Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C:9]1[CH:14]=[CH:13][C:12]([C:15]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:16])=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].BrBr.C[O-:27].[Na+].Cl>ClC(F)(F)C(Cl)(Cl)F.C(O)C>[CH2:1]([C:9]1[CH:10]=[CH:11][C:12]([C:15]([CH:17]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[OH:27])=[O:16])=[CH:13][CH:14]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: C[O-]
Reactant: CCCCCCCCc1ccc(C(=O)Cc2ccccc2)cc1
Agent: BrBr
Agent: Cl
Agent: [Na+]
Solvent: FC(F)(Cl)C(F)(Cl)Cl
Solvent: CCO
Product: CCCCCCCCc1ccc(C(=O)C(O)c2ccccc2)cc1
Temperature: 35 °C
Reaction time: 15 h
Yield: 90.9 %

Procedure:
120 g (0.35 mole) of 4-n-octyldeoxybenzoin are dissolved in 500 ml of 1,2,2-trichloro-1,1,2-trifluoroethane. 16 ml (56 g, 0.35 mole) of bromine are added dropwise in the course of one hour, while irradiating with UV light, so that the solution is continuously decolorized. Thereafter, the reaction solution is heated at the boil for one hour, and thin layer chromatography is used to check for complete conversion. The solvent is completely stripped off, 140 g of crude product being obtained as the residue. This is dissolved in 100 ml of ethanol, and a solution of 56.7 g (1.05 moles) of sodium methylate in 200 ml of ethanol is added dropwise at room temperature to the stirred solution, the internal temperature increasing to 35° C. The reaction mixture is stirred for a further 15 hours at room temperature, after which it is discharged onto 1 l of semiconcentrated hydrochloric acid and stirring is continued for about a further 30 minutes. The precipitate is filtered off, washed with water and recrystallized from petroleum ether (60°-80° C.) to give 103.2 g (91% yield) of 4-n-octylbenzoin of melting point 65°-70° C.). According to thin layer chromatography, this product is only slightly contaminated. Column chromatography over silica gel 60 using methylene chloride as the mobile phase gives 70 g (62%) of analytically pure 4-n-octylbenzoin (thin layer chromatography over silica gel/CH2Cl2 : R=0.78; toluene: R=0.18).
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:3]=1[NH2:4].Br[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.CC(C)([O-])C.[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC1C=CC=CC=1C>[Cl:1][C:2]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:3]=1[NH:4][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: Nc1ccc(F)cc1Cl
Reactant: Brc1ccccc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(C)P(C(C)(C)C)C(C)(C)C
Solvent: Cc1ccccc1C
Product: Fc1ccc(Nc2ccccc2)c(Cl)c1
Yield: 44 %

Procedure:
A mixture of 35 g (240 mmole) 2-chloro-4-fluoroaniline, 37.7 g (240 mmole) of bromobenzene, 0.6 g (12 mmole) of palladium (II)acetate, 4.8 g (24 mmole) of tri-tert-butylphosphine, 46 g (480 mmole) of sodium tert-butoxide and o-xylene 800 ml were refluxed under nitrogen for about overnight. Then, the solution was filtered at 100° C. To receive the filtrate, And the o-xylene was removed under reduced pressure from the filtrate. The filtrate was extracted with 500 ml dichloromethane and 2000 ml water, the organic layer was dried with anhydrous magnesium sulfate, the solvent was removed and the residue was purified by column chromatography on silica (hexane-ethyl acetate) to give product 23.4 g (44%).
Reaction SMILES: [F:1][C:2]1[C:3]([C:9]([OH:11])=O)=[N:4][CH:5]=[C:6]([F:8])[CH:7]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.Cl.[CH3:25][NH:26][O:27][CH3:28].CCN(C(C)C)C(C)C>C1COCC1>[F:1][C:2]1[C:3]([C:9]([N:26]([O:27][CH3:28])[CH3:25])=[O:11])=[N:4][CH:5]=[C:6]([F:8])[CH:7]=1
Reactant: O=C(O)c1ncc(F)cc1F
Reactant: CNOC
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: CON(C)C(=O)c1ncc(F)cc1F
Temperature: 50 °C
Reaction time: 1 h
Yield: 56.2 %

