Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]([NH:36][C:37]([O:39][CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[O:38])([CH3:35])[CH2:3][C:4]([NH:6][C@@H:7]1[CH2:13][CH2:12][C:11]2[CH:14]=[CH:15][CH:16]=[CH:17][C:10]=2[N:9]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]3[C:26]([C:31]([OH:33])=O)=[CH:27][CH:28]=[CH:29][CH:30]=3)=[CH:21][CH:20]=2)[C:8]1=[O:34])=[O:5].C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[CH2:81]([CH2:83][NH2:84])[OH:82]>C(Cl)Cl.C(OCC)(=O)C>[OH:82][CH2:81][CH2:83][NH:84][C:31]([C:26]1[C:25]([C:22]2[CH:23]=[CH:24][C:19]([CH2:18][N:9]3[C:10]4[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=4[CH2:12][CH2:13][C@@H:7]([NH:6][C:4](=[O:5])[CH2:3][C:2]([NH:36][C:37]([O:39][CH2:40][C:41]4[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=4)=[O:38])([CH3:35])[CH3:1])[C:8]3=[O:34])=[CH:20][CH:21]=2)=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:33]
Reactant: CC(C)(CC(=O)N[C@@H]1CCc2ccccc2N(Cc2ccc(-c3ccccc3C(=O)O)cc2)C1=O)NC(=O)OCc1ccccc1
Reactant: NCCO
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: CC(C)(CC(=O)N[C@@H]1CCc2ccccc2N(Cc2ccc(-c3ccccc3C(=O)NCCO)cc2)C1=O)NC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 79.6 %

Procedure:
To a solution of 70 mg (0.11 mmol) of 4'-[[2,3,4,5-tetrahydro-3(R)-[[3-methyl-1-oxo-3-[(benzyloxycarbonyl)amino]butyl]amino]-2-oxo-1H-1-benzazepin-1-yl]methyl][1,1'-biphenyl]-2-carboxylic acid (Example 72, Step B) in 2 mL of dry methylene chloride under nitrogen at 0° C. was added 0.023 mL (0.17 mmol) of triethylamine followed by 55 mg (0.12 mmol) of benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate. After 5 minutes, 0.010 mL (0.33 mmol) of ethanolamine was added to the reaction by syringe. The reaction mixture was slowly warmed to room temperature. After 2 hours, the reaction was diluted with 75 mL of ethyl acetate, washed with 25 mL of 5% aqueous citric acid, 25 mL of saturated sodium bicarbonate and 25 mL of brine. The organic layer was dried over magnesium sulfate, filtered and the solvent removed under vacuum. The residue was purified by flash chromatography on silica gel eluting with ethyl acetate/methanol (97:3) to afford 58 mg (78%) of the product as a white foam. 1H NMR (200 MHz,CDCl3): 1.30 (s,3H), 1.35 (s,3H), 1.80 (m,1H), 2.20-2.75 (m,7H), 3.10-3.40 (m,4H), 4.51 (m,1H), 4.92 (d, 14 Hz, 1H), 5.00 (s,2H), 5.10 (d,14 Hz, 1H), 5.68 (s, 1H), 6.53 (d,6 Hz, 1H), 7.12-7.48 (m,16H), 7.65 (d;1.6 Hz;1H). FAB-MS: calculated for C39H42N4O6 662; found 686 (M+Na).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][NH2:6].[F:7][C:8]1[CH:9]=[C:10]([CH:13]=[CH:14][C:15]=1[F:16])[CH2:11]Br.[N:17]#[C:18]Br>>[F:7][C:8]1[CH:9]=[C:10]([CH:13]=[CH:14][C:15]=1[F:16])[CH2:11][N:1]1[CH2:2][CH2:3][CH2:4][CH2:5][N:6]([CH2:11][C:10]2[CH:13]=[CH:14][C:15]([F:16])=[C:8]([F:7])[CH:9]=2)[C:18]1=[NH:17]
Reactant: N#CBr
Reactant: Fc1ccc(CBr)cc1F
Reactant: NCCCCN
Product: N=C1N(Cc2ccc(F)c(F)c2)CCCCN1Cc1ccc(F)c(F)c1
Reaction time: 1 h

