Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N-:1]=[N+:2]=[N-:3].[Na+].[CH2:5]([N:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[N:10]2[CH:17]=[C:18]([C:20]#[N:21])[CH:19]=[C:9]2[C:8]1=[O:22])[CH3:6].[Cl-].[NH4+].CN(C)C=O>O>[CH2:5]([N:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[N:10]2[CH:17]=[C:18]([C:20]3[NH:21][N:3]=[N:2][N:1]=3)[CH:19]=[C:9]2[C:8]1=[O:22])[CH3:6]
Reactant: CCn1c(=O)c2cc(C#N)cn2c2ccccc21
Reactant: [N-]=[N+]=[N-]
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCn1c(=O)c2cc(-c3nnn[nH]3)cn2c2ccccc21
Reaction time: 12 h
Yield: 48 %

Procedure:
0.48 g (7.4 mmole) of sodium azide were added to a suspension of 1.3 g (5.5 mmole) of the product of Step B, 0.425 g (8.0 mmole) of ammonium chloride and 50 ml of dimethylformamide and the mixture was stirred at 130°-140° C. for 12 hours and was then cooled. 200 ml of water were added thereto and the mixture was filtered. The recovered product was crystallized from a methanol-ethyl acetate mixture to obtain 0.74 g (48% yield) of 5-ethyl-2-(1H-tetrazol-5-yl)-pyrrolo-[1,2-a]-quinoxaline-4(5H)-one in the form of off-white crystals melting at 295°-297° C. with decomposition.
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[N:9]=[N:8][C:7]([C:10]2[CH:11]=[C:12]([NH:16][C:17](=[O:19])[CH3:18])[CH:13]=[CH:14][CH:15]=2)=[CH:6][CH:5]=1.[CH2:20](I)[CH3:21]>O1CCCC1>[CH2:20]([N:16]([C:12]1[CH:13]=[CH:14][CH:15]=[C:10]([C:7]2[N:8]=[N:9][C:4]([Cl:3])=[CH:5][CH:6]=2)[CH:11]=1)[C:17](=[O:19])[CH3:18])[CH3:21]
Reactant: CCI
Reactant: CC(=O)Nc1cccc(-c2ccc(Cl)nn2)c1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCN(C(C)=O)c1cccc(-c2ccc(Cl)nn2)c1
Reaction time: 0.5 h

Procedure:
To a solution of 4.0 g of sodium hydride (50% dispersion in oil) in 400 ml of anhydrous tetrahydrofuran was added 18.0 g of N-[3-(6-chloro-3-pyridazinyl)phenyl]acetamide. The solution was stirred for 0.5 hrs, then 6.4 ml ethyl iodide was added. After stirring for 18 hours, the reaction mixture was treated as described in Example 63 to give 19.8 g of colorless crystals, mp 116°-119° C. Recrystalization from acetone-hexane gave colorless crystals, mp 120°-121° C.
Reaction SMILES: [CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:15]([C:20]#[C:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:16][C:17](Cl)=[O:18])[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C)C1C=CC=CC=1.[CH:37]([OH:40])([CH3:39])[CH3:38]>CCOCC>[CH:37]([O:40][C:17](=[O:18])[CH2:16][CH:15]([C:9]1[CH:10]=[CH:11][C:12]([O:13][CH3:14])=[C:7]([O:6][CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)[CH:8]=1)[C:20]#[C:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)([CH3:39])[CH3:38]
Reactant: CC(C)O
Reactant: COc1ccc(C(C#Cc2ccccc2)CC(=O)Cl)cc1OC1CCCC1
Solvent: CN(C)c1ccccc1
Solvent: CCOCC
Product: COc1ccc(C(C#Cc2ccccc2)CC(=O)OC(C)C)cc1OC1CCCC1
Reaction time: 18 h

