Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:4][N:5]([C:16]([CH3:19])([CH3:18])[CH3:17])[C:6]([CH3:15])([CH3:14])[C:7]([NH:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH:2]=[CH2:3].C(N(C(C)(C)C(NC(C)(C)C)=O)O)(C)(C)C.C(Br)C#C>>[CH2:1]([O:4][N:5]([C:16]([CH3:19])([CH3:18])[CH3:17])[C:6]([CH3:15])([CH3:14])[C:7]([NH:9][C:10]([CH3:12])([CH3:11])[CH3:13])=[O:8])[C:2]#[CH:3]
Reactant: C=CCON(C(C)(C)C)C(C)(C)C(=O)NC(C)(C)C
Agent: C#CCBr
Agent: CC(C)(C)NC(=O)C(C)(C)N(O)C(C)(C)C
Product: C#CCON(C(C)(C)C)C(C)(C)C(=O)NC(C)(C)C
Yield: 78 %

Procedure:
The compound is prepared in analogy to compound (204) from tert-butyl-(dimethyl-tert-butylaminocarbonyl-methyl)-hydroxylamine and propargylbromide in 78% yield as colorless oil.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:13][CH2:12][NH:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:14][C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][C:22]=1[F:23])[CH2:18]Br.C(N(C(C)C)CC)(C)C.O.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]1[CH2:13][CH2:12][N:11]([CH2:18][C:17]2[CH:20]=[CH:21][C:22]([F:23])=[C:15]([F:14])[CH:16]=2)[CH2:10]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N[C@H]1CCNC1
Reactant: Fc1ccc(CBr)cc1F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N[C@H]1CCN(Cc2ccc(F)c(F)c2)C1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
To a methylene chloride (10 mL) solution of (3S)-3-(tert-butoxycarbonylamino)pyrrolidine (916 mg), 3,4-difluorobenzylbromide (0.7 mL) and IPEA (2.2 mL) were added one by one, and the reaction solution was agitated at room temperature for 20 hours. A saturated sodium bicarbonate water was added to the reaction solution after the reaction ended, and the organic layer was partitioned. It was dried over anhydrous magnesium sulfate and the obtained organic layer was concentrated under reduced pressure. 1.55 g of the title compound was obtained by purifying the residue by silica gel chromatography (elution solvent: heptane:ethyl acetate=1:1). The physical properties of the compound are as follows.
Reaction SMILES: [N+](C1C=CC(O[C:11](=[O:24])[CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH:21]=[CH2:22])=[C:15]([Cl:23])[CH:14]=2)=CC=1)([O-])=O.Cl.[CH3:26][O:27][C:28](=[O:31])[CH2:29][NH2:30].C(N(CC)CC)C>C(Cl)(Cl)Cl>[CH3:26][O:27][C:28](=[O:31])[CH2:29][NH:30][C:11](=[O:24])[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH:21]=[CH2:22])=[C:15]([Cl:23])[CH:14]=1
Reactant: COC(=O)CN
Reactant: C=CCOc1ccc(CC(=O)Oc2ccc([N+](=O)[O-])cc2)cc1Cl
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: C=CCOc1ccc(CC(=O)NCC(=O)OC)cc1Cl
Temperature: 40 °C
Reaction time: 4 h

Procedure:
4-Allyloxy-3-chloro-phenylacetic acid p-nitrophenyl ester (3.69 g) was dissolved in chloroform (30 ml). To the solution was added glycine methyl ester hydrochloride (1.5 g) in dry chloroform (30 ml) containing dry triethylamine (1.4 ml), and the solution was stirred at 40° C. for 4 hrs.
Reaction SMILES: [C:1]12([S:11][CH2:12][CH2:13][N:14]([N:20]=O)[C@H:15]([C:17]([OH:19])=[O:18])[CH3:16])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.O>C(OC(=O)C)(=O)C>[C:1]12([S:11][CH2:12][CH2:13][N+:14]3[N-:20][O:19][C:17](=[O:18])[C:15]=3[CH3:16])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2
Reactant: C[C@@H](C(=O)O)N(CCSC12CC3CC(CC(C3)C1)C2)N=O
Solvent: O
Solvent: CC(=O)OC(C)=O
Product: Cc1c(=O)o[n-][n+]1CCSC12CC3CC(CC(C3)C1)C2
Temperature: 25 °C
Reaction time: 24 h

