Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[S:3][C:4]([C:7]2[CH:12]=[CH:11][C:10]([O:13][CH:14]([CH3:16])[CH3:15])=[C:9]([C:17]([F:20])([F:19])[F:18])[CH:8]=2)=[N:5][N:6]=1.[CH2:21]([C:23]1[C:30](B2OC(C)(C)C(C)(C)O2)=[CH:29][CH:28]=[CH:27][C:24]=1[CH:25]=[O:26])[CH3:22].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C)C=O.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>[CH2:21]([C:23]1[C:30]([C:2]2[S:3][C:4]([C:7]3[CH:12]=[CH:11][C:10]([O:13][CH:14]([CH3:16])[CH3:15])=[C:9]([C:17]([F:20])([F:19])[F:18])[CH:8]=3)=[N:5][N:6]=2)=[CH:29][CH:28]=[CH:27][C:24]=1[CH:25]=[O:26])[CH3:22]
Reactant: CC(C)Oc1ccc(-c2nnc(Br)s2)cc1C(F)(F)F
Reactant: CCc1c(C=O)cccc1B1OC(C)(C)C(C)(C)O1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCc1c(C=O)cccc1-c1nnc(-c2ccc(OC(C)C)c(C(F)(F)F)c2)s1
Temperature: 130 °C
Yield: 52.7 %

Procedure:
To a solution of 2-bromo-5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazole (D4) (100 mg), 2-ethyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde (D5) (85 mg) and tripotassium phosphate (145 mg) in N,N-dimethylformamide (DMF) (6 mL) and water (1.5 mL) stirred under nitrogen at room temperature was added Pd(Ph3P)4 (31.5 mg). The reaction vessel was sealed and heated under microwave at 130° C. for 8 min. After cooling the reaction, water was added to quench the reaction. After filtered through the celite, the filtrate was partitioned between the organic and aqueous layers. The aqueous layer was extracted with EA for 3 times. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate. The dried solution was concentrated, and purified by column chromatography to afford 2-ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}benzaldehyde (D6) (60.4 mg). MS (ES): C21H19F3N2O2S requires 420. found 421.1 (M+H+).
Reaction SMILES: [CH2:1]([O:4]C(F)=C(F)F)[CH:2]=C.C(N(CC)CC)C.[F:17][C:18]([F:25])([CH2:22][CH:23]=[CH2:24])[C:19](F)=[O:20]>C(O)C>[F:17][C:18]([F:25])([CH2:22][CH:23]=[CH2:24])[C:19]([O:4][CH2:1][CH3:2])=[O:20]
Reactant: C=CCC(F)(F)C(=O)F
Reactant: C=CCOC(F)=C(F)F
Solvent: CCO
Solvent: CCN(CC)CC
Product: C=CCC(F)(F)C(=O)OCC
Temperature: 0 °C

