Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:11]3([C:15](=[O:16])[N:14]([CH3:17])[C:13](SC)=[N:12]3)[CH2:10][CH:9]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=3)[O:8][C:5]2=[CH:6][CH:7]=1.[NH4+:27].[I-].N.CCO>>[NH2:27][C:13]1[N:14]([CH3:17])[C:15](=[O:16])[C:11]2([C:4]3[C:5](=[CH:6][CH:7]=[C:2]([Br:1])[CH:3]=3)[O:8][CH:9]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=3)[CH2:10]2)[N:12]=1
Reactant: [NH4+]
Reactant: CSC1=NC2(CC(c3cccc(Cl)c3)Oc3ccc(Br)cc32)C(=O)N1C
Agent: N
Agent: [I-]
Solvent: CCO
Product: CN1C(=O)C2(CC(c3cccc(Cl)c3)Oc3ccc(Br)cc32)N=C1N
Yield: 45.4 %

Procedure:
A solution of 6-bromo-2-(3-chlorophenyl)-1′-methyl-2′-(methylthio)spiro[chroman-4,4′-imidazol]-5′(1′H)-one (100 mg, 0.22 mmol) and NH4I (64 mg, 0.44 mmol) in a solution of NH3/EtOH (4 mL, 1.5 N) was heated at 110° C. in a tube under microwave reactor for 2-2.5 h. After cooling, the mixture was concentrated in vacuo to give a residue, which was purified by preparative TLC to afford 2′-amino-6-bromo-2-(3-chlorophenyl)-1′-methylspiro[chroman-4,4′-imidazol]-5′(1′H)-one (42 mg, 46%).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][C:5]([O:8][C:9]2[CH:10]=[C:11]([NH:15][C:16](=[O:28])[C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([C:26]#[N:27])([CH3:25])[CH3:24])[CH:18]=3)[CH:12]=[CH:13][CH:14]=2)=[CH:4][CH:3]=1.[C:29]([N:34]=[C:35]=[S:36])(=[O:33])[O:30][CH2:31][CH3:32].O>CS(C)=O>[C:26]([C:23]([C:19]1[CH:18]=[C:17]([C:16]([NH:15][C:11]2[CH:10]=[C:9]([CH:14]=[CH:13][CH:12]=2)[O:8][C:5]2[CH:4]=[CH:3][C:2]([NH:1][C:35]([NH:34][C:29](=[O:33])[O:30][CH2:31][CH3:32])=[S:36])=[N:7][CH:6]=2)=[O:28])[CH:22]=[CH:21][CH:20]=1)([CH3:24])[CH3:25])#[N:27]
Reactant: CC(C)(C#N)c1cccc(C(=O)Nc2cccc(Oc3ccc(N)nc3)c2)c1
Reactant: CCOC(=O)N=C=S
Solvent: CS(C)=O
Solvent: O
Product: CCOC(=O)NC(=S)Nc1ccc(Oc2cccc(NC(=O)c3cccc(C(C)(C)C#N)c3)c2)cn1
Temperature: 25 °C
Reaction time: 21 h

Procedure:
To a solution of N-{3-[(6-aminopyridin-3-yl)oxy]phenyl}-3-(1-cyano-1-methylethyl)benzamide (4.32 g, 11.6 mmol) in DMSO (100 mL) was added ethyl isothiocyanatocarbonate (1.64 mL, 13.9 mmol), and the mixture was stirred at room temperature for 21 hr. Water (300 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (250 mL, 50 mL). The combined organic layer was washed with saturated brine (30 mL) and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure to give ethyl ({5-[3-({[3-(1-cyano-1-methylethyl)phenyl]carbonyl}amino)phenoxy]pyridin-2-yl}carbamothioyl)carbamate as a yellow amorphous solid. The obtained compound was used in the next reaction without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8](=[O:13])[CH2:9][C:10](=[O:12])[CH3:11])[CH:5]=[CH:6][CH:7]=1.[N:14]([O-])=[O:15].[Na+].C(=O)(O)[O-].[Na+]>C(O)(=O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:8](=[O:13])[C:9](=[N:14][OH:15])[C:10](=[O:12])[CH3:11])[CH:5]=[CH:6][CH:7]=1
Reactant: CC(=O)CC(=O)c1cccc(Cl)c1
Reactant: O=N[O-]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: CC(=O)C(=NO)C(=O)c1cccc(Cl)c1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 89.3 %