Procedure:
The N-[2-(1-adamantylthio)ethyl]-N-nitrosoalanine prepared in Example 6 is dissolved in 163 parts of acetic anhydride, then allowed to stand at room temperature for 24 hours. The solution is heated briefly to 65° on a steam bath and allowed to cool to room temperature. Then the solution is added to 1000 parts of water and stirred for 3 hours. The solid which forms is collected by filtration, washed successively with water, and saturated sodium bicarbonate and water, and dried. Recrystallization of the solid from methylene chloride-ether affords pure 3-[2-(1-adamantylthio)ethyl] 4-methylsydnone, melting at about 92°-93° and represented by the following structural formula ##STR8##
Reaction SMILES: [CH3:1][NH:2][C:3]([C@H:5]1[CH2:9][CH2:8][CH2:7][N:6]1[C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]([NH2:19])=[NH:18])=[CH:12][CH:11]=1)=[O:4].CN(C)/[CH:22]=[C:23](\[F:35])/[C:24]([C:26]1[N:30]([CH:31]([CH3:33])[CH3:32])[C:29]([CH3:34])=[N:28][CH:27]=1)=O>COCCO>[CH3:1][NH:2][C:3]([C@H:5]1[CH2:9][CH2:8][CH2:7][N:6]1[C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[N:19]=[C:24]([C:26]3[N:30]([CH:31]([CH3:32])[CH3:33])[C:29]([CH3:34])=[N:28][CH:27]=3)[C:23]([F:35])=[CH:22][N:18]=2)=[CH:12][CH:11]=1)=[O:4]
Reactant: Cc1ncc(C(=O)/C(F)=C/N(C)C)n1C(C)C
Reactant: CNC(=O)[C@H]1CCCN1c1ccc(NC(=N)N)cc1
Solvent: COCCO
Product: CNC(=O)[C@H]1CCCN1c1ccc(Nc2ncc(F)c(-c3cnc(C)n3C(C)C)n2)cc1
Temperature: 200 °C
Yield: 39.9 %

Procedure:
(R)-1-(4-Guanidino-phenyl)-pyrrolidine-2-carboxylic acid methylamide (Method 59; 0.22 g, 0.82 mmol) and (2Z)-3-(dimethylamino)-2-fluoro-1-(1-isopropyl-2-methyl-1H-imidazol-5-yl)prop-2-en-1-one (Method 14; 0.15 g, 0.63 mmol) were added to 2-methoxyethanol (4 ml) and heated at 200° C. for 2 hours in the microwave. Solvent was removed in vacuo and chromatographed. The product was passed purified by HPLC, and the required fractions were combined and basified with K2CO3 (0.5 g), extracted with DCM (2×50 ml), dried and solvent removed in vacuo to yield a yellow solid (110 mg, 40%). NMR (400.132 MHz, CDCl3) 8.21 (d, 1H), 7.56 (d, 1H), 7.34 (d, 2H), 6.79 (s, 1H), 6.60 (d, 2H), 6.56 (s, 1H), 5.56 (septet, 1H), 3.99 (t, 1H), 3.64 (t, 1H), 3.20 (q, 1H), 2.80 (d, 3H), 2.58 (s, 3H), 2.29-2.24 (m, 2H), 2.06-1.89 (m, 2H), 1.45 (d, 6H); m/z 438.
Reaction SMILES: Cl.[NH2:2][C@H:3]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:13]3[CH:18]=[CH:17][C:16]([C:19]([N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)=[O:20])=[CH:15][N:14]=3)[CH:11]=2)[N:6]([C:27](=[O:29])[CH3:28])[C@@H:5]([CH3:30])[CH2:4]1.Br[C:32]1[CH:37]=[N:36][C:35]([CH3:38])=[CH:34][N:33]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(N(C)C)=CC=CC=2)CCCCC1.CC(C)([O-])C.[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:30][C@H:5]1[CH2:4][C@@H:3]([NH:2][C:32]2[CH:37]=[N:36][C:35]([CH3:38])=[CH:34][N:33]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:13]3[CH:18]=[CH:17][C:16]([C:19]([N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)=[O:20])=[CH:15][N:14]=3)[CH:11]=2)[N:6]1[C:27](=[O:29])[CH3:28]
Reactant: Cc1cnc(Br)cn1
Reactant: CC(=O)N1c2ccc(-c3ccc(C(=O)N4CCOCC4)cn3)cc2[C@H](N)C[C@@H]1C
Agent: [Pd]
Agent: CC(C)(C)[O-]
Agent: CN(C)c1ccccc1-c1ccccc1P(C1CCCCC1)C1CCCCC1
Solvent: C1COCCO1
Product: CC(=O)N1c2ccc(-c3ccc(C(=O)N4CCOCC4)cn3)cc2[C@H](Nc2cnc(C)cn2)C[C@@H]1C
Temperature: 130 °C
Yield: 34 %

