Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][N:2]=[CH:3][C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[CH:6][CH:5]=1.Cl[O-].[Na+].[CH3:14][C:15]1[S:16][C:17]2[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH:26]([OH:37])[CH2:27][N:28]3[CH2:33][CH2:32][N:31]([CH2:34][CH:35]=[CH2:36])[CH2:30][CH2:29]3)=[CH:20][C:18]=2[N:19]=1.C(N(CC)CC)C>ClCCl.CO>[CH3:14][C:15]1[S:16][C:17]2[CH:23]=[CH:22][C:21]([O:24][CH2:25][C@H:26]([OH:37])[CH2:27][N:28]3[CH2:33][CH2:32][N:31]([CH2:34][CH:35]4[O:1][N:2]=[C:3]([C:4]5[CH:9]=[CH:8][C:7]([CH3:10])=[CH:6][CH:5]=5)[CH2:36]4)[CH2:30][CH2:29]3)=[CH:20][C:18]=2[N:19]=1
Reactant: Cc1ccc(C=NO)cc1
Reactant: C=CCN1CCN(CC(O)COc2ccc3sc(C)nc3c2)CC1
Agent: [Na+]
Agent: [O-]Cl
Solvent: ClCCl
Solvent: CO
Solvent: CCN(CC)CC
Product: Cc1ccc(C2=NOC(CN3CCN(C[C@@H](O)COc4ccc5sc(C)nc5c4)CC3)C2)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 5.2 %

Procedure:
To a solution of (hydroxyimino)(4-methylphenyl)methane (97 mg, 0.72 mmol) in 1 ml of dichloromethane was added aqueous sodium hypochlorite solution (>4%, 1.33 ml, 0.72 mmol). The reaction mixture was stirred at room temperature for 30 minutes, after which time TLC (20:1 dichloromethane:methanol) showed conversion of oxime to chlorinated oxime (17). 1-(2-Methylbenzothiazol-5-yloxy)-3-(4-prop-2-enylpiperazinyl)propan-2-ol (50 mg, 0.144 mmol) in 0.5 ml of dichloromethane and triethylamine (0.022 ml, 0.145 mmol) were added. The reaction was stirred at room temperature overnight. Thin layer chromatography (10:1 dichloromethane:methanol) showed consumption of starting material and product formation. The solution was evaporated under reduced pressure, and the residue purified by preperative HPLC, to yield (2R)-1-(2-methylbenzothiazol-5-yloxy)-3-(4-{[3-(4-methylphenyl)(4,5-dihydroisoxazol-5-yl)]methyl}piperazinyl)propan-2-ol (3.6 mg, M+1=481.35)
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:11][CH:12]([C:14]3[CH:15]=[N:16][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:18][CH:19]=3)O)[C:6]3[CH2:24][CH2:25][N:26]([CH3:28])[CH2:27][C:5]=3[C:4]=2[CH:3]=1.S(=O)(=O)(O)O.[OH-].[K+]>>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7](/[CH:11]=[CH:12]/[C:14]3[CH:15]=[N:16][C:17]([C:20]([F:21])([F:23])[F:22])=[CH:18][CH:19]=3)[C:6]3[CH2:24][CH2:25][N:26]([CH3:28])[CH2:27][C:5]=3[C:4]=2[CH:3]=1
Reactant: CN1CCc2c(c3cc(Cl)ccc3n2CC(O)c2ccc(C(F)(F)F)nc2)C1
Agent: O=S(=O)(O)O
Agent: [K+]
Agent: [OH-]
Product: CN1CCc2c(c3cc(Cl)ccc3n2/C=C/c2ccc(C(F)(F)F)nc2)C1
Temperature: 5 °C

