Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[F:3][C:4]1[CH:20]=[CH:19][C:7]([NH:8][S:9]([C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=2)(=[O:11])=[O:10])=[C:6]([N+:21]([O-:23])=[O:22])[CH:5]=1.[CH2:24](I)[CH3:25].O>CN(C=O)C>[CH2:24]([N:8]([S:9]([C:12]1[CH:13]=[CH:14][C:15]([CH3:18])=[CH:16][CH:17]=1)(=[O:11])=[O:10])[C:7]1[CH:19]=[CH:20][C:4]([F:3])=[CH:5][C:6]=1[N+:21]([O-:23])=[O:22])[CH3:25]
Reactant: Cc1ccc(S(=O)(=O)Nc2ccc(F)cc2[N+](=O)[O-])cc1
Reactant: CCI
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCN(c1ccc(F)cc1[N+](=O)[O-])S(=O)(=O)c1ccc(C)cc1
Temperature: 25 °C
Yield: 73.9 %

Procedure:
To a suspension of sodium hydride (60%, 0.05 g (1.25 mmol)) in DMF (2.0 ml), 4′-fluoro-2′-nitro-p-toluenesulfonanilide (0.31 g (1.00 mmol)) was added with stirring at room temperature. To the resulting mixture, after 15 minutes' stirring at room temperature, ethyl iodide (0.30 ml (3.75 mmol)) was added dropwise. After 30 minutes' heating at 100° C. with stirring, the reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with water and saturated sodium chloride solution, successively, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. Diisopropyl ether was added to the residue and the solid separated was filtered and washed to give 0.25 g (74%) of the title compound as pale yellow crystals.
Reaction SMILES: [CH2:1]([O:8][C:9](Cl)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:12][C@H:13]([C:17]([OH:19])=[O:18])[C@H:14]([CH3:16])[OH:15].C([O-])(O)=O.[Na+]>O>[C:9]([NH:12][C@H:13]([C:17]([OH:19])=[O:18])[C@H:14]([CH3:16])[OH:15])([O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:10]
Reactant: C[C@H](O)[C@H](N)C(=O)O
Reactant: O=C(Cl)OCc1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Product: C[C@H](O)[C@H](NC(=O)OCc1ccccc1)C(=O)O
Reaction time: 3 h
Yield: 60.2 %

Procedure:
Benzylchloroformate (0.35 ml; 2.3 mmol) was added to a mixture of L-allothreonine (0.25 g; 2.1 mmol) and NaHCO3 (435 mg; 5.18 mmol) in 2.5 ml of H2O at RT. After 3 h, the reaction mixture was partitioned between Et2O and H2O. The aqueous layer was washed with Et2O, acidified to pH<2 with 6N HCl, and extracted with CH2Cl2. The organic layer was dried (MgSO4) and concentrated to afford 320 mg (63%) of Cbz-L-allothreonine. ##STR398##
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[CH2:9][S:10]([C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17](=[O:22])[CH2:16]2)(=[O:12])=[O:11].[CH:23]([C:25]1[NH:29][C:28]([CH3:30])=[C:27]([C:31]([OH:33])=[O:32])[C:26]=1[CH3:34])=O>>[Cl:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=1[CH2:9][S:10]([C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17](=[O:22])/[C:16]/2=[CH:23]\[C:25]1[NH:29][C:28]([CH3:30])=[C:27]([C:31]([OH:33])=[O:32])[C:26]=1[CH3:34])(=[O:12])=[O:11]
Reactant: O=C1Cc2cc(S(=O)(=O)Cc3c(Cl)cccc3Cl)ccc2N1
Reactant: Cc1[nH]c(C=O)c(C)c1C(=O)O
Product: Cc1[nH]c(/C=C2\C(=O)Nc3ccc(S(=O)(=O)Cc4c(Cl)cccc4Cl)cc32)c(C)c1C(=O)O

