Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.[S:10]1[CH:14]=[CH:13][CH:12]=[CH:11]1.C([O-])(=O)C.[K+]>CC(N(C)C)=O.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>[S:10]1[CH:14]=[CH:13][CH:12]=[C:11]1[C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1
Reactant: O=Cc1ccc(Br)cc1
Reactant: c1ccsc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: CC(=O)[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Product: O=Cc1ccc(-c2cccs2)cc1
Temperature: 150 °C
Reaction time: 16 h

Procedure:
3.7 g (20 mmol) of 4-bromobenzaldehyde, 9.5 ml (120 mmol) of thiophene, 2.94 g (30 mmol) of potassium acetate and 1.16 g (1 mmol) of tetrakis(triphenylphosphine)palladium (Fluka, Buchs, Switzerland) in 50 ml of dimethylacetamide are placed in a pressure reactor and stirred at 150° C. under nitrogen for 16 hours. The reaction mixture is concentrated by evaporation; the residue is taken up in water and extracted three times with methylene chloride. After removal of the solvent, the residue is chromatographed on silica gel (hexane/ethyl acetate 4:1). The title compound is obtained in the form of a yellow solid. TLC: Rf =0.36 (hexane/ethyl acetate 4:1). HPLC20-100 : tRet =15.26. 1H-NMR (CD3OD; 200 MHz): 9.98/s (1 H); 7.93 and 7.85/each d, J=9.5 (2×2 H); 7.60/d, J=2.5 (1 H); 7.52/d, J=5 (1 H); 7.17/dxd, J=2.5 and 5 (1 H).
Reaction SMILES: [CH3:1][Si:2]([C:5]#[CH:6])([CH3:4])[CH3:3].C([Li])CCC.CCCCCC.[CH2:18]([Sn:22](Cl)([CH2:27][CH2:28][CH2:29][CH3:30])[CH2:23][CH2:24][CH2:25][CH3:26])[CH2:19][CH2:20][CH3:21]>O1CCCC1>[CH3:1][Si:2]([CH3:4])([CH3:3])[C:5]#[C:6][Sn:22]([CH2:23][CH2:24][CH2:25][CH3:26])([CH2:27][CH2:28][CH2:29][CH3:30])[CH2:18][CH2:19][CH2:20][CH3:21]
Reactant: CCCC[Sn](Cl)(CCCC)CCCC
Reactant: C#C[Si](C)(C)C
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CCCC[Sn](C#C[Si](C)(C)C)(CCCC)CCCC
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 52.1 %

Procedure:
Under argon stream, 3.53 ml (25 mmol) of trimethylsilylacetylene was dissolved in 25 ml of tetrahydrofuran and cooled to -78° C. Into the solution was added dropwise 145.9 ml (24 mmol) of butyllithium-hexane solution, and the reaction was carried out with stirring for 30 minutes. Then, 6.5 ml (24 mmol) of tributyltin chloride was added dropwise, and the reaction was carried out with stirring for 22 hours, while elevating gradually the temperature of the reaction mixture to room temperature. After the reaction, the solvent was evaporated and the residue was distilled under reduced pressure (0.6 mm Hg, 100°-102° C.) to obtain 4.84 g of a transparent liquid (yield: 52.2%).
Reaction SMILES: [N:1]1([CH2:6][CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]([CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)=[O:17])=[CH:11][CH:10]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[F:26][C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][CH:34]=1)[CH2:30]Br.O>CN(C)C=O>[F:26][C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][CH:34]=1)[CH2:30][N:15]([C:12]1[CH:13]=[CH:14][C:9]([O:8][CH2:7][CH2:6][N:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)=[CH:10][CH:11]=1)[C:16]([CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1)=[O:17]
Reactant: O=C(Nc1ccc(OCCN2CCCC2)cc1)C1CCCCC1
Reactant: Fc1cccc(CBr)c1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: O=C(C1CCCCC1)N(Cc1cccc(F)c1)c1ccc(OCCN2CCCC2)cc1
Temperature: 0 °C
Reaction time: 0.08 h

