Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.C[Si](C)(C)[C:11]#[C:12][CH3:13].C(N(CC)CC)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1(C)C=CC=CC=1.[Cu]I.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.O>[Br:8][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([C:11]#[C:12][CH3:13])[CH:7]=1
Reactant: Brc1cncc(Br)c1
Reactant: CC#C[Si](C)(C)C
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Solvent: O
Product: CC#Cc1cncc(Br)c1
Reaction time: 8 h
Yield: 65.8 %

Procedure:
3,5-Dibromopyridine (30 g, 127 mmol), copper(I) iodide (7.24 g, 38.0 mmol) and tetrakis(triphenylphosphine)palladium(0) (4.39 g, 3.80 mmol) were mixed in toluene (120 mL) under nitrogen atmosphere. 1-(Trimethylsilyl)-1-propyne (26.36 mL, 164.5 mmol), triethylamine (53.0 mL, 380 mmol) and tetra-n-butylammonium fluoride (12.66 mL, 12.66 mmol) were added. The mixture was heated to reflux and stirred under nitrogen overnight. Water (100 mL) was added to the reaction mixture was filtered and the phases separated. The organic phase was washed with 1 M HCl aq. (100 mL). The organic phase was concentrated and dissolved in MeOH (200 mL), filtered and concentrated. The mixture was dissolved in DCM and evaporated with silica gel to dryness, and then transferred to a silica gel column (300 g). The product was eluted with a gradient of EtOAc (0-5%) in heptane. The fractions containing the pure product was combined and evaporated to give the title compound (16.39 g, 66% yield): 1H NMR (500 MHz, CDCl3) δ ppm 2.08 (s, 3 H), 7.82 (t, 1 H), 8.52 (d, 1 H), 8.55 (d, 1 H); MS (APCI+) m/z 197.0 [M+H]+.
Reaction SMILES: C([O:3][P:4]([CH2:9][C:10]1[S:14][C:13]2[CH:15]=[CH:16][C:17]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([CH2:26][CH3:27])=[CH:22][CH:21]=3)=[CH:18][C:12]=2[CH:11]=1)(=[O:8])[O:5]CC)C.Cl>C(O)C>[CH2:26]([C:23]1[CH:24]=[CH:25][C:20]([CH2:19][C:17]2[CH:16]=[CH:15][C:13]3[S:14][C:10]([CH2:9][P:4](=[O:3])([OH:5])[OH:8])=[CH:11][C:12]=3[CH:18]=2)=[CH:21][CH:22]=1)[CH3:27]
Reactant: CCOP(=O)(Cc1cc2cc(Cc3ccc(CC)cc3)ccc2s1)OCC
Agent: Cl
Solvent: CCO
Product: CCc1ccc(Cc2ccc3sc(CP(=O)(O)O)cc3c2)cc1
Yield: 78.4 %

Procedure:
To a solution of [5-(4-ethylbenzyl)benzo[b]thiophen-2-ylmethyl]phosphonic acid diethylester (0.80 g) in ethanol (8.0 mL) was added 6N—HCl (8.0 mL), and the reaction mixture was refluxed for 42 hr. Evaporation and crystallization from ethyl acetate-n-hexane gave the title compound (0.54 g) as a colorless crystal.
Reaction SMILES: Cl.Cl[CH2:3][C:4]1[N:5]=[C:6]([CH2:9][N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[S:7][CH:8]=1.[Cl:16][C:17]1[CH:18]=[C:19]([NH:24][C:25]2[C:34]3[C:29](=[CH:30][C:31]([OH:37])=[C:32]([O:35][CH3:36])[CH:33]=3)[N:28]=[CH:27][N:26]=2)[CH:20]=[CH:21][C:22]=1[Cl:23].C(=O)([O-])[O-].[K+].[K+]>>[Cl:16][C:17]1[CH:18]=[C:19]([NH:24][C:25]2[C:34]3[C:29](=[CH:30][C:31]([O:37][CH2:3][C:4]4[N:5]=[C:6]([CH2:9][N:10]5[CH2:15][CH2:14][O:13][CH2:12][CH2:11]5)[S:7][CH:8]=4)=[C:32]([O:35][CH3:36])[CH:33]=3)[N:28]=[CH:27][N:26]=2)[CH:20]=[CH:21][C:22]=1[Cl:23]
Reactant: COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1O
Reactant: ClCc1csc(CN2CCOCC2)n1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Product: COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1csc(CN2CCOCC2)n1
Temperature: 70 °C
Reaction time: 21 h
Yield: 55.1 %