Procedure:
5-(2,6-Dichloro-phenylmethanesulfonyl)-1,3-dihydro-indol-2-one was condensed with 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid using the general condensation method to give 5-[5-(2,6-dichloro-phenylmethanesulfonyl)-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid. This was then coupled with cyclopropyl-piperidin-4-yl-amine TFA salt (prepared as in lit. procedure by H. C. Hansen et al. Bioorg. Med. Chem. Lett. 10, 2000, 2435-2439.) using the general amidation procedure to give an orange solid.
Reaction SMILES: [N+](C1[CH:17]=[C:16]2[C:11]([N:12]=[CH:13][CH:14]=[CH:15]2)=[C:10]2[C:5]=1[CH:6]=[CH:7][CH:8]=[N:9]2)([O-])=O.C([O-])(=O)C([O-])=[O:20].[K+].[K+].[OH-].[Na+].O>C(OCC)(=O)C>[N:12]1[CH:13]=[CH:14][CH:15]=[C:16]2[C:17](=[O:20])[C:5]3[C:10](=[N:9][CH:8]=[CH:7][CH:6]=3)[C:11]=12
Reactant: O=C([O-])C(=O)[O-]
Reactant: O=[N+]([O-])c1cc2cccnc2c2ncccc12
Agent: [K+]
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: O
Product: O=C1c2cccnc2-c2ncccc21
Temperature: 100 °C
Reaction time: 2 h
Yield: 53.8 %

Procedure:
To a 1 L one-necked flask was added a mixture of 30 g (0.13 mol, 68%) 5-nitro-1,10-phenanthroline, 51 g (0.61 mol) potassium oxalate, 12.5% NaOH(aq) 150 ml and 450 ml water. The mixture was then heated to reflux (100° C.) and stirred for 2 hours. After completion of the reaction, the reaction mixture was cooled to room temperature. The reaction mixture was added with 1 L ethyl acetate, stirred for 30 minutes, and filtered to collect the filtrate. The residual solids were added into 300 ml ethyl acetate, stirred for 30 minutes and filtered to collect the filtrate. The combined filtrates were extracted to separate the organic layer, dehydrated by MgSO4, concentrated, and recrystallized from 200 ml methanol, so as to obtain light yellow solids cyclopenta[2,1-b;3,4-b′]dipyridin-5-one 13.3 g (0.07 mol, yield 54%).
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:14][CH:13]([C:21](O)=[O:22])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>O1CCCC1.CO>[CH2:1]([O:8][C:9]([N:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:14][CH:13]([CH2:21][OH:22])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(O)C1Cc2ccccc2N(C(=O)OCc2ccccc2)C1
Solvent: C1CCOC1
Solvent: CO
Product: O=C(OCc1ccccc1)N1CC(CO)Cc2ccccc21

Procedure:
14.0 g of N-benzyloxycarbonyl-3(R,S)-carboxy-1,2,3,4-tetrahydroquinoline are stirred in 400 ml of tetrahydrofuran with 9.0 ml of 10M borane-dimethylsulfide complex at 25° C. for 16 h. The reaction mixture is diluted several times with methanol and evaporated. The crude product is recrystallized from ethyl acetate/hexane: mp 62°-4° C.; Rf (X)=0.50; FAB-MS: (M+H)+ =298; anal. calc. for C18H19NO3 : C 72.71%, H 6.44%, N 4.71%; found C 72.84%, H 6.35%, N 4.75%.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:4]=1[S:10]([NH:13][C:14]1[C:23]([C:24]([O:26][CH3:27])=[O:25])=[C:22]2[C:17]([CH:18]3[CH2:28][CH:19]3[CH2:20][O:21]2)=[CH:16][CH:15]=1)(=[O:12])=[O:11].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:53]([N:55]1[CH2:59][CH2:58][CH2:57][C@H:56]1[C:60](O)=[O:61])[CH3:54].C(N(C(C)C)CC)(C)C>CN(C=O)C>[CH2:53]([N:55]1[CH2:59][CH2:58][CH2:57][C@H:56]1[C:60]([CH:2]([NH2:1])[C:3]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:4]=1[S:10]([NH:13][C:14]1[C:23]([C:24]([O:26][CH3:27])=[O:25])=[C:22]2[C:17]([CH:18]3[CH2:28][CH:19]3[CH2:20][O:21]2)=[CH:16][CH:15]=1)(=[O:11])=[O:12])=[O:61])[CH3:54]
Reactant: CCN1CCC[C@H]1C(=O)O
Reactant: COC(=O)c1c(NS(=O)(=O)c2ccc(F)cc2CN)ccc2c1OCC1CC21
Agent: CN(C)C(On1nnc2cccnc21)=[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: CCN1CCC[C@H]1C(=O)C(N)c1cc(F)ccc1S(=O)(=O)Nc1ccc2c(c1C(=O)OC)OCC1CC21
Temperature: 25 °C
Reaction time: 2 h
Yield: 75 %