Procedure:
To a solution of cyclohexanecarboxylic acid (4-(2-pyrrolidin-1-yl-ethoxy)phenyl]-amide (0.250 g, 0.79 mmol) in 5 mL N,N-dimethylformamide at 0° C. was added sodium hydride (0.041 g of a 60% dispersion in mineral oil, 1.03 mmol). The reaction mixture was stirred at 0° C. for 5 minutes and 3-fluorobenzyl bromide (0.117 mL, 0.95 mmol) was added. The reaction mixture was stirred at room temperature for 24 hr. and water was added. The aqueous solution was washed with ethyl acetate (2×). The combined organic layers were dried (magnesium sulfate), filtered, and concentrated. Medium pressure silica gel chromatography (methylene chloride to 5% methanol/methylene chloride) afforded the title compound. MS 425.2 (M+1)+
Reaction SMILES: [C:1]1([NH:7][CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC[O:17][C:18]([CH:20]1[C:25](=O)[CH:24](Br)[CH2:23][CH2:22][CH2:21]1)=[O:19]>O.[Cl-].[Zn+2].[Cl-]>[CH2:8]([N:7]1[C:22]2[CH2:23][CH2:24][CH2:25][CH:20]([C:18]([OH:19])=[O:17])[C:21]=2[C:2]2[C:1]1=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1
Reactant: CCOC(=O)C1CCCC(Br)C1=O
Reactant: c1ccc(CNc2ccccc2)cc1
Agent: [Cl-]
Agent: [Zn+2]
Solvent: O
Product: O=C(O)C1CCCc2c1c1ccccc1n2Cc1ccccc1

Procedure:
A mixture of 53 g. of phenylbenzylamine and 30 g. of ethyl 6-bromocyclohexanone-2-carboxylate was maintained in a nitrogen atmosphere at 35° C. for several days. Fused powdered zinc chloride (48 g.) was added and the mixture was heated at 125°-130°C. for 11/2 hours. The cooled mixture was slurried in water and extracted with ether. The ether extract was washed with 5% hydrochloric acid and water, dried, and evaporated to dryness to give 38.5 g. crude ethyl ester of the title compound which was treated with a solution of 48 g. potassium hydroxide in 200 ml. water and 200 ml. ethyl alcohol at reflux temperature for three hours. The solution was evaporated to dryness under reduced pressure, the resulting residue was dissolved in water and the aqueous solution was extracted with ether and acidified with 10% hydrochloric acid. The resulting solids were collected and dried to give 27.4 g. of the title compound; m.p. 212°-215°C. (tetrahydrofuran-pentane).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:14])[CH2:10][N:11]([CH3:13])[CH3:12].[CH2:15]([O:17][C:18]([N:20]=[C:21]=[S:22])=[O:19])[CH3:16]>C(#N)C>[CH2:15]([O:17][C:18]([NH:20][C:21]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:14])[CH2:10][N:11]([CH3:12])[CH3:13])=[S:22])=[O:19])[CH3:16]
Reactant: CCOC(=O)N=C=S
Reactant: CN(C)CC(=O)Nc1ccccc1N
Solvent: CC#N
Product: CCOC(=O)NC(=S)Nc1ccccc1NC(=O)CN(C)C
Reaction time: 0.08 h
Yield: 62.9 %

