Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH:9][C:10]([C:12]2[CH:17]=[N:16][CH:15]=[CH:14][N:13]=2)=O)[CH:3]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:27])=CC=1>C1(C)C=CC=CC=1>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH:9][C:10]([C:12]2[CH:17]=[N:16][CH:15]=[CH:14][N:13]=2)=[S:27])[CH:3]=1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: Cc1cc(C)nc(NC(=O)c2cnccn2)c1
Solvent: Cc1ccccc1
Product: Cc1cc(C)nc(NC(=S)c2cnccn2)c1

Procedure:
2.5 g of product obtained in Example 21 and 5.31 g of Lawesson's reagent are dissolved in 50 ml of toluene, and the solutions maintained at reflux for 4 h. It is filtered and the solvent is evaporated off. The product is purified by chromatography on silica gel, eluting with dichloromethane.
Reaction SMILES: [CH2:1]([N:3]([CH2:5][CH3:6])[NH2:4])[CH3:2].C1C=CC=CC=1.[C:13](OC(=O)C)(=[O:15])[CH3:14]>C(Cl)(Cl)(Cl)Cl>[CH2:1]([N:3]([CH2:5][CH3:6])[NH:4][C:13](=[O:15])[CH3:14])[CH3:2]
Reactant: CC(=O)OC(C)=O
Reactant: CCN(N)CC
Solvent: c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: CCN(CC)NC(C)=O

Procedure:
N',N'-diethylacethydrazide was prepared following essentially the teaching of Hinman and Fulton, J. Amer. Chem. Soc. 80, 1895-1900 (1958). A mixture of 8.2 g (0.094 mole) of freshly distilled N,N-diethylhydrazine and 75 ml of benzene was added to a three-necked 250-ml round bottom flask equipped with a stirrer, a thermometer and a pressure equilibrating addition funnel capped with a drying tube. The flask was cooled in an ice bath. To this stirred solution was added 12.3 g (0.12 mole) of acetic anhydride. The ice bath was removed and the reaction mixture was heated for 1 hr. at 48°-58°. A fractional distillation of the reaction mixture gave a cut, b.p. 83°-84° at 3 mm, which melted at 47.5°-49.5°. NMR (CCl4, TMS) τ 1.0 (3 H, t), 1.9 (3 H, s), 2.6 (2 H, quad), 8.5 (1 H, broad).
Reaction SMILES: [O:1]=[C:2]1[CH2:10][CH2:9][CH2:8][C:7]2[NH:6][CH:5]=[C:4]([CH2:11][CH2:12][C:13]([OH:15])=O)[C:3]1=2.[C:16](N1C=CN=C1)([N:18]1C=CN=[CH:19]1)=O.CNC>ClCCl.O1CCCC1>[CH3:16][N:18]([CH3:19])[C:13](=[O:15])[CH2:12][CH2:11][C:4]1[C:3]2[C:2](=[O:1])[CH2:10][CH2:9][CH2:8][C:7]=2[NH:6][CH:5]=1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: O=C(O)CCc1c[nH]c2c1C(=O)CCC2
Agent: CNC
Solvent: C1CCOC1
Solvent: ClCCl
Product: CN(C)C(=O)CCc1c[nH]c2c1C(=O)CCC2
Reaction time: 1 h
Yield: 56.9 %

Procedure:
3-(4-Oxo-4,5,6,7-tetrahydro-1H-indol-3-yl)-propionic acid (12 g, 0.06 mol) was suspended in 80 ml of dichloromethane and carbonyldiimidazole (11.3 g, 0.07 mol) was added with stirring. After 30 minutes 58 ml of 2.0 M dimethylamine in tetrahydrofuran was added. After one hour the solvent was rotary evaporated. The residue was redissolved in dichloromethane, washed with 1 N hydrochloric acid and brine, dried over anhydrous magnesium sulfate and rotary evaporated. The solid residue was washed with ethyl acetate and dried under vacuum to give N, N-dimethyl-3-(4-oxo-4,5,6,7-tetrahydro-1H-indol-3-yl)-propionamide (8 g, 60% yield).
Reaction SMILES: [CH:1]([Si:3]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)=[CH2:2].[C:22]1([PH:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C1CCCCC1>[C:10]1([Si:3]([CH2:1][CH2:2][P:28]([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)([C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: c1ccc(Pc2ccccc2)cc1
Reactant: C=C[Si](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: C1CCCCC1
Product: c1ccc(P(CC[Si](c2ccccc2)(c2ccccc2)c2ccccc2)c2ccccc2)cc1
Temperature: 25 °C