Procedure:
1-((2S,4R)-4-amino-2-methyl-6-(5-(morpholine-4-carbonyl)pyridin-2-yl)-3,4-dihydroquinolin-1(2H)-yl)ethanone hydrochloride (for a preparation see Intermediate 65) (100 mg, 0.232 mmol), 2-bromo-5-methylpyrazine (80 mg, 0.464 mmol), 2′-(dicyclohexylphosphino)-N,N-dimethyl-[1,1′-biphenyl]-2-amine (27.4 mg, 0.070 mmol), tris(dibenzylideneacetone)dipalladium(0) (42.5 mg, 0.046 mmol) and sodium tert-butoxide (66.9 mg, 0.696 mmol) were combined in 1,4-dioxane (2 mL) and the mixture degassed over a period of 15 mins, before being heated under microwave irradiation to 130° C. for 40 mins. The reaction mixture was partitioned between saturated aqueous sodium bicarbonate (50 mL) and DCM (3×50 mL). The organics were combined, dried by passing through a hydrophobic frit and concentrated in vacuo to give a residue which was purified by MDAP (HpH) to give 1-((2S,4R)-2-methyl-4-((5-methylpyrazin-2-yl)amino)-6-(5-(morpholine-4-carbonyl)pyridin-2-yl)-3,4-dihydroquinolin-1(2H)-yl)ethanone (38 mg, 0.078 mmol, 34% yield). LCMS: (Formate, 2 min), Rt=0.71 mins, MH+487
Reaction SMILES: CC(C)[C@H](N1CC2C(=CC(C3C=CC(NS(C4C=CC=CC=4)(=O)=O)=CC=3)=CC=2)C1=O)C(O)=O.[CH3:34][O:35][C:36]1[CH:41]=[CH:40][C:39]([S:42]([NH:45][C:46]2[CH:51]=[CH:50][C:49]([C:52]3[CH:60]=[C:59]4[C:55]([CH2:56][N:57]([C@@H:62]([CH:67]([CH3:69])[CH3:68])[C:63]([O:65]C)=[O:64])[C:58]4=[O:61])=[CH:54][CH:53]=3)=[CH:48][CH:47]=2)(=[O:44])=[O:43])=[CH:38][CH:37]=1>>[CH3:34][O:35][C:36]1[CH:41]=[CH:40][C:39]([S:42]([NH:45][C:46]2[CH:47]=[CH:48][C:49]([C:52]3[CH:60]=[C:59]4[C:55]([CH2:56][N:57]([C@@H:62]([CH:67]([CH3:69])[CH3:68])[C:63]([OH:65])=[O:64])[C:58]4=[O:61])=[CH:54][CH:53]=3)=[CH:50][CH:51]=2)(=[O:44])=[O:43])=[CH:38][CH:37]=1
Reactant: COC(=O)[C@H](C(C)C)N1Cc2ccc(-c3ccc(NS(=O)(=O)c4ccc(OC)cc4)cc3)cc2C1=O
Agent: CC(C)[C@@H](C(=O)O)N1Cc2ccc(-c3ccc(NS(=O)(=O)c4ccccc4)cc3)cc2C1=O
Product: COc1ccc(S(=O)(=O)Nc2ccc(-c3ccc4c(c3)C(=O)N([C@H](C(=O)O)C(C)C)C4)cc2)cc1
Yield: 87 %

