Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([S:14]([C:17]2[CH:22]=[CH:21][C:20]([N+:23]([O-])=O)=[CH:19][CH:18]=2)(=[O:16])=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(O)C.[Cl-].[NH4+]>[Fe].O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([S:14]([C:17]2[CH:18]=[CH:19][C:20]([NH2:23])=[CH:21][CH:22]=2)(=[O:16])=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCN(S(=O)(=O)c2ccc([N+](=O)[O-])cc2)CC1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CCO
Product: CC(C)(C)OC(=O)N1CCN(S(=O)(=O)c2ccc(N)cc2)CC1
Temperature: 80 °C
Yield: 16.3 %

Procedure:
4-(4-Nitro-benzenesulfonyl)-piperazine-1-carboxylic acid tert-butyl ester (10.0 g, 27 mmol) was suspended in a 5:1 mixture of ethanol and water (80 ml). To this solution was added iron powder (3.9 g, 70.2 mmol) and saturated ammonium chloride solution (8 ml), the mixture was heated to 80° C. for three hours. After this time, the reaction mixture was cooled to room temperature and filtered through a pad of celite, the celite was washed with ethanol (10 ml) and ethyl acetate (50 ml) and the solution was concentrated under vacuum. The resulting residue was partitioned between DCM (50 ml) and water (20 ml), the organic layer was separated, dried with MgSO4, filtered and concentrated to afford the title compound (1.5 g, 89% yield) as a white solid. δH (500 MHz, CDCl3) 7.53 (2H, d), 6.73 (2H, d), 4.36 (2H, br s), 3.56-3.49 (4H, m), 2.98-2.91 (4H, m), 1.42 (9H, s). Tr=1.81 min, m/z (ES+) ([(M−100)+H]+) 242.
Reaction SMILES: [NH2:1][CH2:2][C@@H:3]1[N:8]2[C:9]3[C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[N:12]=[C:11]([NH2:19])[C:10]=3[N:20]=[C:7]2[CH2:6][O:5][CH2:4]1.C(N(CC)CC)C.[CH3:28][S:29](Cl)(=[O:31])=[O:30].O>C(Cl)Cl>[NH2:19][C:11]1[C:10]2[N:20]=[C:7]3[CH2:6][O:5][CH2:4][C@H:3]([CH2:2][NH:1][S:29]([CH3:28])(=[O:31])=[O:30])[N:8]3[C:9]=2[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:12]=1
Reactant: CS(=O)(=O)Cl
Reactant: NC[C@H]1COCc2nc3c(N)nc4ccccc4c3n21
Solvent: O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)NC[C@H]1COCc2nc3c(N)nc4ccccc4c3n21
Temperature: 0 °C
Reaction time: 1.25 h
Yield: 48.5 %

Procedure:
(11S)-11-(Aminomethyl)-10,11-dihydro-8H-[1,4]oxazino[4′,3′:1,2]imidazo[4,5-c]quinolin-6-amine (778 mg, 2.89 mmol) was dissolved in 60 mL of CH2Cl2 and treated with triethylamine (804 μL, 5.78 mmol). The solution was cooled to 0° C. under N2. Methanesulfonyl chloride (224 μL, 2.89 mmol) was then added dropwise. After 75 minutes, the reaction was treated with H2O and extracted repeatedly with 10% methanol/CHCl3. The combined organic layers were washed successively with H2O and brine. The organic portion was dried over Na2SO4, filtered and concentrated under reduced pressure. Chromatography (SiO2, 10-15% methanol/CHCl3) gave an off-white solid. Crystallization from methanol gave N-{[(11S)-6-amino-10,11-dihydro-8H-[1,4]oxazino[4′,3′:1,2]imidazo[4,5-c]quinolin-11-yl]methyl}methanesulfonamide (487 mg) as white, powdery crystals, mp 285-288° C.
Reaction SMILES: [C:1](OCCOC(=O)C(C)=C)(=O)[C:2](C)=[CH2:3].COC.[C:18]1([CH:25]=[CH:24][C:22](O)=[CH:21][CH:20]=1)O>>[CH:2]([C:18]1[CH:25]=[CH:24][CH:22]=[CH:21][CH:20]=1)([CH3:3])[CH3:1]
Reactant: Oc1ccc(O)cc1
Reactant: C=C(C)C(=O)OCCOC(=O)C(=C)C
Agent: COC
Product: CC(C)c1ccccc1