Procedure:
The start of the reaction in the reactor is indicated by a rise in temperature within the reaction chamber 5 from originally -74° C. to about -45° C. During the rest of the reaction period the temperature in the reaction chamber varies from about -45° C. to about -55° C. The reaction mixture from outlet conduit 18 containing the 1,2,2-trifluorovinyl allyl ether is conducted to a stirred solution of 434 g (600 mL, 4.3 mol) of triethylamine in 358 g (450 mL, 7.8 mol) of absolute ethanol cooled in an ice bath. Upon warming to the ice bath temperature, the 1,2,2-trifluorovinyl allyl ether spontaneously rearranges to 2,2-difluoro-4-pentenoyl fluoride, which in the presence of ethanol reacts to yield the desired ethyl 2,2-difluoro-4-pentenoate. The reaction mixture is divided into two equal batches which are treated separately. The following describes the workup of one batch.
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=O)[CH3:10])=[CH:5][CH:4]=1.[Cl:12][C:13]1[CH:21]=[CH:20][C:16]([CH2:17][O:18][NH2:19])=[CH:15][C:14]=1[C:22]([F:25])([F:24])[F:23].C(O)(=O)C>CO>[Cl:12][C:13]1[CH:21]=[CH:20][C:16]([CH2:17][O:18][N:19]=[C:9]([C:6]2[CH:7]=[CH:8][C:3]([CH2:2][OH:1])=[CH:4][CH:5]=2)[CH3:10])=[CH:15][C:14]=1[C:22]([F:23])([F:24])[F:25]
Reactant: NOCc1ccc(Cl)c(C(F)(F)F)c1
Reactant: CC(=O)c1ccc(CO)cc1
Solvent: CC(=O)O
Solvent: CO
Product: CC(=NOCc1ccc(Cl)c(C(F)(F)F)c1)c1ccc(CO)cc1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
To a solution of 1-(4-hydroxymethyl-phenyl)-ethanone (1 eq) in methanol is added O-(4-chloro-3-trifluoromethyl-benzyl)-hydroxylamine (1 eq) followed by the addition of acetic acid (0.05 eq). The mixture is stirred at room temperature for 5 hours. After concentrated, the residue is purified by column chromatography (30% EtOAc in hexane) to give 1-(4-hydroxymethyl-phenyl)-ethanone O-(4-chloro-3-trifluoromethyl-benzyl)-oxime as an oil [MS: (ES+) 358.1 (M+1)+].
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH2:5][CH2:6][CH2:7][C:8]2=O.C[O:15][NH3+:16].[Cl-].C([O-])(=O)C.[Na+]>CO>[CH3:1][O:2][C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH2:5][CH2:6][CH2:7]/[C:8]/2=[N:16]/[OH:15]
Reactant: CO[NH3+]
Reactant: COc1cccc2c1CCCC2=O
Agent: CC(=O)[O-]
Agent: [Cl-]
Agent: [Na+]
Solvent: CO
Product: COc1cccc2c1CCC/C2=N/O
Temperature: 60 °C
Yield: 96.5 %

Procedure:
To a solution of 5-methoxy-3,4-dihydronaphthalen-1(2H)-one (200 mg, 1.14 mmol) and hydroxylamine methyl ether hydrochloride (284 mg, 3.40 mmol) in MeOH (5 mL) was added sodium acetate (279 mg, 3.40 mmol). The reaction mixture was heated at 60° C. for 1 h, cooled and partitioned between H2O and EtOAc. The organic layer was separated, dried over Na2SO4, filtered, and concentrated in vacuo to give Intermediate 34A (0.20 g, 1.1 mmol, 92% yield) which was used directly in the next step without further purification. LCMS=1.78 min [M+1]=192.1 (Method B).
Reaction SMILES: [O:1]=[C:2]1[N:7]2[CH2:8][C:9]3[C:14]([C:6]2=[C:5]([C:15]([O:17]CC2C=CC=CC=2)=[O:16])[CH:4]=[C:3]1[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[CH:13][CH:12]=[CH:11][CH:10]=3.C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.O.[Pd]>[O:1]=[C:2]1[N:7]2[CH2:8][C:9]3[C:14]([C:6]2=[C:5]([C:15]([OH:17])=[O:16])[CH:4]=[C:3]1[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[CH:13][CH:12]=[CH:11][CH:10]=3
Reactant: O=C(OCc1ccccc1)c1cc(-c2ccccc2)c(=O)n2c1-c1ccccc1C2
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: O=C(O)c1cc(-c2ccccc2)c(=O)n2c1-c1ccccc1C2
Reaction time: 16 h
Yield: 95.3 %