Procedure:
To a suspension of 3,5-difluoropicolinic acid (3.5 g) in THF (70 ml) was added CDI (3.92 g) at room temperature. The mixture was stirred at room temperature for 30 min and at 50° C. for 1 h. After cooling to room temperature, N,O-dimethylhydroxylamine hydrochloride (3.22 g) and DIPEA (5.76 mL) were added. The mixture was stirred at room temperature for 12 h, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/AcOEt) to give the title compound (2.5 g).
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH:11]4[CH2:17][CH2:16][N:14]([CH2:15][C:5]=3[C:4]=2[CH:3]=1)[CH2:13][CH2:12]4.Br[C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([N:25]2[CH:29]=[CH:28][CH:27]=[N:26]2)[N:20]=1>>[F:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([N:25]4[CH:29]=[CH:28][CH:27]=[N:26]4)[N:20]=3)[C:6]3[CH:11]4[CH2:12][CH2:13][N:14]([CH2:15][C:5]=3[C:4]=2[CH:3]=1)[CH2:16][CH2:17]4
Reactant: Fc1ccc2[nH]c3c(c2c1)CN1CCC3CC1
Reactant: Brc1cccc(-n2cccn2)n1
Product: Fc1ccc2c(c1)c1c(n2-c2cccc(-n3cccn3)n2)C2CCN(CC2)C1

Procedure:
The reaction of 9-fluoro-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole (230 mg, 1.0 mmol; Example 161) and 2-bromo-6-(1H-pyrazol-1-yl)pyridine (336 mg, 1.5 mmol; Maybridge) was performed as described in Example 68 to afford the title compound: 1H NMR (300 MHz, methanol-d4) δ ppm 1.99-2.14 (m, 2H) 2.15-2.30 (m, 2H) 3.09-3.29 (m, 5H) 4.29 (s, 2H) 6.52-6.57 (m, 1H) 6.90 (td, J=9, 3 Hz, 1H) 7.11 (dd, J=9, 3 Hz, 1H) 7.37 (d, J=8 Hz, 1H) 7.43 (dd, J=9, 4 Hz, 1H) 7.80 (s, 1H) 7.97 (d, J=8 Hz, 1H) 8.16 (t, J=8 Hz, 1H) 8.50 (d, J=3 Hz, 1H); MS (DCI/NH3) m/z 374 (M+H)+.
Reaction SMILES: [Mg].II.[CH2:4](Br)[CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11]/[CH:12]=[CH:13]\[CH2:14]/[CH:15]=[CH:16]\[CH2:17][CH2:18][CH2:19][CH2:20][CH3:21].C([O:25][CH2:26][CH3:27])=O.[OH-].[K+]>C(OCC)C>[CH2:4]([CH:26]([CH2:27][CH2:20][CH2:19][CH2:18][CH2:17]/[CH:16]=[CH:15]\[CH2:14]/[CH:13]=[CH:12]\[CH2:11]/[CH:10]=[CH:9]\[CH2:8][CH2:7][CH2:6][CH2:5][CH3:4])[OH:25])[CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11]/[CH:12]=[CH:13]\[CH2:14]/[CH:15]=[CH:16]\[CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]
Reactant: CCCCC/C=C\C/C=C\C/C=C\CCCCCBr
Reactant: CCOC=O
Agent: II
Agent: [K+]
Agent: [Mg]
Solvent: CCOCC
Product: CCCCC/C=C\C/C=C\C/C=C\CCCCCC(O)CCCCC/C=C\C/C=C\C/C=C\CCCCC
Temperature: 25 °C
Reaction time: 8 h
Yield: 58.9 %