Procedure:
A suspension of N-(2-aminophenyl)-2-dimethylaminoacetamide (8.9 g) (prepared as described in Example 6) in acetonitrile (50 ml) was treated with ethoxycarbonyl isothiocyanate (6.4 g), dropwise with stirring, maintaining the temperature at 15°-20° C. by external cooling. When the addition was complete, the solid had dissolved but after being left to stand for a further 5 minutes, another solid precipitated. This was filtered off and washed with ice-cold acetonitrile to give 1-ethoxycarbonyl-3-(2-dimethylaminoacetamidophenyl)thiourea (9.4 g), m.p. 159°-160° C. (with decomposition).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:6]([CH2:7][N:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH2:11][CH2:10][C:9]2=[O:18])=[CH:5][CH:4]=1.[Li+].CC([N-]C(C)C)C.Br[CH2:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32]>C1COCC1>[C:34]([O:33][C:31](=[O:32])[CH2:30][CH:10]1[CH2:11][C:12]2[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:8]([CH2:7][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:20][CH:19]=2)[C:9]1=[O:18])([CH3:37])([CH3:36])[CH3:35]
Reactant: CC(C)(C)OC(=O)CBr
Reactant: COc1ccc(CN2C(=O)CCc3ccccc32)cc1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: COc1ccc(CN2C(=O)C(CC(=O)OC(C)(C)C)Cc3ccccc32)cc1
Temperature: -78 °C
Reaction time: 0.17 h
Yield: 53 %

Procedure:
The 1-(4-methoxy-benzyl)-3,4-dihydro-1H-quinolin-2-one (7.86 mmol) obtained in the previous step is dissolved in 10 mL of anhydrous THF. A solution of freshly prepared LDA (9.43 mmol) in 3.5 mL of anhydrous THF is added dropwise at −78° C. The reaction mixture is stirred at −78° C. for 10 minutes, warmed up to 0° C. for 15 minutes, and then cooled down to −78° C. again before it is transferred dropwise through a double-ended needle to a solution of tert-butyl bromoacetate (10.2 mmol) in 5 mL of anhydrous THF. The resultant solution is stirred at −78° C. for 1 hour before it is allowed to warm up to 0° C. within another hour and then quenched with MeOH. After removal of the solvent, the residue is purified by silica gel chromatography (hexane/EtOAc) to give [1-(4-methoxy-benzyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid tert-butyl ester as a light yellow oil. Yield: 53%. 1H NMR (400 MHz, CDCl3): δ 7.13 (m, 4H), 6.96 (t, 1H), 6.90 (d, 1H), 6.83 (d, 2H), 5.25 (d, 1H), 4.95 (d, 1H), 3.76 (s, 3H), 3.13 (m, 1H), 3.00-2.85 (m, 3H), 2.41 (dd, 1H), 1.48 (s, 9H). MS: (ES+): 404.2 [M+23].
Reaction SMILES: [F-].C([N+](CCCC)(CCCC)CCCC)CCC.[CH3:19][O:20][C:21](=[O:61])[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:34]=[CH:33][C:32]([C:35]([CH2:58][CH3:59])([C:38]3[CH:43]=[CH:42][C:41]([C:44]#[C:45][C:46]4([O:52][Si](C)(C)C)[CH2:51][CH2:50][S:49][CH2:48][CH2:47]4)=[C:40]([CH3:57])[CH:39]=3)[CH2:36][CH3:37])=[CH:31][C:30]=2[CH3:60])=[CH:25][CH:24]=1.O>O1CCCC1>[CH3:19][O:20][C:21](=[O:61])[CH2:22][C:23]1[CH:24]=[CH:25][C:26]([C:29]2[CH:34]=[CH:33][C:32]([C:35]([CH2:36][CH3:37])([C:38]3[CH:43]=[CH:42][C:41]([C:44]#[C:45][C:46]4([OH:52])[CH2:51][CH2:50][S:49][CH2:48][CH2:47]4)=[C:40]([CH3:57])[CH:39]=3)[CH2:58][CH3:59])=[CH:31][C:30]=2[CH3:60])=[CH:27][CH:28]=1
Reactant: CCC(CC)(c1ccc(C#CC2(O[Si](C)(C)C)CCSCC2)c(C)c1)c1ccc(-c2ccc(CC(=O)OC)cc2)c(C)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: O
Product: CCC(CC)(c1ccc(C#CC2(O)CCSCC2)c(C)c1)c1ccc(-c2ccc(CC(=O)OC)cc2)c(C)c1
Reaction time: 0.5 h
Yield: 71.9 %