Procedure:
To a 0° C. solution of 1-(3-chlorophenyl)butane-1,3-dione (0.75 g, 3.8 mmol) in 15 mL acetic acid was slowly added sodium nitrite (0.560 g, 8.11 mmol) as a solution in 1.5 mL water. The reaction was stirred at 0° C. for 30 minutes and then warmed to room temperature. After an additional 4 hours, the reaction was poured into aqueous saturated sodium bicarbonate and extracted three times with dichloromethane. The combined extracts were dried over magnesium sulfate and concentrated to yield 765.7 mg (89%) of 1-(3-chlorophenyl)-2-(hydroxyimino)butane-1,3-dione, which was carried forward without further purification. LCMS (ESI) m+H=226; 1H NMR (400 MHz, DMSO-d6) δ: 7.81 (d, 1H), 7.80 (s, 1H), 7.75 (d, 1H), 7.62 (t, 1H), 2.60 (s, 1H), 2.48 (s, 3H).
Reaction SMILES: [CH2:1]([NH2:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[N+:20]([C:23]1[CH:30]=[CH:29][CH:28]=[CH:27][C:24]=1[CH2:25]Cl)([O-:22])=[O:21]>C(O)C>[N+:20]([C:23]1[CH:30]=[CH:29][CH:28]=[CH:27][C:24]=1[CH2:25][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][CH2:1][NH2:19])([O-:22])=[O:21]
Reactant: CCCCCCCCCCCCCCCCCCN
Reactant: O=[N+]([O-])c1ccccc1CCl
Solvent: CCO
Product: NCCCCCCCCCCCCCCCCCCCc1ccccc1[N+](=O)[O-]
Reaction time: 72 h

Procedure:
Octadecylamine (13.5 g, 0.05 mol) was dissolved in warm absolute ethanol (300 ml) and 2-nitrobenzyl chloride was added. After three days at room temperature, the mixture was cooled and the unreacted octadecylamine which crystallized was removed by filtration. The filtrate was evaporated to dryness and the residue dissolved in dilute aqueous hydrochloric acid. Ether extraction of the acidic solution removed unreacted 2-nitrobenzyl chloride. The aqueous layer was made basic with potassium hydroxide solution and the resulting mixture was extracted with ether. The dried ether layer was evaporated to yield an oil which crystallized. Crystallization from methanol gave pure product (0.8 g, m.p. 53°-56° C.).
Reaction SMILES: [CH:1]1[NH:2][C:3]2[N:9]=[C:8]([NH2:10])[N:7]=[C:6](Cl)[C:4]=2[N:5]=1.NC(N)=[Se:14]>C(O)C>[NH:7]1[C:6](=[Se:14])[C:4]2[NH:5][CH:1]=[N:2][C:3]=2[N:9]=[C:8]1[NH2:10]
Reactant: NC(N)=[Se]
Reactant: Nc1nc(Cl)c2nc[nH]c2n1
Solvent: CCO
Product: Nc1nc2nc[nH]c2c(=[Se])[nH]1
Yield: 70 %

Procedure:
1.7 g (10 mmol) of 6-chloroguanine and 1.2 g (10 mmol) of selenourea were put in 30 ml of absolute ethanol and boiled under reflux for 2 hours. After completion of the reaction, the resulting precipitate was separated by filtration, washed with water and dissolved in 200 ml of 2 wt% aqueous sodium carbonate solution by heating. The resulting solution was acidified with acetic acid to form crystals. The crystals were separated by filtration and dried to obtain 1.5 g (7 mmol) of 6-selenoguanine.
Reaction SMILES: [CH3:1]N(C)C=O.[H-].[Na+].[Cl:8][C:9]1[CH:14]=[C:13]([O:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([O:28][CH3:29])=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][N:17]=2)[CH:12]=[CH:11][C:10]=1[NH:30][C:31](=[O:41])[O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[CH3:40].CI>O>[Cl:8][C:9]1[CH:14]=[C:13]([O:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([O:28][CH3:29])=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][N:17]=2)[CH:12]=[CH:11][C:10]=1[N:30]([CH3:1])[C:31](=[O:41])[O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[CH3:40]
Reactant: CN(C)C=O
Reactant: COc1cc2ncnc(Oc3ccc(NC(=O)OCc4ccccc4C)c(Cl)c3)c2cc1OC
Agent: [H-]
Agent: [Na+]
Solvent: CI
Solvent: O
Product: COc1cc2ncnc(Oc3ccc(N(C)C(=O)OCc4ccccc4C)c(Cl)c3)c2cc1OC
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 89 %

