Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[C:7]([O:8][CH3:9])=[CH:6][CH:5]=[C:4]([N+:10]([O-:12])=[O:11])[N:3]=1.[F-].[Cs+].[CH2:15](B1OC(C)(C)C(C)(C)O1)[CH:16]=[CH2:17]>C1COCC1.O.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:17]([C:2]1[C:7]([O:8][CH3:9])=[CH:6][CH:5]=[C:4]([N+:10]([O-:12])=[O:11])[N:3]=1)[CH:16]=[CH2:15]
Reactant: COc1ccc([N+](=O)[O-])nc1Br
Reactant: C=CCB1OC(C)(C)C(C)(C)O1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cs+]
Agent: [F-]
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: C=CCc1nc([N+](=O)[O-])ccc1OC
Temperature: 66 °C
Yield: 74.6 %

Procedure:
2-Bromo-3-methoxy-6-nitropyridine (3.22 g, 13.8 mmol), cesium fluoride (6.3 g, 41.5 mmol) and tetrakis(triphenylphosphine)palladium (0) (1.6 g, 1.38 mmol) were combined with 2-allyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2.55 g, 2.85 mL, 15.2 mmol) in THF (27 mL) and heated at 66° C. for 20 h. The mixture was cooled then diluted with water and ethyl acetate. The phases were separated then the organic phase was washed with water (2×) and brine, concentrated in vacuo and then purified by chromatography (silica, 10 to 50% ethyl acetate in hexanes) to give 2-allyl-3-methoxy-6-nitropyridine (2.0 g, 10.3 mmol, 75%) as a blue solid. MS (EI/CI) m/z: 194.8 [M+H].
Reaction SMILES: FC(F)(F)S(O[C:7]1[C:16]([O:17][CH3:18])=[CH:15][C:14]2[N:13]=[CH:12][C:11]3[N:19]([CH3:32])[C:20](=[O:31])[N:21]([C:22]4[CH:27]=[CH:26][C:25]([C:28]#[N:29])=[CH:24][C:23]=4[F:30])[C:10]=3[C:9]=2[CH:8]=1)(=O)=O.CC1(C)C(C)(C)OB([C:43]2[CH:44]=[N:45][C:46]3[C:51]([CH:52]=2)=[CH:50][CH:49]=[CH:48][CH:47]=3)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O=O>[F:30][C:23]1[CH:24]=[C:25]([CH:26]=[CH:27][C:22]=1[N:21]1[C:10]2[C:9]3[CH:8]=[C:7]([C:43]4[CH:44]=[N:45][C:46]5[C:51]([CH:52]=4)=[CH:50][CH:49]=[CH:48][CH:47]=5)[C:16]([O:17][CH3:18])=[CH:15][C:14]=3[N:13]=[CH:12][C:11]=2[N:19]([CH3:32])[C:20]1=[O:31])[C:28]#[N:29]
Reactant: COc1cc2ncc3c(c2cc1OS(=O)(=O)C(F)(F)F)n(-c1ccc(C#N)cc1F)c(=O)n3C
Reactant: CC1(C)OB(c2cnc3ccccc3c2)OC1(C)C
Agent: O=O
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Product: COc1cc2ncc3c(c2cc1-c1cnc2ccccc2c1)n(-c1ccc(C#N)cc1F)c(=O)n3C
Temperature: 130 °C
Reaction time: 0.5 h
Yield: 54.1 %

