Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([SiH2:5][O:6][C:7]([CH3:25])([CH3:24])[CH:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][C:12]([CH2:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[CH:13][CH:14]=2)[C:9]1=[O:23])([CH3:4])([CH3:3])[CH3:2].B1(C)OC(C2C=CC=CC=2)(C2C=CC=CC=2)[C@H]2N1CCC2.B.CSC>O1CCCC1>[C:1]([SiH2:5][O:6][C:7]([CH3:25])([CH3:24])[CH:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][C:12]([CH2:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[CH:13][CH:14]=2)[CH:9]1[OH:23])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)Cc1ccc2c(c1)C(=O)C(C(C)(C)O[SiH2]C(C)(C)C)CC2
Agent: B
Agent: CB1OC(c2ccccc2)(c2ccccc2)[C@@H]2CCCN12
Solvent: C1CCOC1
Solvent: CSC
Product: CC(C)(C)Cc1ccc2c(c1)C(O)C(C(C)(C)O[SiH2]C(C)(C)C)CC2
Temperature: -12.5 °C
Reaction time: 8 h
Yield: 44.4 %

Procedure:
To a −30° C. cooled solution of 2-(tert-Butyl-dimethyl-silanyloxymethyl)-7-(2,2-dimethyl-propyl)-3,4-dihydro-2H-naphthalen-1-one (2.20 g, 6.09 mmol) in tetrahydrofuran (20 mL) was added (S)-2-methyl-Cbs-oxazaborolidine (1 M in toluene, 0.61 mL, 0.61 mmol) and a solution of borane-methyl sulfide complex (2 M in tetrahydrofuran, 2.15 mL, 4.3 mmol) in tetrahydrofuran (5 mL). The reaction mixture was heated at −20 to −5° C. for 5 h. The reaction mixture was quenched with methanol (8.3 mL) at −5° C. and then allowed to warm to room temperature and stirred overnight. The solvent was removed under reduced pressure. Flash column chromatography (silica gel, 0–5% ethyl acetate/hexanes) recovered 790 mg of ketone and provided chiral 2-(tert-Butyl-dimethyl-silanyloxymethyl)-7-(2,2-dimethyl-propyl)-1,2,3,4-tetrahydro-naphthalen-1-ol (980 mg, 70%): 1H NMR (300 MHz, CDCl3) δ 7.14 (s, 1H), 7.03–6.96 (m, 2H), 4.84 (d, J=2.5 Hz, 1H), 3.92–3.82 (m, 2H), 3.04 (d, J=3.7 Hz, 1H), 2.92–2.67 (m, 2H), 2.46 (s, 2H), 2.04–1.86 (m, 2H), 1.75–1.63 (m, 1H), 0.91 (s, 9H), 0.90 (s, 9H), 0.10 (s, 3H), 0.09 (s, 3H).
Reaction SMILES: [CH2:1]([C:3]1[C:4](=[O:12])[N:5]=[C:6]2[C:11]=1[CH:10]=[CH:9][CH:8]=[CH:7]2)[CH3:2].[CH2:13]([Li])[CH2:14]CC.CN(C)CCN(C)C.ICC.[NH4+].[Cl-]>C1COCC1>[CH2:1]([C:3]1([CH2:13][CH3:14])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[NH:5][C:4]1=[O:12])[CH3:2]
Reactant: [Li]CCCC
Reactant: CCC1=c2ccccc2=NC1=O
Agent: CN(C)CCN(C)C
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCI
Solvent: C1CCOC1
Product: CCC1(CC)C(=O)Nc2ccccc21
Temperature: 25 °C
Yield: 47.6 %