Procedure:
Dimethylformamide (5 ml) was added to sodium hydride (11 mg), and 2-methylbenzyl N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}carbamate (62 mg) was added to the mixture. Subsequently, a dimethylformamide solution (2 ml) of methyl iodide (77 mg) was added thereto, and the mixture was stirred at room temperature for 10 min. Water was added to stop the reaction, and the reaction solution was then extracted with ethyl acetate, followed by washing with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (57 mg, yield 89%).
Reaction SMILES: [CH2:1]([N:3]1[CH2:15][CH2:14][C:6]2[NH:7][C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:13]=3[C:5]=2[CH2:4]1)[CH3:2].[CH3:16][C:17]1[CH:25]=[CH:24][C:20]([CH:21]2[O:23][CH2:22]2)=[CH:19][CH:18]=1.[H-].[Na+]>CN(C=O)C>[CH2:1]([N:3]1[CH2:15][CH2:14][C:6]2[N:7]([CH2:22][CH:21]([C:20]3[CH:24]=[CH:25][C:17]([CH3:16])=[CH:18][CH:19]=3)[OH:23])[C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:13]=3[C:5]=2[CH2:4]1)[CH3:2]
Reactant: Cc1ccc(C2CO2)cc1
Reactant: CCN1CCc2[nH]c3ccccc3c2C1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCN1CCc2c(c3ccccc3n2CC(O)c2ccc(C)cc2)C1

Procedure:
2-Ethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (400 mg, 2.0 mmol), 4-methylstyrene oxide (2.01 g, 15 mmol) and NaH (240 mg, 6 mmol) were heated in DMF (6 mL) at 120° C. for 16 h to obtain 120 mg of racemic-2-(2-ethyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)-1-p-tolyethanol as a TFA salt after purification by reverse-phase chromatography (C-18, 500 mm×50 mm, Mobile Phase A=0.05% TFA in water, B=0.05% TFA in acetonitrile, Gradient: 10% B to 80% B in 30 min., injection vol. 5 mL). 1H NMR (CDCl3, TFA salt) δ (ppm): 13.40-13.10 (bs, 1H), 7.40-7.30 (t, 2H), 7.29-7.10 (m, 6H), 5.07-4.95 (m, 1H), 4.75-4.60 (t, 1H), 4.25-4.02 (m, 3H), 3.75-3.65 (m, 1H), 3.40-3.0 (m, 5H), 2.35 (S, 3H), 1.47-1.40 (t, 3H).
Reaction SMILES: [F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][C:8]32[C:14](=[O:15])[NH:13][C:12](=[O:16])[NH:11]3)=[CH:4][CH:3]=1.C[Si](N([Si](C)(C)C)C(=[O:27])C(F)(F)F)(C)C.BrBr>C(Cl)CCl>[OH:27][CH:6]1[C:5]2[C:9](=[CH:10][C:2]([F:1])=[CH:3][CH:4]=2)[C:8]2([C:14](=[O:15])[NH:13][C:12](=[O:16])[NH:11]2)[CH2:7]1
Reactant: C[Si](C)(C)N(C(=O)C(F)(F)F)[Si](C)(C)C
Reactant: O=C1NC(=O)C2(CCc3ccc(F)cc32)N1
Agent: BrBr
Solvent: ClCCCl
Product: O=C1NC(=O)C2(CC(O)c3ccc(F)cc32)N1
Yield: 85 %