Procedure:
A mixture of methyl (1aRS,7bSR)-5-(2-aminomethyl-4-fluorobenzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 102, 0.515 g), HATU (0.483 g), (S)—N-ethylpyrrolidine-2-carboxylic acid (Intermediate 106, 0.182 g) and N,N-di-isopropyl-N-ethylamine (0.328 g) in dry DMF (25 mL) was stirred at room temperature for 2 hours. The mixture was concentrated under vacuum and the residue was diluted with water and extracted with ethyl acetate, washed with water, dried (MgSO4) and filtered. The filtrate was evaporated to dryness and the residue was purified by chromatography on silica, eluting with a mixture of methanol and DCM, with a gradient of 1-2% to give methyl (1aRS,7bSR)-5-{2-[((S)-1-ethylpyrrolidin-2-yl)cabonyl-aminomethyl]-4-fluorobenzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate (0.505 g) as a glassy solid.
Reaction SMILES: C[O-].[K+].[CH3:4][N:5]1[C:9]([O:10][C:11]2[CH:16]=[C:15]([O:17][C:18]3N(C)N=C(C(F)(F)F)C=3)[CH:14]=[C:13]([O:28][C:29]3[N:33]([CH3:34])[N:32]=[C:31]([C:35]([F:38])([F:37])[F:36])[CH:30]=3)[N:12]=2)=[CH:8][C:7]([C:39]([F:42])([F:41])[F:40])=[N:6]1>CO>[CH3:34][N:33]1[C:29]([O:28][C:13]2[CH:14]=[C:15]([O:17][CH3:18])[CH:16]=[C:11]([O:10][C:9]3[N:5]([CH3:4])[N:6]=[C:7]([C:39]([F:40])([F:41])[F:42])[CH:8]=3)[N:12]=2)=[CH:30][C:31]([C:35]([F:38])([F:36])[F:37])=[N:32]1
Reactant: Cn1nc(C(F)(F)F)cc1Oc1cc(Oc2cc(C(F)(F)F)nn2C)nc(Oc2cc(C(F)(F)F)nn2C)c1
Agent: C[O-]
Agent: [K+]
Solvent: CO
Product: COc1cc(Oc2cc(C(F)(F)F)nn2C)nc(Oc2cc(C(F)(F)F)nn2C)c1
Reaction time: 2 h
Yield: 43.4 %