Procedure:
68.5 g ethylene glycol dimethacrylate (Aldrich, 98%, 100 ppm methyl ether of hydroquinone (MEHQ)
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH:13]=O)[C@H:10]([C:15]([CH3:23])([CH3:22])[O:16][SiH2:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:24]([NH2:27])([CH3:26])[CH3:25].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][NH:27][CH:24]([CH3:26])[CH3:25])[C@H:10]([C:15]([CH3:23])([CH3:22])[O:16][SiH2:17][C:18]([CH3:20])([CH3:19])[CH3:21])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1C[C@@H](C=O)[C@H](C(C)(C)O[SiH2]C(C)(C)C)C1
Reactant: CC(C)N
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Solvent: ClCCCl
Product: CC(C)NC[C@@H]1CN(C(=O)OC(C)(C)C)C[C@H]1C(C)(C)O[SiH2]C(C)(C)C
Reaction time: 5 h

Procedure:
A solution of (3S,4S)-3-(tert-butyl-dimethyl-silanyloxymethyl)-4-formyl-pyrrolidine-1-carboxylic acid tert-butyl ester (7.7 g, 22.41 mmol) and isopropylamine (5.78 mL, 67.24 mmol) in 1,2-dichloroethane (200 mL) is stirred 25 min before the addition of NaBH(OAc)3 (11.88 g, 56.03 mmol). The solution is stirred for 5 h, then diluted with CH2Cl2 and washed with an aqueous saturated solution of NaHCO3. The aqueous layer is back extracted twice with CH2Cl2 and the combined organic extracts are dried over Na2SO4, filtered and concentrated. The crude material is used in the next step without further purification. TLC, Rf (CH2Cl2/MeOH 9:1)=0.39. MS (LC-MS): 387.2 [M+H]+.
Reaction SMILES: Cl.[C:2]([C:4]1[CH:5]=[C:6]([NH:10][C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([N+:21]([O-])=O)[CH:19]=3)[N:14]=[CH:13][N:12]=2)[CH:7]=[CH:8][CH:9]=1)#[CH:3].S(S([O-])=O)([O-])=O.[Na+].[Na+]>C(O)=O>[NH2:21][C:18]1[CH:19]=[C:20]2[C:15](=[CH:16][CH:17]=1)[N:14]=[CH:13][N:12]=[C:11]2[NH:10][C:6]1[CH:7]=[CH:8][CH:9]=[C:4]([C:2]#[CH:3])[CH:5]=1
Reactant: C#Cc1cccc(Nc2ncnc3ccc([N+](=O)[O-])cc23)c1
Agent: Cl
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: O=CO
Product: C#Cc1cccc(Nc2ncnc3ccc(N)cc23)c1