Procedure:
1-(4-Cyano-2-fluorophenyl)-7-methoxy-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]quinolin-8-yl trifluoromethanesulfonate (79 mg, 159 μmol), 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoline (325 mg, 1.27 mmol), tripotassium phosphate (70 mg, 319 μmol) and trans-bis(tricyclohexylphosphine)palladium(II) dichloride (35 mg, 48 μmol) were dissolved in oxygen-free N,N-dimethylformamide (4.7 ml). The reaction mixture was subsequently heated at 130° C. for 90 min (microwave). The mixture was then decanted off into water (50 ml) and stirred for a further 30 min. The precipitate formed was filtered off with suction and rinsed with water. The filter cake was subsequently suspended in a little cold dimethyl sulfoxide, filtered off and rinsed with 2-propanol, giving 3-fluoro-4-(7-methoxy-3-methyl-2-oxo-8-quinolin-3-yl-2,3-dihydroimidazo[4,5-c]quinolin-1-yl)benzonitrile (41 mg, 86 μmol) as colourless solid after drying in a high vacuum. MS: 476.1 (M+H+), TLC (HPTLC): Rf=0.24 (ethyl acetate/ethanol 5:1, parts by volume).
Reaction SMILES: [C:1]([NH:8][CH2:9][CH2:10][CH2:11][CH2:12][C@@H:13]([C:32]([OH:34])=[O:33])[NH:14]C(OCC1C2C(=CC=CC=2)C2C1=CC=CC=2)=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CN(C=O)C.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:46][O:47][C:48]1[CH:55]=[CH:54][C:51]([CH2:52]Cl)=[CH:50][CH:49]=1>CCCCCC.CCOC(C)=O>[CH3:46][O:47][C:48]1[CH:55]=[CH:54][C:51]([CH2:52][O:34][C:32](=[O:33])[CH:13]([NH2:14])[CH2:12][CH2:11][CH2:10][CH2:9][NH:8][C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])=[CH:50][CH:49]=1
Reactant: COc1ccc(CCl)cc1
Reactant: CC(C)(C)OC(=O)NCCCC[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)O
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: COc1ccc(COC(=O)C(N)CCCCNC(=O)OC(C)(C)C)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 83 %

Procedure:
Compound 2 was prepared in two steps. Into a 250 mL, flame dried three necked round bottom flask under nitrogen was placed Nε-Boc-Nα-Fmoc-L-lysine (7.0 g, 15 mmol) and 60 mL of dry DMF. To this was added cesium carbonate (7 g, 21 mmol) and 4-methoxybenzyl chloride (2.5 g, 16 mmol). The suspension was stirred at room temperature under nitrogen for 4 h, then filtered and washed with ethyl acetate. Product isolation (EtOAc, 5% Na2CO3, water, Na2SO4) followed by recrystallization from 60/40 (v/v) hexane/EtOAc gave 2 crops of a colorless solid. mp 118-120° C. TLC Rf=0.33 (70/30 Hexane/EtOAc). Yield: 8.22 g, 14 mmol, 93.43%. 1H NMR(CDCl3) δ: 7.75 (d, J=7.2 Hz, 2H), 7.55 (d, J=7.2 Hz, 2H), 7.38 (t, J=7.5 Hz, 2H), 7.32-7.20 (m, 4H), 6.85-6.80 (m, 2H), 5.4 (d, J=7.6 Hz, 1H), 5.18-5.00 (m, 2H), 4.44-4.38 (m, 3H), 4.17 (t, J=6.0 Hz 1H), 3.80-3.70 (m, 4H), 3.00 (m, 2H), 1.90-1.11 (m, 15H). ESIMS m/z: 588.40 [M+1]+.
Reaction SMILES: [C:1]([O:10][CH2:11][CH3:12])(=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4].[H-].[Na+].Cl[C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][N:17]=1>CN(C)C=O>[CH2:11]([O:10][C:1](=[O:9])[C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[O:4][C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][N:17]=1)[CH3:12]
Reactant: Clc1ccc(Cl)nc1
Reactant: CCOC(=O)c1ccccc1O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)c1ccccc1Oc1ccc(Cl)cn1
Reaction time: 1 h
Yield: 67.6 %

Procedure:
Ethyl salicylate (30 g, 0.18 mol) was added dropwise with stirring to a suspension of oil-free sodium hydride (5 g, 0.21 mol) in dry dimethylformamide (100 ml) under a nitrogen atmosphere. After one hour, 2,5-dichloropyridine (26 g, 0.17 mol) was added and the reaction mixture refluxed for 48 hours. The dimethylformamide was then removed in vacuo and 11 of a 50:50 (v/v) mixture of water and trichloromethane added to the remaining residue. The organic layer was separated, washed, dried and, finally, chromatographed on a silica column using trichloromethane and hexane (3:1, v/v) as eluant to give the title compound as a colourless oil (32.1 g, 0.115 mol, 64% yield).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[OH:8].C([O-])([O-])=O.[K+].[K+].I[CH2:16][CH3:17]>CC(C)=O>[CH2:16]([O:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[Br:1])[CH3:17]
Reactant: Oc1ccccc1Br
Reactant: CCI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCOc1ccccc1Br
Temperature: 25 °C
Yield: 87 %

