Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5](I)=[CH:4][CH:3]=1.C1N2CCN(CC2)C1.[C:18]([OH:23])(=[O:22])[C:19]([CH3:21])=O>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:1][C:2]1[N:7]=[C:6]2[NH:8][C:19]([C:18]([OH:23])=[O:22])=[CH:21][C:5]2=[CH:4][CH:3]=1
Reactant: CC(=O)C(=O)O
Reactant: Nc1nc(Cl)ccc1I
Agent: [Pd+2]
Agent: C1CN2CCN1CC2
Agent: CC(=O)[O-]
Solvent: CN(C)C=O
Product: O=C(O)c1cc2ccc(Cl)nc2[nH]1
Temperature: 110 °C
Yield: 194.8 %

Procedure:
To a solution of 6-chloro-3-iodopyridin-2-amine (24 g, 94 mmol) in DMF is added DABCO (32 g, 283 mmol) and pyruvic acid (20 mL, 283 mmol). The mixture is degassed by bubbling argon gas through the mixture for 20 min. Pd(OAc)2 (1 g, 4.7 mmol) is added and the mixture is again degassed. The reaction mixture is heated at 110° C. for 3 h, and the solvent is evaporated to afford the title compound as a viscous liquid (36 g, >99%) which is used in the next step without purification.
Reaction SMILES: [CH:1]1[C:13]2[C:12](=[CH:14][C:15]([NH:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23](O)=[O:24])=[O:16])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.Cl.C(N=C=NCCCN(C)C)C.OC1C2N=NNC=2C=CC=1.C(N(CC)CC)C.[F:55][C:56]([F:66])([F:65])[C:57]1[CH:62]=[CH:61][C:60]([NH2:63])=[C:59]([NH2:64])[CH:58]=1>[Cl-].[Na+].O.CN(C=O)C>[CH:10]1[C:11]2[C:12](=[CH:14][C:15]([NH:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]([NH:63][C:60]3[CH:61]=[CH:62][C:57]([C:56]([F:65])([F:66])[F:55])=[CH:58][C:59]=3[NH2:64])=[O:24])=[O:16])[C:13]3[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=3)[C:6]=2[CH:7]=[CH:8][CH:9]=1
Reactant: Nc1ccc(C(F)(F)F)cc1N
Reactant: O=C(O)CCCCCNC(=O)C=C1c2ccccc2-c2ccccc21
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: Oc1cccc2[nH]nnc12
Solvent: CCN(CC)CC
Solvent: O
Solvent: CN(C)C=O
Product: Nc1cc(C(F)(F)F)ccc1NC(=O)CCCCCNC(=O)C=C1c2ccccc2-c2ccccc21
Temperature: 25 °C
Reaction time: 24 h
Yield: 58 %

Procedure:
6-(2-(9H-fluoren-9-ylidene)acetamido)hexanoic acid (335 mg, 1 mmol), and 8 ml of DMF were stirred at room temperature while 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (394 mg, 2 mmol), hydroxy-benzotriazole (162 mg, 1.2 mmol), triethylamine (404 mg, 4 mmol) and 4-trifluoromethyl-o-phenylenediamine (211 mg, 1.2 mmol) were added. The mixture was stirred for 24 hours at room temperature. The mixture was diluted with 400 mL of brine. The solids were collected by vacuum filtration, washed with water and dried under vacuum to give the title compound (286 mg, 58% yield) as a brown solid. LC-MS (m/z) 494 (M+1).
Reaction SMILES: FC1C=CC(C[N:9]2[C:17]([S:18][CH:19]3[CH2:24][CH2:23][N:22](S(C4C=CC(C)=CC=4)(=O)=O)[CH2:21][CH2:20]3)=[N:16][C:15]3[C:10]2=[N:11][CH:12]=[N:13][CH:14]=3)=CC=1.Br>C(O)(=O)C>[NH:22]1[CH2:23][CH2:24][CH:19]([S:18][C:17]2[NH:9][C:10]3[C:15]([N:16]=2)=[CH:14][N:13]=[CH:12][N:11]=3)[CH2:20][CH2:21]1
Reactant: Cc1ccc(S(=O)(=O)N2CCC(Sc3nc4cncnc4n3Cc3ccc(F)cc3)CC2)cc1
Agent: Br
Solvent: CC(=O)O
Product: c1ncc2nc(SC3CCNCC3)[nH]c2n1

