Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:3]([O:25][CH3:26])=[CH:4][C:5]([O:23][CH3:24])=[C:6]([CH2:8][CH2:9][C:10]2([CH:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)[O:15][C:14](=[O:16])[CH2:13][C:12](=[O:17])[CH2:11]2)[CH:7]=1.[Cl:27][C:28]1[CH:29]=[C:30](CCC2(C3CCCC3)OC(=O)CC(=O)C2)C=C[C:33]=1OC(C)C.CC1C=C(C)[N:57]2[N:61]=C(C=O)N=[C:56]2N=1>>[Cl:1][C:2]1[C:3]([O:25][CH3:26])=[CH:4][C:5]([O:23][CH3:24])=[C:6]([CH2:8][CH2:9][C:10]2([CH:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)[O:15][C:14](=[O:16])[C:13]([CH2:30][C:29]3[C:28]([Cl:27])=[CH:33][N:57]([CH3:56])[N:61]=3)=[C:12]([OH:17])[CH2:11]2)[CH:7]=1
Reactant: CC(C)Oc1ccc(CCC2(C3CCCC3)CC(=O)CC(=O)O2)cc1Cl
Reactant: COc1cc(OC)c(CCC2(C3CCCC3)CC(=O)CC(=O)O2)cc1Cl
Reactant: Cc1cc(C)n2nc(C=O)nc2n1
Product: COc1cc(OC)c(CCC2(C3CCCC3)CC(O)=C(Cc3nn(C)cc3Cl)C(=O)O2)cc1Cl

Procedure:
The title compound was prepared analogously to Example B(31), where 6-[2-(5-Chloro-2,4-dimethoxy-phenyl)-ethyl]-6-cyclopentyl-dihydro-pyran-2,4-dione (described in Step 1 of example B(35)) was substituted in place of 6-[2-(3-Chloro-4-isopropoxy-phenyl)-ethyl]-6-cyclopentyl-dihydro-pyran-2,4-dione and 4-chloro-1-methyl-1H-pyrazole-3-carbalehyde was substituted in place of 5,7-Dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carbaldehyde of that example.
Reaction SMILES: [OH:1][C:2]1[C:7]([CH2:8][CH2:9][CH:10]([CH3:12])[CH3:11])=[C:6]([O:13][CH3:14])[CH:5]=[CH:4][C:3]=1[C:15](=[O:25])[CH2:16][CH2:17][C:18]1[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:33][C:34]([O:36][CH3:37])=[O:35].Cl>CC(C)=O>[OH:1][C:2]1[C:7]([CH2:8][CH2:9][CH:10]([CH3:11])[CH3:12])=[C:6]([O:13][CH3:14])[CH:5]=[CH:4][C:3]=1[C:15](=[O:25])[CH2:16][CH2:17][C:18]1[CH:19]=[CH:20][C:21]([O:24][CH2:33][C:34]([O:36][CH3:37])=[O:35])=[CH:22][CH:23]=1
Reactant: COC(=O)CBr
Reactant: COc1ccc(C(=O)CCc2ccc(O)cc2)c(O)c1CCC(C)C
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: COC(=O)COc1ccc(CCC(=O)c2ccc(OC)c(CCC(C)C)c2O)cc1
Reaction time: 0.5 h
Yield: 94.6 %

Procedure:
Then, 32.3 g of 1-(2-hydroxy-4-methoxy-3-isopentylphenyl)-3-(4-hydroxyphenyl)-1-propanone was dissolved in 150 ml of anhydrous acetone, 32.6 g of anhydrous potassium carbonate was added to the solution, and the mixture was stirred for 30 minutes. Then, 17.3 g of methyl α-bromoacetate was added to the reaction mixture, and the mixture was stirred at room temperature for 1 day to effect a reaction. After the reaction, the reaction mixture was neutralized with dilute hydrochloric acid and extracted with ethyl acetate, and the solvent was removed from the extract by distillation to obtain 37.0 g (yield=94.6%) of 1-(2-hydroxy-4-methoxy-3-isopentylphenyl)-3-(4-methoxycarbonylmethoxyphenyl)-1-propanone in the form of a colorless prism.
Reaction SMILES: [F:1][C:2]([F:22])([F:21])[C:3]1[CH:4]=[C:5]([N:12]2[C:16](=[O:17])[C:15]([CH3:19])([CH3:18])[NH:14][C:13]2=[O:20])[CH:6]=[CH:7][C:8]=1[N+:9]([O-:11])=[O:10].[H-].[Na+].[CH3:25]I>CN(C)C=O>[N+:9]([C:8]1[CH:7]=[CH:6][C:5]([N:12]2[C:16](=[O:17])[C:15]([CH3:19])([CH3:18])[N:14]([CH3:25])[C:13]2=[O:20])=[CH:4][C:3]=1[C:2]([F:1])([F:21])[F:22])([O-:11])=[O:10]
Reactant: CC1(C)NC(=O)N(c2ccc([N+](=O)[O-])c(C(F)(F)F)c2)C1=O
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CN1C(=O)N(c2ccc([N+](=O)[O-])c(C(F)(F)F)c2)C(=O)C1(C)C
Reaction time: 0.25 h

