Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][S:2]([O:5][C:6]1[CH:11]=[CH:10][C:9]([S:12]([CH2:15][S:16]([C:19]2[CH:24]=[CH:23][C:22]([O:25][S:26]([CH3:29])(=[O:28])=[O:27])=[CH:21][CH:20]=2)(=[O:18])=[O:17])(=[O:14])=[O:13])=[CH:8][CH:7]=1)(=[O:4])=[O:3].C1(C)C=CC(S([N:39]=[N+:40]=[N-])(=O)=O)=CC=1.C1CCN2C(=NCCC2)CC1.Cl>ClCCl>[CH3:29][S:26]([O:25][C:22]1[CH:23]=[CH:24][C:19]([S:16]([C:15]([S:12]([C:9]2[CH:8]=[CH:7][C:6]([O:5][S:2]([CH3:1])(=[O:4])=[O:3])=[CH:11][CH:10]=2)(=[O:14])=[O:13])=[N+:39]=[N-:40])(=[O:17])=[O:18])=[CH:20][CH:21]=1)(=[O:28])=[O:27]
Reactant: Cc1ccc(S(=O)(=O)N=[N+]=[N-])cc1
Reactant: CS(=O)(=O)Oc1ccc(S(=O)(=O)CS(=O)(=O)c2ccc(OS(C)(=O)=O)cc2)cc1
Agent: Cl
Solvent: ClCCl
Solvent: C1CCC2=NCCCN2CC1
Product: CS(=O)(=O)Oc1ccc(S(=O)(=O)C(=[N+]=[N-])S(=O)(=O)c2ccc(OS(C)(=O)=O)cc2)cc1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 29 %

Procedure:
The bis(4-methylsulfonyloxyphenylsulfonyl)methane in Synthesis Example 3, 9.7 g (0.02 mol), was dispersed in 97 g of dichloromethane. To the dispersion was added 4.6 g (0.03 mol) of p-toluenesulfonylazide which had been separately prepared. With stirring at room temperature, 5.9 g (0.03 mol) of 1,8-diazabicyclo[5.4.0]-7-undecene (DBU) was added to the dispersion, and after 5 minutes, 150 g of a 0.2N aqueous hydrochloric acid was added to stop reaction. The organic layer was separated and washed with 100 g of water. The organic layer was concentrated and 14 g of the residue was purified by silica gel column chromatography using dichloromethane as an elute. The thus obtained oily product was combined with 40 g of hexane for crystallization, followed by filtration and vacuum drying. There was obtained 3.0 g (yield 29%) of fine yellow crystals.
Reaction SMILES: S(Cl)(Cl)=O.[CH3:5][O:6][C:7]1[CH:8]=[C:9]([CH2:15][C@@H:16]([C:18]([OH:20])=[O:19])[NH2:17])[CH:10]=[CH:11][C:12]=1[O:13][CH3:14].[CH3:21]O>C(Cl)Cl>[CH3:21][O:19][C:18](=[O:20])[C@@H:16]([NH2:17])[CH2:15][C:9]1[CH:10]=[CH:11][C:12]([O:13][CH3:14])=[C:7]([O:6][CH3:5])[CH:8]=1
Reactant: COc1ccc(C[C@H](N)C(=O)O)cc1OC
Reactant: CO
Solvent: O=S(Cl)Cl
Solvent: ClCCl
Product: COC(=O)[C@@H](N)Cc1ccc(OC)c(OC)c1
Temperature: 25 °C
Reaction time: 72 h
Yield: 93 %