Procedure:
Magnesium turnings (2.1 g, 87 mmol), 5 crystals of iodine and a stirbar were added to a 1000 mL round-bottom flask. The flask was flushed with nitrogen and a solution of γ-linolenyl bromide (Compound 6) (18.9 g, 57 mmol) in anhydrous diethyl ether (500 mL) added via cannula. The mixture turned cloudy and was refluxed overnight. The mixture was cooled to RT and ethyl formate (4.66 mL, 58 mmol) added dropwise. The suspension was stirred overnight, turning bright yellow. The R.M. was transferred to a 2000-mL sep. funnel with ether (50 mL), and washed with 10% sulphuric acid (200 mL), water (2×200 mL) and brine (200 mL). The organic was dried over anhydrous MgSO4, filtered and concentrated. Crude yield was 14.5 g. TLC indicated that majority of product was the methyl formate, which was purified by column chromatography. The purified formate was transferred to a 1000 mL round bottom flask and EtOH (600 mL) and a stirbar added. With stirring, water (25 mL—forming ˜5% aqueous solution) was slowly added, followed by KOH (2.0 g, 35.7 mmol). After 1 hour, solution had turned pale yellow. TLC indicated reaction had gone to completion. The solution was concentrated by rotovap to 50% of its volume and then poured into 200 mL of 5% HCl. The aqueous phase was extracted with ether (3×200 mL). The ether fractions were combined and washed with water (3×200 mL), dried (MgSO4) and concentrated to yield 8.8 g of di-γ-linolenyl methanol (16.8 mmol, 58%).
Reaction SMILES: [Si]([O:8][CH2:9][C@H:10]1[CH2:21][CH2:20][C:19]2[S:18][C:17]3[N:16]=[CH:15][N:14]=[C:13]([O:22][CH:23]4[CH2:32][CH2:31][C:26]5(OCC[O:27]5)[CH2:25][CH2:24]4)[C:12]=3[C:11]1=2)(C(C)(C)C)(C)C.Cl.C(=O)(O)[O-].[Na+]>C1COCC1>[OH:8][CH2:9][C@H:10]1[CH2:21][CH2:20][C:19]2[S:18][C:17]3[N:16]=[CH:15][N:14]=[C:13]([O:22][CH:23]4[CH2:32][CH2:31][C:26](=[O:27])[CH2:25][CH2:24]4)[C:12]=3[C:11]1=2
Reactant: CC(C)(C)[Si](C)(C)OC[C@H]1CCc2sc3ncnc(OC4CCC5(CC4)OCCO5)c3c21
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Product: O=C1CCC(Oc2ncnc3sc4c(c23)[C@@H](CO)CC4)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 80.3 %

Procedure:
To a solution of (3S)-3-[[(tert-butyldimethylsilyl)oxy]methyl]-12-[1,4-dioxaspiro[4.5]decan-8-yloxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraene (840 mg, 1.76 mmol, 1.00 equiv) in THF (20 mL) was added hydrochloric acid (3 M, 10 mL) at 0° C. and stirred overnight at room temperature. The pH value of the solution was adjusted to 10 with sodium bicarbonate (sat.), extracted with dichloromethane (100 mL), dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied on a silica gel column and eluted with EtOAc/petroleum ether (1:1) to give 450 mg (80%) of 4-[[(3S)-3-(hydroxymethyl)-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexan-1-one as a yellow oil.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[C:5]([NH2:11])=[C:4]([O:12][CH3:13])[CH:3]=1.OS(O)(=O)=O.[CH3:19][C:20](O)=[O:21]>CC(OC(C)=O)=O>[Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[C:5]([NH:11][C:20](=[O:21])[CH3:19])=[C:4]([O:12][CH3:13])[CH:3]=1
Reactant: CC(=O)O
Reactant: COc1cc(Br)cc([N+](=O)[O-])c1N
Agent: O=S(=O)(O)O
Solvent: CC(=O)OC(C)=O
Product: COc1cc(Br)cc([N+](=O)[O-])c1NC(C)=O
Temperature: 70 °C
Reaction time: 0.5 h
Yield: 75 %