Procedure:
(3-Ethynyl-phenyl)-(6-nitro-quinazolin-4-yl)-amine hydrochloride (500 mg, 1.50 mmol) was dissolved in 10 mL of formic acid and treated portion-wise with sodium dithionite (1.10 g, 6.28 mmol) at room temperature. After 2 hours the mixture was quenched with 120 mL of water and filtered. The filtrate was evaporated in vacuo to a residue which was dissolved in 100 mL of 1:1 methanol:chloroform, filtered and evaporated in vacuo to a second residue. This was triturated with 200 mL of 5% sodium bicarbonate for 30 minutes, filtered, washed with water and dried in vacuo for 16 hours. Flash chromatography on silica gel eluted with ethyl acetate afforded pure (6-aminoquinazolin-4-yl)-(3-ethynylphenyl)-amine; 140 mg (34%); mp 165° C. dec.
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[CH3:12][O:13][C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[CH:18][CH:19]=1.O.C([O-])([O-])=O.[K+].[K+]>COCCOC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OCC)(=O)C>[CH3:12][O:13][C:14]1[CH:19]=[C:18]([C:2]2[CH:11]=[CH:10][C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[N:3]=2)[CH:17]=[CH:16][CH:15]=1
Reactant: COc1cccc(B(O)O)c1
Reactant: Clc1ccc2ccccc2n1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: COCCOC
Solvent: CCOC(C)=O
Solvent: O
Product: COc1cccc(-c2ccc3ccccc3n2)c1
Yield: 102.1 %

Procedure:
2-Chloroquinoline (5.38 g, 32.9 mmol), and 3-methoxyphenylboronic acid (6.0 g, 39.5 mmol) were dissolved in 130 mL of ethylene glycol dimethyl ether. To the solution was added 44 mL of water of a 2M K2CO3 solution followed by triphenylphosphine (0.86, g 3.29 mmol) and palladium(II) acetate (0.184 g, 0.82 mmol,). The reaction mixture was stirred at reflux under N2 atmosphere overnight. The reaction mixture was cooled and the aqueous layer discarded. An additional 200 mL of ethyl acetate was added and the solvent was washed twice with 150 mL portions of brine. The organic layer was dried with anhydrous sodium sulfate, filtered and evaporated. The crude product was purified by column chromatography on a silica gel column using 20% ethyl acetate/hexanes as the eluants. The pure fraction was collected and the solvent was reduced to give 2-(3-methoxyphenyl)quinoline (7.90 g, 94.8% yield).
Reaction SMILES: [CH3:1][C:2]1[CH:22]=[C:21]([N:23]([CH2:26][CH3:27])[CH2:24][CH3:25])[CH:20]=[CH:19][C:3]=1[C:4]([C:6]1[C:14]([Cl:15])=[C:13]([Cl:16])[C:12]([Cl:17])=[C:11]([Cl:18])[C:7]=1[C:8](O)=[O:9])=[O:5].[CH3:28][N:29]([CH3:39])[C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([N:36]([CH3:38])[CH3:37])[CH:31]=1.C(OC(=O)C)(=O)C.Cl>O>[CH3:37][N:36]([CH3:38])[C:32]1[CH:31]=[C:30]([N:29]([CH3:39])[CH3:28])[CH:35]=[CH:34][C:33]=1[C:4]1([C:3]2[CH:19]=[CH:20][C:21]([N:23]([CH2:24][CH3:25])[CH2:26][CH3:27])=[CH:22][C:2]=2[CH3:1])[C:6]2[C:7](=[C:11]([Cl:18])[C:12]([Cl:17])=[C:13]([Cl:16])[C:14]=2[Cl:15])[C:8](=[O:9])[O:5]1
Reactant: CN(C)c1cccc(N(C)C)c1
Reactant: CCN(CC)c1ccc(C(=O)c2c(Cl)c(Cl)c(Cl)c(Cl)c2C(=O)O)c(C)c1
Agent: Cl
Solvent: O
Solvent: CC(=O)OC(C)=O
Product: CCN(CC)c1ccc(C2(c3ccc(N(C)C)cc3N(C)C)OC(=O)c3c(Cl)c(Cl)c(Cl)c(Cl)c32)c(C)c1
Temperature: 95 °C