Procedure:
A suspension of 3.88 g of benzyl 4,6-dihydro-4-oxo-3-phenylpyrido[2,1-a]isoindole-1-carboxylate in 140 ml of ethanol was treated with 0.78 g of 10 percent palladium/carbon, whereupon the mixture was hydrogenated for 16 hours. The reaction mixture was diluted with 1400 ml of water and treated with 4.18 g of sodium carbonate. The catalyst was filtered off and the filtrate was acidified with 25 percent hydrochloric acid. The separated crystals were filtered off under suction, washed with water and dried in a vacuum. There was obtained 2.85 g of 4,6-dihydro-4-oxo-3-phenylpyrido[2,1-a]isoindole-1-carboxylic acid as white crystals with a m.p. of 295° (decomposition).
Reaction SMILES: [ClH:1].Cl.[CH3:3][N:4]([CH2:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]([CH2:13][Cl:14])[CH:8]=1)[CH3:5].[NH2:15][C:16]([NH2:18])=[S:17]>C(O)C>[ClH:14].[ClH:1].[ClH:14].[CH3:3][N:4]([CH2:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]([CH2:13][NH:18][C:16](=[NH:15])[SH:17])[CH:8]=1)[CH3:5]
Reactant: NC(N)=S
Reactant: CN(C)Cc1ccnc(CCl)c1
Agent: Cl
Solvent: CCO
Product: CN(C)Cc1ccnc(CNC(=N)S)c1

Procedure:
4-Dimethylaminomethyl-2-chloromethylpyridine dihydrochloride is reacted with thiourea in ethanol under reflux. Removal of the ethanol yields 4-dimethylaminomethyl-2-pyridylmethyl isothiourea trihydrochloride.
Reaction SMILES: C([O:3][C:4]([CH:6]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:8]2([CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)[CH2:7]1)=[O:5])C>CO.C(OCC)(=O)C.[Pd]>[CH3:19][C:17]([CH3:20])([O:16][C:14]([N:11]1[CH2:10][CH2:9][C:8]2([C:21]3[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH:6]([C:4]([OH:5])=[O:3])[CH2:7]2)[CH2:13][CH2:12]1)=[O:15])[CH3:18]
Reactant: CCOC(=O)C1CC2(CCN(C(=O)OC(C)(C)C)CC2)c2ccccc21
Agent: [Pd]
Solvent: CO
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N1CCC2(CC1)CC(C(=O)O)c1ccccc12
Reaction time: 1 h
Yield: 916.7 %

Procedure:
To a suspension of Pd/C (300 mg) in methanol (20 ml) and ethyl acetate (10 ml) was added the title compound (1.2 g, 3.6 mmol) from Step B. The reaction mixture was purged with hydrogen and then stirred under a hydrogen balloon for 1 h. The mixture was filtered through celite and concentrated to give the title compound (1.1 g, 33 mmol). 1HNMR (200 MHz, CDCl3): 7.50-7.42 (m, 1 H), 7.34-7.12 (m, 3 H), 4.22-4.04 (m, 3 H), 3.06-2.84 (m, 2 H), 2.40 (d, 2 H), 1.88-1.6 (m, 4 H), 1.50 (s, 9 H).
Reaction SMILES: [C:1](Cl)(=[O:5])[C:2]([CH3:4])=[CH2:3].[F:7][C:8]([F:17])([CH:11]([F:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][OH:10].COC1C=CC(OC)=CC=1>>[C:1]([O:10][CH2:9][C:8]([F:17])([F:7])[CH:11]([F:16])[C:12]([F:15])([F:13])[F:14])(=[O:5])[C:2]([CH3:4])=[CH2:3]
Reactant: C=C(C)C(=O)Cl
Reactant: OCC(F)(F)C(F)C(F)(F)F
Agent: COc1ccc(OC)cc1
Product: C=C(C)C(=O)OCC(F)(F)C(F)C(F)(F)F