Procedure:
2-(8-Chloro-1,2,3,4-tetrahydro-2-methylpyrido[4,3-b]indol-5-yl)-1-(6-(trifluoromethyl)pyridin-3-yl)ethanol (1 equiv.) is refluxed with 25% sulfuric acid for 2 h. The reaction mixture is cooled to 5° C. with an ice-water bath. KOH (15% aq. solution) is added dropwise to the reaction mixture until pH 9-10 is achieved. The reaction mixture is extracted with EtOAc. The combined organic layers are washed with water followed by brine, dried over sodium sulfate and evaporated under vacuum. The crude product is purified by column chromatography over silica gel (100-200 mesh) using a gradient of MeOH-EtOAc (0-10%).
Reaction SMILES: [N:1]([CH2:4][CH:5]([N:7]([C:22]([CH:24]1[CH2:29][CH2:28][CH:27]([CH3:30])[CH2:26][CH2:25]1)=[O:23])[C:8]1[CH:12]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[S:10][C:9]=1[C:19]([OH:21])=[O:20])[CH3:6])=[N+]=[N-]>CCO.[Pd]>[NH2:1][CH2:4][CH:5]([N:7]([C:22]([CH:24]1[CH2:25][CH2:26][CH:27]([CH3:30])[CH2:28][CH2:29]1)=[O:23])[C:8]1[CH:12]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[S:10][C:9]=1[C:19]([OH:21])=[O:20])[CH3:6]
Reactant: CC1CCC(C(=O)N(c2cc(-c3ccccc3)sc2C(=O)O)C(C)CN=[N+]=[N-])CC1
Agent: [Pd]
Solvent: CCO
Product: CC1CCC(C(=O)N(c2cc(-c3ccccc3)sc2C(=O)O)C(C)CN)CC1
Reaction time: 1.5 h

Procedure:
A solution of 3-[(2-Azido-1-methyl-ethyl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid (8 mg, 0.19 mmol) in EtOH (0.2 ml) at 210, was treated with 10% Pd/C (4 mg, 50% w/w) and stirred under an atmosphere of H2 for 1.5 h. The reaction mixture was filtered through a pad of celite with hot EtOAc and the combined filtrate and washings dried and evaporated to a glass to provide 3-[(2-Amino-1-methyl-ethyl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid (Compound 36). (7 mg, %); 1H NMR (300 MHz, Acetone-d6) 0.43-0.65 and 0.75-0.90 (m, 4H), 1.17-1.64 (m, 6H), 1.81-1.90 and 2.01-2.40 (m, 3H), 2.54 (bs, 1H), 3.00 (bs, 1H), 3.50 and 3.70 (bs, 1H), 7.20 (s, 1H), 7.22-7.25 and 7.29-7.34 (m, 3H), 7.58-7.62 (m, 2H).
Reaction SMILES: Cl[Si:2]([CH:9]1[CH2:13][CH2:12][CH2:11][CH2:10]1)([O:6][CH2:7][CH3:8])[O:3][CH2:4][CH3:5].[CH2:14]([Mg]Br)[CH:15]([CH3:17])[CH3:16].[Cl-].[NH4+]>C(OCC)C>[CH:9]1([Si:2]([CH2:14][CH:15]([CH3:17])[CH3:16])([O:6][CH2:7][CH3:8])[O:3][CH2:4][CH3:5])[CH2:13][CH2:12][CH2:11][CH2:10]1
Reactant: CCO[Si](Cl)(OCC)C1CCCC1
Reactant: CC(C)C[Mg]Br
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOCC
Product: CCO[Si](CC(C)C)(OCC)C1CCCC1
Reaction time: 6 h
Yield: 78 %