Procedure:
To a solution of 4-bromo-2-methoxy-6-nitrobenzenamine (27.85 g) in HOAc (150 mL) and Ac2O (17 mL) was added conc. H2SO4 at 70° C. and the mixture was stirred at 70° C. for 30 min and kept at rt overnight. The formed precipitate was collected by filtration and washed with hexane to afford the desired product as a light yellow solid (24.45 g, 75%). 1H NMR (300 MHz, DMSO-d6) δ ppm 2.01 (s, 3H), 3.92 (s, 3H), 7.61 (d, 1H, J=1.8 Hz), 7.65 (d, 1H, J=1.8 Hz), 9.91 (s, 1H); LC-MS: m/e=289 [M+1]+
Reaction SMILES: [C:1]12([CH2:11][OH:12])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[H-].[Na+].Cl[CH2:16][C:17]([OH:19])=[O:18].O>CN(C=O)C>[C:1]12([CH2:11][O:12][CH2:16][C:17]([OH:19])=[O:18])[CH2:8][CH:7]3[CH2:6][CH:5]([CH2:4][CH:3]([CH2:9]3)[CH2:2]1)[CH2:10]2
Reactant: OCC12CC3CC(CC(C3)C1)C2
Reactant: O=C(O)CCl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: O=C(O)COCC12CC3CC(CC(C3)C1)C2
Temperature: 80 °C
Yield: 38.4 %

Procedure:
A solution of 1-adamantanemethanol (3.11 g, 18.7 mmol) in dry DMF (50 ml) was added to a suspension of sodium hydride (60% dispersion in oil, 1.55 g, 38.6 mmol) in DMF (20 ml). The mixture was warmed to 80° C. for 1 h, cooled to room temperature and a solution of chloroacetic acid (1.86 g, 19.6 mmol) in DMF (25 ml) was added dropwise. The mixture was heated at 80° C. for 17 h. On cooling, the mixture was poured into water (100 ml), extracted with ethyl acetate (2×80 ml), and the extracts were washed with 5%KHSO4 (150 ml), brine (150 ml) and dried (MgSO4). Filtration and evaporation of the solvent gave a white solid which was washed with diethyl ether and water, isolated by filtration and dried in vacuo at 50° C. The product was obtained as a white fluffy solid (1.61 g, 38%). 1H NMR (300 MHz, CDCl3) 4.08 (2H, s), 3.14 (2H, s), 2.00 (3H, br s), 1.70 (6H, q), 1.57 (6H, br s).
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][N:9]2[C:12]([C:15]([OH:17])=O)=[CH:13][N:14]=[C:8]2[CH:7]=1.C(Cl)(=O)C(Cl)=O.[CH2:24]([N:31]1[C:39]2[CH:38]=[CH:37][CH:36]=[C:35]([NH2:40])[C:34]=2[C:33]([CH2:41][CH3:42])=[N:32]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(N(CC)CC)C>ClCCl.CN(C)C=O>[CH2:24]([N:31]1[C:39]2[C:34](=[C:35]([NH:40][C:15]([C:12]3[N:9]4[CH:10]=[CH:11][C:6]([O:5][CH2:4][CH2:3][O:2][CH3:1])=[CH:7][C:8]4=[N:14][CH:13]=3)=[O:17])[CH:36]=[CH:37][CH:38]=2)[C:33]([CH2:41][CH3:42])=[N:32]1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1
Reactant: COCCOc1ccn2c(C(=O)O)cnc2c1
Reactant: CCc1nn(Cc2ccccc2)c2cccc(N)c12
Agent: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCc1nn(Cc2ccccc2)c2cccc(NC(=O)c3cnc4cc(OCCOC)ccn34)c12
Temperature: 5 °C
Reaction time: 0.17 h
Yield: 18.8 %

