Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]2[N:12]3[CH:13]=[CH:14][C:15]([F:17])=[CH:16][C:11]3=[N:10][C:9]=2[C:18]2[CH:19]=[CH:20][C:21]([O:35][CH3:36])=[C:22]([CH:34]=2)[C:23]([NH:25][C:26]2[C:31]([F:32])=[CH:30][CH:29]=[CH:28][C:27]=2[F:33])=[O:24])[CH:5]=[CH:4][N:3]=1.[CH3:37][O:38][C:39]1[CH:45]=[C:44]([N:46]2[CH2:51][CH2:50][CH:49]([N:52]3[CH2:57][CH2:56][N:55]([S:58]([CH3:61])(=[O:60])=[O:59])[CH2:54][CH2:53]3)[CH2:48][CH2:47]2)[CH:43]=[CH:42][C:40]=1[NH2:41].Cl.O1CCOCC1.C[O-].[Na+]>FC(F)(F)CO.CO.C(Cl)Cl.CCCCCC>[F:33][C:27]1[CH:28]=[CH:29][CH:30]=[C:31]([F:32])[C:26]=1[NH:25][C:23](=[O:24])[C:22]1[CH:34]=[C:18]([C:9]2[N:10]=[C:11]3[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][N:12]3[C:8]=2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:41][C:40]3[CH:42]=[CH:43][C:44]([N:46]4[CH2:51][CH2:50][CH:49]([N:52]5[CH2:57][CH2:56][N:55]([S:58]([CH3:61])(=[O:60])=[O:59])[CH2:54][CH2:53]5)[CH2:48][CH2:47]4)=[CH:45][C:39]=3[O:38][CH3:37])[N:7]=2)[CH:19]=[CH:20][C:21]=1[O:35][CH3:36]
Reactant: COc1ccc(-c2nc3cc(F)ccn3c2-c2ccnc(Cl)n2)cc1C(=O)Nc1c(F)cccc1F
Reactant: COc1cc(N2CCC(N3CCN(S(C)(=O)=O)CC3)CC2)ccc1N
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: ClCCl
Solvent: CCCCCC
Solvent: CO
Product: COc1cc(N2CCC(N3CCN(S(C)(=O)=O)CC3)CC2)ccc1Nc1nccc(-c2c(-c3ccc(OC)c(C(=O)Nc4c(F)cccc4F)c3)nc3cc(F)ccn23)n1
Temperature: 175 °C
Yield: 58.8 %

Procedure:
To 5-[3-(2-chloro-4-pyrimidinyl)-7-fluoroimidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluoro-phenyl)-2-(methyloxy)benzamide (Example 197, step A) (85 mg, 0.17 mmol) and 2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}aniline (Example 58, step B) (61 mg, 0.17 mmol) in 2,2,2-trifluoroethanol (0.80 mL) was added 4 M HCl in dioxane (83 μL, 0.33 mmol). The mixture was stirred and heated on a microwave at 175° C. for 35 min, then cooled to rt. The mixture was neutralized with 0.5M sodium methoxide in MeOH. The mixture was concentrated under vacuum and the residue purified by silica gel chromatography to give a yellow oil. The oil was dissolved in minimal DCM, then hexane was added until a precipitate was formed. The slurry was cooled at −10° C. for 30 min, then poured through a Teflon filter, washing the solids with cold hexanes. The solids were dried under vacuum to give the title compound (85 mg, 0.10 mmol, 61%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ9.78 (s, 1H), 9.44 (br s, 1H), 8.49 (s, 1H), 8.20 (d, 1H, J=5.31 Hz), 8.07-8.11 (m, 1H), 7.75-7.80 (m, 1H), 7.58 (dd, 1H, J=2.56, 9.52 Hz), 7.35-7.42 (m, 2H), 7.29 (d, 1H, J=8.61 Hz), 7.18 (t, 2H, J=7.97 Hz), 6.97-7.04 (m, 1H), 6.68-6.70 (m, 1H), 6.48-6.53 (m, 2H), 3.99 (s, 3H), 3.73-3.81 (m, 5H), 3.06-3.11 (m, 4H), 2.85 (s, 3H), 2.68 (t, 2H, J=11.54 Hz), 2.58-2.62 (m, 4H), 2.38-2.46 (m, 1H), 1.80-1.87 (m, 2H), 1.48-1.60 (m, 2H). MS (ESI): 842 [M+H]+.
Reaction SMILES: C(OCl)(C)(C)C.CCOCC.[NH:12]1[CH2:20][CH2:19][CH2:18][C@H:13]1[C:14]([O:16][CH3:17])=[O:15]>C(N(CC)CC)C>[NH:12]1[CH2:20][CH2:19][CH:18]=[C:13]1[C:14]([O:16][CH3:17])=[O:15]
Reactant: COC(=O)[C@@H]1CCCN1
Agent: CC(C)(C)OCl
Solvent: CCOCC
Solvent: CCN(CC)CC
Product: COC(=O)C1=CCCN1
Temperature: -50 °C
Reaction time: 1 h

