Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1(OC2C=CC=CC=2)C=CC=C[CH:2]=1.C([C:16]1[C:21]([NH:22]/[C:23](=[CH:27]\[C:28]([O-:30])=O)/[C:24]([O-:26])=[O:25])=[C:20](CC)[C:19]([Cl:33])=[CH:18][C:17]=1[Cl:34])C>>[Cl:33][C:19]1[CH:18]=[C:17]([Cl:34])[CH:16]=[C:21]2[C:20]=1[C:28](=[O:30])[CH:27]=[C:23]([C:24]([O:26][CH2:1][CH3:2])=[O:25])[NH:22]2
Reactant: CCc1c(Cl)cc(Cl)c(CC)c1N/C(=C\C(=O)[O-])C(=O)[O-]
Reactant: c1ccc(Oc2ccccc2)cc1
Product: CCOC(=O)c1cc(=O)c2c(Cl)cc(Cl)cc2[nH]1
Temperature: 244 °C

Procedure:
A 5-L three-neck flask equipped with a thermocouple, an addition funnel, and a distillation apparatus was charged with diphenyl ether (about 2.8 L), which was heated to about 244° C. The concentrated reaction mixture containing Compound 3 (about 1.1 mole) from Reaction 1, above, was added from the dropping funnel into the hot diphenyl ether over about 10 minutes with a nitrogen purge. The funnel was rinsed with about 200 mL of diphenyl ether, which was also added to the flask. The resulting mixture was heated at about 244° C. for about 1 hour to cyclize Compound 3 to form Compound 4. The reaction mixture then was cooled to room temperature, at which point Compound 4 crystallized out. The crystallized product was isolated and slurried with ethyl acetate (EtOAc; about 1 L). The crystals were collected and rinsed with EtOAc (3×500 mL), and then dried under high vacuum at room temperature to afford about 269.95 g of Compound 4 (85.8% yield over two steps).
Reaction SMILES: [OH2:1].S(=O)(=O)(O)O.[Cl:7][C:8]1[CH:13]=[C:12]([Cl:14])[CH:11]=[CH:10][C:9]=1[CH2:15][CH2:16][CH2:17][CH2:18][OH:19]>CC(C)=O.[O-2].[O-2].[O-2].[Cr+6]>[Cl:7][C:8]1[CH:13]=[C:12]([Cl:14])[CH:11]=[CH:10][C:9]=1[CH2:15][CH2:16][CH2:17][C:18]([OH:1])=[O:19]
Reactant: OCCCCc1ccc(Cl)cc1Cl
Reactant: O
Agent: [Cr+6]
Agent: O=S(=O)(O)O
Agent: [O-2]
Solvent: CC(C)=O
Product: O=C(O)CCCc1ccc(Cl)cc1Cl

Procedure:
By the method of Example 1, Step A, 3.63 g (0.0363 mole) of chromium trioxide, 5 mL of water, 5.6 g (0.056 mole) of 18M sulfuric acid, 10.4 mL of water, and 11.4 g (0.052 mole) of 4-(2,4-dichlorophenyl)-1-butanol in 332 mL of acetone are reacted, yielding 4-(2,4-dichlorophenyl)butanoic acid.
Reaction SMILES: C1C[O:4][CH2:3]C1.Br[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)=[CH:9][CH:8]=1.[Li]CCCC.CN(C=O)C>CCCCCC>[F:22][C:19]1[CH:20]=[CH:21][C:16]([O:15][CH2:14][CH2:13][C:10]2[CH:11]=[CH:12][C:7]([CH:3]=[O:4])=[CH:8][CH:9]=2)=[CH:17][CH:18]=1
Reactant: Fc1ccc(OCCc2ccc(Br)cc2)cc1
Reactant: C1CCOC1
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: CN(C)C=O
Product: O=Cc1ccc(CCOc2ccc(F)cc2)cc1
Temperature: -40 °C
Reaction time: 0.5 h