Procedure:
To a magnetically stirred suspension of 7-(2-methoxyethoxy)imidazo[1,2-a]pyridine-3-carboxylic acid (32.1 mg, 0.136 mmol) (prepared as in Example 1, steps A-D) in dry dichloromethane (1.5 mL), in a sealed vial, was added dry N,N-dimethylformamide (5 μL). The stirred mixture was cooled to 5° C. using ice bath. A solution of oxalyl chloride (86.8 μL, 0.174 mmol; 2M in dichloromethane) was added and the mixture was stirred for 10 minutes, occasionally allowing the resulting gases to vent. To the resulting solution was added 1-benzyl-3-ethyl-1H-indazol-4-amine (40 mg, 0.159 mmol) and triethylamine (30.2 μL, 0.217 mmol). The mixture was allowed to warm to ambient temperature and stirred for 16 hours. The mixture was evaporated to dryness under a stream of nitrogen. The resulting residue was purified using preparative thin layer chromatography, eluting with 5% methanol in dichloromethane. The material was further purified with a second preparative thin layer chromatography, eluting with 8% methanol in chloroform containing 0.5% ammonium hydroxide solution to provide N-(1-benzyl-3-ethyl-1H-indazol-4-yl)-7-(2-methoxyethoxy)imidazo[1,2-a]pyridine-3-carboxamide (12 mg). MS (APCI), positive scan, m/z=470.3 (M+H).
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7](=[O:13])[C:8]([O:10][CH2:11][CH3:12])=[O:9])[N:6]=1.[F:14][C:15]1[CH:20]=[CH:19][C:18]([N:21]=[C:22]=[O:23])=[CH:17][C:16]=1[N+:24]([O-:26])=[O:25]>CN(C)C=O>[F:14][C:15]1[CH:20]=[CH:19][C:18]([NH:21][C:22](=[O:23])[NH:1][C:2]2[S:3][CH:4]=[C:5]([C:7](=[O:13])[C:8]([O:10][CH2:11][CH3:12])=[O:9])[N:6]=2)=[CH:17][C:16]=1[N+:24]([O-:26])=[O:25]
Reactant: CCOC(=O)C(=O)c1csc(N)n1
Reactant: O=C=Nc1ccc(F)c([N+](=O)[O-])c1
Solvent: CN(C)C=O
Product: CCOC(=O)C(=O)c1csc(NC(=O)Nc2ccc(F)c([N+](=O)[O-])c2)n1

Procedure:
Following a procedure similar to that described in Preparation 1, the desired compound was prepared from 5 g of ethyl 2-aminothiazol-4-ylglyoxylate. 5.5 g of 4-fluoro-3-nitrophenyl isocyanate and 30 ml of dimethylformamide. The resulting product was a yellow powder having the following physical properties.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[C:7]2[S:21][CH:20]=[CH:19][C:8]=2[N:9]=[C:10]([CH2:12][CH2:13][C:14]([O:16]CC)=[O:15])[N:11]=1.[OH-].[Li+]>C1COCC1.O>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[C:7]2[S:21][CH:20]=[CH:19][C:8]=2[N:9]=[C:10]([CH2:12][CH2:13][C:14]([OH:16])=[O:15])[N:11]=1
Reactant: CCOC(=O)CCc1nc(-c2ccco2)c2sccc2n1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)CCc1nc(-c2ccco2)c2sccc2n1
Temperature: 25 °C
Reaction time: 16 h
Yield: 82.4 %

Procedure:
A solution of ethyl 3-(4-(2-furyl)thieno[3,2-d]pyrimidine-2-yl)propionate (0.07 g, 0.23 mmol) in THF (1.0 mL) and water (1.0 mL) was treated with lithium hydroxide (0.10 g, 2.32 mmol), stirred at room temperature for 16 h, concentrated in vacuo, dissolved in water, acidified to pH 2 by the addition of HCl (0.1 mL, 6.0-M), cooled in ice and filtered to give the title compound (0.052 g, 81%) as a white solid.
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:10][CH2:11][C:12]([CH3:15])([CH3:14])[N:13]=2)=[CH:5][CH:4]=1)[CH3:2].C([Li])CCC.C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:31])(=O)=O)=CC=1>C1COCC1.CCCCCC>[F:31][C:7]1[CH:8]=[C:3]([CH2:1][CH3:2])[CH:4]=[CH:5][C:6]=1[C:9]1[O:10][CH2:11][C:12]([CH3:14])([CH3:15])[N:13]=1
Reactant: CCc1ccc(C2=NC(C)(C)CO2)cc1
Reactant: O=S(=O)(c1ccccc1)N(F)S(=O)(=O)c1ccccc1
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CCc1ccc(C2=NC(C)(C)CO2)c(F)c1
Temperature: -70 °C
Reaction time: 8 h
Yield: 94529.8 %