Procedure:
Triethylamine (8.4 mL) was added to H-Pro-OMe HCl (7.512 g) in ether (27 mL) and the reaction was stirred for 2 hours. The reaction mixture was filtered, and Et2O was removed by evaporation. The residue was purified by vacuum distillation, affording 4.119 g of H-Pro-OMe as colorless oil. t-BuOCl (3.59 mL) was added dropwise to an Et2O (100 mL) solution of H-Pro-OMe (4.089 g) and the reaction was stirred at −50° C. for 1 hour. The reaction mixture was warmed to room temperature and triethylamine (4.64 mL) was added to the reaction mixture, followed by stirring for 3 days. The reaction mixture was filtered, and concentrated under reduced pressure. The residue was purified by vacuum distillation to obtain Methyl pyrroline-2-carboxylate (3647-154) as a colorless oil. ESI-MS calculated for C6H9NO2 [MH]+: 128.1; observed: 128.2. 1H NMR (400 MHz, CDCl3): 4.09 (tt, J=7.6 Hz, 2.5 Hz, 2H), 3.85 (s, 3H), 2.81 (tt, J=8.2 Hz, 2.8 Hz, 2H), 1.97 (quintet, J=8.0 Hz, 2H). 13C NMR (100 MHz, CDCl3): 168.2, 163.1, 62.5, 52.5, 35.2, 22.1. ESI-MS calculated for C5H7NO2 [MH]+: 114.1; observed: 114.2. 1H NMR (400 MHz, D2O): 3.84 (tt, J=7.4 Hz, 2.5 Hz, 2H), 2.73 (tt, J=8.2 Hz, 2.6 Hz, 2H), 1.92 (quintet, J=7.8 Hz, 2H). 13C NMR (100 MHz, D2O): 175.5, 171.8, 60.1, 35.6, 21.8ESI-MS calculated for C5H7NO2 [MH]+: 114.1; observed: 114.2. 1H NMR (400 MHz, D2O): 3.84 (tt, J=7.4 Hz, 2.5 Hz, 2H), 2.73 (tt, J=8.2 Hz, 2.6 Hz, 2H), 1.92 (quintet, J=7.8 Hz, 2H). 13C NMR (100 MHz, D2O): 175.5, 171.8, 60.1, 35.6, 21.8.
Reaction SMILES: [CH:1]1([C:4]2[N:5]=[CH:6][C:7]([C:15]([OH:17])=O)=[N:8][C:9]=2[O:10][CH2:11][CH:12]2[CH2:14][CH2:13]2)[CH2:3][CH2:2]1.[CH3:18][C:19]([NH2:30])([CH3:29])[CH2:20][CH:21]([C:23]1[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=1)[CH3:22]>>[CH3:18][C:19]([NH:30][C:15]([C:7]1[CH:6]=[N:5][C:4]([CH:1]2[CH2:2][CH2:3]2)=[C:9]([O:10][CH2:11][CH:12]2[CH2:13][CH2:14]2)[N:8]=1)=[O:17])([CH3:29])[CH2:20][CH:21]([C:23]1[CH:24]=[CH:25][N:26]=[CH:27][CH:28]=1)[CH3:22]
Reactant: O=C(O)c1cnc(C2CC2)c(OCC2CC2)n1
Reactant: CC(CC(C)(C)N)c1ccncc1
Product: CC(CC(C)(C)NC(=O)c1cnc(C2CC2)c(OCC2CC2)n1)c1ccncc1