Procedure:
A mixture of 24.8 parts of 4-[[9-[(4-fluorophenyl)methyl]-9H-purin-8-yl]thio]-1-[(4-methylphenyl)sulfonyl]piperidine and 300 parts of acetic acid, saturated with hydrogen bromide was stirred overnight at room temperature. After evaporation, the residue was taken up in water. The whole was treated with a sodium hydroxide solution and extracted with dichloromethane. The extract was acidified with a hydrochloric acid solution and extracted with water. The aqueous layer was treated with a sodium hydroxide solution and the product was extracted with dichloromethane. The extract was washed with water, dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol, (95:5 by volume)→trichloromethane and methanol, saturated with ammonia, (90:10 by volume) as eluents. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetonitrile. The product was filtered off and dried, yielding 3.0 parts (17.4%) of 9-[(4-fluorophenyl)methyl[-8-(4-piperidinylthio)-9H-purine; mp. 113.5° C. (compound 31).
Reaction SMILES: I[CH:2]([CH3:4])[CH3:3].[C:5]([O:9][C:10]([C:12]1[CH:28]=[C:27]([OH:29])[C:15]2[CH2:16][CH:17]([CH2:19][O:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[O:18][C:14]=2[CH:13]=1)=[O:11])([CH3:8])([CH3:7])[CH3:6].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O>[C:5]([O:9][C:10]([C:12]1[CH:28]=[C:27]([O:29][CH:2]([CH3:4])[CH3:3])[C:15]2[CH2:16][CH:17]([CH2:19][O:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[O:18][C:14]=2[CH:13]=1)=[O:11])([CH3:8])([CH3:6])[CH3:7]
Reactant: CC(C)(C)OC(=O)c1cc(O)c2c(c1)OC(COc1ccccc1)C2
Reactant: CC(C)I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)Oc1cc(C(=O)OC(C)(C)C)cc2c1CC(COc1ccccc1)O2
Temperature: 60 °C
Reaction time: 8 h
Yield: 46.4 %

Procedure:
2-Iodopropane (174 mg, 1.02 mmol)) was added to a mixture of 4-hydroxy-2-phenoxymethyl-2,3-dihydro-benzofuran-6-carboxylic acid tert-butyl ester (214b) (350 mg, 1.02 mmol) and K2CO3 (141 mg, 1.02 mmol) in DMF (5 mL). The reaction mixture was stirred at 60° C. overnight. The mixture was diluted with H2O (50 mL) and extracted with EtOAc (2×50 mL). The organic layers were washed with H2O (2×70 mL), dried over MgSO4 and concentrated. The residue was purified by flash column chromatograph eluting with 5% EtOAc in hexanes to give a white solid (182 mg, 46% yield). 1H NMR (400 MHz, CDCl3) δ 7.29 (d, J=1.26 Hz, 1 H) 7.22-7.26 (m, 1 H) 7.13 (s, 1 H) 7.07 (s, 1 H) 6.91-7.00 (m, 3 H) 6.85 (d, J=7.58 Hz, 1 H) 5.17-5.25 (m, 1 H) 4.59-4.68 (m, 1 H) 4.07-4.17 (m, 1 H) 3.34 (dd, J=16.55, 9.47 Hz, 1 H) 3.09 (dd, J=16.55, 6.95 Hz, 1 H) 1.58 (s, 9 H) 1.35 (d, J=6.06 Hz, 6 H); LCMS for C23H28O5 m/z 385.20 (M+H+).
Reaction SMILES: C([O:4][CH2:5][C:6](Cl)=[O:7])(=O)C.[NH2:9][C:10]1[C:11]([I:28])=[C:12]([C:21]([NH:23][CH2:24][CH:25]([OH:27])[CH3:26])=[O:22])[C:13]([I:20])=[C:14]([C:18]=1[I:19])[C:15]([OH:17])=[O:16].CC(N(C)C)=O>O>[OH:4][CH2:5][C:6]([NH:9][C:10]1[C:11]([I:28])=[C:12]([C:21]([NH:23][CH2:24][CH:25]([OH:27])[CH3:26])=[O:22])[C:13]([I:20])=[C:14]([C:18]=1[I:19])[C:15]([OH:17])=[O:16])=[O:7]
Reactant: CC(=O)OCC(=O)Cl
Reactant: CC(O)CNC(=O)c1c(I)c(N)c(I)c(C(=O)O)c1I
Solvent: CC(=O)N(C)C
Solvent: O
Product: CC(O)CNC(=O)c1c(I)c(NC(=O)CO)c(I)c(C(=O)O)c1I
Temperature: 25 °C
Reaction time: 16 h