Procedure:
The 4-ethylphenyloxazoline (2.03 g, 10 mmol) was dried in a vacuum oven at 60° C. for 2-3 hours, dissolved in 50 mL of dry THF, and charged to a 300 mL round bottom flask equipped with a thermometer, nitrogen inlet, and magnetic stir bar. The mixture was cooled under nitrogen to −70° C. in a dry ice/acetone bath. Butyl lithium in hexane (7.5 mL, 0.012 mmol) was added in two portions and warmed to −25° C. over 2 hours. The mixture was cooled again to 65° C. and N-fluorobenzenesulfonimide (3.79 g, 0.012 mmol) was added in three portions. The mixture was allowed to warm to room temperature and was stirred overnight. The reaction mixture was quenched with 100 mL of saturated NH4Cl, and transferred to a separatory funnel with ethyl ether washes. 25% NaOH was added slowly and mixed until an aqueous phase with pH=10 was achieved. The aqueous phase was extracted with ether and the ether was washed with a small volume of water. The ether extracts were dried over MgSO4 and evaporated to give 2.51 g of 2-(2-fluoro-4-ethyl-phenyl)-4,4-dimethyl-4,5-dihydro-oxazole as a brown oil. In a second experiment, a rate of 70% fluorination was achieved (highest) with a reactant ratio of 1:1.5:1.5 oxazoline: BuLi: N-fluorobenzenesulfonimide. 1H NMR (300 MHz, CDCl3) δ (ppm): 7.0 (d, 2H), 7.78 (t, 1H), 4.1 (s, 2H), 2.7 (q, 2H), 1.39 (s, 6H), 1.2 (t, 3H).
Reaction SMILES: [Cl-].C[SiH](C)C.Br[CH:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[F:15])[CH3:8].[Cl:16][C:17]1[CH:22]=[C:21](Cl)[N:20]=[CH:19][N:18]=1.O>O1CCCC1.BrC(Br)C.[Zn]>[Cl:16][C:17]1[CH:22]=[C:21]([CH:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[F:15])[CH3:8])[N:20]=[CH:19][N:18]=1
Reactant: Clc1cc(Cl)ncn1
Reactant: CC(Br)c1ccccc1F
Agent: CC(Br)Br
Agent: C[SiH](C)C
Agent: [Cl-]
Solvent: O
Solvent: C1CCOC1
Product: CC(c1cc(Cl)ncn1)c1ccccc1F
Reaction time: 0.33 h
Yield: 28.7 %

Procedure:
In 10 ml of tetrahydrofuran was suspended 1.3 g of zinc (powder), to which dibromoethane (2 drops) was added. The mixture was heated under reflux for 5 minutes, to which trimethylsilane chloride was added. The mixture was further heated under reflux for 5 minutes, to which a solution of 2.0 g of 1-(1-bromoethyl)-2-fluorobenzene dissolved in 20 ml of tetrahydrofuran was slowly added with heating under reflux, followed by stirring for 20 minutes. (The solution thus obtained is referred to as solution N). In 10 ml of tetrahydrofuran were suspended 1.5 g of 4,6-dichloropyrimidine and 0.2 g of tetrakistriphenylphosphine palladium, to which the above solution N was added, followed by heating under reflux for 3 hours and further stirring at room temperature for 12 hours. The reaction mixture was then poured into water and extracted three times with ethyl acetate. The organic layers were combined, washed with water, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel column chromatography to give 0.67 g of 4-chloro-6-(1-(2-fluorophenyl)ethyl)pyrimidine.
Reaction SMILES: C([NH:4][C:5]1[CH:6]=[C:7](N)[C:8]([S:11]([OH:14])(=[O:13])=[O:12])=[CH:9][CH:10]=1)(=O)C.Cl.N([O-])=O.[Na+].NC1C2C(=CC(S(O)(=O)=O)=CC=2O)C=C(S(O)(=O)=O)C=1.[Na].[OH-].[Na+].C(=O)(O)[O-].[Na+]>O>[S:11]([OH:14])(=[O:13])([C:8]1[CH:7]=[CH:6][C:5]([NH2:4])=[CH:10][CH:9]=1)=[O:12]
Reactant: CC(=O)Nc1ccc(S(=O)(=O)O)c(N)c1
Agent: Cl
Agent: Nc1cc(S(=O)(=O)O)cc2cc(S(=O)(=O)O)cc(O)c12
Agent: O=C([O-])O
Solvent: O
Product: Nc1ccc(S(=O)(=O)O)cc1