Procedure:
Tetrabutylammonium fluoride (1 M solution in tetrahydrofuran, 0.13 mL, 0.13 mmol) was added to a solution of (4′-{1-ethyl-1-[3-methyl-4-(4-trimethylsilanyloxy-tetrahydro-thiopyran-4-ylethynyl)-phenyl]-propyl}-2′-methyl-biphenyl-4-yl)-acetic acid methyl ester (Example 136-(5); 53 mg, 0.09 mmol) in tetrahydrofuran (1 mL) at 0° C., and the mixture was stirred at the same temperature for 30 minutes. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=1:1) to give the target compound as a colorless oil (35 mg, 78%).
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][NH2:10])=[CH:5][CH:4]=1.[OH-].[Na+].C(O)(=O)C.CN([CH:20]=[N:21][C:22]([C:24]1[CH:29]=[N:28][CH:27]=[CH:26][N:25]=1)=O)C>O1CCOCC1>[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:22]([C:24]3[CH:29]=[N:28][CH:27]=[CH:26][N:25]=3)=[N:21][CH:20]=[N:10]2)=[CH:5][CH:4]=1
Reactant: NNc1ccc(Cl)cc1
Reactant: CN(C)C=NC(=O)c1cnccn1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: C1COCCO1
Product: Clc1ccc(-n2ncnc2-c2cnccn2)cc1

Procedure:
To a solution of 12.1 g. of 4-chlorophenylhydrazine hydrochloride in a mixture of 13.5 ml. of 5 N sodium hydroxide, 100 ml. of 30% aqueous acetic acid and 50 ml. of p-dioxane is added 10.0 g. of N-(dimethylaminomethylene pyrazinecarboxamide. The procedure of Example 2 is then followed giving 3.8 g. of the desired product as tan crystals, mp. 129°-131° C.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:7]([OH:24])=[C:8]2[C:15]([Br:16])=[C:14]([Br:17])[N:13]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:9]2=[C:10](Br)[N:11]=1)=[O:5])[CH3:2].[C:25]([Cu])#[N:26]>>[CH2:1]([O:3][C:4]([C:6]1[C:7]([OH:24])=[C:8]2[C:15]([Br:16])=[C:14]([Br:17])[N:13]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:9]2=[C:10]([C:25]#[N:26])[N:11]=1)=[O:5])[CH3:2]
Reactant: N#C[Cu]
Reactant: CCOC(=O)c1nc(Br)c2c(c1O)c(Br)c(Br)n2-c1ccccc1
Product: CCOC(=O)c1nc(C#N)c2c(c1O)c(Br)c(Br)n2-c1ccccc1

Procedure:
Prepared in analogy to that of Example 105(a) from 2,3,7-tribromo-4-hydroxy-1-phenyl-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid ethyl ester and CuCN. The title compound, ESI MS (m/z): 464 (M+H)+.
Reaction SMILES: C([O:4][C@@H:5]1[CH2:10][CH2:9][CH2:8][C@@H:7]([N:11]2[C:15]3[CH:16]=[C:17]([Cl:21])[C:18]([Cl:20])=[CH:19][C:14]=3[N:13]=[C:12]2Br)[C@@H:6]1[O:23]C(=O)C)(=O)C.[CH:27]1([NH2:30])[CH2:29][CH2:28]1.[OH-].[Na+]>>[Cl:20][C:18]1[C:17]([Cl:21])=[CH:16][C:15]2[N:11]([C@@H:7]3[CH2:8][CH2:9][CH2:10][C@@H:5]([OH:4])[C@H:6]3[OH:23])[C:12]([NH:30][CH:27]3[CH2:29][CH2:28]3)=[N:13][C:14]=2[CH:19]=1
Reactant: CC(=O)O[C@H]1[C@H](n2c(Br)nc3cc(Cl)c(Cl)cc32)CCC[C@H]1OC(C)=O
Reactant: NC1CC1
Agent: [Na+]
Agent: [OH-]
Product: O[C@@H]1[C@H](O)CCC[C@H]1n1c(NC2CC2)nc2cc(Cl)c(Cl)cc21
Yield: 76 %