Procedure:
A solution of 3-ethyl-indol-2-one (16 g, 0.1 mol) in dry THF (200 ml) under N2 was cooled to −25° C. and treated drop wise with n-butyllithium (2.5M in hexanes, 80 ml, 0.2 mol). To the resulting solution was added N,N,N′,N′-tetramethylethylenediamine (30 ml, 0.2 mol). After 30 min. iodoethane (8 ml, 0.1 mol) was added and the reaction mixture was allowed to warm to RT and stirred over night. The reaction mixture was poured into an aqueous NH4Cl solution, extracted with EtOAc (2×) and the combined organic layers were washed with dil. HCl, water, brine, dried (MgSO4) and concentrated. The residual oil was triturated with hexane to afford 3,3-diethylindol-2-one (9 g, 45%), mp. 156-159° C.; 1H NMR (DMSO-d6) δ 10.44 (s, 1H), 7.70-7.69 (t, 1H), 7.62-7.59 (m, 1H), 7.58 (d, 1H J=1.7 Hz), 7.53-7.50 (m, 1H), 7.45-7.41 (t, 1H), 7.36-7.35 (m, 1H), 7.34-7.33 (m, 1H), 6.91-6.89 (d, 1H J=8.2 Hz), 1.87-1.80 (m, 2H), 1.77-1.70 (m, 2H), 0.54-0.50 (t, 6H); MS (+ESI) m/z 190 (M+H).
Reaction SMILES: C([O:3][C:4](=O)[CH:5]=[C:6]([C:13]1[CH:14]=[C:15]2[C:19](=[C:20]([F:22])[CH:21]=1)[NH:18][CH:17]=[CH:16]2)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)C.C(OC(=O)C=C(C1C=CC=C2C=1C(C#N)=[CH:39][NH:40]2)C1C=CC=CC=1)C>>[F:22][C:20]1[CH:21]=[C:13]([C:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[CH:5][C:4]([NH:40][CH3:39])=[O:3])[CH:14]=[C:15]2[C:19]=1[NH:18][CH:17]=[CH:16]2
Reactant: CCOC(=O)C=C(c1ccccc1)c1cc(F)c2[nH]ccc2c1
Reactant: CCOC(=O)C=C(c1ccccc1)c1cccc2[nH]cc(C#N)c12
Product: CNC(=O)C=C(c1ccccc1)c1cc(F)c2[nH]ccc2c1
Yield: 59 %

Procedure:
3-(7-Fluoro-1H-indol-5-yl)-N-Methyl-3-phenyl-acrylamide LXXXII (120 mg, 59% yield) was prepared from 3-(7-fluoro-1H-indol-5-yl)-3-phenyl-acrylic acid ethyl ester using the procedure described above for 3-(1H-Indol-7-yl)-N-methyl-3-phenyl-acrylamide XVIII (see Example 4).
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[NH2:6][CH2:7][C:8]1[CH:38]=[CH:37][C:11]([CH2:12][N:13]2[C:25]3[C:24]4[CH:23]=[CH:22][C:21]([C:26]5[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=5)=[CH:20][C:19]=4[N:18]=[C:17]([NH2:32])[C:16]=3[N:15]=[C:14]2[CH2:33][O:34][CH2:35][CH3:36])=[CH:10][CH:9]=1.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl>[NH2:32][C:17]1[C:16]2[N:15]=[C:14]([CH2:33][O:34][CH2:35][CH3:36])[N:13]([CH2:12][C:11]3[CH:10]=[CH:9][C:8]([CH2:7][NH:6][S:2]([CH3:1])(=[O:4])=[O:3])=[CH:38][CH:37]=3)[C:25]=2[C:24]2[CH:23]=[CH:22][C:21]([C:26]3[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=3)=[CH:20][C:19]=2[N:18]=1
Reactant: CCOCc1nc2c(N)nc3cc(-c4cccnc4)ccc3c2n1Cc1ccc(CN)cc1
Reactant: CS(=O)(=O)Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Product: CCOCc1nc2c(N)nc3cc(-c4cccnc4)ccc3c2n1Cc1ccc(CNS(C)(=O)=O)cc1
Reaction time: 16 h
Yield: 38.7 %