Procedure:
The compound of example 90 was prepared analogous to compound of example 78 by hydrolysis of compound of example 89.
Reaction SMILES: [CH3:1][C:2]1([CH3:20])[C:6]2[CH:7]=[C:8]([NH2:11])[CH:9]=[CH:10][C:5]=2[C:4]([C:13]2[CH:18]=[CH:17][C:16]([NH2:19])=[CH:15][CH:14]=2)([CH3:12])[CH2:3]1.[CH:21]1[C:26]([C:27]([C:29]2[CH:34]=[CH:33][C:32]3[C:35]([O:37][C:38](=[O:39])[C:31]=3[CH:30]=2)=[O:36])=[O:28])=[CH:25][C:24]2[C:40]([O:42][C:43](=[O:44])[C:23]=2[CH:22]=1)=[O:41].CN1[C:50](=[O:51])[CH2:49][CH2:48][CH2:47]1>>[CH3:1][C:2]1([CH3:20])[C:6]2[CH:7]=[C:8]([NH2:11])[CH:9]=[CH:10][C:5]=2[C:4]([C:13]2[CH:14]=[CH:15][C:16]([NH2:19])=[CH:17][CH:18]=2)([CH3:12])[CH2:3]1.[CH:21]1[C:26]([C:27]([C:29]2[CH:34]=[CH:33][C:32]3[C:35]([O:37][C:38](=[O:39])[C:31]=3[CH:30]=2)=[O:36])=[O:28])=[CH:25][C:24]2[C:40]([O:42][C:43](=[O:44])[C:23]=2[CH:22]=1)=[O:41].[CH:47]1[CH:24]=[CH:25][C:26]2[C:27](=[O:28])[CH:29]=[CH:30][C:50](=[O:51])[C:49]=2[CH:48]=1
Reactant: CN1CCCC1=O
Agent: CC1(C)CC(C)(c2ccc(N)cc2)c2ccc(N)cc21
Agent: O=C(c1ccc2c(c1)C(=O)OC2=O)c1ccc2c(c1)C(=O)OC2=O
Product: O=C1C=CC(=O)c2ccccc21

Procedure:
The positive photosensitive polyimide resin composition of the present invention was prepared in solution form from 30 g of the NMP solution of the organic solvent-soluble polyimide resin obtained in Preparation Example 1 and 0.67 g of naphthoquinone-type positive photosensitive agent (a compound formed by substituting 2,3,4,4'-tetrahydroxybenzophenone with 3 mol of 1,2-naphthoquinone-2-diazide-5-sulfonic acid), by stirring at room temperature for 3 hours. The mixture was filtered through a 1.0-μm filter to give the desired solution.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5](Br)=[CH:4][N:3]=1.C([Li])CCC.CN([CH:17]=[O:18])C.[NH4+].[Cl-]>C(OCC)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:17]=[O:18])=[CH:4][N:3]=1
Reactant: CN(C)C=O
Reactant: Brc1ccc(Br)nc1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCOCC
Product: O=Cc1ccc(Br)nc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 85.6 %