Procedure:
The vinyl triphenyl silane was reacted with 10% excess of diphenyl phosphine. To maintain a homogeneous reaction mixture, a temperature of 80° C. and cyclohexane solvent ere employed. After the usual u.v. initiated addition, the reaction mixture was allowed to cool to room temperature. This resulted in the crystallization of the triphenylsilyethyl diphenyl phosphine adduct. To obtain it in a pure form, the adduct was filtered and recrystallized from a four to one mixture of cyclohexane and toluene. A white crystalline product having a melting point of 128°-131° C. was obtained.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([C:26]2[C:31]([CH3:32])=[CH:30][C:29]([O:33][CH2:34][C:35]3([OH:41])[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)=[CH:28][C:27]=2[CH3:42])=[C:6]2[C:10]=1[C@H:9]([O:11][C:12]1[CH:25]=[CH:24][C:15]3[C@H:16]([CH2:19][C:20]([O:22]C)=[O:21])[CH2:17][O:18][C:14]=3[CH:13]=1)[CH2:8][CH2:7]2>C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:26]2[C:31]([CH3:32])=[CH:30][C:29]([O:33][CH2:34][C:35]3([OH:41])[CH2:36][CH2:37][O:38][CH2:39][CH2:40]3)=[CH:28][C:27]=2[CH3:42])=[C:6]2[C:10]=1[C@H:9]([O:11][C:12]1[CH:25]=[CH:24][C:15]3[C@H:16]([CH2:19][C:20]([OH:22])=[O:21])[CH2:17][O:18][C:14]=3[CH:13]=1)[CH2:8][CH2:7]2
Reactant: COC(=O)C[C@@H]1COc2cc(O[C@@H]3CCc4c(-c5c(C)cc(OCC6(O)CCOCC6)cc5C)ccc(F)c43)ccc21
Solvent: CCOC(C)=O
Product: Cc1cc(OCC2(O)CCOCC2)cc(C)c1-c1ccc(F)c2c1CC[C@H]2Oc1ccc2c(c1)OC[C@H]2CC(=O)O

Procedure:
The title compound is prepared from methyl 2-((S)-6-((R)-7-fluoro-4-(4-((4-hydroxytetrahydro-2H-pyran-4-yl)methoxy)-2,6-dimethylphenyl)-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate following a procedure analogous to that described in example 4. TLC: rf=0.2 (silicagel, ethyl acetate); Mass spectrum (ESI+): m/z=563 [M+H]+.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:4]=[C:5]([CH:26]=[CH:27][N:28]=1)[C:6]([NH:8][C:9]1[S:10][C:11]2[C:17]([CH:18]3[CH2:23][O:22][CH2:21][CH2:20][O:19]3)=[CH:16][CH:15]=[C:14]([O:24][CH3:25])[C:12]=2[N:13]=1)=[O:7].C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:35]([NH:37][CH2:38][CH3:39])[CH3:36]>C(Cl)(Cl)Cl>[CH2:35]([N:37]([CH2:2][C:3]1[CH:4]=[C:5]([CH:26]=[CH:27][N:28]=1)[C:6]([NH:8][C:9]1[S:10][C:11]2[C:17]([CH:18]3[CH2:23][O:22][CH2:21][CH2:20][O:19]3)=[CH:16][CH:15]=[C:14]([O:24][CH3:25])[C:12]=2[N:13]=1)=[O:7])[CH2:38][CH3:39])[CH3:36]
Reactant: CCNCC
Reactant: COc1ccc(C2COCCO2)c2sc(NC(=O)c3ccnc(CCl)c3)nc12
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: ClC(Cl)Cl
Product: CCN(CC)Cc1cc(C(=O)Nc2nc3c(OC)ccc(C4COCCO4)c3s2)ccn1