Procedure:
To 12 parts of methacrylic acid chloride were added 60 parts of 2,2,3,4,4,4-hexafluorobutyl alcohol as a reactant and a solvent and 0.1 part of hydroquinone dimethyl ether as a polymerization inhibitor. The mixture was heated at a temperature of 90° to 100° C. for 3 hours. The reaction mixture was distilled to give 15 parts of 2,2,3,4,4,4-hexafluorobutyl methacrylate (hereinafter referred to as "HFBMA") having a boiling point of 60° to 63° C./20 mmHg.
Reaction SMILES: [NH2:1][C@H:2]([CH3:17])[C:3]([NH:5][CH:6]1[CH2:9][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:7]1)=[O:4].[N+:18]([C:21]1[CH:51]=[CH:50][C:24]([CH2:25][O:26][C:27]([N:29]=[C:30]([NH:36][C:37](=[O:49])[O:38][CH2:39][C:40]2[CH:45]=[CH:44][C:43]([N+:46]([O-:48])=[O:47])=[CH:42][CH:41]=2)N2C=CC=N2)=[O:28])=[CH:23][CH:22]=1)([O-:20])=[O:19]>O1CCCC1>[N+:18]([C:21]1[CH:22]=[CH:23][C:24]([CH2:25][O:26][C:27]([N:29]=[C:30]([NH:36][C:37]([O:38][CH2:39][C:40]2[CH:45]=[CH:44][C:43]([N+:46]([O-:48])=[O:47])=[CH:42][CH:41]=2)=[O:49])[NH:1][C@H:2]([CH3:17])[C:3]([NH:5][CH:6]2[CH2:9][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:7]2)=[O:4])=[O:28])=[CH:50][CH:51]=1)([O-:20])=[O:19]
Reactant: O=C(N=C(NC(=O)OCc1ccc([N+](=O)[O-])cc1)n1cccn1)OCc1ccc([N+](=O)[O-])cc1
Reactant: C[C@@H](N)C(=O)NC1CN(C(=O)OC(C)(C)C)C1
Solvent: C1CCOC1
Product: C[C@@H](NC(=NC(=O)OCc1ccc([N+](=O)[O-])cc1)NC(=O)OCc1ccc([N+](=O)[O-])cc1)C(=O)NC1CN(C(=O)OC(C)(C)C)C1
Yield: 76.3 %

Procedure:
To a solution of tert-butyl 3-[(2R)-2-amino-2-methylacetylamino]-1-azetidinecarboxylate (443 mg) in anhydrous tetrahydrofuran (20 ml), 4-nitrobenzyl [(4-nitrobenzyloxy)carbonylimino-pyrazol-1-ylmethyl]carbamate (820 mg) was added under ice cooling. The resulting mixture was then treated in a similar manner to that described in Referential Example 16-(1), whereby the title compound (0.860 g) was obtained as an amorphous substance.
Reaction SMILES: [CH3:1][C:2]1[N:6]2[CH:7]=[C:8]([C:11]([F:14])([F:13])[F:12])[CH:9]=[CH:10][C:5]2=[N:4][C:3]=1[NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19].[H-].[Na+].[C:25]1([S:31](Cl)(=[O:33])=[O:32])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>CN(C=O)C>[C:18]([O:17][C:16]([N:15]([C:3]1[N:4]=[C:5]2[CH:10]=[CH:9][C:8]([C:11]([F:13])([F:12])[F:14])=[CH:7][N:6]2[C:2]=1[CH3:1])[S:31]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)(=[O:33])=[O:32])=[O:22])([CH3:19])([CH3:21])[CH3:20]
Reactant: Cc1c(NC(=O)OC(C)(C)C)nc2ccc(C(F)(F)F)cn12
Reactant: O=S(=O)(Cl)c1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1c(N(C(=O)OC(C)(C)C)S(=O)(=O)c2ccccc2)nc2ccc(C(F)(F)F)cn12
Reaction time: 0.17 h
Yield: 72.5 %