Procedure:
To a suspension of 2,5-dibromopyridine (18.6 g, 78.5 mmol) in dry diethyl ether (400 mL) at −78° C. was added n-butyllithium (2.5 M in hexanes, 31.4 mL, 78.5 mmol) over a period of 20 min. After stirring 30 min at this temperature, anhydrous DMF (9.1 mL, 118 mmol) was added over a period of 5 min, and the reaction mixture was stirred for 30 min then warmed to room temperature. Saturated NH4Cl (10 mL) was added to the reaction mixture. The layers were separated, and the organic layer was dried (Na2SO4), concentrated. The crude product was purified by column chromatography (1:5 ethyl acetate/hexanes) to afford a brown solid (12.5 g, 86%); 1H NMR (300 MHz, CDCl3) δ 7.61 (dd, J=8.10, 0.60 Hz, 1 H), 7.95 (dd, J=8.10, 2.10 Hz, 1 H), 8.74 (dd, J=2.10, 0.60 Hz, 1 H), 10.02 (s, 1 H); 13C NMR (75 MHz, CDCl3) 129.2, 130.8, 137.7, 148.4, 152.6, 189.7.
Reaction SMILES: [Cl-].C1([P+](C2C=CC=CC=2)(C2C=CC=CC=2)[CH2:9][C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]=2)C=CC=CC=1.C([Li])CCC.[CH3:37][O:38][CH2:39][CH2:40][O:41][CH2:42][O:43][C:44]1[CH:45]=[C:46]([CH:49]=[CH:50][CH:51]=1)[CH:47]=O>C1COCC1>[CH3:37][O:38][CH2:39][CH2:40][O:41][CH2:42][O:43][C:44]1[CH:51]=[CH:50][CH:49]=[C:46]([CH:47]=[CH:9][C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]=2)[CH:45]=1
Reactant: c1ccc([P+](Cc2ccc3ccccc3n2)(c2ccccc2)c2ccccc2)cc1
Reactant: COCCOCOc1cccc(C=O)c1
Agent: [Cl-]
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: COCCOCOc1cccc(C=Cc2ccc3ccccc3n2)c1
Reaction time: 0.5 h

Procedure:
To a cooled (−78° C.) suspension of triphenyl-(quinolin-2-yl-methyl)-phosphonium chloride (1.76 g, 4 mmol, example 17) in THF (24 mL) is added, dropwise, n-butyl lithium solution (1.7 mL, 2.5 M in hexanes). The resulting mixture is stirred for 30 min. then a solution of 3-[(2-methoxyethoxy)-methoxy]-benzaldehyde (756 mg, 3.6 mmol, example 8a) in THF (3 mL) is added. This mixture is stirred for 30 min then the cold bath removed and stirring continued for 2 h. The reaction mixture is then diluted with ethyl acetate, washed with sat. ammonium acetate solution and brine, dried over MgSO4 and concentrated. The residue is purified by flash chromatography (silica, 40% ethyl acetate in hexanes) to give the title compound as an oil. MS (ESI) 336 (M+H)+.
Reaction SMILES: Br[C:2]1[C:3]([N:22]([CH2:24][CH2:25][OH:26])[CH3:23])=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([S:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].[N:27]1[CH:32]=[C:31](B(O)O)[CH:30]=[N:29][CH:28]=1>>[OH:26][CH2:25][CH2:24][N:22]([CH3:23])[C:3]1[C:2]([C:31]2[CH:32]=[N:27][CH:28]=[N:29][CH:30]=2)=[CH:21][C:6]([C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([S:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=2)=[O:8])=[CH:5][N:4]=1
Reactant: CN(CCO)c1ncc(C(=O)Nc2ccc(SC(F)(F)F)cc2)cc1Br
Reactant: OB(O)c1cncnc1
Product: CN(CCO)c1ncc(C(=O)Nc2ccc(SC(F)(F)F)cc2)cc1-c1cncnc1