Procedure:
6'-Fluoro-spiro[imidazolidine-4,1'-indan]-2,5-dione, (C.A. reg. no. 66892-38-4)(1.1 g, 5 mmol) was combined with 2.65 ml (10 mmol) bis-(trimethylsilyl) trifluoroacetamide, 0.8 g (5 mmol) bromine and 30 ml ethylene dichloride and heated at reflux for 2.5 hours. During this time color was lost from the reaction mixture. The reaction mixture was concentrated in vacuo to an amber oil which was diluted with 10 ml water. Over a period of 16 hours at 25° C. a solid gradually formed. This material was isolated by filtration and dried in vacuo at 100° C. to give 1.0 g (85% yield) of the title compound: mp 209°-211° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[S:9](Cl)(=[O:11])=[O:10].N1C=CC=CC=1.[NH2:19][C:20]1[CH:21]=[C:22]2[C:27](=[CH:28][CH:29]=1)[N:26]=[C:25]([CH3:30])[CH:24]=[CH:23]2.C([O-])(O)=O.[Na+]>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[S:9]([NH:19][C:20]1[CH:21]=[C:22]2[C:27](=[CH:28][CH:29]=1)[N:26]=[C:25]([CH3:30])[CH:24]=[CH:23]2)(=[O:11])=[O:10]
Reactant: Cc1ccc2cc(N)ccc2n1
Reactant: O=S(=O)(Cl)c1cc(Cl)ccc1Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccncc1
Solvent: ClCCl
Product: Cc1ccc2cc(NS(=O)(=O)c3cc(Cl)ccc3Cl)ccc2n1
Reaction time: 0.08 h
Yield: 51.7 %

Procedure:
To a solution of 2,5-dichlorobenzenesulphonyl chloride (163 mg, 0.664 mmol) in dichloromethane (4 mL) was added pyridine (130 μL, 1.58 mmol) and the mixture was stirred under N2 for 5 min, after which time 6-amino-2-methylquinoline (100 mg, 0.632 mmol) was added. The resulting mixture was stirred for 2 h at room temperature, then saturated NaHCO3 solution (10 mL) was added and the mixture was extracted into ethyl acetate (20 mL). The organic phase was washed with brine, dried (Na2SO4), filtered and evaporated to give a residue that was purified using flash chromatography to afford an off-white solid (120 mg, 52%), single spot at Rf 0.68 (ethyl acetate). mp 124.6-125.0° C., HPLC purity 99+% (tR 2.22 min in 10% water-acetonitrile). 1H NMR (CDCl3): δ 7.98 (1H, d, 2.2 Hz), 7.94 (1H, d, J=8.4 Hz), 7.88 (1H, d, J=8.9 Hz), 7.57 (1H, d, J=2.2 Hz), 7.45-7.35 (3H, m), 7.27-7.24 (2H, m), 2.68 (3H, s). LCMS: 365.10 (M−). FAB-MS (MH+, C16H12Cl2N2O2S): calcd 367.0075, found 367.0074.
Reaction SMILES: C(OC([N:8]1[CH2:12][CH:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O.[OH-].[Na+]>C(Cl)Cl>[C:13]1([CH:11]2[CH2:12][NH:8][CH2:9][CH2:10]2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: CC(C)(C)OC(=O)N1CCC(c2ccccc2)C1
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: c1ccc(C2CCNC2)cc1
Temperature: 25 °C
Reaction time: 0.75 h

