Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(NC1CCCCC1)(C)C.C([Li])CCC.[CH3:16][O:17][C:18](=[O:28])[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[O:26][CH3:27].[Cl:29][C:30]1[N:35]=[C:34]([Cl:36])[C:33]([CH2:37]I)=[CH:32][N:31]=1>O1CCCC1.C(OCC)(=O)C>[CH3:16][O:17][C:18](=[O:28])[CH:19]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[O:26][CH3:27])[CH2:37][C:33]1[C:34]([Cl:36])=[N:35][C:30]([Cl:29])=[N:31][CH:32]=1
Reactant: Clc1ncc(CI)c(Cl)n1
Reactant: COC(=O)Cc1ccccc1OC
Agent: CC(C)NC1CCCCC1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: COC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccccc1OC
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
To a solution of N-isopropylcyclohexylamine (1.44 g, 10.0 mmol) (Aldrich) in dry tetrahydrofuran (20 mL) was added n-butyllithium (2.5 M in hexanes, 4.0 mL, 10.0 mmol) (Aldrich) at −78° C. under argon. After 30 minutes, a solution of 2-methoxyphenylacetic acid methyl ester (1.8 g, 10.0 mmol) (TCI-US) in tetrahydrofuran (5 mL) was added by injection via a syringe and the reaction mixture was stirred at −78° C. for another 30 minutes. To the reaction mixture was added a solution of 2,4-dichloro-5-iodomethyl-pyrimidine (1.45 g, 5.0 mmol) (from Example 1c supra) in tetrahydrofuran (5 mL) at −78° C. and the reaction mixture was stirred at the same temperature for 1 hour then slowly allowed to warm up to −30° C. and stirred for 10 minutes. The reaction mixture was diluted with ethyl acetate (100 mL) and successively washed with saturated aqueous ammonium chloride solution (100 mL), water (50 mL) and brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography to give 3-(2,4-dichloro-pyrimidin-5-yl)-2-(2-methoxy-phenyl)-propionic acid methyl ester as a yellow oil. (Yield 1.40 g, 82.3%).
Reaction SMILES: [N+:1]([C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[O:9])=[CH:6][CH:5]=1)([O-:3])=[O:2].[N:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[CH3:18].O>CO.O>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([CH:8]([CH2:18][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][N:12]=2)[OH:9])=[CH:10][CH:11]=1)([O-:3])=[O:2]
Reactant: Cc1ccccn1
Reactant: O=Cc1ccc([N+](=O)[O-])cc1
Solvent: O
Solvent: CO
Product: O=[N+]([O-])c1ccc(C(O)Cc2ccccn2)cc1
Temperature: 25 °C
Reaction time: 19 h
Yield: 79 %

Procedure:
A stainless steel bomb containing p-nitrobenzaldehyde (300 g, 1.99 moles), α-picoline (650 ml, 6.59 moles) and distilled water (100 ml, 5.56 moles) was sealed and held in an oil bath at 140°-160° C. for 19 hours. It was cooled to room temperature and opened to the atmosphere. The contents of the reactor, a mass of crystals and some dark liquid, were added to one liter of a 60:40 methanol-water mixture and the resulting mixture stirred for two hours. The solid was recovered by filtration, washed with one liter of the same solvent mixture and dried under vacuum at 50° C. to give 383-396 g (79%-82% yield) of ##STR29## 4-nitrophenyl-(α-picolyl)carbinol.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:21]=[CH:20][C:8]([CH2:9][C:10]2[CH:11]=[C:12]([CH:17]=[CH:18][N:19]=2)[C:13]([O:15][CH3:16])=[O:14])=[CH:7][CH:6]=1)(=[O:4])=[O:3]>C(O)(=O)C.O=[Pt]=O>[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([CH2:9][CH:10]2[CH2:11][CH:12]([C:13]([O:15][CH3:16])=[O:14])[CH2:17][CH2:18][NH:19]2)=[CH:20][CH:21]=1)(=[O:4])=[O:3]
Reactant: COC(=O)c1ccnc(Cc2ccc(S(C)(=O)=O)cc2)c1
Agent: O=[Pt]=O
Solvent: CC(=O)O
Product: COC(=O)C1CCNC(Cc2ccc(S(C)(=O)=O)cc2)C1
Reaction time: 0.5 h
Yield: 65.9 %