Procedure:
To a THF (100 mL) solution of 1-bromo-4-[2-(4-fluorophenoxy)ethyl]benzene (3.05 g) was added 1.6 M solution of n-BuLi in n-hexane (6.80 mL) dropwise at −70° C. under an argon atmosphere. After stirring for 30 minutes, DMF (1.20 mL) was slowly added at −70° C. The resultant mixture was stirred and slowly warmed to −40° C. for 3 hours. The reaction mixture was quenched by addition of saturated aqueous NH4Cl, and extracted with AcOEt. The organic layer was washed with water, saturated aqueous NaCl, dried over anhydrous MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane/AcOEt=9/1 to 1/1) to afford 4-[2-(4-fluorophenoxy)ethyl]benzaldehyde as a light yellow solid (1.63 g).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:13])[C:4](=[N:8][O:9][CH2:10][O:11][CH3:12])[C:5]([CH3:7])=[O:6].C1(C)C=CC=CC=1.[CH3:21][N:22]([CH:24](OC)OC)[CH3:23]>C(OC(C)C)(C)C>[CH3:1][O:2][C:3](=[O:13])[C:4](=[N:8][O:9][CH2:10][O:11][CH3:12])[C:5]([CH:7]=[CH:21][N:22]([CH3:24])[CH3:23])=[O:6]
Reactant: COC(OC)N(C)C
Reactant: COCON=C(C(C)=O)C(=O)OC
Solvent: CC(C)OC(C)C
Solvent: Cc1ccccc1
Product: COCON=C(C(=O)C=CN(C)C)C(=O)OC

Procedure:
6.4 g of 2-(methoxymethoxyimino)acetoacetic acid methyl ester in 30 of toluene are heated with 9 ml of N,N-dimethylformamidedimethylacetal for 5 hours at boiling. After cooling, the semi-crystalline residue is dissolved by heating in diisopropylether, the mixture is filtered. The precipitate obtained after cooling is filtered and dried to obtain the heading compound, m.p. 99°-100°.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]([O:13][CH3:14])[CH:10]=[C:9]2[C:4]=1[C:5](O)=[CH:6][CH:7]=[N:8]2.O=P(Cl)(Cl)[Cl:18]>C1(C)C=CC=CC=1>[Cl:18][C:5]1[C:4]2[C:9](=[CH:10][C:11]([O:13][CH3:14])=[CH:12][C:3]=2[O:2][CH3:1])[N:8]=[CH:7][CH:6]=1
Reactant: COc1cc(OC)c2c(O)ccnc2c1
Reactant: O=P(Cl)(Cl)Cl
Solvent: Cc1ccccc1
Product: COc1cc(OC)c2c(Cl)ccnc2c1

Procedure:
To a mixture of crude 5,7-dimethoxyquinolin-4-ol (5.36 g, 26 mmol) and Hunig'sBase (9.1 ml, 52 mmol) in toluene, was added POCl3(29 ml, 313 mmol). The mixture was refluxed for 5 h. Excess POCl3 was removed under reduced pressure and the mixture was azeotroped with toluene. The resultant gum was treated with sat. NaHCO3 until no gas generated. The mixture was extracted with EtOAc, the organic extracts were combined and washed with sodium bicarbonate and solvent removed under reduced pressure. The crude product was purified via column chromatography on silica gel (RediSep 120 g column, gradient elution with 0-50% EtOAc/DCM) to afford 4-chloro-5,7-dimethoxyquinoline as a yellow solid. MS: m/z=[M+H]+. 224.2 Calc'd for C11H10ClN: 223.7.
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[C:12]([N:14]([CH3:16])[CH3:15])[C:11]([C:17]#[C:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:10][C:9]=1[NH:25][C:26](=[O:38])[CH2:27][C:28]([C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([C:36]#[N:37])[CH:31]=1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:15][N:14]([CH3:16])[C:12]1[C:11]([C:17]#[C:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:10][C:9]2[NH:25][C:26](=[O:38])[CH2:27][C:28]([C:30]3[CH:31]=[C:32]([CH:33]=[CH:34][CH:35]=3)[C:36]#[N:37])=[N:7][C:8]=2[CH:13]=1
Reactant: CN(C)c1cc(NC(=O)OC(C)(C)C)c(NC(=O)CC(=O)c2cccc(C#N)c2)cc1C#Cc1ccccc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CN(C)c1cc2c(cc1C#Cc1ccccc1)NC(=O)CC(c1cccc(C#N)c1)=N2