Procedure:
From (+)-2-chloromethyl-N-(7-[1,4]dioxan-2-yl-4-methoxy-benzothiazol-2-yl)-isonicotinamide with cesium carbonate and diethylamine. [α]D20=+48.9° (c=1.02, CHCl3), ES-MS m/e (%): 457 (M+H+, 100).
Reaction SMILES: Cl[CH2:2][C:3]([NH:5][C:6]1[N:24]=[C:9]2[CH:10]=[CH:11][CH:12]=[C:13]([C:14]3[CH:23]=[CH:22][C:17]4[O:18][CH2:19][CH2:20][O:21][C:16]=4[CH:15]=3)[N:8]2[N:7]=1)=[O:4].C(N(CC)CC)C.[CH3:32][N:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1>ClCCl>[O:18]1[C:17]2[CH:22]=[CH:23][C:14]([C:13]3[N:8]4[N:7]=[C:6]([NH:5][C:3](=[O:4])[CH2:2][N:36]5[CH2:37][CH2:38][N:33]([CH3:32])[CH2:34][CH2:35]5)[N:24]=[C:9]4[CH:10]=[CH:11][CH:12]=3)=[CH:15][C:16]=2[O:21][CH2:20][CH2:19]1
Reactant: O=C(CCl)Nc1nc2cccc(-c3ccc4c(c3)OCCO4)n2n1
Reactant: CN1CCNCC1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CN1CCN(CC(=O)Nc2nc3cccc(-c4ccc5c(c4)OCCO5)n3n2)CC1
Reaction time: 8 h

Procedure:
To a solution of 2-chloro-N-[5-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-acetamide (0.1 g, 0.29 mmol) in dichloromethane (2 mL), triethylamine (0.061 mL, 0.43 mmol) and N-methylpiperazine (0.036 mL, 0.32 mmol) were added successively and the mixture was stirred overnight. The solvent was removed under reduced pressure and the crude then purified by prep LCMS. LCMS Method: 2, RT=2.19 min, MI=409 [M+1], NMR 1H (DMSO): 2.29 (s, 3H), 2.48-2.50 (m, 4H), 2.53-2.58 (m, 4H), 3.25 (brs, 2H), 4.33 (brs, 4H), 7.03 (d, 1H), 7.25 (dd, 1H), 7.47 (dd, 1H), 7.62-7.71 (m, 3H).
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=1.Cl[CH2:23][C:24]1[N:34]=[CH:33][CH:32]=[CH:31][C:25]=1[C:26]([O:28][CH2:29][CH3:30])=[O:27].CN(C)C=O.[H-].[Na+]>O>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:16]=[CH:17][C:18]([O:21][CH2:23][C:24]2[N:34]=[CH:33][CH:32]=[CH:31][C:25]=2[C:26]([O:28][CH2:29][CH3:30])=[O:27])=[CH:19][CH:20]=1
Reactant: Cc1oc(-c2ccccc2)nc1COc1ccc(O)cc1
Reactant: CCOC(=O)c1cccnc1CCl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)c1cccnc1COc1ccc(OCc2nc(-c3ccccc3)oc2C)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 63.2 %