Procedure:
Methyl 2-(4-(methylsulfonyl)benzyl)isonicotinate (8.0 g, 26.2 mmol) was dissolved in acetic acid (250 mL). Activated carbon was added and stirred for 30 min. The activated carbon was filtered off. To the solution was added PtO2 (0.119 g, 0.52 mmol) and the reaction mixture hydrogenated in a Büchi hydrogenator overnight at room temperature and 9 bar. The catalyst was filtered off. The solvent was evaporated. The crude was partitioned between Na2CO3 (aq) and ethyl acetate. The organic layer was dried over Na2SO4, filtered through celite and evaporated to yield methyl 2-(4-(methylsulfonyl)benzyl)piperidine-4-carboxylate (5.38 g, 65.9%).
Reaction SMILES: S(O[C:12]1[C:25]2[C:24](=[O:26])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:17](=[O:27])[C:16]=2[C:15]([O:28][S:29]([C:32]2[CH:38]=[CH:37][C:35]([CH3:36])=[CH:34][CH:33]=2)(=[O:31])=[O:30])=[CH:14][CH:13]=1)(C1C=CC(C)=CC=1)(=O)=O.[CH:39]([NH2:42])([CH3:41])[CH3:40]>>[CH:39]([NH:42][C:12]1[C:25]2[C:24](=[O:26])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:17](=[O:27])[C:16]=2[C:15]([O:28][S:29]([C:32]2[CH:38]=[CH:37][C:35]([CH3:36])=[CH:34][CH:33]=2)(=[O:31])=[O:30])=[CH:14][CH:13]=1)([CH3:41])[CH3:40]
Reactant: CC(C)N
Reactant: Cc1ccc(S(=O)(=O)Oc2ccc(OS(=O)(=O)c3ccc(C)cc3)c3c2C(=O)c2ccccc2C3=O)cc1
Product: Cc1ccc(S(=O)(=O)Oc2ccc(NC(C)C)c3c2C(=O)c2ccccc2C3=O)cc1
Yield: 76 %

Procedure:
1-(isopropylamino)-4-tosyloxyanthraquinone was prepared by reaction of 1,4-ditosyloxyanthraquinone with isopropyl amine. The isolated and purified reaction product has the structure illustrated below (where "Ts" is ##STR8## The yield was 76% and the m.p. 164°-165° C.; mass spec m/e/ 435 (M+), 420 (M-CH3), 280 (M-C7H7SO2), 238 (280-CH3H7 +H), 210 (238-CO), 182 (210-CO), 155 (C7H7SO2), 91 (C7H7); 1H-NMR (CD2Cl2)δ9.97 (br s, 1H), 8.19-8.10 (m, 2H), 7.85-7.67 (m, 4H), 7.27-6.97 (m, 4H), 4.02-3.68 (m, 1H), 2.30 (s, 3H), 1.38, 1.31 (d, 6H); IR (Nujol) 1180 cm-1 (symmetrical SO2 stretch), 890 cm-1, 860, 820, 780 (S--O--C stretch); UV/VIS max (Xylenes(500 nm (ε6660).
Reaction SMILES: [CH3:1][C:2]([C:6]1[CH2:10][CH:9]=[CH:8][CH:7]=1)([CH3:5])[CH2:3][CH3:4].[CH3:11][C:12]([CH3:14])=O.N1CCCC1>CO.CCOCC.O>[CH3:1][C:2]([C:6]1[CH:10]=[CH:9][C:8](=[C:12]([CH3:14])[CH3:11])[CH:7]=1)([CH3:5])[CH2:3][CH3:4]
Reactant: CCC(C)(C)C1=CC=CC1
Reactant: CC(C)=O
Solvent: CO
Solvent: C1CCNC1
Solvent: CCOCC
Product: CCC(C)(C)C1=CC(=C(C)C)C=C1
Temperature: 25 °C
Yield: 47.7 %