Procedure:
To 612 mg (1.23 mmol) of (3S,4S)-3-[1-isopropyl-3-methyl-bicyclo[3.2.1]-2-oxo-1β,3,8-triaza-spiro[4.5]dodec-8-ylmethyl]-4-phenyl-pyrrolidine-1-carboxylic acid tert-butyl ester in DCM (12 mL) was added TFA (3.3 mL). The reaction mixture was stirred for 0.75 hour at room temperature, neutralized with 1N NaOH (40 mL) and extracted with DCM. The organic layer was dried over sodium sulfate and concentrated to give 448 mg (88%) of (3R,4S)-3-[(1-isopropyl-3-methyl-bicyclo[3.2.1]-2-oxo-1β,3,8-triaza-spiro[4.5]dodec-8-ylmethyl]-4-phenyl-pyrrolidine as a white foam.
Reaction SMILES: [C:1]([N:5]1[C:9]([CH3:10])=[C:8]([NH:11][C:12]([NH:14][C:15]2[CH:20]=[C:19]([C:21]3[C:32](=[O:33])[N:31]([CH3:34])[C:24]4[N:25]=[C:26](SC)[N:27]=[CH:28][C:23]=4[CH:22]=3)[C:18]([Cl:35])=[CH:17][C:16]=2[F:36])=[O:13])[CH:7]=[N:6]1)([CH3:4])([CH3:3])[CH3:2].C1C=C(Cl)C=C(C(OO)=O)C=1.[CH3:48][NH2:49]>C1COCC1>[C:1]([N:5]1[C:9]([CH3:10])=[C:8]([NH:11][C:12]([NH:14][C:15]2[CH:20]=[C:19]([C:21]3[C:32](=[O:33])[N:31]([CH3:34])[C:24]4[N:25]=[C:26]([NH:49][CH3:48])[N:27]=[CH:28][C:23]=4[CH:22]=3)[C:18]([Cl:35])=[CH:17][C:16]=2[F:36])=[O:13])[CH:7]=[N:6]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CSc1ncc2cc(-c3cc(NC(=O)Nc4cnn(C(C)(C)C)c4C)c(F)cc3Cl)c(=O)n(C)c2n1
Reactant: CN
Agent: O=C(OO)c1cccc(Cl)c1
Solvent: C1CCOC1
Product: CNc1ncc2cc(-c3cc(NC(=O)Nc4cnn(C(C)(C)C)c4C)c(F)cc3Cl)c(=O)n(C)c2n1
Yield: 62 %

Procedure:
Using a procedure analogous to Example A1, 1-(1-tert-butyl-5-methyl-1H-pyrazol-4-yl)-3-(4-chloro-2-fluoro-5-(8-methyl-2-(methylthio)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-6-yl)phenyl)urea (80 mg, 0.151 mmol), MCPBA (47 mg, 0.189 mmol) and 2.0N methylamine in THF (0.8 mL) were combined to afford 1-(1-tert-butyl-5-methyl-1H-pyrazol-4-yl)-3-(4-chloro-2-fluoro-5-(8-methyl-2-(methylamino)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-6-yl)phenyl)urea (48 mg, 62% yield). 1H NMR (300 MHz, DMSO-d6): δ 1.49 (s, 9H), 2.27 (s, 3H), 2.89 (s, 3H), 3.49-3.56 (m, 3H), 7.39 (s, 1H), 7.49 (d, 1H), 7.74 (s, 1H), 7.94 (br. s, 1H), 8.17 (d, 1H), 8.29 (s, 1H), 8.62-8.74 (m, 2H); MS (ESI) m/z: 513.0 (M+H+).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[N:22]=[CH:21][N:20]=[C:19]([NH:23]NC3C=CC=CC=3)[CH:18]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.Cl.[CH3:32][N:33]([CH3:40])[CH2:34]/[CH:35]=[CH:36]/[C:37](Cl)=[O:38].C(=O)(O)[O-].[Na+]>CN1CCCC1=O.C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[N:22]=[CH:21][N:20]=[C:19]([NH:23][C:2]3[CH:3]=[C:4]([NH:16][C:37](=[O:38])/[CH:36]=[CH:35]/[CH2:34][N:33]([CH3:40])[CH3:32])[CH:5]=[CH:6][CH:7]=3)[CH:18]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1
Reactant: Clc1cc(Nc2cc(NNc3ccccc3)ncn2)ccc1OCc1ccccn1
Reactant: CN(C)C/C=C/C(=O)Cl
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN1CCCC1=O
Solvent: CC#N
Product: CN(C)C/C=C/C(=O)Nc1cccc(Nc2cc(Nc3ccc(OCc4ccccn4)c(Cl)c3)ncn2)c1
Temperature: 0 °C
Reaction time: 2 h
Yield: 6.4 %

