Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CCCCCCCCCCCCCCC.C[OH:17].[C:18]([N:21]1[CH2:25][CH2:24][CH:23]=[CH:22]1)(=[O:20])[CH3:19].[O:26]1[CH2:30]CC[CH2:27]1>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:27][O:26][C:30](=[O:17])[C@@H:22]1[CH2:23][CH2:24][CH2:25][N:21]1[C:18](=[O:20])[CH3:19]
Reactant: CO
Reactant: C1CCOC1
Reactant: CC(=O)N1C=CCC1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: CCCCCCCCCCCCCCC
Product: COC(=O)[C@@H]1CCCN1C(C)=O
Temperature: 100 °C
Reaction time: 18 h
Yield: 18.5 %

Procedure:
A 70 mL stainless steel high pressure reactor having a Pyrex glass liner nd a magnetic stir bar was charged with 5 mL of tetrahydrofuran, 0.5 mmol of n-pentadecane internal standard, 0.5 mmol of CH3OH, 45.8 mg of (PPh3)2PdCl2, and 53.3 mg of N-acetyl-2-pyrroline. The reactor was pressurized with 700 psi of CO and 300 psi of H2 at room temperature, and the reaction mixture was stirred at 100° C. for 18 hours. Thereafter, the reactor was cooled to room temperature and vented to atmospheric pressure. The product mixture was analyzed by gas chromatography, and the analysis indicated 99.0% conversion of N-acetyl-2-pyrroline. The reactor was pressurized with 700 psi of CO and 300 psi of H2 at room temperature, and the reaction mixture was stirred at 100° C. for 18 hours. Thereafter, the reactor was cooled to room temperature and vented to atmospheric pressure. The product mixture was analyzed by gas chromatography, and the analysis indicated 99.0% conversion of N-acetyl-2-pyrroline and 18.5% yield of N-acetylproline methyl ester.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[NH:9][C:10]1[N:11]=[CH:12][C:13]2[CH:19]=[C:18]([C:20]3[C:25]([Cl:26])=[C:24]([O:27][CH3:28])[CH:23]=[C:22]([O:29][CH3:30])[C:21]=3[Cl:31])[C:17](=[O:32])[N:16]([CH3:33])[C:14]=2[N:15]=1.[C:34](Cl)(=[O:37])[CH:35]=[CH2:36]>C(Cl)Cl>[Cl:26][C:25]1[C:24]([O:27][CH3:28])=[CH:23][C:22]([O:29][CH3:30])=[C:21]([Cl:31])[C:20]=1[C:18]1[C:17](=[O:32])[N:16]([CH3:33])[C:14]2[N:15]=[C:10]([NH:9][C:3]3[C:4]([CH3:8])=[CH:5][CH:6]=[CH:7][C:2]=3[NH:1][C:34](=[O:37])[CH:35]=[CH2:36])[N:11]=[CH:12][C:13]=2[CH:19]=1
Reactant: C=CC(=O)Cl
Reactant: COc1cc(OC)c(Cl)c(-c2cc3cnc(Nc4c(C)cccc4N)nc3n(C)c2=O)c1Cl
Solvent: ClCCl
Product: C=CC(=O)Nc1cccc(C)c1Nc1ncc2cc(-c3c(Cl)c(OC)cc(OC)c3Cl)c(=O)n(C)c2n1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
2-(2-amino-6-methylphenylamino)-6-(2,6-dichloro-3,5-dimethoxyphenyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one (11) was taken up in DCM (2 ml) and cooled to 0° C., followed by addition of acryloyl chloride (0.010 mL, 0.13 mmol). The reaction was allowed to warm to room temperature and stirred overnight. The mixture was loaded directly onto silica gel and purified by flash chromatography using 0-100% EtOAc/Hexanes gradient to provide the product, N-(2-((6-(2,6-dichloro-3,5-dimethoxyphenyl)-8-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)-3-methylphenyl)acrylamide (Compound E). The product was obtained as an off-white solid (10 mg; 19% yield). MS (ES+) C26H23Cl2N5O4, 540 [M+H]+.
Reaction SMILES: C[Al](C)C.[CH2:5]([O:7][C:8]([C:10]1[C:11]([I:20])=[C:12]([S:16]([NH2:19])(=[O:18])=[O:17])[CH:13]=[CH:14][CH:15]=1)=[O:9])[CH3:6].[CH3:21][C:22]1[N:27]=[C:26]([O:28][CH3:29])[N:25]=[C:24]([NH:30][C:31](=O)[O:32]C)[N:23]=1.Cl>CCCCCC.ClCCl>[I:20][C:11]1[C:12]([S:16]([NH:19][C:31]([NH:30][C:24]2[N:25]=[C:26]([O:28][CH3:29])[N:27]=[C:22]([CH3:21])[N:23]=2)=[O:32])(=[O:18])=[O:17])=[CH:13][CH:14]=[CH:15][C:10]=1[C:8]([O:7][CH2:5][CH3:6])=[O:9]
Reactant: COC(=O)Nc1nc(C)nc(OC)n1
Reactant: CCOC(=O)c1cccc(S(N)(=O)=O)c1I
Agent: C[Al](C)C
Agent: Cl
Solvent: ClCCl
Solvent: CCCCCC
Product: CCOC(=O)c1cccc(S(=O)(=O)NC(=O)Nc2nc(C)nc(OC)n2)c1I
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 32.2 %