Procedure:
A solution of (+/-)-3-(3-cyclopentyloxy-4-methoxyphenyl)-3-phenylethynylpropionic acid chloride (150 mg, 0.42 mmol) and dimethylaniline (100 mg, 0.83 mmol) in Et2O (5 ml) was treated with i-propanol (1 ml) and stirred at 23° for 18 hr. The solvents were evaporated, and the residue taken up in Et2O, washed with 3N HCl, H2O, dried, and the solvent evaporated. The residue was purified by flash chromatography (silica gel, 20% EtOAc/hexane), and gave the titled compound, 82 mg (54%). MP . 1H NMR (400 MHz, CDCl3) δ 7.38 (m, 2 H), 7.30 (m, 3 H), 6.94 (m, 2 H), 6.78 (d, 1 H), 5.02 (m, 1 H), 4.78 (m, 1 H), 4.30 (t, 1 H), 3.80 (s, 3 H), 2.82 (d of d, 1 H), 2.72 (d of d, 1 H), 1.78-1.96 (m, 6 H), 1.60 (m, 2 H), 1.22 (d, 3 H), 1.16 (d, 3 H).
Reaction SMILES: [OH:1][CH2:2][CH2:3][S:4][C:5]1[CH:10]=[CH:9][C:8]([C:11](=[O:21])[C:12]([CH3:20])([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[CH3:13])=[CH:7][CH:6]=1.[CH2:22]([S:26][CH2:27][C:28](=[CH2:32])[C:29](O)=[O:30])[CH2:23][CH2:24][CH3:25].Cl.C(N=C=NCCCN(C)C)C.C(OCC)(=O)C>CC(N(C)C)=O>[CH3:20][C:12]([N:14]1[CH2:15][CH2:16][O:17][CH2:18][CH2:19]1)([CH3:13])[C:11]([C:8]1[CH:9]=[CH:10][C:5]([S:4][CH2:3][CH2:2][O:1][C:29](=[O:30])[C:28]([CH2:27][S:26][CH2:22][CH2:23][CH2:24][CH3:25])=[CH2:32])=[CH:6][CH:7]=1)=[O:21]
Reactant: CC(C)(C(=O)c1ccc(SCCO)cc1)N1CCOCC1
Reactant: C=C(CSCCCC)C(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CC(=O)N(C)C
Solvent: CCOC(C)=O
Product: C=C(CSCCCC)C(=O)OCCSc1ccc(C(=O)C(C)(C)N2CCOCC2)cc1
Temperature: -20 °C
Reaction time: 8 h

Procedure:
1.0 g (3.2 mmol) of 1-[4-(2-Hydroxyethylthio)phenyl]-2-methyl-2-morpholin-4-yl-propane-1-one and 0.56 g (3.2 mmol) of 2-(butylthiomethyl)acrylic acid are dissolved in 20 ml of dry dimethylacetamide and cooled to −20° C. To the solution is added 0.68 g (3.54 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride in 5 ml of dry dimethylacetamide. The mixture is gradually warmed to room temperature and stirred overnight. To the mixture is added ethyl acetate. The mixture then is washed with saturated sodium chloride solution and dried over MgSO4. After distilling off the ethyl acetate, the residue is purified by means of column chromatography on silica gel with ethyl acetate-hexane (1:2) as an eluent, and an oily product is obtained.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:25]=[CH:24][C:6]([CH2:7][N:8]2[CH2:17][CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:18]4([C:21]#N)[CH2:20][CH2:19]4)[CH:14]=3)[C:9]2=[O:23])=[CH:5][CH:4]=1.CC(C[AlH]CC(C)C)C.C1C[O:38]CC1>ClCCl.C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:25]=[CH:24][C:6]([CH2:7][N:8]2[CH2:17][CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:18]4([CH:21]=[O:38])[CH2:20][CH2:19]4)[CH:14]=3)[C:9]2=[O:23])=[CH:5][CH:4]=1
Reactant: COc1ccc(CN2CCc3cc(C4(C#N)CC4)ccc3C2=O)cc1
Reactant: C1CCOC1
Agent: CC(C)C[AlH]CC(C)C
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: COc1ccc(CN2CCc3cc(C4(C=O)CC4)ccc3C2=O)cc1
Temperature: -50 °C
Reaction time: 1 h