Procedure:
To a solution of 3.00 g (22.0 mmol) of (1,1-dimethylpropyl)cyclopentadiene in 30 ml of methanol, 16.2 ml (220.4 mmol) of acetone and 3.7 ml (44.0 mmol) of pyrrolidine were added with ice cooling, followed by stirring at room temperature for one night. After the reaction solution was diluted with 100 ml of ether, 50 ml of water was added. The organic phase was separated, washed with water and a saturated saline solution, then dried over anhydrous magnesium sulfate and filtered. From the filtrate, the solvent was removed under reduced pressure to obtain a liquid. The liquid was subjected to vacuum distillation (100° C./1 mmHg) to obtain 1.85 g (10.49 mmol) of a yellow liquid (yield: 48%). The analyzed values are given below.
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]1[CH2:11][OH:12].O[C:14]1[CH:46]=[CH:45][C:17]([CH2:18][CH:19]2[S:23][C:22](=[O:24])[N:21]([C:25]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:20]2=[O:44])=[CH:16][CH:15]=1.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1C=CC=CC=1>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]1[CH2:11][O:12][C:14]1[CH:46]=[CH:45][C:17]([CH2:18][CH:19]2[S:23][C:22](=[O:24])[N:21]([C:25]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)([C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:20]2=[O:44])=[CH:16][CH:15]=1
Reactant: Cn1c(CO)cc2ccccc21
Reactant: O=C1SC(Cc2ccc(O)cc2)C(=O)N1C(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: c1ccccc1
Product: Cn1c(COc2ccc(CC3SC(=O)N(C(c4ccccc4)(c4ccccc4)c4ccccc4)C3=O)cc2)cc2ccccc21
Yield: 46.6 %

Procedure:
A procedure similar to that described in Preparation 4 was repeated, except that 4.30 g of 1-methylindol-2-ylmethanol (prepared as described in Preparation 23), 10.3 g of 5-(4-hydroxybenzyl)-3-triphenylmethylthiazolidine-2,4-dione, 6.65 ml of tributylphosphine, 6.73 g of 1,1'-(azodicarbonyl)dipiperidine and 120 ml of benzene were used, to give 6.28 g of the title compound, melting at 134.3-136.0° C.
Reaction SMILES: [NH2:1][C:2]1[N:6]=[CH:5][NH:4][N:3]=1.[OH:7][C:8]([CH3:19])([CH3:18])[CH2:9][O:10][CH:11]1[CH2:16][CH2:15][C:14](=O)[CH2:13][CH2:12]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C>[CH3:19][C:8]([OH:7])([CH3:18])[CH2:9][O:10][CH:11]1[CH2:16][CH2:15][CH:14]([NH:1][C:2]2[N:6]=[CH:5][NH:4][N:3]=2)[CH2:13][CH2:12]1
Reactant: CC(C)(O)COC1CCC(=O)CC1
Reactant: Nc1nc[nH]n1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Product: CC(C)(O)COC1CCC(Nc2nc[nH]n2)CC1
Temperature: 25 °C
Reaction time: 15 h
Yield: 64.3 %

Procedure:
To a solution of 3-amino-1H-1,2,4-triazole (1.46 g) and 4-(2-hydroxy-2-methylpropoxy)cyclohexanone (3.25 g) in acetic acid (30 mL) was added sodium triacetoxyborohydride (5.53 g), and the mixture was stirred at room temperature for 15 hr. The solvent was evaporated under reduced pressure, and the residue was diluted with saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate-isopropyl alcohol (3:1). The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography [eluent: methanol/ethyl acetate=0/100→6/94 (volume ratio)] to give colorless amorphous 2-methyl-1-{[4-(1H-1,2,4-triazol-3-ylamino)cyclohexyl]oxy}propan-2-ol (2.84 g, 64%) as a diastereomixture.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][CH:10]=[C:11]([CH2:13][N:14]3[CH2:19][CH2:18][CH2:17][CH2:16][CH:15]3[CH3:20])[N:12]=2)=[CH:4][CH:3]=1.[N:21]1[CH:26]=[CH:25][CH:24]=[C:23](B(O)O)[CH:22]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1>[CH3:20][CH:15]1[CH2:16][CH2:17][CH2:18][CH2:19][N:14]1[CH2:13][C:11]1[N:12]=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([C:23]3[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=3)=[CH:3][CH:4]=2)[O:9][CH:10]=1
Reactant: CC1CCCCN1Cc1coc(-c2ccc(Br)cc2)n1
Reactant: OB(O)c1cccnc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Product: CC1CCCCN1Cc1coc(-c2ccc(-c3cccnc3)cc2)n1