Procedure:
The title compound was prepared in an analogous fashion to that described in Example 185 using 5-bromo-6-((2-hydroxyethyl)(methyl)amino)-N-(4-((trifluoromethyl)thio)phenyl)nicotinamide (Stage 192.1) and pyrimidin-5-ylboronic acid to afford an off-white solid. HPLC (Condition 4) tR=5.26 min, UPLC-MS (Condition 3) tR=1.00 min, m/z=450.3 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 2.69 (s, 3H) 3.40-3.62 (m, 4H) 4.67 (t, J=1.00 Hz, 1H) 7.69 (d, J=8.60 Hz, 2H) 7.90 (d, J=1.00 Hz, 2H) 8.14 (d, J=2.30 Hz, 1H) 8.76 (d, J=2.50 Hz, 1H) 8.95 (s, 2H) 9.17 (s, 1H) 10.32 (s, 1H).
Reaction SMILES: Cl.[F:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:18]3[C:13](=[CH:14][C:15]([O:19][CH:20]4[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]4)=[CH:16][CH:17]=3)[CH2:12][CH2:11][C:10]2=[O:26])=[CH:5][CH:4]=1.C(=O)([O-])[O-].[K+].[K+].I[CH:34]([CH3:36])[CH3:35]>CN(C)C=O.O>[F:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:18]3[C:13](=[CH:14][C:15]([O:19][CH:20]4[CH2:21][CH2:22][N:23]([CH:34]([CH3:36])[CH3:35])[CH2:24][CH2:25]4)=[CH:16][CH:17]=3)[CH2:12][CH2:11][C:10]2=[O:26])=[CH:5][CH:4]=1
Reactant: CC(C)I
Reactant: O=C1CCc2cc(OC3CCNCC3)ccc2N1c1ccc(F)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)N1CCC(Oc2ccc3c(c2)CCC(=O)N3c2ccc(F)cc2)CC1
Temperature: 100 °C
Reaction time: 1 h
Yield: 52 %

Procedure:
A suspension of 1-(4-fluorophenyl)-6-(piperidin-4-yloxy)-3,4-dihydroquinolin-2(1H)-one hydrochloride prepared in Example 7-(3) (0.30 g), potassium carbonate (0.55 g) and 2-iodopropane (0.68 g) in N,N-dimethylformamide (10 mL) was stirred at 100° C. for 1 hour. The reaction mixture was cooled to room temperature, diluted with water and extracted with chloroform. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluting solvent: chloroform→chloroform/methanol=4/1) to give the titled compound (0.16 g, 52%) as a colorless solid.
Reaction SMILES: [OH:1][N:2]=[C:3]([NH2:10])[C:4]1[CH:9]=[CH:8][CH:7]=[N:6][CH:5]=1.[N+:11]([C:14]1[CH:15]=[C:16]([CH:20]=[CH:21][CH:22]=1)[C:17](Cl)=O)([O-:13])=[O:12].N>>[N+:11]([C:14]1[CH:15]=[C:16]([C:17]2[O:1][N:2]=[C:3]([C:4]3[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=3)[N:10]=2)[CH:20]=[CH:21][CH:22]=1)([O-:13])=[O:12]
Reactant: NC(=NO)c1cccnc1
Reactant: O=C(Cl)c1cccc([N+](=O)[O-])c1
Agent: N
Product: O=[N+]([O-])c1cccc(-c2nc(-c3cccnc3)no2)c1

Procedure:
The title compound was prepared according to the procedure of Example 8 using N′-hydroxynicotinimidamide (Aldrich) and 3-nitrobenzoyl chloride (Aldrich). 1H NMR (300 MHz, CDCl3) δ 7.44-7.55 (m, 1H), 7.82 (t, J=8.3 Hz, 1H), 8.43-8.60 (m, 3H), 8.80 (dd, J=4.7, 1.7 Hz, 1H), 9.07-9.13 (m, 1H), 9.42 (d, J=2.0 Hz, 1H) ppm; MS (DCI/NH3) m/z 269 (M+H)+.
Reaction SMILES: [BH4-].[Na+].C[O:4][C:5]([C@H:7]1[N:10]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=2[O:20][CH3:21])[C:9](=[O:22])[C@H:8]1[NH:23][C:24](=[O:32])[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=O>O1CCCC1>[CH3:21][O:20][C:13]1[CH:14]=[C:15]([O:18][CH3:19])[CH:16]=[CH:17][C:12]=1[CH2:11][N:10]1[C@H:7]([CH2:5][OH:4])[C@H:8]([NH:23][C:24](=[O:32])[CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:9]1=[O:22]
Reactant: COC(=O)[C@@H]1[C@H](NC(=O)Cc2ccccc2)C(=O)N1Cc1ccc(OC)cc1OC
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1ccc(CN2C(=O)[C@@H](NC(=O)Cc3ccccc3)[C@H]2CO)c(OC)c1
Reaction time: 1.5 h
Yield: 91 %