Procedure:
To a solution of 722 mg of 1-[2-(4-Methoxy-benzyl)-1-oxo-1,2,3,4-tetrahydro-isoquinolin-6-yl]-cyclopropanecarbonitrile in 3 ml of dichloromethane and 9 ml toluene, cooled at −50° C. was added dropwise 4.8 mL of 1.0 M DIBAL in THF. After stirring 1 hour at −50° C., the reaction was quenched with 5 ml of 1N HCl, left to warm to room temperature and stirred 0.5 hour. Next the mixture was extracted with ethyl acetate and the organic layer was washed with 0.5 N HCl, sodium carbonate 5% solution, and brine. After drying over sodium sulfate and removal of solvent in vacuo, the residue was purified by silica gel column chromatography using 30%-60% ethylacetate in hexane to provide 0.075 g of 1-[2-(4-Methoxy-benzyl)-1-oxo-1,2,3,4-tetrahydro-isoquinolin-6-yl]-cyclopropanecarbaldehyde.
Reaction SMILES: [C:1]1([CH:7]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:8]([OH:10])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CN(C1C=CC=CN=1)C.[CH2:26]([O:33][C:34]1[C:43]2[C:38](=[C:39]([CH2:44][CH2:45][NH2:46])[CH:40]=[CH:41][CH:42]=2)[CH:37]=[CH:36][CH:35]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl.O>[CH2:26]([O:33][C:34]1[C:43]2[C:38](=[C:39]([CH2:44][CH2:45][NH:46][C:8]([CH:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[O:10])[CH:40]=[CH:41][CH:42]=2)[CH:37]=[CH:36][CH:35]=1)[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1
Reactant: NCCc1cccc2c(OCc3ccccc3)cccc12
Reactant: O=C(O)C(c1ccccc1)c1ccccc1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccccn1
Agent: Cl
Solvent: ClCCl
Solvent: O
Product: O=C(NCCc1cccc2c(OCc3ccccc3)cccc12)C(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 51.6 %

Procedure:
To a solution of diphenylacetic acid (0.171 g) in methylene chloride (10 ml), dimethylaminopyridine (0.01 g) and 1-benzyloxy-5-(2-aminoethyl)naphthalene (0.196 g) were added at room temperature. After 10 minutes, EDC·HCl (0.154 g) was added to the mixture solution. The mixture was stirred overnight at room temperature for 1 night. After termination of reaction, water and methylene chloride were added to the reaction mixture. The organic layer was washed with a saturated aqueous solution of ammonium chloride, water and a saturated aqueous solution of sodium chloride, dried over and concentrated under reduced pressure. The residue was purified on silica gel chromatography to give the title compound (0.172 g) having the following physical data.
Reaction SMILES: [C:1]([O:4][C@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[C:7](=[CH:8][CH2:9][C@@H:10]3[C@@H:19]2[CH2:18][CH2:17][C@@:15]2([CH3:16])[C@H:11]3[CH2:12][CH2:13][C@@H:14]2[O:24][C:25](=[O:27])[CH3:26])[CH2:6]1)(=[O:3])[CH3:2].CC1(C)N(Br)C(=O)N(Br)C1=O.C(=O)(O)[O-].[Na+]>CCCCCC>[C:1]([O:4][C@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[C:7](=[CH:8][CH:9]=[C:10]3[C@@H:19]2[CH2:18][CH2:17][C@@:15]2([CH3:16])[C@H:11]3[CH2:12][CH2:13][C@@H:14]2[O:24][C:25](=[O:27])[CH3:26])[CH2:6]1)(=[O:3])[CH3:2]
Reactant: CC(=O)O[C@H]1CC[C@@]2(C)C(=CC[C@H]3[C@@H]4CC[C@H](OC(C)=O)[C@@]4(C)CC[C@@H]32)C1
Agent: CC1(C)C(=O)N(Br)C(=O)N1Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCCCCC
Product: CC(=O)O[C@H]1CC[C@@]2(C)C(=CC=C3[C@@H]4CC[C@H](OC(C)=O)[C@@]4(C)CC[C@@H]32)C1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
A mixture of androst-5-ene-3β,17β-diol diacetate (3.75 g, 10 mmol), dibromantin (2.03 g, 7 mmol), and sodium bicarbonate (4.54 g, 54 mmol) in hexane (200 ml) is heated under reflux for 0.5 hours. The mixture is then cooled and filtered and the filtrate evaporated to dryness. The residue is dissolved in 50 ml toluene and treated with lithium bromide (2 g) in 5 ml of acetone. The mixture is stirred at 0° C. for 2 hours and then treated with 2 ml triethylamine and 1.5 ml benzenethiol. After stirring at room temperature for 1.5 hours, 100 ml ethyl acetate is added and the organic solution is washed with 1 N hydrochloric acid and water. The organic phase is dried and concentrated. The residue is then redissolved in 75 ml ethyl acetate, cooled to 0° C. and treated with 2.6 g of m-chloroperbenzoic acid for 2 hours. The mixture is washed with 10% sodium bicarbonate solution and then concentrated. The residue is dissolved in 100 ml toluene, treated with triethylamine (3.6 ml), heated at 70° C. for 24 hours, cooled, and washed with water. The organic solution was concentrated and chromatographed to yield androst-5,7-diene-3β,17β-diol diacetate. The diacetate is treated with K2CO3 in a 10:1 methanol:water solution overnight to yield, after extractive workup, androst-5,7-diene-3β,17β-diol.
Reaction SMILES: [I:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][CH3:12])=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].[C:13](Cl)(=O)[CH3:14]>C(O)C>[I:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][CH3:12])=[C:6]([CH:10]=1)[C:7]([O:9][CH2:13][CH3:14])=[O:8]
Reactant: COc1ccc(I)cc1C(=O)O
Reactant: CC(=O)Cl
Solvent: CCO
Product: CCOC(=O)c1cc(I)ccc1OC