Procedure:
Methanesulfonyl chloride (0.13 mL, 1.7 mmol) was added dropwise to a mixture of 1-(4-aminomethylbenzyl)-2-ethoxymethyl-7-(pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-4-amine (0.520 g, 1.2 mmol) in dichloromethane (10 mL). The reaction was stirred for 16 hours and then saturated aqueous sodium carbonate was added. The layers were separated and the aqueous fraction was extracted with 95:5 chloroform/methanol. The organic fractions were combined and washed sequentially with water and saturated aqueous sodium chloride, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting solid was purified by flash column chromatography with a gradient of CMA (2%–10%) in chloroform as the eluent. A final recrystallization from 2-propanol provided 0.240 g of N-{4-[4-amino-2-ethoxymethyl-7-(pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-1-ylmethyl]benzyl}methanesulfonamide as white granular crystals, mp 228.0–229.0° C.
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH:11]=O)=[CH:6][CH:5]=1.[F:13][C:14]1[CH:19]=[CH:18][CH:17]=C(F)[N:15]=1>CN(C)C=O>[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]2[CH:17]=[CH:18][CH:19]=[C:14]([F:13])[N:15]=2)=[CH:6][CH:5]=1
Reactant: O=CNc1ccc(Cl)cc1
Reactant: Fc1cccc(F)n1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Fc1cccc(Nc2ccc(Cl)cc2)n1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 104 %

Procedure:
Sodium hydride (1.2 g, 30.9 mmol) was added to a solution of N-(4-chloro-phenyl)-formamide (4 g, 25.7 mmol) in N,N-dimethylformamide (40 mL) and stirred for 15 minutes. 2,6-Difluoropyridine (2.96 g, 25.7 mmol) was added, the reaction mixture was stirred at 70° C. overnight and poured into a stirred ice-water solution. The resulting participate was filtrated off and dried to give (4-chloro-phenyl)-(6-fluoro-pyridin-2-yl)-amine (5.95 g) as the crude product. The crude product was used without further purification.
Reaction SMILES: O[CH2:2][NH:3][C:4](=[O:9])[C:5]([F:8])([F:7])[F:6].[CH3:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([CH3:17])[C:12]=1[N+:18]([O-:20])=[O:19].OS(O)(=O)=O>>[N+:18]([C:12]1[C:11]([CH3:10])=[C:16]([CH:15]=[CH:14][C:13]=1[CH3:17])[CH2:2][NH:3][C:4](=[O:9])[C:5]([F:8])([F:7])[F:6])([O-:20])=[O:19]
Reactant: Cc1cccc(C)c1[N+](=O)[O-]
Reactant: O=C(NCO)C(F)(F)F
Agent: O=S(=O)(O)O
Product: Cc1ccc(CNC(=O)C(F)(F)F)c(C)c1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 8 h

Procedure:
N-(Hydroxymethyl)trifluoroacetamide (6.6 mmol; 0.946 g) is added to a mixture of 2,6-dimethyl-nitrobenzene (0.899 mL; 6.6 mmol) and conc. H2SO4 (15 mL). The mixture is stirred at rt overnight, poured into ice water and stirred for 2 h. The precipitate is collected by filtration and dried. Yield 1.5 g (84%). MS [M−H]−=275, TLC: Rf=0.67 (silica gel, DCM:EtOH 95:5)).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:31]=[C:32]([O:34][CH2:35][C:36]2[N:37]=[C:38]([C:41]3[CH:46]=[N:45][CH:44]=[CH:43][N:42]=3)[S:39][CH:40]=2)[CH:33]=1)[CH2:12][N:13]1[CH:17]=[C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:15]([CH2:24][CH2:25][C:26]([O:28]CC)=[O:27])=[CH:14]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].O1CCCC1.Cl>C(O)C>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:31]=[C:32]([O:34][CH2:35][C:36]2[N:37]=[C:38]([C:41]3[CH:46]=[N:45][CH:44]=[CH:43][N:42]=3)[S:39][CH:40]=2)[CH:33]=1)[CH2:12][N:13]1[CH:17]=[C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:15]([CH2:24][CH2:25][C:26]([OH:28])=[O:27])=[CH:14]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOC(=O)CCc1cn(Cc2cc(OCc3ccccc3)cc(OCc3csc(-c4cnccn4)n3)c2)cc1-c1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Product: O=C(O)CCc1cn(Cc2cc(OCc3ccccc3)cc(OCc3csc(-c4cnccn4)n3)c2)cc1-c1ccccc1
Reaction time: 8 h
Yield: 82.6 %