Procedure:
4-([4-(Chloromethyl)-1,3-thiazol-2-yl]methyl}morpholine hydrochloride (0.024 g, 0.089 mmol) and 4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-ol (0.030 g, 0.089 mmol) were suspended in DMP (2 mL) and potassium carbonate (0.062 g, 0.449 mmol) was added. The mixture was stirred at 70° C. for 21 h. The reaction mixture was concentrated in vacuo and the residue was purified by reverse phase HPLC to afford the title compound as a colorless solid (0.026 g, 0.049 mmol, 54% yield). 1H NMR (400 MHz; CDCl3): 2.50 (br s, 1H); 2.57-2.64 (m, 4H); 3.75 (t, 4H); 3.84 (s, 2H); 3.96 (s, 3H); 5.28 (s, 2H); 7.09 (s, 1H); 7.31 (s, 1H); 7.37 (s, 1H); 7.43 (d, 1H); 7.60 (dd, 1H); 7.97 (d, 1H); 8.61 (s, 1H); MS (EI) for C24H23Cl2N5O3S: 532 (MH+).
Reaction SMILES: CO.[OH-].[Na+].[C:5]1([C:11]2[CH:23]=[CH:22][C:14]([C:15]([O:17]C(C)(C)C)=[O:16])=[C:13]([NH:24][C:25](=[O:37])[C:26]3[CH:31]=[CH:30][C:29]([N:32]4[CH:36]=[CH:35][CH:34]=[CH:33]4)=[CH:28][CH:27]=3)[CH:12]=2)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.Cl>C(OCC)(=O)C.O1CCOCC1>[C:5]1([C:11]2[CH:23]=[CH:22][C:14]([C:15]([OH:17])=[O:16])=[C:13]([NH:24][C:25](=[O:37])[C:26]3[CH:31]=[CH:30][C:29]([N:32]4[CH:33]=[CH:34][CH:35]=[CH:36]4)=[CH:28][CH:27]=3)[CH:12]=2)[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1
Reactant: CC(C)(C)OC(=O)c1ccc(-c2ccccc2)cc1NC(=O)c1ccc(-n2cccc2)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: CO
Solvent: CCOC(C)=O
Product: O=C(Nc1cc(-c2ccccc2)ccc1C(=O)O)c1ccc(-n2cccc2)cc1
Temperature: 50 °C
Reaction time: 0.5 h
Yield: 86 %

Procedure:
1.0 mL of methanol and 0.5 mL of 2.0 mol/L aqueous sodium hydroxide were added to 1.0 mL of dioxane solution containing 20 mg of tert-butyl 4-phenyl-2-(4-(1H-pyrrol-1-yl)benzamido)benzoate at room temperature and stirred at 50° C. for 30 minutes. Ethyl acetate and 1.0 mol/L hydrochloric acid were added after the reaction mixture was cooled to room temperature. The organic layer was separated and dried over anhydrous magnesium sulfate after washed with a saturated sodium chloride aqueous solution, and the solvent was evaporated under reduced pressure, Diisopropyl ether were added to toe obtained residue and a solid substance was separated by filtration to obtain 15 mg of 4-phenyl-2-(4-(1H-pyrrol-1-yl)benzamido)benzoic acid as white solid.
Reaction SMILES: C([O:8][CH2:9][C:10]([O:12][CH2:13][O:14][C:15](=[O:25])[CH2:16][O:17]CC1C=CC=CC=1)=[O:11])C1C=CC=CC=1.[H][H]>[Pd].C(O)C>[OH:8][CH2:9][C:10]([O:12][CH2:13][O:14][C:15](=[O:25])[CH2:16][OH:17])=[O:11]
Reactant: [H][H]
Reactant: O=C(COCc1ccccc1)OCOC(=O)COCc1ccccc1
Agent: [Pd]
Solvent: CCO
Product: O=C(CO)OCOC(=O)CO
Reaction time: 16 h
Yield: 93.4 %