Procedure:
To a solution of 2-bromophenol (1.3 ml, 0.012 mol) in 50 ml acetone was added K2CO3 (4.1 g, 0.03 mol) and iodoethane (1.0 ml, 0.013 mol). The reaction mixture was heated to reflux for 8 h, cooled to ambient temperature and filtered. The solvent was removed under reduced pressure and the residue was taken up in EtOAc. The organic phase was washed with 1N NaOH×2, water and brine. Drying over Na2SO4 afforded 2.1 g (88%) of 2-ethoxybromobenzene.
Reaction SMILES: Cl.[C:2]([O:5][C:6]([CH3:27])([CH2:13][CH2:14][CH2:15][C:16]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)OCC[O:17]1)[CH2:7][CH2:8][CH:9]=[C:10]([CH3:12])[CH3:11])(=[O:4])[CH3:3]>C1COCC1>[C:2]([O:5][C:6]([CH3:27])([CH2:13][CH2:14][CH2:15][C:16](=[O:17])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[CH2:7][CH2:8][CH:9]=[C:10]([CH3:11])[CH3:12])(=[O:4])[CH3:3]
Reactant: CC(=O)OC(C)(CCC=C(C)C)CCCC1(c2ccccc2)OCCO1
Agent: Cl
Solvent: C1CCOC1
Product: CC(=O)OC(C)(CCC=C(C)C)CCCC(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
1.76 ml of HCl (1N) was added slowly to a solution of 1.63 g (4.53 mmol) of 1,5-dimethyl-1-[3-(2-phenyl-1,3-dioxolan-2-yl)propyl]-4-hexenyl acetate obtained under d) in 30 ml of THF. The reaction mixture was stirred at 40° or 4 h, cooled down to room temperature, extracted with ether, washed with a saturated solution of NaCl (3×), dried (Na2SO4), filtered and concentrated. Column chromatography (SiO2, heptane/ether 4:1) yielded 1.34 g (94%) of a slightly yellow oil.
Reaction SMILES: [NH2:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=2)=[O:10])[CH2:5][CH2:4]1.Cl[C:21]1[N:26]=[CH:25][CH:24]=[CH:23][N:22]=1>>[N:22]1[CH:23]=[CH:24][CH:25]=[N:26][C:21]=1[NH:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][CH2:12][C:13]2[CH:14]=[CH:15][C:16]([CH3:19])=[CH:17][CH:18]=2)=[O:10])[CH2:5][CH2:4]1
Reactant: Cc1ccc(COC(=O)N2CCC(CN)CC2)cc1
Reactant: Clc1ncccn1
Product: Cc1ccc(COC(=O)N2CCC(CNc3ncccn3)CC2)cc1

Procedure:
The title compound was prepared as described in EXAMPLE 13, except using 4-methylbenzyl 4-(aminomethyl)-1-piperidinecarboxylate (300 mg, 1.14 mmol), 2-chloropyrimidine (131 mg, 1.14 mmol) as starting materials gave the title compound as a yellow oil.
Reaction SMILES: C([O:5][C:6](=[O:22])[CH:7]([C:9]1[CH:14]=[CH:13][C:12]([N:15]2[CH:19]=[C:18]([Cl:20])[CH:17]=[N:16]2)=[C:11]([Cl:21])[CH:10]=1)[CH3:8])(C)(C)C.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[Cl:21][C:11]1[CH:10]=[C:9]([CH:7]([CH3:8])[C:6]([OH:22])=[O:5])[CH:14]=[CH:13][C:12]=1[N:15]1[CH:19]=[C:18]([Cl:20])[CH:17]=[N:16]1
Reactant: CC(C(=O)OC(C)(C)C)c1ccc(-n2cc(Cl)cn2)c(Cl)c1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: CC(C(=O)O)c1ccc(-n2cc(Cl)cn2)c(Cl)c1
Yield: 94.7 %

Procedure:
341 mg (1 mmole) of 2-[3-chloro-4-(4-chloropyrazol-1-yl)phenyl]propionic acid tert.-butylester are heated to the boil for 2 hours with 10 mg of p-toluenesulfonic acid in toluene. The reaction solution is washed with water, dried and concentrated to obtain 270 mg (94.7% of theory) of 2-[3-chloro-4-(4-chloropyrazol-1-yl)phenyl]propionic acid (m.p. 102° to 103° C.).
Reaction SMILES: C([NH:8][C@@H:9]([C:18]([OH:20])=[O:19])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([I:17])[CH:12]=1)(OC(C)(C)C)=O.O1CCOCC1.[ClH:27]>>[ClH:27].[NH2:8][C@H:9]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([I:17])[CH:12]=1)[C:18]([OH:20])=[O:19]
Reactant: CC(C)(C)OC(=O)N[C@H](Cc1cccc(I)c1)C(=O)O
Agent: Cl
Solvent: C1COCCO1
Product: N[C@H](Cc1cccc(I)c1)C(=O)O

