Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[CH:10]([CH2:14][CH2:15][OH:16])[CH2:9][CH2:8]2)([CH3:4])([CH3:3])[CH3:2].C1C=C[NH+]=CC=1.[O-][Cr](Cl)(=O)=O>C(Cl)Cl>[C:1]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[CH:10]([CH2:14][CH:15]=[O:16])[CH2:9][CH2:8]2)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)c1ccc2c(c1)CCC2CCO
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: CC(C)(C)c1ccc2c(c1)CCC2CC=O
Yield: 62 %

Procedure:
Prepared in an analogous manner to that described in Example 4, via oxidation of 2-(5-tert-butyl-1-indanyl)-1-ethanol (3.85 g, 17.6 mmole) in CH2Cl2 (40 ml), by means of PCC (5.73 g, 25 mmole) in CH2Cl2 (60 ml). After the treatment described and bulb-to-bulb distillation (150°/40 Pa), there was obtained the desired carbaldehyde (2.34 g, yield 62%).
Reaction SMILES: [CH:1](NC(C)C)(C)[CH3:2].C([Li])CCC.CN(P(N(C)C)(N(C)C)=O)C.[CH:24]1([C:34]([O:36][CH3:37])=[O:35])[CH2:29][CH2:28][CH:27]([C:30]([O:32][CH3:33])=[O:31])[CH2:26][CH2:25]1.BrCCCl.[Li+].CC([N-]C(C)C)C>C1COCC1.CCCCCC>[CH3:37][O:36][C:34]([C:24]12[CH2:2][CH2:1][C:27]([C:30]([O:32][CH3:33])=[O:31])([CH2:26][CH2:25]1)[CH2:28][CH2:29]2)=[O:35]
Reactant: COC(=O)C1CCC(C(=O)OC)CC1
Reactant: CC(C)NC(C)C
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Solvent: C1CCOC1
Product: COC(=O)C12CCC(C(=O)OC)(CC1)CC2
Temperature: -30 °C
Reaction time: 0.5 h

Procedure:
To a stirred solution of diisopropylamine (84.5 ml, 600 mmol) in THF (anhydrous, 700 ml) cooled to −30° C. under nitrogen is added n-butyl lithium (2.5 M in hexane, 220 ml, 550 mmol) by a syringe. The misture is stirred for 30 min at −30° C. and then cooled to −78° C. HMPA (360 ml, 4 equivalents, 2 mol) is added by a syringe and a dolution of dimethyl cyclohexane-1,4-dicarboxylate (100 g, 500 mmol) in THF (anhydrous, 100 ml is added by a syringe subsequently. The mixture is stirred for an additional 40 min. Then 1-bromo-2-chloroethane (41.5 ml, 500 mmol) is added and the mixture stirred at −78° C. for an additional 20 min. The cold bath is removed and stirring is continued for 1 hr. The reaction mixture is cooled back to −78° and a mixture of HMPA (360 ml, 4 eq, 2 mol) in THF 600 ml) is added. By cannula, freshly prepared LDA (200 ml of n-butyl lithium, 2.5 M in hexane, 500 mmol is added to diisopropylamine (78 ml, 556 mmol) in THF (anhydrous, 700 ml)) is transferred into the reaction mixture at −78°. The reaction mixture is stirred at −78° for 1.33 hr followed by removal of the cooling bath and additional stirring for 5-6 hr. The mixture is quenched with saturated aqueous ammonium chloride (400 ml) and concentrated under reduced pressure at 35° to remove the THF. The residue is diluted with water (800 ml) and extracted with hexance (3×600 ml). The combined extracts are washed with saline (700 ml) and dried over sodium sulfate. Using a bath temperature of 35° the solvents are are removed under reduced pressure to give a residue. The residue is stirred with hexane (50 ml) at 20-25° for 0.5 hr. The resulting suspension is cooled to 0° for 2 hr and filtered to give the title compound.
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([CH2:13][CH2:14][NH:15]C(=O)C)=[CH:9][CH:8]=2)[N:6]=1>C(O)C>[NH2:15][CH2:14][CH2:13][C:10]1[CH:9]=[CH:8][C:7]([C:5]2[N:6]=[C:2]([NH2:1])[S:3][CH:4]=2)=[CH:12][CH:11]=1
Reactant: CC(=O)NCCc1ccc(-c2csc(N)n2)cc1
Solvent: CCO
Product: NCCc1ccc(-c2csc(N)n2)cc1