Procedure:
The title compound was prepared from {2-[3-(3-cyano-phenyl)-3-oxo-propionyl-amino]-5-dimethylamino-4-phenylethynyl-phenyl}-carbamic acid tert.-butyl ester (Example M4) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (65 mg).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]([C:12]#[N:13])[N:3]=1.[NH:14]1[CH2:18][CH2:17][CH:16]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH2:15]1.CCN(CC)CC>CN1C(=O)CCC1>[C:12]([C:4]1[N:3]=[C:2]([N:14]2[CH2:18][CH2:17][CH:16]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:24])([CH3:23])[CH3:25])[CH2:15]2)[C:11]2[C:6]([CH:5]=1)=[CH:7][CH:8]=[CH:9][CH:10]=2)#[N:13]
Reactant: N#Cc1cc2ccccc2c(Cl)n1
Reactant: CC(C)(C)OC(=O)NC1CCNC1
Solvent: CCN(CC)CC
Solvent: CN1CCCC1=O
Product: CC(C)(C)OC(=O)NC1CCN(c2nc(C#N)cc3ccccc23)C1
Temperature: 160 °C

Procedure:
A mixture of 1-chloroisoquinoline-3-carbonitrile (438 mg, 2.322 mmol), tert-butyl pyrrolidin-3-ylcarbamate (519 mg, 2.79 mmol) and Et3N (0.653 mL, 4.64 mmol) in NMP (3 mL) was heated at 160° C. for 30 minutes in a microwave reactor. The crude reaction mixture, which contained the title compound, was used directly in the next step.
Reaction SMILES: [C:1]([C:5]1[N:9]([CH2:10][CH:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[C:8]2[CH:17]=[CH:18][C:19]([S:21](Cl)(=[O:23])=[O:22])=[CH:20][C:7]=2[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH:25]1[CH2:28][CH:27]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:26]1>CN(C1C=CN=CC=1)C.CC#N>[C:1]([C:5]1[N:9]([CH2:10][CH:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[C:8]2[CH:17]=[CH:18][C:19]([S:21]([N:25]3[CH2:28][CH:27]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:34])([CH3:33])[CH3:35])[CH2:26]3)(=[O:23])=[O:22])=[CH:20][C:7]=2[N:6]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)c1nc2cc(S(=O)(=O)Cl)ccc2n1CC1CCOCC1
Reactant: CC(C)(C)OC(=O)NC1CNC1
Agent: CN(C)c1ccncc1
Solvent: CC#N
Product: CC(C)(C)OC(=O)NC1CN(S(=O)(=O)c2ccc3c(c2)nc(C(C)(C)C)n3CC2CCOCC2)C1
Yield: 82.9 %

Procedure:
Following the same procedure in Example 1, Step A, using 2-tert-butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazole-5-sulfonyl chloride (0.74 g, 2.0 mmol), tert-butyl azetidin-3-ylcarbamate (0.35 g, 2.0 mmol) and DMAP (0.75 g, 6.1 mmol) in MeCN (60 mL). The crude product was purified by MPLC using Hex/EtOAc (1:1) on silica gel to give 0.84 g (83%) of a white solid as the title compound. 1H NMR (400 MHz, METHANOL-D4) δ 1.32 (s, 9 H), 1.49-1.64 (m, 4 H), 1.66 (s, 9 H), 2.29-2.45 (m, 1 H), 3.30-3.41 (m, 2 H), 3.63 (m, 2 H), 3.88-4.01 (m, 4 H), 4.03-4.14 (m, 1 H), 4.52 (d, J=7.62 Hz, 2 H), 7.90 (dd, J=8.59, 1.37 Hz, 1 H), 8.05 (d, J=8.79 Hz, 1 H), 8.15 (d, J=1.17 Hz, 1 H); MS (ESI) (M+H)+=506.8; Anal. Calcd for C25H38N4O5S+0.90 TFA+0.10 EtOAc+0.50H2O (628.31): C, 52.19; H, 6.53; N, 8.92. Found: C, 52.13; H, 6.53; N, 8.84.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[N:2]1.[I-].[Na+].[OH-].[Na+].Cl[CH2:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>C(O)(CC)(C)C.C1(C)C=CC=CC=1>[C:13]1([CH2:12][CH2:11][N:1]2[CH:5]=[CH:4][N:3]=[N:2]2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: c1c[nH]nn1
Reactant: ClCCc1ccccc1
Agent: [I-]
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1
Solvent: CCC(C)(C)O
Product: c1ccc(CCn2ccnn2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 73.1 %