Procedure:
The title compound was synthesized in analogy to Example 69, using 5-cyclopropyl-6-cyclopropylmethoxy-pyrazine-2-carboxylic acid (Example 10 g 10 mg, 0.043 mmol) and 1,1-dimethyl-3-pyridin-4-yl-butylamine (12 mg, 0.064 mmol) as starting materials and isolated (10 mg, 59.38%) as white solid; LC-MS (UV peak area, ESI) 99.2%, 395.2 (M+H)+.
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].[C:5](Cl)(=[O:7])[CH3:6].[CH2:9]([CH:17]1[CH2:25][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:18]1)[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].S(=O)(=O)(O)O>ClCCl>[CH2:9]([CH:17]1[CH2:25][C:24]2[C:19](=[CH:20][CH:21]=[C:22]([C:5](=[O:7])[CH3:6])[CH:23]=2)[CH2:18]1)[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: CCCCCCCCC1Cc2ccccc2C1
Reactant: CC(=O)Cl
Agent: O=S(=O)(O)O
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: CCCCCCCCC1Cc2ccc(C(C)=O)cc2C1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
Subsequently, 450 ml of dry dichloromethane and 68.7 g (5.15×10-1M) of anhydrous aluminum chloride were placed in a 1 liter-reaction vessel and cooled below 0° C. To the mixture, 37.2 g (4.74×10-1M) of acetyl chloride was added dropwise in 10 minutes below 0° C. and then 90 g (3.91×10-1M) of the above prepared 2-octylindan was added dropwise below 0° C., followed by stirring for 2 hours below 0° C. and further stirring for 2 hours at room temperature. After the reaction, the reaction mixture was poured into 1 liter of ice water and 90 ml of concentrated sulfuric acid was added. The dichloromethane layer was separated from the above mixture and washed with water, followed by drying with anhydrous magnesium sulfate and distilling-off of the solvent to obtain a crude product. The crude product was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=20/1) to obtain 57.6 g of 2-octyl-5-acetylindan.
Reaction SMILES: O[CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH:11]2[O:23][CH2:24][C:25]2[CH:34]=[CH:33][C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH:26]=2)=[CH:6][CH:5]=1.C(P(CCCC)CCCC)CCC.[C:48]1([S:54]C2C=CC=CC=2)[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1>N1C=CC=CC=1>[CH:26]1[C:27]2[C:32](=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:33]=[CH:34][C:25]=1[CH2:24][O:23][CH:11]1[CH:10]([C:7]2[CH:8]=[CH:9][C:4]([CH2:3][CH2:2][S:54][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)=[CH:5][CH:6]=2)[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17])[CH2:12]1
Reactant: CC(C)(C)OC(=O)N1CCC(c2ccc(CCO)cc2)C(OCc2ccc3ccccc3c2)C1
Reactant: c1ccc(Sc2ccccc2)cc1
Agent: CCCCP(CCCC)CCCC
Solvent: c1ccncc1
Product: CC(C)(C)OC(=O)N1CCC(c2ccc(CCSc3ccccc3)cc2)C(OCc2ccc3ccccc3c2)C1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A mixture of 200 mg (0.43 mmol) of tert-butyl (3RS,4RS)-4-[4-(2-hydroxy-ethyl)-phenyl]-3-naphthalen-2-ylmethoxy-piperidine-1-carboxylate, 263 mg (1.29 mmol) of tributylphosphine and 284 mg (1.29 mmol) of diphenyl sulphide in 1 ml of pyridine was stirred at room temperature for 18 hours. Subsequently, the reaction mixture was evaporated under reduced pressure and the residue, without further working-up, was chromatographed directly on silica gel using methylene chloride as the eluent. The tert-butyl (3RS,4RS)-3-naphthalen-2-ylmethoxy-4-[4-(2-phenylsulphanyl-ethyl)-phenyl]-piperidine-1-carboxylate was obtained as a colourless oil in quantitative yield; MS: 554 (M+H)+.
Reaction SMILES: [CH:1]1([CH2:7][NH2:8])[CH2:6][CH2:5][CH:4]=[CH:3][CH2:2]1.C(N(CC)CC)C.Cl[C:17]([O:19][CH2:20][CH3:21])=[O:18]>ClCCl>[CH:1]1([CH2:7][NH:8][C:17](=[O:18])[O:19][CH2:20][CH3:21])[CH2:6][CH2:5][CH:4]=[CH:3][CH2:2]1
Reactant: NCC1CC=CCC1
Reactant: CCOC(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCOC(=O)NCC1CC=CCC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 84.9 %