Procedure:
A solution of 3.17 g of 1-(3-trifluoromethyl-4-nitro-phenyl)-4,4-dimethyl-imidazoline-2,5-dione (French Patent No. 2,329,276) and 32 ml of dimethylformamide were added at 23° C. to 26° C. to a 50% suspension of 492 mg of sodium hydride in oil and 3 ml of dimethylformamide and after stirring for 15 minutes, a solution of 0.7 ml of methyl iodide in 2 ml of dimethylformamide was added. The mixture was stirred for 25 minutes at 24° C. to 28° C. and was then poured into 200 g of a 1-1 water-ice mixture. The mixture was extracted with ether and the organic phase was washed with saturated aqueous sodium chloride, dried, filtered and evaporated to dryness under reduced pressure to obtain 3.6 g of the desired product melting at 116° C. An analytical sample was crystallized from isopropyl alcohol to obtain 2.73 g of the product melting at 116° C.
Reaction SMILES: C(C1OC2C(C(=O)CC3C=CC=CC=3)(C(=O)N2C(=C(C)C)C(OC)=O)N1)(O)=O.S(Cl)(Cl)=O.[N+](=[CH:35][C:36]([CH:38]1[O:44][CH:43]2[C:40]([C:54](=[O:62])[CH2:55][C:56]3[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=3)([C:41](=[O:53])[N:42]2[C:45](=[C:50]([CH3:52])[CH3:51])[C:46]([O:48][CH3:49])=[O:47])[NH:39]1)=[O:37])=[N-].[ClH:63]>C(Cl)Cl>[Cl:63][CH2:35][C:36]([CH:38]1[O:44][CH:43]2[C:40]([C:54](=[O:62])[CH2:55][C:56]3[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=3)([C:41](=[O:53])[N:42]2[C:45](=[C:50]([CH3:52])[CH3:51])[C:46]([O:48][CH3:49])=[O:47])[NH:39]1)=[O:37]
Reactant: COC(=O)C(=C(C)C)N1C(=O)C2(C(=O)Cc3ccccc3)NC(C(=O)C=[N+]=[N-])OC12
Reactant: Cl
Agent: COC(=O)C(=C(C)C)N1C(=O)C2(C(=O)Cc3ccccc3)NC(C(=O)O)OC12
Solvent: O=S(Cl)Cl
Solvent: ClCCl
Product: COC(=O)C(=C(C)C)N1C(=O)C2(C(=O)Cc3ccccc3)NC(C(=O)CCl)OC12
Reaction time: 0.5 h
Yield: 75.3 %

Procedure:
To a solution of 1.45 g of methyl α-(3ξ-carboxy-2-phenylacetyl-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]heptan-6-yl)-α-isopropylideneacetate in 7 ml of methylene chloride is added 1.2 ml of thionyl chloride, and the mixture refluxed under heating for 2 hours and concentrated under reduced pressure. The resulting residue [methyl α-(3ξ-chlorocarbonyl-2-phenylacetyl-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]heptan-6-yl)-α-isopropylideneacetate] is dissolved in 20 ml of tetrahydrofuran and mixed with 15 ml of ether solution of diazomethane which has been prepared from 1.5 g of nitrosomethylurea, and the mixture is kept at room temperature for 30 minutes. Into the resulting solution of methyl α-(3ξ-diazoacetyl-2-phenylacetyl-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]heptan-6-yl)-α-isopropylideneacetate is introduced hydrogen chloride gas under ice-cooling until the spot of diazo ketone disappears. The mixture is concentrated under reduced pressure, and the residue is purified by chromatography on 17 g of silica gel containing 10% water and eluted with benzene containing 10% ethyl acetate to yield 1.19 g of methyl α-(3ξ-chloroacetyl-2-phenylacetyl-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]heptan-6-yl)-α-isopropylideneacetate in 75.3% yield.
Reaction SMILES: [CH:1]1([N:6]2[C:10]([NH2:11])=[C:9]([C:12]([NH2:14])=[O:13])[C:8]([CH2:15][CH3:16])=[N:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:17][O:18][C:19]1[CH:26]=[CH:25][C:22]([CH:23]=O)=[CH:21][C:20]=1[O:27][CH2:28][CH2:29][N:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1>CCOC(C)=O>[CH:1]1([N:6]2[C:10]3=[N:11][C:23]([C:22]4[CH:25]=[CH:26][C:19]([O:18][CH3:17])=[C:20]([O:27][CH2:28][CH2:29][N:30]5[CH2:35][CH2:34][O:33][CH2:32][CH2:31]5)[CH:21]=4)=[N:14][C:12](=[O:13])[C:9]3=[C:8]([CH2:15][CH3:16])[NH:7]2)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: COc1ccc(C=O)cc1OCCN1CCOCC1
Reactant: CCc1nn(C2CCCC2)c(N)c1C(N)=O
Solvent: CCOC(C)=O
Product: CCc1[nH]n(C2CCCC2)c2nc(-c3ccc(OC)c(OCCN4CCOCC4)c3)nc(=O)c1-2
Temperature: 160 °C