Procedure:
Thionyl chloride (3.2 g, 2.0 mL, 26.8 mmol) was added dropwise to a suspension 3-(3,4-dimethoxyphenyl)-L-alanine 1 (2.0 g, 8.9 mmol) in anhydrous MeOH (50 mL) at 0° C. under a nitrogen blanket. The mixture was slowly warmed to room temperature, then stirred for 72 hours. The solvent was removed under reduced pressure to provide a solid. The crude product was taken up in CH2Cl2, then washed with saturated NaHCO3 and saturated NaCl. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated to yield a light brown oil (1.97 g, 93%).
Reaction SMILES: [H-].[Na+].[NH:3]1[CH2:8][CH2:7][CH2:6][CH2:5][C:4]1=[O:9].Br[CH:11]1[CH2:15][CH2:14][O:13][C:12]1=[O:16]>C1C=CC=CC=1.CN(C)C=O>[O:16]=[C:12]1[CH:11]([N:3]2[CH2:8][CH2:7][CH2:6][CH2:5][C:4]2=[O:9])[CH2:15][CH2:14][O:13]1
Reactant: O=C1OCCC1Br
Reactant: O=C1CCCCN1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: c1ccccc1
Product: O=C1OCCC1N1CCCCC1=O
Temperature: 60 °C
Reaction time: 5 h
Yield: 107 %

Procedure:
1.25 g (0.05 mol) of sodium hydride (2.5 g of a 50% commercial suspension in paraffin, previously washed twice with benzene) are suspended in 50 ml of anhydrous N,N-dimethylformamide. A solution of 4.95 g (0.05 mol) of 2-piperidinone in 20 ml of N,N-dimethylformamide is added dropwise to the suspension. The mixture is then heated to 60° C. until no more gas is evolved, whereafter it is cooled. A solution of 8.25 g (0.05 mol) of 3-bromodihydro-2(3H)-furanone in 20 ml of anhydrous N,N-dimethylformamide is added dropwise while keeping the temperature at 5° to 10° C. The mixture is then stirred at 60° C. for 5 hours. N,N-Dimethylformamide is evaporated off under reduced pressure. The residue is taken up in chloroform and the insoluble matter filtered off on Norit. The filtrate is again evaporated and 9.8 g of a heavy syrup are obtained. Mass spectrum: M+. at 183 m/e.
Reaction SMILES: C(=C(O)[C@@H](O)[C@@H](O)[C@@H](O)C=[O:9])(C)C.N1C=CC=CC=1.[C:20](Cl)([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>>[C:21]1([C:20]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[OH:9])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: CC(C)=C(O)[C@@H](O)[C@@H](O)[C@@H](O)C=O
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: c1ccncc1
Product: OC(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
To a solution of 3.0 g (15.8 mmoles) of isopropylidene-ribose in 50 ml of absolute pyridine 4.4 g (15.8 mmoles) of trityl chloride are added and the mixture is stirred in a closed flask for 3 days at room temperature. The yellow-brown solution produced is poured into approximately 1 l of ice water. The brown sirup which separates is decanted off and is thoroughly mixed several times with water. Following this this sirup is dissolved in 50 ml of CHCl3 and washed twice with KHSO4 -solution and 3 times with water. After drying over sodium sulfate the solvent is abstracted. A light brown sirup containing crystals remains. By crystallisation from methanol it is possible to obtain 1 g of triphenylcarbinol.
Reaction SMILES: [CH2:1]([O:3][CH:4]([O:6][CH2:7][C:8]#[CH:9])[CH3:5])[CH3:2].C([Li])CCC.[F:15][C:16]1[CH:23]=[CH:22][C:19]([CH:20]=[O:21])=[CH:18][CH:17]=1.[Cl-].[NH4+]>O1CCCC1>[CH2:1]([O:3][CH:4]([O:6][CH2:7][C:8]#[C:9][CH:20]([C:19]1[CH:22]=[CH:23][C:16]([F:15])=[CH:17][CH:18]=1)[OH:21])[CH3:5])[CH3:2]
Reactant: O=Cc1ccc(F)cc1
Reactant: C#CCOC(C)OCC
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: C1CCOC1
Product: CCOC(C)OCC#CC(O)c1ccc(F)cc1
Reaction time: 0.5 h