Procedure:
A mixture of ethyl 3-[1-[3-benzyloxy-5-[2-(2-pyrazinyl)-4-thiazolylmethoxy]benzyl]-4-pheny-3-pyrrolyl]propionate (347 mg), 1N aqueous sodium hydroxide solution (5 ml), tetrahydrofuran (5 ml), and ethanol (5 ml) was stirred overnight under reflux conditions, and then 1N hydrochloric acid (5 ml) was added to the mixture, which was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), then concentrated. The colorless crystals obtained were collected by filtration to yield 3-[1-[3-benzyloxy-5-[2-(2-pyrazinyl)-4-thiazolylmethoxy]benzyl]-4-phenyl-3-pyrrolyl]propionic acid (274 mg, yield: 83%). This was recrystallized from ethanol-hexane. Melting point: 109–110° C.
Reaction SMILES: [C:1]([O:5][C:6]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]1[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br:21]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[Br:21][CH2:20][C:17]1[CH:18]=[CH:19][C:14]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[CH:15][CH:16]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1ccc(-c2ccccc2C(=O)OC(C)(C)C)cc1
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: CC(C)(C)OC(=O)c1ccccc1-c1ccc(CBr)cc1
Temperature: 25 °C
Yield: 81.8 %

Procedure:
To a solution of 2-t-butoxycarbonyl-4'-methylbiphenyl (25.3 g, 95 mmol) in CCl4 (200 ml) were added freshly opened N-bromosuccinimide (17.6 g, 0.099 mole) and dibenzoyl peroxide (2.28 g, 0.0094 moles). the mixture was refluxed for 4 hours, cooled to room temperature and filtered. The filtrate was washed with sat. NaHSO3 (1×50 ml), sat. NaHCO3 (1×50 ml), water (1×50 ml), sat. NaCl (1×50 ml) and dried over MgSO4. The solution was filtered, and concentrated in vacuo. The residue was dissolved in 100 ml of hot hexane. Crystallization gradually took place as the solution cooled. The flask was finally cooled to -20° C. and the precipitate recovered by filtration. The solid was washed with ice cold hexanes and dried in vacuo to give 27 g (88%) of a white solid. 1H-NMR (CDCl3): 1.23 (s, 9H), 4.53 (s, 2H), 7.2-7.5 (m, 7H), 7.68 (d, 1H).
Reaction SMILES: [BH4-].[Na+].[Cl:3][C:4]1[CH:5]=[N:6][CH:7]=[CH:8][C:9]=1[CH:10]=[O:11].O>CO>[Cl:3][C:4]1[CH:5]=[N:6][CH:7]=[CH:8][C:9]=1[CH2:10][OH:11]
Reactant: O=Cc1ccncc1Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: OCc1ccncc1Cl
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of sodium borohydride (601 mg, 15.9 mmol) in anhydrous methanol (25 mL) was added a solution of 3-chloropyridine-4-carbaldehyde (1.5 g, 10.6 mmol) in anhydrous methanol (5 mL) at 0° C. The mixture was stirred for 1 hour at room temperature. Water was added and extracted 3 times with ethyl acetate. The combined organic phase was washed with brine and dried over sodium sulfate. After evaporation of the solvent, (3-chloropyridin-4-yl)methanol was obtained as a white solid (1.4 g, 90% yield) and used for next step without further purification; 1H NMR (400 MHz, CDCl3): δ 2.41 (t, J=5.9 Hz, 1H), 4.83 (dd, J=0.8 Hz, J=5.9 Hz, 2H), 7.52-7.55 (m, 1H), 8.51 (m, 2H).
Reaction SMILES: CS(OC)(=O)=O.[NH2:7][C:8]1[N:9]=[N:10][C:11]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[C:16]=2[Cl:22])=[C:12]([NH2:14])[N:13]=1.[CH3:23]N(C)C=O>C1(C)C=CC=CC=1>[NH2:14][C:12]1[C:11]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[C:16]=2[Cl:22])=[N:10][N:9]([CH3:23])[C:8](=[NH:7])[N:13]=1
Reactant: CN(C)C=O
Reactant: Nc1nnc(-c2cccc(Cl)c2Cl)c(N)n1
Agent: COS(C)(=O)=O
Solvent: Cc1ccccc1
Product: Cn1nc(-c2cccc(Cl)c2Cl)c(N)nc1=N
Temperature: 100 °C
Reaction time: 0.5 h