Procedure:
To a mixture of 4-[(5-methyl-2-phenyl-4-oxazolyl)methoxy]phenol (2.70 g), ethyl 2-chloromethylnicotinate (1.74 g) and N,N-dimethylformamide (100 mL) was added sodium hydride (60%, oil, 0.42 g) under ice-cooling. The reaction mixture was stirred at room temperature for 2 hrs. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated. The obtained residue was subjected to silica gel column chromatography to give ethyl 2-[[4-[(5-methyl-2-phenyl-4-oxazolyl)methoxy]phenoxy]methyl]nicotinate as a colorless oil (2.45 g, 63%) from a fraction eluted with ethyl acetate-hexane (1:4, v/v).
Reaction SMILES: [N:1]1([C:8]2[C:13]([CH2:14][NH:15][C:16]3[N:20]([C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[C:22]=4[Cl:28])[CH:19]=[N:18][N:17]=3)=[CH:12][CH:11]=[CH:10][N:9]=2)[CH2:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[CH3:29][C:30]([CH3:32])=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClCCCl>[Cl:28][C:22]1[C:23]([Cl:27])=[CH:24][CH:25]=[CH:26][C:21]=1[N:20]1[CH:19]=[N:18][N:17]=[C:16]1[NH:15][CH2:14][C:13]1[C:8]([N:1]2[CH2:7][CH2:6][CH2:5][N:4]([CH:30]([CH3:32])[CH3:29])[CH2:3][CH2:2]2)=[N:9][CH:10]=[CH:11][CH:12]=1
Reactant: Clc1cccc(-n2cnnc2NCc2cccnc2N2CCCNCC2)c1Cl
Reactant: CC(C)=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCCl
Product: CC(C)N1CCCN(c2ncccc2CNc2nncn2-c2cccc(Cl)c2Cl)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of Example 113A in 1,2-dichloroethane (10 ml) was added acetone (3 mL) and sodium triacetoxyborohydride (253 mg, 1.194 mmol). The reaction mixture was stirred at room temperature overnight. Saturated sodium bicarbonate was added and the layers were separated. The aqueous layer was extracted with dichloromethane. The combined organic layer was washed with brine, dried over magnesium sulfate, filtered and concentrated. The residue was purified by flash column chromatography using dichloromethane/methanol (80:20) to give the title compound. MS (ESI+) m/z 460.6 (M+H)+; Rt=1.47. 1H NMR (DMSO-d6) δ 8,171 (s, 1H); 8,049 (d, 1H); 7,831(d, 1H); 7,586(m, 3H); 6,837 (dd, 1H); 6,521 (t, 1H); 4,353 (d, 2H); 3,377 (m, 4H); 3,289 (m, 1H); 2,862 (m, 2H); 2,642 (m, 2H); 1,773 (m, 2H); 0,949 (m, 6H).
Reaction SMILES: [CH3:1][O:2][CH2:3][C:4]([CH3:8])([CH3:7])[CH:5]=O.Cl.[NH2:10][OH:11].C([O-])(=O)C.[Na+].O>C(O)C>[CH3:1][O:2][CH2:3][C:4]([CH3:8])([CH3:7])[CH:5]=[N:10][OH:11]
Reactant: NO
Reactant: COCC(C)(C)C=O
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: COCC(C)(C)C=NO
Temperature: 40 °C
Reaction time: 24 h
Yield: 69 %