Procedure:
1-[2-(4-Bromo-phenyl)-oxazol-4-ylmethyl]-2-methyl-piperidine (See Example 21) (1.0 mmol; N96-A03858-154), 3-pyridyl boronic acid (1.2 mmol), tetrakis-(triphenylphosphine)palladium (0.044 mmol), 2M aqueous sodium carbonate (3 mmol) and dioxane (0.1M) is placed in a microwave reactor vessel with a stirbar. Run the reaction in a CEM microwave reactor at 90° C. with 30 W power and cooling for 30 minutes. After this time, perform an aqueous workup and purify via radial chromatography eluting with 2M ammonia in methanol and dichloromethane to provide the titled compound. MS (m/e): 334.2 (M+1)
Reaction SMILES: P(Cl)(Cl)(Cl)=O.[CH2:6]([N:8]([CH2:22][CH3:23])[CH2:9][CH2:10][N:11]1[CH2:16][CH2:15][C:14]2[NH:17][CH:18]=[C:19]([CH3:20])[C:13]=2[C:12]1=[O:21])[CH3:7].O.[OH-].[Na+].CN(C)[CH:29]=[O:30]>>[CH2:22]([N:8]([CH2:6][CH3:7])[CH2:9][CH2:10][N:11]1[CH2:16][CH2:15][C:14]2[NH:17][C:18]([CH:29]=[O:30])=[C:19]([CH3:20])[C:13]=2[C:12]1=[O:21])[CH3:23]
Reactant: CCN(CC)CCN1CCc2[nH]cc(C)c2C1=O
Reactant: CN(C)C=O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: O=P(Cl)(Cl)Cl
Product: CCN(CC)CCN1CCc2[nH]c(C=O)c(C)c2C1=O
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 38 %

Procedure:
A stirred solution of N,N-dimethylformamide (2 ml) was added slowly with 104 μl of phosphorus oxychloride under an argon atmosphere while maintaining the temperature at 0° C. Upon completion of the addition, the mixture was stirred for 15 minutes at room temperature, and cooled down to 0˜5° C. in an ice-water bath. A mixture of 5-(2-diethylamino-ethyl)-3-methyl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one (249 mg, 1 mmol) in 2 ml of N,N-dimethylformamide was added dropwise to the above solution. Upon completion of the addition, the mixture was stirred for 2 hours at 0° C., added with cold water (15 ml), stirred for 5 minutes. The resulting mixture was adjusted to pH 12 with 10% aqueous sodium hydroxide solution and extracted with dichloromethane (15 ml×6). The combined organic extracts were washed with brine (15 ml), dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with triethylamine:methanol:dichloromethane (1:20:500) as eluents to give 5-(2-diethylamino-ethyl)-3-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carbaldehyde (105 mg, 38%) as a pink oil which was used as such.
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][S:5][C:6]1[C:14]2[C:13](=[O:15])[N:12]([CH3:16])[C:11](=[O:17])[N:10]([CH2:18][CH:19]([CH3:21])[CH3:20])[C:9]=2[NH:8][N:7]=1.C(=O)([O-])[O-].[K+].[K+].[C:28]1([S:34]([CH2:37][C:38]2[CH:45]=[CH:44][CH:43]=[CH:42][C:39]=2[CH2:40]Br)(=[O:36])=[O:35])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>CS(C)=O.C(OCC)(=O)C>[OH:1][CH2:2][CH2:3][CH2:4][S:5][C:6]1[N:7]([CH2:40][C:39]2[CH:42]=[CH:43][CH:44]=[CH:45][C:38]=2[CH2:37][S:34]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)(=[O:36])=[O:35])[N:8]=[C:9]2[C:14]=1[C:13](=[O:15])[N:12]([CH3:16])[C:11](=[O:17])[N:10]2[CH2:18][CH:19]([CH3:21])[CH3:20]
Reactant: O=S(=O)(Cc1ccccc1CBr)c1ccccc1
Reactant: CC(C)Cn1c(=O)n(C)c(=O)c2c(SCCCO)n[nH]c21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CS(C)=O
Product: CC(C)Cn1c(=O)n(C)c(=O)c2c(SCCCO)n(Cc3ccccc3CS(=O)(=O)c3ccccc3)nc21
Yield: 41.8 %