Procedure:
A mixture of 2-(2-methyl-4-(diethylamino)benzoyl)-3,4,5,6-tetrachlorobenzoic acid (22.4 g.), N,N,N',N'-tetramethyl-m-phenylenediamine (8.20 g.) and acetic anhydride (75 g.) was heated (to 95° C.) during one to two hours, then refluxed with dilute hydrochloric acid (32 g. concentrated hydrochloric acid plus 160 ml. water) during one and one-half hours. The resulting mixture was poured into water and the pH was adjusted. Recrystallization of the resulting product from toluene afforded 3-(2,4-bis(dimethylamino)phenyl)-3-(2-methyl-4-(diethylamino)phenyl)-4,5,6,7-tetrachlorophthalide (I: X=(CH3)2N, Y2 =CH3, Y4 =(CH3CH2)2N, Z4 =Z5 =Z6 =Z7 =Cl) (m.p. 236°-238° C.; after slurrying in acetone, 237°-239° C.).
Reaction SMILES: [CH:1]([N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1)([CH3:3])[CH3:2].Br[C:11]1[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[C:13]([N+:25]([O-:27])=[O:26])[CH:12]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1.C1(C)C=CC=CC=1>[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[C:13]([N+:25]([O-:27])=[O:26])[CH:12]=2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)Nc1ccc(Br)cc1[N+](=O)[O-]
Reactant: CC(C)N1CCNCC1
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Solvent: Cc1ccccc1
Product: CC(C)N1CCN(c2ccc(NC(=O)OC(C)(C)C)c([N+](=O)[O-])c2)CC1
Temperature: 100 °C
Reaction time: 0.08 h
Yield: 69.9 %

Procedure:
1-isopropylpiperazine (1.29 g, 5.66 mmol) and tert-butyl (4-bromo-2-nitrophenyl)carbamate (1.5 g, 4.71 mmol) were taken in a mixture of dry toluene (15 mL) and dioxane (2 mL) in a seal tube under argon atmosphere at room temperature. The Argon gas was purged for 5-10 min. Then Cs2CO3 (3.06 g, 9.43 mmol) and Xantphos (0.54 g, 0.94 mmol) were added and the resulting reaction mixture was purged with argon gas for 5 min., followed by Pd2(dba)3 (0.43 g, 0.47 mmol). The argon gas purging was continued for additional 5 min. before sealing the reaction vial. Then the reaction mixture was heated at 100° C. for 12 hr. After completion of the reaction by TLC, the reaction mixture was cooled to room temperature, filtered through celite bed and concentrated. The residue was purified by silica gel column chromatography (DCM:MeOH/97:3) to afford the title compound (1.2 g, yield: 70.5%). MS (ESI): 365.5 [M+H]+.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:7]2[C:22](=O)[CH:21]([C:24](=O)[CH3:25])[CH2:20][CH2:19][CH2:18][C:8]=2[N:9](C(OC(C)(C)C)=O)[CH:10]=1)=[O:5])[CH3:2].C(O)(=O)C.[CH:31]([NH2:33])=[NH:32]>CCO>[CH2:1]([O:3][C:4]([C:6]1[C:7]2[C:22]3[N:32]=[CH:31][N:33]=[C:24]([CH3:25])[C:21]=3[CH2:20][CH2:19][CH2:18][C:8]=2[NH:9][CH:10]=1)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1cn(C(=O)OC(C)(C)C)c2c1C(=O)C(C(C)=O)CCC2
Reactant: N=CN
Solvent: CCO
Solvent: CC(=O)O
Product: CCOC(=O)c1c[nH]c2c1-c1ncnc(C)c1CCC2
Temperature: 120 °C
Yield: 36 %