Procedure:
50 ml of dry diethyl ether and 14.0 gram (0.063 mole) of chlorocyclopentyldiethoxysilane (d) were charged in a 250 ml flask equipped with a reflux condenser and a stirring apparatus in an atmosphere of nitrogen and above prepared solution of isobutyl magnesium bromide was slowly added while keeping the internal temperature below 10° C. After completion of addition stirring was carried out at room temperature for 6 hours and at reflux temperature for 2 hours. To the resulting reaction mass 10-20 ml of saturated aqueous ammonium chloride solution was added drop wise to dissolve magnesium salt. The organic layer was separated from the aqueous phase, dried and evaporated to give crude cyclopentylisobutyldiethoxysilane. This crude was purified by fractional distillation under reduced pressure, yielding 12 gram (78%) of pure cyclopentylisobutyldiethoxysilane.
Reaction SMILES: [O:1]1[CH2:3][CH:2]1[CH2:4][O:5][C:6]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:7]=1[CH2:8][C@H:9]([O:27][CH2:28][C:29]([N:31]([CH2:35][CH2:36][CH3:37])[CH2:32][CH2:33][CH3:34])=[O:30])[C@H:10]([O:16][CH2:17][C:18]([N:20]([CH2:24][CH2:25][CH3:26])[CH2:21][CH2:22][CH3:23])=[O:19])[CH2:11]2.[C:38]([NH2:42])([CH3:41])([CH3:40])[CH3:39]>CO>[CH3:39][C:38]([NH:42][CH2:3][CH:2]([OH:1])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:7]=1[CH2:8][CH:9]([O:27][CH2:28][C:29]([N:31]([CH2:32][CH2:33][CH3:34])[CH2:35][CH2:36][CH3:37])=[O:30])[CH:10]([O:16][CH2:17][C:18]([N:20]([CH2:24][CH2:25][CH3:26])[CH2:21][CH2:22][CH3:23])=[O:19])[CH2:11]2)([CH3:41])[CH3:40]
Reactant: CC(C)(C)N
Reactant: CCCN(CCC)C(=O)CO[C@H]1Cc2c(cccc2OCC2CO2)C[C@H]1OCC(=O)N(CCC)CCC
Solvent: CO
Product: CCCN(CCC)C(=O)COC1Cc2cccc(OCC(O)CNC(C)(C)C)c2CC1OCC(=O)N(CCC)CCC

Procedure:
A solution of 1.5 g (0.0029 M) of cis-2,2'-[[1,2,3,4-tetrahydro-5-(oxiranyl-methoxy)-2,3-naphthalenediyl]bis(oxy)]bis-[N,N-dipropylacetamide] in 5 ml of methanol and 20 ml of t-butylamine is stirred at room temperature overnight. The solution is evaporated in vacuo to give 1.7 g of oil. This material is dissolved in ether and extracted with 5% aqueous HCl. The aqueous layer is basified with aqueous NaOH and extracted with ether. The ether is washed (saturated NaCl solution), dried (Na2SO4), filtered and evaporated in vacuo to give the title compound as a dense oil, 1.52 g.
Reaction SMILES: C[O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:13]3[CH2:14][CH2:15][N:16]=[C:17]([CH3:18])[C:12]3=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.Br.C(Cl)Cl.[C:23]([OH:30])(=[O:29])/[CH:24]=[CH:25]/[C:26]([OH:28])=[O:27]>CO>[C:23]([OH:30])(=[O:29])/[CH:24]=[CH:25]/[C:26]([OH:28])=[O:27].[OH:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[N:13]3[CH2:14][CH2:15][N:16]=[C:17]([CH3:18])[C:12]3=[CH:11][CH:10]=2)=[CH:7][CH:8]=1
Reactant: COc1ccc(-c2ccc3n2CCN=C3C)cc1
Agent: Br
Agent: O=C(O)/C=C/C(=O)O
Solvent: CO
Solvent: ClCCl
Product: CC1=NCCn2c1ccc2-c1ccc(O)cc1
Reaction time: 2 h
Yield: 62 %