Procedure:
(±)-(1R*,2S*,3R*)-3-(2-Bromo-5,6-dichloro-1H-benzimidazol-1-yl)-1,2-cyclohexanediyl diacetate (464 mg, 1.00 mmol) and cyclopropylamine were reacted as in example 46. The solution was cooled and 1 N sodium hydroxide (one equivalent) was added. Volatiles were evaporated in vacuo and the residual solid was crystallized from methanol to provide title compound as off-white powder (271 mg, 76%), m.p. >25° C.; 1H-NMR (DMSO-d6, 200 MHz) δ: 7.62, 7.44 (both s, each 1, 2 aromatic CH), 7.00-6.95 (m, 1, NH), 4.66 (d, J=6.2 Hz, 1, OH), 4.56 (d, J=2.7 Hz, 1, OH), 4.3-3.9 (m, 3, 2 OCH and NCH), 2.8-2.65 (m, 1, NCH), 2.1-1.4 (m, 6, 3 CH2), 0.75-0.45 (m, 4, 2 CH2 of cyclopropyl).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:14]=[CH:15][CH:16]=1)[O:6][CH:7]1[CH2:10][N:9]([C:11](Cl)=[O:12])[CH2:8]1.[CH3:17][NH2:18]>O1CCCC1.O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:14]=[CH:15][CH:16]=1)[O:6][CH:7]1[CH2:10][N:9]([C:11]([NH:18][CH3:17])=[O:12])[CH2:8]1
Reactant: COc1cccc(OC2CN(C(=O)Cl)C2)c1
Reactant: CN
Solvent: O
Solvent: C1CCOC1
Product: CNC(=O)N1CC(Oc2cccc(OC)c2)C1
Reaction time: 16 h
Yield: 20.7 %

Procedure:
A solution of 4.8 g (0.02 mole) of 3-(3-methoxyphenoxy)-1-azetidinecarbonyl chloride in 20 ml of tetrahydrofuran was treated with 4.7 g (0.06 mole) of 40% aqueous monomethylamine and stirred for 16 hr. The reaction mixture was diluted with 200 ml of water and the oil which separated was extracted into methylene chloride (2×50 ml). The extracts were dried by passing through Whatman phase separating paper and concentrated in vacuo (3.85 g). The residue was purified by chromatography on two 4 mm (silica gel) chromatotron plates by eluting with an ethyl acetate/methylene chloride gradient to give 0.98 g (21%) of tan solid. Recrystallization from benzene with a trace of ligroin yielded 600 mg of tan crystalline powder, m.p. 109°-111° C.
Reaction SMILES: [CH2:1]([C:17](Cl)=[O:18])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15]C.[NH2:20][C:21]1[C:29]2[O:28][C:27]([CH3:31])([CH3:30])[CH2:26][C:25]=2[CH:24]=[CH:23][C:22]=1[CH3:32].C(N(CC)CC)C.C(=O)([O-])O.[Na+]>ClCCl>[CH3:30][C:27]1([CH3:31])[CH2:26][C:25]2[CH:24]=[CH:23][C:22]([CH3:32])=[C:21]([NH:20][C:17](=[O:18])[CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])[C:29]=2[O:28]1
Reactant: Cc1ccc2c(c1N)OC(C)(C)C2
Reactant: CCCCCCCCCCCCCCCCC(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCCCCCCCCCCCCCC(=O)Nc1c(C)ccc2c1OC(C)(C)C2
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A 171 mg amount of hexadecanecarboxylic acid chloride was added to a solution of 100 mg of 7-amino-2,2,6-trimethyl-2,3-dihydrobenzofuran and 63 mg of triethylamine in 2 ml of dichloromethane, and the mixture was stirred at room temperature for one hour. A 10 ml amount of a saturated sodium hydrogencarbonate solution was added thereto, and the mixture was extracted twice with 20 ml of ethyl acetate.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=[N:11][O:12][CH2:13][CH2:14][OH:15])[CH3:10])=[CH:5][N:4]=1.O[C:17]1[CH:49]=[CH:48][C:20]([CH2:21][CH:22]2[S:26][C:25](=[O:27])[N:24]([C:28]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[C:23]2=[O:47])=[CH:19][CH:18]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=[N:11][O:12][CH2:13][CH2:14][O:15][C:17]2[CH:49]=[CH:48][C:20]([CH2:21][CH:22]3[S:26][C:25](=[O:27])[N:24]([C:28]([C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=4)([C:35]4[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=4)[C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[C:23]3=[O:47])=[CH:19][CH:18]=2)[CH3:10])=[CH:5][N:4]=1
Reactant: COc1ccc(C(C)=NOCCO)cn1
Reactant: O=C1SC(Cc2ccc(O)cc2)C(=O)N1C(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: COc1ccc(C(C)=NOCCOc2ccc(CC3SC(=O)N(C(c4ccccc4)(c4ccccc4)c4ccccc4)C3=O)cc2)cn1
Yield: 78.2 %