Procedure:
A solution of Boc-3-iodo-D-phenylalanine (5 g, 12.8 mmol, available from Matrix Scientific and 3BSC) in 4M HCl in dioxane (63.9 mL, 256 mmol) under argon was stirred at RT for 15 h. The resulting suspension was filtered, washed with Et2O and dried in vacuo to give the title compound as a white solid. LC-MS B: tR=0.42 min; [M+H]+=291.98.
Reaction SMILES: [CH3:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[NH:8][C:9](=[O:14])[CH2:10][C:11](=[O:13])[CH3:12].CO[CH:17](OC)[N:18]([CH3:20])[CH3:19]>CN(C)C=O>[CH3:17][N:18]([CH:20]=[C:10]([C:11](=[O:13])[CH3:12])[C:9]([NH:8][CH:3]1[CH2:4][CH2:5][CH2:6][CH2:7][CH:2]1[CH3:1])=[O:14])[CH3:19]
Reactant: COC(OC)N(C)C
Reactant: CC(=O)CC(=O)NC1CCCCC1C
Solvent: CN(C)C=O
Product: CC(=O)C(=CN(C)C)C(=O)NC1CCCCC1C
Temperature: 25 °C
Reaction time: 8 h
Yield: 76.2 %

Procedure:
To a solution of N-(2-methylcyclohexyl)-3-oxobutanamide obtained in Step A (1.99 g) in N,N-dimethylformamide (20 mL) was added dropwise 1,1-dimethoxy-N,N-dimethylmethanamine (2.41 g) over 10 min at room temperature, and the reaction mixture was stirred overnight at room temperature. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (methanol/dichloromethane) to give the title compound (1.94 g).
Reaction SMILES: [C:1]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([OH:14])[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C(N(CC)CC)C.[CH3:22][S:23](Cl)(=[O:25])=[O:24].C(=O)(O)[O-].[Na+]>O1CCCC1.C(OCC)(=O)C>[CH3:22][S:23]([O:14][CH:10]1[CH2:11][CH2:12][CH2:13][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:9]1)(=[O:25])=[O:24]
Reactant: CC(C)(C)OC(=O)N1CCCC(O)C1
Reactant: CS(=O)(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCCC(OS(C)(=O)=O)C1
Reaction time: 0.17 h

Procedure:
1-Boc-3-hydroxypiperidine (0.5 g, 2.49 mmol) was dissolved in tetrahydrofuran (5 ml), triethylamine (0.75 g, 7.46 mmol) was added and the mixture was cooled. Methanesulfonic acid chloride (0.23 ml, 3 mmol) was added, the mixture was stirred in an ice bath for 10 min, saturated sodium bicarbonate solution (10 ml) was then added, as well as ethyl acetate (10 ml). Phase separation, the aqueous phase was extracted with ethyl acetate (2×20 ml) and the combined organic phases were washed with saturated sodium chloride solution (20 ml), dried over sodium sulfate and concentrated in vacuo. Yield: 0.54 g (77%)
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[C@@H:9]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH3:10])=[CH:4][CH:3]=1.[CH3:20][C:21]([S@:24]([NH2:26])=[O:25])([CH3:23])[CH3:22]>>[C:21]([S@:24]([N:26]=[C:8]([C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)[C@@H:9]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH3:10])=[O:25])([CH3:23])([CH3:22])[CH3:20]
Reactant: C[C@H](NC(=O)OC(C)(C)C)C(=O)c1ccc(F)cc1
Reactant: CC(C)(C)[S@](N)=O
Product: C[C@H](NC(=O)OC(C)(C)C)C(=N[S@](=O)C(C)(C)C)c1ccc(F)cc1