Procedure:
The title compound was prepared from 1,4-diaminobutane in four steps by Procedure A, using 3,4-difluorobenzyl bromide as benzylating reagent. After reacting with cyanogen bromide (this step performed at 200° C. for 60 min using MW heating), the crude product was isolated upon aqueous work-up and purified by preparative LCMS to give the title compound as the free base. MS (ES+) m/z 366 ([M+1]+, 100); HR-MS: 366.1599 ([M+1]+, C19H20F4N3; calc. 366.159334).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[C:4]([CH2:14][C:15]([CH:21]2[O:26][CH2:25][CH2:24][N:23](CC3C=CC=CC=3)[CH2:22]2)([OH:20])[CH2:16][CH:17]([CH3:19])[CH3:18])[CH:3]=1.[Cl:34]C(OC(Cl)C)=O.CCN(C(C)C)C(C)C>C(Cl)Cl>[ClH:34].[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)=[C:4]([CH2:14][C:15]([CH:21]2[O:26][CH2:25][CH2:24][NH:23][CH2:22]2)([OH:20])[CH2:16][CH:17]([CH3:19])[CH3:18])[CH:3]=1
Reactant: CC(C)CC(O)(Cc1cc(F)ccc1-c1ccccc1)C1CN(Cc2ccccc2)CCO1
Reactant: CC(Cl)OC(=O)Cl
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)CC(O)(Cc1cc(F)ccc1-c1ccccc1)C1CNCCO1
Product: Cl
Yield: 62 %

Procedure:
40 is prepared from 39 (1.31 g, 2.92 mmol), α-chloroethyl chloroformate (0.9 mL) and solid supported Hünig's base (1.64 g) in anhydrous DCM (30 mL) following General Procedure 3. Purification by ion exchange ion exchange chromatography gives the free base of 40 as a viscous oil (0.71 g, 62%). After further purification using UV-guided preparative LCMS, the hydrochloride salt 40 (0.451 g, 39%) is obtained following General Procedure 4. MW 393.95; C22H28FNO2. HCl; 1H NMR (DMSO-d6): δ 9.16 (1H, s), 8.98 (1H, s), 7.44-7.32 (4H, m), 7.23-7.06 (4H, m), 3.83 (1H, dd, 12 Hz, 3 Hz), 3.59-3.50 (3H, m), 3.18 (1H, d, 12.5 Hz), 3.08 (1H, d, 12.5 Hz), 2.92-2.67 (4H, m), 1.54-1.40 (1H, m), 1.03 (1H, dd, 14.5 Hz, 5 Hz), 0.88 (1H, dd, 14.5 Hz, 6.5 Hz), 0.74 (3H, d, 6.5 Hz), 0.67 (3H, d, 6.5 Hz); LCMS: (12 minute method) m/z 358 [M−HCl+H]+ RT 5.47 min.
Reaction SMILES: C([NH:4][C:5]1[CH:20]=[CH:19][C:8]2[C:9](=[O:18])[CH:10]=[C:11]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[O:12][C:7]=2[C:6]=1[CH2:21][CH2:22][CH3:23])(=O)C.Cl>C(O)C.O>[NH2:4][C:5]1[CH:20]=[CH:19][C:8]2[C:9](=[O:18])[CH:10]=[C:11]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[O:12][C:7]=2[C:6]=1[CH2:21][CH2:22][CH3:23]
Reactant: CCCc1c(NC(C)=O)ccc2c(=O)cc(C(=O)OCC)oc12
Agent: Cl
Solvent: CCO
Solvent: O
Product: CCCc1c(N)ccc2c(=O)cc(C(=O)OCC)oc12
Yield: 55.3 %