Procedure:
Cyclohex-3-enylmethylamine (10 g, 90 mmol) was dissolved in 200 mL of dichloromethane and cooled in an ice bath. Triethylamine (16.8 mL, 120 mmol) was added, followed by drop-wise addition of ethyl chloroformate (10.9 g, 0.100 mol). The mixture was stirred overnight at ambient temperature, then washed with water, dilute HCl, dilute aqueous sodium hydroxide, and brine (50 mL each). The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give the crude carbamate (14 g, 85%).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:24])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([O:14][C:15]2[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=2[CH2:22]Br)[CH:7]=1)[CH3:2].[CH3:25][N:26]1[CH2:30][CH2:29][NH:28][C:27]1=[O:31]>>[CH2:1]([O:3][C:4](=[O:24])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([O:14][C:15]2[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=2[CH2:22][N:28]2[CH2:29][CH2:30][N:26]([CH3:25])[C:27]2=[O:31])[CH:7]=1)[CH3:2]
Reactant: CCOC(=O)Cc1ccc(OC)c(Oc2ccc(Br)cc2CBr)c1
Reactant: CN1CCNC1=O
Product: CCOC(=O)Cc1ccc(OC)c(Oc2ccc(Br)cc2CN2CCN(C)C2=O)c1

Procedure:
Prepared according to the procedure described in Example 116, Step 1, using the following starting materials: [3-(4-bromo-2-bromomethyl-phenoxy)-4-methoxy-phenyl]-acetic acid ethyl ester and 1-methyl-2-imidazolidinone.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:9]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[CH3:17][O:18][C:19]1[CH:56]=[CH:55][C:22]([CH2:23][N:24]([CH2:46][C:47]2[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][CH:48]=2)[C:25]2[N:30]=[CH:29][C:28]([C:31]3[C:32]4[CH2:45][CH2:44][NH:43][C:33]=4[N:34]=[C:35]([N:37]4[CH2:42][CH2:41][O:40][CH2:39][CH2:38]4)[N:36]=3)=[CH:27][N:26]=2)=[CH:21][CH:20]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.ClCCl.CN(C)C=O>[CH3:54][O:53][C:50]1[CH:49]=[CH:48][C:47]([CH2:46][N:24]([CH2:23][C:22]2[CH:21]=[CH:20][C:19]([O:18][CH3:17])=[CH:56][CH:55]=2)[C:25]2[N:26]=[CH:27][C:28]([C:31]3[C:32]4[CH2:45][CH2:44][N:43]([C:2]5[CH:3]=[C:4]([C:9]([N:11]6[CH2:16][CH2:15][O:14][CH2:13][CH2:12]6)=[O:10])[CH:5]=[CH:6][C:7]=5[F:8])[C:33]=4[N:34]=[C:35]([N:37]4[CH2:42][CH2:41][O:40][CH2:39][CH2:38]4)[N:36]=3)=[CH:29][N:30]=2)=[CH:52][CH:51]=1
Reactant: O=C(c1ccc(F)c(Br)c1)N1CCOCC1
Reactant: COc1ccc(CN(Cc2ccc(OC)cc2)c2ncc(-c3nc(N4CCOCC4)nc4c3CCN4)cn2)cc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1
Solvent: CN(C)C=O
Solvent: ClCCl
Product: COc1ccc(CN(Cc2ccc(OC)cc2)c2ncc(-c3nc(N4CCOCC4)nc4c3CCN4c3cc(C(=O)N4CCOCC4)ccc3F)cn2)cc1
Temperature: 100 °C
Reaction time: 6 h
Yield: 93 %