Procedure:
At temperatures no higher than 10° C., 13.3 ml. of acetoxyacetyl chloride is gradually added dropwise with agitation to a solution of 30.8 g. (50 mmol) of 5-amino-(2-hydroxypropyl)-2,4,6-triiodoisophthalamic acid in 60 ml. of dimethylacetamide. After 16 hours of agitation at room temperature and the addition of 10 ml. of water, the mixture is stirred for 30 minutes at room temperature and then concentrated under vacuum. The residue, after having been treated repeatedly with fresh water, is saponified on a steam bath with agitation with 70 ml. of 2N sodium hydroxide solution in 250 ml. of water. After cooling, the reaction mixture is acidified with 12.5 ml. of concentrated hydrochloric acid, stirred for 16 hours at room temperature, and, after adding approximately the same volume of saturated NaCl solution, allowed to stand for 4 days. Thereafter, the mixture is vacuum-filtered from the thus-separated precipitate, which is washed with minimum portions of water and dried under vacuum. Yield: 17.2 g. (51%), m.p. 275°-277° C., with decomposition.
Reaction SMILES: [C:1](#[N:10])[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[OH-:11].[Na+]>C(O)(C)(C)C>[C:6]([C:5]1[CH:8]=[CH:9][C:2]([C:1]([NH2:10])=[O:11])=[CH:3][CH:4]=1)#[N:7]
Reactant: [OH-]
Reactant: N#Cc1ccc(C#N)cc1
Agent: [Na+]
Solvent: CC(C)(C)O
Product: N#Cc1ccc(C(N)=O)cc1
Temperature: 80 °C
Yield: 49 %