Procedure:
Methyl methanesulfonate (0.50 g, 4.5 mmol), 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine (0.50 g, 2.0 mmol) and dimethylformamide (4 ml) were stirred and heated at 100° C. for 10 min. The solution was cooled, toluene (20 ml) added, and the mixture stirred for 0.5 h. The solid was collected by filtration and recrystallised from propan-2-ol to give the methanesulfonate salt of the title compound as a white solid (0.40 g), mp 274-276° C.
Reaction SMILES: C([O:5][C:6](=[O:48])[C@H:7]([CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[NH:8][C:9](=[O:40])[CH2:10][N:11]([C:21](=[O:39])[C@H:22]([CH3:38])[NH:23][C@H:24]([C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH2:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH:12]1[CH2:20][C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:13]1)(C)(C)C.[BrH:49].CCOCC>C(O)(=O)C>[BrH:49].[CH2:36]([O:35][C:33]([C@@H:24]([NH:23][C@H:22]([C:21]([N:11]([CH:12]1[CH2:13][C:14]2[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:20]1)[CH2:10][C:9]([NH:8][C@H:7]([C:6]([OH:48])=[O:5])[CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)=[O:40])=[O:39])[CH3:38])[CH2:25][CH2:26][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)=[O:34])[CH3:37]
Reactant: CCOC(=O)[C@H](CCc1ccccc1)N[C@@H](C)C(=O)N(CC(=O)N[C@@H](Cc1ccccc1)C(=O)OC(C)(C)C)C1Cc2ccccc2C1
Agent: Br
Solvent: CCOCC
Solvent: CC(=O)O
Product: CCOC(=O)[C@H](CCc1ccccc1)N[C@@H](C)C(=O)N(CC(=O)N[C@@H](Cc1ccccc1)C(=O)O)C1Cc2ccccc2C1

Procedure:
N-[1(S)-Ethoxycarbonyl-3-phenylpropyl]-L-alanyl-N-(2-indanyl)glycyl-L-phenylalanine tert-butyl ester (1.8 g) is dissolved in 2 ml of acetic acid, and 3 ml of 30% hydrogen bromide in acetic acid is added. The mixture is reacted at room temperature for 10 minutes. The reaction mixture is shaken with 300 ml of ether and allowed to stand. The ether is then decanted off and to the precipitate is added ethyl acetate, whereby 1.35 g of N-[1(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanyl-N-(2-indanyl)glycyl-L-phenylalanine hydrobromide is obtained as colorless prisms melting at 177°-181° C. (decomposition).
Reaction SMILES: FC(F)(F)C(O)=O.C(OC([CH2:15][NH:16][C:17]1[CH:18]=[C:19]([C:23]2[CH:24]=[N:25][C:26]([CH2:29][CH2:30][C:31]([O:33][CH3:34])=[O:32])=[N:27][CH:28]=2)[CH:20]=[CH:21][CH:22]=1)=O)(C)(C)C.[OH-].[Na+]>ClCCl>[CH3:15][NH:16][C:17]1[CH:18]=[C:19]([C:23]2[CH:28]=[N:27][C:26]([CH2:29][CH2:30][C:31]([O:33][CH3:34])=[O:32])=[N:25][CH:24]=2)[CH:20]=[CH:21][CH:22]=1
Reactant: COC(=O)CCc1ncc(-c2cccc(NCC(=O)OC(C)(C)C)c2)cn1
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CNc1cccc(-c2cnc(CCC(=O)OC)nc2)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 187.7 %