Procedure:
14 mmol of trimethylaluminum (7 ml of a 2M solution in hexane) are added dropwise under a nitrogen protective atmosphere to a suspension of 3.6 g of 3-ethoxycarbonyl-2-iodobenzenesulfonamide in 100 ml of absolute dichloromethane. The mixture is stirred at room temperature for 30 minutes, and 2.2 g of O-methyl (4-methyl-6-methoxy-1,3,5-triazin-2-yl)carbamate in 25 ml of dichloromethane are then added, and the mixture is refluxed for 13 hours. The solution is cooled to room temperature, 25 ml of 2N hydrochloric acid are added dropwise with ice-cooling, and the hydrochloric acid phase is extracted twice using dichloromethane. The organic phase is concentrated in vacuo, and the residue is treated with acetone and 100 ml of 10% aqueous sodium acetate solution. The mixture is stirred for 3 hours and then filtered off with suction, followed by a washing step with diethyl ether, the aqueous phase is brought to pH 2-3 using concentrated hydrochloric acid and stirred for 15 minutes, and the product is filtered off with suction. After drying in vacuo at 50° C., 1.7 g of ethyl 2-iodo-3-[[[[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)amino]carbonyl]amino]sulfonyl]-benzoate of m.p. 177°-9° C. are obtained.
Reaction SMILES: [CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([NH:14][C:15]3([C:21]#[CH:22])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]3)=[C:10]([CH3:13])[N:11]=2)[C:6](=[O:23])[C:5]([C:24]([O:26]CC)=[O:25])=[CH:4]1)[CH3:2].[OH-].[Na+].C(#N)C>O1CCOCC1.O>[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([NH:14][C:15]3([C:21]#[CH:22])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]3)=[C:10]([CH3:13])[N:11]=2)[C:6](=[O:23])[C:5]([C:24]([OH:26])=[O:25])=[CH:4]1)[CH3:2]
Reactant: C#CC1(Nc2cc3c(=O)c(C(=O)OCC)cn(CC)c3nc2C)CCCCC1
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: O
Solvent: CC#N
Product: C#CC1(Nc2cc3c(=O)c(C(=O)O)cn(CC)c3nc2C)CCCCC1
Temperature: 60 °C

Procedure:
Ethyl 1-ethyl-6-(1-ethynylcyclohexylamino)-7-methyl-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylate (10 mg) was dissolved in 5 ml of dioxane, 2.5 equivalents of a 1 N NaOH solution were added, and the mixture was heated at 60° C. for 4 h. Removal of the solvent in vacuo was followed by chromatography on an HPLC system to purify the product. The pure product was isolated from the reaction solution by chromatography on an HPLC system. This entailed use of a Merck Purospher-RP18 column and an acetonitrile:water mixture as eluent; the initial acetonitrile content was 15% and rose to 95% over the course of 20 minutes.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([S:9][C:10]2[N:14]([CH2:15][O:16][CH2:17][CH2:18][OH:19])[C:13]([CH3:20])=[N:12][C:11]=2[CH:21]([CH3:23])[CH3:22])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[C:24]([O:30][CH2:31]I)(=[O:29])[C:25]([CH3:28])([CH3:27])[CH3:26]>>[CH3:26][C:25]([CH3:28])([CH3:27])[C:24]([O:30][CH2:31][O:19][CH2:18][CH2:17][O:16][CH2:15][N:14]1[C:10]([S:9][C:4]2[CH:5]=[C:6]([Cl:8])[CH:7]=[C:2]([Cl:1])[CH:3]=2)=[C:11]([CH:21]([CH3:23])[CH3:22])[N:12]=[C:13]1[CH3:20])=[O:29]
Reactant: CC(C)(C)C(=O)OCI
Reactant: Cc1nc(C(C)C)c(Sc2cc(Cl)cc(Cl)c2)n1COCCO
Product: Cc1nc(C(C)C)c(Sc2cc(Cl)cc(Cl)c2)n1COCCOCOC(=O)C(C)(C)C
Yield: 32.3 %