Procedure:
3-[(3-Hydroxypropyl)thio]-5-methyl-7-(2-methylpropyl)-1H-pyrazolo[3,4-d]-pyrimidine-4,6(5H,7H)-dione (94 mg), potassium carbonate (90 mg) and 2-(phenylsulfonylmethyl)benzyl bromide (105 mg) were combined in dimethylsulfoxide (11 ml). After 5 hours at room temperature the reaction mixture was diluted with ethyl acetate and washed thrice with water, twice with dilute hydrochloric acid, once with brine, then dried over magnesium sulfate and then concentrated in vacuo. Chromatography on silica gel (isohexane:isopropanol 4:1) gave the title compound (70 mg).
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:11]=[CH:10][C:6]([C:7](O)=[O:8])=[CH:5][CH:4]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C(OCC)C>[NH2:1][CH2:2][C:3]1[CH:11]=[CH:10][C:6]([CH2:7][OH:8])=[CH:5][CH:4]=1
Reactant: NCc1ccc(C(=O)O)cc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Product: NCc1ccc(CO)cc1
Reaction time: 20 h
Yield: 82.6 %

Procedure:
A solution of 4-aminomethyl-benzoic acid (0.20 g) in 20 mL diethyl ether was cooled to 0° C. Lithium aluminum hydride (0.19 g) was added in portions to the stirring carboxylic acid solution. The resulting slurry was stirred for 20 h and then cooled to 0 C. The mixture was carefully quenched by the sequential addition of 0.2 mL of water followed by 0.2 mL of 3 N sodium hydroxide followed by 0.6 mL of more water. The mixture was stirred for 15 min, then filtered to remove the aluminum salts. The filtrate was collected and the volatile material was evaporated to give 150 mg of (4-aminomethyl-phenyl)-methanol.
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:11](=[C:12](Br)[CH:13]=[CH:14][CH:15]=2)[C:10]([CH3:18])=[C:9]1[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[CH3:31][O:32][C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1.ClCCl>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:1]([N:8]1[C:16]2[C:11](=[C:12]([C:36]3[CH:37]=[CH:38][C:33]([O:32][CH3:31])=[CH:34][CH:35]=3)[CH:13]=[CH:14][CH:15]=2)[C:10]([CH3:18])=[C:9]1[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Cc1c(-c2ccccc2)n(Cc2ccccc2)c2cccc(Br)c12
Reactant: COc1ccc(B(O)O)cc1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: ClCCl
Solvent: C1COCCO1
Product: COc1ccc(-c2cccc3c2c(C)c(-c2ccccc2)n3Cc2ccccc2)cc1

Procedure:
The desired product was prepared using a procedure similar to step 3 of example 3. Thus, 1-benzyl-4-bromo-3-methyl-2-phenyl-1H-indole (1.286 g, 3.651 mmol) was reacted with aqueous 2M K2CO3 (3.7 ml), 4-methoxyphenylboronic acid (0.777 g, 5.111 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) complex with dichloromethane (1:1) (0.089 g, 0.110 mmol) in dioxane (37 ml) to give the product (1.029 g, 2.550 mmol, 70%) as a white solid, mp 93-95° C. 1H NMR (DMSO-d6) δ 1.73 (s, 3H), 3.80 (s, 3H), 5.29 (s, 2H), 6.84 (dd, J=0.8, 7.2 Hz, 1H), 6.88 (d, J=7.2 Hz, 2H), 6.97-7.00 (m, 2H), 7.11 (t, J=7.3 Hz, 1H), 7.17 (t, J=7.2 Hz, 1H), 7.22 (t, J=6.9 Hz, 2H), 7.30-7.35 (m, 5H), 7.39-7.47 (m, 3H); [ESI(+)], m/z 404 (M+H)+.
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:7]=[C:8](B(O)O)[CH:9]=[CH:10][CH:11]=1)=[O:5])C.Br[C:16]1[C:17]([Cl:36])=[C:18]([C:32]([Cl:35])=[CH:33][CH:34]=1)[CH2:19][CH:20]1[CH2:24][CH2:23][N:22]([CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)[C:21]1=[O:31].COCCOC.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(Cl)Cl>[Cl:35][C:32]1[C:18]([CH2:19][CH:20]2[CH2:24][CH2:23][N:22]([CH:25]3[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]3)[C:21]2=[O:31])=[C:17]([Cl:36])[CH:16]=[CH:34][C:33]=1[C:8]1[CH:9]=[CH:10][CH:11]=[C:6]([C:4]([OH:3])=[O:5])[CH:7]=1
Reactant: CCOC(=O)c1cccc(B(O)O)c1
Reactant: O=C1C(Cc2c(Cl)ccc(Br)c2Cl)CCN1C1CCCCC1
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: COCCOC
Solvent: ClCCl
Product: O=C(O)c1cccc(-c2ccc(Cl)c(CC3CCN(C4CCCCC4)C3=O)c2Cl)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 94.1 %