Procedure:
A solution of 8 g (62.4 mmol) of 1 (1-ethoxyethoxy)-2-propyne in 134 ml of tetrahydrofuran was treated at -78° under argon with 39 ml of n-butyllithium (1.6M in hexane). The mixture was stirred at -40° for 30 minutes and then a solution of 6.6 ml (62 mmol) of 4-fluorobenzaldehyde in 54 ml of tetrahydrofuran was added within 10 minutes. The reaction mixture was warmed to 0° , stirred at 0° for a further 1 hour and then treated with 100 ml of saturated ammonium chloride solution. The aqueous phase was extracted twice with ethyl acetate. The combined organic phases were washed in succession with saturated sodium chloride solution and with water, dried over magnesium sulphate and concentrated. The residue was purified by chromatography on 600 g of silica gel (elution agent ether/hexane 1:1). There was obtained 4-(1-ethoxyethoxy)-1-(4-fluorophenyl)-2-butyn- 1-ol as an oil.
Reaction SMILES: [C:1]1([C@H:7]2[C@@H:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[N:10]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:9](SC)=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F:27][C:28]1[CH:35]=[CH:34][C:31]([CH2:32][NH2:33])=[CH:30][CH:29]=1>CO>[C:21]([O:20][C:18]([N:10]1[C@H:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C@H:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[N:8]=[C:9]1[NH:33][CH2:32][C:31]1[CH:34]=[CH:35][C:28]([F:27])=[CH:29][CH:30]=1)=[O:19])([CH3:24])([CH3:23])[CH3:22]
Reactant: CSC1=N[C@@H](c2ccccc2)[C@@H](c2ccccc2)N1C(=O)OC(C)(C)C
Reactant: NCc1ccc(F)cc1
Solvent: CO
Product: CC(C)(C)OC(=O)N1C(NCc2ccc(F)cc2)=N[C@@H](c2ccccc2)[C@H]1c1ccccc1
Temperature: 100 °C
Yield: 41.6 %

Procedure:
A mixture of intermediate 59 (1.0 g, 0.0027 mol), 4-fluorobenzylamine (0.372 mL, 0.00321 mol) and MeOH (0.4 mL) is heated at 100° C. for 2 days. The reaction mixture is cooled to RT, and partitioned between dichloromethane and water. The organic solution is separated, dried (MgSO4), and concentrated in vacuo. The residue is purified by chromatography on silica gel; gradient elution with heptane:EtOAc (80:20-40:60) gives 0.50 g of the product 85. 1H NMR (CDCl3) δ 7.60-7.35 (m, 3H), 7.15-6.90 (m, 10H), 6.85-6.70 (m, 2H), 5.50-5.30 (m, 2H), 5.75-5.55 (m, 2H), 1.12 (s, 9H); MS: m/z 446 (M++1).
Reaction SMILES: I[CH:2]1[CH2:8][CH2:7][C:6]2[CH:9]=[C:10]([F:13])[CH:11]=[CH:12][C:5]=2[NH:4][C:3]1=[O:14].[N-:15]=[N+:16]=[N-:17].CN(C)C(=[NH2+])N(C)C.O>C(Cl)Cl>[N:15]([CH:2]1[CH2:8][CH2:7][C:6]2[CH:9]=[C:10]([F:13])[CH:11]=[CH:12][C:5]=2[NH:4][C:3]1=[O:14])=[N+:16]=[N-:17]
Reactant: [N-]=[N+]=[N-]
Reactant: O=C1Nc2ccc(F)cc2CCC1I
Agent: CN(C)C(=[NH2+])N(C)C
Solvent: O
Solvent: ClCCl
Product: [N-]=[N+]=NC1CCc2cc(F)ccc2NC1=O
Temperature: 25 °C
Reaction time: 16 h
Yield: 90.9 %