Procedure:
To a solution of compound 10-E (0.063 g, 0.2 mmol) in DMF (1 mL) at 0° C. was added 95% NaH (0.012 g, 0.5 mmol) and the reaction mixture was stirred for 10 minutes. Benzenesulfonyl chloride (0.053 g, 0.3 mmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction was quenched by the addition of H2O and the solution was extracted with ethyl acetate. After separation of the organic and aqueous layers a sufficient amount of water was added to remove any dissolved DMF from the organic layer. The organic layer was dried over Na2SO4, filtered, and the solvent evaporated under reduced pressure to afford the crude product. The crude material was purified by flash column chromatography, eluting with a hexanes-EtOAc gradient to give compound 10-F as a white solid (0.066 g, 72%); MS m/z (M+H+) 456.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][Si:5]([CH3:12])([O:9][CH2:10]C)[O:6][CH2:7]C.C(N)C=C.C[Si](C)(C)N(CC=C)[Si](C)(C)C.C[SiH](OC)OC>[Pt].CO>[NH2:1][CH2:2][CH2:3][CH2:4][Si:5]([CH3:12])([O:9][CH3:10])[O:6][CH3:7]
Reactant: CCO[Si](C)(CCCN)OCC
Agent: [Pt]
Agent: C=CCN([Si](C)(C)C)[Si](C)(C)C
Agent: CO[SiH](C)OC
Solvent: C=CCN
Solvent: CO
Product: CO[Si](C)(CCCN)OC

Procedure:
German Patent No. 2408480 describes the reaction of a silazane derivative from allylamine and an organohydrochlorosilane, in the presence of a proton acceptor to form an intermediate silazane which then undergoes a hydrosilylation reaction catalyzed by a platinum catalyst. Upon alcoholysis, the intermediate hydrosilylation product forms 3-aminopropylmethyldiethoxysilane in 70% overall yield. A molar excess of at least 50% of allylamine is used in this process. Identification of the beta-isomer in the product was not made. Japanese Patent No. 10017578 describes another method of synthesis by hydrosilylation of N,N-bis(tri-methylsilyl)allylamine by methyldimethoxysilane. The product of that reaction is then heated with methanol to form 3-aminopropylmethyldimethoxysilane in at least 85% overall yield. The presence of the beta-isomer in the product was not identified. Japanese Patent No. 11209384 describes the use of a rhodium:cyclooctadiene complex as a hydrosilylation catalyst for the addition of methyldiethoxysilane to allylamine to form 3-aminopropylmethyldiethoxy-silane in 78% yield. 2-Aminopropylmethyldiethoxysilane is formed in very low levels in this process not exceeding 0.5%.
Reaction SMILES: [Br:1][CH2:2][C:3]1([CH2:17]O)[CH2:6][N:5]([S:7]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)(=[O:9])=[O:8])[CH2:4]1.C(Br)(Br)(Br)[Br:20].CCOCC>C(Cl)Cl>[Br:1][CH2:2][C:3]1([CH2:17][Br:20])[CH2:6][N:5]([S:7]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)(=[O:9])=[O:8])[CH2:4]1
Reactant: BrC(Br)(Br)Br
Reactant: Cc1ccc(S(=O)(=O)N2CC(CO)(CBr)C2)cc1
Solvent: CCOCC
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)N2CC(CBr)(CBr)C2)cc1
Temperature: 0 °C
Reaction time: 2 h
Yield: 66.2 %

Procedure:
(3-(Bromomethyl)-1-(p-toluenesulfonyl)azetidin-3-yl)methanol (10.2 g, 30.6 mmol) was dissolved in DCM (100 mL) and CBr4 (16.9 g, 51 mmol) was added. The solution was cooled to 0° C. and then PPh3 (13.4 g, 51 mmol) was added in one portion. The resulting mixture was stirred at 0° C. for 2 h, then warmed to rt and stirred for 4 h. Et2O (100 mL) was added and the yellow precipitate was filtered. The filtrate was concentrated under reduced pressure and purification by flash chromatography (Biotage Isolera, 100 g KP-SIL, 0-30% EtOAc in hexanes) gave the title compound as colourless crystals (8.05 g, 67%). 1H NMR (400 MHz, CDCl3) δ ppm 7.74 (d, J=8.3 Hz, 2H), 7.41 (d, J=8.0 Hz, 2H), 3.60 (s, 4H), 3.54 (s, 4H), 2.48 (s, 3H); MS ESI 398.1 [M+H]+, calcd for [C12H15Br2NO2S+H]+397.9.
Reaction SMILES: [Cl:1][C:2]1[C:12]([Cl:13])=[C:11]([C:14](=[O:16])[CH3:15])[CH:10]=[CH:9][C:3]=1[O:4][CH2:5][C:6]([OH:8])=[O:7].[F:17][C:18]1[CH:25]=[CH:24][CH:23]=[CH:22][C:19]=1[CH:20]=O.[OH-].[Na+]>O.C(O)C>[Cl:1][C:2]1[C:12]([Cl:13])=[C:11]([C:14](=[O:16])[CH:15]=[CH:20][C:19]2[CH:22]=[CH:23][CH:24]=[CH:25][C:18]=2[F:17])[CH:10]=[CH:9][C:3]=1[O:4][CH2:5][C:6]([OH:8])=[O:7]
Reactant: O=Cc1ccccc1F
Reactant: CC(=O)c1ccc(OCC(=O)O)c(Cl)c1Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: O=C(O)COc1ccc(C(=O)C=Cc2ccccc2F)c(Cl)c1Cl
Yield: 54.9 %