Procedure:
1,2,3-Triazole (1634 mg, 23.7 mmol), sodium iodide (2364 mg, 15.8 mmol), sodium hydroxide (946 mg, 23.7 mmol) were added to t-amyl alcohol (6.2 ml), and the mixture was refluxed under stirring for 1 hour. 1-Chloro-2-phenylethane (2217 mg, 15.8 mmol) was dissolved in t-amyl alcohol (6.2 ml) and added dropwise under reflux over 1 hour. The mixture was refluxed under stirring for 3.5 hours. The mixture was cooled to room temperature and toluene (50 ml) was added. The mixture was washed with water (50×2), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=3/1→1/3) to give 1-(2-phenylethyl)-1H-1,2,3-triazole as a colorless oil (2.0 g, yield 73%). 2-(2-Phenylethyl)-2H-1,2,3-triazole (315 mg) was obtained as a colorless oil (yield 12%). 1-(4-phenylethyl)-1H-1,2,3-triazole
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:10][C@H:9]2[NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[F:25][C:26]([F:37])([F:36])[C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][CH:32]=1>C(#N)C.O>[F:25][C:26]([F:37])([F:36])[C:27]1[CH:32]=[C:31]([C:2]2[CH:7]=[CH:6][C:5]([C@@H:8]3[CH2:10][C@H:9]3[NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:4][CH:3]=2)[CH:30]=[CH:29][CH:28]=1
Reactant: CC(C)(C)OC(=O)N[C@@H]1C[C@H]1c1ccc(Br)cc1
Reactant: OB(O)c1cccc(C(F)(F)F)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC#N
Product: CC(C)(C)OC(=O)N[C@@H]1C[C@H]1c1ccc(-c2cccc(C(F)(F)F)c2)cc1
Yield: 66.2 %

Procedure:
To a solution of tert-butyl (trans)-2-(4-bromophenyl)cyclopropylcarbamate (Intermediate E[a2]) (1 g, 3.2 mmol), potassium carbonate (1.31 g, 9.6 mmol), 3-(trifluoromethyl) phenylboronic acid (0.73 g, 3.8 mmol) in acetonitrile:water (4:1) were degassed for 30 mins, added tetrakis triphenylphosphine palladium (36 mg, 0.032 mmol), degassed again for 10 mins, heated the reaction mixture at reflux temperature for 5 h. After completion, the reaction mixture was poured in ice water (50 mL), extracted with, ethyl acetate (2×50 mL). Combined extracts were washed with water (70 mL), brine (70 mL), dried over anhydrous Na2SO4, filtered and evaporated. The crude residue was purified by column chromatography (SiO2), by using EtOAc:Petroleum ether (2:8) to get tert-butyl (trans)-2-(3′-(trifluoromethyl)biphenyl-4-yl)cyclopropylcarbamate (0.8 g, 66%) as a white solid.
Reaction SMILES: N1C=CC=NC=1NC(NC1C=CC=CC=1C(F)(F)F)=O.[NH2:21][C:22]1[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:23]=1[S:29]([NH2:32])(=[O:31])=[O:30].[F:33][C:34]([F:45])([F:44])[C:35]1[CH:36]=[C:37]([N:41]=[C:42]=[O:43])[CH:38]=[CH:39][CH:40]=1>>[Cl:28][C:26]1[CH:25]=[CH:24][C:23]([S:29]([NH2:32])(=[O:31])=[O:30])=[C:22]([NH:21][C:42]([NH:41][C:37]2[CH:38]=[CH:39][CH:40]=[C:35]([C:34]([F:33])([F:44])[F:45])[CH:36]=2)=[O:43])[CH:27]=1
Reactant: O=C=Nc1cccc(C(F)(F)F)c1
Reactant: Nc1cc(Cl)ccc1S(N)(=O)=O
Agent: O=C(Nc1ncccn1)Nc1ccccc1C(F)(F)F
Product: NS(=O)(=O)c1ccc(Cl)cc1NC(=O)Nc1cccc(C(F)(F)F)c1