Procedure:
101 mg (0.33 mmol) of 3-iodo-7-fluoro-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (Step B) was dissolved in 8.3 mL of methylene chloride and 105 mg (0.66 mmol, 2 eq) of tetramethylguanidinium azide was added. The mixture was stirred at room temperature for 16 hours then water was added and the layers allowed to separate. The organic layer was removed, washed with water and brine, then dried over magnesium sulfate, filtered and solvents removed under vacuum to afford 66 mg (0.30 mmol, 90%) of the product. 1H NMR (200MHz, CDCl3): 2.28 (m,1H), 2.45 (m,1H), 2.73 (m,1H), 2.93 (m,1H), 3.86 (dd:8,11 Hz;1H), 7.0 (m,3H), 8.15 (br s,1H). FAB-MS: calculated for C10H9FN4O 220: found 221 (M+H,100%).
Reaction SMILES: [Cl:1][C:2]1[C:11]([O:12][CH3:13])=[C:10]2[C:5]([CH:6]=[C:7]([C:14]([OH:16])=O)[N:8]=[CH:9]2)=[CH:4][CH:3]=1.[NH:17]1[CH:21]=[CH:20][N:19]=[C:18]1[NH:22][C:23]([C:25]1[C:33]2[NH:32][C:31]([NH2:34])=[N:30][C:29]=2[CH:28]=[CH:27][CH:26]=1)=[O:24].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[NH:19]1[CH:20]=[CH:21][N:17]=[C:18]1[NH:22][C:23]([C:25]1[C:33]2[N:32]=[C:31]([NH:34][C:14]([C:7]3[N:8]=[CH:9][C:10]4[C:5]([CH:6]=3)=[CH:4][CH:3]=[C:2]([Cl:1])[C:11]=4[O:12][CH3:13])=[O:16])[NH:30][C:29]=2[CH:28]=[CH:27][CH:26]=1)=[O:24]
Reactant: Nc1nc2cccc(C(=O)Nc3ncc[nH]3)c2[nH]1
Reactant: COc1c(Cl)ccc2cc(C(=O)O)ncc12
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COc1c(Cl)ccc2cc(C(=O)Nc3nc4c(C(=O)Nc5ncc[nH]5)cccc4[nH]3)ncc12
Yield: 13 %

Procedure:
10 mg (13%) of 7-chloro-8-methoxy-isoquinoline-3-carboxylic acid [4-(1H-imidazol-2-ylcarbamoyl)-1H-benzoimidazol-2-yl]-amide was synthesized according to the general procedure A using 7-chloro-8-methoxy-isoquinoline-3-carboxylic acid (from previous step), 36.3 mg (0.15 mmol) of intermediate B (2-amino-3H-benzoimidazole-4-carboxylic acid (1H-imidazol-2-yl)-amide), 69 mg (0.18 mmol) of HBTU, 0.106 mL (0.6 mmol) of DIEA in 2 mL of DMF stirring at 80° C. for 2 h. LCMS: 462 (M+1)+.
Reaction SMILES: [C:1]1([S:7]([CH2:10][C:11]#[N:12])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH:13][C:14]1[CH:21]=[CH:20][C:17]([CH:18]=O)=[CH:16][CH:15]=1>CN(C=O)C.C1(C)C=CC=CC=1>[C:1]1([S:7]([C:10](=[CH:18][C:17]2[CH:20]=[CH:21][C:14]([OH:13])=[CH:15][CH:16]=2)[C:11]#[N:12])(=[O:8])=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: N#CCS(=O)(=O)c1ccccc1
Reactant: O=Cc1ccc(O)cc1
Solvent: CN(C)C=O
Solvent: Cc1ccccc1
Product: N#CC(=Cc1ccc(O)cc1)S(=O)(=O)c1ccccc1
Yield: 66 %

Procedure:
Phenylsulphonyl acetonitrile (2.0 g, 11.04 mmol) was mixed with 4-hydroxybenzaldehyde (1.35 g, 11.04 mmol) in DMF (10 mL) and toluene (20 mL). The mixture was refluxed for 3 hours and subsequently evaporated to dryness in vacuo. The residue was treated with diethyl ether and toluene. The solid formed was filtered to afford 2.08 g (66%) of 2-benzenesulfonyl-3-(4-hydroxyphenyl)acrylonitrile.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:14])[C:4]([C:7]1[CH:12]=[CH:11][C:10](Br)=[CH:9][CH:8]=1)([CH3:6])[CH3:5].[I-:15].[Na+].CNCCNC>O1CCOCC1.CCOC(C)=O.[Cu]I>[CH3:1][O:2][C:3](=[O:14])[C:4]([C:7]1[CH:12]=[CH:11][C:10]([I:15])=[CH:9][CH:8]=1)([CH3:6])[CH3:5]
Reactant: [I-]
Reactant: COC(=O)C(C)(C)c1ccc(Br)cc1
Agent: [Cu]I
Agent: CNCCNC
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: COC(=O)C(C)(C)c1ccc(I)cc1
Temperature: 110 °C
Reaction time: 12 h