Procedure:
Terephthalonitrile (128 g) and tert-butanol (2432 g) were placed in a four-neck flask, and the mixture was heated to 80° C. with stirring. To the mixture, a 20% aqueous solution (13.4 g) of sodium hydroxide was added over three hours by use of a tube pump. Liquid chromatographic analysis revealed that the reaction mixture contained 71.5 g of p-cyanobenzamide (yield 49%) and 64 g of terephthalonitrile (conversion 50%). The reaction mixture was cooled to 25° C., neutralized with concentrated sulfuric acid (98% by weight), and heated under reduced pressure so as to concentrate the mixture and to remove tert-butanol (1824 g). After normal pressure was restored, the mixture was cooled to 25° C., and water (540 g) was added thereto. Subsequently, an aqueous solution (887.5 g) of sodium hypochlorite (effective chlorine 12%) was added to the reaction mixture over six hours while a 50% aqueous solution of sulfuric acid was added so as to maintain the pH of the mixture at 5-6. Liquid chromatographic analysis revealed that the reaction mixture contained 69.1 g of crude p-cyanobenzoic acid (yield 47%) and terephthalonitrile (64 g). Subsequently, the residual solvent (1090 g) was removed from the reaction mixture through distillation under reduced pressure. To the resultant mixture, a 48% aqueous solution of sodium hydroxide was added to thereby adjust the pH to 8, and the terephthalonitrile precipitated (60.2 g) was recovered through filtration. To the filtrate, concentrated sulfuric acid was added so as to adjust the pH to 3.0 and precipitate p-cyanobenzoic acid from its salt. The precipitate was dissolved by adding methanol (309 g) with heat, and the solution was cooled for crystallization, to thereby obtain 60.0 g of p-cyanobenzoic acid having a purity of 98% (yield 40%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:12]([CH2:16][CH:17]2[CH2:21][CH2:20][CH2:19][C:18]2=[O:22])[C:13](O)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].C(Cl)(=O)C(Cl)=O.[NH2:29][C:30]1[CH:35]=[N:34][CH:33]=[CH:32][N:31]=1.N1C=CC=CC=1>C(Cl)Cl.CN(C)C=O.O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:12]([CH2:16][CH:17]2[CH2:21][CH2:20][CH2:19][C:18]2=[O:22])[C:13]([NH:29][C:30]2[CH:35]=[N:34][CH:33]=[CH:32][N:31]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9]
Reactant: Nc1cnccn1
Reactant: CS(=O)(=O)c1ccc(C(CC2CCCC2=O)C(=O)O)cc1Cl
Agent: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: C1CCOC1
Solvent: c1ccncc1
Product: CS(=O)(=O)c1ccc(C(CC2CCCC2=O)C(=O)Nc2cnccn2)cc1Cl
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 29.5 %

Procedure:
A solution of 2(R)-(3-chloro-4-methylsulfonyl-phenyl)-N-methyl-N-(1(R)-methyl-2-oxo-2(R)-phenyl-ethyl)-3-(2-oxo-cyclopentyl)-propionamide (1.29 g, 2.63 mmol) in dioxane (4.43 mL) was treated with an 18M aqueous hydrochloric acid solution (4.43 mL). The reaction was then heated to 120° C. for 18 h. At this time, the reaction was cooled to 25° C., diluted with water (50 mL), and extracted with a 90/10 methylene chloride/methanol solution (3×100 mL). The organics were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, ethyl acetate) afforded racemic 2-(3-chloro-4-methylsulfonyl-phenyl)-3-(2-oxo-cylopentyl)-propionic acid (563.3 mg, 62.1%) as a light tan foam. A solution of 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(2-oxo-cyclopentyl)-propionic acid (563.3 mg, 1.6 mmol) in methylene chloride (16.4 mL) cooled to 0° C. was treated with a 2.0M solution of oxalyl chloride in methylene chloride (0.90 mL, 1.80 mmol) and a few drops of N,N-dimethylformamide. The reaction mixture was stirred at 0° C. for 10 min and at 25° C. for 20 min. The reaction mixture was then treated with a solution of 2-aminopyrazine (342 mg, 3.60 mmol) and pyridine (0.3 mL, 3.60 mmol) in tetrahydrofuran (8.2 mL). This solution was stirred at 25° C. for 18 h. At this time, the reaction was concentrated in vacuo. The residue was dissolved in methylene chloride (100 mL) and washed with a 1N aqueous hydrochloric acid solution (2×100 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 75/25 ethyl acetate/hexanes) afforded 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(2-oxo-cyclopentyl)-N-pyrazin-2-yl-propionamide (198.8 mg, 28.9%) as a clear oil.
Reaction SMILES: [H-].[Na+].[CH2:3]([C:7]1[CH:8]=[C:9]([NH:24][C:25]([C:27]2[C:32]([CH3:33])=[N:31][CH:30]=[CH:29][N:28]=2)=[O:26])[CH:10]=[CH:11][C:12]=1[C:13]([O:22][CH3:23])([C:18]([F:21])([F:20])[F:19])[C:14]([F:17])([F:16])[F:15])[CH:4]([CH3:6])[CH3:5].[C:34](Cl)(=[O:36])[CH3:35].Cl>C1COCC1>[C:34]([N:24]([C:9]1[CH:10]=[CH:11][C:12]([C:13]([O:22][CH3:23])([C:18]([F:20])([F:21])[F:19])[C:14]([F:17])([F:16])[F:15])=[C:7]([CH2:3][CH:4]([CH3:6])[CH3:5])[CH:8]=1)[C:25]([C:27]1[C:32]([CH3:33])=[N:31][CH:30]=[CH:29][N:28]=1)=[O:26])(=[O:36])[CH3:35]
Reactant: CC(=O)Cl
Reactant: COC(c1ccc(NC(=O)c2nccnc2C)cc1CC(C)C)(C(F)(F)F)C(F)(F)F
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COC(c1ccc(N(C(C)=O)C(=O)c2nccnc2C)cc1CC(C)C)(C(F)(F)F)C(F)(F)F
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 30.4 %