Procedure:
In a sealed tube are 5-acetyl-4-oxo-5,6,7,8-tetrahydro-4H-cyclohepta[b]pyrrole-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester (1.1 mmol) and formamidine acetate (5.5 mmol) and 10 mL EtOH. The mixture is heated at 120° C. for 48 hours. The solvent is evaporated in vacuo and the residue is taken up in CH2Cl2 and washed two times with NaHCO3 (aq). The organic layer is dried over Na2SO4 and evaporated in vacuo and the residue chromatographed using 10% MeOH in CH2Cl2 as mobile phase to yield 7-Methyl-3,4,5,6-tetrahydro-3,8,10-triaza-benzo[e]azulene-1-carboxylic acid ethyl ester (36%). LRMS 271.1 found (M+1) 272
Reaction SMILES: N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[C:19]([O:23][C:24]([NH:26][C:27]1[CH:31]=[N:30][S:29][N:28]=1)=[O:25])([CH3:22])([CH3:21])[CH3:20].[CH2:32]([N:39]1[CH2:44][CH2:43][C:42]([C:45]2[C:50]([F:51])=[CH:49][C:48]([N:52]3[CH2:56][C@H:55]([CH2:57]O)[O:54][C:53]3=[O:59])=[CH:47][C:46]=2[F:60])=[CH:41][CH2:40]1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C(P(CCCC)CCCC)CCC>O1CCCC1>[CH2:32]([N:39]1[CH2:44][CH2:43][C:42]([C:45]2[C:50]([F:51])=[CH:49][C:48]([N:52]3[CH2:56][C@H:55]([CH2:57][N:26]([C:27]4[CH:31]=[N:30][S:29][N:28]=4)[C:24]([O:23][C:19]([CH3:22])([CH3:20])[CH3:21])=[O:25])[O:54][C:53]3=[O:59])=[CH:47][C:46]=2[F:60])=[CH:41][CH2:40]1)[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1
Reactant: O=C1O[C@@H](CO)CN1c1cc(F)c(C2=CCN(Cc3ccccc3)CC2)c(F)c1
Reactant: CC(C)(C)OC(=O)Nc1cnsn1
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N(C[C@H]1CN(c2cc(F)c(C3=CCN(Cc4ccccc4)CC3)c(F)c2)C(=O)O1)c1cnsn1
Reaction time: 0.5 h
Yield: 63.7 %

Procedure:
1,1′-(Azodicarbonyl)dipiperidine (680 mg, 2.7 mM) was added portionwise to a stirred solution of 3-t-butyloxycarbonylamino-1,2,5-thiadiazole (543 mg, 2.7 mM, see WO 93-13091), 3-(4-(1-benzyl-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)-5(R)-hydroxymethyloxazolidin-2-one (720 mg, 1.8 mM; prepared by analogy with 3-fluoro compound—see WO 97-30995) and tributylphosphine (540 mg, 2.7 mM) in dry tetrahydrofuran (25 ml) at 0° under nitrogen. The mixture was stirred at 0° for 30 minutes and then at ambient temperature for 3 hours. The mixture was filtered and the filtrate evaporated. The residue was purified, firstly on a silica Mega Bond Elut® column, eluting with a gradient increasing in polarity from 0 to 30% ethyl acetate in isohexane and then on an Isolute SCX ion exchange column, washing with a gradient increasing, in polarity from 0 to 10% methanol in dichloromethane and then eluting with dichloromethane/methanol/0.88SG ammonia 87:10:3 to give the title product as a solid (669 mg, 64% ). NMR (DMSO-d6) δ: 1.49 (s, 9H); 2.30 (brs, 2H); 2.61 (t, 2H); 3.04 (m, 2H); 3.58 (s, 2H); 3.88 (dd, 1H); 4.13 (dd, 1H); 4.20 (dd, 1 H); 4.35 (dd, 1H); 5.02 (m, 1H); 5.79 (brs, 1H); 7.20-7.33 (m, 7H); 8.96 (s, 1H). MS (ESP): 584 (MH+) for C29H31F2N5O4S
Reaction SMILES: [CH3:1][NH:2][C:3]1[CH:4]=[N:5][CH:6]=[CH:7][C:8]=1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH3:15].[F:16][C:17]1[CH:18]=[C:19]([CH:23]=[C:24]([F:27])[C:25]=1[F:26])[C:20]([OH:22])=O>>[F:27][C:24]1[CH:23]=[C:19]([CH:18]=[C:17]([F:16])[C:25]=1[F:26])[C:20]([N:2]([CH3:1])[C:3]1[CH:4]=[N:5][CH:6]=[CH:7][C:8]=1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH3:15])=[O:22]
Reactant: O=C(O)c1cc(F)c(F)c(F)c1
Reactant: CNc1cnccc1-c1ccccc1C
Product: Cc1ccccc1-c1ccncc1N(C)C(=O)c1cc(F)c(F)c(F)c1