Procedure:
A 3 ml aliquot of a 25 % solution of potassium methylate (10 mmol) in dry methanol is added to a solution of 5.7 g (10 mmol) 2,4,6-tris-(1-methyl-3-trifluoromethylpyrazol-5-yloxy)pyridine in 20 ml anhydrous methanol. After 2 hours at ambient temperature, the reaction mixture is heated to reflux. The solvent is removed under reduced pressure and ethyl acetate is added to the residue. The mixture is washed with a 2 N sodium hydroxide solution. After drying and filtration of the organic layer, the solvents are removed and the residue is washed with diisopropyl ether and pentane. Colorless crystals (1.9 g, 43 % yield) of melting point 107° C. are obtained.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][CH:15]=1)[C:12]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[N:6]([S:16]([C:19]1[CH:24]=[CH:23][C:22]([O:25]C)=[CH:21][CH:20]=1)(=[O:18])=[O:17])[CH:5]2[CH3:27].C1CCCCC=1.B(Br)(Br)Br.ClCCl>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][CH:15]=1)[C:12]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[N:6]([S:16]([C:19]1[CH:20]=[CH:21][C:22]([OH:25])=[CH:23][CH:24]=1)(=[O:18])=[O:17])[CH:5]2[CH3:27]
Reactant: COc1ccc(S(=O)(=O)N2c3ccccc3-c3ccc(Cl)cc3C2C)cc1
Agent: BrB(Br)Br
Solvent: C1=CCCCC1
Solvent: ClCCl
Product: CC1c2cc(Cl)ccc2-c2ccccc2N1S(=O)(=O)c1ccc(O)cc1
Yield: 42 %

Procedure:
The title compound was prepared from 8-chloro-5-[(4-methoxyphenyl)sulfonyl]-6-methyl-5,6-dihydrophenanthridine (0.6 g, 1.50 mmol), cyclohexene (0.304 mL, 3.75 mmol), and 1.0 M boron tribromide in dichloromethane (9.0 mL, 9.0 mmol) according to the procedure and in the same manner as described in Example 1, step b. The crude product was purified by flash column chromatography on silica gel, eluting with dichloromethane to yield 4-[(8-chloro-6-methylphenanthridin-5(6H)-yl)sulfonyl]phenol (0.24 g, 0.63 mmol, 42%) as a white solid, m.p. 176-178° C.;
Reaction SMILES: Cl.[CH3:2][N:3]([CH3:21])[CH2:4][CH2:5][N:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([CH3:16])[N:14]=2)[C:9](=[O:17])[C:8]([C:18]([OH:20])=O)=[CH:7]1.[NH2:22][C:23]1[NH:27][N:26]=[N:25][N:24]=1>CN(C)C=O>[CH3:21][N:3]([CH3:2])[CH2:4][CH2:5][N:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([CH3:16])[N:14]=2)[C:9](=[O:17])[C:8]([C:18]([NH:22][C:23]2[NH:27][N:26]=[N:25][N:24]=2)=[O:20])=[CH:7]1
Reactant: Nc1nnn[nH]1
Reactant: Cc1ccc2c(=O)c(C(=O)O)cn(CCN(C)C)c2n1
Agent: Cl
Solvent: CN(C)C=O
Product: Cc1ccc2c(=O)c(C(=O)Nc3nnn[nH]3)cn(CCN(C)C)c2n1
Reaction time: 36 h

Procedure:
1(2-Dimethylaminoethyl)-1,4-dihydro-7-methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid, hydrochloride (4.6 g) and N,N'-carbonyldiimidazole (2.75 g) in dimethylformamide (40 ml) were stirred and heated to 90° for 2 hours. 5-Amino-1H-tetrazole (1.45 G) was added and the mixture was heated to 40° and stirred for 36 hours. The solid was collected, m.p. 305°-307° (d). (39%).
Reaction SMILES: C(O[C:4]([C:6]1[C:11]([NH:12][C:13]2[N:14]([CH3:18])[N:15]=[CH:16][CH:17]=2)=[CH:10][CH:9]=[C:8]([CH3:19])[N:7]=1)=[O:5])C.[NH2:20][C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][N:22]=1>>[F:27][C:24]1[CH:25]=[CH:26][C:21]([NH:20][C:4]([C:6]2[C:11]([NH:12][C:13]3[N:14]([CH3:18])[N:15]=[CH:16][CH:17]=3)=[CH:10][CH:9]=[C:8]([CH3:19])[N:7]=2)=[O:5])=[N:22][CH:23]=1
Reactant: CCOC(=O)c1nc(C)ccc1Nc1ccnn1C
Reactant: Nc1ccc(F)cn1
Product: Cc1ccc(Nc2ccnn2C)c(C(=O)Nc2ccc(F)cn2)n1

