Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[NH:8][C:9](=[O:18])[N:10]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C:3]=12.[N:19]([CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])=[C:20]=[O:21]>O1CCOCC1>[CH2:22]([NH:19][C:20]([N:8]1[C:4]2=[N:5][CH:6]=[CH:7][C:2]([CH3:1])=[C:3]2[N:10]([C:11]([O:13][C:14]([CH3:15])([CH3:17])[CH3:16])=[O:12])[C:9]1=[O:18])=[O:21])[CH2:23][CH2:24][CH2:25][CH2:26][CH3:27]
Reactant: Cc1ccnc2[nH]c(=O)n(C(=O)OC(C)(C)C)c12
Reactant: CCCCCCN=C=O
Solvent: C1COCCO1
Product: CCCCCCNC(=O)n1c(=O)n(C(=O)OC(C)(C)C)c2c(C)ccnc21

Procedure:
Analogously to Example 1, tert-butyl 7-methyl-2-oxo-2,3-dihydroimidazo[4,5-b]pyridine-1-carboxylate (200 mg, 0.8 mmol) and 1-isocyanatohexane (113 mg, 0.88 mmol) were reacted in dioxane. Yield: 5 mg (2%), M+H+: 377.20.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:28]([F:31])([F:30])[F:29])[O:13][N:12]=[C:11]([C:14]3[C:22]4[N:18]([CH:19]=[CH:20][CH:21]=4)[C:17]([C:23]([O:25]CC)=[O:24])=[CH:16][CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.[OH-].[Na+].[ClH:34]>O.CO>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:28]([F:30])([F:31])[F:29])[O:13][N:12]=[C:11]([C:14]3[C:22]4[N:18]([CH:19]=[CH:20][CH:21]=4)[C:17]([C:23]([OH:25])=[O:24])=[CH:16][CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[C:7]=1[Cl:34]
Reactant: CCOC(=O)c1ccc(C2=NOC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)c2cccn12
Reactant: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: O=C(O)c1ccc(C2=NOC(c3cc(Cl)c(Cl)c(Cl)c3)(C(F)(F)F)C2)c2cccn12
Yield: 65 %

Procedure:
A solution of ethyl 8-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)indolizine-5-carboxylate (130 mg, 0.26 mmol) and NaOH (52 mg, 1.29 mmol) in H2O-MeOH (1:1, 20 mL) was stirred at rt for 3 h. The mixture was acidified with 2 N HCl and extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by prep-TLC to give 8-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)indolizine-5-carboxylic acid (80 mg; yield 65%) as a yellow solid. MS: m/z=477.0 (M+1, ESI+).
Reaction SMILES: [O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][N:3]1[C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH2:21][C@H:20]([CH2:22]OS(C)(=O)=O)[O:19][C:18]2=[O:28])=[CH:13][C:12]=1[F:29].[N-:30]=[N+:31]=[N-:32].[Na+].O>CN(C=O)C>[N:30]([CH2:22][C@@H:20]1[O:19][C:18](=[O:28])[N:17]([C:14]2[CH:15]=[CH:16][C:11]([N:3]3[CH2:4][C:5]4[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=4)[C:2]3=[O:1])=[C:12]([F:29])[CH:13]=2)[CH2:21]1)=[N+:31]=[N-:32]
Reactant: [N-]=[N+]=[N-]
Reactant: CS(=O)(=O)OC[C@H]1CN(c2ccc(N3Cc4ccccc4C3=O)c(F)c2)C(=O)O1
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: [N-]=[N+]=NC[C@H]1CN(c2ccc(N3Cc4ccccc4C3=O)c(F)c2)C(=O)O1
Temperature: 70 °C
Yield: 73.4 %

Procedure:
To the mesylate from Example 2 (0.95 g, 1.78 mmols) in DMF (25 mL) was added sodium azide (0.47 g, 7.23 mmols) and heated to 70° C. for 16 hrs. After cooling to rt water was added and the mixture extracted with ethyl acetate (6×25 mL), washed with brine (4×10 mL), dried over Na2SO4, concentrated to give 0.48 g of a tan solid. MS (M+1)=354 m/z.
Reaction SMILES: Br[C:2]1[N:6]([S:7]([C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)(=[O:9])=[O:8])[CH:5]=[C:4]([CH2:16][N:17]([CH3:25])[C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH:3]=1.[CH3:26][C:27]1[CH:32]=[CH:31][N:30]=[CH:29][C:28]=1B(O)O.C(=O)([O-])O.[Na+].COCCOC>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>[CH3:25][N:17]([CH2:16][C:4]1[CH:3]=[C:2]([C:28]2[CH:29]=[N:30][CH:31]=[CH:32][C:27]=2[CH3:26])[N:6]([S:7]([C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)(=[O:9])=[O:8])[CH:5]=1)[C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21]
Reactant: Cc1ccncc1B(O)O
Reactant: CN(Cc1cc(Br)n(S(=O)(=O)c2cccnc2)c1)C(=O)OC(C)(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: COCCOC
Solvent: O
Product: Cc1ccncc1-c1cc(CN(C)C(=O)OC(C)(C)C)cn1S(=O)(=O)c1cccnc1
Temperature: 80 °C
Reaction time: 6 h
Yield: 51.9 %