Procedure:
A dimethylformamide solution (2 ml) of the obtained (3-bromo-4-fluoro-phenyl)-morpholin-4-yl-methanone crude product (56.1 mg), bis-(4-methoxy-benzyl)-[5-(2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrimidin-2-yl]-amine (70.0 mg, 0.130 mmol), palladium acetate (2.9 mg, 0.013 mmol), X-Phos (12.4 mg, 0.0261 mmol) and potassium phosphate (55.1 mg, 0.260 mmol) was degassed under ultrasonic irradiation, followed by stirring at 100° C. for 6 hours under a nitrogen atmosphere. The reaction mixture was cooled to room temperature, followed by dilution with dichloromethane (10 ml), which was washed with saturated aqueous sodium chloride solution (10 ml). The organic layer was dried over sodium sulfate, followed by concentration under reduced pressure, and the residue was purified by silica gel column chromatography (dichloromethane/methanol=50/1), to obtain [3-(4-{2-[bis-(4-methoxy-benzyl)-amino]-pyrimidin-5-yl}-2-morpholin-4-yl-5,6-dihydro-pyrrolo[2,3-d]pyrimidin-7-yl)-4-fluoro-phenyl]-morpholin-4-yl-methanone as a pale brown solid (90.0 mg, 93%).
Reaction SMILES: [NH2:1][C:2]1[C:3](=[O:18])[NH:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[O:14][CH2:15][CH2:16][CH3:17])=[N:6][CH:7]=1.[C:19](O)(=[O:21])[CH3:20]>C(OC(=O)C)(=O)C>[C:19]([NH:1][C:2]1[C:3](=[O:18])[NH:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[O:14][CH2:15][CH2:16][CH3:17])=[N:6][CH:7]=1)(=[O:21])[CH3:20]
Reactant: CC(=O)O
Reactant: CCCOc1ccccc1-c1ncc(N)c(=O)[nH]1
Solvent: CC(=O)OC(C)=O
Product: CCCOc1ccccc1-c1ncc(NC(C)=O)c(=O)[nH]1
Reaction time: 1 h

Procedure:
A solution of 5-amino-2-(2-propoxyphenyl)pyrimidin-4(3H)-one (0.90 g) and 10 drops of acetic anhydride in acetic acid (50 ml) was heated on a steam bath for 4 hours. A further 10 drops of acetic anhydride was added and heating was continued for one hour. Acetic acid was removed under reduced pressure and water was added to the residue which afforded a light brown solid, 0.87 g. This was recrystallised from isopropylacetate to give the title compound, 0.32 g, m.p. 195°-197° C.
Reaction SMILES: CC(C)([O-])C.[K+].Cl.[NH2:8][C:9]1[CH:13]=[C:12]([Cl:14])[S:11][C:10]=1[S:15]([NH2:18])(=[O:17])=[O:16].[CH:19]([N:22]=[C:23]=[S:24])([CH3:21])[CH3:20]>CN(C)C=O>[NH2:8][C:9]1[CH:13]=[C:12]([Cl:14])[S:11][C:10]=1[S:15]([NH:18][C:23]([NH:22][CH:19]([CH3:21])[CH3:20])=[S:24])(=[O:16])=[O:17]
Reactant: CC(C)N=C=S
Reactant: Nc1cc(Cl)sc1S(N)(=O)=O
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)NC(=S)NS(=O)(=O)c1sc(Cl)cc1N
Reaction time: 0.08 h
Yield: 79.7 %