Procedure:
The title compound, was prepared from 6-Methyl-3-(2-methyl-2H-pyrazol-3-ylamino)-pyridine-2-carboxylic acid ethyl ester and 2-Amino-5-fluoropyridine in accordance with the general method of Example 78, step 2 to yield the final compound as a yellow crystalline solid, MS (ISP): m/e=327.0 (M+H+).
Reaction SMILES: Cl.[S:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[CH2:7][CH2:8][NH:9][CH:10]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[Cl:21])[C:11]([O:13][CH3:14])=[O:12].[CH2:22]=O>ClC(Cl)C.O>[CH3:14][O:13][C:11](=[O:12])[CH:10]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[Cl:21])[N:9]1[CH2:8][CH2:7][C:3]2[S:2][CH:6]=[CH:5][C:4]=2[CH2:22]1
Reactant: C=O
Reactant: COC(=O)C(NCCc1cccs1)c1ccccc1Cl
Agent: Cl
Solvent: O
Solvent: CC(Cl)Cl
Product: COC(=O)C(c1ccccc1Cl)N1CCc2sccc2C1
Temperature: 60 °C
Yield: 90.1 %

Procedure:
6 g (0.017 mol) of dextrorotatory methyl [2-(2-thienyl)ethylamino](2-chlorophenyl)acetate hydrochloride is suspended in 6.7 ml of 38% aqueous formaline solution and heated to 60° C. under stirring. The starting material dissolves at 60° C., the resulting solution is stirred at the temperature for 30 minutes, till the completion of the reaction. The reaction mixture is then diluted with 100 ml of 1.2 dichloroethane and 150 ml of water, and after shaking well, the phases are separated. The aqueous phase is extracted with 2×30 ml of 1,2-dichloroethane, the united organic phase is extracted with 100 ml of water, dried over anhydrous sodium sulfate, filtered and evaporated in vacuo. The residual 6 g of material is dissolved in 30 ml of diethyl ether, and while cooling the reaction mixture, 0.6 g of dry hdyrogen chloride gas is introduced into the solution, at room temperature. The precipitated crystalline material is filtered off, washed with ether and dried. Weight: 5.5 g. Mp.: 130-132° C., [α]22D=+60°. Yield: 90.1%. Optical purity: 99% (by HPLC investigation).
Reaction SMILES: [OH:1][CH:2]([C:16]1[CH:17]=[C:18]2[C:41](=[CH:42][CH:43]=1)[C:22]1=[N:23][O:24][C:25]([C:26]3[C:30]([C:31]([F:34])([F:33])[F:32])=[C:29]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)[O:28][N:27]=3)=[C:21]1[CH2:20][CH2:19]2)[CH2:3][N:4]1[CH2:9][CH2:8][CH2:7][C@H:6]([CH2:10][C:11]([O:13]CC)=[O:12])[CH2:5]1.C(#N)C.[ClH:47]>O>[OH:1][CH:2]([C:16]1[CH:17]=[C:18]2[C:41](=[CH:42][CH:43]=1)[C:22]1=[N:23][O:24][C:25]([C:26]3[C:30]([C:31]([F:34])([F:33])[F:32])=[C:29]([C:35]4[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=4)[O:28][N:27]=3)=[C:21]1[CH2:20][CH2:19]2)[CH2:3][N:4]1[CH2:9][CH2:8][CH2:7][C@H:6]([CH2:10][C:11]([OH:13])=[O:12])[CH2:5]1.[ClH:47]
Reactant: CCOC(=O)C[C@H]1CCCN(CC(O)c2ccc3c(c2)CCc2c-3noc2-c2noc(-c3ccccc3)c2C(F)(F)F)C1
Agent: Cl
Solvent: O
Solvent: CC#N
Product: O=C(O)C[C@H]1CCCN(CC(O)c2ccc3c(c2)CCc2c-3noc2-c2noc(-c3ccccc3)c2C(F)(F)F)C1
Temperature: 60 °C