Procedure:
Following a procedure similar to that described in Example 1(a), but using 346 mg of 2-[1-(2-methoxy-5-pyridyl)ethylideneaminooxy]-ethanol (prepared as described in Preparation 31), 766 mg of 5-(4-hydroxybenzyl)-3-tritylthiazolidine-2,4-dione, 475 mg of triphenylphosphine and 301 mg of diethyl azodicarboxylate, 846 mg of the title compound were obtained as a foam-like solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][CH:12]([CH2:27][O:28]S(C)(=O)=O)[C:13]([NH:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]([O:25][CH3:26])=[O:24])=[O:14])(=[O:10])=[O:9])=[CH:4][CH:3]=1.O[C:34]1[CH:35]=[N:36][CH:37]=[CH:38][CH:39]=1>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][CH:12]([CH2:27][O:28][C:34]2[CH:35]=[N:36][CH:37]=[CH:38][CH:39]=2)[C:13]([NH:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]([O:25][CH3:26])=[O:24])=[O:14])(=[O:10])=[O:9])=[CH:4][CH:3]=1
Reactant: COC(=O)CCCCCCCNC(=O)C(COS(C)(=O)=O)NS(=O)(=O)c1ccc(Cl)cc1
Reactant: Oc1cccnc1
Product: COC(=O)CCCCCCCNC(=O)C(COc1cccnc1)NS(=O)(=O)c1ccc(Cl)cc1

Procedure:
The procedure described in Example 105 was repeated, except that (RS)-2-(4-chlorobenzenesulfonylamino)-3-methanesulfonyloxy-N-(7-methoxycarbonylheptyl)propanamide (69.0 mg) was reacted with 3-hydroxypyridine to obtain (RS)-2-(4-chlorobenzenesulfonylamino)-N-(7-methoxycarbonylheptyl)-3-(pyridin-3-yloxy)propanamide (36.7 mg).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]2[O:13][CH2:12][CH2:11][CH2:10][N:9]([C:14](=[O:21])[CH2:15][N:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[C:8]=2[CH:22]=1)([O-])=O>[Pd].O1CCCC1.C(O)C>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]2[O:13][CH2:12][CH2:11][CH2:10][N:9]([C:14](=[O:21])[CH2:15][N:16]3[CH2:17][CH2:18][CH2:19][CH2:20]3)[C:8]=2[CH:22]=1
Reactant: O=C(CN1CCCC1)N1CCCOc2ccc([N+](=O)[O-])cc21
Agent: [Pd]
Solvent: CCO
Solvent: C1CCOC1
Product: Nc1ccc2c(c1)N(C(=O)CN1CCCC1)CCCO2