Procedure:
A solution of the amide of step (d) (10 g) in ethanol (300 ml), containing concentrated hydrochloric acid (5 ml), was refluxed for 8 hours. The reaction mixture was diluted with water and extracted into ethyl acetate. The extract was washed with water, dried and the solvent was evaporated to leave a dark brown semisolid. This was chromatographed on a silica gel column, using ether as eluant to give 4.8 g of the required product whose structure was confirmed by mass and NMR spectral evidence; mp 84°-87° C.
Reaction SMILES: [O:1]1[C:6]2=[CH:7][CH:8]=[CH:9][C:10]3[C:11](=[O:14])[C:12](=[O:13])[N:4]([C:5]=32)[CH2:3][CH2:2]1.[N+:15]([O-])([OH:17])=[O:16]>C(OC(=O)C)(=O)C>[N+:15]([C:8]1[CH:7]=[C:6]2[O:1][CH2:2][CH2:3][N:4]3[C:12](=[O:13])[C:11](=[O:14])[C:10]([CH:9]=1)=[C:5]23)([O-:17])=[O:16]
Reactant: O=[N+]([O-])O
Reactant: O=C1C(=O)N2CCOc3cccc1c32
Solvent: CC(=O)OC(C)=O
Product: O=C1C(=O)N2CCOc3cc([N+](=O)[O-])cc1c32
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 65.5 %

Procedure:
To a stirred solution of 2,3-dihydropyrrolo[1,2,3-de]-1,4-benzoxazine-5,6-dione (33.1 g) in acetic acid-acetic anhydride (200 ml, 1:1) under ice-cooling was added fuming nitric acid (9.4 ml) dropwise. The mixture was stirred for 0.5 hours at the same temperature (0° C.) and for an hour at room temperature. The reaction mixture was poured into ice water (500 ml) and the resultant precipitate was collected by filtration. This precipitate was washed with water and dried to give 26.9 g (65.5%) of the title compound. The filtrate was extracted with chloroform, washed with water, saturated aqueous sodium bicarbonate, water and saturated aqueous sodium chloride solution successively and then dried over anhydrous sodium sulfate. Evaporation of chloroform further afforded 2.9 g of the title compound. This compound was recrystallized from acetonitrile to give yellow needles, mp 230°-232° C.
Reaction SMILES: CN(C)C=O.S([O:16][CH:17]1[CH2:20][N:19]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:18]1)(C1C=CC(C)=CC=1)(=O)=O.[F:28][C:29]1[CH:34]=[CH:33][C:32](O)=[CH:31][CH:30]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(OCC)(=O)C.O>[F:28][C:29]1[CH:34]=[CH:33][C:32]([O:16][CH:17]2[CH2:18][N:19]([C:21]([O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:22])[CH2:20]2)=[CH:31][CH:30]=1
Reactant: Oc1ccc(F)cc1
Reactant: Cc1ccc(S(=O)(=O)OC2CN(C(=O)OC(C)(C)C)C2)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CC(Oc2ccc(F)cc2)C1
Yield: 72.9 %