Procedure:
A mixture of 5-iodo-2-methoxybenzoic acid (13.4 g, 48 mmol), acetyl chloride (1 mL) and ethanol (50 mL) was heated 4 hours with stirring at reflux. The mixture was concentrated and the residue was dissolved in diethyl ether. The solution was poured into ice-cold saturated sodium bicarbonate and the organic phase was washed with brine, dried (K2 CO3), filtered and concentrated to give ethyl 5-iodo-2-methoxybenzoate (13.5 g, 44 mmol) as an oil.
Reaction SMILES: [NH2:1][C:2]1[NH:7][C:6](=[O:8])[N:5]([CH3:9])[C:4](=[O:10])[C:3]=1[NH:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[CH:19](OCC)(OCC)OCC>CN(C=O)C>[CH3:9][N:5]1[C:4](=[O:10])[C:3]2[N:11]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH:19]=[N:1][C:2]=2[NH:7][C:6]1=[O:8]
Reactant: CCOC(OCC)OCC
Reactant: Cn1c(=O)[nH]c(N)c(NCc2ccccc2)c1=O
Solvent: CN(C)C=O
Product: Cn1c(=O)[nH]c2ncn(Cc3ccccc3)c2c1=O
Temperature: 110 °C

Procedure:
To 6-amino-3-methyl-5-(phenylmethylamino)pyrimidine-2,4-dione (24.6 g=0.1 mol) in DMF (125 ml) at 60° C. add triethyl orthoformate (75 ml=0.45 mol). Heat to 110° C. for 5 hr, cool in ice, filter, and wash with methanol, then ether, to obtain the title compound, m.p. 268°-71° C.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5](Cl)=[O:6].C[NH2:12]>C1COCC1.CO>[Br:1][C:2]1[CH:3]=[C:4]([C:5]([NH2:12])=[O:6])[CH:8]=[CH:9][CH:10]=1
Reactant: O=C(Cl)c1cccc(Br)c1
Reactant: CN
Solvent: CO
Solvent: C1CCOC1
Product: NC(=O)c1cccc(Br)c1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a solution of 3-bromobenzoyl chloride (21.75 g) in THF (20 ml) was added a 40% solution (50 ml) of methylamine in methanol at 0° C. and the mixture was stirred at 0° C. for 1 h. The solvent was evaporated under reduced pressure, and the residue was dissolved in ethyl acetate, the mixture was washed with water and brine, dried (magnesium sulfate) and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate-hexane to give the title compound (18.6 g) as colorless powder crystals.
Reaction SMILES: [CH2:1]([O:8][C:9]([C@@H:11]1[CH2:15][CH2:14][CH2:13][N:12]1[C:16](=[O:30])[C@H:17]([N:27]=[C:28]=[O:29])[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:31]([NH2:33])[CH3:32]>ClCCl>[CH2:1]([O:8][C:9]([C@@H:11]1[CH2:15][CH2:14][CH2:13][N:12]1[C:16](=[O:30])[C@H:17]([NH:27][C:28]([NH:33][CH2:31][CH3:32])=[O:29])[CH2:18][C:19]1[CH:20]=[CH:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COc1ccc(C[C@@H](N=C=O)C(=O)N2CCC[C@H]2C(=O)OCc2ccccc2)cc1
Reactant: CCN
Solvent: ClCCl
Product: CCNC(=O)N[C@H](Cc1ccc(OC)cc1)C(=O)N1CCC[C@H]1C(=O)OCc1ccccc1
Reaction time: 16 h
Yield: 42 %