Procedure:
N-{2-[4-(2-Amino-1,3-thiazol-4-yl)phenyl]ethyl}acetamide (0.6 g) was dissolved in ethanol (10 mL) and hydrochloric acid concentrate (10 mL). The mixture was refluxed for 5 hours. The solvent was evaporated in vacuo. The residue was washed with ethyl ether to give 4-[4-(2-aminoethyl)phenyl]-1,3-thiazol-2-amine dihydrochrolide (0.5 g, 84.6%).
Reaction SMILES: [C:1]1([C:15](O)=[O:16])[C:14]2[C:5](=[CH:6][C:7]3[C:12]([CH:13]=2)=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH:4]=[CH:3][CH:2]=1.C(Cl)(=O)C(Cl)=O.Cl.[F:25][C:26]1[CH:31]=[CH:30][C:29]([CH:32]([OH:46])[CH:33]([NH2:45])[CH2:34][C:35]2[CH:40]=[CH:39][C:38]([C:41]([F:44])([F:43])[F:42])=[CH:37][CH:36]=2)=[CH:28][CH:27]=1.C(=O)([O-])O.[Na+]>O1CCCC1.C(OCC)(=O)C.O.CN(C)C=O>[F:25][C:26]1[CH:27]=[CH:28][C:29]([CH:32]([OH:46])[CH:33]([NH:45][C:15]([C:1]2[C:14]3[C:5](=[CH:6][C:7]4[C:12]([CH:13]=3)=[CH:11][CH:10]=[CH:9][CH:8]=4)[CH:4]=[CH:3][CH:2]=2)=[O:16])[CH2:34][C:35]2[CH:40]=[CH:39][C:38]([C:41]([F:44])([F:43])[F:42])=[CH:37][CH:36]=2)=[CH:30][CH:31]=1
Reactant: NC(Cc1ccc(C(F)(F)F)cc1)C(O)c1ccc(F)cc1
Reactant: O=C(O)c1cccc2cc3ccccc3cc12
Agent: Cl
Agent: O=C(Cl)C(=O)Cl
Agent: O=C([O-])O
Solvent: CN(C)C=O
Solvent: O
Solvent: CCOC(C)=O
Product: O=C(NC(Cc1ccc(C(F)(F)F)cc1)C(O)c1ccc(F)cc1)c1cccc2cc3ccccc3cc12
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 66.1 %

Procedure:
To a solution of 1-anthracenecarboxylic acid (143 mg, 0.64 mmol). in tetrahydrofuran (5 ml) were added oxalyl chloride (0.11 ml, 1.72 mmol) and N,N-dimethylformamide (0.01 ml), and the mixture was stirred at room temperature for 30 min. The reaction solution was evaporated under reduced pressure. To a solution of the residue in ethyl acetate (5 ml) were added (1RS,2SR)-1-(4-fluorophenyl)-1-hydroxy-3-(4-(trifluoromethyl)phenyl)-2-propylamine hydrochloride (150 mg, 0.43 mmol) and saturated aqueous sodium hydrogen carbonate (5 ml) and the mixture was stirred overnight at room temperature. The reaction solution was diluted with water (50 ml) and extracted with ethyl acetate (50 ml×2). The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1) and recrystallized from ethyl acetate-hexane to give the title compound (147 mg, 66%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH:9]([S:20]([C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1)(=[O:22])=[O:21])[C:10]1[C:11]([CH3:19])=[CH:12][C:13]([C:16](O)=[O:17])=[N:14][CH:15]=1.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.CN1CCOCC1>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH:9]([S:20]([C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1)(=[O:22])=[O:21])[C:10]1[C:11]([CH3:19])=[CH:12][C:13]([C:16]([N:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)=[O:17])=[N:14][CH:15]=1
Reactant: C1COCCN1
Reactant: Cc1cc(C(=O)O)ncc1C(c1cc(F)ccc1F)S(=O)(=O)c1ccc(F)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCl
Solvent: CN1CCOCC1
Product: Cc1cc(C(=O)N2CCOCC2)ncc1C(c1cc(F)ccc1F)S(=O)(=O)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 120 h
Yield: 68.1 %