Procedure:
An N,N-dimethylformamide solution (1.5 mL) of tert-butyl 3-(tosyloxy)azetidine-1-carboxylate (164 mg, 0.50 mmol), 4-fluorophenol (67.3 mg, 0.60 mmol), and cesium carbonate (116 mg, 0.60 mmol) was stirred at 80° C. for 16 hours. After completion of the reaction, water was added to the reaction solution and extraction with ethyl acetate from the resultant mixture was performed three times. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (97.4 mg, yield 73%).
Reaction SMILES: COCCOC.[Cl:7][C:8]1[CH:9]=[C:10]([C:15]([C:29]([F:32])([F:31])[F:30])=[CH:16][C:17]([C:19]2[CH:27]=[CH:26][C:22]([C:23]([OH:25])=[O:24])=[C:21]([CH3:28])[CH:20]=2)=O)[CH:11]=[C:12]([Cl:14])[CH:13]=1.C1(C)C=CC=CC=1.[OH2:40].S(O)(O)(=O)=O.[NH2:46]O>[OH-].[Na+]>[Cl:7][C:8]1[CH:9]=[C:10]([C:15]2([C:29]([F:32])([F:31])[F:30])[O:40][N:46]=[C:17]([C:19]3[CH:27]=[CH:26][C:22]([C:23]([OH:25])=[O:24])=[C:21]([CH3:28])[CH:20]=3)[CH2:16]2)[CH:11]=[C:12]([Cl:14])[CH:13]=1
Reactant: NO
Reactant: O
Reactant: Cc1cc(C(=O)C=C(c2cc(Cl)cc(Cl)c2)C(F)(F)F)ccc1C(=O)O
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1
Solvent: COCCOC
Product: Cc1cc(C2=NOC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)ccc1C(=O)O
Temperature: 0 °C
Reaction time: 3 h

Procedure:
6.27 g of 1,2-dimethoxyethane was added to solution in which 1.61 g of 4-(3-(3,5-dichlorophenyl)-4,4,4-trifluoro-2-butenoyl)-2-methylbenzoic acid was dissolved into 10.5 g of toluene, and the mixture was cooled to 0° C. A solution in which 0.64 g of sodium hydroxide was dissolved into 1.6 g of water was carefully added to the mixture so that the temperature of the reaction solution did not exceed 5° C. Moreover, a solution in which 0.46 g of hydroxylamine sulfate was dissolved into 2.24 g of water was carefully added to the mixture so that the temperature of the reaction solution did not exceed 5° C. The reaction was performed for 3 hours with stirring while keeping the reaction temperature at 0° C. The reaction solution was analyzed by high-performance liquid chromatography (detected by UV detector at a wavelength of 254 nm, and calculated with omitting the peak of toluene). The target product of 4-(5-(3,5-dichlorophenyl)-5-tri fluoromethyl-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid was produced in 88.4% of relative area.
Reaction SMILES: [H][H].[C:3].[N+]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)([O-])=O>>[CH3:3][C:7]1[C:12]2[C:11](=[CH:12][CH:7]=[CH:8][CH:9]=2)[CH:10]=[CH:9][CH:8]=1
Reactant: O=[N+]([O-])c1ccccc1
Reactant: [C]
Reactant: [H][H]
Product: Cc1cccc2ccccc12

Procedure:
80 parts by weight of a pitch and 20 parts by weight of methylnaphthalene were thermally mixed with each other by the use of a small-scale test spinning machine. The pitch used was a residue obtained by reduced pressure distillation of a botton oil which was produced in the production of ethylene, and had a softening point of 180° C, a carbon content of 92 wt%, a hydrogen/carbon ratio of 0.84 and a nitrobenzene-insoluble fraction of 2 wt%. The mixture was spinned out together with an air flow through a nozzle having a diameter of 0.5 mm at a nozzle temperature of 130° C to form a filament. The filament was immersed in naphtha to remove therefrom methylnaphthalene to obtain a fibrous material composed substantially of the pitch. The fibrous material which was dried contained methylnaphthalene only in an amount less than 1 %. The fibrous pitch material was heated by means of heating air up to 300° C at a heating rate of 25° C/hr, and maintained at 300° C for 1 hour to obtain an infusible fibrous pitch mat. Then, the resultant fibre, was thermally treated in an atmosphere of nitrogen up to 1000° C at a heating rate of 300° C/hr and maintained at 1000° C for 1 hour to obtain a porous fibrous carbon material.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:15][CH:14]([OH:16])[C:13]2[CH:17]=[CH:18][CH:19]=[CH:20][C:12]=2[N:11]([CH2:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:10]1=[O:29])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:30](OC(=O)C)(=[O:32])[CH3:31]>>[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:15][CH:14]([O:16][C:30](=[O:32])[CH3:31])[C:13]2[CH:17]=[CH:18][CH:19]=[CH:20][C:12]=2[N:11]([CH2:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:10]1=[O:29])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(=O)OC(C)=O
Reactant: CC(C)(C)OC(=O)CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)CC(O)c2ccccc21
Product: CC(=O)OC1C[C@H](NC(=O)OC(C)(C)C)C(=O)N(CC(=O)OC(C)(C)C)c2ccccc21