Procedure:
Methylene bis(benzyloxyacetate) (0.52 g, 1.5 mmol) and Pd/C (100 mg, 10%) are added to dry ethanol (100 ml). Hydrogen (1 atm) is introduced and the reaction is complete after 16 hours at room temperature, whereupon the reaction mixture is filtered and the solvent is evaporated under reduced pressure (0.01 mmHg) to yield 0.23 g (95%) product. 1H NMR (200 MHz, MeOH): δ 4.2 (CH2, s), 4.9 (OH), 5.9 (OCH2O, s). The product may be used to form polyesters with di- or poly-acids and to form polyurethanes with isocyanates.
Reaction SMILES: Cl[CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][OH:10].[I-:11].[Na+]>CC(C)=O>[I:11][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][OH:10]
Reactant: [I-]
Reactant: OCCOCCOCCCl
Agent: [Na+]
Solvent: CC(C)=O
Product: OCCOCCOCCI
Reaction time: 16 h
Yield: 53 %

Procedure:
One hundred grams (0.59 mole) of 2-[2-(2-chloroethoxy)ethoxy]-ethanol (Aldrich 16,297-3) was added to a solution of 450 g. (3 mol) of sodium iodide in 2.5 l acetone and stirred, in the dark, for 5 hours at reflux and then at room temperature for 16 hours. The precipitate was filtered and the acetone evaporated off at 30° C. The residue was dissolved in chloroform, extracted with saturated sodium chloride solution, and then with saturated sodium bisulfate solution. The chloroform extract was dried (MgSO4) and evaporated at room temperature to yield 137 g. (53%) of the title compound.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([O:13][S:14]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([CH3:23])[CH:18]=2)(=[O:16])=[O:15])[CH:5]=[C:6]([CH:12]=1)[O:7][CH2:8][CH2:9][CH2:10][OH:11].C(N(CC)C(C)C)(C)C.CS(C)=O>ClCCl>[CH3:1][C:2]1[CH:3]=[C:4]([O:13][S:14]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([CH3:23])[CH:18]=2)(=[O:16])=[O:15])[CH:5]=[C:6]([CH:12]=1)[O:7][CH2:8][CH2:9][CH:10]=[O:11]
Reactant: Cc1cc(OCCCO)cc(OS(=O)(=O)c2cccc(C)c2)c1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Solvent: CS(C)=O
Product: Cc1cc(OCCC=O)cc(OS(=O)(=O)c2cccc(C)c2)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 89.7 %

Procedure:
Sulfur trioxide pyridine complex (720 mg, 4.5 mmol) was added to a solution of 3-[5-methyl-3-(3-methylphenylsulfonyloxy)phenoxy]propanol (505 mg, 1.5 mmol), as prepared in the preceding step, N,N-diisopropylethylamine (0.6 mL, 4.7 mmol) and anhydrous dimethyl sulfoxide (0.3 mL, 4.2 mmol) in anhydrous dichloromethane (15 mL). The reaction mixture was stirred at ambient temperature for 1 hour and then quenched with 10% aqueous citric acid (50 mL). The mixture was extracted into dichloromethane (3×50 mL), and the dichloromethane solution was washed with 10% aqueous citric acid (40 mL) and dried over Na2SO4. After removing the solvent in vacuo, the residue was purified by flash column chromatography (dichloromethane) to give the title compound as a colorless oil (450 mg, 89%). 1H-NMR (300 MHz, CDCl3) δ 9.83 (s, 1H), 7.69 (s, 1H), 7.65 (d, J=7.6 Hz, 1H), 7.46 (t, J=7.7 Hz, 1H), 7.41 (t, J=7.6 Hz, 1H), 6.61 (s, 1H), 6.44 (s, 1H), 6.35 (s, 1H), 4.18 (t, J=6.0 Hz, 2H), 2.85 (t, J=6.1 Hz, 2H), 2.43 (s, 3H), 2.24 (s, 3H).
Reaction SMILES: [CH3:1][CH:2]([CH3:13])[C@@H:3]([NH2:12])[CH2:4][O:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.C([O:22][C@@H:23]1[C@H:27]([O:28]C(=O)C2C=CC=CC=2)[C@@H:26]([CH2:37][O:38]C(=O)C2C=CC=CC=2)[O:25][C@H:24]1[N:47]1[CH:55]=[N:54][C:53]2[C:48]1=[N:49][C:50]([Cl:57])=[N:51][C:52]=2Cl)(=O)C1C=CC=CC=1.C(N(CC)CC)C.ClCCl>O1CCOCC1>[Cl:57][C:50]1[N:51]=[C:52]([NH:12][C@H:3]([CH:2]([CH3:13])[CH3:1])[CH2:4][O:5][C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:53]2[N:54]=[CH:55][N:47]([C:48]=2[N:49]=1)[C@@H:24]1[O:25][C@H:26]([CH2:37][OH:38])[C@@H:27]([OH:28])[C@H:23]1[OH:22]
Reactant: CC(C)[C@@H](N)COc1ccccc1
Reactant: O=C(OC[C@H]1O[C@@H](n2cnc3c(Cl)nc(Cl)nc32)[C@H](OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1)c1ccccc1
Solvent: C1COCCO1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)[C@H](COc1ccccc1)Nc1nc(Cl)nc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Temperature: 25 °C
Reaction time: 40 h
Yield: 45.1 %