Procedure:
3,4-Dihydro-6-(p-methoxyphenyl)-1-methylpyrrolo[1,2-a]pyrazine (20.9 g) was boiled with 500 ml of 48% hydrobromic acid in an argon atmosphere while stirring for 11/2 hours. The hydrobromic acid was removed in a vacuum and the residue was dissolved in 900 ml of ethyl acetate with the addition of 100 ml of methanol. The solution was stirred for 15 minutes with a mixture of 500 ml of saturated sodium hydrogen carbonate solution and 100 ml of 2N sodium hydroxide solution. The aqueous phase was brought to a pH value of 8-9 with 2N hydrochloric acid and extracted four times with 500 ml of an ethyl acetate/methanol mixture (9:1) each time. The aqueous phase was neutralized (pH=7) with 2N hydrochloric acid and continuously extracted overnight with 1000 ml of ethyl acetate. The organic phases were filtered, combined and concentrated to 150 ml. Then, 150 ml of ethyl acetate were added, the suspension was boiled and stored in a refrigerator overnight. 16.3 g of crude product were filtered off. 1.6 g thereof were dissolved in a 50-fold amount of methanol and a 10-fold amount of methylene chloride and treated with 1.1 equivalents of fumaric acid in 20 ml of methanol. There were obtained 1.8 g (62%) of 3,4-dihydro-6-(4-hydroxyphenyl)-1-methylpyrrolo[1,2-a]pyrazine fumarate (1:1 ); m.pt.: 209°-213° C. (dec.).
Reaction SMILES: [F:1][C:2]1[C:3]([F:16])=[C:4]([F:15])[C:5]([F:14])=[C:6]([C:11]([OH:13])=[O:12])[C:7]=1[C:8](O)=[O:9].C1(C)C(C)=CC=CC=1>O>[F:1][C:2]1[C:3]([F:16])=[C:4]([F:15])[C:5]([F:14])=[C:6]2[C:11](=[O:13])[O:12][C:8](=[O:9])[C:7]=12
Reactant: O=C(O)c1c(F)c(F)c(F)c(F)c1C(=O)O
Solvent: Cc1ccccc1C
Solvent: O
Product: O=C1OC(=O)c2c(F)c(F)c(F)c(F)c21
Yield: 93 %

Procedure:
350 g of crude tetrafluorophthalic acid are heated with 800 g of xylene using a water separator, until no further water passes over (5 hours). The resulting suspension is allowed to cool and the anhydride which has precipitated is filtered off. 301 g of tetrafluorophthalic anhydride are obtained, the mother liquor, which still contains about 5 g of tetrafluorophthalic anhydride, being used for further dehydrations. The tetrafluorophthalic anhydride is then purified by fractionation, whereupon it passes over as a colorless liquid (under 1 mbar/95° C.-105° C.) and solidifies as a colorless, crystalline mass of melting point 93°-94° C. 255 g (1.16 mol) of tetrafluorophthalic anhydride with a purity of >99% (GC, HPLC) are obtained in this manner.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][C:6]=1[Cl:12])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].Br[CH2:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22]>CC(C)=O>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[CH:7][C:6]=1[Cl:12])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)c1ccc(O)cc1Cl
Reactant: CC(C)(C)OC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CC(C)(C)OC(=O)COc1ccc(C(C)(C)C)c(Cl)c1
Temperature: 65 °C
Yield: 100 %

Procedure:
To an acetone (5 ml) solution of 4-tert-butyl-3-chlorophenol (440 mg, 2.4 mmol) were added potassium carbonate (994 mg, 7.2 mmol) and tert-butyl bromoacetate (0.7 ml, 4.8 mmol). The stirred mixture was refluxed at 65° C. for 14 hours. The precipitate was filtered off and washed with acetone. The filtrate was concentrated under reduced pressure to give a residue, which was applied to a silica gel chromatography column and eluted with ethyl acetate/hexane= 1/9 to furnish 0.83 g (100% yield) of the title as a colorless oil.
Reaction SMILES: C([O:5][P:6]([CH2:18][CH:19]([CH2:27][CH2:28][C:29]([O:31]C(C)(C)C)=[O:30])[C:20]([O:22]C(C)(C)C)=[O:21])([CH2:8][NH:9][C:10]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:11])=[O:7])(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[C:12]1([C:10]([NH:9][CH2:8][P:6]([CH2:18][CH:19]([CH2:27][CH2:28][C:29]([OH:31])=[O:30])[C:20]([OH:22])=[O:21])([OH:7])=[O:5])=[O:11])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: CC(C)(C)OC(=O)CCC(CP(=O)(CNC(=O)c1ccccc1)OC(C)(C)C)C(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C(O)CCC(CP(=O)(O)CNC(=O)c1ccccc1)C(=O)O
Temperature: 25 °C
Reaction time: 18 h
Yield: 75.3 %