Procedure:
1-[2-(R)-Isocyanato-3-(4-methoxyphenyl)-propionyl]-pyrrolidine-2-(S)-carboxylic acid benzyl ester (0.60 g) was dissolved under nitrogene in 20 mL of dichloromethane and ethyl amine was allowed to pass through at-20° C. for 5 minutes. The mixture was kept stirring for 16 h. The volatiles were pumped off and the remaining residue was purified by silica chromatography (dichloromethane/methanol 80/20) to give 0.29 g (42%) of the title compound as a colorless oil. (+)-APCI-MS: 454(MH−).
Reaction SMILES: C(Cl)(=O)C([Cl:4])=O.[CH3:7][Si:8]([CH2:11][C:12](=[CH2:16])[C:13](O)=[O:14])([CH3:10])[CH3:9]>C1(C)C=CC=CC=1>[CH3:7][Si:8]([CH2:11][C:12](=[CH2:16])[C:13]([Cl:4])=[O:14])([CH3:10])[CH3:9]
Reactant: C=C(C[Si](C)(C)C)C(=O)O
Reactant: O=C(Cl)C(=O)Cl
Solvent: Cc1ccccc1
Product: C=C(C[Si](C)(C)C)C(=O)Cl
Temperature: 50 °C
Reaction time: 2 h

Procedure:
With stirring at 50° C., 60.0 g of oxalyl chloride was slowly added dropwise to a mixture of 69.8 g of 2-(trimethylsilylmethyl)acrylic acid obtained in Example 2 and 300 ml of toluene. Stirring was continued at the temperature. After gas evolution ceased, stirring was continued at 70° C. for 2 hours. After cooling, the product in toluene solution was directly used in the subsequent step.
Reaction SMILES: C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.[NH2:13][CH:14]1[C:35](=[O:36])[N:16]2[C:17]([C:32]([OH:34])=[O:33])=[C:18]([CH2:21][S:22][C:23]3[N:24]([CH3:31])[N:25]=[C:26]([OH:30])[C:27](=[O:29])[N:28]=3)[CH2:19][S:20][C@H:15]12.S1C2C=CC=CC=2N=C1S[C:47](=[O:56])[C:48]([C:50]1[N:51]=[C:52]([NH2:55])[S:53][CH:54]=1)=[O:49].C(O)C>ClCCl>[NH2:55][C:52]1[S:53][CH:54]=[C:50]([C:48](=[O:49])[C:47]([NH:13][CH:14]2[C:35](=[O:36])[N:16]3[C:17]([C:32]([OH:34])=[O:33])=[C:18]([CH2:21][S:22][C:23]4[N:24]([CH3:31])[N:25]=[C:26]([OH:30])[C:27](=[O:29])[N:28]=4)[CH2:19][S:20][C@H:15]23)=[O:56])[N:51]=1
Reactant: Cn1nc(O)c(=O)nc1SCC1=C(C(=O)O)N2C(=O)C(N)[C@H]2SC1
Reactant: Nc1nc(C(=O)C(=O)Sc2nc3ccccc3s2)cs1
Agent: C/C(=N\[Si](C)(C)C)O[Si](C)(C)C
Solvent: CCO
Solvent: ClCCl
Product: Cn1nc(O)c(=O)nc1SCC1=C(C(=O)O)N2C(=O)C(NC(=O)C(=O)c3csc(N)n3)[C@H]2SC1
Reaction time: 2 h