Procedure:
Potassium tert-butoxide (0.49 g, 4.4 mmol) was added to a solution of 3-amino-5-chlorothiophene-2-sulfonamide hydrochloride (0.5 g, 2.0 mmol) in dry N,N-dimethylformamide (5 ml) with stirring on an ice bath. After 5 min, isopropyl isothiocyanate (0.26 ml, 2.4 mmol) was added dropwise to the resulting suspension, and the mixture was stirred for 30 min at 0° C. The cooling bath was removed, and stirring was continued at room temperature for 30 min. The solvent was evaporated at <50° C., and the residue was taken up in 25 ml of water, treated with decolorising charcoal, and filtered. Acidification of the filtrate with acetic acid to pH 3-4 and filtration afforded 0.50 g (80%) the title compound; mp 142.0°-142.5° C. decomp., 1H-NMR (DMSO-d6): δ 1.12 (d, 6H), 4.25 (m, 1H), 6.48 (br s, 2H), 6.65 (s, 1H), 8.02 (d, 1H), 11.2 (br s, 1H).
Reaction SMILES: [CH2:1]([CH:3]([CH2:6][CH2:7][CH2:8][CH3:9])[CH2:4][Mg])[CH3:2].C([CH:12]([CH2:15][CH2:16][CH2:17][CH3:18])[CH2:13]Br)C.BrC1C=CC=CC=1>>[CH2:1]([CH:3]([CH2:6][CH2:7][CH2:8][CH3:9])[CH2:4][C:13]1[CH:12]=[CH:15][CH:16]=[CH:17][CH:18]=1)[CH3:2]
Reactant: CCCCC(CC)CBr
Reactant: CCCCC(CC)C[Mg]
Solvent: Brc1ccccc1
Product: CCCCC(CC)Cc1ccccc1

Procedure:
19.3 g of 2-ethylhexyl-magnesium prepared from 2-ethylhexyl bromide, are reacted with 15.7 g of bromobenzene in the presence of a catalyst based on bis[bis(diphenylphosphionethane]palladium(0). 19 g of 2-ethylhexyl-benzene thus obtained were dissolved in 60 ml of an equal volume mixture of trifluoroacetic acid and anhydride maintained at 0° C. under stirring, to which 3.5 g of sodium iodide and 4.2 g of iodic anhydride are added. The solvent is removed with a rotary evaporator. Then the residual product is dissolved in 30 ml of acetonitrile and poured in 200 ml of water containing 10 g of sodium acetate and 2 g of sodium sulfite and 14 g of potassium bis-fluorosulfonylimide. The organic phase is extracted with dichloromethane and washed with water. The solvent is eliminated by means of a rotary evaporator to leave an oily liquid of bis-fluorosulfonylimide of bis-[4-(2-ethylhexyl)]phenyl-iodonium. This ionic compound presents characteristics of solubility in hydrocarbons and silicon oils comparable to those of compounds with longer alkyl chains such as bis(dodecylbenzene) iodonium associated to the anion PF6-. It has a lipophilic character more noticeable than that of the compound of Example 3. It is particularly advantageous to catalyze the cross-linking of antiadhesive silicon coating and the polymerization of the monomers of low polarity such as cyclohexanedimethanoldivinylether, 2-ethylhexylglycidylether or 2-ethylhexylvinylether.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:8]2[CH2:13][CH2:12][N:11]([C:14](OC(C)(C)C)=O)[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.C=O>C(O)=O>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)N1CCC(c2cccc(Br)c2)CC1
Agent: C=O
Solvent: O=CO
Product: CN1CCC(c2cccc(Br)c2)CC1
Temperature: 150 °C
Yield: 99.3 %

Procedure:
A mixture of 4-(3-bromophenyl)-1-N-Boc piperidine (430 mg, 1.26 mmol), formic acid (5 mL) and formaldehyde (0.5 mL) was heated under microwave irradiation at 150° C. for 10 minutes. The cooled reaction mixture was loaded onto a 70 g SCX-2 cartridge which was washed with methanol (200 mL) and then eluted with 2N ammonia in methanol (200 mL). Concentration of the combined basic fractions in vacuo afforded the title compound (318 mg, 99%) as a brown oil. 1H NMR (CDCl3, 300 MHz): 7.38-7.36 (m, 1H); 7.35-7.29 (m, 1H); 7.17-7.14 (m, 2H); 3.03-2.92 (m, 2H); 2.52-2.37 (m, 1H); 2.32 (s, 3H); 2.10-1.99 (m, 2H); 1.87-1.69 (m, 4H).
Reaction SMILES: [C:1]([C:3]1([O:20][CH2:21][CH3:22])[CH:8]=[CH:7][C:6]([C:9]2(C(OC)=O)[CH2:14][CH2:13][CH2:12][CH2:11][C:10]2=[O:15])=[CH:5][CH2:4]1)#[N:2].OS(O)(=O)=O>C(O)(=O)C>[C:1]([C:3]1([O:20][CH2:21][CH3:22])[CH:4]=[CH:5][C:6]([CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]2=[O:15])=[CH:7][CH2:8]1)#[N:2]
Reactant: CCOC1(C#N)C=CC(C2(C(=O)OC)CCCCC2=O)=CC1
Agent: O=S(=O)(O)O
Solvent: CC(=O)O
Product: CCOC1(C#N)C=CC(C2CCCCC2=O)=CC1
Yield: 87.9 %