Procedure:
A mixture of 1-cyclopentyl-3-ethyl-5-amino-1H-pyrazole-4-carboxamide (1.25 g, 5.63 mmol), 4-methoxy-3-[2-(4-morpholinyl)ethoxy]benzaldehyde (1.64 g), and xylenes (12 ml) was heated at 160° C. overnight. Additional aldehyde (0.5 g) was added and the mixture was refluxed until complete, then cooled to room temperature. The solvent was stripped, the residue was slurried with EtOAc and the product was collected by filtration and combined with the product from a similar experimental run. The combined product was recrystallized from CH3CN to afford 1-cyclopentyl-3-ethyl-6-[4-methoxy-3-[2-(4-morpholinyl)ethoxy]phenyl]pyrazolo[3,4-d]pyrimidin-4-one, m.p. 205-206° C.
Reaction SMILES: [OH-].[K+].O.[C:4]1([SH:10])[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[C:11]1([N:17]2[CH2:22][C:21]3[C:23]4[C:32]([C:33](Cl)=[CH:34][C:20]=3[N:19]=[CH:18]2)=[CH:31][C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:24]=4)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>CN(C)C=O>[C:11]1([N:17]2[CH2:22][C:21]3[C:23]4[C:32]([C:33]([S:10][C:4]5[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=5)=[CH:34][C:20]=3[N:19]=[CH:18]2)=[CH:31][C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:24]=4)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: Sc1ccccc1
Reactant: Clc1cc2c(c3cc4ccccc4cc13)CN(c1ccccc1)C=N2
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CN(C)C=O
Product: C1=Nc2cc(Sc3ccccc3)c3cc4ccccc4cc3c2CN1c1ccccc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A solution of 40 parts of potassium hydroxide in 60 parts of water is added to a solution of 66 parts of thiophenol in 1,000 parts of dimethylformamide and 171 parts of 2-phenyl-6-chloroanthrapyrimidine are then introduced. The mixture is stirred for 16 hours at room temperature and afterwards for a further hour at 50°-60°C. After cooling to room temperature, the colorant, which has precipitated in orange crystalline platelets, is filtered off, washed with DMF and alcohol and dried at 80°-90°C in vacuo. 194 parts (93.2% of theory) are obtained of 2-phenyl-6-phenylmercaptoanthrapyrimidine, which dyes polyester in bulk in fast, yellow shades.
Reaction SMILES: [CH3:1][C:2]1[N:3]=[C:4]([C:8]2[C:13]([O:14][C:15]3[C:24]4[C:19](=[CH:20][C:21]([O:27][CH2:28][CH:29]5[CH2:31][O:30]5)=[C:22]([O:25][CH3:26])[CH:23]=4)[N:18]=[CH:17][CH:16]=3)=[CH:12][C:11]([CH3:32])=[C:10]([CH3:33])[N:9]=2)[S:5][C:6]=1[CH3:7].FC(F)(F)C(O)=[O:37].[OH-].[Na+].O>C(Cl)Cl>[CH3:1][C:2]1[N:3]=[C:4]([C:8]2[C:13]([O:14][C:15]3[C:24]4[C:19](=[CH:20][C:21]([O:27][CH2:28][CH:29]([OH:30])[CH2:31][OH:37])=[C:22]([O:25][CH3:26])[CH:23]=4)[N:18]=[CH:17][CH:16]=3)=[CH:12][C:11]([CH3:32])=[C:10]([CH3:33])[N:9]=2)[S:5][C:6]=1[CH3:7]
Reactant: COc1cc2c(Oc3cc(C)c(C)nc3-c3nc(C)c(C)s3)ccnc2cc1OCC1CO1
Reactant: O=C(O)C(F)(F)F
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: ClCCl
Product: COc1cc2c(Oc3cc(C)c(C)nc3-c3nc(C)c(C)s3)ccnc2cc1OCC(O)CO
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 100 %