Procedure:
0.12 ml (1.6 mmol, 5 eq) of trifluoroacetic acid is added to a solution of 118 mg (0.32 mmol, 1 eq) of methyl 3-{5-[3-(tert-butoxycarbonylmethylamino)phenyl]pyrimidin-2-yl}propanoate in 4 ml of dichloromethane. The reaction mixture is stirred for 16 hours at room temperature. The reaction is stopped by adding 20 mL of 1N sodium hydroxide solution and is then extracted with ethyl acetate. The organic phases are combined and dried over sodium sulfate. The solvents are evaporated off and the residue is then chromatographed on silica gel (99/1 dichloromethane/methanol). 163 mg of methyl 3-[5-(3-methylaminophenyl)pyrimidin-2-yl]propanoate are obtained in the form of a colorless oil. Yield=99%.
Reaction SMILES: [CH3:1][N:2]1[C:7](=[O:8])[CH:6]=[C:5]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[N:4]=[C:3]1[CH2:15][C:16]([O-:18])=O.[Na+].[I:20][C:21]1[CH:22]=[C:23]([CH:25]=[CH:26][C:27]=1[F:28])[NH2:24]>>[I:20][C:21]1[CH:22]=[C:23]([NH:24][C:16](=[O:18])[CH2:15][C:3]2[N:2]([CH3:1])[C:7](=[O:8])[CH:6]=[C:5]([N:9]3[CH2:10][CH2:11][O:12][CH2:13][CH2:14]3)[N:4]=2)[CH:25]=[CH:26][C:27]=1[F:28]
Reactant: Cn1c(CC(=O)[O-])nc(N2CCOCC2)cc1=O
Reactant: Nc1ccc(F)c(I)c1
Agent: [Na+]
Product: Cn1c(CC(=O)Nc2ccc(F)c(I)c2)nc(N2CCOCC2)cc1=O
Yield: 54.2 %

Procedure:
The product is prepared according to the procedure described in example 68, using 200 mg of sodium [1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate and 210 mg of 3-iodo-4-fluoroaniline. 186 mg of N-(3-iodo-4-fluorophenyl)-2-[1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide are obtained in the form of a white solid, the characteristics of which are the following:
Reaction SMILES: [CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([NH:16]C(=O)C(OCC)=O)=[C:10]([N+:13]([O-:15])=[O:14])[CH:11]=2)[NH:6][C:5](=[O:24])[C:4]1=[O:25])[CH3:2].O.C(O)C>S(=O)(=O)(O)O>[NH2:16][C:9]1[CH:8]=[C:7]2[C:12](=[CH:11][C:10]=1[N+:13]([O-:15])=[O:14])[N:3]([CH2:1][CH3:2])[C:4](=[O:25])[C:5](=[O:24])[NH:6]2
Reactant: CCOC(=O)C(=O)Nc1cc2[nH]c(=O)c(=O)n(CC)c2cc1[N+](=O)[O-]
Agent: O=S(=O)(O)O
Solvent: CCO
Solvent: O
Product: CCn1c(=O)c(=O)[nH]c2cc(N)c([N+](=O)[O-])cc21
Yield: 94.4 %