Procedure:
25.3 parts of 3-acetylamino-1-aminobenzene-6-sulphonic acid are diazotised in 500 parts of water with hydrochloric acid and sodium nitrite. The resultant strongly acid diazo comppound is treated with 32 parts of 1-amino-8-hydroxy-naphthalene-3,6-disulphonic acid in the form of the monosodium salt and the mixture is stirred at room temperature until no more diazo compound can be detected. The coupling mixture is then neutralised with sodium hydroxide solution, treated first with 20 parts of sodium bicarbonate and then with the diazo compound obtained from 17.3 parts of sulphanilic acid. After termination of the coupling, sufficient sodium hydroxide is added to give a 6 % solution and this is heated for 2 hours to 90°C in order to split off the acetyl group. After acidification with hydrochloric acid, the aminazo dye is precipitated with sodium chloride, filtered off and again dissolved neutral in 1000 parts of water with the addition of sodium carbonate. A solution of 18.5 parts of cyanuric chloride in 80 parts of acetone is added and the mixture is stirred for 2 hours between 0° and 10°C, the pH being kept between 5 and 6 by the dropwise addition of a dilute sodium hydroxide solution. Then an aqueous solution of 5.4 parts of 1,3-diaminobenzene is added and the reaction mixture is stirred for 2 hours between 30° and 40°C, the pH being kept between 6 and 7. After termination of the condensation, the resultant dye is salted out, filtered off and dried. It dyes cellulose fibres in strong, greenish blue shades. The dye has the formula ##SPC10##
Reaction SMILES: C([O:3][C:4](=[O:20])[CH2:5][N:6]([CH2:8][CH2:9][C:10]1[C:15]([N+:16]([O-:18])=[O:17])=[CH:14][CH:13]=[CH:12][C:11]=1[Cl:19])[CH3:7])C>Br.C(#N)C>[Cl:19][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]([N+:16]([O-:18])=[O:17])[C:10]=1[CH2:9][CH2:8][N:6]([CH2:5][C:4]([OH:20])=[O:3])[CH3:7]
Reactant: CCOC(=O)CN(C)CCc1c(Cl)cccc1[N+](=O)[O-]
Agent: Br
Solvent: CC#N
Product: CN(CCc1c(Cl)cccc1[N+](=O)[O-])CC(=O)O
Temperature: 70 °C
Reaction time: 8 h

Procedure:
{[2-(2-chloro-6-nitro-phenyl)-ethyl]-methyl-amino}-acetic acid ethyl ester (11.0 g, 0.0365 mole) dissolved in concentrated hydrobromic acid (48 wt. % in water, 200 mL) was allowed to stir at 70° C. overnight and then reduced to a small volume in vacuo. The residue oil was taken up in acetonitrile and the solution was evaporated in vacuo. This procedure was repeated until the water was removed and a crystalline residue remained. This material was used in the next step without further purification.
Reaction SMILES: [F:1][C:2]([F:26])([F:25])[C:3]1[CH:4]=[C:5]([NH:13][C:14](=[N:22][C:23]#[N:24])OC2C=CC=CC=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:27][CH:28]([CH3:32])[CH2:29][CH2:30][NH2:31].C(N(CC)CC)C>C(#N)C>[C:23]([NH:22][C:14]([NH:13][C:5]1[CH:6]=[C:7]([C:9]([F:11])([F:10])[F:12])[CH:8]=[C:3]([C:2]([F:1])([F:26])[F:25])[CH:4]=1)=[N:31][CH2:30][CH2:29][CH:28]([CH3:32])[CH3:27])#[N:24]
Reactant: N#CN=C(Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1)Oc1ccccc1
Reactant: CC(C)CCN
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CC(C)CCN=C(NC#N)Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Yield: 27.3 %

Procedure:
A solution of N-(3,5-bis(trifluoromethyl)phenyl)-N'-cyano-O-phenylisourea (1 mmol, 373 mg), 3-methylbutylamine (1.15 mmol,100 mg) and triethylamine (1.5 mmol, 150 mg) in acetonitrile (2 ml) was stirred for 24 h at 60° C. After concentration the residue was purified by column chromatography (heptane:ethyl acetate 1:1) to give the title compound (100 mg, 27%).