Procedure:
This compound was prepared in a manner analogous to 1-Pyrimidin-2-yl-3-(2-trifluoromethyl-phenyl)-urea (Compound 2) from 2-amino-4-chloro-benzenesulfonamide and 3-trifluoromethylphenylisocyanate, yielding 4-chloro-2-[3-(3-trifluromethyl-phenyl)-ureido]-benzenesulfonamide (550 mg). Mp.=163-165° C.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([C:8](=[O:11])[NH:9][CH3:10])[CH:5]=[CH:4][C:3]=1[N:12]1[CH2:17][CH2:16][N:15](C(OC(C)(C)C)=O)[CH2:14][CH2:13]1.Cl>O1CCOCC1.CCOCC>[CH3:10][NH:9][C:8](=[O:11])[C:6]1[CH:5]=[CH:4][C:3]([N:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)=[C:2]([CH3:1])[CH:7]=1
Reactant: CNC(=O)c1ccc(N2CCN(C(=O)OC(C)(C)C)CC2)c(C)c1
Agent: Cl
Solvent: C1COCCO1
Solvent: CCOCC
Product: CNC(=O)c1ccc(N2CCNCC2)c(C)c1
Temperature: 23 °C
Reaction time: 0.5 h

Procedure:
To tert-butyl 4-(2-methyl-4-(methylcarbamoyl)phenyl)piperazine-1-carboxylate (1.90 g, 5.70 mmol) was added hydrochloric acid solution (17.10 mL, 68.4 mmol) in dioxane at 23° C. The reaction was stirred at 23° C. for 30 min. The resulting suspension was diluted with Et2O (20 mL), filtered, rinsed with Et2O (3×10 mL), and the resulting solid was dried in vacuo to provide the title compound as an off-white, hygroscopic solid (1.70 g, 5.55 mmol, 97% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.28 (s, 3H) 2.72-2.79 (m, 3H) 3.05-3.14 (m, 4H) 3.17-3.28 (m, 4H) 7.06 (d, J=8.34 Hz, 1H) 7.64-7.68 (m, 1H) 7.68-7.70 (m, 1H) 8.29-8.39 (m, 1H) 9.36 (br. s., 2H). ESI-MS: m/z 234.2 (M+H)+.
Reaction SMILES: [CH2:1]([O:3][C:4]([S-:6])=[S:5])[CH3:2].[K+].[PH:8](=[O:11])([OH:10])[OH:9].[CH2:12]([C:14]([CH2:42][CH3:43])([CH:16](Br)[C:17]1[N:21]=[CH:20][N:19]([C:22]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:18]=1)[CH3:15])[CH3:13].O>O1CCCC1.C1OCCOCCOCCOCCOCCOC1>[PH:8](=[O:9])([OH:11])[OH:10].[CH2:42]([C:14]([CH2:12][CH3:13])([CH:16]([S:5][C:4]([O:3][CH2:1][CH3:2])=[S:6])[C:17]1[N:21]=[CH:20][N:19]([C:22]([C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:18]=1)[CH3:15])[CH3:43]
Reactant: CCOC(=S)[S-]
Reactant: CCC(C)(CC)C(Br)c1ncn(C(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Agent: C1COCCOCCOCCOCCOCCO1
Agent: O=[PH](O)O
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Product: CCOC(=S)SC(c1ncn(C(c2ccccc2)(c2ccccc2)c2ccccc2)n1)C(C)(CC)CC
Reaction time: 48 h
Yield: 80.2 %