Procedure:
(R)-3-methyl-1-phenoxy-2-butylamine (0.6 g, 2.8 mmol) was reacted with 9-(2,3,5-tri- O-benzoyl-β-D-ribofuranosyl)-2,6-dichloro-9H-purine (1.4 g, 2.2 mmol) in dioxan (20 ml) in the presence of triethylamine (0.5 g, 5.0 mmol). The reaction mixture was stirred at room temperature for 40 h before being filtered and evaporated. The product (after purification by flash chromatography) was debenzoylated with methanolic ammonia to provide the product (after column chromatography) as a foam which solidified on coevaporation with dichloromethane. 2-Chloro- N-[(R)-3-methyl-1-phenoxy2-butyl]adenosine (0.46 g, 44%) was obtained as a white solid, mp 95°-100° C., 1H NMR (DMSO-d6)δ 0.95, 0.98 (6H, 2d, 2×--CH3), 2.10 (1H, m, --C H(CH3)2), 3.53-3.60 (1H, m, H-5'a), 3.63-3.71 (1H, m, H-5'b), 3.95 (1H, q, H-4), 4.07-4.23 (3H, m, H-3' and --CH2 --), 4.96 (1H, m, --C--H), 4.56 (1H, q, H-2'), 5.08 (1H, t, 5'-OH), 5.23, 5.49 (2H, 2d, 2' and 3'-OH), 5.84 (1H, d, H-1'), 6.87-6.97 (3H, m, Ar--H), 7.24-7.31 (2H, dd, Ar--H), 8.36 (1H, d, --N--H), 8.40 (1H, s, H-8).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH2:10][C:11]1[CH:12]=[C:13]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[N:14]([S:16]([C:19]2[CH:20]=[C:21]([CH:25]=[CH:26][CH:27]=2)[C:22]([OH:24])=O)(=[O:18])=[O:17])[CH:15]=1)[CH3:9])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.C(N=C=N[CH2:40][CH2:41][CH2:42][N:43](C)C)C.ON1C2C=CC=CC=2N=N1.C1(N)CC1>CN(C)C=O.O>[CH:42]1([NH:43][C:22]([C:21]2[CH:20]=[C:19]([S:16]([N:14]3[C:13]([C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)=[CH:12][C:11]([CH2:10][N:8]([CH3:9])[C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[CH:15]3)(=[O:18])=[O:17])[CH:27]=[CH:26][CH:25]=2)=[O:24])[CH2:40][CH2:41]1
Reactant: CCN=C=NCCCN(C)C
Reactant: CN(Cc1cc(-c2ccccc2)n(S(=O)(=O)c2cccc(C(=O)O)c2)c1)C(=O)OC(C)(C)C
Agent: Cl
Agent: NC1CC1
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: O
Product: CN(Cc1cc(-c2ccccc2)n(S(=O)(=O)c2cccc(C(=O)NC3CC3)c2)c1)C(=O)OC(C)(C)C
Reaction time: 0.5 h