Procedure:
To a solution of di-tert-butyl 2-({(tert-butoxy)-[(phenylcarbonylamino)methyl]phosphoryl}methyl)pentane-1,5-dioate (1.230 g, 2.4 mmol) in dichloromethane (10 ML) was added trifluoroacetic acid (5 mL) at room temperature, and the mixture was stirred at room temperature for 18 hours. The solvent was removed under reduced pressure. The residual oil was taken up with dichloromethane (10 mL) and concentrated. This process was repeated three times to remove trifluoroacetic acid completely. The resulting oil was crystallized from acetonitrile-water to give 0.620 g of white solid (75% yield).
Reaction SMILES: [C:1]([C:3]1[CH:4]=[N:5][N:6]2[C:11]([C:12]([F:15])([F:14])[F:13])=[CH:10][C:9]([C:16]3[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=3)=[N:8][C:7]=12)#[CH:2].Br[C:27]1[C:28]([CH3:33])=[N:29][CH:30]=[CH:31][CH:32]=1>>[CH3:33][C:28]1[C:27]([C:2]#[C:1][C:3]2[CH:4]=[N:5][N:6]3[C:11]([C:12]([F:14])([F:13])[F:15])=[CH:10][C:9]([C:16]4[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=4)=[N:8][C:7]=23)=[CH:32][CH:31]=[CH:30][N:29]=1
Reactant: Cc1ncccc1Br
Reactant: C#Cc1cnn2c(C(F)(F)F)cc(-c3ccc(C(F)(F)F)cc3)nc12
Product: Cc1ncccc1C#Cc1cnn2c(C(F)(F)F)cc(-c3ccc(C(F)(F)F)cc3)nc12

Procedure:
The title compound was prepared from 3-ethynyl-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine (example C.1) (355 mg, 1.0 mmol) and 3-bromo-2-methyl-pyridine [CAS 38749-79-0; commercially available] (252 mg, 1.3 mmol) according to general procedure II. Obtained as a light brown solid (270 mg, 60%). MS (ISP) 447.0 [(M+H)+]; mp 198° C.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[C:5]([F:11])=[CH:4][C:3]=1[F:12]>CCO.C1COCC1.[NH4+].[Cl-].O.[Fe]>[Br:1][C:2]1[C:3]([F:12])=[CH:4][C:5]([F:11])=[C:6]([CH:7]=1)[NH2:8]
Reactant: O=[N+]([O-])c1cc(Br)c(F)cc1F
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: C1CCOC1
Solvent: CCO
Product: Nc1cc(Br)c(F)cc1F
Yield: 58.7 %

Procedure:
To a solution of 1-bromo-2,4-difluoro-5-nitrobenzene (5.04 g, 21.3 mmol) in EtOH (100 mL), THF (50 mL), NH4Cl (sat) (25 mL) and H2O (25 mL) was added iron powder (5.0 g, 89.5 mmol). The mixture was refluxed for 2 h and filtered through celite. The filter pad was washed with EtOAc (3×50 mL). The filtrate was concentrated and the residue was partitioned between EtOAc and brine. The organic layer was dried over MgSO4 and concentrated. Purification by flash chromatography (5–10% EtOAc/Hexane) provided 2.6 g (59%) of 5-bromo-2,4-difluoroaniline: ESMS m/e: 208.2 (M+H)+.
Reaction SMILES: O.[OH-].[Li+].[CH3:4][O:5][C:6]([C:8]1[C:9]([S:22][CH3:23])=[C:10]([CH:15]=[CH:16][C:17]=1[C:18]([F:21])([F:20])[F:19])[C:11]([O:13]C)=[O:12])=[O:7]>CO.O>[CH3:4][O:5][C:6]([C:8]1[C:9]([S:22][CH3:23])=[C:10]([CH:15]=[CH:16][C:17]=1[C:18]([F:19])([F:20])[F:21])[C:11]([OH:13])=[O:12])=[O:7]
Reactant: COC(=O)c1ccc(C(F)(F)F)c(C(=O)OC)c1SC
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: COC(=O)c1c(C(F)(F)F)ccc(C(=O)O)c1SC
Temperature: 25 °C
Reaction time: 8 h
Yield: 82.9 %