Procedure:
tert-Butyl {[5-bromo-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]methyl}methylcarbamate (431 mg), (4-methylpyridin-3-yl)boronic acid (206 mg), sodium hydrogencarbonate (253 mg) and tetrakis(triphenylphosphine)palladium (87 mg) were added to a degassed mixture of 1,2-dimethoxyethane (8 mL) and water (2 mL), and the mixture was stirred under a nitrogen atmosphere at 80° C. for 6 hr. The reaction mixture was allowed to cool, a saturated aqueous sodium hydrogencarbonate solution was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=1:1→0:1) to give the title compound as a colorless oil (yield 230 mg, 52%).
Reaction SMILES: [C:1]([O:5][C:6](=[O:18])[NH:7][C:8]1[CH:13]=[CH:12][C:11](I)=[CH:10][C:9]=1[N+:15]([O-:17])=[O:16])([CH3:4])([CH3:3])[CH3:2].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.[Cl:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1I>>[C:1]([O:5][C:6](=[O:18])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=2[Cl:37])=[CH:10][C:9]=1[N+:15]([O-:17])=[O:16])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)Nc1ccc(I)cc1[N+](=O)[O-]
Reactant: Clc1ccccc1I
Agent: CC1(C)OB(B2OC(C)(C)C(C)(C)O2)OC1(C)C
Product: CC(C)(C)OC(=O)Nc1ccc(-c2ccccc2Cl)cc1[N+](=O)[O-]

Procedure:
Prepared from (4-iodo-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example A1), bis(pinacolato)diboron and 1-chloro-2-iodobenzene according to the general procedure C. Obtained as a yellow oil (886 mg).
Reaction SMILES: [C:1]1([NH:7][C:8]2[NH:13][C:12](=[O:14])[CH:11]=[CH:10][N:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Li+].I[CH3:18]>CN(C=O)C>[CH3:18][N:13]1[C:12](=[O:14])[CH:11]=[CH:10][N:9]=[C:8]1[NH:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CI
Reactant: O=c1ccnc(Nc2ccccc2)[nH]1
Agent: [H-]
Agent: [Li+]
Solvent: CN(C)C=O
Product: Cn1c(Nc2ccccc2)nccc1=O
Reaction time: 0.42 h
Yield: 61.6 %

Procedure:
To a solution of 2-(phenylamino)pyrimidin-4(3H)-one (0.250 g, 1.34 mmol) in DMF (10 mL) was added LiH (0.012 g, 1.47 mmol). The reaction mixture was stirred for 25 minutes and then iodomethane (0.166 mL, 2.67 mmol) was added. The reaction was stirred at room temperature for 18 hours, the quenched with H2O and partitioned between EtOAc and saturated aqueous NaCl. The phases were separated, and the aqueous phase was re-extracted with EtOAc (1×). The combined organic layers were dried (Na2SO4), filtered and concentrated to yield a crude yellow oil. The crude product was purified by flash column chromatography, eluting with 30:1 dichloromethane/methanol. The desired product (0.166 g, 62%) was obtained as a white crystalline solid. 1H NMR (400 MHz, CDCl3) δ 7.68 (d, J=6.2 Hz, 1H), 7.46 (m, 2H), 7.39 (t, J=7.8 Hz, 2H), 7.19 (t, J=7.4 Hz, 1H), 6.48 (s, 1H), 6.01 (d, J=6.6 Hz, 1H), 3.58 (s, 3H). LRMS (ESI pos) m/e 202 (M+1).
Reaction SMILES: FC(F)(F)S(O[CH:7]1[CH:11]=[C:10]([O:12][CH3:13])[C:9](=[CH:14][C:15]2[NH:16][C:17]3[C:22]([CH:23]=2)=[CH:21][CH:20]=[CH:19][CH:18]=3)[NH:8]1)(=O)=O.C(OC([N:33]1[CH:37]=[CH:36][CH:35]=[C:34]1B(O)O)=O)(C)(C)C.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1>C(OCC)(=O)C>[CH3:13][O:12][CH:10]1[C:9](=[CH:14][C:15]2[NH:16][C:17]3[C:22]([CH:23]=2)=[CH:21][CH:20]=[CH:19][CH:18]=3)[NH:8][C:7]([C:34]2[NH:33][CH:37]=[CH:36][CH:35]=2)=[CH:11]1
Reactant: COC1=CC(OS(=O)(=O)C(F)(F)F)NC1=Cc1cc2ccccc2[nH]1
Reactant: CC(C)(C)OC(=O)n1cccc1B(O)O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: COC1C=C(c2ccc[nH]2)NC1=Cc1cc2ccccc2[nH]1
Temperature: 90 °C
Reaction time: 3 h