Procedure:
To a solution of 5-[(2,5-difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-4-methylpyridine-2-carboxylic acid (119 mg, 0.282 mmol) obtained in Example 12 in methylene chloride (3 ml), morpholine (30 μl, 0.339 mmol), 1-hydroxybenzotriazole (38 mg, 0.282 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride mg, 0.339 mmol) and 4-methylmorpholine (37 μl, 0.339 mmol) were added. The reaction solution was stirred for 5 days at room temperature, and was concentrated under reduced pressure. The resulting concentration residue was subjected to silica gel column chromatography, and the fraction obtained from an elution with 65% ethyl acetate/hexane was concentrated under reduced pressure. Ethyl acetate-hexane was added to the resulting concentration residue, and the solid thus precipitated was collected by filtration, to obtain the title compound (94 mg, 0.192 mmol, 68%) as a white powder.
Reaction SMILES: C(O)(=O)C.[Si]([O:12][C@H:13]1[CH2:17][N:16]([CH:18]2[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]2)[C:15](=[O:24])[CH2:14]1)(C(C)(C)C)(C)C.CCN(CC)CC.[S:32]1[C:40]2[C:35](=[N:36][CH:37]=[CH:38][CH:39]=2)[N:34]=[C:33]1[O:41][C:42]1[CH:49]=[CH:48][C:45]([CH:46]=O)=[CH:44][CH:43]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl>ClCCCl.C(Cl)Cl>[OH:12][C@H:13]1[CH2:17][N:16]([CH:18]2[CH2:19][CH2:20][N:21]([CH2:46][C:45]3[CH:44]=[CH:43][C:42]([O:41][C:33]4[S:32][C:40]5[C:35]([N:34]=4)=[N:36][CH:37]=[CH:38][CH:39]=5)=[CH:49][CH:48]=3)[CH2:22][CH2:23]2)[C:15](=[O:24])[CH2:14]1
Reactant: O=Cc1ccc(Oc2nc3ncccc3s2)cc1
Reactant: CC(C)(C)[Si](C)(C)O[C@@H]1CC(=O)N(C2CCNCC2)C1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: ClCCCl
Solvent: CC(=O)O
Product: O=C1C[C@@H](O)CN1C1CCN(Cc2ccc(Oc3nc4ncccc4s3)cc2)CC1
Temperature: 25 °C
Reaction time: 17 h
Yield: 20.5 %