Procedure:
4-Cyano-4-(2-ethoxy)phenyl-2-methoxycarbonylcyclohexanone (1.06 g, 3.5 mmol) was heated at reflux in acetic acid (24 mL) and 10% H2SO4 (13 mL) for 6 h. Extraction with benzene (3×10 mL), which was washed with K2CO3 solution, dried (Na2SO4), filtered and concentrated, gave a white solid (0.755 g, 88%): mp 116-121 C.
Reaction SMILES: [CH3:1][N:2]([C:4]([NH:6][CH3:7])=[S:5])[NH2:3].[Cl:8][C:9]1[C:14]([O:15][CH3:16])=[CH:13][C:12]([C:17](=O)[C:18](O)=[O:19])=[C:11]([F:22])[CH:10]=1>CO>[Cl:8][C:9]1[C:14]([O:15][CH3:16])=[CH:13][C:12]([C:17]2[C:18](=[O:19])[N:6]([CH3:7])[C:4](=[S:5])[N:2]([CH3:1])[N:3]=2)=[C:11]([F:22])[CH:10]=1
Reactant: CNC(=S)N(C)N
Reactant: COc1cc(C(=O)C(=O)O)c(F)cc1Cl
Solvent: CO
Product: COc1cc(-c2nn(C)c(=S)n(C)c2=O)c(F)cc1Cl
Yield: 54.3 %

Procedure:
A solution of 2,4-dimethylthiosemicarbazide (0.20 g) and 2-(4-chloro-2-fluoro-5-methoxyphenyl)-2-oxoacetic acid (0.38 g) in methanol (10 ml) was refluxed for 16 hours. Filtration of the reaction mixture afforded 6-(4-chloro-2-fluoro-5-methoxy-phenyl)-2,4-dimethyl-5-oxo-3-thioxo-2,3,4,5-tetrahydro-1,2,4-triazine (0.28 g). 1H NMR, CDCl3, 3.77 (3H, s), 3.91 (3H, s), 4.07 (3H, s), 7.08 (1H, d, J=6.09 Hz), 7.25 (1H, d, J=9.22 Hz).
Reaction SMILES: [CH2:1]([O:5][C:6]1[N:14]=[C:13]2[C:9]([N:10]=[C:11]([O:24][CH3:25])[N:12]2[CH2:15][CH2:16][CH2:17][NH:18][C@@H:19]2[CH2:23][CH2:22][CH2:21][O:20]2)=[C:8]([NH2:26])[N:7]=1)[CH2:2][CH2:3][CH3:4].F[C:28](F)(F)C(O)=O.C(OC1NC(N)=C2C(N=1)=NC(OC)=N2)CCC.Cl.O1CCC(CN)C1>>[CH2:1]([O:5][C:6]1[N:14]=[C:13]2[C:9]([N:10]=[C:11]([O:24][CH3:25])[N:12]2[CH2:15][CH2:16][CH2:17][NH:18][CH2:19][CH:23]2[CH2:22][CH2:21][O:20][CH2:28]2)=[C:8]([NH2:26])[N:7]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCOc1nc(N)c2nc(OC)n(CCCN[C@@H]3CCCO3)c2n1
Reactant: O=C(O)C(F)(F)F
Agent: CCCCOc1nc2nc(OC)nc-2c(N)[nH]1
Agent: Cl
Agent: NCC1CCOC1
Product: CCCCOc1nc(N)c2nc(OC)n(CCCNCC3CCOC3)c2n1