Procedure:
3-{[6-(3-chloro-4-(2-pyridyl)methoxyphenylamino)-pyrimidin-4-ylamino]phenylamine (IR-9) was dissolved in N-methylpyrrolidinone (1.2 mL) and added dropwise over 10 minutes to the ice-cold solution of (E)-4-(dimethylamino)but-2-enoyl chloride hydrochloride in acetonitrile. The reaction was stirred in an ice bath for 2 hr. To the mixture was added sodium bicarbonate to pH greater than 9. The oil that formed was extracted with EtOAc (3×25 mL). A portion of the material was insoluble and set aside. The organic layer was dried (MgSO4) filtered and evaporated to a dark red oil. Both oils contained substantial amount of product as shown by TLC: SiO2 CHCl3:MeOH/NH4OH (8:1) 19:1. The oils were combined and purified by flash column chromatography silica gel (25×300 mm) eluted first with 5% methanol/ammonium hydroxide 8/1 to remove non-polar impurities followed by 10% methanol/ammonium hydroxide 8/1 to elute 59 mg of product. The sample was further purified by a second flash column chromatography silica gel (25×250 mm) eluted with 10% methanol/ammonium hydroxide 8/1 to give the title compound (16.3 mg, 0.03 mmol, 6.4% yield). MS (ES+) 530 (M+): 552, (M+Na); 1H NMR (DMSO-d6, 500 MHz) δ (ppm): 10.04 (s, 1H), 9.19 (s, 1H), 9.14 (s, 1H), 8.60 (s, 1H), 8.27 (s, 1H), 7.88 (s, 2H), 7.57 (s, 1H), 7.36 (d, 1H, J=7.4 Hz), 7.29 (d, 2H, J=7.8 Hz), 7.22 (d, 2H, J=7.9 Hz), 7.18 (m, 2H), 6.74 (m, 1H), 6.30 (d, 1H, J=15 Hz) 6.10 (s, 1H), 5.24 (s, 2H), 3.06 (s, 2H), 2.18 (s, 6H) ppm; HPLC: tR=5.15 min, 97.5% (YMC-Pack ODS-A 4.6×100 mm, 80% water/20% acetonitrile to 5% water/95% acetonitrile over 5.5 min, hold to 9 min.).
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[CH:11]=[CH:10][C:9]([F:12])=[CH:8][C:7]=2[C:13]2[C:14]3[NH:21][CH:20]=[C:19]([C:22]([OH:24])=O)[C:15]=3[N:16]=[CH:17][N:18]=2)[CH2:3][CH2:2]1.[C:25]([O:29][C:30]([N:32]1[CH2:37][CH2:36][CH:35]([NH2:38])[CH2:34][CH2:33]1)=[O:31])([CH3:28])([CH3:27])[CH3:26]>>[C:25]([O:29][C:30]([N:32]1[CH2:37][CH2:36][CH:35]([NH:38][C:22]([C:19]2[C:15]3[N:16]=[CH:17][N:18]=[C:13]([C:7]4[CH:8]=[C:9]([F:12])[CH:10]=[CH:11][C:6]=4[O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)[C:14]=3[NH:21][CH:20]=2)=[O:24])[CH2:34][CH2:33]1)=[O:31])([CH3:28])([CH3:26])[CH3:27]
Reactant: O=C(O)c1c[nH]c2c(-c3cc(F)ccc3OCC3CC3)ncnc12
Reactant: CC(C)(C)OC(=O)N1CCC(N)CC1
Product: CC(C)(C)OC(=O)N1CCC(NC(=O)c2c[nH]c3c(-c4cc(F)ccc4OCC4CC4)ncnc23)CC1

Procedure:
Starting from 4-(2-cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid (example A77) and 4-amino-piperidine-1-carboxylic acid tert-butyl ester the title compound is obtained as colorless solid.
Reaction SMILES: [CH3:1][C:2]([N:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1)([CH3:13])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([S:11][CH3:12])=[CH:7][CH:6]=1)=[O:4].[CH:20]([Si:22]([O:29][CH2:30][CH3:31])([O:26][CH2:27][CH3:28])[O:23][CH2:24][CH3:25])=[CH2:21]>C1(C)C=CC=CC=1>[CH3:13][C:2]([N:14]1[CH2:15][CH2:16][O:17][CH2:18][CH2:19]1)([CH3:1])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([S:11][CH3:12])=[CH:7][C:6]=1[CH2:21][CH2:20][Si:22]([O:23][CH2:24][CH3:25])([O:26][CH2:27][CH3:28])[O:29][CH2:30][CH3:31])=[O:4]
Reactant: C=C[Si](OCC)(OCC)OCC
Reactant: CSc1ccc(C(=O)C(C)(C)N2CCOCC2)cc1
Solvent: Cc1ccccc1
Product: CCO[Si](CCc1cc(SC)ccc1C(=O)C(C)(C)N1CCOCC1)(OCC)OCC
Yield: 5.4 %