Procedure:
The compound 8 (375 mg, 1 mmol) was alkylated with the pivaloyloxymethyl iodide (1.21 g, 5 mmol) under potassium carbonate (415 mg, 3 mmol) in the same manner as the example 61 to give the compound 77 (158 mg, 32%) as oil. Rf 0.26 (1:1 EtOAc - hexane).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH:4]1[O:10][CH2:9][CH2:8][N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:6][CH:5]1[C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=1.C(N(CC)CC)C.[CH3:33][O:34][CH2:35][C:36](Cl)=[O:37].O>C1COCC1>[Cl:25][C:20]1[CH:19]=[C:18]([CH:5]2[CH:4]([CH2:3][CH2:2][NH:1][C:36](=[O:37])[CH2:35][O:34][CH3:33])[O:10][CH2:9][CH2:8][N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:6]2)[CH:23]=[CH:22][C:21]=1[Cl:24]
Reactant: COCC(=O)Cl
Reactant: CC(C)(C)OC(=O)N1CCOC(CCN)C(c2ccc(Cl)c(Cl)c2)C1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Solvent: O
Product: COCC(=O)NCCC1OCCN(C(=O)OC(C)(C)C)CC1c1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of tert-butyl (6RS,7RS)-7-(2-aminoethyl)-6-(3,4-dichlorophenyl)-1,4-oxazepane-4-carboxylate (140 mg) obtained in Example 484, step A in THF (3.0 ml) were added triethylamine (0.150 ml) and methoxyacetyl chloride (0.066 ml) under ice-cooling, and the mixture was stirred at room temperature for 2 hr. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel chromatography (hexane/ethyl acetate) to give the title compound (157 mg).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[C:11]1[CH2:12][CH2:13][NH:14][CH2:15][CH:16]=1>[Pd].O1CCCC1>[OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:11]1[CH2:12][CH2:13][NH:14][CH2:15][CH2:16]1
Reactant: Oc1ccc2[nH]cc(C3=CCNCC3)c2c1
Agent: [Pd]
Solvent: C1CCOC1
Product: Oc1ccc2[nH]cc(C3CCNCC3)c2c1
Reaction time: 15 h
Yield: 95 %

Procedure:
Tetrahydrofuran (96 ml) was added to an argon degassed flask containing 4-(5-hydroxyindol-3-yl)-1,2,3,6-tetrahydropyridine (2.67 g, 7.64 mmol), [prepared as described in Step 1, above] and 10% Palladium on carbon (2.67 g). The reaction mixture was hydrogenated for 15 h at 60 psi on a parr apparatus. The reaction mixture was degassed, filtered through Celite and concentrated in vacuo to give 4-(5-hydroxyindol-3-yl)piperidine as a white solid (95%). This material was converted to 1-[4-(5-hydroxyindol-3-yl)-piperidine-1-sulfonyl]piperidine-2-(RS)-carboxylic acid (99%) by proceeding as described in Example 16, Step 2 above, by substituting 4-(5-fluoroindol-3-yl)piperidine and 2-(R)-methoxycarbonylpiperidine-1-sulfamoyl chloride with 4-(5-hydroxyindol-3-yl)piperidine and 2-(RS)- methoxycarbonylpiperidine-1-sulfamoyl chloride respectively.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:17]2[CH:21]=[N:20][N:19]=[C:18]2[CH2:22][N:23]2[C:27](=[O:28])[C:26]3=[CH:29][CH:30]=[CH:31][CH:32]=[C:25]3[C:24]2=[O:33])=[C:6]([CH:16]=1)[C:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[F:15])=[O:8].[Br:34]N1C(=O)CCC1=O>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:17]2[C:18]([CH2:22][N:23]3[C:27](=[O:28])[C:26]4=[CH:29][CH:30]=[CH:31][CH:32]=[C:25]4[C:24]3=[O:33])=[N:19][N:20]=[C:21]2[Br:34])=[C:6]([CH:16]=1)[C:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[F:15])=[O:8]
Reactant: O=C(c1ccccc1F)c1cc(Cl)ccc1-n1cnnc1CN1C(=O)c2ccccc2C1=O
Reactant: O=C1CCC(=O)N1Br
Product: O=C(c1ccccc1F)c1cc(Cl)ccc1-n1c(Br)nnc1CN1C(=O)c2ccccc2C1=O