Procedure:
To 0.45 g (1.7 mmol) 2-(4-bromo-phenyl)-2-methyl-propionic acid methyl ester (WO2008/002671) in 1.5 mL 1,4-dioxane are added 34 mg (0.18 mmol) copper(I) iodide, 0.53 g (3.5 mmol) sodium iodide and 0.04 mL (0.35 mmol) N,N′-dimethylethylendiamine under inert gas atmosphere. The mixture is stirred at 110° C. for 12 h. After cooling, the mixture is diluted with EtOAc and washed with 5% ammonia and water. The organic layer is dried over sodium sulphate. The solvent is evaporated to yield the desired product.
Reaction SMILES: [CH3:1][C:2]1[O:3][C:4]([C:7]2[CH:8]=[CH:9][C:10]3[O:14][CH:13]=[C:12]([C:15]4[CH:20]=[CH:19][C:18]([O:21][CH2:22][CH2:23][S:24][CH3:25])=[CH:17][CH:16]=4)[C:11]=3[CH:26]=2)=[N:5][N:6]=1.CN(C)C(=[O:31])C.ClC1C=CC=C(C(OO)=O)C=1.S([O-])([O-])(=O)=S.[Na+].[Na+]>C(#N)C>[CH3:1][C:2]1[O:3][C:4]([C:7]2[CH:8]=[CH:9][C:10]3[O:14][CH:13]=[C:12]([C:15]4[CH:16]=[CH:17][C:18]([O:21][CH2:22][CH2:23][S:24]([CH3:25])=[O:31])=[CH:19][CH:20]=4)[C:11]=3[CH:26]=2)=[N:5][N:6]=1
Reactant: CC(=O)N(C)C
Reactant: CSCCOc1ccc(-c2coc3ccc(-c4nnc(C)o4)cc23)cc1
Agent: O=C(OO)c1cccc(Cl)c1
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: CC#N
Product: Cc1nnc(-c2ccc3occ(-c4ccc(OCCS(C)=O)cc4)c3c2)o1
Reaction time: 2 h
Yield: 27 %

Procedure:
To a mixture of 2-methyl-5-[3-[4-[2-(methylthio)ethoxy]phenyl]-1-benzofuran-5-yl]-1,3,4-oxadiazole (186 mg, 0.51 mmol), N,N-dimethylacetamide (2.5 mL) and acetonitrile (2.5 mL) was added m-chloroperbenzoic acid (122 mg, 0.51 mmol) at room temperature, and the resulting mixture was stirred for 2 hr. A saturated aqueous sodium thiosulfate solution was added to the reaction mixture, and the mixture was stirred for 30 min and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=10/1-0/1) and recrystallized from hexane/ethyl acetate to give the title compound (53.0 mg, yield 27%) as colorless crystals.
Reaction SMILES: [C:1]([C:5]1[C:6]([O:31][CH3:32])=[C:7]([NH:19][C:20](=[O:30])[C:21]2[CH:26]=[CH:25][C:24]([N+:27]([O-])=O)=[CH:23][CH:22]=2)[CH:8]=[C:9]([C:11]2[C:12]([O:17][CH3:18])=[N:13][CH:14]=[CH:15][CH:16]=2)[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].I[CH3:36]>C1COCC1>[NH2:27][C:24]1[CH:25]=[CH:26][C:21]([C:20]([N:19]([C:7]2[CH:8]=[C:9]([C:11]3[C:12]([O:17][CH3:18])=[N:13][CH:14]=[CH:15][CH:16]=3)[CH:10]=[C:5]([C:1]([CH3:2])([CH3:4])[CH3:3])[C:6]=2[O:31][CH3:32])[CH3:36])=[O:30])=[CH:22][CH:23]=1
Reactant: COc1ncccc1-c1cc(NC(=O)c2ccc([N+](=O)[O-])cc2)c(OC)c(C(C)(C)C)c1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1ncccc1-c1cc(N(C)C(=O)c2ccc(N)cc2)c(OC)c(C(C)(C)C)c1
Temperature: 25 °C
Yield: 99.7 %