Procedure:
1-(2-Nitro-7,8-dihydro-6H-5-oxa-9-aza-benzocyclohepten-9-yl)-2-pyrrolidin-1-yl-ethanone (0.402 g, 1.32 mmol) and 10% Palladium on Carbon (50% Wet) (0.1 g) in Tetrahydrofuran (10 mL; EMD) and Ethanol (10 mL) was shaken under an atmosphere of Hydrogen (25 psi) overnight. Filtration and washing with ethanol (50 mL) followed by conc. afforded 1-(2-Amino-7,8-dihydro-6H-5-oxa-9-aza-benzocyclohepten-9-yl)-2-pyrrolidin-1-yl-ethanone as an oil in quantitative yield. 1H-NMR (CDCl3): 6.93 (d, 1H, J=8 Hz), 6.58 (d, 1H, J=8 Hz), 6.57 (s, 1H), 4.77 (m, 1H), 4.36 (m, 1H), 4.01 (br s, 2H), 3.76 (m, 1H), 3.56 (m, 1H), 3.10 (m, 1H), 2.94 (m, 4H), 2.71 (m, 1H), 2.25 (m, 1H), 1.91 (m, 4H), 1.71 (m, 1H), 0.86 (m, 1H).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([CH3:9])=[C:7]([CH3:10])[C:6]([O:11][CH3:12])=[C:5]([CH3:13])[C:4]=1[Mg]Br.[O:16]1[C@:20]([CH3:37])([CH2:21][CH2:22][CH2:23][C@H:24]([CH3:36])[CH2:25][CH2:26][CH2:27][C@H:28]([CH3:35])[CH2:29][CH2:30][CH2:31][CH:32]([CH3:34])[CH3:33])[C@@H:17]1[CH:18]=[O:19].O>O1CCCC1>[CH3:1][O:2][C:3]1[C:8]([CH3:9])=[C:7]([CH3:10])[C:6]([O:11][CH3:12])=[C:5]([CH3:13])[C:4]=1[CH:18]([OH:19])[C@H:17]1[O:16][C@:20]1([CH3:37])[CH2:21][CH2:22][CH2:23][C@H:24]([CH3:36])[CH2:25][CH2:26][CH2:27][C@H:28]([CH3:35])[CH2:29][CH2:30][CH2:31][CH:32]([CH3:33])[CH3:34]
Reactant: CC(C)CCC[C@@H](C)CCC[C@@H](C)CCC[C@@]1(C)O[C@H]1C=O
Reactant: COc1c(C)c(C)c(OC)c([Mg]Br)c1C
Solvent: C1CCOC1
Solvent: O
Product: COc1c(C)c(C)c(OC)c(C(O)[C@H]2O[C@]2(C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)c1C
Temperature: 25 °C
Reaction time: 3 h
Yield: 94.1 %