Procedure:
A stirred solution of 18-Crown-6 (0.03 g) in dry tetrahydrofuran (25 ml) was treated successively with potassium ethylxanthate (0.44 g) and diethyl 3-bromo-3(1-trityl-1,2,4-triazol-3-yl)propane phosphonate (1.0 g, prepared as described in Example 29). The mixture was allowed to stand for two days, poured into water and extracted with ethyl acetate. The extracts were washed with brine, dried over magnesium sulphate, and evaporated under reduced pressure. The residue was chromatographed on silica, using dichloromethane-ethanol (49:1) as eluant, to give diethyl 3(ethoxythiocarbonylthio)-3(1-trityl-1,2,4-triazol-3-yl)propane phosphonate (0.86 g) as a colourless gum. NMR(CDCl3): δ 1.25(6H,m), 1.4(3H,t), 1.7-1.9(2H,m), 2.3-2.4(2H,m), 4.0(4H,m), 4.6(2H,m), 5.05(1H,t), 7.1(6H,m), 7.3(9H,m), 7.9(1H,S). M/S: M+ 609.
Reaction SMILES: [CH2:1]([N:8]=[N+:9]=[N-:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:11][C:12]([CH3:16])([CH3:15])[C:13]#[CH:14]>C[C-]1C(C)=C(C)C(C)=C1C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Ru+].C1C=CC=CC=1>[CH2:1]([N:8]1[C:13]([C:12]([CH3:16])([CH3:15])[CH3:11])=[CH:14][N:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: [N-]=[N+]=NCc1ccccc1
Reactant: C#CC(C)(C)C
Agent: Cl[Ru+]
Agent: Cc1c(C)c(C)[c-](C)c1C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: c1ccccc1
Product: CC(C)(C)c1cnnn1Cc1ccccc1

Procedure:
Benzyl azide (0.400 g, 3.00 mmol), 3,3-dimethyl-1-butyne (0.556 ml, 4.51 mmol), Cp*RuCl(PPh3)2 (50 mg, 0.063 mmol). Solvent, benzene; reaction temperature, 80° C.; reaction time, 4 hours; yield, 0.54 g (83%). EI-MS: m/z 216 [M+1].
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[C:12]([F:15])([F:14])[F:13])[NH:8][C:7](=[O:16])[N:6]([NH:17][S:18]([CH3:21])(=[O:20])=[O:19])[C:5]2=[O:22].[CH3:23][C:24]1(OC)[CH2:28][CH2:27][CH:26](OC)O1>C(O)(=O)C>[CH3:23][C:24]1[N:1]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][C:11]=2[C:12]([F:13])([F:15])[F:14])[NH:8][C:7](=[O:16])[N:6]([NH:17][S:18]([CH3:21])(=[O:20])=[O:19])[C:5]3=[O:22])[CH:26]=[CH:27][CH:28]=1
Reactant: COC1CCC(C)(OC)O1
Reactant: CS(=O)(=O)Nn1c(=O)[nH]c2cc(C(F)(F)F)c(N)cc2c1=O
Solvent: CC(=O)O
Product: Cc1cccn1-c1cc2c(=O)n(NS(C)(=O)=O)c(=O)[nH]c2cc1C(F)(F)F

Procedure:
To a solution of 200 mg (0.59 mmol) of N-(6-amino-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulfonamide in 10 ml of acetic acid, 87 mg (0.60 mmol) of 2-methyl-2,5-dimethoxy-tetrahydrofuran is added and the reaction mixture is stirred at reflux for 5 hours. Subsequently the solvent is evaporated and the residue is dried for I day at 60° C. and high vacuum to yield N-[6-(2-methyl-pyrrol-1-yl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide. 1H-NMR; DMSO-d6 (400 MHz, ppm): 7.69 (s, 1H, aromatic); 7.54 (s, 1H , aromatic); 6.6 (s, 1H, N-CH═CH in pyrrol); 5.97 (t, 1H, CH═CH═CH in pyrrol); 5.83 (m, 1H, CH═CH-C(CH3)-N in pyrrol); 3.05 (s, 3H, SO2-CH3); 1.82 (s, 3H, pyrrol-1-CH3). LC-MS: 403 [M+H]+; Agilent LC/MSD 1100 Series; LC-MS method: Column: SunFireC18, 4.6*50 mm, 3.5 μm; positive MS; water/acetonitril 95:5 to 5:95 in 5 min, flow: 1.5 ml/min.
Reaction SMILES: [CH3:1][C:2]1([CH3:9])[NH:6][C:5](=[O:7])[NH:4][C:3]1=[O:8].C(=O)([O-])[O-].[K+].[K+].[Cl:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]Cl>O>[Cl:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][N:4]1[C:3](=[O:8])[C:2]([CH3:9])([CH3:1])[NH:6][C:5]1=[O:7]
Reactant: ClCCCCCCCl
Reactant: CC1(C)NC(=O)NC1=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Product: CC1(C)NC(=O)N(CCCCCCCl)C1=O
Reaction time: 0.42 h