Procedure:
4-[2-(4,5-Dimethyl-thiazol-2-yl)-5,6-dimethyl-pyridin-3-yloxy]-6-methoxy-7-oxiranylmethoxy-quinoline (compound 458) (40 mg) was dissolved in methylene chloride (2 ml) to prepare a solution which was then brought to 0° C. Trifluoroacetic acid (0.4 ml) was added thereto, the mixture was stirred at 0° C. for 30 min, and the mixture was then stirred at room temperature for 5 hr. The reaction solution was brought to 0° C., was stirred, and was made alkaline by the addition of a 10% aqueous sodium hydroxide solution. Water was added to the reaction solution, the mixture was extracted with chloroform, and the chloroform layer was then washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by thin layer chromatography using chloroform-methanol to give the title compound (41 mg, yield 100%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([OH:9])=[CH:4][C:3]=1[N:10]1[C:14](=[O:15])[N:13]([CH2:16][CH3:17])[N:12]=[N:11]1.CN(C)C(=O)C.[H-].[Na+].[CH3:26][O:27][CH2:28]Cl>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([O:9][CH2:26][O:27][CH3:28])=[CH:4][C:3]=1[N:10]1[C:14](=[O:15])[N:13]([CH2:16][CH3:17])[N:12]=[N:11]1
Reactant: COCCl
Reactant: CCn1nnn(-c2cc(O)c(Cl)cc2Cl)c1=O
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CC(=O)N(C)C
Product: CCn1nnn(-c2cc(OCOC)c(Cl)cc2Cl)c1=O
Temperature: 25 °C
Reaction time: 18 h
Yield: 20.5 %

Procedure:
To a stirred mixture of 0.8 g (0.0029 mole) of 1-(2,4-dichloro-5-hydroxyphenyl)-1,4-dihydro-4-ethyl-5H-tetrazol-5-one, 2.8 g (0.032 mole) of N,N-dimethylacetamide, and 0.14 g (0.0029 mole) of sodium hydride (50% in oil) in 25 mL of toluene was added 0.47 g (0.0058 mole) of chloromethyl methyl ether. The reaction mixture was stirred at room temperature for approximately 18 hours then poured into ice water and extracted with diethyl ether. The extract was dried over anhydrous magnesium sulfate, filtered, and the filtrate evaporated to leave a solid. The solid was purified by recrystallization from heptane to yield 0.19 g of 1-(2,4-dichloro-5-methoxymethoxyphenyl)-1,4-dihydro-4-ethyl-5H-tetrazol-5-one, mp 112°-113° C.
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[CH:3]([C:8]([F:11])([F:10])[F:9])[CH:4]([NH2:7])[CH2:5][OH:6].N1C=CC=CC=1.[S:20]1[CH:24]=[CH:23][CH:22]=[C:21]1[S:25](Cl)(=[O:27])=[O:26]>C(Cl)Cl>[F:1][C:2]([F:12])([F:13])[CH:3]([C:8]([F:9])([F:10])[F:11])[CH:4]([NH:7][S:25]([C:21]1[S:20][CH:24]=[CH:23][CH:22]=1)(=[O:27])=[O:26])[CH2:5][OH:6]
Reactant: NC(CO)C(C(F)(F)F)C(F)(F)F
Reactant: O=S(=O)(Cl)c1cccs1
Solvent: c1ccncc1
Solvent: ClCCl
Product: O=S(=O)(NC(CO)C(C(F)(F)F)C(F)(F)F)c1cccs1
Temperature: 25 °C