Procedure:
To ethyl 2-((3R)-1-(2-hydroxy-2-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)ethyl)piperidin-3-yl)acetate (Preparation 19A, 125 mg, 0.210 mmol were added acetonitrile (3 mL) and 6N hydrochloric acid (3 mL). The reaction mixture was heated at 60° C. for 4 h. The reaction mixture was concentrated under reduced pressure to yield a solid. To the solid was added acetonitrile (0.5 mL) and water (10 mL). The contents were sonicated and lyophilized to yield 2-((3R)-1-(2-hydroxy-2-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)ethyl)piperidin-3-yl)acetic acid, hydrochloric acid (150 mg, 0.248 mmol, 70.3% yield) as a white solid.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].Cl[C:13]1[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][N:14]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[N+:19]([C:16]1[CH:17]=[CH:18][C:13]([O:1][C:2]2[CH:3]=[C:4]([CH:9]=[CH:10][CH:11]=2)[C:5]([O:7][CH3:8])=[O:6])=[N:14][CH:15]=1)([O-:21])=[O:20]
Reactant: COC(=O)c1cccc(O)c1
Reactant: O=[N+]([O-])c1ccc(Cl)nc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)c1cccc(Oc2ccc([N+](=O)[O-])cn2)c1
Temperature: 60 °C
Reaction time: 3 h
Yield: 103 %

Procedure:
A mixture of methyl 3-hydroxybenzoate (8.14 g, 53.5 g), 2-chloro-5-nitropyridine (8.08 g, 51.0 mmol), potassium carbonate (11.1 g, 80.3 mmol) and N,N-dimethylformamide (100 mL) was stirred at 60° C. for 3 hr. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure, and the residue was collected by filtration and washed with ethyl acetate-hexane to give the title compound (14.4 g, 98%) as a white solid.
Reaction SMILES: [Cl-].[OH:2][NH3+:3].[F:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH:12]=O)=[CH:7][CH:6]=1.C(=O)([O-])[O-].[Na+].[Na+]>O.C(Cl)Cl>[F:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH:12]=[N:3][OH:2])=[CH:7][CH:6]=1
Reactant: O=CCc1ccc(F)cc1
Reactant: [NH3+]O
Agent: O=C([O-])[O-]
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Product: ON=CCc1ccc(F)cc1
Reaction time: 48 h
Yield: 90.8 %

Procedure:
113 g of hydroxylammonium chloride in 300 ml of water are added to 160 g of p-fluorophenylacetaldehyde in 500 ml of methylene chloride. A solution of 87 g of sodium carbonate in 300 ml of water is slowly added dropwise to the stirred mixture at room temperature, and the reaction is allowed to continue for 2 days. The organic phase is separated off, washed with water, dried over Na2SO4 and filtered, and the filtrate is freed from the solvent. 161 g of p-fluorophenylacetaldoxime of melting point 113°-115° C. are obtained. 200 MHz NMR spectrum in CDCl3 : ##STR10## (cis/trans isomer mixture=1:1)
Reaction SMILES: [Si:1]([O:18][CH2:19][CH2:20][CH2:21][CH2:22][OH:23])([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>ClCCl>[Si:1]([O:18][CH2:19][CH2:20][CH2:21][CH:22]=[O:23])([C:14]([CH3:16])([CH3:17])[CH3:15])([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)[Si](OCCCCO)(c1ccccc1)c1ccccc1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Product: CC(C)(C)[Si](OCCCC=O)(c1ccccc1)c1ccccc1
Reaction time: 1 h