Procedure:
To a solution (5 mL) of 3-[(4-{[(tert-butoxycarbonyl)(methyl)amino]methyl}-2-phenyl-1H-pyrrol-1-yl)sulfonyl]benzoic acid (150 mg) in N,N-dimethylformamide were added 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (92 mg), 1-hydroxy-1H-benzotriazole (73 mg) and cyclopropylamine (27 mg) at room temperature. After stirring at the same temperature for 30 min, water was added and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=9:1→4:1) to give the title compound as a colorless amorphous (yield 162 mg, quantitative).
Reaction SMILES: CCOC(/N=N/C(OCC)=O)=O.[C:13]([O:17][C:18](=[O:26])[NH:19][CH2:20][C:21]([CH3:25])([CH3:24])[CH2:22][OH:23])([CH3:16])([CH3:15])[CH3:14].O[N:28]1[C:32](=[O:33])[C:31]2=[CH:34][CH:35]=[CH:36][CH:37]=[C:30]2[C:29]1=[O:38].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1.ClCCl>[C:13]([O:17][C:18](=[O:26])[NH:19][CH2:20][C:21]([CH3:25])([CH3:24])[CH2:22][O:23][N:28]1[C:32](=[O:33])[C:31]2[C:30](=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:29]1=[O:38])([CH3:16])([CH3:14])[CH3:15]
Reactant: O=C1c2ccccc2C(=O)N1O
Reactant: CC(C)(CO)CNC(=O)OC(C)(C)C
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: C1CCOC1
Product: CC(C)(CNC(=O)OC(C)(C)C)CON1C(=O)c2ccccc2C1=O
Temperature: 25 °C
Reaction time: 16 h
Yield: 11.4 %

Procedure:
Diethylazodicarboxylate (8.26 mL, 52.4 mmol) was added to a solution of (3-hydroxy-2,2-dimethyl-propyl)-carbamic acid tert-butyl ester (10.2 g, 49.9 mmol), N-hydroxyphthalimide (8.15 g, 49.9 mmol) and triphenylphosphine (13.1 g, 49.9 mmol) in THF (200 mL). The solution was stirred at room temperature for 16 hours after which time it was diluted with dichloromethane and passed through a plug of silica gel, eluting with dichloromethane. The product containing fractions were concentrated to a yellow liquid, which was further purified by flash column chromatography (dichloromethane to 4:1 dichloromethane/ethyl acetate) to provide pure desired product (1.98 g, 11%) as a waxy white solid.
Reaction SMILES: COC1C=C(OC)C=CC=1C[N:12]1[C:21]2[C:16](=[C:17]([CH3:23])[CH:18]=[C:19]([Cl:22])[N:20]=2)[C:15](=[O:24])[C:14]([C:25]([O:27]CC)=[O:26])=[CH:13]1.O.[OH-].[Li+]>O1CCOCC1>[Cl:22][C:19]1[N:20]=[C:21]2[C:16]([C:15](=[O:24])[C:14]([C:25]([OH:27])=[O:26])=[CH:13][NH:12]2)=[C:17]([CH3:23])[CH:18]=1
Reactant: CCOC(=O)c1cn(Cc2ccc(OC)cc2OC)c2nc(Cl)cc(C)c2c1=O
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: Cc1cc(Cl)nc2[nH]cc(C(=O)O)c(=O)c12
Temperature: 60 °C
Reaction time: 16 h

Procedure:
A solution of Example 65D (0.200 g) in 1.4-dioxane (5 mL) was treated with lithium hydroxide monohydrate (0.100 g), stirred for 16 hours, and concentrated. The concentrate was dissolved in trifluoroacetic acid (8 mL), heated at 60° C. for 12 hours, and concentrated; and this concentrate was purified by reverse phase HPLC to afford the desired product. NMR (300 MHz, DMSO-d6) δ 14.95 (s, 1H), 13.79 (s, 1H), 8.72 (s, 1H), 7.57 (s, 1H), 2.89 (s, 3H).
Reaction SMILES: [CH3:1][C:2]1([CH3:18])[C:14]2[CH:13]=[C:12](B(O)O)[CH:11]=[CH:10][C:9]=2[C:8]2[C:3]1=[CH:4][CH:5]=[CH:6][CH:7]=2.Cl[C:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=[CH:22][N:21]=1.C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>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.C(O)C>[CH3:1][C:2]1([CH3:18])[C:14]2[CH:13]=[C:12]([C:20]3[C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH:23]=[CH:22][N:21]=3)[CH:11]=[CH:10][C:9]=2[C:8]2[C:3]1=[CH:4][CH:5]=[CH:6][CH:7]=2
Reactant: Clc1nccc2ccccc12
Reactant: CC1(C)c2ccccc2-c2ccc(B(O)O)cc21
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: Cc1ccccc1
Product: CC1(C)c2ccccc2-c2ccc(-c3nccc4ccccc34)cc21
Reaction time: 5 h
Yield: 54.3 %