Procedure:
14.85 ml of N,O-bis(trimethylsilyl)acetamide are added at 30° to 7.4 g of 7-amino-3-[(2,5-dihydro-6-hydroxy-2-methyl-5-oxo-1,2,4-triazin-3-yl)thiomethyl]ceph-3-em-4-carboxylic acid (water content: 3.7%) in 50 ml of dichloromethane. After two hours at 30°, the mixture is cooled to -15°. 8.1 g of 2-(2-amino-4-thiazolyl)-2-oxothioacetic-acid-S-benzothiazol-2-ylester are added, and stirred for six hours at -15°. The preparation is added to 500 ml of ethanol which has been warmed to 50°, then cooled whilst stirring and stirred for one hour at 0°. The deposit is filtered off, washed and dried. 9.1 g of the title compound are obtained as a yellow powder.
Reaction SMILES: [SH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.CC(N(C)C)=O.[F:14][C:15]([F:27])([F:26])[C:16]1[CH:17]=[C:18](Cl)[CH:19]=[CH:20][C:21]=1[N+:22]([O-:24])=[O:23].[OH-].[Na+]>O>[F:14][C:15]([F:26])([F:27])[C:16]1[CH:17]=[C:18]([S:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=2)[CH:19]=[CH:20][C:21]=1[N+:22]([O-:24])=[O:23]
Reactant: O=[N+]([O-])c1ccc(Cl)cc1C(F)(F)F
Reactant: Sc1ccccn1
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)N(C)C
Solvent: O
Product: O=[N+]([O-])c1ccc(Sc2ccccn2)cc1C(F)(F)F
Yield: 85.5 %

Procedure:
A mixture of 25 g of 2-mercaptopyridine, 70 ml of dimethylacetamide and 45.7 g of 3-trifluoromethyl-4-nitrochlorobenzene was heated at 80° to 90° C. and 35 g of 40% NaOH aq. solution was added to the mixture. After the reaction, the reaction mixture was poured into water and the product was extracted with ethyl ether and the ether phase was washed with a dilute NaOH aq. solution and then, with water and dried with anhydrous sodium sulfate and ether was distilled off to obtain 52 g of 2-trifluoromethyl-4-(pyridine-2-ylthio) nitrobenzene.
Reaction SMILES: [C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[C:18]([OH:20])[CH:17]=[CH:16][C:15]=2[F:21])=[O:12])[N:7]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl[C:29]1[C:38]2[C:33](=[CH:34][C:35]([O:41][CH3:42])=[C:36]([O:39][CH3:40])[CH:37]=2)[N:32]=[CH:31][N:30]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[C:18]([O:20][C:29]3[C:38]4[C:33](=[CH:34][C:35]([O:41][CH3:42])=[C:36]([O:39][CH3:40])[CH:37]=4)[N:32]=[CH:31][N:30]=3)[CH:17]=[CH:16][C:15]=2[F:21])=[O:12])[N:7]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[N:6]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: COc1cc2ncnc(Cl)c2cc1OC
Reactant: CC(C)(C)c1cc(NC(=O)Nc2cc(O)ccc2F)n(-c2ccccc2)n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1cc2ncnc(Oc3ccc(F)c(NC(=O)Nc4cc(C(C)(C)C)nn4-c4ccccc4)c3)c2cc1OC
Temperature: 35 °C
Reaction time: 15 h
Yield: 5.8 %

Procedure:
To a stirred solution of 1-(3-tert-butyl-1-phenyl-1H-pyrazol-5-yl)-3-(2-fluoro-5-hydroxyphenyl)urea (217 mg, 0.59 mmol) and 4-chloro-6,7-dimethoxyquinazoline (132 mg, 0.59 mmol) in DMF (4 mL) at rt, was added potassium carbonate (163 mg, 1.18 mmol). The reaction mixture was stirred at 35° C. for 15 h. The mixture was poured into water, and the resulting brown solid was filtrated, washed with water, and dried to afford the crude product. Purification via reverse-phase preparative HPLC afforded 1-(3-tert-butyl-1-phenyl-1H-pyrazol-5-yl)-3-(5-(6,7-dimethoxyquinazolin-4-yloxy)-2-fluorophenyl)urea (19 mg, 6%) as a solid. 1H NMR (400 MHz, DMSO-d6) δ 9.02 (brs, 1H), 8.89 (brs, 1H), 8.57 (s, 1H), 8.16 (m, 1H), 7.53-7.59 (m, 5H), 7.37-7.46 (m, 3H), 7.15 (m, 1H), 6.43 (s, 1H), 4.00 (s, 3H), 3.98 (s, 3H), 1.29 (s, 9H); LC-MS (ESI) m/z 557 (M+H)+.