Procedure:
The crude triflate 78 was mixed with about 3 equivalent of boronic acid 8, 8 equivalents of potassium carbonate and about 0.1 equivalent of tetrakistriphenylphosphine palladium under argon. Anhydrous 1,4-dioxane (10 mL) was added to the reaction mixture, and it was heated at 90° C. in a sand bath. After three hours, the mixture was cooled and added to ethyl acetate (100 mL). The organic layer was washed with brine (3×100 mL) and was then dried over sodium sulfate, filtered and concentrated in vacuo. The resulting crude mixture was passed through a short column of neutral alumina using 50/50 hexanes/ethyl acetate as an eluent. The relevant fractions were combined and concentrated, and the resulting crude product was purified using a preparative plate of neutral alumina and eluted using 80/20 hexanes/ethyl acetate. The alumina band containing Compound 79 was washed with ethyl acetate and concentrated to provide the Compound 79 as a red dark solid (2 mg, 20%). (500 MHz, CD3OD) : δ (ppm), 7.55 (m, 2H); 7.20 (t, 1H); 7.13 (s, 1H); 7.03 (t, 1H); 6.90 (s, 1H), 6.88 (s, 1H); 6.85 (s, 1H); 6.32 (s, 1H), 6.17 (s, 1H); 3.97 (s, 3H). MS (M+H): 290.0.
Reaction SMILES: [Na].Cl[C:3]1[C:4]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)=[N:5][S:6][N:7]=1.[CH2:14]([OH:18])[CH2:15][CH2:16][CH3:17]>>[CH2:14]([O:18][C:3]1[C:4]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)=[N:5][S:6][N:7]=1)[CH2:15][CH2:16][CH3:17]
Reactant: Clc1nsnc1-c1cccnc1
Reactant: CCCCO
Agent: [Na]
Product: CCCCOc1nsnc1-c1cccnc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 100 %

Procedure:
To a solution of sodium (290 mg, 12.5 mmol) in n-butanol (10 ml) was added 3-(4-chloro-1,2,5-thiadiazol-3-yl)pyridine (490 mg, 2.5 mmol). The mixture was stirred at 25° C. for 18 h and evaporated. The residue was dissolved in water and extracted with methylene chloride. The combined organic phases were dried and evaporated to yield 580 mg (100%) of the title compound.
Reaction SMILES: [F:1][C:2]([F:11])([F:10])[C:3]1[N:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1.C(=O)([O-])[O-].[Na+].[Na+].[Cl:18][O-].[Na+].C(O)(=O)C>O>[Cl:18][C:7]1[C:6]([OH:9])=[CH:5][CH:4]=[C:3]([C:2]([F:1])([F:10])[F:11])[N:8]=1
Reactant: [O-]Cl
Reactant: Oc1ccc(C(F)(F)F)nc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: Oc1ccc(C(F)(F)F)nc1Cl
Temperature: 0 °C
Reaction time: 2 h
Yield: 188.8 %

Procedure:
A solution of 6-(trifluoromethyl)pyridine-3-ol (7 g, 40 mmol) and sodium carbonate (4.5 g, 4.2 mmol) in water (200 mL) was cooled in an ice bath. 0.7N Sodium hypochlorite solution (63.9 mL, 4.29 mmol) was added portionwise over 30 minutes, and the reaction stirred at 0° C. for 2 hours. The reaction mixture was acidified using acetic acid, and extracted into EtOAc (3×50 mL). The combined organics were washed with brine (2×50 mL), dried (MgSO4), filtered and concentrated. The product was purified by flash chromatography (0 to 25% EtOAc in hexanes) giving the title compound (1.6 g, 20%) as a solid. 1H NMR (400 MHz; CDCl3) δ 7.61 (1H, d), 7.45 (1H, d), 5.83 (1H, s).
Reaction SMILES: [CH3:1][CH:2]1[CH2:9][C@H:8]2[C@H:4]([CH2:5][NH:6][C@@H:7]2[CH2:10][NH:11][C:12]([C:14]2[N:21]3[C:17]([S:18][CH:19]=[CH:20]3)=[N:16][C:15]=2[CH3:22])=[O:13])[CH2:3]1.[CH3:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]2[C:31]([C:36](O)=[O:37])=[CH:32][CH:33]=[CH:34][CH:35]=2)=[CH:26][CH:25]=1>>[CH3:1][CH:2]1[CH2:9][C@H:8]2[C@H:4]([CH2:5][N:6]([C:36]([C:31]3[C:30]([C:27]4[CH:26]=[CH:25][C:24]([CH3:23])=[CH:29][CH:28]=4)=[CH:35][CH:34]=[CH:33][CH:32]=3)=[O:37])[C@@H:7]2[CH2:10][NH:11][C:12]([C:14]2[N:21]3[C:17]([S:18][CH:19]=[CH:20]3)=[N:16][C:15]=2[CH3:22])=[O:13])[CH2:3]1
Reactant: Cc1ccc(-c2ccccc2C(=O)O)cc1
Reactant: Cc1nc2sccn2c1C(=O)NC[C@H]1NC[C@@H]2CC(C)C[C@@H]21
Product: Cc1ccc(-c2ccccc2C(=O)N2C[C@@H]3CC(C)C[C@@H]3[C@H]2CNC(=O)c2c(C)nc3sccn23)cc1