Procedure:
steps 1 & 2—To a solution of 102 (0.24 g, 0.55 mmol) in THF (5 mL) was added sodium hydride (0.033 g, 0.83 mmol). The mixture was stirred at RT until the evolution of gas subsided, and iodomethane (0.069 mL, 1.1 mmol) was added. The resulting mixture was stirred for 3 h and then quenched with water and the mixture extracted with EtOAc. The solvent was evaporated, and the crude residue was dissolved in EtOAc/hexane (2:1, 10 mL) to which was added 10% Pd/C (0.025 g). A stream of hydrogen gas was bubbled through the solution for 20 min, and the resulting solution was stirred at RT for 3 h. The solution was filtered, the filtrate concentrated, and the crude residue purified by SiO2 chromatography eluting with EtOAc/hexane to afford 0.23 g (97%) of 4-amino-N-[3-tert-butyl-2-methoxy-5-(2-methoxypyridin-3-yl)phenyl]-N-methylbenzamide (140) as a white foam.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]=1[CH2:13][O:14][NH:15][C:16](=[O:18])[CH3:17].[C:19](Cl)(=O)[CH3:20].C(Cl)(=O)/C=C/C>>[CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]=1[CH2:13][O:14][NH:15][C:16](=[O:18])/[CH:17]=[CH:19]/[CH3:20]
Reactant: CC(=O)Cl
Reactant: COc1ccc2ccccc2c1CONC(C)=O
Agent: C/C=C/C(=O)Cl
Product: C/C=C/C(=O)NOCc1c(OC)ccc2ccccc12

Procedure:
By carrying out the procedure in the same manner as for the synthesis of the compound of Example 7, but replacing, in the acylation step, acetic acid chloride with crotonic acid chloride, the title compound is obtained.
Reaction SMILES: [Mg].[CH2:2](I)[CH3:3].[CH:5]([C:8]1[C:16]([C:17](=[O:21])[CH:18]([CH3:20])[CH3:19])=[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][N:10]2[N:9]=1)([CH3:7])[CH3:6].[Cl-].[NH4+]>CCOCC.C1C=CC=CC=1>[CH:5]([C:8]1[C:16]([C:17]([OH:21])([CH2:2][CH3:3])[CH:18]([CH3:20])[CH3:19])=[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][N:10]2[N:9]=1)([CH3:7])[CH3:6]
Reactant: CC(C)C(=O)c1c(C(C)C)nn2ccccc12
Reactant: CCI
Agent: [Cl-]
Agent: [Mg]
Agent: [NH4+]
Solvent: c1ccccc1
Solvent: CCOCC
Product: CCC(O)(c1c(C(C)C)nn2ccccc12)C(C)C