Procedure:
116 parts of methoxypivalaldehyde were dissolved in 600 parts of ethanol, and a solution of 76.5 parts of hydroxylamine hydrochloride and 86 parts of sodium acetate in 500 parts of water was added dropwise to the above, vigorously stirred solution, the temperature increasing temporarily to 40° C. Stirring was continued for 24 hours at room temperature, after which the mixture was poured into 4,000 parts of water and then saturated with sodium chloride and extracted with eight times 400 parts of ether. The combined extracts were dried over sodium sulfate, the solvent was stripped off, and the residue was distilled, giving 90.4 parts of methoxypivalaldoxime as a colourless liquid at 48°-49° C./0.1 mbar. Yield: 69% of theory.
Reaction SMILES: [H-].[Na+].[CH2:3](P([O-])(=O)[O-])[P:4]([O:9][CH2:10][CH3:11])(=[O:8])[O:5][CH2:6][CH3:7].C([N:23]1[CH2:28][CH2:27][C:26](=O)[CH2:25][CH2:24]1)C1C=CC=CC=1>O1CCCC1>[NH:23]1[CH2:28][CH2:27][CH:26]([CH2:3][P:4](=[O:8])([O:9][CH2:10][CH3:11])[O:5][CH2:6][CH3:7])[CH2:25][CH2:24]1
Reactant: CCOP(=O)(CP(=O)([O-])[O-])OCC
Reactant: O=C1CCN(Cc2ccccc2)CC1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOP(=O)(CC1CCNCC1)OCC
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
2.11 g (528 mmol) of 60% strength sodium hydride are initially charged in 50 ml of absolute tetrahydrofuran, and 15.7 g (52.8 mmol) of diethyl methanediphosphonate are added dropwise. The mixture is stirred at room temperature for another 30 minutes, and 10.1 g (52.8 mmol) of 1-benzyl-4-piperidone are then added. The mixture is stirred for one hour at room temperature and for one hour under reflux, concentrated, admixed with water and extracted three times with dichloromethane, and the organic phases are dried over sodium sulphate and concentrated. The residue is hydrogenated in 50 ml of ethanol over 1.7 g 10% palladium-carbon at room temperature and 3 bar. The catalyst is filtered off with suction and the filtrate is concentrated.
Reaction SMILES: [N:1]1([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:28][CH2:27][CH2:26][C@H:2]1[C:3]([NH:5][C@H:6]([C:12]([NH:14][CH2:15][C:16]([O:18]CC1C=CC=CC=1)=[O:17])=[O:13])[CH2:7][CH2:8][C:9](=[O:11])[NH2:10])=[O:4].[H][H]>CO.[Pd]>[N:1]1([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:28][CH2:27][CH2:26][C@H:2]1[C:3]([NH:5][C@H:6]([C:12]([NH:14][CH2:15][C:16]([OH:18])=[O:17])=[O:13])[CH2:7][CH2:8][C:9](=[O:11])[NH2:10])=[O:4]
Reactant: [H][H]
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)OCc1ccccc1
Agent: [Pd]
Solvent: CO
Product: CC(C)(C)OC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)O

Procedure:
Boc-Pro-Gln-Gly-OBzl (4.0 g, 8.2 m mol) was dissolved in 90% methanol (60 ml), and hydrogen gas was passed through the solution in the presence of a spoonful of Pd-C for 6 hours. After removing the catalyst by filtration, the filtrate was concentrated under reduced pressure, and the residue was solidified by the addition of ether and recrystallized from methanol-ether.
Reaction SMILES: C1(S([C:10](=[CH:15][C:16]2[CH:21]=[C:20]([C:22]([CH3:25])([CH3:24])[CH3:23])[C:19]([OH:26])=[C:18]([C:27]([CH3:30])([CH3:29])[CH3:28])[CH:17]=2)[C:11]([NH:13][CH3:14])=[O:12])(=O)=O)C=CC=CC=1.COCCO.[N-:36]=[N+:37]=[N-:38].[Na+]>O>[CH3:30][C:27]([C:18]1[CH:17]=[C:16]([C:15]2[NH:36][N:37]=[N:38][C:10]=2[C:11]([NH:13][CH3:14])=[O:12])[CH:21]=[C:20]([C:22]([CH3:23])([CH3:24])[CH3:25])[C:19]=1[OH:26])([CH3:28])[CH3:29]
Reactant: [N-]=[N+]=[N-]
Reactant: CNC(=O)C(=Cc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1)S(=O)(=O)c1ccccc1
Agent: [Na+]
Solvent: O
Solvent: COCCO
Product: CNC(=O)c1nn[nH]c1-c1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1
Temperature: 105 °C
Reaction time: 1 h
Yield: 91.4 %

Procedure:
A 250 mL 3-neck round-bottom flask immersed in an oil bath, equipped with a mechanical stirrer, thermometer, reflux condenser and nitrogen bubbler, was charged with 42.96 g (0.100 mol) of 2-(benzenesulfonyl)-3-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]-N-methylacrylamide (II), 100 mL of 2-methoxyethanol and 6.83 g (0.105 mol) of sodium azide. The yellow mixture was heated at 105° C. for 30 h. The cooled orange solution was poured onto a mixture of 150 g of ice and 150 mL of deionized water. The yellow suspension was agitated for 1 h at 5° C. The resulting solid precipitate was filtered off and washed with 5×50 mL of cold deionized water. The recovered solids were dried in vacuo over potassium hydroxide flakes to afford yellow solids, 30.2 g of crude product (I), 98.7% purity by HPLC.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH2:5][C:4]([CH3:9])([CH3:8])[C:3]=1[C:10]#[C:11][CH:12](OC(=O)C)[CH3:13].C(Cl)Cl.C1(C)C=CC(S(O)(=O)=[O:28])=CC=1>O>[C:10]([C:3]1[C:4]([CH3:9])([CH3:8])[CH2:5][CH:6]=[CH:7][C:2]=1[CH3:1])(=[O:28])/[CH:11]=[CH:12]/[CH3:13]
Reactant: CC(=O)OC(C)C#CC1=C(C)C=CCC1(C)C
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Solvent: ClCCl
Solvent: O
Product: C/C=C/C(=O)C1=C(C)C=CCC1(C)C
Yield: 60 %