Procedure:
To 500 ml of ethanol was added [2,3-dichloro-4-(1-oxo-ethyl)phenoxy]acetic acid (19.73 g, 0.075 mole), 2-fluorobenzaldehyde (13.63 g, 0.11 mole), sodium hydroxide (10 g, 0.25 mole) in 20 ml of water and 50 ml of ethanol with stirring under nitrogen. The reaction mixture was refluxed for a total of 11/2 hours. The reaction mixture was cooled, filtered, the gelatineous solid dispersed in water acidified with hydrochloric acid, stirred, filtered and washed with water. The residue was extracted with methylene chloride and ethyl acetate, washed with water, and concentrated under reduced pressure to give 15.2 g of [2,3-dichloro-4-(3-(2-fluorophenyl)-1-oxo-2-propenyl)phenoxy]acetic acid which melted at 191°-194° C. after purification.
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:18](I)=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][C:10]=1[C:20]([CH3:23])([CH3:22])[CH3:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:24][C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1.[F-].[Cs+]>O1CCOCC1.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>[CH2:1]([O:8][C:9]1[C:18]([C:28]2[CH:29]=[CH:30][C:25]([CH3:24])=[CH:26][CH:27]=2)=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][C:10]=1[C:20]([CH3:23])([CH3:22])[CH3:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COC(=O)c1cc(I)c(OCc2ccccc2)c(C(C)(C)C)c1
Reactant: Cc1ccc(B(O)O)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cs+]
Agent: [F-]
Solvent: C1COCCO1
Product: COC(=O)c1cc(-c2ccc(C)cc2)c(OCc2ccccc2)c(C(C)(C)C)c1
Yield: 83 %

Procedure:
12 g (28 mmol) of methyl 4-benzyloxy-3-tert-butyl-5-iodobenzoate are dissolved with 5.8 g (42 mmol) of 4-methylbenzeneboronic acid and 12.7 g (84 mmol) of caesium fluoride in 400 mL of dioxane. The reaction medium is degassed with a flow of nitrogen for 15 minutes, and 1.7 g (1.4 mmol) of tetrakis(triphenylphosphine)palladium are then added. The reaction medium is refluxed for 4 hours and then cooled and hydrolysed. After extraction with ethyl acetate, the organic phase is filtered and concentrated. The residue is purified by chromatography (eluent: 98 heptane/2 ethyl acetate): a colorless oil is obtained (m=9 g, yield=83%).
Reaction SMILES: [CH:1]1[C:14]2[C:5](=[C:6]([CH:17]=O)[C:7]3[C:12]([C:13]=2[CH:15]=O)=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH:4]=[CH:3][CH:2]=1.[NH:19]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=1)[NH2:20]>C(O)(=O)C.C(O)C>[N:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1[NH:19][N:20]=[CH:15][C:13]1[C:14]2[C:5]([C:6]([CH:17]=[N:20][NH:19][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=3)=[C:7]3[C:12]=1[CH:11]=[CH:10][CH:9]=[CH:8]3)=[CH:4][CH:3]=[CH:2][CH:1]=2
Reactant: O=Cc1c2ccccc2c(C=O)c2ccccc12
Reactant: NNc1ccccn1
Solvent: CCO
Solvent: CC(=O)O
Product: C(=NNc1ccccn1)c1c2ccccc2c(C=NNc2ccccn2)c2ccccc12