Procedure:
Lithium hydroxide monohydrate (1.87 g) was added to a solution of methyl 3-methoxycarbonyl-2-(methylsulphenyl)-4-trifluoromethylbenzoate (13.71 g) in methanol and water. The mixture was stirred at room temperature overnight and the methanol was removed by evaporation. The residual aqueous solution was acidified to pH 1 and extracted with ether, washed with water, dried (MgSO4) and filtered. The filtrate was evaporated to dryness to give 3-methoxycarbonyl-2-(methylsulphenyl)-4-trifluoromethylbenzoic acid (10.85 g) as an off-white solid, NMR (CDCl3) 2.45(s, 3H), 3.95(s,3H), 5.45-6.1(bs,1H), 7.2(d,1H), 7.95(d,1H).
Reaction SMILES: [C:1]([C:4]1[S:5][C:6]2[CH:12]=[C:11]([OH:13])[CH:10]=[CH:9][C:7]=2[N:8]=1)(=[O:3])[NH2:2].C(N(CC)CC)C.[CH3:21][O:22][P:23](Cl)([O:25]C)=[O:24]>C1COCC1>[CH3:21][O:22][P:23]([OH:25])([O:13][CH3:11])=[O:24].[C:1]([C:4]1[S:5][C:6]2[CH:12]=[C:11]([OH:13])[CH:10]=[CH:9][C:7]=2[N:8]=1)(=[O:3])[NH2:2]
Reactant: COP(=O)(Cl)OC
Agent: NC(=O)c1nc2ccc(O)cc2s1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: COP(=O)(O)OC
Temperature: 25 °C
Reaction time: 72 h

Procedure:
Three grams (0.015moles) of 2-carbamyl-6-hydroxybenzothiazole (ABT) was dissolved in 30 mLs of THF. Then 1.72 g (0.017 moles) triethylamine was added to the stirring reaction solution, followed immediately by the addition over 5 minutes of 2.6 g (0.018 moles) of dimethylchlorophosphate dissolved in 7 mLs of THF. This solution was stirred for 72 hours at room temperature.
Reaction SMILES: [C:1]1([S:11]([C:14]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([O:23][CH2:24][CH2:25][CH2:26]OS(C4C=CC(C)=CC=4)(=O)=O)[CH:21]=3)[NH:16][N:15]=2)(=[O:13])=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[CH:38]1([NH2:41])[CH2:40][CH2:39]1>C1COCC1>[CH:38]1([NH:41][CH2:26][CH2:25][CH2:24][O:23][C:20]2[CH:21]=[C:22]3[C:17](=[CH:18][CH:19]=2)[NH:16][N:15]=[C:14]3[S:11]([C:1]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH:4]=[CH:3][CH:2]=2)(=[O:12])=[O:13])[CH2:40][CH2:39]1
Reactant: NC1CC1
Reactant: Cc1ccc(S(=O)(=O)OCCCOc2ccc3[nH]nc(S(=O)(=O)c4cccc5ccccc45)c3c2)cc1
Solvent: C1CCOC1
Product: O=S(=O)(c1cccc2ccccc12)c1n[nH]c2ccc(OCCCNC3CC3)cc12
Temperature: 25 °C