Procedure:
In a 100 ml. three-necked flask fitted with a mechanical stirrer and a Dean-Stark water separator provided with a reflux condenser, a solution of 5 g. of 2,6,6-trimethyl-1-(3-acetoxy-but-1-ynyl)cyclohexa-1,3-diene in 70 ml. of methylene chloride is refluxed while stirring. Then 0.2 g. of p-toluenesulfonic acid is added and the reaction mixture is refluxed for an additional 4 to 5 hours. The reaction mixture is cooled and poured into 70 ml. of water. The organic layer is separated, subsequently washed with 10% sodium bicarbonate solution and water, and finally dried over sodium sulfate. Concentration yields 5 g. of a residue which gives on distillation 2.5 g. or 60% yield of 1-crotonoyl-2,6,6-trimethylcyclohexa-1,3-diene, b.p. 75°-80° C./0.1 mm., nD20 1.5150.
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)=[C:5]([C:7]([N:9]2[C@H:14]([CH2:15][NH2:16])[CH2:13][C@H:12]3[C@@H:10]2[CH2:11]3)=[O:8])[N:6]=1.[CH3:24][N:25]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:27]([C:34](O)=[O:35])=[C:26]1[CH3:37]>>[NH2:1][C:2]1[S:3][C:4]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)=[C:5]([C:7]([N:9]2[C@H:14]([CH2:15][NH:16][C:34]([C:27]3[C:28]4[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=4)[N:25]([CH3:24])[C:26]=3[CH3:37])=[O:35])[CH2:13][C@H:12]3[C@@H:10]2[CH2:11]3)=[O:8])[N:6]=1
Reactant: Cc1c(C(=O)O)c2ccccc2n1C
Reactant: NC[C@@H]1C[C@@H]2C[C@@H]2N1C(=O)c1nc(N)sc1-c1cccc(F)c1
Product: Cc1c(C(=O)NC[C@@H]2C[C@@H]3C[C@@H]3N2C(=O)c2nc(N)sc2-c2cccc(F)c2)c2ccccc2n1C

Procedure:
prepared by reaction of [2-amino-5-(3-fluoro-phenyl)-thiazol-4-yl]-((1S,3S,5S)-3-aminomethyl-2-aza-bicyclo[3.1.0]hex-2-yl)-methanone with 1,2-dimethyl-1H-indole-3-carboxylic acid. LC-MS (basic): tR=0.83 min; [M+H]+=504.2.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:5]=[CH:4][C:3]=1[OH:14].C[O:16][C:17]([C:19]1[O:20][C:21]([CH2:24]Cl)=[CH:22][CH:23]=1)=[O:18]>>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:5]=[CH:4][C:3]=1[O:14][CH2:24][C:21]1[O:20][C:19]([C:17]([OH:18])=[O:16])=[CH:23][CH:22]=1
Reactant: Oc1ccc(-c2ccccc2)cc1Cl
Reactant: COC(=O)c1ccc(CCl)o1
Product: O=C(O)c1ccc(COc2ccc(-c3ccccc3)cc2Cl)o1