Procedure:
The title compound was prepared in analogy to example 90, from N-methyl-4-o-tolylpyridin-3-amine (example 1, intermediate a) and 3,4,5-trifluorobenzoic acid (CAS RN 121602-93-5) after a reaction time of 64 hours. The compound was purified by silica gel chromatography on a 10 g column using a MPLC system eluting with a gradient of n-heptane:EtOAc (100:0 to 50:50). The product-containing fractions were pooled and evaporated. The resulting brown solid was chromatographed a second time by silica gel chromatography on a 10 g column using a MPLC system eluting with a gradient of n-heptane:EtOAc (100:0 to 50:50). Light brown solid (22%). MS (ESI): m/z=357.12 [M+H]+.
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=[O:16])[CH3:15])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:17]([O:21][C:22]1[CH:27]=[CH:26][C:25]([CH2:28][C:29](OC)=[O:30])=[CH:24][CH:23]=1)([CH3:20])([CH3:19])[CH3:18]>>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=[O:16])[CH2:15][C:29](=[O:30])[CH2:28][C:25]2[CH:26]=[CH:27][C:22]([O:21][C:17]([CH3:19])([CH3:18])[CH3:20])=[CH:23][CH:24]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(=O)C1CCN(Cc2ccccc2)CC1
Reactant: COC(=O)Cc1ccc(OC(C)(C)C)cc1
Product: CC(C)(C)Oc1ccc(CC(=O)CC(=O)C2CCN(Cc3ccccc3)CC2)cc1
Yield: 87 %

Procedure:
The title compound was prepared using a procedure similar to that described in Example 13 Step C from 1-benzyl-4-acetylpiperidine and methyl 4-t-butoxyphenylacetate in 87% yield. 1H NMR (500 MHz) δ 7.30˜7.35 (m, 4H), 7.24˜7.29 (m, 1H), 7.12˜7.15 (m, 2H), 6.95˜6.97 (m, 2H), 3.57 (s, 2H), 3.50 (s, 2H), 2.91˜2.95 (m, 2H), 2.15 (tt, 3.9 & 11.8 Hz, 1H), 1.95˜2.01 (m, 2H), 1.75˜1.80 (m, 2H), 1.63˜1.72 (m, 2H), 1.36 (s, 9H).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:8]([OH:18])[CH2:9][CH2:10][NH:11][C:12](=[O:17])[C:13]([F:16])([F:15])[F:14])[CH:5]=[CH:6][CH:7]=1.[C:19]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)#[CH:20]>>[F:14][C:13]([F:16])([F:15])[C:12]([NH:11][CH2:10][CH2:9][CH:8]([OH:18])[C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([C:20]#[C:19][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:3]=1)=[O:17]
Reactant: O=C(NCCC(O)c1cccc(Br)c1)C(F)(F)F
Reactant: C#Cc1ccccc1
Product: O=C(NCCC(O)c1cccc(C#Cc2ccccc2)c1)C(F)(F)F