Procedure:
Sodium hydride (32 mg, 60% by weight, 0.8 mmol) was suspended in THF (10 ml) and a THF (5 ml) solution of N-{3-isobutyl-4-[1-methoxy-2,2,2-trifluoro-1-(trifluoromethyl)ethyl]phenyl}-3-methylpyrazine-2-carboxamide (300 mg, 0.67 mmol) was added dropwise thereto. The reaction solution was stirred at room temperature for 30 minutes, and was added with a THF (2 ml) solution of acetyl chloride (63 mg, 0.8 mmol) and stirred overnight. The reaction solution was poured into a diluted HCl solution, followed by extracting with ethyl acetate, and washing with water. The solution was dried over magnesium sulfate, and concentrated under reduced pressure, and then the residue was purified by using silica gel chromatography (hexane:ethyl acetate=3:1) to obtain 0.10 g of the desired compound.
Reaction SMILES: C[Si]([N-][Si](C)(C)C)(C)C.[K+].C1COCC1.[Br-].[C:17]1([CH2:23][CH2:24][CH2:25][CH2:26][P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[CH2:46]([N:53]1[CH2:58][CH2:57][C:56](=O)[CH2:55][CH2:54]1)[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1.Cl>C1(C)C=CC=CC=1>[CH2:46]([N:53]1[CH2:58][CH2:57][C:56](=[CH:26][CH2:25][CH2:24][CH2:23][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:55][CH2:54]1)[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1
Reactant: c1ccc(CCCC[P+](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Reactant: O=C1CCN(Cc2ccccc2)CC1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: Cl
Agent: [Br-]
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: C(CCCc1ccccc1)=C1CCN(Cc2ccccc2)CC1
Temperature: 25 °C
Yield: 58.7 %