Procedure:
To a solution of (4R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1-(piperidin-4-yl)pyrrolidin-2-one acetate (252 mg, 0.70 mmol, 1.2 equiv.) in DCE (3.1 mL) was added Et3N (98 μL, 0.70 mmol, 1.2 equiv.) and stirred at rt for 30 min to free-base the amine. To this solution was added 4-([1,3]thiazolo[4,5-b]pyridine-2-yloxy)benzaldehyde (150 mg, 0.585 mmol) and sodium triacetoxyborohydride (211 mg, 0.995 mmol, 1.7 equiv.). The mixture was stirred at rt for 17 h. The reaction mixture was then partitioned between sat. aq. NaHCO3 (20 mL) and CH2Cl2 (20 mL). The organic layer was washed with brine (20 mL), dried, filtered, and concentrated to an orange oil. To a solution of this oil (158 mg, 0.293 mmol) in CH2Cl2 (2.9 mL) was added HCl (4 M in dioxane, 1.62 mL, 22.0 equiv.). The reaction was stirred at rt for 2.5 h and then concentrated. The residue was dissolved in water (20 mL), and the pH adjusted to ˜pH 7 with 1 M aq. NaOH. The mixture was then extracted with CH2Cl2 (2×15 mL) followed by EtOAc (2×15 mL) and the organic layers (CH2Cl2 and EtOAc) were individually washed with water (30 mL each). The combined organic layers were dried, filtered and concentrated to give the crude product as a white solid. The crude product was purified using preparative reversed phase HPLC to afford the desired product as a white solid (51 mg, 41%). 1H NMR (500 MHz, CDCl3): 8.58 (dd, J=4.8, 1.7, 1H), 8.04 (dd, J=7.9, 1.7, 1H), 7.42-7.40 (m, 2H), 7.39-7.37 (m, 2H), 7.22 (dd, J=7.9, 4.8, 1H), 4.38-4.30 (m, 1H), 4.06-3.95 (m, 1H), 3.56-3.51 (m, 2H), 3.45-3.38 (m, 1H), 3.31-3.22 (m, 1H), 3.03-2.94 (m, 2H), 2.82-2.77 (m, 1H), 2.52-2.43 (m, 1H), 2.20-2.07 (m, 2H), 1.98-1.88 (m, 1H), 1.83-1.73 (m, 2H), 1.72-1.66 (m, 2H). MS (ESI): mass calcd. for C22H24N4O3S, 424.2; m/z found, 425.1 [M+H]+.
Reaction SMILES: C([O:3][P:4]([CH:7]([C:21]1[C:22]2[CH:29]=[C:28]([Cl:30])[CH:27]=[CH:26][C:23]=2[S:24][CH:25]=1)[C:8](=[O:20])[NH:9][CH:10]=[CH:11][C:12]1[CH:17]=[CH:16][C:15]([F:18])=[C:14]([F:19])[CH:13]=1)([CH3:6])=[O:5])C.N1C=CC=CC=1.Br[Si](C)(C)C.S(=O)(=O)(O)O>O.CO.CC(OC)(C)C.C(#N)C>[Cl:30][C:28]1[CH:27]=[CH:26][C:23]2[S:24][CH:25]=[C:21]([CH:7]([P:4]([CH3:6])(=[O:3])[OH:5])[C:8](=[O:20])[NH:9][CH:10]=[CH:11][C:12]3[CH:17]=[CH:16][C:15]([F:18])=[C:14]([F:19])[CH:13]=3)[C:22]=2[CH:29]=1
Reactant: CCOP(C)(=O)C(C(=O)NC=Cc1ccc(F)c(F)c1)c1csc2ccc(Cl)cc12
Agent: C[Si](C)(C)Br
Agent: O=S(=O)(O)O
Solvent: O
Solvent: CO
Solvent: CC#N
Product: CP(=O)(O)C(C(=O)NC=Cc1ccc(F)c(F)c1)c1csc2ccc(Cl)cc12
Temperature: 2.5 °C
Reaction time: 0.25 h

Procedure:
A 1 L four-necked round-bottomed flask equipped with mechanical stirrer, addition funnel, condenser, and a thermocouple was charged with {(5-Chloro-benzo[b]thiophen-3-yl)-[2-(3,4-difluoro-phenyl)-vinylcarbamoyl]methyl}-methyl-phosphinic acid ethyl ester (26.4 g, 0.056 mol), acetonitrile (200 mL) and pyridine (11.0 mL, 0.136 mol). To the resulting mixture was then added bromotrimethylsilane (15.5 mL, 0.117 mol), 15 minutes, while maintaining the temperature of the resulting mixture below about 30° C. The mixture was then stirred for an additional 15 minutes to yield a clear yellow solution, which was aged for about 2 hours. The resulting mixture was then cooled to about 0-5° C. To the mixture was then added concentrated sulfuric acid (5.4 mL) in water (90 mL), using vigorous agitation. To the resulting mixture was then added MTBE (150 mL) and the mixture aged with stirring until two homogeneous layers were obtained. The layers were separated and the organic layer was washed twice with water (45 mL) and then concentrated to yield a residue. The residue was digested with methanol (180 mL) under vigorous stirring. then concentrated to about 50% of its original volume under reduced pressure. The resulting slurry was cooled to about 0-5° C., then aged at this temperature for about 1 hours.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([N+:14]([O-:16])=[O:15])=[CH:11][CH:12]=2)[CH:7]=[CH:6]1.[I-].[K+].C(=O)([O-])[O-].[K+].[K+].[NH:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1>ClCCl>[N+:14]([C:10]1[CH:9]=[C:8]2[C:13](=[CH:12][CH:11]=1)[N:5]([CH2:4][CH2:3][CH2:2][N:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1)[CH:6]=[CH:7]2)([O-:16])=[O:15]
Reactant: O=[N+]([O-])c1ccc2c(ccn2CCCCl)c1
Reactant: C1COCCN1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: ClCCl
Product: O=[N+]([O-])c1ccc2c(ccn2CCCN2CCOCC2)c1
Temperature: 81 °C
Reaction time: 68 h
Yield: 101.2 %