Procedure:
Sonogashira reaction of 25 with ethynyl-benzene yielded 2,2,2-trifluoro-N-(3-hydroxy-3-(3-(2-phenylethynyl)phenyl)propyl)acetamide as yellow oil. Yield (0.78 g, 73%).
Reaction SMILES: [CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][N:2]1[C:10]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:20]3[CH:21]=[C:22]4[CH:28]=[CH:27][N:26]([Si](C(C)C)(C(C)C)C(C)C)[C:23]4=[N:24][CH:25]=3)[CH:18]=2)[N:13]=[CH:12][N:11]=1.[F-].[Cs+]>C(#N)C>[CH2:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH2:1][N:2]1[C:10]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:20]3[CH:21]=[C:22]4[CH:28]=[CH:27][NH:26][C:23]4=[N:24][CH:25]=3)[CH:18]=2)[N:13]=[CH:12][N:11]=1
Reactant: CC(C)[Si](C(C)C)(C(C)C)n1ccc2cc(-c3ccc4ncnc(N5Cc6ccccc6C5)c4c3)cnc21
Agent: [Cs+]
Agent: [F-]
Solvent: CC#N
Product: c1ccc2c(c1)CN(c1ncnc3ccc(-c4cnc5[nH]ccc5c4)cc13)C2
Yield: 95.3 %

Procedure:
0.12 g of 4-(1,3-dihydroisoindol-2-yl)-6-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]-pyridin-5-yl)quinazoline and 0.05 g of caesium fluoride in 1 ml of acetonitrile are stirred at 25° C. in a flask until the reaction is complete (HPLC check about 24 hours). A precipitate precipitates out of the reaction solution. This is filtered off, rinsed with water and dried, giving 0.08 g of 4-(1,3-dihydroisoindol-2-yl)-6-(1H-pyrrolo[2,3-b]pyridin-5-yl)quinazoline (“A2”) as white solid (yield 95%, content 96%); MS-FAB (M+H+)=363.8; Rf (polar method): 1.63 min;
Reaction SMILES: [CH2:1]([C:3]1[NH:4][C:5](=[O:27])[C:6]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]3[C:20]([C:25]#[N:26])=[CH:21][CH:22]=[CH:23][CH:24]=3)=[CH:15][CH:14]=2)=[C:7]([CH2:9][CH2:10][CH3:11])[N:8]=1)[CH3:2].[O:28]1[C:32]2[CH:33]=[CH:34][C:35](B(O)O)=[CH:36][C:31]=2[CH2:30][CH2:29]1.N1C=CC=CC=1.C(N(CC)CC)C>C(OCC)(=O)C.C([O-])(=O)C.[Cu+2].C([O-])(=O)C.ClCCl>[O:28]1[C:32]2[CH:33]=[CH:34][C:35]([N:4]3[C:5](=[O:27])[C:6]([CH2:12][C:13]4[CH:18]=[CH:17][C:16]([C:19]5[C:20]([C:25]#[N:26])=[CH:21][CH:22]=[CH:23][CH:24]=5)=[CH:15][CH:14]=4)=[C:7]([CH2:9][CH2:10][CH3:11])[N:8]=[C:3]3[CH2:1][CH3:2])=[CH:36][C:31]=2[CH2:30][CH2:29]1
Reactant: OB(O)c1ccc2c(c1)CCO2
Reactant: CCCc1nc(CC)[nH]c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CCCc1nc(CC)n(-c2ccc3c(c2)CCO3)c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
Reaction time: 48 h
Yield: 100.2 %