Procedure:
Condensation of t-butyl N-[(1S)-2-(4-fluorophenyl)-1-methyl-2-oxoethyl]carbamate with (R)-(+)-2-methyl-2-propanesulfinamide in the presence of a dehydrating agent gave t-butyl N-[(1S)-2-[((R)-t-butylsulfinyl)imino]-2-(4-fluorophenyl)-1-methylethyl]carbamate. To a solution of the sulfinylimine compound (80 mg) in toluene (2 mL) was added 1.0M trimethylaluminum/hexane solution (0.43 mL) at −78° C., followed by stirring for 5 minutes. The resulting solution was gradually added dropwise at −78° C. to a solution of 2-fluoro-4-pyridyllithium, which had been prepared by reacting 4-fluoro-2-bromopyridine (114 mg) with 1.56M butyllithium/hexane solution (0.46 mL) in diethyl ether (3 mL) at −78° C. After completion of the dropping, tetrahydrofuran (3 mL) was added to the reaction mixture, followed by stirring at −78° C. for 2.5 hours. Saturated brine was added to the reaction mixture and the temperature was elevated to room temperature. The reaction solution was filtered through a Celite pad, and the organic layer in the filtrate was dried over anhydrous magnesium sulfate. After removal of the magnesium sulfate by filtration, the organic solvent was evaporated off in vacuo. The residue was purified by column chromatography on silica gel (C-300; hexane:ethyl acetate=2:1) to give t-butyl N-[(1S,2S)-2-[(t-butylsulfinyl)amino]-2-(4-fluorophenyl)-2-(2-fluoro-4-pyridyl)-1-methylethyl]carbamate (49 mg). The product was treated with 4N hydrogen chloride/dioxane solution to give the optically active diamine indicated in the title.
Reaction SMILES: [CH:1]1[C:13]2[C:12]3[O:11][C:10]4[CH:14]=[CH:15][CH:16]=[CH:17][C:9]=4[C:8]=3[CH:7]=[C:6](B(O)O)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[Br:21][C:22]1[CH:23]=[C:24](I)[CH:25]=[CH:26][CH:27]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1>[Br:21][C:22]1[CH:23]=[C:24]([C:6]2[C:5]3[CH:4]=[CH:3][CH:2]=[CH:1][C:13]=3[C:12]3[O:11][C:10]4[CH:14]=[CH:15][CH:16]=[CH:17][C:9]=4[C:8]=3[CH:7]=2)[CH:25]=[CH:26][CH:27]=1
Reactant: Brc1cccc(I)c1
Reactant: OB(O)c1cc2c3ccccc3oc2c2ccccc12
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: Brc1cccc(-c2cc3c4ccccc4oc3c3ccccc23)c1
Temperature: 25 °C
Yield: 90 %

Procedure:
In the atmosphere of argon, 17.0 g of benzo[b]naphtho[2,1-d]furan-5-boronic acid, 18.4 g of 3-bromoiodobenzene, 1.50 g of tetrakistriphenylphosphine palladium (0), 200 mL of toluene and 100 mL of a 2M aqueous sodium carbonate solution were placed in a flask. The resulting mixture was stirred with heating under reflux for 8 hours. After cooling to room temperature, the reaction solution was extracted with toluene. An aqueous phase was removed. An organic phase was dried with magnesium sulfate and concentrated. Residues were purified by silica gel column chromatography, whereby 21.8 g of 5-(3-bromophenyl)benzo[b]naphtho[2,1-d]furan was obtained.
Reaction SMILES: [C:1]([C:5]([C:8]([C:11]([C:14]([C:17]([C:20](C(F)=O)([F:22])[F:21])([F:19])[F:18])([F:16])[F:15])([F:13])[F:12])([F:10])[F:9])([F:7])[F:6])([F:4])([F:3])[F:2].FF.[C:28]([O:32][C:33]([C:36]([Cl:39])([F:38])[F:37])([Cl:35])[F:34])([F:31])([F:30])F>>[C:1]([C:5]([C:8]([C:11]([C:14]([C:17]([C:20]([C:28]([O:32][C:33]([C:36]([Cl:39])([F:37])[F:38])([Cl:35])[F:34])([F:30])[F:31])([F:22])[F:21])([F:18])[F:19])([F:16])[F:15])([F:13])[F:12])([F:10])[F:9])([F:7])[F:6])([F:4])([F:3])[F:2]
Reactant: FC(F)(F)OC(F)(Cl)C(F)(F)Cl
Reactant: O=C(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Agent: FF
Product: FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)OC(F)(Cl)C(F)(F)Cl
Reaction time: 1.83 h