Procedure:
To a solution of 3,3,3-trifluoro-2-(trifluoromethyl)-1-(hydroxymethyl)propylamine (prepared according to the method of Example 28, Part A, 105 mg, 0.5 mmol) in CH2Cl2 (1 mL) was added pyridine (100 μL) and 2-thiophenesulfonyl chloride (90.5 mg, 0.5 mmol) in CH2Cl2 (1 mL). The solution was stirred for about 8 to about 16 h at 25° C. and then concentrated. EtOAc (1 mL) was added and the solution was washed with 1M HCl (1 mL), brine (1 mL), dried over Na2SO4 and concentrated. The crude solid was purified by the Biotage Flash™ 12 chromatography system, eluting with EtOAc/hexanes (2:3), to give thiophene-2-sulfonic acid (3,3,3-trifluoro-1-hydroxymethyl-2-trifluoromethyl-propyl)-amide (26.5 mg) as a white solid.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[N:6]([NH2:11])[CH:7]=[C:8]([Cl:10])[CH:9]=1)=[O:4].[C:12]1([C:18]2[CH:25]=[CH:24][C:21]([CH:22]=O)=[CH:20][CH:19]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>CO>[CH3:1][O:2][C:3]([C:5]1[N:6]([N:11]=[CH:22][C:21]2[CH:24]=[CH:25][C:18]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)=[CH:19][CH:20]=2)[CH:7]=[C:8]([Cl:10])[CH:9]=1)=[O:4]
Reactant: COC(=O)c1cc(Cl)cn1N
Reactant: O=Cc1ccc(-c2ccccc2)cc1
Solvent: CO
Product: COC(=O)c1cc(Cl)cn1N=Cc1ccc(-c2ccccc2)cc1

Procedure:
Prepared according to the imine formation condition used in Example 18 step b) from 1-amino-4-chloro-1H-pyrrole-2-carboxylic acid methyl ester and 4-phenyl benzaldehyde in refluxing methanol for 12 h. 1H NMR (CDCl3, δ in ppm): 8.43 (s, 1H), 7.91 (d, 2H, J=8.4 Hz), 7.68 (d, 2H, J=8.4 Hz), 7.66-7.16 (m, 5H), 7.20 (d, 1H, J=2.2 Hz), 6.90 (d, 1H, J=1.8 Hz), 3.84 (s, 3H).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([O:22][CH2:23][C:24]2[C:29]([F:30])=[CH:28][CH:27]=[CH:26][C:25]=2[F:31])[C:5]2[N:6]([C:8]([C:12]([NH:14][C@H:15]([CH2:18][CH2:19][CH2:20][CH3:21])[CH2:16][OH:17])=[O:13])=[C:9]([CH3:11])[N:10]=2)[CH:7]=1.[CH3:32][N:33](C)CCN(C)C.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>CN(C=O)C.C(OCC)(=O)C.[C-]#N.[Zn+2].[C-]#N>[C:32]([C:2]1[CH:3]=[C:4]([O:22][CH2:23][C:24]2[C:29]([F:30])=[CH:28][CH:27]=[CH:26][C:25]=2[F:31])[C:5]2[N:6]([C:8]([C:12]([NH:14][C@H:15]([CH2:18][CH2:19][CH2:20][CH3:21])[CH2:16][OH:17])=[O:13])=[C:9]([CH3:11])[N:10]=2)[CH:7]=1)#[N:33]
Reactant: CN(C)CCN(C)C
Reactant: CCCC[C@H](CO)NC(=O)c1c(C)nc2c(OCc3c(F)cccc3F)cc(Br)cn12
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: [C-]#N
Agent: [Zn+2]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCCC[C@H](CO)NC(=O)c1c(C)nc2c(OCc3c(F)cccc3F)cc(C#N)cn12
Temperature: 160 °C

Procedure:
Under argon, 500 mg (1.0 mmol) of 6-bromo-8-[(2,6-difluorobenzyl)oxy]-N-[(2R)-1-hydroxyhexan-2-yl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide, 70.9 mg of zinc(II) cyanide (0.6 mmol, 0.6 equivalents), 30.4 μl of 1,2-bis(dimethylamino)ethane (TMEDA; 0.2 mmol, 0.2 equivalents), 65 mg of tris(dibenzylideneacetone)dipalladium Pd2 dba3 (0.07 mmol, 7 mol %) and 29 mg of xantphos ligand (0.05 mmol, 5 mol %) were dissolved in 2 ml of DMF and, divided into 5 microwave reaction vessels, heated at 160° C. for 5 min (CEM Discovery microwave, 300 Watt irratiation). The combined reaction mixtures were diluted with ethyl acetate and filtered through kieselguhr. The filter cake was washed thoroughly and the filtrate was washed with water, dried over magnesium sulphate, filtered and concentrated. The residue was chromatographed on a 50 g silica gel cartridge (Biotage Isolera, cyclohexane/ethyl acetate gradient as mobile phase). This gave 289 mg of the target compound (64% of theory).
Reaction SMILES: O[CH2:2][C:3]1[CH:8]=[CH:7][C:6](/[CH:9]=[CH:10]/[C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])=[CH:13][CH:12]=2)=[CH:5][CH:4]=1.S(Cl)([Cl:26])=O.O>ClCCl>[Cl:26][CH2:2][C:3]1[CH:8]=[CH:7][C:6](/[CH:9]=[CH:10]/[C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])=[CH:13][CH:12]=2)=[CH:5][CH:4]=1
Reactant: O=S(Cl)Cl
Reactant: CCCCCCOc1ccc(/C=C/c2ccc(CO)cc2)cc1
Solvent: O
Solvent: ClCCl
Product: CCCCCCOc1ccc(/C=C/c2ccc(CCl)cc2)cc1
Yield: 60 %