Procedure:
A suspension of 4.68 g. of 9,10-anthracenedicarboxaldehyde in 200 ml. of ethanol containing 4.37 g. of 2-hydrazinopyridine and 2 drops of acetic acid is stirred and heated under reflux for two hours, then allowed to cool. Collection by filtration and washing with ethanol gives the desired product as an orange solid, which sinters from 267° C. to 272° C. (dec.).
Reaction SMILES: [C:1]1([CH:8]=[CH:7][CH:6]=[C:4]([OH:5])[CH:3]=1)[OH:2].[CH2:9]([P:14](=[O:19])([O:17][CH3:18])[O:15][CH3:16])[CH:10]=[C:11]([CH3:13])[CH3:12]>CCOCC>[OH:2][C:1]1[CH:3]=[C:4]([OH:5])[CH:6]=[CH:7][C:8]=1[C:11]([CH3:13])([CH3:12])[CH2:10][CH2:9][P:14]([O:15][CH3:16])(=[O:19])[O:17][CH3:18]
Reactant: COP(=O)(CC=C(C)C)OC
Reactant: Oc1cccc(O)c1
Solvent: CCOCC
Product: COP(=O)(CCC(C)(C)c1ccc(O)cc1O)OC

Procedure:
55.0 Parts of resorcinol, 17.8 parts of dimethyl prenylphosphonate and 5.0 parts of Fulmont 237® were stirred at 125° C. for 18 hours. The cooled reaction mixture was then diluted with ether, filtered free of catalyst, and poured into 500 parts of water. The oil which separated out was then washed by decantation with water and extracted with ether. Following further washes with sodium bicarbonate solution and water, the ether solution after concentration yielded dimethyl 3-(2',4'-dihydroxyphenyl)-3-methyl-butane-phosphonate, m.p. 142°-3° C., with the following percentage composition by weight.
Reaction SMILES: [OH:1][CH:2]1[CH:7]([C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[CH:10][CH:9]=2)[CH2:6][CH2:5][N:4]([C:21]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:22])[CH2:3]1.Cl[CH2:32][C:33]1[CH:34]=[CH:35][C:36]2[O:41][CH2:40][C:39](=[O:42])[N:38]([CH2:43][CH2:44][CH2:45][O:46][CH3:47])[C:37]=2[CH:48]=1>>[CH3:47][O:46][CH2:45][CH2:44][CH2:43][N:38]1[C:37]2[CH:48]=[C:33]([CH2:32][O:1][CH:2]3[CH:7]([C:8]4[CH:9]=[CH:10][C:11]([O:14][C:15]5[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=5)=[CH:12][CH:13]=4)[CH2:6][CH2:5][N:4]([C:21]([O:23][CH2:24][C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=4)=[O:22])[CH2:3]3)[CH:34]=[CH:35][C:36]=2[O:41][CH2:40][C:39]1=[O:42]
Reactant: O=C(OCc1ccccc1)N1CCC(c2ccc(Oc3ccccc3)cc2)C(O)C1
Reactant: COCCCN1C(=O)COc2ccc(CCl)cc21
Product: COCCCN1C(=O)COc2ccc(COC3CN(C(=O)OCc4ccccc4)CCC3c3ccc(Oc4ccccc4)cc3)cc21