Procedure:
To a suspension of 1.32 g of magnesium in 10 ml of dry ether was gradually added a solution of 17 g of ethyl iodide in 15 ml of dry ether with stirring. After the addition was completed, the stirring was continued for an hour at room temperature. To the mixture was gradually added a solution of 2.5 g of 2-isopropyl-3-isobutyrylpyrazolo[1,5-a]pyridine in 10 ml of dry benzene under stirring. The mixture was stirred for an hour at room temperature, treated with 150 ml of aqueous 20% ammonium chloride solution under ice cooling, and extracted with ether. The ether layer was washed with saturated brine, dried over anhydrous sodium sulfate and cencentrated to dryness. The residue was recrystallized from hexane to give 1.5 g (54%) of the desired derivative as pale gray prisms, mp 96°-98° C.
Reaction SMILES: CC(OC(/N=N/C(OC(C)C)=O)=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:34][C:35]1[CH:42]=[C:41]([OH:43])[CH:40]=[CH:39][C:36]=1[C:37]#[N:38].[S:44]1[C:48]([CH2:49]O)=[CH:47][N:46]=[CH:45]1>O1CCCC1>[F:34][C:35]1[CH:42]=[C:41]([O:43][CH2:49][C:48]2[S:44][CH:45]=[N:46][CH:47]=2)[CH:40]=[CH:39][C:36]=1[C:37]#[N:38]
Reactant: N#Cc1ccc(O)cc1F
Reactant: OCc1cncs1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: N#Cc1ccc(OCc2cncs2)cc1F
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
Diisopropylazodicarboxylate (4.0 g) was dissolved in a little anhydrous tetrahydrofuran (about 10 ml) and added dropwise to a stirred solution of triphenylphosphine (5.2 g) in anhydrous tetrahydrofuran (150 ml) at 0° C. under nitrogen. After stirring at 0° C. for 15 minutes, during which time a white precipitate formed, a mixture of 2-fluoro-4-hydroxybenzonitrile (S. M. Kelly, Helv.Chim.Acta. 1984, Volume 67, P.1572-1579) (2.0 g) and thiazole-5-methanol (2.3 g) in anhydrous tetrahydrofuran (20 ml) was added dropwise whilst maintaining the temperature at or below 5° C. The reaction mixture was stirred in the cooling bath for a further 2 hours then allowed to warm slowly to room temperature. After standing at room temperature overnight the reaction mixture was partitioned between ethyl acetate (200 ml) and saturated aqueous ammonium chloride solution (200 ml). The layers were separated and the organic phase washed with water (100 ml), dried over magnesium sulphate and evaporated. The residue was purified by flash chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane (1:1, v/v). Fractions homogenous in the required product were combined and evaporated affording the title compound as a pale yellow solid (2.0 g).
Reaction SMILES: [NH:1]1[C:10]2[CH2:9][CH2:8][CH2:7][C:6](=[O:11])[C:5]=2[CH:4]=[CH:3][C:2]1=[O:12].[C:13](=O)([O-])[O-].[K+].[K+].CI>CN(C)C=O>[CH3:13][N:1]1[C:10]2[CH2:9][CH2:8][CH2:7][C:6](=[O:11])[C:5]=2[CH:4]=[CH:3][C:2]1=[O:12]
Reactant: O=C([O-])[O-]
Reactant: O=C1CCCc2[nH]c(=O)ccc21
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CI
Product: Cn1c2c(ccc1=O)C(=O)CCC2

Procedure:
3.36 g (0.0206 mol) of 7,8-dihydro-2,5(1H,6H)-quinolinedione are stirred with 5.69 g (2×0.0206 mol) of powdered anhydrous potassium carbonate and 1.92 ml (1.5×0.0206 mol) of methyl iodide in 35 ml of dimethylformamide for 16 hours at ambient temperature. The mixture is then suction filtered, the solvent is evaporated off in vacuo and the residue is recrystallised from chloroform/ethyl acetate. Melting point: 203°-205° C., Yield: 3.1 g (84.9% of theory).
Reaction SMILES: CC(C)=[O:3].OS(O)(=O)=O.O=[Cr](=O)=O.[C:14]([O:17][CH:18]([C:24]1[CH:29]=[CH:28][CH:27]=[C:26](/[CH:30]=[CH:31]/[CH:32]=[CH:33]/[CH:34]([O:43][C:44](=[O:46])[CH3:45])[CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[CH:25]=1)[CH2:19][CH2:20][CH2:21][CH:22]=[O:23])(=[O:16])[CH3:15].C(O)(C)C>CC(C)=O.CCOCC>[C:14]([O:17][CH:18]([C:24]1[CH:29]=[CH:28][CH:27]=[C:26](/[CH:30]=[CH:31]/[CH:32]=[CH:33]/[CH:34]([O:43][C:44](=[O:46])[CH3:45])[CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[CH:25]=1)[CH2:19][CH2:20][CH2:21][C:22]([OH:3])=[O:23])(=[O:16])[CH3:15]
Reactant: CCCCCCCCC(/C=C/C=C/c1cccc(C(CCCC=O)OC(C)=O)c1)OC(C)=O
Reactant: CC(C)=O
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Solvent: CC(C)O
Solvent: CCOCC
Product: CCCCCCCCC(/C=C/C=C/c1cccc(C(CCCC(=O)O)OC(C)=O)c1)OC(C)=O
Temperature: -30 °C