Procedure:
19.65 g of CF3—OCFCl—CF2Cl as solvent, 23.07 g of CFCl═C—FCl (CFC 1112) and 7.57 g of CF3—(CF2)6—COF are introduced into the equipment described in the Example 1. The reaction mixture is maintained at the temperature of −55° C. and 1.5 Nl/h of fluorine diluted with nitrogen (molar ratio fluorine/nitrogen 1/5) are fed therein for 110 minutes.
Reaction SMILES: Cl[C:2]1[C:3]([CH3:22])=[N:4][C:5]2[C:10]([N:11]=1)=[C:9]([C:12]1[NH:20][C:19]3[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=3[CH:13]=1)[CH:8]=[CH:7][CH:6]=2.[CH3:23][C:24]1[C:25]([Sn](CCCC)(CCCC)CCCC)=[N:26][CH:27]=[CH:28][CH:29]=1.[F-].[Cs+].CO.C(Cl)Cl>CN(C=O)C.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:22][C:3]1[C:2]([C:25]2[C:24]([CH3:23])=[CH:29][CH:28]=[CH:27][N:26]=2)=[N:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[C:12]2[NH:20][C:19]3[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=3[CH:13]=2)[N:4]=1
Reactant: Cc1nc2cccc(-c3cc4c([nH]3)CCNC4=O)c2nc1Cl
Reactant: CCCC[Sn](CCCC)(CCCC)c1ncccc1C
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cs+]
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: CO
Product: Cc1cccnc1-c1nc2c(-c3cc4c([nH]3)CCNC4=O)cccc2nc1C
Yield: 41.7 %

Procedure:
A solution of 2-(3-chloro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 425; 33.7 mg, 0.108 mmol), 3-methyl-2-(tributylstannyl)pyridine (Indofine Chemical Company, Inc., Hillsborough, N.J.; 0.040 mL, 0.119 mmol), CuI (2.052 mg, 10.78 μmol), cesium fluoride (32.7 mg, 0.216 mmol), and Pd(PPh3)4 (Strem Chemicals, Inc.; 6.23 mg, 5.39 μmol) in DMF (2.0 mL) was stirred under argon in a microwave process vial at 140° C. for 30 min. The reaction mixture was then concentrated onto silica gel and chromatographically purified (silica gel, 50-100% EtOAc/hexanes, then 0-10% MeOH/DCM) to provide 2-(2-methyl-3-(3-methylpyridin-2-yl)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (16.8 mg, 0.045 mmol, 42% yield) as a yellow-orange solid. 1H NMR (400 MHz, CDCl3) δ ppm 11.91 (1H, br. s.), 8.65 (1H, dd, J=4.5, 0.8 Hz), 8.10 (1H, dd, J=7.4, 1.2 Hz), 7.91 (1H, dd, J=8.2, 1.2 Hz), 7.74-7.82 (2H, m), 7.42 (1H, dd, J=7.8, 4.9 Hz), 7.23 (1H, d, J=2.2 Hz), 5.35 (1H, br. s.), 3.59 (2H, td, J=6.8, 1.9 Hz), 2.86 (2H, t, J=7.0 Hz), 2.64 (3H, s), 2.29 (3H, s). m/z (ESI, +ve) 370.0 (M+H)+.
Reaction SMILES: [CH3:1][CH:2]1[S:7][C:6](=[O:8])[NH:5][N:4]=[C:3]1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][C:13](=[O:18])[C:12]2=[N:19]C1C=CC=CC=1.[CH3:26][N:27]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)N>>[CH3:26][N:27]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[N:19]=[C:12]1[C:11]2[C:15](=[CH:16][CH:17]=[C:9]([C:3]3[CH:2]([CH3:1])[S:7][C:6](=[O:8])[NH:5][N:4]=3)[CH:10]=2)[NH:14][C:13]1=[O:18]
Reactant: CC1SC(=O)NN=C1c1ccc2c(c1)C(=Nc1ccccc1)C(=O)N2
Reactant: CN(N)c1ccccc1
Product: CC1SC(=O)NN=C1c1ccc2c(c1)C(=NN(C)c1ccccc1)C(=O)N2
Yield: 47 %