Procedure:
To a solution of 1.7 g (5.5 mmole) of (E)-4-hydroxymethyl-4′-hexyloxystilbene (21) in 12 ml of dichloromethane cooled in an ice bath under a nitrogen atmosphere were added dropwise 0.5 ml of thionylchloride in 3 ml of dichloromethane. After 1.5 h 16 ml of water were added and the organic layer was separated. It was washed with 12 ml of brine, dried over MgSO4, and the solvent was evaporated. A white solid was obtained which was recrystallized from 80 ml of a 1:1 mixture of hexane and ethanol. 1.1 g of white crystals were obtained (yield 60%).
Reaction SMILES: [OH:1][N:2]=[C:3]([NH2:10])[C:4]1[CH:9]=[CH:8][CH:7]=[N:6][CH:5]=1.[Cl:11][C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][N:20]=1)[C:15](Cl)=O.N>>[Cl:11][C:12]1[CH:13]=[C:14]([C:15]2[O:1][N:2]=[C:3]([C:4]3[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=3)[N:10]=2)[CH:18]=[CH:19][N:20]=1
Reactant: NC(=NO)c1cccnc1
Reactant: O=C(Cl)c1ccnc(Cl)c1
Agent: N
Product: Clc1cc(-c2nc(-c3cccnc3)no2)ccn1

Procedure:
The title compound was prepared according to the procedure of Example 1 using N′-hydroxynicotinimidamide (Aldrich) and 2-chloroisonicotinoyl chloride (Maybridge). 1H NMR (300 MHz, DMSO-d6) δ 7.68 (ddd, J=7.9, 4.8, 0.8 Hz, 1H), 8.16 (dd, J=5.1, 1.4 Hz, 1H), 8.23 (dd, J=1.5, 0.8 Hz, 1H), 8.42-8.54 (m, 1H), 8.77 (dd, J=5.1, 0.7 Hz, 1H), 8.84 (dd, J=4.7, 1.7 Hz, 1H), 9.28 (dd, J=2.2, 0.8 Hz, 1H) ppm; MS (DCl/NH3) m/z 259 (M+H)+, 261 (M+H)+.
Reaction SMILES: [CH3:1][N:2]([CH3:6])[CH2:3][CH2:4][NH2:5].Br[C:8]1[CH:9]=[C:10]2[C:19](=[C:20]3[C:25]=1[CH:24]=[CH:23][CH:22]=[N:21]3)[NH:18][S:17](=[O:27])(=[O:26])[C:16]1[C:11]2=[CH:12][CH:13]=[CH:14][CH:15]=1.C1CCN2C(=NCCC2)CC1.C1C[O:42][CH2:41]C1>>[CH3:1][N:2]([CH3:6])[CH2:3][CH2:4][NH:5][C:41]([C:8]1[CH:9]=[C:10]2[C:19](=[C:20]3[C:25]=1[CH:24]=[CH:23][CH:22]=[N:21]3)[NH:18][S:17](=[O:27])(=[O:26])[C:16]1[C:11]2=[CH:12][CH:13]=[CH:14][CH:15]=1)=[O:42]
Reactant: O=S1(=O)Nc2c(cc(Br)c3cccnc23)-c2ccccc21
Reactant: CN(C)CCN
Reactant: C1CCOC1
Solvent: C1CCC2=NCCCN2CC1
Product: CN(C)CCNC(=O)c1cc2c(c3ncccc13)NS(=O)(=O)c1ccccc1-2
Yield: 39 %