Procedure:
Following the procedure of Example 1, 5-chloro-2-(3-phthalimidomethyl-4H-1,2,4-triazol-4-yl)-2'-fluorobenzophenone is reacted with N-bromosuccinimide to form 5-chloro-2-(3-bromo-5-phthalimidomethyl-4H-1,2,4-triazol-4-yl)-2'-fluorobenzophenone.
Reaction SMILES: [Br:1][C:2]1[C:10]([F:11])=[CH:9][C:5](C(O)=O)=[C:4]([NH:12][CH:13]([C:15]([OH:17])=O)[CH3:14])[CH:3]=1.[C:18]([O-:21])(=O)[CH3:19].[Na+].[C:23](OC(=O)C)(=[O:25])[CH3:24]>>[C:23]([O:17][C:15]1[C:5]2[C:4](=[CH:3][C:2]([Br:1])=[C:10]([F:11])[CH:9]=2)[N:12]([C:18](=[O:21])[CH3:19])[C:13]=1[CH3:14])(=[O:25])[CH3:24]
Reactant: CC(Nc1cc(Br)c(F)cc1C(=O)O)C(=O)O
Reactant: CC(=O)[O-]
Reactant: CC(=O)OC(C)=O
Agent: [Na+]
Product: CC(=O)Oc1c(C)n(C(C)=O)c2cc(Br)c(F)cc12
Temperature: 150 °C
Yield: 72 %

Procedure:
A mixture of 4-bromo-2-((1-carboxyethyl)amino)-5-fluorobenzoic acid (D86) (1.599 g, 5.22 mmol), sodium acetate (1.714 g, 20.90 mmol) and acetic anhydride (19.72 mL, 209 mmol) was heated at 150° C. for 30 min in a microwave. The mixture was evaporated in vacuo. The residue was diluted with DCM and poured into saturated NaHCO3 aq. (200 mL). The mixture extracted with DCM (30 mL×3). The organic layers were combined, washed with brine (100 mL), filtered through phase separator and evaporated in vacuo. The crude residue was purified by chromatography on silica, eluting with a gradient of 0-35% ethyl acetate in cyclohexane to give title compound (1.233 g). LCMS (A): m/z (M+H)+ 328/330, C13H11BrFNO3 requires 327/329 (acidic).
Reaction SMILES: [C:1]1(O)[CH:6]=[CH:5]C=[CH:3][CH:2]=1.B(F)(F)F.[CH3:12][CH2:13][O:14][CH2:15][CH3:16].O1CCOCC1>C(OCC)C>[O:14]1[C:15]2[C:6](=[CH:1][CH:2]=[CH:3][CH:16]=2)[CH2:5][CH2:12][CH2:13]1
Reactant: CCOCC
Reactant: Oc1ccccc1
Agent: FB(F)F
Solvent: C1COCCO1
Product: c1ccc2c(c1)CCCO2
Temperature: 25 °C
Reaction time: 0 h