Procedure:
0.3 ml of Jones reagent (J. Chem. Soc. 1953., 2555) is instilled in a solution of 150 mg of the above-produced aldehyde in 11 ml of acetone with stirring at -30° C. and stirred for one hour at -30° C. Then, 0.23 ml of isopropanol is added, stirred for 15 minutes, diluted with ether, filtered, washed neutral with brine, dried on magnesium sulfate and concentrated by evaporation in a vacuum. The residue is chromatographed on silica gel. With hexane/0-50% ethyl acetate, 52 mg of (5RS)-5-acetoxy-5-{3-[(1E,3E)-(5RS)-5-acetoxy1,3-tridecadienyl]-phenyl}-pentanoic acid is obtained as colorless oil.
Reaction SMILES: [Si:1]([O:8][C@@H:9]1[CH2:13][O:12][CH2:11][C@@H:10]1CS([O-])(=O)=O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[N-:19]=[N+:20]=[N-:21].[Na+].O>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[N:19]([C@@H:10]1[CH2:11][O:12][CH2:13][C@@H:9]1[O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])=[N+:20]=[N-:21]
Reactant: CC(C)(C)[Si](C)(C)O[C@@H]1COC[C@@H]1CS(=O)(=O)[O-]
Reactant: [N-]=[N+]=[N-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [I-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)[Si](C)(C)O[C@H]1COC[C@H]1N=[N+]=[N-]
Temperature: 60 °C
Yield: 52.9 %

Procedure:
[(3S,4S)-4-(Tert-butyl(dimethyl)silyl)oxytetrahydrofuran-3-yl]methanesulfonate (3.00 g, 10.1 mmol) is dissolved in DMF (50 mL). Sodium azide (1.32 g, 20.2 mmol) is added and the reaction is heated to 60° C. for 72 h. Tetra-n-butylammonium iodide (0.400 g, 1.08 mmol) is added and the temperature is raised to 120° C. for 14 days. Water is added and the product is extracted into EtOAc. The organic layer is washed with water a second time and then dried over magnesium sulfate, filtered, and concentrated to give 2.9 g of crude product as a pale yellow oil. The crude product is purified on silica gel (120 g, 2-20% EtOAc/hexanes, observed on TLC with KMnO4 staining) to give the title compound as a colorless oil (1.3 g, 53%). GC-MS m/z 186 (M-tBu)+.
Reaction SMILES: [NH2:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5]([OH:18])=[CH:4][C:3]=1[O:19][CH3:20].[CH2:21]([C:23]([CH2:28][CH3:29])(CO)[CH2:24][OH:25])[CH3:22].[OH-].[K+]>>[NH2:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5]([OH:18])=[CH:4][C:3]=1[O:19][CH2:20][C:23]([CH2:28][CH3:29])([CH2:21][CH3:22])[CH2:24][OH:25]
Reactant: COc1cc(O)c2c(c1N)C(=O)c1ccccc1C2=O
Reactant: CCC(CC)(CO)CO
Agent: [K+]
Agent: [OH-]
Product: CCC(CC)(CO)COc1cc(O)c2c(c1N)C(=O)c1ccccc1C2=O

Procedure:
13 parts of 1-amino-2-methoxy-4-hydroxyanthraquinone, 50 parts of 2,2-diethyl-1,3-propanediol, 2.5 parts of a polyethylene oxide of average molecular weight 200 and 1.5 parts of potassium hydroxide are stirred for 2.5 hours at 160°C under nitrogen. After working up, 10 parts of 1-amino-2-(2',2'-diethyl-3'-hydroxypropanoxy)-4-hydroxyanthraquinone are obtained.