Procedure:
A solution of toluene-4-sulfonic acid 3-[3-(naphthalene-1-sulfonyl)-1H-indazol-5-yloxy]-propyl ester (0.080 mg, 0.15 mmol) and cyclopropylamine (0.45-0.75 mmol) in THF (10 mL) was stirred at 90° C. for about 2 hours in a sealed tube. After cooling to ambient temperature the reaction mixture was solvent evaporated. It was dissolved in ethyl acetate and washed twice with aqueous sodium bicarbonate. The organic phase was dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified twice by flash chromatography using 0.75% ammonium hydroxide/7.5% methanol in chloroform and 0.5% ammonium hydroxide/5.0% methanol in chloroform to give cyclopropyl-{3-[3-(naphthalene-1-sulfonyl)-1H-indazol-5-yloxy]-propyl}-amine as a clear yellow film (51.0 mg, 80.7%). This compound was dissolved in methanol, and ethereal hydrochloride was added. Concentrating and drying in vacuo for 24 hours at 83° C. gave the hydrochloride as a yellow foam (48.9 mg, 71.2%); Mass Spectrum (+EI, [M+H]+) m/z 422. 1HNMR (500 MHz, DMSO-d6): δ14.15 (s, 1H), 9.01 (s, 2H), 8.74-8.76 (m, 1H), 8.51-8.53 (m, 1H), 8.27 (d, 1H, J=8.29 Hz), 8.02-8.05 (m, 1H), 7.71-7.75 (m, 1H), 7.51-7.65 (m, 3H), 7.29 (d, 1H, J=2.19 Hz), 7.08-7.11 (m, 1H), 4.11 (t, 2H, J=6.10 Hz), 3.11-3.20 (br, s, 2H), 2.65-2.75 (m, 1H), 2.08-2.15 (m, 2H), 0.83-0.87 (m, 2H), 0.70-0.77 ppm (m, 2H). Elemental Analysis for C23H23N3O3S.1.00 mol HCl.0.70 mol H2O: Calcd: C, 58.70; H, 5.44; N, 8.93; Found: C, 58.70; H, 5.09; N, 8.68.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N+:8]([O-:10])=[O:9].[Cl:11][C:12]1[CH:18]=[CH:17][C:15]([NH2:16])=[CH:14][CH:13]=1.[F-].[K+].Cl>C(Cl)Cl>[Cl:11][C:12]1[CH:18]=[CH:17][C:15]([NH:16][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[N+:8]([O-:10])=[O:9])=[CH:14][CH:13]=1
Reactant: O=[N+]([O-])c1ccccc1F
Reactant: Nc1ccc(Cl)cc1
Agent: Cl
Agent: [F-]
Agent: [K+]
Solvent: ClCCl
Product: O=[N+]([O-])c1ccccc1Nc1ccc(Cl)cc1
Temperature: 180 °C
Reaction time: 10 h
Yield: 96 %

Procedure:
A mixture of 2-fluoro-nitrobenzene (33.7 g), 4-chloroaniline (61.0 g) and anhydrous potassium fluoride (13.9 g) was stirred at 180° C. for 10 h. After being cooled to rt, 3 M HCl was added and the mixture was stirred at 100° C. for 30 min. Then cooled to rt, filtered by suction, washed with water to give a brown solid. The solid was dissolved in CH2Cl2 and filtered through a thin pad of silica gel, washed with CH2Cl2. The filtrate was concentrated to dryness, and the residue was recrystallized with 95% ethanol to give 57.0 g of orange solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([NH:24][C:25]2[O:26][C:27]([CH3:43])([CH3:42])[C:28]([F:41])([F:40])[C@:29]([C:32]3[CH:37]=[C:36](Br)[CH:35]=[CH:34][C:33]=3[F:39])([CH3:31])[N:30]=2)([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:5][CH:4]=1.[Cl:44][C:45]1[CH:50]=[CH:49][C:48]([C:51]#[N:52])=[CH:47][C:46]=1B(O)O>>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([NH:24][C:25]2[O:26][C:27]([CH3:43])([CH3:42])[C:28]([F:41])([F:40])[C@:29]([C:32]3[CH:37]=[C:36]([C:46]4[C:45]([Cl:44])=[CH:50][CH:49]=[C:48]([C:51]#[N:52])[CH:47]=4)[CH:35]=[CH:34][C:33]=3[F:39])([CH3:31])[N:30]=2)([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:5][CH:4]=1
Reactant: COc1ccc(C(NC2=N[C@](C)(c3cc(Br)ccc3F)C(F)(F)C(C)(C)O2)(c2ccccc2)c2ccc(OC)cc2)cc1
Reactant: N#Cc1ccc(Cl)c(B(O)O)c1
Product: COc1ccc(C(NC2=N[C@](C)(c3cc(-c4cc(C#N)ccc4Cl)ccc3F)C(F)(F)C(C)(C)O2)(c2ccccc2)c2ccc(OC)cc2)cc1
Yield: 22 %