Procedure:
1 mmol of 2,5-dimethoxy-3,4,6-trimethylphenylmagnesium bromide in 2 ml of tetrahydrofuran was added dropwise at 0° C. while stirring to a solution of 300 mg (0.97 mmol) of (2R,3R,7R,11R)-2,3-epoxy-3,7,11,15-tetramethylhexadecanal in 10 ml of tetrahydrofuran. After completion of the dropwise addition, the mixture was stirred at room temperature for a further 3 hours. 20 ml of water weree then added and the mixture was extracted three times with 20 ml of ether each time. The combined organic phases were dried over sodium sulphate and concentrated on a rotary evaporator. The thus-obtained crude produce (502 mg) was chromatographed on silica gel with toluene/ethyl acetate (2:1 parts by volume) and there were obtained 448 mg(94%) of (1RS,2R,3R,7R, 11R)-1-(2',5'-dimethoxy-3',4',6'-trimethylphenyl)-2,3-epoxy-3,7,11,15-tetramethylhexadecanol, [α]D20 =-0.66° (c=1.51% in chloroform).
Reaction SMILES: [C:1]1([C:7]2[N:11]([S:12]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([OH:21])[CH:16]=3)(=[O:14])=[O:13])[CH:10]=[C:9]([CH2:22][N:23]([CH3:31])[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:39][C:40]([NH:42][CH:43]1[CH2:45][CH2:44]1)=[O:41]>CN(C)C=O>[C:1]1([C:7]2[N:11]([S:12]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH2:39][C:40]([NH:42][CH:43]4[CH2:45][CH2:44]4)=[O:41])[CH:16]=3)(=[O:13])=[O:14])[CH:10]=[C:9]([CH2:22][N:23]([CH3:31])[C:24](=[O:30])[O:25][C:26]([CH3:27])([CH3:28])[CH3:29])[CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1
Reactant: O=C(CBr)NC1CC1
Reactant: CN(Cc1cc(C2=CCCCC2)n(S(=O)(=O)c2cccc(O)c2)c1)C(=O)OC(C)(C)C
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CN(Cc1cc(C2=CCCCC2)n(S(=O)(=O)c2cccc(OCC(=O)NC3CC3)c2)c1)C(=O)OC(C)(C)C
Reaction time: 16 h

Procedure:
tert-Butyl ((5-(cyclo ex-1-en-1-yl)-1-((3-hydroxyphenyl)sulfonyl)-1H-pyrrol-3-yl)methyl)(methyl)carbamate 7d (100 mg, 0.22 mmol) was dissolved in 20 mL of N,N-dimethylformamide, followed by addition of cesium carbonate (146 mg, 0.45 mmol) and 2-bromo-N-cyclopropyl-acetamide (79 mg, 0.45 mmol, prepared by a known method disclosed in “Journal of Medicinal Chemistry, 1987, 30(1), 20-24”), and then the reaction solution was stirred for 16 h. The reaction solution was concentrated under reduced pressure, and the resulting residue was purified by thin layer chromatography with elution system C to obtain the title product tert-butyl ((5-(cyclohex-1-en-1-yl)-1-((3-(2-(cyclopropylamino)-2-oxoethoxy)phenyl)sulfonyl)-1H-pyrrol-3-yl)methyl)(methyl)carbamate 7e (117 mg, a light yellow oily product) in 98% yield.
Reaction SMILES: [C:1]([C:3](=[C:15]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:4]([O:6][CH2:7][CH:8]([CH2:13][CH3:14])[CH2:9][CH2:10][CH2:11][CH3:12])=[O:5])#[N:2].O.[3H][3H]>O1CCCC1.[Pd]>[C:1]([CH:3]([CH:15]([C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:4]([O:6][CH2:7][CH:8]([CH2:13][CH3:14])[CH2:9][CH2:10][CH2:11][CH3:12])=[O:5])#[N:2]
Reactant: CCCCC(CC)COC(=O)C(C#N)=C(c1ccccc1)c1ccccc1
Agent: [Pd]
Agent: [3H][3H]
Solvent: C1CCOC1
Solvent: O
Product: CCCCC(CC)COC(=O)C(C#N)C(c1ccccc1)c1ccccc1

Procedure:
2-Ethylhexyl 2-cyano-3,3-diphenylacrylate (Eusolex® OCR; Merck) is dissolved in tetrahydrofuran (THF), and 5% Pd/C (56% water; Merck: Art. No. 275175) is added. The hydrogenation is subsequently carried out with hydrogen 3.0 at room temperature and atmospheric pressure. The catalyst is separated off by filtration. The filtrate is freed from solvent in vacuo, and the residue is washed. The organic phase is dried over sodium sulfate, and the solvent is removed in vacuo. The purification is carried out by filtration through silica gel, giving analytically pure product.