Procedure:
To a solution of phenol 4 (0.01 mol) and a catalyst, preferably boron trifluoride diethyl etherate (0.016 mol) in an organic solvent, preferably dry dioxane (10 mL), Is added vinyl lactone 2 (0.016 mol) In an organic solvent, preferably dry dioxane (5.0 mL) over 1-60 minutes, preferably 60 minutes, at 0-150° C., preferably 110° C., under an inert gas. The reaction mixture is stirred for 0 to 8 hours, preferably 0 hours, at the selected temperature, cooled to room temperature, and diluted with an organic solvent, preferably diethyl ether (200 mL). The reaction mixture is then washed with water (100 mL, 2×50 mL), dried over sodium sulfate (Na2SO4), and solvent is removed under reduced pressure to afford a brown oily residue. The residue is dissolved in alcohol, preferably methanol (30 mL), and the alcohol is then removed under reduced pressure. The brown oily liquid or semisolid is further purified by chromatography, preferably on silica gel, to afford pure racemic chroman derivative 5.
Reaction SMILES: I[CH2:2][C:3]1([CH3:19])[O:18][C:6]2=[C:7]([CH3:17])[C:8]3[CH2:9][C:10]([CH3:16])([CH3:15])[NH:11][C:12]=3[C:13]([CH3:14])=[C:5]2[CH2:4]1.[CH2:20]1[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[CH2:24][CH2:23][NH:22][CH2:21]1.C(=O)([O-])[O-].[K+].[K+].[ClH:37].CO>CN(C)C(=O)C.CO.O>[ClH:37].[CH3:19][C:3]1([CH2:2][CH:24]2[CH2:25][CH2:30][C:29]3[CH:28]=[CH:27][CH:26]=[CH:20][C:21]=3[NH:22][CH2:23]2)[O:18][C:6]2=[C:7]([CH3:17])[C:8]3[CH2:9][C:10]([CH3:16])([CH3:15])[NH:11][C:12]=3[C:13]([CH3:14])=[C:5]2[CH2:4]1
Reactant: Cc1c2c(c(C)c3c1NC(C)(C)C3)OC(C)(CI)C2
Reactant: c1ccc2c(c1)CCNCC2
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: CC(=O)N(C)C
Solvent: O
Product: Cc1c2c(c(C)c3c1NC(C)(C)C3)OC(C)(CC1CCc3ccccc3NC1)C2
Temperature: 180 °C
Reaction time: 3.5 h
Yield: 45 %

Procedure:
A suspension of 3,5,6,7-tetrahydro-2-(iodomethyl)-2,4,6,6,8-pentamethyl-2H-furo[2,3-f]indole (520 mg, 1.40 mmol), 2,3,4,5-tetrahydro-1H-3-benzazepine (309 mg, 2.10 mmol) and potassium carbonate (387 mg, 2.80 mmol) in N,N-dimethylacetamide (3 ml) was stirred for 3.5 hours at 180° C. under nitrogen atmosphere. Water was added to the reaction mixture and the mixture was extracted twice with ethyl acetate. The organic layers were combined, washed with water and saturated brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was subjected to basic silica gel column chromatography (hexane:ethyl acetate=5:1) to obtain an oil. The oil was dissolved in methanol and combined with 10% hydrogen chloride-methanol solution (1.5 ml), and concentrated under reduced pressure. The residue was crystallized from methanol-diisopropyl ether to obtain 269 mg of the title compound.
Reaction SMILES: O1CCC[CH2:2]1.[C:6]([C:9]1[C:17]2[C:16](=[O:18])[NH:15][N:14]=[CH:13][C:12]=2[N:11]([CH2:19][O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:10]=1)(=[O:8])[CH3:7].C[Mg]Br.[Cl-].[NH4+]>C(OCC)C>[CH2:21]([O:20][CH2:19][N:11]1[C:12]2[CH:13]=[N:14][NH:15][C:16](=[O:18])[C:17]=2[C:9]([C:6]([OH:8])([CH3:2])[CH3:7])=[CH:10]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: CC(=O)c1cn(COCc2ccccc2)c2cn[nH]c(=O)c12
Reactant: C1CCOC1
Agent: C[Mg]Br
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOCC
Product: CC(C)(O)c1cn(COCc2ccccc2)c2cn[nH]c(=O)c12
Temperature: 25 °C
Reaction time: 3 h
Yield: 93 %