Procedure:
A solution of 3-(S)-t-butyloxycarbonylamino-1-t-butyloxycarbonylmethyl-5-hydroxy-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one (described above, 3.0 g) in acetic anhydride (50 ml) was heated at 80° under a dry nitrogen atmosphere for 2 hours. The acetic anhydride was evaporated. The residue was dissolved in ethyl acetate (75 ml) and washed with saturated sodium bicarbonate (50 ml), water (50 ml), and saturated sodium chloride (50 ml). The organic phase was dried (sodium sulfate), evaporated, and the residue triturated with ether (50 ml) to give 3-(S)-t-butyloxycarbonylamino-1-t-butyloxycarbonylmethyl-5-acetoxy-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one, m.p. 164°-166.5° C., [α]D =-169° (C=0.36 in DMF).
Reaction SMILES: COC1C=CC=CC=1S[C:10]1[S:14][C:13]([C:15]([NH2:17])=[NH:16])=[CH:12][C:11]=1[C:18]1[S:19][CH:20]=[C:21]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:22]=1.[CH3:29][O:30]C1C=CC=CC=1SC1SC(C(OC)=O)=CC=1C1SC=C(C2C=CC=CC=2)N=1>>[CH3:29][O:30][C:10]1[S:14][C:13]([C:15]([NH2:17])=[NH:16])=[CH:12][C:11]=1[C:18]1[S:19][CH:20]=[C:21]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[N:22]=1
Reactant: COC(=O)c1cc(-c2nc(-c3ccccc3)cs2)c(Sc2ccccc2OC)s1
Reactant: COc1ccccc1Sc1sc(C(=N)N)cc1-c1nc(-c2ccccc2)cs1
Product: COc1sc(C(=N)N)cc1-c1nc(-c2ccccc2)cs1
Yield: 91 %

Procedure:
5-(Methoxyphenylthio)-4-(4-phenyl(1,3-thiazol-2-yl))thiophene-2-carboxamidine: Methyl 5-(methoxyphenylthio)-4-(4-phenyl(1,3-thiazol-2-yl))thiophene-2-carboxylate (100 mg, 0.22 mmol) was treated in a manner similar to that for Example 10, step (b), to give 5-methoxy-4-(4-phenyl(1,3-thiazol-2-yl))thiophene-2-carboxamidine (94 mg, 91%) as an orange solid. 1H-NMR (DMSO-d6; 300 MHz) δ 9.49 (br s, 2H), 9.15 (br s, 2H), 8.70 (s, 1H), 8.26 (s, 1H), 8.07 (m, 2H), 7.49 (m, 2H), 7.40 (m, 1H), 7.35 and 6.90 (AB quartet, 2H, J=8.7 Hz), 4.41 (s, 2H), 3.73 (s, 3H). Mass spectrum (MALDI-TOF, CHCA matrix, m/z): Calcd. for C22H19N3OS3 438.5 (M+H), found 438.1.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.[OH:10][C:11]1[CH:16]=[CH:15][C:14]([C:17](=O)[CH3:18])=[CH:13][CH:12]=1.C(OCC)C.S(=O)(=O)(O)O>C(O)C>[OH:10][C:11]1[CH:16]=[CH:15][C:14]([CH:17]=[CH:18][C:6]([C:5]2[CH:8]=[CH:9][C:2]([OH:1])=[CH:3][CH:4]=2)=[O:7])=[CH:13][CH:12]=1
Reactant: CC(=O)c1ccc(O)cc1
Reactant: O=Cc1ccc(O)cc1
Agent: O=S(=O)(O)O
Solvent: CCOCC
Solvent: CCO
Product: O=C(C=Cc1ccc(O)cc1)c1ccc(O)cc1
Reaction time: 3 h