Procedure:
Under ice-cooling and stirring, 12 ml of an aqueous solution containing 570 mg of sodium borohydride is added to a solution of 2.06 of cis-1-(2,4-dimethoxybenzyl)-3-phenylacetamido-2-oxoazetidine-4-carboxylic acid methyl ester in 24 ml of tetrahydrofuran. The reaction mixture is stirred for 30 minutes under ice-cooling and then for 1.5 hours at room temperature. The tetrahydrofuran is distilled off in vacuo and an aqueous sodium chloride solution and ethyl acetate are added to the residue. The resulting ethyl acetate layer is separated and washed successively with an aqueous sodium hydrogen carbonate and an aqueous sodium chloride. It is then dried over magnesium sulfate and the solvent is distilled off in vacuo. Ether is added to the residue and the precipitated crystals are collected by filtration to give 1.75 g (91%) of cis-1-(2,4-dimethoxybenzyl)-4-hydroxymethyl-3-phenylacetamido-2-oxoazetidine, m.p. 152°-154° C.
Reaction SMILES: [Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=O.[K+].[K+].[C:12]1([C:18]2[C:26]3[N:25]=[C:24]([CH:27]([OH:29])[CH3:28])[NH:23][C:22]=3[C:21]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[CH:20][CH:19]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[NH4+].[OH-]>OS(O)(=O)=O>[C:12]1([C:18]2[C:26]3[N:25]=[C:24]([C:27](=[O:29])[CH3:28])[NH:23][C:22]=3[C:21]([C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)=[CH:20][CH:19]=2)[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: CC(O)c1nc2c(-c3ccccc3)ccc(-c3ccccc3)c2[nH]1
Agent: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Agent: O=S(=O)(O)O
Agent: [K+]
Product: CC(=O)c1nc2c(-c3ccccc3)ccc(-c3ccccc3)c2[nH]1
Temperature: 90 °C
Reaction time: 10 h

Procedure:
A solution of 1.38 g (4.7 mmol) potassium dichromate in 8.5 ml 40% H2SO4 was added dropwise to a stirred suspension of 1.10 g (3.5 mmol) 1-(4,7-diphenyl-1H-benzimidazol-2-yl)ethanol in 15 ml 5% H2SO4. The slurry was stirred at 90° C. for 10 hours, cooled to room temperature and treated with 7 ml conc. NH4OH. The residue was filtered, washed with water (5×10 ml) and extracted with acetone (10×30 ml). The combined extracts were filtered trough a 0.5 cm layer of silica and the filtrate evaporated. The residue was re-crystallized from ethyl acetate-cyclohexane. Yield—0.57 g (52.1%). 1H NMR (250 MHz, CDCl3), δ, ppm: 2.83 (s, 3H), 7.44–7.64 (m, 10H); 8.14 (d, 7.6 Hz, 2H), 10.22 (br.s).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:12]([NH:14][C:15]2[O:16][C:17]([C:20]3[O:21][CH:22]=[CH:23][CH:24]=3)=[N:18][N:19]=2)=[O:13])[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[CH2:25]([C:27]1[CH:32]=[CH:31][C:30]([C:33]2[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=2)=[CH:29][CH:28]=1)[CH3:26]>>[CH2:25]([C:27]1[CH:32]=[CH:31][C:30]([C:33]2[CH:38]=[CH:37][C:36]([C:2]3[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([C:12]([NH:14][C:15]4[O:16][C:17]([C:20]5[O:21][CH:22]=[CH:23][CH:24]=5)=[N:18][N:19]=4)=[O:13])[CH:3]=3)=[CH:35][CH:34]=2)=[CH:29][CH:28]=1)[CH3:26]
Reactant: CCc1ccc(-c2ccc(B(O)O)cc2)cc1
Reactant: O=C(Nc1nnc(-c2ccco2)o1)c1cc(Br)cc(C(F)(F)F)c1
Product: CCc1ccc(-c2ccc(-c3cc(C(=O)Nc4nnc(-c5ccco5)o4)cc(C(F)(F)F)c3)cc2)cc1