Procedure:
To a small reaction vial containing a magnetic stirbar was added compound 38 (155 mg, 0.649 mmol), potassium iodide (1.078 g, 6.49 mmol) and potassium carbonate (898.0 mg, 6.49 mmol). The vial was sealed and purged with argon. Anhydrous acetonitrile (4 mL) was added through the septum, followed by morpholine (0.57 mL, 6.54 mmol). The vial was placed in the heating block and stirred at 81° C. for 68 hours. The reaction was cooled to room temperature. The non-homogenous reaction was diluted with dichloromethane (5 mL) and filtered through celite. Additional dichloromethane (10 mL) followed by methanol (5 mL) was used to wash the celite plug. The filtrate was concentrated on the rotary evaporator and dried further under high vacuum. The product was purified using silica gel column chromatography (2M NH3 in methanol:CH2Cl2, 5:95) to obtain compound 39 (190 mg, 100%) as a yellow oil. 1H NMR (CDCl3) δ 8.59 (d, J=2.1 Hz, 1H), 8.11 (dd, J=2.7, 9.0 Hz, 1H), 7.42 (d, J=9.0 Hz, 1H), 7.28 (d, J=3.3 Hz, 1H), 6.69 (d, J=3.0 Hz, 1H), 4.30 (t, J=6.3 Hz, 2H), 3.75 (brs, 4H), 2.41 (brs, 4H), 2.27 (brs, 2H), 2.04 (brs, 2H); ESI-MS (m/z, %): 290 (M+1, 100).
Reaction SMILES: C(N(C(C)C)CC)(C)C.[NH2:10][C@@H:11]1[CH2:15][CH2:14][N:13]([C:16]2[C:25]3[C:20](=[CH:21][C:22]([CH3:26])=[CH:23][CH:24]=3)[N:19]=[C:18]([C:27]3[C:32]([F:33])=[CH:31][CH:30]=[CH:29][C:28]=3[OH:34])[N:17]=2)[CH2:12]1.Cl[C:36]([O:38][CH2:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:37].ClC([O-])=O>C1COCC1>[F:33][C:32]1[CH:31]=[CH:30][CH:29]=[C:28]([OH:34])[C:27]=1[C:18]1[N:17]=[C:16]([N:13]2[CH2:14][CH2:15][C@@H:11]([NH:10][C:36](=[O:37])[O:38][CH2:39][C:40]([CH3:43])([CH3:42])[CH3:41])[CH2:12]2)[C:25]2[C:20](=[CH:21][C:22]([CH3:26])=[CH:23][CH:24]=2)[N:19]=1
Reactant: CC(C)(C)COC(=O)Cl
Reactant: Cc1ccc2c(N3CC[C@@H](N)C3)nc(-c3c(O)cccc3F)nc2c1
Agent: O=C([O-])Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: Cc1ccc2c(N3CC[C@@H](NC(=O)OCC(C)(C)C)C3)nc(-c3c(O)cccc3F)nc2c1
Temperature: -60 °C
Yield: 95.1 %