Procedure:
First, 4-hydroxybenzaldehyde (0.488 g, 4 mmole) and 4′-hyroxyacetophenone (0.66 g, 4.84 mmole) are introduced to a 25 mL flask and dissolved completely by adding 10 mL of diethyl ether and 4 mL of ethanol thereto. Next, 4 mL of sulfuric acid is introduced thereto and the reaction mixture is agitated for 3 hours. The reaction mixture is precipitated in water (300 mL) and filtered to obtain a solid, which in turn is washed with distilled water three times, dried under vacuum, and purified by column chromatography using diethyl ether/hexane (1/1, v/v) as eluent to obtain 4,4′-dihydroxychalcone (DHC) having the following structure. The resultant product has a yield and melting point of 30% and 203° C., respectively.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[CH2:10][C:11]([NH:13][CH3:14])=[O:12].C1C(=O)N([Br:22])C(=O)C1.C(OOCC1C=CC=CC=1)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[Br:22][CH:10]([C:3]1[CH:4]=[CH:5][C:6]([O:8][CH3:9])=[CH:7][C:2]=1[Cl:1])[C:11]([NH:13][CH3:14])=[O:12]
Reactant: CNC(=O)Cc1ccc(OC)cc1Cl
Reactant: O=C1CCC(=O)N1Br
Agent: c1ccc(COOCc2ccccc2)cc1
Solvent: ClC(Cl)(Cl)Cl
Product: CNC(=O)C(Br)c1ccc(OC)cc1Cl
Temperature: 80 °C
Yield: 61.4 %

Procedure:
A mixture of 2-(2-chloro-4-methoxy-phenyl)-N-methyl-acetamide (70a) (0.22 g, 1.03 mmol), NBS (183 mg, 1.03 mmol), and 70% benzyl peroxide (36 mg, 0.103 mmol) in 6 mL of CCl4 was refluxed at 80° C. for three hours, cooled to room temperature, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography eluting with 1:1 EtOAc and hexanes to provide 185 mg white solid as the intermediate 70b. 1H NMR (300 MHz, CDCl3) δ 7.42 (d, 1H, J=8.85 Hz), 6.90 (d, 1H, J=2.63 Hz), 6.83–6.76 (m, 1H), 5.83 (s, 1H), 3.78 (s, 3H), 2.90 (d, 3H, J=4.90 Hz). LCMS (ESI+) [M+H]/z Calc'd 294, found 294.
Reaction SMILES: C/C=C/[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[C:10](=[O:13])([O-])[O-].[K+].[K+].O.[CH3:17][C:18](C)=[O:19]>[Fe-3](C#N)(C#N)(C#N)(C#N)(C#N)C#N.[K+].[K+].[K+]>[C:4]1([CH:10]([OH:13])[CH:18]([OH:19])[CH3:17])[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: CC(C)=O
Reactant: O=C([O-])[O-]
Reactant: C/C=C/c1ccccc1
Agent: N#C[Fe-3](C#N)(C#N)(C#N)(C#N)C#N
Agent: [K+]
Solvent: O
Product: CC(O)C(O)c1ccccc1
Reaction time: 1 h
Yield: 85 %