Procedure:
24 g (68.6 mmol) of this amide were refluxed in a mixture of 13 ml of concentrated sulfuric acid, 240 ml of water and 250 ml of ethanol for 3 h. The precipitate was then filtered off with suction to yield 16.2 g (98%) of the product.
Reaction SMILES: [CH3:1][N:2]([C:4](=O)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[NH2:3].C1C=CC(P2([Se]P(C3C=CC=CC=3)(=[Se])[Se]2)=[Se:19])=CC=1>C1(C)C=CC=CC=1>[CH3:1][N:2]([C:4](=[Se:19])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[NH2:3]
Reactant: [Se]=P1(c2ccccc2)[Se]P(=[Se])(c2ccccc2)[Se]1
Reactant: CN(N)C(=O)c1ccccc1
Solvent: Cc1ccccc1
Product: CN(N)C(=[Se])c1ccccc1
Temperature: 25 °C
Yield: 194.7 %

Procedure:
A mixture of N-methylbenzohydrazide (450 mg, 3.0 mmol) and the Woollins' Reagent (540 mg, 1 mmol) in anhydrous toluene (10 ml), was heated at 120° C. for Ih. The resulting orange solution was cooled to room temperature, the solvent was removed in vacuo and the selenoamide purified by column chromatography on silica gel (3:1 Hexane:EtOAc) and to give N-methylbenzoselenohydrazide (415 mg) in 65% yield.
Reaction SMILES: [CH3:1][N:2]1[C:6]2=[N:7][CH:8]=[CH:9][CH:10]=[C:5]2[N:4]=[C:3]1S(C)(=O)=O.[Cl:15][C:16]1[CH:17]=[C:18]2[N:24]([CH:25]([CH3:27])[CH3:26])[C:23](=[O:28])[N:22]([C:29]3[CH:34]=[CH:33][C:32]([OH:35])=[CH:31][CH:30]=3)[C:19]2=[N:20][CH:21]=1.[H-].[Na+]>CN(C=O)C.CO>[Cl:15][C:16]1[CH:17]=[C:18]2[N:24]([CH:25]([CH3:27])[CH3:26])[C:23](=[O:28])[N:22]([C:29]3[CH:34]=[CH:33][C:32]([O:35][C:3]4[N:2]([CH3:1])[C:6]5=[N:7][CH:8]=[CH:9][CH:10]=[C:5]5[N:4]=4)=[CH:31][CH:30]=3)[C:19]2=[N:20][CH:21]=1
Reactant: Cn1c(S(C)(=O)=O)nc2cccnc21
Reactant: CC(C)n1c(=O)n(-c2ccc(O)cc2)c2ncc(Cl)cc21
Agent: [H-]
Agent: [Na+]
Solvent: CO
Solvent: CN(C)C=O
Product: CC(C)n1c(=O)n(-c2ccc(Oc3nc4cccnc4n3C)cc2)c2ncc(Cl)cc21
Temperature: 180 °C
Yield: 58.3 %

Procedure:
3-Methyl-2-(methylsulfonyl)-3H-imidazo[4,5-b]pyridine (100 mg) was added to a solution of 6-chloro-3-(4-hydroxyphenyl)-1-(1-methylethyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (148 mg) and NaH (20.83 mg) in DMF (3 mL) at room temperature. The mixture was heated at 180° C. for 30 min under microwave irradiation. The reaction mixture was diluted with MeOH and concentrated in vacuo. The residue was purified by column chromatography (silica gel, eluted with 0%-50% EtOAc in hexane) to give 6-chloro-1-(1-methylethyl)-3-{4-[(3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)oxy]phenyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (120 mg) as white crystals.
Reaction SMILES: [S:1]1[C:5]([C:6]2[O:7][C:8]3[C:9](=[C:11]([C:15]([OH:17])=O)[CH:12]=[CH:13][CH:14]=3)[N:10]=2)=[CH:4][C:3]2[CH2:18][CH2:19][CH2:20][C:2]1=2.Cl.Cl.[NH2:23][CH:24]1[CH2:31][CH:30]2[N:32]([CH3:33])[CH:26]([CH2:27][CH2:28][CH2:29]2)[CH2:25]1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C=O)C>[CH3:33][N:32]1[CH:26]2[CH2:27][CH2:28][CH2:29][CH:30]1[CH2:31][CH:24]([NH:23][C:15]([C:11]1[CH:12]=[CH:13][CH:14]=[C:8]3[O:7][C:6]([C:5]4[S:1][C:2]5[CH2:20][CH2:19][CH2:18][C:3]=5[CH:4]=4)=[N:10][C:9]=13)=[O:17])[CH2:25]2
Reactant: CN1C2CCCC1CC(N)C2
Reactant: O=C(O)c1cccc2oc(-c3cc4c(s3)CCC4)nc12
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CN1C2CCCC1CC(NC(=O)c1cccc3oc(-c4cc5c(s4)CCC5)nc13)C2
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 40.8 %