Procedure:
In a similar fashion using route 58 general procedure 128, N*1*,N*1*-dimethyl-ethane-1,2-diamine (73 mg, 0.83 mmol), 12-bromo-5H-6-thia-4,5-diaza-chrysene 6,6-dioxide 545 (100 mg, 0.28 mmol), Hermann's palladacycle (13 mg, 14 μmol, Mo(CO)6 (73 mg, 0.28 mmol), DBU (126 mg, 0.83 mmol) and THF (2 ml) gave the title compound (43 mg, 39%).
Reaction SMILES: [OH:1][CH:2]1[C:9](=[CH2:10])[CH2:8][C@H:7]2[C@@H:3]1[CH2:4][C@@H:5]([O:27][Si:28]([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29])[C@H:6]2/[CH:11]=[CH:12]/[C@@H:13]([O:19][Si:20]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21])[CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].C(N(CC)CC)C.[CH3:42][S:43](Cl)(=[O:45])=[O:44]>C(Cl)Cl>[CH3:42][S:43]([O:1][CH:2]1[C:9](=[CH2:10])[CH2:8][C@H:7]2[C@@H:3]1[CH2:4][C@@H:5]([O:27][Si:28]([C:31]([CH3:33])([CH3:32])[CH3:34])([CH3:29])[CH3:30])[C@H:6]2/[CH:11]=[CH:12]/[C@@H:13]([O:19][Si:20]([C:23]([CH3:24])([CH3:25])[CH3:26])([CH3:21])[CH3:22])[CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])(=[O:45])=[O:44]
Reactant: C=C1C[C@@H]2[C@H](/C=C/[C@H](CCCCC)O[Si](C)(C)C(C)(C)C)[C@H](O[Si](C)(C)C(C)(C)C)C[C@@H]2C1O
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C=C1C[C@@H]2[C@H](/C=C/[C@H](CCCCC)O[Si](C)(C)C(C)(C)C)[C@H](O[Si](C)(C)C(C)(C)C)C[C@@H]2C1OS(C)(=O)=O
Temperature: -25 °C
Reaction time: 2 h
Yield: 84 %

Procedure:
The (1S,2RS,5S,6S,7R)-2-hydroxy-3-methylene-6-[(E,3S)-3-t-butyldimethylsilyloxy-l-octenyl]-7-t-butyldimethylsilyloxybicyclo[3.3.0]octane (127 mg, 0.25 mmole) obtained in Example 3 was dissolved in 1 ml of methylene chloride. The solution was cooled to -25° C., and triethylamine (38 mg, 0.375 mmole) and then a solution of methanesulfonyl chloride (43 mg, 0.375 mmole) in 1 ml of methylene chloride were added. The mixture was stirred for 2 hours. Ice water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The separated organic layer was washed with an aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and concentrated. The crude product was subjected to column chromatography (silica gel 15 g; hexane/ethyl acetate=30/1) to give (1S,2RS,5S,6S,7R)-2-methanesulfonyloxy-3-methylene-6-[(E,3S)-3-t-butyldimethylsilyloxy-1-octenyl]-7-t-butyldimethylsilyloxybicyclo[3.3.0]octane (123 mg, 0.21 mmole, 84%).
Reaction SMILES: [CH3:1][C:2]1[C@@H:19]([O:20][C:21]([C@H:23]([OH:40])[C@@H:24]([NH:31][C:32]([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)=[O:33])[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)=[O:22])[CH2:18][C@:14]2([OH:41])[C:15]([CH3:17])([CH3:16])[C:3]=1[C@@H:4]([O:59][C:60]([CH3:62])=[O:61])[C:5]([C@@:7]1([CH3:58])[C@H:12]([C@@H:13]2[O:42][C:43]([C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)=[O:44])[C@:11]2([O:53][C:54]([CH3:56])=[O:55])[CH2:51][O:52][C@@H:10]2[CH2:9][C@@H:8]1[OH:57])=[O:6].[C:63]1(=[O:69])[O:68][C:66](=[O:67])[CH2:65][CH2:64]1>N1C=CC=CC=1>[CH3:1][C:2]1[C@@H:19]([O:20][C:21]([C@H:23]([O:40][C:63]([CH2:64][CH2:65][C:66]([OH:68])=[O:67])=[O:69])[C@@H:24]([NH:31][C:32]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)=[O:33])[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)=[O:22])[CH2:18][C@:14]2([OH:41])[C:15]([CH3:16])([CH3:17])[C:3]=1[C@@H:4]([O:59][C:60]([CH3:62])=[O:61])[C:5]([C@@:7]1([CH3:58])[C@H:12]([C@@H:13]2[O:42][C:43]([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)=[O:44])[C@:11]2([O:53][C:54]([CH3:56])=[O:55])[CH2:51][O:52][C@@H:10]2[CH2:9][C@@H:8]1[OH:57])=[O:6]
Reactant: CC(=O)O[C@H]1C(=O)[C@@]2(C)[C@H]([C@H](OC(=O)c3ccccc3)[C@]3(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)c4ccccc4)c4ccccc4)C(C)=C1C3(C)C)[C@]1(OC(C)=O)CO[C@@H]1C[C@@H]2O
Reactant: O=C1CCC(=O)O1
Solvent: c1ccncc1
Product: CC(=O)O[C@H]1C(=O)[C@@]2(C)[C@H]([C@H](OC(=O)c3ccccc3)[C@]3(O)C[C@H](OC(=O)[C@H](OC(=O)CCC(=O)O)[C@@H](NC(=O)c4ccccc4)c4ccccc4)C(C)=C1C3(C)C)[C@]1(OC(C)=O)CO[C@@H]1C[C@@H]2O
Reaction time: 0.33 h