Procedure:
A 0.62M solution of potassium bis(trimethylsilyl)amide in THF (180 mL, 112 mmol) in toluene (250 mL) was added to a mixture of (4-phenylbut-1-yl)triphenylphosphonium bromide from Step B (53 g) in toluene (250 mL) in an ice bath over 15 min with stirring under nitrogen. After stirring for a further 15 min, a solution of 1-benzyl-4-piperidone (16.9 g) in toluene (100 mL) was added over 30 min with stirring. The reaction mixture was allowed to warm to rt over 15 h. The reaction mixture was then poured into cold 1N HCl (400 mL) and the layers were separated. The organic layer was extracted with two more portions of 1N HCl. The combined cloudy HCl solution and an oil layer in between were washed with toluene (200 mL) before the aqueous layer was basified by the addition of potassium hydroxide (30 g). The aqueous layer was extracted with ether (3×150 mL) and the combined organic layers were washed with water and brine, dried over sodium sulfate and concentrated. The crude product was purified by FC (10-15% ethyl acetate in hexanes having 4% (v/v) TEA) to give the title compound (16 g) as a colorless oil. Rf: 0.47 (20% ethyl acetate in hexanes having 4% (v/v) TEA).
Reaction SMILES: [OH-].[Na+].C[O:4][C:5](=[O:49])[CH:6]([NH:35][C:36](=[O:48])[C:37]1[CH:42]=[C:41]([C:43]([F:46])([F:45])[F:44])[CH:40]=[CH:39][C:38]=1[F:47])[CH2:7][S:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:21]=[CH:20][C:19]([C:22]3[C:27]4[O:28][C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=5[C:26]=4[CH:25]=[CH:24][CH:23]=3)=[CH:18][CH:17]=2)=[CH:12][CH:11]=1.Cl>O1CCCC1.CO.O>[CH:25]1[C:26]2[C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=3[O:28][C:27]=2[C:22]([C:19]2[CH:18]=[CH:17][C:16]([C:13]3[CH:14]=[CH:15][C:10]([CH2:9][S:8][CH2:7][CH:6]([NH:35][C:36](=[O:48])[C:37]4[CH:42]=[C:41]([C:43]([F:46])([F:44])[F:45])[CH:40]=[CH:39][C:38]=4[F:47])[C:5]([OH:49])=[O:4])=[CH:11][CH:12]=3)=[CH:21][CH:20]=2)=[CH:23][CH:24]=1
Reactant: COC(=O)C(CSCc1ccc(-c2ccc(-c3cccc4c3oc3ccccc34)cc2)cc1)NC(=O)c1cc(C(F)(F)F)ccc1F
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: O=C(NC(CSCc1ccc(-c2ccc(-c3cccc4c3oc3ccccc34)cc2)cc1)C(=O)O)c1cc(C(F)(F)F)ccc1F
Temperature: 25 °C

Procedure:
2 N Sodium hydroxide solution (0.25 mL, 0.5 mmol) was added dropwise to a stirred solution of methyl-3-(4′-dibenzofuran-4-yl-biphen-4ylmethylsulfanyl)-2(2-fluoro-5-trifluoromethylbenzoylamino)-propionate (110 mg, 0.17 mmol) in tetrahydrofuran (5 mL) and methanol (1 mL). The clear reaction mixture was stirred at room temperature until the reaction was complete (TLC control), and then diluted with water (5 mL), and acidified to pH 3 with 2 N hydrochloric acid. The reaction mixture was extracted with ethyl acetate (2×10 mL). The combined extract was washed with water, sat'd aq NaCl, dried over anhydrous MgSO4, filtered and concentrated in vacuo. Purification by flash column chromatography (5-10% methanol in methylene chloride) afforded the title compound has a white solid (98 mg).
Reaction SMILES: [C:1]([C:3]1[CH:26]=[CH:25][C:6]2[O:7][C:8]([CH3:24])([CH3:23])[CH:9]=[C:10]([N:11]3[CH:16]=[CH:15][C:14]([CH:17]([OH:21])[CH2:18][CH2:19][OH:20])=[CH:13][C:12]3=[O:22])[C:5]=2[CH:4]=1)#[N:2].C(N(CC)CC)C.[Si:34](Cl)([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35].P([O-])([O-])([O-])=O>C(Cl)Cl>[C:1]([C:3]1[CH:26]=[CH:25][C:6]2[O:7][C:8]([CH3:23])([CH3:24])[CH:9]=[C:10]([N:11]3[CH:16]=[CH:15][C:14]([CH:17]([OH:21])[CH2:18][CH2:19][O:20][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35])=[CH:13][C:12]3=[O:22])[C:5]=2[CH:4]=1)#[N:2]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: CC1(C)C=C(n2ccc(C(O)CCO)cc2=O)c2cc(C#N)ccc2O1
Agent: O=P([O-])([O-])[O-]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC1(C)C=C(n2ccc(C(O)CCO[Si](C)(C)C(C)(C)C)cc2=O)c2cc(C#N)ccc2O1
Yield: 104 %