Procedure:
128 g of 5,5-dimethyl-hydantoin (1.0 mol), 69 g of anhydrous potassium carbonate (0.5 mol) and 775 g of 1,6-dichlorohexane are reacted at 132°-150°C internal temperature (external temperature 160°C) and the resulting water of reaction is removed continuously by azeotropic circulatory distillation. After 6 hours 25 minutes, the reaction is complete and the reaction mixture is filtered hot to remove the potassium chloride formed. The filtrate is concentrated on a rotary evaporator and dried to constant weight at 100°C and 10-1 mm Hg.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([O:23][CH2:24][CH:25]=[C:26]([Cl:28])[Cl:27])[CH:5]=[C:6]([Cl:22])[C:7]=1[O:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][CH2:14][CH:15](O)[C:16]([Cl:20])=[C:17]([F:19])[F:18].C(N(S(F)(F)[F:35])CC)C.O>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([O:23][CH2:24][CH:25]=[C:26]([Cl:28])[Cl:27])[CH:5]=[C:6]([Cl:22])[C:7]=1[O:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][CH2:14]/[CH:15]=[C:16](\[Cl:20])/[C:17]([F:35])([F:19])[F:18]
Reactant: OC(COCCCCOc1c(Cl)cc(OCC=C(Cl)Cl)cc1Cl)C(Cl)=C(F)F
Reactant: CCN(CC)S(F)(F)F
Solvent: ClCCl
Solvent: O
Product: FC(F)(F)/C(Cl)=C/COCCCCOc1c(Cl)cc(OCC=C(Cl)Cl)cc1Cl
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 55.3 %

Procedure:
A solution of 0.36 g of 3,5-dichloro-1-(3,3-dichloro-2-propenyloxy)-4-(4-(3-chloro-4,4-difluoro-2-hydroxy-3-butenyloxy)butyloxy)benzene in 5 ml of dichloromethane was slowly added dropwise to a solution of 0.12 g of diethylaminosulfur trifluoride (DAST) in 10 ml of dichloromethane with stirring at -78° C. After complement of the dropwise addition, the reaction mixture was returned to room temperature over 30 minutes and poured into water. The dichloromethane layer was separated, washed with water, dried over magnesium sulfate and then evaporated to give a crude product. The crude product was subjected to silica gel chromatography, which afforded 0.20 g of (Z)-3,5-dichloro-1-(3,3-dichloro-2-propenyloxy)-4-(4-(3-chloro-4,4,4-trifluoro-2-butenyloxy)butyloxy)benzene (yield, 55%), nD23.7 1.5160.
Reaction SMILES: [NH2:1][C:2]1([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([Cl:11])[CH:9]=2)[NH:4][C:3]1=[O:12].[H-].[Na+].[CH3:21][O:22][C:23]1[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=[CH:25][C:24]=1[S:31](Cl)(=[O:33])=[O:32].O>CN(C=O)C>[NH2:1][C:2]1([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([Cl:11])[CH:9]=2)[N:4]([S:31]([C:24]2[CH:25]=[CH:26][C:27]([O:29][CH3:30])=[CH:28][C:23]=2[O:22][CH3:21])(=[O:33])=[O:32])[C:3]1=[O:12]
Reactant: NC1(c2ccccc2)C(=O)Nc2ccc(Cl)cc21
Reactant: COc1ccc(S(=O)(=O)Cl)c(OC)c1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccc(S(=O)(=O)N2C(=O)C(N)(c3ccccc3)c3cc(Cl)ccc32)c(OC)c1
Reaction time: 0.33 h