Procedure:
To a solution of the 4-(tert-butyidiphenylsilyloxy)butan-1-ol (0.5 g, 1.5 mmol) in dichloromethane (20 mL) was added Dess-Martin periodinane (775 mg, 1.83 mmol). The mixture was stirred for 1 h. The reaction mixture was poured into hexanes and the resulting white precipitant was removed via filtration. The solution was concentrated to give form a slurry, which was dissolved in dichloromethane (5 mL) and again poured into hexanes resulting in the precipitation of white solid. The solids were removed via filtration and the resulting solution was concentrated. This gave 475 mg (97%) of a clear oil: 1H NMR (CDCl3); δ1.04 (s, 9H), 1.89 (m, 2H), 2.55 (m, 2H), 3.69 (t, 2H, J=6.1 Hz)), 7.38 (m, 6H), 7.63 (d, 4H, J=1.7 Hz), 9.79 (t, 1H, J=1.8 Hz).
Reaction SMILES: [CH2:1]([N:4]1[CH2:9][CH2:8][O:7][C:6]2[CH:10]=[CH:11][C:12]([C:15]3[N:20]4[N:21]=[C:22]([C:24]5[CH:29]=[CH:28][CH:27]=[C:26](Br)[CH:25]=5)[CH:23]=[C:19]4[N:18]=[C:17]([CH3:31])[C:16]=3[C@H:32]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[C:33]([O:35][CH3:36])=[O:34])=[C:13]([Cl:14])[C:5]1=2)[CH:2]=[CH2:3].[CH2:42]([C:46]1[CH:47]=[C:48](B2OC(C)(C)C(C)(C)O2)[CH:49]=[CH:50][CH:51]=1)[CH2:43][CH:44]=[CH2:45].C([O-])([O-])=O.[Na+].[Na+].O>CN(C=O)C>[CH2:1]([N:4]1[CH2:9][CH2:8][O:7][C:6]2[CH:10]=[CH:11][C:12]([C:15]3[N:20]4[N:21]=[C:22]([C:24]5[CH:25]=[C:26]([C:50]6[CH:49]=[CH:48][CH:47]=[C:46]([CH2:42][CH2:43][CH:44]=[CH2:45])[CH:51]=6)[CH:27]=[CH:28][CH:29]=5)[CH:23]=[C:19]4[N:18]=[C:17]([CH3:31])[C:16]=3[C@H:32]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[C:33]([O:35][CH3:36])=[O:34])=[C:13]([Cl:14])[C:5]1=2)[CH:2]=[CH2:3]
Reactant: C=CCN1CCOc2ccc(-c3c([C@H](OC(C)(C)C)C(=O)OC)c(C)nc4cc(-c5cccc(Br)c5)nn34)c(Cl)c21
Reactant: C=CCCc1cccc(B2OC(C)(C)C(C)(C)O2)c1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: C=CCCc1cccc(-c2cccc(-c3cc4nc(C)c([C@H](OC(C)(C)C)C(=O)OC)c(-c5ccc6c(c5Cl)N(CC=C)CCO6)n4n3)c2)c1
Temperature: 90 °C
Reaction time: 0.08 h
Yield: 61.5 %