Procedure:
In 15 ml of anhydrous methylene chloride, is dissolved 1.06 g of 6-cyano-2,2-dimethyl-4-{1,2-dihydro-2-oxo-4-(1,3-dihydroxypropyl)-1-pyridinyl}-2H-benzo[b]pyran obtained in Example 37. Thereto are added 0.46 ml of triethylamine and 6 ml of a solution containing 0.48 g t-butyldimethylsilyl chloride in anhydrous methylene chloride at 0° C., and the resulting mixture is reacted at room temperature for 8 hours. After stopping the reaction by adding 0.2M phosphate buffer, the reaction mixture is extracted with methylene chloride. The organic layer is washed with saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. The inorganic matter is filtered off and the filtrate is concentrated under reduced pressure. Thus, 1.46 g of 6-cyano-2,2-dimethyl-4-{1,2-dihydro-2-oxo-4-(1-hydroxy-3-t-butyldimethylsilyloxypropyl)-1-pyridinyl}-2H-benzo[b]pyran is obtained.
Reaction SMILES: [CH:1]([N:4]([CH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1)[C:5](=[O:13])[C:6]1[CH:11]=[CH:10][C:9](Br)=[CH:8][CH:7]=1)([CH3:3])[CH3:2].[CH3:20][O:21][C:22]1[CH:23]=[C:24]([OH:30])[CH:25]=[C:26]([O:28][CH3:29])[CH:27]=1>N1C(C)=CC(C)=CC=1C>[CH:14]1([N:4]([CH:1]([CH3:3])[CH3:2])[C:5](=[O:13])[C:6]2[CH:11]=[CH:10][C:9]([O:30][C:24]3[CH:25]=[C:26]([O:28][CH3:29])[CH:27]=[C:22]([O:21][CH3:20])[CH:23]=3)=[CH:8][CH:7]=2)[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1
Reactant: CC(C)N(C(=O)c1ccc(Br)cc1)C1CCCCC1
Reactant: COc1cc(O)cc(OC)c1
Solvent: Cc1cc(C)nc(C)c1
Product: COc1cc(OC)cc(Oc2ccc(C(=O)N(C(C)C)C3CCCCC3)cc2)c1

Procedure:
The reaction and workup were carried out in the same manner as described in Example 1 using p-bromobenzoic acid N-isopropyl-N-cyclohexyl amide (2.353 g, 7.26 mmol), 3,5-dimethoxy phenol (1.061 g, 6.88 mmol) and cuprous oxide (492 mg, 3.44 mmol) in 2,4,6-collidine (15 ml). The crude product was chromatographed on silica gel using mixtures of ethyl acetate and hexane as eluents to give the title compound as a crystalline solid that could be recrystallized from ethyl acetate and hexane, m. pt. 140.12° C. (DSC).
Reaction SMILES: [C:1]([C:9]1[S:13][C:12]2[CH:14]=[C:15]([O:18][CH3:19])[CH:16]=[CH:17][C:11]=2[C:10]=1[OH:20])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])(=O)C.[NH4+:25]>>[NH2:25]/[C:1](/[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[C:9]1\[C:10](=[O:20])[C:11]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:12]=2[S:13]\1
Reactant: [NH4+]
Reactant: COc1ccc2c(O)c(C(=O)c3ccccc3)sc2c1
Agent: CC(=O)[O-]
Product: COc1ccc2c(c1)S/C(=C(/N)c1ccccc1)C2=O
Yield: 64 %