Procedure:
To 3.5 ml of a water-acetone (1:1) solvent were added 66.6 mg of the osmium oxide carried by the carrier of the present invention obtained in Example 4, 21.5 mg of 1,4-bis(9-o-dihydroquinidil)phthalazine, 362.2 mg of potassium ferricyanide and 152.0 mg of potassium carbonate, followed by reacting at 30° C. for 1 hour while stirring. And 59.0 mg of trans-β-methylstyrene dissolved in 1.5 ml of a water-acetone (1:1) solvent were added to the reaction solution and followed by reacting for another 2 hours while stirring. And further, 362.2 mg of potassium ferricyanide and 152.0 mg of potassium carbonate were added to the reaction solution and followed by reacting for another 2 hours while stirring. After the reaction was terminated by adding methanol, the filtrate obtained by filtrating the reaction solution was concentrated to some extent. The obtained product was dissolved in 5 ml of methylene chloride and filtrated using Celite. The filtrate was concentrated and purified using a silica gel thin-layer chromatography, to obtain 70.6 mg of a desired diol, 1-phenyl-1,2-propane diol (yield 85%) (97% ee).
Reaction SMILES: C(O[C:6]([N:8]1[CH2:12][C:11](=[N:13][O:14][CH3:15])[CH2:10][C@H:9]1[C:16]([OH:18])=O)=[O:7])(C)(C)C.[C:19]([C:27]1[CH:35]=[CH:34][C:30](C(O)=O)=[CH:29][CH:28]=1)(=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.[NH2:36][CH2:37][CH:38]([C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[OH:39]>>[C:19]([C:20]1[CH:21]=[CH:22][C:23]([C:6]([N:8]2[CH2:12][C:11](=[N:13][O:14][CH3:15])[CH2:10][C@H:9]2[C:16]([NH:36][CH2:37][CH:38]([OH:39])[C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)=[O:18])=[O:7])=[CH:24][CH:25]=1)(=[O:26])[C:27]1[CH:28]=[CH:29][CH:30]=[CH:34][CH:35]=1
Reactant: NCC(O)c1ccccc1
Reactant: CON=C1C[C@@H](C(=O)O)N(C(=O)OC(C)(C)C)C1
Reactant: O=C(O)c1ccc(C(=O)c2ccccc2)cc1
Product: CON=C1C[C@@H](C(=O)NCC(O)c2ccccc2)N(C(=O)c2ccc(C(=O)c3ccccc3)cc2)C1

Procedure:
Following the general method as outlined in Example 22, starting from (2S,4EZ)-1-(tert-butoxycarbonyl)-4-(methoxyimino)-2-pyrrolidinecarboxylic acid, 4-benzoylbenzoic acid, and (1RS)-2-amino-1-phenylethanol, the title compound was obtained in 93% purity by HPLC. MS(ESI+): m/z=486.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1I.C([Mg]Cl)(C)C.[CH3:14][C:15]1[CH:16]=[C:17]([P:24]([C:26]2[CH:31]=[C:30]([CH3:32])[C:29]([O:33][CH3:34])=[C:28]([CH3:35])[CH:27]=2)Cl)[CH:18]=[C:19]([CH3:23])[C:20]=1[O:21][CH3:22]>C1COCC1.CC(OC)(C)C>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[P:24]([C:26]1[CH:31]=[C:30]([CH3:32])[C:29]([O:33][CH3:34])=[C:28]([CH3:35])[CH:27]=1)[C:17]1[CH:16]=[C:15]([CH3:14])[C:20]([O:21][CH3:22])=[C:19]([CH3:23])[CH:18]=1
Reactant: Brc1ccccc1I
Reactant: COc1c(C)cc(P(Cl)c2cc(C)c(OC)c(C)c2)cc1C
Agent: CC(C)[Mg]Cl
Solvent: C1CCOC1
Solvent: COC(C)(C)C
Product: COc1c(C)cc(P(c2cc(C)c(OC)c(C)c2)c2ccccc2Br)cc1C
Temperature: -78 °C
Reaction time: 1 h
Yield: 76 %