Procedure:
In a 100 ml-three-necked flask, 2.91 g (12.2 mmole) of 9,9-dimethylfluorene-2-boronic acid, 2.00 g (12.2 mmole) of 1-chloroisoquinoline, 10 ml of toluene, 5 ml of ethanol and 10 ml of 2M-sodium carbonate aqueous solution were placed and stirred at room temperature under nitrogen stream, and 0.44 g (0.38 mmole) of tetrakis(triphenylphosphine)palladium (0) was added thereto. Thereafter, reflux under stirring was performed for 5 hours under nitrogen stream. After completion of the reaction, the reaction product was cooled and extracted by addition of cold water and toluene. The organic layer was washed with saline water and dried on magnesium sulfate, followed by removal of the solvent under a reduced pressure to provide dry solid. The residue was purified by silica gel column chromatography (eluent: toluene/ethyl acetate=50/1) to obtain 2.13 g (yield=54.2%) of 1-(9,9-dimethylfluorene-2-yl)isoquinoline.
Reaction SMILES: C([S:4][CH2:5][C:6]([N:8]1[CH2:12][C:11]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:10][C@H:9]1[C:20]([OH:22])=[O:21])=[O:7])(=O)C.N>>[SH:4][CH2:5][C:6]([N:8]1[CH2:12][C:11]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:10][C@H:9]1[C:20]([OH:22])=[O:21])=[O:7]
Reactant: CC(=O)SCC(=O)N1CC(Cc2ccccc2)=C[C@H]1C(=O)O
Agent: N
Product: O=C(O)[C@@H]1C=C(Cc2ccccc2)CN1C(=O)CS

Procedure:
The product from part (b) is treated with concentrated ammonia according to the procedure of Example 4 to yield (2S)-2,5-dihydro-1-(2-mercapto-1-oxoethyl)-4-(phenylmethyl)-1H-pyrrole-2-carboxylic acid.
Reaction SMILES: C([O-])([O-])=O.[K+].[K+].[S:7]1[C:11]([C:12]2[CH:17]=[CH:16][C:15]([CH2:18][N:19]([NH:38][C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:20][C@H:21]([OH:37])[C@@H:22]([NH:30]C(=O)C(F)(F)F)[CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:14][CH:13]=2)=[CH:10][N:9]=[CH:8]1.C(Cl)Cl.O>CO>[S:7]1[C:11]([C:12]2[CH:17]=[CH:16][C:15]([CH2:18][N:19]([NH:38][C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:20][C@H:21]([OH:37])[C@@H:22]([NH2:30])[CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:14][CH:13]=2)=[CH:10][N:9]=[CH:8]1
Reactant: CC(C)(C)OC(=O)NN(Cc1ccc(-c2cncs2)cc1)C[C@H](O)[C@H](Cc1ccccc1)NC(=O)C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: ClCCl
Solvent: CO
Product: CC(C)(C)OC(=O)NN(Cc1ccc(-c2cncs2)cc1)C[C@H](O)[C@@H](N)Cc1ccccc1
Temperature: 70 °C
Reaction time: 15 h

Procedure:
100 ml of a 1N K2CO3 solution are added dropwise to a solution of 5.646 g (10.0 mmol) of 1-[4-(thiazol-5-yl)-phenyl]-4(S)-hydroxy-2-(tert-butoxycarbonyl)amino-5(S)-(trifluoroacetyl)amino-6-phenyl-2-azahexane in 100 ml of methanol and the mixture is stirred at 70° C. for 15 hours. Methylene chloride and water are added; the aqueous phase is separated off and extracted 2× with methylene chloride. The organic phases are washed 2× with water, dried (Na2SO4) and concentrated by evaporation, yielding the title compound: Anal. (C25H32N4O3S (0.53 H2O)) calc. C 62.80, H 6.97, N 11.72, S 6.71, H2O 2.00: found C 63.2, H 7.01, N 11.57, S 6.49, H2O 1.98; HPLC20-100 : tRet =11.5.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[C:7]1([C:13]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:14])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.O.[OH-].[Na+]>C(OCC)C>[C:7]1([CH:13]([OH:14])[CH2:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: O=C(Cc1ccccc1)c1ccccc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Solvent: O
Product: OC(Cc1ccccc1)c1ccccc1
Temperature: 25 °C