Procedure:
5-(3-Chloro-biphenyl-4-yloxymethyl)-furan-2-carboxylic acid was prepared using general procedure A from 2-chloro-4-phenylphenol (available from TCI America, Portland, Oreg.) and 5-chloromethylfuran-2-carboxylic acid methyl ester (available from Aldrich, Milwaukee, Wis., or from Maybridge plc, Tintagel, UK). Yield: 66 mg. Mass spectrum (ES) MH+=329.
Reaction SMILES: [C:1]1([CH3:29])[CH:6]=[CH:5][C:4]([S:7]([N:10]2[C:18]3[CH:17]=[CH:16][CH:15]=[C:14]([C:19]([O:21]CC4C=CC=CC=4)=[O:20])[C:13]=3[CH:12]=[CH:11]2)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[H][H]>[Pd].CO.O>[C:1]1([CH3:29])[CH:2]=[CH:3][C:4]([S:7]([N:10]2[C:18]3[CH:17]=[CH:16][CH:15]=[C:14]([C:19]([OH:21])=[O:20])[C:13]=3[CH:12]=[CH:11]2)(=[O:8])=[O:9])=[CH:5][CH:6]=1
Reactant: [H][H]
Reactant: Cc1ccc(S(=O)(=O)n2ccc3c(C(=O)OCc4ccccc4)cccc32)cc1
Agent: [Pd]
Solvent: O
Solvent: CO
Product: Cc1ccc(S(=O)(=O)n2ccc3c(C(=O)O)cccc32)cc1
Yield: 77.1 %

Procedure:
The mixture of benzyl 1-(4-toluenesulfonyl)indole-4-carboxylate (550 mg) and 10% palladium on charcoal (200 mg) in methanol (20 ml) and water (2 ml) was hydrogenated at ambient temperature (an initial hydrogen pressure was set to 3.5 atm.). The theoretical amount of hydrogen was absorbed in 6 hours. The resulting mixture was filtered through a bed of celite and the filtrate was evaporated in vacuo. The residue was diluted with chloroform and the solution was dried over magnesium sulfate. Filtering and removal of solvents afforded a crude product. The crude product was triturated with diethyl ether-n-hexane (1:3) to give 1-(4-toluenesulfonyl)indole-4-carboxylic acid (330 mg) as a brown powder.
Reaction SMILES: [CH3:1][N:2]1[C:11]2[C:6](=[CH:7][C:8](B3OC(C)(C)C(C)(C)O3)=[CH:9][CH:10]=2)[CH2:5][CH2:4][C:3]1=[O:21].Br[C:23]1[CH:24]=[N:25][CH:26]=[C:27]([N:29]2[CH2:33][CH2:32][CH2:31][C@@H:30]2[C:34]([CH3:42])([CH3:41])[O:35][SiH2:36][C:37]([CH3:40])([CH3:39])[CH3:38])[CH:28]=1>>[C:37]([SiH2:36][O:35][C:34]([CH3:42])([CH3:41])[C@H:30]1[CH2:31][CH2:32][CH2:33][N:29]1[C:27]1[CH:28]=[C:23]([C:8]2[CH:7]=[C:6]3[C:11](=[CH:10][CH:9]=2)[N:2]([CH3:1])[C:3](=[O:21])[CH2:4][CH2:5]3)[CH:24]=[N:25][CH:26]=1)([CH3:40])([CH3:38])[CH3:39]
Reactant: CC(C)(C)[SiH2]OC(C)(C)[C@H]1CCCN1c1cncc(Br)c1
Reactant: CN1C(=O)CCc2cc(B3OC(C)(C)C(C)(C)O3)ccc21
Product: CN1C(=O)CCc2cc(-c3cncc(N4CCC[C@@H]4C(C)(C)O[SiH2]C(C)(C)C)c3)ccc21