Procedure:
To 87 ml of tetrahydrofuran solution containing 1.69 g (5.7 mmol) of 3-acetyl-1-benzyloxymethyl-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one obtained in Reference example 21-(c) was added dropwise 7.5 ml of 3M methyl magnesium bromide in diethyl ether solution under ice-cooling, and the mixture was stirred at room temperature for 3 hours. After completion of the reaction, a saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer after separation was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained residue was applied to silica gel column chromatography (Eluent; toluene:ethyl acetate=7:3 (V/V)), and the fractions containing the desired compound were concentrated under reduced pressure to obtain 1.66 g of the title compound as a white solid. (Yield: 93%)
Reaction SMILES: Br[CH2:2][C:3]1[O:7][N:6]=[CH:5][CH:4]=1.[CH2:8]([NH2:10])[CH3:9]>C1COCC1>[CH2:8]([NH:10][CH2:2][C:3]1[O:7][N:6]=[CH:5][CH:4]=1)[CH3:9]
Reactant: BrCc1ccno1
Reactant: CCN
Solvent: C1CCOC1
Product: CCNCc1ccno1

Procedure:
prepared by reaction of the 5-bromomethyl-isoxazole (Deshong P. et al J. Org. Chem. 1988, 53, 7, 1356-1364) with 2M ethylamine in THF.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[Si:11]([O:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25]([CH3:29])([CH3:28])[CH2:26][OH:27])([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12].C(N(CC)CC)C>ClCCl>[C:14]([Si:11]([CH3:13])([CH3:12])[O:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25]([CH3:29])([CH3:28])[CH:26]=[O:27])([CH3:17])([CH3:16])[CH3:15]
Reactant: CC(C)(CO)CCCCCCO[Si](C)(C)C(C)(C)C
Agent: O=C(Cl)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Solvent: ClCCl
Product: CC(C)(C=O)CCCCCCO[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Oxalyl Chloride (5.9 mL) was added at −70° C. to a solution of dimethylsulfoxide (4.98 mL) in dry dichloromethane (60 mL) and the mixture stirred for 1 hour. 8-(tert-Butyldimethylsilyloxy)-2,2-dimethyloctan-1-ol (example 279, step b) (10.11 g), dissolved in dichloromethane (20 mL), was added dropwise and the mixture allowed to stir for 1 hour. Triethylamine (19.4 mL) was then added and stirring continued for 1 hour. The cooling bath was removed and the mixture allowed to warm to room temperature, at which point DCM (15 mL) was added. 1N HCl was added dropwise to dissolve the salts present in the reaction mixture and the layers separated. The aqueous layer was extracted with DCM (2×250 mL) then the combined organic layers were washed with saturated aqueous sodium carbonate (250 mL), dried over magnesium sulfate, filtered and concentrated under vacuum to give an orange liquid. The residue was filtered through a short plug of silica using diethyl ether as the eluent to afford 8-(tert-butyl-dimethyl-silanyloxy)-2,2-dimethyl-octanal as a yellow liquid which was used without further purification.
Reaction SMILES: Cl.[NH2:2][NH:3][C:4]([NH2:6])=[O:5].O.[OH:8][CH:9]1[CH2:13][C:12](=O)[C:11]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21]([OH:23])=[O:22])=[C:10]1[CH:24]=[CH:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>N1C=CC=CC=1.C(O)C>[OH:8][CH:9]1[CH2:13][C:12](=[N:2][NH:3][C:4]([NH2:6])=[O:5])[C:11]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21]([OH:23])=[O:22])=[C:10]1[CH:24]=[CH:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1
Reactant: NNC(N)=O
Reactant: O=C(O)CCCCCCC1=C(C=Cc2ccccc2)C(O)CC1=O
Agent: Cl
Solvent: c1ccncc1
Solvent: O
Solvent: CCO
Product: NC(=O)NN=C1CC(O)C(C=Cc2ccccc2)=C1CCCCCCC(=O)O
Reaction time: 16 h

Procedure:
A solution of 2 parts of semicarbazide hydrochloride in 3 parts of water is combined with a solution of 2 parts of 3-hydroxy-5-oxo-2-styrylcyclopent-1-eneheptanoic acid dissolved in 2.95 parts of pyridine and 15.8 parts of ethanol. The resulting solution is allowed to stand for about 16 hours at room temperature. Then the crystalline precipitate is filtered, washed with an aqueous 80% ethanol solution and then with water. After drying, the material is recrystallized from boiling isopropanol to afford pale yellow crystals of 3-hydroxy-5-semicarbazono-2-styrylcyclopent-1-eneheptanoic acid, melting at about 208°-210°, and displaying, in potassium bromide, an infrared absorption spectrum with maxima at about 3480, 1720, 1693 and 1586 reciprocal centimeters. That compound further displays, in methanol, an absorption band in the ultraviolet spectrum at about 355 millimicrons with a molecular extinction coefficient of about 54,000 and is characterized by the following structural formula ##SPC20##
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][N:10]=[CH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:5][CH:4]=1.[Cl:18][C:19]1[C:28]2[C:23](=[CH:24][C:25]([Cl:29])=[CH:26][CH:27]=2)[N:22]=[CH:21][N:20]=1>>[ClH:18].[Cl:29][C:25]1[CH:24]=[C:23]2[C:28]([C:19]([N:9]([C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=3)[N:10]=[CH:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[N:20][CH:21]=[N:22]2)=[CH:27][CH:26]=1
Reactant: Clc1ccc2c(Cl)ncnc2c1
Reactant: COc1ccc(NN=Cc2ccccc2)cc1
Product: COc1ccc(N(N=Cc2ccccc2)c2ncnc3cc(Cl)ccc23)cc1
Product: Cl