Procedure:
A solution of 0.3 g of 3-amino-5-chloro-1,3-dihydro-3-phenylindol-2-one in 7 ml of DMF is cooled to 0° C. under an argon atmosphere and 0.037 g of sodium hydride as an 80% dispersion in oil is added. After stirring for 20 minutes, 0.275 g of 2,4-dimethoxybenzenesulfonyl chloride is added and the reaction mixture is stirred overnight, the temperature being allowed to rise to RT. It is poured into water, extracted with AcOEt, washed with water and with a saturated solution of NaCl, dried over sodium sulfate and evaporated under vacuum. The residue is chromatographed on silica using a DCM/AcOEt mixture (95/5; v/v) as the eluent to give the expected product after crystallization from a DCM/iso ether/hexane mixture. m=0.31 g. M.p.=108°-110° C.
Reaction SMILES: [NH:1]1[CH2:6][CH:5]=[C:4]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]([N:16]3[CH2:24][C:23]4[CH:22]=[CH:21][N:20]=[CH:19][C:18]=4[CH2:17]3)=[O:15])=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.[O:25]1[CH2:30][CH2:29][CH:28]([CH:31]=O)[CH2:27][CH2:26]1>>[O:25]1[CH2:30][CH2:29][CH:28]([CH2:31][N:1]2[CH2:2][CH2:3][CH:4]([C:7]3[CH:12]=[CH:11][C:10]([NH:13][C:14]([N:16]4[CH2:24][C:23]5[CH:22]=[CH:21][N:20]=[CH:19][C:18]=5[CH2:17]4)=[O:15])=[CH:9][CH:8]=3)[CH2:5][CH2:6]2)[CH2:27][CH2:26]1
Reactant: O=CC1CCOCC1
Reactant: O=C(Nc1ccc(C2=CCNCC2)cc1)N1Cc2ccncc2C1
Product: O=C(Nc1ccc(C2CCN(CC3CCOCC3)CC2)cc1)N1Cc2ccncc2C1

Procedure:
The title compound was prepared as described in Example 926, substituting N-(4-(piperidin-4-yl)phenyl)-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide for N-(4-(1,2,3,6-tetrahydropyridin-4-yl)phenyl)-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide and tetrahydro-2H-pyran-4-carbaldehyde for isobutraldehyde. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.60 (s, 1H), 8.49 (d, J=5.0 Hz, 1H), 8.33 (s, 1H), 7.44 (m, 3H), 7.12 (m, 2H), 4.79 (m, 4H), 3.83 (m, 2H), 3.27 (m, 2H), 2.92 (m, 2H), 2.40 (m, 1H), 2.14 (d, J=7.2 Hz, 2H), 1.95 (m, 2H), 1.74 (m, 3H), 1.61 (m, 4H), 1.12 (m, 2H); MS (ESI(+)) m/e 421 (M+H).
Reaction SMILES: C([O:5][C:6](=[O:35])[CH2:7][O:8][C:9]1[C:14]2=[CH:15][CH:16]=[C:17]3[C:26]([N:25]=[C:24]4[C:19]([CH:20]=[CH:21][CH:22]=[C:23]4[C:27](=[O:34])[NH:28][CH2:29][CH2:30][N:31]([CH3:33])[CH3:32])=[N:18]3)=[C:13]2[CH:12]=[CH:11][CH:10]=1)(C)(C)C.[F:36][C:37]([F:42])([F:41])[C:38]([OH:40])=[O:39]>ClCCl>[F:36][C:37]([F:42])([F:41])[C:38]([OH:40])=[O:39].[CH3:32][N:31]([CH3:33])[CH2:30][CH2:29][NH:28][C:27]([C:23]1[C:24]2[C:19](=[N:18][C:17]3[C:26]([N:25]=2)=[C:13]2[CH:12]=[CH:11][CH:10]=[C:9]([O:8][CH2:7][C:6]([OH:35])=[O:5])[C:14]2=[CH:15][CH:16]=3)[CH:20]=[CH:21][CH:22]=1)=[O:34]
Reactant: CN(C)CCNC(=O)c1cccc2nc3ccc4c(OCC(=O)OC(C)(C)C)cccc4c3nc12
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CN(C)CCNC(=O)c1cccc2nc3ccc4c(OCC(=O)O)cccc4c3nc12
Reaction time: 4 h

Procedure:
To a solution of [11-(2-dimethylamino-ethylcarbamoyl)-benzo[a]phenazin-4-yloxy]-acetic acid tert-butyl ester (18 mg) in dry dichloromethane (1 mL) was added trifluoroacetic acid (1 mL). After stirring for 4 hours the solvent was removed in vacuo to yield crude product. This was triturated with ether to yield the title compound as a yellow solid (10 mg).