Procedure:
A mixture of 4′-[(2-ethyl-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrile (3.0 g), 2,3-dihydro-1-benzofuran-5-ylboronic acid (2.8 g), copper(II) acetate (3.1 g), pyridine (3.1 mL), triethylamine (3.4 mL), molecular sieves 4 A (6.0 g) and dichloromethane (60 mL) was stirred for 2 days. The reaction mixture was diluted with ethyl acetate, and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound (4.0 g, 100%) as a pale-yellow liquid.
Reaction SMILES: [N:1]1([C:7]2[N:8]=[C:9]([CH2:14][C:15]([O-])=O)[NH:10][C:11](=[O:13])[CH:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[Na+].Cl.[F:20][C:21]1[CH:22]=[C:23]([NH2:32])[C:24]([NH:27][CH2:28][CH2:29][O:30][CH3:31])=[CH:25][CH:26]=1.Cl.CN(C)CCCN=C=NCC>N1C=CC=CC=1.CN(C)C=O.C(O)(=O)C>[F:20][C:21]1[CH:26]=[CH:25][C:24]2[N:27]([CH2:28][CH2:29][O:30][CH3:31])[C:15]([CH2:14][C:9]3[NH:10][C:11](=[O:13])[CH:12]=[C:7]([N:1]4[CH2:2][CH2:3][O:4][CH2:5][CH2:6]4)[N:8]=3)=[N:32][C:23]=2[CH:22]=1
Reactant: COCCNc1ccc(F)cc1N
Reactant: O=C([O-])Cc1nc(N2CCOCC2)cc(=O)[nH]1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: c1ccncc1
Solvent: CC(=O)O
Product: COCCn1c(Cc2nc(N3CCOCC3)cc(=O)[nH]2)nc2cc(F)ccc21
Yield: 27 %

Procedure:
The product is prepared according to the procedure described in Example 3, using 300 mg of sodium [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate, 760 mg of 4-fluoro-N1-(2-methoxyethyl)benzene-1,2-diamine hydrochloride and 330 mg of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride in a mixture of 5 ml of pyridine and 5 ml of dimethylformamide and then in 5 ml of acetic acid. After refluxing for one hour and purification by silica column chromatography, eluent: CH2Cl2/MeOH: 95/05, the residue obtained is purified by preparative HPLC/MS (method 1). After the acetonitrile has been evaporated off, the pH is brought to 8 using sodium bicarbonate (solid), then the aqueous phase is extracted with twice 25 ml of ethyl acetate, and the combined organic phases are dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure. 120 mg of 2-{[5-fluoro-1-(2-methoxyethyl)-1H-benzimidazol-2-yl]methyl}-6-(morpholin-4-yl)pyrimidin-4(3H)-one are obtained in the form of a white powder, the characteristics of which are the following:
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:23])[CH2:5][C:6]1[N:7]=[C:8]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=2)[S:9][C:10]=1[CH2:11][CH3:12])[CH3:2].[CH:24]([N-]C(C)C)(C)C.[Li+].CI>O1CCCC1>[CH2:1]([O:3][C:4](=[O:23])[CH:5]([C:6]1[N:7]=[C:8]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:21])([F:22])[F:20])=[CH:15][CH:14]=2)[S:9][C:10]=1[CH2:11][CH3:12])[CH3:24])[CH3:2]
Reactant: CCOC(=O)Cc1nc(-c2ccc(C(F)(F)F)cc2)sc1CC
Reactant: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: CI
Solvent: C1CCOC1
Product: CCOC(=O)C(C)c1nc(-c2ccc(C(F)(F)F)cc2)sc1CC
Temperature: 25 °C
Reaction time: 18 h
Yield: 59 %

Procedure:
[5-Ethyl-2-(4-trifluoromethyl-phenyl)-thiazol-4-yl]-acetic acid ethyl ester (2.02 g, 6.13 mmol) is dissolved into anhydrous tetrahydrofuran (THF) (10 mL) and lithium diisopropylamide (LDA) is slowly added at room temperature. This solution is allowed to stir at room temperature and monitored by TLC. After complete conversion, methyl iodide (582 mg, 4.00 mmol) is added slowly and the reaction is followed by TLC. After 18 h., the reaction is not complete, but is quenched with saturated ammonium chloride solution and diluted with diethyl ether. The two phases are separated and the organic layer is washed with water and brine, dried over anhydrous sodium sufate, then concentrated and purified using flash column chromatography (10% EtOAc/Hexanes). The pure 2-[5-Ethyl-2-(4-trifluoromethyl-phenyl)-thiazol-4-yl]-propionic acid ethyl ester (1.30 g, 3.64 mmol) is obtained in 59% yield.