Procedure:
To a solution of 9.67 g (34.2 mmol) of 1-bromo-2-iodobenzene in 30 ml of THF are added dropwise, at −78° C., 17.6 ml (37.6 mmol) of an isopropylmagnesium chloride solution (2 molar in THF). The mixture is stirred at a temperature between −30° C. and −40° C. for a further 1 hour, then cooled again to −78° C., and a solution of 12.66 g (37.6 mmol) of bis(3,5-dimethyl-4-methoxyphenyl)chlorophosphine in 10 ml of THF and 10 ml of TBME is added. The cooling is removed and the reaction mixture is stirred at room temperature overnight. The resulting solution is admixed with 50 ml of water and extracted with water/TBME. The organic phases are collected and dried over sodium sulphate, and the solvent is distilled off under reduced pressure on a rotary evaporator. The crude product is purified by chromatography (silica gel 60; eluent=1:1 heptane/ethyl acetate). The desired product is obtained in the form of white crystals in a yield of 76%.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][CH:20]=1)[C:5]([NH:7][C:8]1[CH:9]=[C:10]([CH:15]=[CH:16][CH:17]=1)[C:11](OC)=[O:12])=[O:6].O.[NH2:22][NH2:23]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][CH:20]=1)[C:5]([NH:7][C:8]1[CH:9]=[C:10]([CH:15]=[CH:16][CH:17]=1)[C:11]([NH:22][NH2:23])=[O:12])=[O:6]
Reactant: NN
Reactant: COC(=O)c1cccc(NC(=O)c2cccc(Cl)c2)c1
Solvent: C1CCOC1
Solvent: O
Product: NNC(=O)c1cccc(NC(=O)c2cccc(Cl)c2)c1
Temperature: 65 °C

Procedure:
To a solution of 1.0 gm (3.45 mmol) of methyl 3-(3-chlorobenzamido)benzoate in 24 mL of tetrahydrofuran was added 1.18 mL (34.5 mmol) of hydrazine hydrate. The reaction was heated overnight at 65° C. After cooling, the reaction mixture was concentrated under rotevaporation, and ether and water were added. The solid product was separated by filtration and dried in vacuo to give 3-(3-chlorobenzamido)benzhydrazide. MS m/z: 290.0 (M+H).
Reaction SMILES: [OH-].[Na+].[OH:3][C:4]1[C:9](=[O:10])[CH:8]=[C:7]([CH:11]([OH:16])[C:12]([F:15])([F:14])[F:13])[N:6]([CH3:17])[C:5]=1[CH2:18][OH:19].[CH2:20](Br)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>CO>[CH2:20]([O:3][C:4]1[C:9](=[O:10])[CH:8]=[C:7]([CH:11]([OH:16])[C:12]([F:15])([F:13])[F:14])[N:6]([CH3:17])[C:5]=1[CH2:18][OH:19])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: BrCc1ccccc1
Reactant: Cn1c(C(O)C(F)(F)F)cc(=O)c(O)c1CO
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: Cn1c(C(O)C(F)(F)F)cc(=O)c(OCc2ccccc2)c1CO
Temperature: 25 °C
Yield: 76 %

Procedure:
A 6.00 N sodium hydroxide solution (785 μL, 4.71 mmol) was added to a suspension of 3-hydroxy-2-hydroxymethyl-1-methyl-6-(2,2,2-trifluoro-1-hydroxy-ethyl)-1H-pyridin-4-one (1.08 g, 4.26 mmol) in methanol (5 mL). Benzyl bromide (650 μL, 5.46 mmol) was added to the clear solution, and the resulting solution was heated to reflux for 45 min Some solid had separated out in the solution. Analysis of the reaction mixture using HPLC Method 1 (Example 24) indicated that the starting material was consumed. The reaction mixture was allowed to cool down to room temperature, and the first crop of solid product was collected by suction filtration, and washed with acetonitrile. The title compound was thus obtained as a solid product (1.11 g, 76% yield, HPLC Method 1 (Example 24), RT=12.6 min, HPLC purity (peak percent area): 99% at x=280 nm). 1H NMR (DMSO-d6+D2O) δ ppm: 7.36 (m, 5H), 6.59 (s, 1H), 5.53 (q, J=6.5 Hz, 1H), 5.01 (s, 2H), 4.58 (s, 2H), 3.72 (s, 3H).