Procedure:
11.18 g (40 mmol) of 2-methyl-1-(4-methylthiophenyl)-2-morpholino-1-propanone, 735 mg (0.8 mmol) of RuH2 (CO) (PPh3)3 and 10.0 ml (48 mmol) of vinyltriethoxysilane in 60 ml of anhydrous toluene were degase with argon for 1/2 hour and boiled at reflux for 50 hours. Concentration and chromatography (silica gel, CH2Cl2 /ethyl acetate) gave 1.02 g (6%) of a yellowish oil. 1H-NMR (CDCl3): 0.99 ppm (2H, mc, Et-H2); 1.22 ppm (6H, s, CH3); 1.24 ppm (9H, t, CH3 of Si(OEt)3); 2.50 ppm (3H, s, SCH3); 2.59 ppm (4H, mc, morpholine-N--CH2); 2,69 ppm (2H, mc, Et-H1); 3.70 ppm (4H, mc, morpholine-O--CH2); 3.85 ppm (6H, q, SiOCH2, 3JH,H =6.8 Hz); 7.03 ppm (1H, dd, Ph-H5, 3 JH5,H6 =8.2 Hz, 4JH3, H5 =2.0 Hz); 7.13 ppm (1H, d, Ph-H3); 8.40 ppm (1H, d, Ph-H6).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][CH:17]=1)[CH2:5][NH:6][C:7]1[C:12]([Cl:13])=[CH:11][N:10]=[C:9]([Cl:14])[N:8]=1.Cl.C(N(CC)CC)C.[N+:26]([C:29]1[CH:30]=[C:31]([S:35](Cl)(=[O:37])=[O:36])[CH:32]=[CH:33][CH:34]=1)([O-:28])=[O:27]>C1COCC1>[Cl:14][C:9]1[N:8]=[C:7]([NH:6][CH2:5][C:4]2[CH:3]=[C:2]([NH:1][S:35]([C:31]3[CH:32]=[CH:33][CH:34]=[C:29]([N+:26]([O-:28])=[O:27])[CH:30]=3)(=[O:36])=[O:37])[CH:17]=[CH:16][CH:15]=2)[C:12]([Cl:13])=[CH:11][N:10]=1
Reactant: O=[N+]([O-])c1cccc(S(=O)(=O)Cl)c1
Reactant: Nc1cccc(CNc2nc(Cl)ncc2Cl)c1
Agent: Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: O=[N+]([O-])c1cccc(S(=O)(=O)Nc2cccc(CNc3nc(Cl)ncc3Cl)c2)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 95 %

Procedure:
To a mixture of N-(3-aminobenzyl)-2,5-dichloropyrimidin-4-amine.hydrogen chloride (0.20 g, 0.58 mmol) and triethylamine (0.32 mL, 2.3 mmol) in THF (3 mL) was added slowly m-nitrobenzenesulfonyl chloride (0.13 g, 0.58 mmol). The resulting mixture was stirred at rt for 2 hours and the solvent was removed under vacuum. The residue was treated with EtOAc and water. The organic layer was dried over Na2SO4, filtered, and concentrated under vacuum to provide the desired product (0.30 g, 95%). LCMS for C17H14Cl2N5O4S (M+H)+: m/z=453.9, 455.9.
Reaction SMILES: [ClH:1].[CH2:2]([NH:5][CH:6]1[CH2:11][S:10][C:9]2[S:12][CH:13]=[CH:14][C:8]=2[CH2:7]1)[CH2:3][CH3:4].C(=O)([O-])[O-].[Na+].[Na+].[CH2:21](I)[CH2:22][CH2:23][CH3:24].Cl>O.C1(C)C=CC=CC=1>[ClH:1].[CH2:21]([N:5]([CH2:2][CH2:3][CH3:4])[CH:6]1[CH2:11][S:10][C:9]2[S:12][CH:13]=[CH:14][C:8]=2[CH2:7]1)[CH2:22][CH2:23][CH3:24]
Reactant: CCCNC1CSc2sccc2C1
Reactant: CCCCI
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: Cc1ccccc1
Product: CCCCN(CCC)C1CSc2sccc2C1