Procedure:
To a stirring suspension of 1.20 g of lithium aluminum hydride in 100 mL of diethyl ether under an argon atmosphere at 0° C. Is slowly added a solution of 5.50 g of commercially available deoxybenzoin in 25.0 mL of diethyl ether. After 0.5 hours the grey suspension is warmed to room temperature. After 1 hour the reaction mixture is re-cooled to 0° C. and slowly treated with 1.25 mL of water followed by 5.50 mL of 1N sodium hydroxide. After 0.5 hour the resulting white precipitant is filtered through a pad of magnesium sulfate with diethyl ether washings. The filtrate is concentrated under reduced pressure to afford 5.50 g of the title product as off-white crystals. This product may be used directly in the next reaction without further purification.
Reaction SMILES: [Cl:1][C:2]([Cl:9])([Cl:8])[CH:3]1[NH:7][CH2:6][CH2:5][O:4]1.[C:10](=[S:12])=[S:11].C([O-])(=O)C.[Zn+2:17].C([O-])(=O)C>C(O)(C)C.O>[Cl:1][C:2]([Cl:9])([Cl:8])[CH:3]1[N:7]([C:10]([S-:12])=[S:11])[CH2:6][CH2:5][O:4]1.[Cl:1][C:2]([Cl:9])([Cl:8])[CH:3]1[N:7]([C:10]([S-:12])=[S:11])[CH2:6][CH2:5][O:4]1.[Zn+2:17]
Reactant: S=C=S
Reactant: ClC(Cl)(Cl)C1NCCO1
Agent: CC(=O)[O-]
Agent: [Zn+2]
Solvent: O
Solvent: CC(C)O
Product: S=C([S-])N1CCOC1C(Cl)(Cl)Cl
Temperature: 25 °C

Procedure:
Ninety-five and two-tenths g. of 2-trichloromethyloxazolidine (preparation described by W. Ruske and I. Hartmann J. Prakt, Chem. 18 146 (1962) was dissolved in a mixture of 300 ml isopropanol, and 50.5 g. (0.50 mole) of carbon disulfide was added dropwise followed by 43.9 g. (0.25 mole) of anhydrous zinc acetate. The reaction mixture was heated for two hours at 45°- 50°C, cooled to room temperature, and diluted with 1 liter water; the precipitated product was filtered, washed thoroughly with water and dried in vacuo to give 86.3 g. of the crude product, melting at 193°-195°C (decomp.). Hot benzene extractions of the crude product gave 38 g. of the desired carbodithioate sintering at 208°C, and melting 213°- 216°C (decomp.). It had the following analysis: Found: C, 20.19; H, 2.08; N, 4.67; S, 20.96%. Calcd for C10H10Cl6N2O2S4Zn: C, 20.12; H, 1,68; N, 4.69; S, 21.46%.
Reaction SMILES: C[O:2][C:3](=[O:23])[C:4]1[C:5](=[CH:10][C:11]([CH2:14][NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[CH:12][CH:13]=1)[C:6]([O:8]C)=[O:7].[OH-].[Na+].Cl>CO>[C:19]([O:18][C:16]([NH:15][CH2:14][C:11]1[CH:10]=[C:5]([C:6]([OH:8])=[O:7])[C:4](=[CH:13][CH:12]=1)[C:3]([OH:23])=[O:2])=[O:17])([CH3:22])([CH3:20])[CH3:21]
Reactant: COC(=O)c1ccc(CNC(=O)OC(C)(C)C)cc1C(=O)OC
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CC(C)(C)OC(=O)NCc1ccc(C(=O)O)c(C(=O)O)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 93.6 %

Procedure:
The compound (76.4 mg) obtained in Example 7-3 was dissolved in methanol (4.5 ml). A 1 mol/l sodium hydroxide aqueous solution (2.3 ml) was dropped in this solution and the whole was stirred at room temperature for 2 hours. The solution was neutralized by addition of 1 mol/l hydrochloric acid (2.3 ml). The residue obtained by distilling the solvent off was purified through silica gel column chromatography (chloroform/methanol), thereby obtaining the subject compound (65.3 mg) as a pale-yellow oily substance.