Procedure:
The title compound was synthesized in accordance with the synthesis method of compound Ia-50, using 3-bromo-N-[5-(2-furyl)-1,3,4-oxadiazol-2-yl]-5-trifluoromethylbenzenecarboxamide prepared in Reference Example 39 instead of compound Ia-50 and using commercially available 4′-ethyl-4-biphenylboronic acid instead of 1-methyl-5-indoleboronic acid pinacol ester.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH:9]=2)=[CH:4][CH:3]=1.[H][H].C1(C2C=CC(O)=CC=2)C=CC=CC=1>>[C:2]1([OH:1])[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)=[CH:6][CH:7]=1
Reactant: [H][H]
Reactant: Oc1ccc(C2=CCC(O)CC2)cc1
Agent: Oc1ccc(-c2ccccc2)cc1
Product: Oc1ccc(-c2ccc(O)cc2)cc1

Procedure:
It was found that a novel compound 4-(4-hydroxyphenyl)-3-cyclohexene-1ol can be obtained in good yield by conducting a decomposition reaction in the initial stage of a reaction in the absence of a dehydrogenation catalyst and a hydrogen acceptor, and that by-products such as p-phenylphenol can be virtually inhibited by conducting the dehydrogenation reaction of the novel compound to give 4,4'-biphenol of high purity.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH3:13])=[CH:11][CH:10]=[C:9]2[CH3:14])=[CH:4][CH:3]=1.CC1C(P(C2C(C)=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.[C:37]([OH:41])(=[O:40])[CH:38]=[CH2:39].Cl>C(N(CC)CC)C.O.[Pd](Cl)Cl>[CH3:14][C:9]1[N:8]([C:5]2[CH:6]=[CH:7][C:2]([CH:39]=[CH:38][C:37]([OH:41])=[O:40])=[CH:3][CH:4]=2)[C:12]([CH3:13])=[CH:11][CH:10]=1
Reactant: Cc1ccc(C)n1-c1ccc(Br)cc1
Reactant: C=CC(=O)O
Agent: Cl[Pd]Cl
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Agent: Cl
Solvent: CCN(CC)CC
Solvent: O
Product: Cc1ccc(C)n1-c1ccc(C=CC(=O)O)cc1
Temperature: 25 °C

Procedure:
To a stirred solution of 50.0 g 1-(4-bromophenyl)-2,5-dimethylpyrrole (Meakins et al, J. Chem. Soc., Perkin Trans. I, 1984, 2801-2807) and tri-O-tolylphosphine (2.5 g) in triethylamine (100.0 ml), under a nitrogen atmosphere, is added decolorizing carbon (5.0 g) and palladium chloride (0.35 g). To this stirred slurry is added acrylic acid (20.0 g) followed by triethylamine (39.0 ml). The reaction mixture is refluxed for 4.5 hours, cooled to room temperature and diluted with water (700 ml). The pH of the reaction mixture is adjusted to ca. 2 by the slow addition of concentrated hydrochloric acid (63 ml). The solids are collected by filtration and the filter cake is washed with water until the pH is ca. 7 and then dried. The dried filter cake is suspended in boiling ethanol (350 ml), clarified, cooled to room temperature and diluted with water (450 ml) to induce crystallization. The slurry is cooled to -10° C. and the product collected by filtration. The filter cake is dried in vacuo at 45°. The dried solid is slurried in cold toluene, filtered and to dried to afford 3-[4-(2,5-dimethyl-1H-pyrrol-1-yl)phenyl)-2-propenoic acid, m.p. 184°-185°.