Procedure:
Place 3-(ethoxycarbonyl)phenylboronic acid (670 mg, 3.46 mmol), 3-(3-bromo-2,6-dichlorobenzyl)-1-cyclohexylpyrrolidin-2-one (Example 50) (700 mg, 1.73 mmol), and Pd(PPh3)4 (173 mg, 0.173 mmol) into a flask and purge with nitrogen. Add DME (50 mL) and 2M sodium carbonate (5 mL) and heat to 75° C. for 24 hr. Cool reaction, add DCM and wash with saturated sodium bicarbonate. Dry, filter, and concentrate organic layer. Purify by silica gel (30-45% EtOAc in Hex). Dissolve ester in ethanol (3 mL) and water (1 mL) and add KOH (291 mg, 5.18 mmol. Stir for 1 hour at room temperature. Strip off solvent and add water. Bring to a pH of 2 with 1M HCl. Filter precipitate to give 727 mg (94%) of title compound as a white solid. Mass spectrum (apci) m/z=446.2 (M+H).
Reaction SMILES: [P:1]([O-:39])([O:33][CH2:34][CH:35]([OH:38])[CH2:36]Cl)([O:3][C:4]([F:32])([F:31])[C:5]([F:30])([F:29])[C:6]([F:28])([F:27])[C:7]([F:26])([F:25])[C:8]([F:24])([F:23])[C:9]([F:22])([F:21])[C:10]([F:20])([F:19])[CH2:11][CH2:12][CH2:13][CH2:14][C:15]([F:18])([F:17])[F:16])=[O:2].[Na+:40].C(O)C.[OH-].[Na+]>C(O)C>[P:1]([O-:39])([O:33][CH2:34][CH:35]1[O:38][CH2:36]1)([O:3][C:4]([F:32])([F:31])[C:5]([F:30])([F:29])[C:6]([F:28])([F:27])[C:7]([F:26])([F:25])[C:8]([F:24])([F:23])[C:9]([F:22])([F:21])[C:10]([F:20])([F:19])[CH2:11][CH2:12][CH2:13][CH2:14][C:15]([F:18])([F:17])[F:16])=[O:2].[Na+:40]
Reactant: O=P([O-])(OCC(O)CCl)OC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)CCCCC(F)(F)F
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=P([O-])(OCC1CO1)OC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)CCCCC(F)(F)F
Temperature: 70 °C
Reaction time: 4 h
Yield: 99 %