Procedure:
Prepared as in Example 31 from 2-benzoyl-6-methoxy-benzo[b]thiophen-3-ol and ammonium acetate with a yield of 64% of theory.
Reaction SMILES: [CH2:1]([S:13]([C:16]1[CH:24]=[CH:23][CH:22]=[CH:21][C:17]=1[C:18](O)=[O:19])(=[O:15])=[O:14])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].CN(C)C=O.C(Cl)(=O)C([Cl:33])=O>C(Cl)Cl>[CH2:1]([S:13]([C:16]1[CH:24]=[CH:23][CH:22]=[CH:21][C:17]=1[C:18]([Cl:33])=[O:19])(=[O:15])=[O:14])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCCCCCCCCCCS(=O)(=O)c1ccccc1C(=O)O
Reactant: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CCCCCCCCCCCCS(=O)(=O)c1ccccc1C(=O)Cl
Temperature: 25 °C

Procedure:
The o-dodecanesulfonylbenzoic acid (30.0 g, 0.084 mol) was dissolved in 100 ml of methylene chloride, then 0.5 ml of N,N-dimethylformamide was added, and they were stirred at room temperature. Then 12 ml of oxalyl chloride was added dropwise over 15 min, and after the addition the reaction mixture was stirred for 1 hour. The reaction solution was concentrated, to obtain o-dodecanesulfonylbenzoyl chloride.
Reaction SMILES: P(Cl)(Cl)(Cl)=O.[CH2:6]([O:13][C:14]([NH:16][C@@H:17]([C:27](=O)[NH2:28])[CH2:18][CH2:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[O:15])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.O>ClCCl.N1C=CC=CC=1>[CH2:6]([O:13][C:14]([NH:16][C@@H:17]([C:27]#[N:28])[CH2:18][CH2:19][C:20]([O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:21])=[O:15])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: CC(C)(C)OC(=O)CC[C@@H](NC(=O)OCc1ccccc1)C(N)=O
Solvent: c1ccncc1
Solvent: O=P(Cl)(Cl)Cl
Solvent: O
Product: CC(C)(C)OC(=O)CC[C@H](C#N)NC(=O)OCc1ccccc1
Temperature: 25 °C
Yield: 85.9 %

Procedure:
A solution of phosphorus oxychloride (2.05 g, 13.4 mmol) in dichloromethane (5.5 ml) was added during 20 minutes to a stirred solution of tert-butyl (4R)-4-(benzyloxycarbonylamino)-4-carbamoylbutyrate (3.0 g, 8.9 mmol) in dry pyridine (16 ml) at -5° C. under argon. The mixture was allowed to warm to room temperature and after 25 hours was poured into cold water (110 ml). The products were extracted with ethyl acetate (4×40 ml) and the combined ethyl acetate solution was washed successively with 10% aqueous citric acid solution (4×15 ml) and water (25 ml), then dried (Na2SO4) and evaporated. Toluene (4×25 ml) was added and evaporated and the residue was chromatographed with increasingly polar mixtures of hexane and ethyl acetate (100:0 to 2:1) as eluant to give tert-butyl (4R)-4-(benzyloxycarbonylamino)-4-cyanobutyrate (2.433 g, 86%) as a pale yellow oil.
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH:10]([CH:15]([OH:17])[CH3:16])[CH2:9]1)C1C=CC=CC=1>C(O)C.[C].[Pd]>[OH:17][CH:15]([CH:10]1[C:11](=[O:14])[CH2:12][CH2:13][NH:8][CH2:9]1)[CH3:16]
Reactant: CC(O)C1CN(Cc2ccccc2)CCC1=O
Agent: [Pd]
Solvent: CCO
Product: CC(O)C1CNCCC1=O
Temperature: 60 °C
Reaction time: 8 h
Yield: 104.1 %

Procedure:
In 100 ml of ethanol, 4.68 g (20 mmol) of the resulting 1-benzyl-3-(1-hydroxyethyl)-4-piperidone were dissolved. To the resulting solution, 0.5 g of 5% palladium-carbon were added, followed by stirring at 60° C. for 8 hours under a hydrogen gas atmosphere. After the completion of the reaction, the palladium-carbon was removed by filtration through Celite. The solvent was then distilled off under reduced pressure, whereby 2.98 g of 3-(1-hydroxyethyl)-4-piperidone were obtained as a colorless oil in a quantitative yield.