Procedure:
In a manner analogous to that described in Example 9 a), the cross-coupling reaction of [bis-(4-methoxy-phenyl)-phenyl-methyl]-[(R)-4-(5-bromo-2-fluoro-phenyl)-5,5-difluoro-4,6,6-trimethyl-5,6-dihydro-4H-[1,3]oxazin-2-yl]-amine (intermediate C4.1) with 2-chloro-5-cyanophenylboronic acid yielded the title compound (22% yield) as a white foam.
Reaction SMILES: Cl[CH2:2][C:3]1[N:13]=[C:6]2[N:7]=[C:8]([CH3:12])[CH:9]=[C:10]([OH:11])[N:5]2[N:4]=1.[NH3:14]>>[NH2:14][CH2:2][C:3]1[N:13]=[C:6]2[N:7]=[C:8]([CH3:12])[CH:9]=[C:10]([OH:11])[N:5]2[N:4]=1
Reactant: N
Reactant: Cc1cc(O)n2nc(CCl)nc2n1
Product: Cc1cc(O)n2nc(CN)nc2n1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
2-(Chloromethyl)-5-methyl-s-triazolo[1.5-a]pyrimidin-7-ol (1.0 g) (known from C.A. 104/09-068678) is dissolved in 20 ml of conc. aqueous ammonia and stirred at room temperature overnight. The precipitate formed is filtered off under suction. The mother liquor is concentrated and the residue is taken up in ethanol. The product thereby crystallizes. There is obtained 0.66 g of 2-(aminomethyl)-5-methyl-s-triazolo[1,5-a]pyrimidin-7-ol as a white powder of m.p. 204°-207° C.
Reaction SMILES: [OH:1][CH:2]1[CH2:6][C:5](=[O:7])[CH:4]=[CH:3]1.ClC(Cl)(Cl)C(=N)O[C:12]([CH3:15])([CH3:14])[CH3:13].B(F)(F)F.CCOCC.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[C:12]([O:7][CH:5]1[CH2:6][C:2](=[O:1])[CH:3]=[CH:4]1)([CH3:15])([CH3:14])[CH3:13]
Reactant: CC(C)(C)OC(=N)C(Cl)(Cl)Cl
Reactant: O=C1C=CC(O)C1
Agent: FB(F)F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOCC
Solvent: ClCCl
Product: CC(C)(C)OC1C=CC(=O)C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 19.7 %

Procedure:
A solution of 4-hydroxy-2-cyclopentenone (1.15 g, 11.7 mmol) in methylene chloride is cooled to 3° C. and treated sequentially with tert-butyl trichloroacetimidate (4.2 mL, 23.7 mmol) and boron trifluoride diethyl etherate (0.15 mL). The reaction mixture is stirred at 3°-10° C. for 2 hours and then allowed to warm to room temperature and stirred for 22 hours. The reaction mixture is then treated with sodium bicarbonate (250 mg) and filtered. The filtrate is concentrated under vacuum and the residue is purified by chromatography (silica gel, 39 g, 20% ethyl acetate/hexane, 600 mL) to provide the title compound (355 mg, 40%) as a yellow oil; 1H NMR (CDCl3) δ 7.44 (dd, 1 H, J=18 Hz), 6.2 (d, 1 H, J=5.4 Hz), 4.8 (m, 1 H), 2.68 (dd, 1 H, J=5.8, 18 Hz), 2.25 (d, 1 H, J=18 Hz), 1.27 (s, 9 H); IR (neat) νmax 2976, 2936, 1721, 1368, 1352, 1188, 1103, 1161 cm-1 ; MS (CI) m/e (% relative intensity) 155 (M+H+, 22), 99 (100).