Procedure:
A mixture of 2-(5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl)benzo[d]oxazole-4-carboxylic acid (90 mg, 0.32 mmol), 3-amino-9-methyl-9-azabicyclo[3.3.1]nonane dihydrochloride (86 mg, 0.38 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (122 mg, 0.64 mmol) and 1-hydroxybenzotriazole (86 mg, 0.64 mmol) in DMF (5 mL) was stirred under nitrogen at room temperature for 10 min, and then triethylamine (0.27 mL, 1.92 mmol) was added. The resulting reaction mixture was stirred at room temperature overnight, and then was quenched with a saturated solution of sodium bicarbonate, extracted with methylene chloride. The combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated. The crude material was purified by column chromatography (silica gel, 90:9:1 ethyl acetate/methanol/concentrated ammonium hydroxide) and semi-preparative HPLC to afford N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl)benzoxazole-4-carboxamide (55 mg, 41%) as a light yellow solid: 1H NMR (500 MHz, CDCl3) δ 9.01 (d, J=7.5 Hz, 1H), 8.16 (dd, J=8.0, 1.0 Hz, 1H), 7.65 (s, 1H), 7.61 (dd, J=8.0, 1.0 Hz, 1H), 7.39 (t, J=8.0 Hz, 1H), 4.60-4.50 (m, 1H), 3.10 (d, J=10.0 Hz, 2H), 3.03-3.00 (m, 2H), 2.86-2.82 (m, 2H), 2.65-2.52 (m, 4H), 2.54 (s, 3H), 2.18-1.96 (m, 3H), 1.62-1.46 (m, 3H), 1.25-1.18 (m, 2H); MS (ESI+) m/z 422 (M+H); HPLC>99% (AUC), tR=13.28 min.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([C:11](=O)[CH2:12][CH3:13])[CH:6]=[C:7]([Br:10])[C:8]=1[OH:9].Cl.[CH3:16][O:17][NH2:18].C(O)C.C>N1C=CC=CC=1>[CH3:16][O:17][N:18]=[C:11]([C:5]1[CH:6]=[C:7]([Br:10])[C:8]([OH:9])=[C:3]([CH2:2][NH2:1])[CH:4]=1)[CH2:12][CH3:13]
Reactant: CON
Reactant: CCC(=O)c1cc(Br)c(O)c(CN)c1
Agent: Cl
Solvent: CCO
Solvent: c1ccncc1
Product: CCC(=NOC)c1cc(Br)c(O)c(CN)c1
Yield: 78.9 %

Procedure:
A solution of 9.0 g of 3'-aminomethyl-5'-bromo-4'-hydroxypropiophenone and 9.0 g of O-methylhydroxylamine hydrochloride in 80 ml of pyridine and 40 m of ethanol is refluxed with heating for 25 minutes. Activated charcoal is added to the reaction mixture and then filtered off. The filtrate is concentrated under reduced pressure and to the residue are added 200 ml of ice-cold water and 6.0 g of sodium hydrogencarbonate and stirred. The insoluble substance is collected by filtration and washed with water and then dried to give 7.9 g of 3'-aminomethyl-5'-bromo-4'-hydroxypropiophenone O-methyloxime as fine powdery solid, melting at 178°-178.5° C. with decomposition.