Procedure:
The starting materials were obtained as described in Example 18 for acetaldehyde N1 -(7-chloroquinazolin-4-yl)-p-methoxyphenylhydrazone hydrochloride. Thus, from acetone p-methoxyphenylhydrazone and 4,7-dichloroquinazoline, there was obtained acetone N1 -(7-chloroquinazolin-4-yl)-p-methoxyphenylhydrazone hydrochloride [this compound was unstable; the free base was shown to be pure by TLC (system C) when first isolated, but it decomposed on keeping] and from benzaldehyde p-methoxyphenylhydrazone and 4,7-dichloroquinazoline, there was obtained benzaldehyde N1 -(7-chloroquinazolin-4-yl)-p-methoxyphenylhydrazone hydrochloride, m.p. 227°-228° C.
Reaction SMILES: [NH2:1][C:2]1[C:7]([NH2:8])=[CH:6][CH:5]=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].[Br:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]([C:21]([C:23]2[CH:28]=[CH:27][C:26]([Br:29])=[CH:25][CH:24]=2)=O)=O)=[CH:15][CH:14]=1>C(O)(=O)C.CO>[Br:12][C:13]1[CH:14]=[CH:15][C:16]([C:19]2[C:21]([C:23]3[CH:24]=[CH:25][C:26]([Br:29])=[CH:27][CH:28]=3)=[N:1][C:2]3[C:7](=[CH:6][CH:5]=[CH:4][C:3]=3[N+:9]([O-:11])=[O:10])[N:8]=2)=[CH:17][CH:18]=1
Reactant: O=C(C(=O)c1ccc(Br)cc1)c1ccc(Br)cc1
Reactant: Nc1cccc([N+](=O)[O-])c1N
Solvent: CC(=O)O
Solvent: CO
Product: O=[N+]([O-])c1cccc2nc(-c3ccc(Br)cc3)c(-c3ccc(Br)cc3)nc12

Procedure:
1.53 g (10 mmol) of 2,3-diaminonitrobenzene and 3.68 g (10 mmol) of 4,4′-dibromobenzil were dissolved in 80 g of a mixed solvent of acetic acid and methanol (1:1) and reacted at a reaction temperature of 70° C. for 30 hours. After completion of the reaction, the solvent was removed and a reaction product was extracted by means of a silica gel.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([Br:8])[CH:5]=[C:4]([Br:9])[C:3]=1[OH:10].Cl[CH2:12][C:13]([CH3:15])=[O:14].C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>O>[Br:1][C:2]1[CH:7]=[C:6]([Br:8])[CH:5]=[C:4]([Br:9])[C:3]=1[O:10][CH2:12][C:13](=[O:14])[CH3:15]
Reactant: Oc1c(Br)cc(Br)cc1Br
Reactant: CC(=O)CCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(=O)COc1c(Br)cc(Br)cc1Br
Temperature: 27 °C
Yield: 96.5 %

Procedure:
A mixture of 5 g 2,4,6-tribromophenol (15 mmol), 1.4 g 1-chloroacetone (15 mmol), 4.16 g anhydrous potassium carbonate (30 mmol) and 20 ml DMF is stirred at 27° C. Completion of the reaction is confirmed by TLC. The reaction mass is diluted with water and extracted with ethylacetate The organic layer is washed with water and brine, dried over anhydrous sodium sulphate and concentrated to obtain 5.6 g 1-(2,4,6-tribromo-phenoxy)-propan-2-one (97%).