Procedure:
At RT, diisopropyl ethylamine (273 μL, 1.57 mmol) was added to a solution of (R)-2-(4-(3-aminopyrrolidin-1-yl)-7-methylquinazolin-2-yl)-3-fluorophenol (266 mg, 0.79 mmol) in THF (15 mL), and the reaction was cooled to −60° C. Neopentyl chloroformate (116 μL in 2.0 mL THF, 0.79 mmol) was added dropwise over a period of 10 minutes. After addition of the chloroformate was complete, the reaction mixture was warmed to RT, quenched with H2O, and extracted with CH2Cl2. The organic phase was dried over MgSO4, filtered, and concentrated. The residue was purified via silica gel chromatography using 0-10% EtOAc in a 1:1 mixture of hexanes and CH2Cl2 to give (R)-neopentyl 1-(2-(2-fluoro-6-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamate (compound 11) (340 mg, 94%). 1H NMR (400 MHz, DMSO-d6) δ 8.37 (s, 1H), 7.64-7.58 (m, 3H), 7.47 (q, J=7.8 Hz, 1H), 6.95 (d, J=8.3 Hz, 1H), 6.87 (t, J=9.2 Hz, 1H), 4.28-3.99 (m, 5H), 3.71-3.64 (m, 2H), 2.56 (s, 3H), 2.23-2.14 (m, 1H), 2.07-1.92 (m, 1H), 0.89 (s, 9H) ppm. LC/MS: m/z 453.5 (M+H)+ at 2.66 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][C:7]([NH:11][C:12](=[O:28])[CH:13]([C:23]3[CH:27]=[CH:26][S:25][CH:24]=3)[CH2:14][NH:15]C(=O)OC(C)(C)C)=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.[ClH:29]>C(Cl)Cl>[ClH:29].[ClH:29].[NH2:15][CH2:14][CH:13]([C:23]1[CH:27]=[CH:26][S:25][CH:24]=1)[C:12]([NH:11][C:7]1[CH:6]=[C:5]2[C:10](=[CH:9][CH:8]=1)[CH:1]=[N:2][CH:3]=[CH:4]2)=[O:28]
Reactant: CC(C)(C)OC(=O)NCC(C(=O)Nc1ccc2cnccc2c1)c1ccsc1
Agent: Cl
Solvent: ClCCl
Product: NCC(C(=O)Nc1ccc2cnccc2c1)c1ccsc1
Reaction time: 9 h

Procedure:
To tert-butyl 3-(isoquinolin-6-ylamino)-3-oxo-2-(thiophen-3-yl)propylcarbamate (E432) in CH2Cl2 was added HCl (4 N in dioxane) and the solution was stirred for 8-10 h. The solvents were evaporated to give pure 3-amino-N-(isoquinolin-6-yl)-2-(thiophen-3-yl)propanamide dihydrochloride (E433).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:9]=1[CH2:10][CH2:11][NH:12]2.Cl.CN(C)CCCN=C=NCC.[N:29]1([C:35]2[N:36]=[C:37]([CH2:42][C:43]([O-])=[O:44])[NH:38][C:39](=[O:41])[CH:40]=2)[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.[Na+]>N1C=CC=CC=1.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:9]=1[CH2:10][CH2:11][N:12]2[C:43](=[O:44])[CH2:42][C:37]1[NH:38][C:39](=[O:41])[CH:40]=[C:35]([N:29]2[CH2:30][CH2:31][O:32][CH2:33][CH2:34]2)[N:36]=1
Reactant: O=C([O-])Cc1nc(N2CCOCC2)cc(=O)[nH]1
Reactant: Fc1ccccc1-c1cccc2c1CCN2
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: [Na+]
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Product: O=C(Cc1nc(N2CCOCC2)cc(=O)[nH]1)N1CCc2c(-c3ccccc3F)cccc21
Temperature: 25 °C
Reaction time: 72 h
Yield: 79.8 %