Procedure:
A mixture of (2S)-methyl 2-(7-(4-allyl-5-chloro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (75 mg, 0.117 mmol), 2-(3-(but-3-en-1-yl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (45.4 mg, 0.176 mmol) and 2N Na2CO3 (0.117 mL, 0.234 mmol) in DMF (1 mL) was degassed for 15 min. tetrakis(triphenylphosphine)pallafium(0) (9.48 mg, 8.20 μmol) was then added and the degassing was continue for another 5 min. The mixture was then heated at 90° C. for 16 h. After cooling to room temperature, water was added and the mixture was extracted with ether (2×25 mL), washed with brine (15 mL), dried (Na2SO4), filtered and concentrated. Crude was then purified by biotage (0-15% EtOAc/hexane) to afford (2S)-methyl 2-(7-(4-allyl-5-chloro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-2-(3′-(but-3-en-1-yl)-[1,1′-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (50 mg, 0.072 mmol, 61.7% yield) as light yellow solid. 1H NMR (500 MHz, CDCl3) δ: 8.05 (t, J=1.6 Hz, 1H), 7.85-7.82 (m, 1H), 7.57-7.54 (m, 1H), 7.45 (dd, J=4.6, 2.5 Hz, 3H), 7.41-7.35 (m, 1H), 7.21 (d, J=7.6 Hz, 1H), 7.00 (d, J=5.0 Hz, 2H), 6.95-6.93 (m, 1H), 6.11-6.00 (m, 1H), 5.91 (ddt, J=17.0, 10.3, 6.6 Hz, 1H), 5.35 (dd, J=17.2, 1.6 Hz, 1H), 5.26 (dd, J=10.2, 1.6 Hz, 1H), 5.12-5.07 (m, 2H), 5.04-5.00 (m, 1H), 4.27 (t, J=4.4 Hz, 2H), 3.79-3.72 (m, 1H), 3.67 (s, 3H), 3.63 (dd, J=15.1, 6.1 Hz, 1H), 3.28-3.17 (m, 2H), 2.86 (s, 3H), 2.83-2.78 (m, 2H), 2.49-2.41 (m, 2H), 1.20 (s, 9H). LCMS (M+H)=691.5.
Reaction SMILES: [NH:1]1[CH:5]=[N:4][CH:3]=[N:2]1.[Na].[Cl:7][C:8]1[CH:13]=[C:12]([Cl:14])[CH:11]=[CH:10][C:9]=1[CH2:15][C:16]([C:19]1([CH2:22][N:23]2[CH:27]=[N:26][CH:25]=[N:24]2)[CH2:21][O:20]1)([CH3:18])[CH3:17]>C(O)CC>[Cl:7][C:8]1[CH:13]=[C:12]([Cl:14])[CH:11]=[CH:10][C:9]=1[CH2:15][C:16]([CH3:18])([CH3:17])[C:19]([CH2:22][N:23]1[CH:27]=[N:26][CH:25]=[N:24]1)([OH:20])[CH2:21][N:1]1[CH:5]=[N:4][CH:3]=[N:2]1
Reactant: c1nc[nH]n1
Reactant: CC(C)(Cc1ccc(Cl)cc1Cl)C1(Cn2cncn2)CO1
Agent: [Na]
Solvent: CCCO
Product: CC(C)(Cc1ccc(Cl)cc1Cl)C(O)(Cn1cncn1)Cn1cncn1
Yield: 18.8 %

Procedure:
3.7 g (52.5 millimoles) of 1,2,4-triazole are added to a solution of 0.11 g (47 millimoles) of sodium in 30 ml of n-propanol at room temperature, while stirring. The mixture is heated to the reflux temperature and a solution of 15.4 g (47 millimoles) of 2-(2,4-dichlorophenyl-tert.-butyl)-2-(1,2,4-triazol-1-yl-methyl)-oxirane in 20 ml of n-propanol is added. The reaction mixture is heated under reflux for 15 hours and then cooled and poured onto water. The mixture is extracted with methylene chloride and the organic phase is dried over sodium sulphate and concentrated. The residue is purified by column chromatography (silica gel; ethyl acetate:cyclohexane=3:1). 3.5 g (18.8% of theory) of 4-(2,4-dichlorophenyl)-3,3-dimethyl-2-(1,2,4-triazol-1-yl-methyl)-1-(1,2,4-triazol-1-yl)-2-butanol of melting point 126° C. are obtained.