Procedure:
Prepared similarly to Intermediate 14 from 2-(butyloxy)-8-(methyloxy)-1H-purin-6-amine trifluoroacetate and (tetrahydro-3-furanylmethyl)amine hydrochloride.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[C:6]([C:15]([O:17]C)=[O:16])[C:7]([C:11]([O:13]C)=[O:12])=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[OH-].[Na+].CO.Cl>O>[N:1]1[C:10]2[C:5](=[C:6]([C:15]([OH:17])=[O:16])[C:7]([C:11]([OH:13])=[O:12])=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: COC(=O)c1ccc2ncccc2c1C(=O)OC
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: O=C(O)c1ccc2ncccc2c1C(=O)O
Temperature: 80 °C
Reaction time: 2 h
Yield: 92.1 %

Procedure:
A mixture of dimethyl 5,6-quinolinedicarboxylate (2.46 g, 10.0 mmol), aqueous sodium hydroxide (5.0 mL, 5m, 25.0 mmol) and methanol is heated to 80° C., treated with water at 80° C. until the mixture is homogeneous, stirred for 2 hours at reflux temperature, cooled to 0° C., acidified to pH 4 with concentrated hydrochloric acid and filtered. The filter cake is air dried to give the title product as a white powder 2.00 g, 91.7%) mp >360 C, identified by H1NMR spectroscopy.
Reaction SMILES: [Si:1]([O:8][CH2:9][C@@H:10]([N:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:30]=[CH:29][N:28]=[C:27](S(C)(=O)=O)[N:26]=2)=[CH:21][C:20]1=[O:35])[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([F:18])[CH:12]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:36][N:37]1[CH:41]=[C:40]([NH2:42])[C:39]([CH3:43])=[N:38]1.O>C(O)(CC)C>[Si:1]([O:8][CH2:9][C@@H:10]([N:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:30]=[CH:29][N:28]=[C:27]([NH:42][C:40]3[C:39]([CH3:43])=[N:38][N:37]([CH3:36])[CH:41]=3)[N:26]=2)=[CH:21][C:20]1=[O:35])[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([F:18])[CH:12]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: Cc1nn(C)cc1N
Reactant: CC(C)(C)[Si](C)(C)OC[C@H](c1ccc(Cl)c(F)c1)n1ccc(-c2ccnc(S(C)(=O)=O)n2)cc1=O
Solvent: O
Solvent: CCC(C)O
Product: Cc1nn(C)cc1Nc1nccc(-c2ccn([C@H](CO[Si](C)(C)C(C)(C)C)c3ccc(Cl)c(F)c3)c(=O)c2)n1
Temperature: 110 °C
Yield: 66.1 %

Procedure:
(S)-1-(2-(tert-Butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-4-(2-(methylsulfonyl)pyrimidin-4-yl)pyridin-2(1H)-one (0.100 g, 0.186 mmol) and 1,3-dimethyl-1H-pyrazol-4-amine (0.413 g, 3.72 mmol) were placed in s-BuOH (2 mL), heated to 110° C. overnight, then poured into water and extracted with DCM. The combined organic fractions were dried (MgSO4), filtered, and concentrated to give the crude product, which was purified by column chromatography (500:10 DCM/MeOH) to give the product (S)-1-(2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-4-(2-((1,3-dimethyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (0.070 g, 66.2% yield).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[N:6]=[CH:7][C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[CH:10][C:9]=2I)=[O:4].[CH3:17][O:18][C:19]1[CH:20]=[C:21]([OH:25])[CH:22]=[CH:23][CH:24]=1>>[CH3:1][O:2][C:3]([C:5]1[N:6]=[CH:7][C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[CH:10][C:9]=2[O:25][C:21]1[CH:22]=[CH:23][CH:24]=[C:19]([O:18][CH3:17])[CH:20]=1)=[O:4]
Reactant: COc1cccc(O)c1
Reactant: COC(=O)c1ncc2c(I)cccc2c1O
Product: COC(=O)c1ncc2c(Oc3cccc(OC)c3)cccc2c1O

Procedure:
The title compound was synthesized from 4-hydroxy-8-iodo-isoquinoline-3-carboxylic acid methyl ester and 3-methoxy-phenol in analogy to example 19d; MS-(+)-ion: M+1=326.4.