was dissolved in dichloromethane and washed with water. The dichloromethane was evaporated and the crude compound was purified by silica chromatography using 10% methanol in dichloromethane to afford the title compound (25.0 mg, 19.6% yield). 1H NMR (400 MHz, CDCl3): δ 7.53 (d, 1H), 6.88 (d, 1H), 6.78 (d, 1H), 6.50 (d, 1H), 6.21 (d, 1H), 5.90 (d, 1H), 4.85 (m, 1H), 3.90 (s, 3H), 3.85 (s, 3H), 3.74 (m, 2H), 3.24 (m, 1H), 3.05 (s, 3H), 2.76 (q, 2H), 2.26 (s, 6H), 1.78 (t, 2H), 1.55 (d, 3H), 1.45 (m, 2H); MS (ESI) m/z: 496.1 (M+).
Reaction SMILES: [Si:1]([O:8][C:9]1[C:16]([CH2:17][CH2:18][CH3:19])=[CH:15][C:12]([CH2:13]O)=[CH:11][C:10]=1[CH2:20][CH2:21][CH3:22])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:23][C:24]1[N:29]=[C:28]2[N:30]=[C:31]([CH2:33][CH3:34])[NH:32][C:27]2=[C:26]([CH3:35])[CH:25]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[CH3:23][C:24]1[N:29]=[C:28]2[N:30]([CH2:13][C:12]3[CH:15]=[C:16]([CH2:17][CH2:18][CH3:19])[C:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])=[C:10]([CH2:20][CH2:21][CH3:22])[CH:11]=3)[C:31]([CH2:33][CH3:34])=[N:32][C:27]2=[C:26]([CH3:35])[CH:25]=1
Reactant: CCc1nc2nc(C)cc(C)c2[nH]1
Reactant: CCCc1cc(CO)cc(CCC)c1O[Si](C)(C)C(C)(C)C
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CCCc1cc(Cn2c(CC)nc3c(C)cc(C)nc32)cc(CCC)c1O[Si](C)(C)C(C)(C)C
Reaction time: 1 h
Yield: 80.2 %

Procedure:
To a solution of 4.2 g (13.0 mmol) of the product of Step E, 2.5 g (14.0 mmol) of 5,7-dimethyl-2-ethylimidazo[4,5-b]pyridine (Example 24, Step C), and 5.62 (20.0 mmol) of triphenylphosphine dissolved in 40 mL of THF, was added 3.396 g (20.0 mmol) of diethyl azodicarboxylate and the mixture was stirred for 1 hour. The reaction mixture was then concentrated in vacuo and the residual oil was purified on a silica gel flash chromatography column eluted with 25-40% ethyl acetate/hexane to afford 5 g (80%) of the title compound.
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:16]=[C:17]([CH:28]=[CH:29][CH:30]=1)[CH2:18][S:19][C:20]1[CH:21]=[C:22]([CH:25]=[CH:26][CH:27]=1)[CH:23]=O.[C:31]([O:39][CH2:40][CH3:41])(=[O:38])[CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34].C(O)(=O)C1C=CC=CC=1.N1CCCCC1>C1(C)C=CC=CC=1>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:16]=[C:17]([CH:28]=[CH:29][CH:30]=1)[CH2:18][S:19][C:20]1[CH:21]=[C:22]([CH:25]=[CH:26][CH:27]=1)[CH2:23][CH:32]([C:33]([O:35][CH2:36][CH3:37])=[O:34])[C:31]([O:39][CH2:40][CH3:41])=[O:38]
Reactant: Cc1oc(-c2ccccc2)nc1COc1cccc(CSc2cccc(C=O)c2)c1
Reactant: CCOC(=O)CC(=O)OCC
Agent: O=C(O)c1ccccc1
Solvent: C1CCNCC1
Solvent: Cc1ccccc1
Product: CCOC(=O)C(Cc1cccc(SCc2cccc(OCc3nc(-c4ccccc4)oc3C)c2)c1)C(=O)OCC
Temperature: 0 °C
Reaction time: 1 h
Yield: 65.9 %

Procedure:
A mixture of 3-[3-[(5-methyl-2-phenyl-4-oxazolyl)methoxy]benzylthio]benzaldehyde (0.80 g), diethyl malonate (0.37 g), benzoic acid (0.07 g), piperidine (0.05 g) and toluene (40 mL) was heated under reflux for 4 hrs. with azeotropic dehydration. The reaction mixture was concentrated, water was added to the residue and the mixture was extracted with ethyl acetate. The organic layer was washed successively with saturated aqueous sodium hydrogencarbonate, dilute hydrochloric acid and water, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography to give an oil from a fraction eluted with acetone-hexane (1:5, v/v). To a mixture of the obtained oil, tetrahydrofuran (20 mL) and ethanol (20 mL) was added sodium borohydride (0.02 g) at 0° C. and the mixture was stirred at 0° C. for 1 hr. The reaction mixture was poured into water, acidified with 2N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography to give diethyl 2-[3-[3-[(5-methyl-2-phenyl-4-oxazolyl)methoxy]benzylthio]benzyl]malonate as an oil (0.71 g, yield 66%) from a fraction eluted with ethyl acetate-hexane (1:4, v/v).
Reaction SMILES: [C:1]12([C:11]3[CH:20]=[C:19]4[C:14]([CH:15]=[CH:16][C:17]([C:21]5[CH:32]=[CH:31][C:24]([C:25]([O:27]CC=C)=[O:26])=[CH:23][CH:22]=5)=[CH:18]4)=[CH:13][C:12]=3[OH:33])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.Br[CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41]>>[C:1]12([C:11]3[CH:20]=[C:19]4[C:14]([CH:15]=[CH:16][C:17]([C:21]5[CH:22]=[CH:23][C:24]([C:25]([OH:27])=[O:26])=[CH:31][CH:32]=5)=[CH:18]4)=[CH:13][C:12]=3[O:33][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH2:2][CH:3]3[CH2:4][CH:5]([CH2:6][CH:7]([CH2:9]3)[CH2:8]1)[CH2:10]2
Reactant: C=CCOC(=O)c1ccc(-c2ccc3cc(O)c(C45CC6CC(CC(C6)C4)C5)cc3c2)cc1
Reactant: CCOC(=O)CCCCCBr
Product: CCOC(=O)CCCCCOc1cc2ccc(-c3ccc(C(=O)O)cc3)cc2cc1C12CC3CC(CC(C3)C1)C2
Yield: 58.5 %

Procedure:
Following the procedure of Example 12(a), but reacting 3 g (6.8 mmol) of allyl 4-[7-(1-adamantyl)-6-hydroxy-2-naphthyl]benzoate with 2.3 g (10.2 mmol) of ethyl 6-bromohexanoate, 2.15 g (55%) of the expected compound were obtained, which compound had a melting point of 116°-7° C.