Procedure:
In analogy to the procedure described for the preparation of intermediate A-3 [C], 1-methyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-quinolin-2-one (intermediate A-1) has been coupled to 3-bromo-5-[(R)-2-(tert-butyl-dimethyl-silanyloxymethyl)-pyrrolidin-1-yl]-pyridine to give the title compound as a white solid. MS: 452.1 (M+H+).
Reaction SMILES: [C:1]([O:4][C:5]1[C:15]([O:16][CH3:17])=[CH:14][C:8]([CH:9]=[CH:10][C:11](O)=[O:12])=[CH:7][C:6]=1[O:18][CH3:19])(=[O:3])[CH3:2].O1C=CN=C1[Cl:25]>CN(C)C=O.O1CCCC1>[C:1]([O:4][C:5]1[C:15]([O:16][CH3:17])=[CH:14][C:8]([CH:9]=[CH:10][C:11]([Cl:25])=[O:12])=[CH:7][C:6]=1[O:18][CH3:19])(=[O:3])[CH3:2]
Reactant: COc1cc(C=CC(=O)O)cc(OC)c1OC(C)=O
Reactant: Clc1ncco1
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: COc1cc(C=CC(=O)Cl)cc(OC)c1OC(C)=O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a mixture o 4-acetoxy-3,5-dimethoxycinnamic acid (638 mg), dimethylformamide (2 drops) and tetrahydrofuran (8 ml) was added oxazolyl chloride (0.25 ml). The mixture was stirred at room temperature for one hour and then the solvent was distilled off to obtain 4-acetoxy-3,5-dimethoxycinnamic acid chloride as crystals. To a solution of the crystals in dichloromethane (15 ml) were added 5-amino-4-(2-chlorophenyl)-2-ethylthieno[2,3-b]pyridine (576 mg) and N,N-dimethylaniline (0.25 ml) with ice cooling. After warming to room temperature, the mixture was stirred for 5 hours, washed in turn with water, aqueous saturated NaHCO3 solution and water, and then dried over MgSO4. The solvent was distilled off and the residue was crystallized from ethanol (729 mg, 67.4%). 5-(4-Acetoxy-3,5-dimethoxycinnamoylamino)-4-(2-chloropheny ethylthieno[2,3-b]pyridine was obtained as colorless prisms by recrystallization from acetone, mp: 133°-135° C.
Reaction SMILES: [C:1]([C:5]1[CH:35]=[CH:34][C:8]([CH2:9][N:10]2[CH2:14][CH:13]([CH2:15][CH2:16][CH2:17][C:18]3[CH:30]=[CH:29][C:21]([O:22][C:23]([CH3:28])([CH3:27])[C:24]([OH:26])=[O:25])=[C:20]([CH3:31])[CH:19]=3)[N:12]([CH3:32])[C:11]2=[O:33])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:36]O>S(=O)(=O)(O)O>[CH3:36][O:25][C:24](=[O:26])[C:23]([O:22][C:21]1[CH:29]=[CH:30][C:18]([CH2:17][CH2:16][CH2:15][CH:13]2[CH2:14][N:10]([CH2:9][C:8]3[CH:34]=[CH:35][C:5]([C:1]([CH3:2])([CH3:3])[CH3:4])=[CH:6][CH:7]=3)[C:11](=[O:33])[N:12]2[CH3:32])=[CH:19][C:20]=1[CH3:31])([CH3:27])[CH3:28]
Reactant: CO
Reactant: Cc1cc(CCCC2CN(Cc3ccc(C(C)(C)C)cc3)C(=O)N2C)ccc1OC(C)(C)C(=O)O
Agent: O=S(=O)(O)O
Product: COC(=O)C(C)(C)Oc1ccc(CCCC2CN(Cc3ccc(C(C)(C)C)cc3)C(=O)N2C)cc1C
Temperature: 25 °C
Reaction time: 8 h
Yield: 99 %

Procedure:
To a solution of 2-(4-{3-[1-(4-tert-Butyl-benzyl)-3-methyl-2-oxo-imidazolidin-4-yl]-propyl}-2-methyl-phenoxy)-2-methyl-propionic acid (0.610 g, 1.27 mmole) in methanol (10 mL) was added 15 drops of concentrated sulfuric acid. The mixture was stirred at room temperature overnight. After evaporated the solvent, the residue was partitioned between ethyl acetate (50 mL) and water (50 mL). The organic layer was washed by saturated sodium bicarbonate (50 mL), then brine (3×50 mL), dried over Na2SO4, filtered and concentrated in vacuo to produce an oil (0.624 g, 99%). Mass [EI+] 495 (M+H)+.