Procedure:
50 g (0.073 mol) of sodium heptadecafluorododecyl 2-hydroxy-3-chloropropyl phosphate was charged into a reactor, to which 1000 ml of ethanol was added, followed by agitation and heating to 70° C. to obtain a uniform mixture. Thereafter, the reaction system was cooled down to 30° C., to which was gradually added 40.5 g (0.073 mol) of a 0.0018 mol/g sodium hydroxide ethanol solution, followed by agitation for 4 hours while keeping the temperature. The HPLC analysis revealed the disappearance of a peak of the starting material with a peak for the resultant new product appearing. The resultant NaCl precipitate was removed by filtration and the ethanol was distilled off under reduced pressure to obtain 47 g (yield: 99%) of sodium heptadecafluorododecyl glycidyl phosphate.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:44])[C@H:15]([NH:24][C:25]([C@@H:27]2[CH2:36][C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH2:29][N:28]2[C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])=[O:26])[CH2:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[CH2:10][CH2:9]1.[C:45]1([CH3:57])[CH:50]=[C:49]([CH3:51])[CH:48]=[C:47]([CH3:52])[C:46]=1[S:53](Cl)(=[O:55])=[O:54].N1C=CC=CC=1>ClCCCl>[Cl:23][C:20]1[CH:19]=[CH:18][C:17]([CH2:16][C@@H:15]([NH:24][C:25]([C@@H:27]2[CH2:36][C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH2:29][N:28]2[C:37]([O:39][C:40]([CH3:41])([CH3:43])[CH3:42])=[O:38])=[O:26])[C:14](=[O:44])[N:11]2[CH2:12][CH2:13][CH:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[NH:1][S:53]([C:46]3[C:47]([CH3:52])=[CH:48][C:49]([CH3:51])=[CH:50][C:45]=3[CH3:57])(=[O:55])=[O:54])[CH2:9][CH2:10]2)=[CH:22][CH:21]=1
Reactant: Cc1cc(C)c(S(=O)(=O)Cl)c(C)c1
Reactant: CC(C)(C)OC(=O)N1Cc2ccccc2C[C@H]1C(=O)N[C@H](Cc1ccc(Cl)cc1)C(=O)N1CCC(c2ccccc2N)CC1
Solvent: ClCCCl
Solvent: c1ccncc1
Product: Cc1cc(C)c(S(=O)(=O)Nc2ccccc2C2CCN(C(=O)[C@@H](Cc3ccc(Cl)cc3)NC(=O)[C@@H]3Cc4ccccc4CN3C(=O)OC(C)(C)C)CC2)c(C)c1
Yield: 73.1 %

Procedure:
The title compound was prepared according to the procedure described in Example 21 (Step a) by treating tert-butyl 3-(N-{(1R)-2-[4-(2-aminophenyl)piperidyl]-1-[(4-chlorophenyl)methyl]-2-oxoethyl}carbamoyl)(3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate (Example 20) (154 mg, 0.25 mmol) with 2-mesitylenesulfonyl chloride (Aldrich) (55 mg, 0.25 mmol) and pyridine (0.03 mL, 0.375 mmol) in 1,2-dichloroethane (10 mL). Purification by silica gel chromatography (100% EtOAc) provided the title compound as a white foam (146 mg). MS (ESI, pos. ion) m/z: 799 (M+1); MS (ESI, neg. ion) m/z: 797 (M−1) Calc'd for C44H51ClN4O6S: 798.32.
Reaction SMILES: [NH2:1][C:2]1[N:6]=[CH:5][NH:4][N:3]=1.[CH2:7](Br)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>>[CH2:7]([N:4]1[CH:5]=[N:6][C:2]([NH2:1])=[N:3]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: BrCc1ccccc1
Reactant: Nc1nc[nH]n1
Product: Nc1ncn(Cc2ccccc2)n1

Procedure:
Prepared in analogy to example 3a) starting with 3-amino-1,2,4-triazole and benzyl bromide. The title compound was obtained as a colorless solid (Yield=14%). MS ISP (m/e): 175.3 (100) [(M+H)+].
Reaction SMILES: [CH:1]1[C:14]2[CH:13]([C:15](O)=[O:16])[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[NH2:18][C@H:19]1[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:20]1>>[C:26]1([CH2:25][CH2:24][N:21]2[CH2:22][CH2:23][C@H:19]([NH:18][C:15]([CH:13]3[C:12]4[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=4[CH2:6][C:5]4[C:14]3=[CH:1][CH:2]=[CH:3][CH:4]=4)=[O:16])[CH2:20]2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: O=C(O)C1c2ccccc2Cc2ccccc21
Reactant: N[C@H]1CCN(CCc2ccccc2)C1
Product: O=C(N[C@H]1CCN(CCc2ccccc2)C1)C1c2ccccc2Cc2ccccc21

Procedure:
9,10-Dihydroanthracene-9-carboxylic acid and (S)-3-amino-1-(2-phenylethyl)pyrrolidine were reacted under the same conditions as in Example 23 to give (S)-N-(1-(2-phenylethyl)pyrrolidin-3-yl)-9,10-dihydroanthracene-9-carboxamide.