Procedure:
Analogously to Method D, 0.100 g of benzyl 3-hydroxy-4-(4-phenoxyphenyl)piperidine-1-carboxylate and 0.0753 g of 6-chloromethyl-4-(3-methoxypropyl)-4H-benzo[1,4]oxazin-3-one are reacted. The title compound is obtained as a colourless resin. Rf=0.31 (1:1 EtOAc-heptane); Rt=5.74.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:8]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=2)[C:9](=[O:11])[CH3:10])[CH:5]=[CH:6][CH:7]=1.[CH3:20][N:21](C)C=O>[C-]#N.[Zn+2].[C-]#N>[Cl:19][C:16]1[CH:17]=[CH:18][C:13]([CH2:12][CH:8]([C:4]2[CH:3]=[C:2]([CH:7]=[CH:6][CH:5]=2)[C:20]#[N:21])[C:9](=[O:11])[CH3:10])=[CH:14][CH:15]=1
Reactant: CC(=O)C(Cc1ccc(Cl)cc1)c1cccc(Br)c1
Reactant: CN(C)C=O
Agent: [C-]#N
Agent: [Zn+2]
Product: CC(=O)C(Cc1ccc(Cl)cc1)c1cccc(C#N)c1
Temperature: 56 °C
Reaction time: 4.5 h

Procedure:
A 4-neck 12 L flask equipped with a mechanical stirrer, thermocouple, nitrogen inlet, and gas adapter connected to a bubbler was charged with 3-(3-bromophenyl)-4-(4-chlorophenyl)butan-2-one, zinc cyanide (201 g), and dimethylformamide 4.0 L. Nitrogen gas was bubbled through the suspension for 30 min at room temperature and for 1 h at 56° C. using a heating mantle. The bromoketone/Zn(CN)2 slurry (at 56° C.) was added to the catalyst solution (at 56° C.). After the transfer was complete, the reaction mixture was stirred at 56° C. for 4.5 h under N2. The resulting suspension was cooled in an ice bath, and 30% aqueous ammonium hydroxide (971 mL) was added over 5 min, keeping the temperature below 30° C. The suspension was warmed to room temperature, stirred for 60 min, and then filtered through a pad of SOLKA FLOC eluting with toluene (5 L). The filtrate was added into an extractor containing 20% aqueous ammonium hydroxide (6.9 L) and 5 L of toluene. The biphasic mixture was stirred at room temperature for 15 min and then separated. The organic layer was washed with 7 L of brine (1:1 saturated NaCl:Water), then 7 L of water. The organic phase was transferred to a 12 L 4 neck flask equipped with an overhead stirrer, thermocouple, mechanical stirrer, and connected to a batch concentrator. The batch was concentrated under vacuum at 15-38° C. to a volume of 1.5 L, and then heptane (850 mL) was added.
Reaction SMILES: [C:1]([C:4]1[C:9](=[O:10])[C:8]([O:11][CH3:12])=[CH:7][N:6]([C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH:23]=[CH:22][CH:21]=[N:20]3)=[CH:15][C:14]=2[O:24][CH3:25])[N:5]=1)(=[O:3])[CH3:2].CO[CH:28](OC)[N:29]([CH3:31])[CH3:30]>C(#N)C>[CH3:28][N:29]([CH3:31])[CH:30]=[CH:2][C:1]([C:4]1[C:9](=[O:10])[C:8]([O:11][CH3:12])=[CH:7][N:6]([C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH:23]=[CH:22][CH:21]=[N:20]3)=[CH:15][C:14]=2[O:24][CH3:25])[N:5]=1)=[O:3]
Reactant: COc1cc(-n2cccn2)ccc1-n1cc(OC)c(=O)c(C(C)=O)n1
Reactant: COC(OC)N(C)C
Solvent: CC#N
Product: COc1cc(-n2cccn2)ccc1-n1cc(OC)c(=O)c(C(=O)C=CN(C)C)n1

Procedure:
A mixture of 3-acetyl-5-methoxy-1-[2-methoxy-4-(1H-pyrazol-1-yl)phenyl]pyridazin-4(1H)-one (264 mg), N,N-dimethylformamide dimethyl acetal (1.5 mL) and acetonitrile (1.5 mL) was heated under reflux for 3 hr. The reaction mixture was concentrated under reduced pressure, and the residue was crystallized from ethanol to give the title compound (274 mg).