Procedure:
115 mg of 4-(2-fluorophenyl)-2,3-dihydro-1H-indole (diluted in 3 ml of pyridine) and 125 mg of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride are successively added to a solution of 211 mg of sodium [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate (example 1d, step 2d) in 3 ml of pyridine. The reaction mixture is stirred at ambient temperature for 3 days. The reaction medium is diluted in ethyl acetate (100 ml) and then successively washed with an aqueous 1N hydrochloric acid solution, an aqueous 1N sodium hydroxide solution and a saturated aqueous sodium chloride solution. The organic phase is then dried over magnesium sulfate, filtered through sintered glass, and concentrated under reduced pressure. 187 mg of 2-{2-[4-(2-fluorophenyl)-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(morpholin-4-yl)pyrimidin-4(3H)-one are obtained in the form of a beige solid, the characteristics of which are the following:
Reaction SMILES: C1(=O)OC(=O)C=C1.[C:8]([O:12][C:13]([O:15][C:16]1[CH:21]=[CH:20][C:19]([NH:22][C:23](=[O:29])/[CH:24]=[CH:25]\[C:26]([OH:28])=O)=[CH:18][CH:17]=1)=[O:14])([CH3:11])([CH3:10])[CH3:9].C([O-])(=O)C.[Na+].C(OC(=O)C)(=O)C>>[C:8]([O:12][C:13]([O:15][C:16]1[CH:21]=[CH:20][C:19]([N:22]2[C:23](=[O:29])[CH:24]=[CH:25][C:26]2=[O:28])=[CH:18][CH:17]=1)=[O:14])([CH3:11])([CH3:10])[CH3:9]
Reactant: CC(C)(C)OC(=O)Oc1ccc(NC(=O)/C=C\C(=O)O)cc1
Agent: CC(=O)[O-]
Agent: O=C1C=CC(=O)O1
Agent: [Na+]
Solvent: CC(=O)OC(C)=O
Product: CC(C)(C)OC(=O)Oc1ccc(N2C(=O)C=CC2=O)cc1

Procedure:
The poly(N-(4-tert-butyloxycarbonyloxyphenyl) maleimide is synthesized according to the following scheme. Di-t-butylpyrocarbonate is reacted with p-aminophenol to give p-(t-butyloxycarbonyloxy) aniline, I. Reaction of I with maleic anhydride then affords N-(p-t-butyloxycarbonyloxyphenyl)maleamic acid, II. Monomer II is modified by treatment with sodium acetate and acetic anhydride to yield monomer III, N-(p-t-butyloxycarbonyloxyphenyl)maleimide. Monomer III is polymerized in the presence of azoisobutylnitrile (AIBN) to yield poly-N-(4-tert-butyloxycarbonyloxyphenyl) maleimide.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:12]=[CH:11][C:9]([NH2:10])=[C:8]([N+:13]([O-:15])=[O:14])[CH:7]=1.[CH3:16][N:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1>O>[CH3:16][N:17]1[CH2:22][CH2:21][N:20]([CH2:2][CH2:3][CH2:4][O:5][C:6]2[CH:12]=[CH:11][C:9]([NH2:10])=[C:8]([N+:13]([O-:15])=[O:14])[CH:7]=2)[CH2:19][CH2:18]1
Reactant: Nc1ccc(OCCCBr)cc1[N+](=O)[O-]
Reactant: CN1CCNCC1
Solvent: O
Product: CN1CCN(CCCOc2ccc(N)c([N+](=O)[O-])c2)CC1
Temperature: 100 °C
Reaction time: 0.5 h
Yield: 60 %