Procedure:
Starting from 1,3-dihydro-5-(3,6-dihydro-6-methyl-2-oxo -2H-1,3,4-thiadiazin-5-yl)-3-phenylimino-2H-indol-2-one, and 1-methyl 1-phenylhydrazine and following the method described in Example 21, the desired compound was obtained.
Reaction SMILES: C(OC(=O)C)(=O)C.C(N)C/C=C/CCCN.[OH-].[NH4+].[Cl-].[Na+].[CH2:21]([NH:32][C:33](=O)[CH3:34])[CH2:22]/[CH:23]=[CH:24]/[CH2:25][CH2:26][CH2:27][NH:28][C:29](=O)[CH3:30]>O.N1C=CC=CC=1>[CH2:33]([NH:32][CH2:21][CH2:22]/[CH:23]=[CH:24]/[CH2:25][CH2:26][CH2:27][NH:28][CH2:29][CH3:30])[CH3:34]
Reactant: CC(=O)NCC/C=C/CCCNC(C)=O
Agent: NCC/C=C/CCCN
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: CCNCC/C=C/CCCNCC
Reaction time: 0.75 h

Procedure:
The intermediate N,N'-diethyl-trans-3-heptene-1,7-diamine was prepared in two steps as follows: To 100 ml. of pyridine cooled to 0° C. (in an ice-salt bath) was added dropwise with stirring 35.8 g. of acetic anhydride. To the cooled stirred solution was added 18 g. of trans-3-heptene-1,7-diamine in 40 ml. of pyridine at such a rate to keep the temperature less than 10° C.; the addition took about 45 minutes. The reaction mixture was stirred at 5°-10° C. for an additional 30 minutes, was next stirred at room temperature for 6 hours and then allowed to stand at 5° C. overnight. The clear solution was treated with 10 ml. of concentrated ammonium hydroxide with cooling and stirring. The solution was distilled under reduced pressure to remove most of the volatile materials to leave a clear viscous oil. The oil was treated with 100 ml. of water followed by the addition of solid sodium chloride. The mixture was extracted with five 50 ml. portions of chloroform. The combined chloroform extracts were shaken with 100 ml. of saturated brine containing 2 ml. of 6N hydrochloric acid and then dried over anhydrous potassium carbonate. The chloroform was distilled off in vacuo to yield a clear viscous oil which crystallized at room temperature. The solid was purified by dissolving it in chloroform-methanol, treating the solution with decolorizing charcoal and removing the solvents in vacuo to yield, as a clear colorless viscous oil which crystallized at room temperature to yield 28.3 g. of N,N'-(trans-3-heptene-1,7-diyl)bis(acetamide).
Reaction SMILES: Cl[C:2]1[N:11]=[C:10]([NH:12][CH2:13][CH2:14][O:15][CH3:16])[C:9]2[C:8](=[O:17])[N:7]([CH3:18])[CH:6]=[N:5][C:4]=2[CH:3]=1.CC1(C)C(C)(C)OB([C:27]2[CH:28]=[CH:29][C:30]3[O:34][CH:33]=[N:32][C:31]=3[CH:35]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[O:34]1[C:30]2[CH:29]=[CH:28][C:27]([C:2]3[N:11]=[C:10]([NH:12][CH2:13][CH2:14][O:15][CH3:16])[C:9]4[C:8](=[O:17])[N:7]([CH3:18])[CH:6]=[N:5][C:4]=4[CH:3]=3)=[CH:35][C:31]=2[N:32]=[CH:33]1
Reactant: COCCNc1nc(Cl)cc2ncn(C)c(=O)c12
Reactant: CC1(C)OB(c2ccc3ocnc3c2)OC1(C)C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Product: COCCNc1nc(-c2ccc3ocnc3c2)cc2ncn(C)c(=O)c12
Temperature: 140 °C

Procedure:
To a solution of 7-chloro-5-(2-methoxyethylamino)-3-methylpyrido[4,3-d]pyrimidin-4(3H)-one (15.0 mg, 0.0559 mmol) in 1,4-dioxane (0.5 mL) were added 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]oxazole (15.0 mg, 0.0612 mmol), 2M aqueous Na2CO3 solution (83.7 μL, 0.167 mmol), and a catalytic amount of Pd(PPh3)4. The reaction mixture was purged with N2 and heated at 140° C. by a microwave reactor for 15 minutes. The mixture was then cooled, quenched with H2O (5 mL) and extracted with ethyl acetate (3×2.5 mL). The combined organic layers were evaporated under vacuum and the residue was purified by preparatory LC/MS to provide 7-(benzo[d]oxazol-5-yl)-5-(2-methoxyethylamino)-3-methylpyrido[4,3-d]pyrimidin-4(3H)-one, which was completely decomposed to the title compound at room temperature; HPLC-MS calculated for C18H19N5O4 (M+H+) 370.1, found 370.1.