Procedure:
A mixture of 2,5 g of N-propyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-5-amine hydrochloride, 7.5 g of sodium carbonate, 11 ml of n-butyl iodide 25 ml of toluene and 25 ml of water is refluxed for 3 days. Removal of solvent from the organic layer affords an oil which is treated with ethanolic hydrochloric acid to afford N-butyl- N-propyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-5-amine hydrochloride, m.p. 161°-164°.
Reaction SMILES: [P:1]([Cl:5])(Cl)([Cl:3])=[O:2].[CH:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=[CH:8][C:7]=1[OH:16].C(N(CC)CC)C>C(OCC)C>[P:1]([Cl:5])([Cl:3])(=[O:2])[O:16][C:7]1[CH:8]=[CH:9][C:10]2[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:6]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: Oc1ccc2ccccc2c1
Solvent: CCOCC
Solvent: CCN(CC)CC
Product: O=P(Cl)(Cl)Oc1ccc2ccccc2c1
Temperature: 25 °C
Yield: 88 %

Procedure:
Phosphorus oxychloride (3.23 mL, 1 equiv) and β-naphthol (Aldrich, 5 g, 1 equiv) were stirred in anhydrous diethyl ether (25 mL). Anhydrous triethylamine was added (4.84 mL, 1 equiv) at −78° C. and the solution was allowed to warm to room temperature after 25 min. The triethylamine hydrochloride salt was filtered off and the solvent was removed under reduced pressure to give a clear pale yellow oil (7.95 g, 88%). (oil solidified in the freezer).
Reaction SMILES: [Br:1][C:2]1[C:3](=[O:20])[N:4]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[CH:7]=1.[C:21]1(S(OC)(=O)=O)C=CC=CC=1>C(#N)C>[Br:1][C:2]1[C:3](=[O:20])[N:4]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:5]=[C:6]([CH:8]2[CH2:13][CH:12]=[CH:11][CH2:10][N:9]2[CH3:21])[CH:7]=1
Reactant: O=c1c(Br)cc(-c2ccccn2)cn1-c1ccccc1
Reactant: COS(=O)(=O)c1ccccc1
Solvent: CC#N
Product: CN1CC=CCC1c1cc(Br)c(=O)n(-c2ccccc2)c1
Temperature: 100 °C

Procedure:
99 mg of 3-bromo-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one was dissolved in 10 ml of acetonitrile. 2 ml of methyl benzenesulfonate was added thereto, followed by stirring at 100° C. for 2 nights. After cooling to room temperature, the solvent was evaporated. The residue was dissolved in 10 ml of methanol, followed by cooled to 0° C. under stirring. Sodium borohydride was added 5 times at intervals of 5 hours, 1 g for each time, followed by further stirring at 0° C. overnight. Then the solvent was evaporated and a saturated aqueous solution of ammonium chloride was added to the residue, followed by extracting with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel chromatography (hexane/ethyl acetate system), to give 107 mg of 3-bromo-5-(1-methyl-1,2,3,6-tetrahydropyridin-2-yl)-1-phenyl-1,2-dihydropyridin-2-one. The product was dissolved in 10 ml of dimethylformamide. 81 mg of 2-(2-cyanophenyl)-1,3,2-dioxaborinate, 142 mg of cesium carbonate and 7 mg of tetrakistriphenylphosphine palladium were added thereto, followed by stirring at 140° C. for 2 hours. After cooling to room temperature, water was added thereto, followed by extracting with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel chromatography (hexane/ethyl acetate system), to give 41 mg of the title compound.