Procedure:
Taxol (0.5 g, 0.59 mmol) and succinic anhydride (0.90 g, 7.6 mmol) in 12 ml of pyridine were allowed to react for 3 hours at room temperature after which the mixture was evaporated to dryness in vacuo. The residue was treated with 20 ml of water, stirred for 20 min and then filtered. The precipitate was dissolved in acetone, water slowly added, and the fine crystals of 8 were collected; yield (75-85%).
Reaction SMILES: FC1C=C(C[C@H](NC(=O)CN2C3CCCCC=3C(C(F)(F)F)=N2)C2N(C3C=CC(OC)=CC=3)C=CN=2)C=C(F)C=1.Cl.[Cl:42][C:43]1[CH:48]=[CH:47][C:46]([C:49]2[O:50][C:51]([CH:54]([NH2:64])[CH2:55][C:56]3[CH:61]=[C:60]([F:62])[CH:59]=[C:58]([F:63])[CH:57]=3)=[CH:52][N:53]=2)=[CH:45][CH:44]=1.[F:65][C:66]1[CH:67]=[C:68]2[C:72](=[CH:73][CH:74]=1)[NH:71][CH:70]=[C:69]2[CH2:75][C:76](O)=[O:77]>>[Cl:42][C:43]1[CH:48]=[CH:47][C:46]([C:49]2[O:50][C:51]([CH:54]([NH:64][C:76](=[O:77])[CH2:75][C:69]3[C:68]4[C:72](=[CH:73][CH:74]=[C:66]([F:65])[CH:67]=4)[NH:71][CH:70]=3)[CH2:55][C:56]3[CH:61]=[C:60]([F:62])[CH:59]=[C:58]([F:63])[CH:57]=3)=[CH:52][N:53]=2)=[CH:45][CH:44]=1
Reactant: NC(Cc1cc(F)cc(F)c1)c1cnc(-c2ccc(Cl)cc2)o1
Reactant: O=C(O)Cc1c[nH]c2ccc(F)cc12
Agent: COc1ccc(-n2ccnc2[C@H](Cc2cc(F)cc(F)c2)NC(=O)Cn2nc(C(F)(F)F)c3c2CCCC3)cc1
Agent: Cl
Product: O=C(Cc1c[nH]c2ccc(F)cc12)NC(Cc1cc(F)cc(F)c1)c1cnc(-c2ccc(Cl)cc2)o1

Procedure:
The title compound was prepared according to the method presented for the synthesis of compound 5F of Example 5 utilizing 19E and 2-(5-fluoro-1H-indol-3-yl)acetic acid. 1H NMR (400 MHz, CDCl3) δ 8.21 (s, 1H), 7.81 (d, J=8.5 Hz, 2H), 7.43 (d, J=8.5 Hz, 2H), 7.38-7.23 (m, 2H), 7.16 (s, 1H), 7.05 (d, J=9.3 Hz, 1H), 6.95 (dd, J=10.3, 7.7 Hz, 1H), 6.61 (t, J=9.0 Hz, 1H), 6.50 (dd, J=14.6, 7.6 Hz, 3H), 5.27 (q, J=7.4 Hz, 1H), 3.72 (s, 2H), 3.08 (dd, J=13.7, 7.1 Hz, 1H), 2.95 (dd, J=13.7, 7.4 Hz, 1H). MS (m/z) 510.1 [M+H]+.