Procedure:
A 100 mL flask was charged with 4-(3-bromopropoxy)-2-nitroaniline (2.2 g, 8.02 mmol) and 4-methylpiperazine (10 mL) and stirred at 100° C. The reaction was monitored by LCMS and complete in 30 minutes. The reaction mixture was treated with water (100 mL) and sonicated in an ultrasonic bath. The resulting solid were filtered off and dried under reduced pressure to give 1.5 g of 4-(3-(4-methylpiperazin-1-yl)propoxy)-2-nitroaniline (60% yield). MS (EI): 295 (MH+).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([Si:8]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)([CH:10]([Cl:12])[CH3:11])Cl)=[CH:4][CH:3]=1.F[C:21]1[CH:26]=CC([Si](C2C=CC(F)=CC=2)(CCCl)Cl)=C[CH:22]=1.C([Mg]Br)C=C>O1CCCC1.[Cl-].[NH4+].O>[CH2:26]([Si:8]([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1)([C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)[CH:10]([Cl:12])[CH3:11])[CH:21]=[CH2:22]
Reactant: CC(Cl)[Si](Cl)(c1ccc(F)cc1)c1ccc(F)cc1
Reactant: Fc1ccc([Si](Cl)(CCCl)c2ccc(F)cc2)cc1
Agent: C=CC[Mg]Br
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: O
Product: C=CC[Si](c1ccc(F)cc1)(c1ccc(F)cc1)C(C)Cl

Procedure:
A solution of 20 g (63 mmol) of a 1:1 mixture of bis(4-fluorophenyl)-1-chloroethyl(chloro)silane and bis(4-fluorophenyl)-2-chloroethyl(chloro)silane in 100 ml of tetrahydrofuran is treated dropwise with 71 ml (71 mmol) of 1.0 molar allyl magnesium bromide in tetrahydrofuran. The mixture is refluxed two hours, cooled, and diluted with saturated aqueous ammonium chloride and water. The aqueous phase is separated and extracted with ether, and the combined organic phases are washed with water and brine, dried over sodium sulfate, and evaporated to give the title compounds as a 1:1 mixture.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[CH:10]=[C:9]([O:12][C:13]1[CH:14]=[CH:15][C:16]3[N:20]=[C:19]([CH2:21][O:22][C:23]4[CH:36]=[CH:35][C:26]([CH2:27][CH:28]5[S:32][C:31](=[O:33])[NH:30][C:29]5=[O:34])=[CH:25][CH:24]=4)[N:18]([CH3:37])[C:17]=3[CH:38]=1)[CH:8]=[CH:7]2.[CH:39]([C:42]1[CH:47]=[CH:46][CH:45]=[C:44]([CH:48]([CH3:50])[CH3:49])[C:43]=1[N:51]=[C:52]=[O:53])([CH3:41])[CH3:40]>CN(C)C=O>[CH:39]([C:42]1[CH:47]=[CH:46][CH:45]=[C:44]([CH:48]([CH3:49])[CH3:50])[C:43]=1[NH:51][C:52]([NH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][C:13]3[CH:14]=[CH:15][C:16]4[N:20]=[C:19]([CH2:21][O:22][C:23]5[CH:24]=[CH:25][C:26]([CH2:27][CH:28]6[S:32][C:31](=[O:33])[NH:30][C:29]6=[O:34])=[CH:35][CH:36]=5)[N:18]([CH3:37])[C:17]=4[CH:38]=3)[CH:10]=2)[CH:5]=[CH:4][CH:3]=1)=[O:53])([CH3:40])[CH3:41]
Reactant: Cn1c(COc2ccc(CC3SC(=O)NC3=O)cc2)nc2ccc(Oc3ccc4cccc(N)c4c3)cc21
Reactant: CC(C)c1cccc(C(C)C)c1N=C=O
Solvent: CN(C)C=O
Product: CC(C)c1cccc(C(C)C)c1NC(=O)Nc1cccc2ccc(Oc3ccc4nc(COc5ccc(CC6SC(=O)NC6=O)cc5)n(C)c4c3)cc12
Reaction time: 120 h
Yield: 34.6 %

Procedure:
To a mixture of 5-[4-[6-(8-aminonaphthalen-2-yloxy)-1-methyl-1H-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4-dione (0.5 g) and N,N-dimethylformamide (10 ml) was added 2,6-diisopropylphenyl isocyanate (0.20 g) and the mixture was allowed to stand at room temperature for 5 days. The reaction mixture was partitioned between ethyl acetate and water. The extract was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and then concentrated. The residue was chromatographed on a silica gel column using ethyl acetate:n-hexane=3/2→3/1 as the eluant. The product was recrystallized from methanol to afford the title compound (0.24 g, mp 164-169° C.).