Procedure:
prepared by reaction of 6-methyl-imidazo[2,1-b]thiazole-5-carboxylic acid-[(1S,2S,5R)-7-methyl-3-aza-bicyclo[3.3.0]oct-2-ylmethyl]-amide with commercially available 4′-methyl-biphenyl-2-carboxylic acid.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][C:3]=1[OH:12].[F:13][C:14]1[C:22]([F:23])=[C:21]([F:24])[C:20]([F:25])=[C:19]([F:26])[C:15]=1[C:16](Cl)=[O:17]>C(#N)C.CC(C)=O>[F:13][C:14]1[C:22]([F:23])=[C:21]([F:24])[C:20]([F:25])=[C:19]([F:26])[C:15]=1[C:16]([NH:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][C:3]=1[OH:12])=[O:17]
Reactant: Nc1cc(Cl)c([N+](=O)[O-])cc1O
Reactant: O=C(Cl)c1c(F)c(F)c(F)c(F)c1F
Solvent: CC#N
Solvent: CC(C)=O
Product: O=C(Nc1cc(Cl)c([N+](=O)[O-])cc1O)c1c(F)c(F)c(F)c(F)c1F
Yield: 84.9 %

Procedure:
In 100 ml of acetonitrile was dispersed 18.9 g (0.10 mole) of 2-amino-4-chloro-5-nitrophenol and a solution of 23.1 g (0.10 mole) of 2,3,4,5,6-pentafluorobenzoyl chloride in 50 ml of acetone was added dropwide to the resultant dispersion. After heating under reflux for 3 hours, the reaction mixture was ice-cooled and the precipitated solids were collected by filtration, washed with cooled acetonitrile and dried to obtain 32.5 g of 2-(2,3,4,5,6-pentafluorobenzamido)-4-chloro-5-nitrophenol (Yield 85%).
Reaction SMILES: OO.FC(F)(F)C(OC(=O)C(F)(F)F)=[O:6].[CH2:16]([O:18][C:19]1[CH:20]=[CH:21][C:22]2[N+:27]([O-:28])=[N:26][C:25]([NH:29][CH2:30][CH2:31][N:32]([CH3:34])[CH3:33])=[N:24][C:23]=2[CH:35]=1)[CH3:17].FC(F)(F)C(O)=O>C(Cl)Cl.N>[CH2:16]([O:18][C:19]1[CH:20]=[CH:21][C:22]2[N+:27]([O-:28])=[N:26][C:25]([NH:29][CH2:30][CH2:31][N:32]([CH3:34])[CH3:33])=[N+:24]([O-:6])[C:23]=2[CH:35]=1)[CH3:17]
Reactant: CCOc1ccc2c(c1)nc(NCCN(C)C)n[n+]2[O-]
Reactant: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Agent: N
Agent: OO
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCOc1ccc2c(c1)[n+]([O-])c(NCCN(C)C)n[n+]2[O-]
Temperature: 5 °C
Reaction time: 0.08 h
Yield: 30.4 %

Procedure:
Hydrogen peroxide (70%, 0.7 mL, ca. 13.9 mmol) was added dropwise to a stirred solution of trifluoroacetic anhydride (2.0 mL, 13.9 mmol) in DCM (20 mL) at 5° C. The mixture was stirred at 5° C. for 5 min, warmed to 20° C., stirred for 10 min, and cooled to 5° C. The mixture was added to a stirred solution of 1-oxide 18 (385 mg, 1.4 mmol) and trifluoroacetic acid (0.53 mL, 6.9 mmol) in DCM (20 mL) at 5° C. and the mixture stirred at 20° C. for 6 h. The solution was carefully diluted with dil. aq. NH3 solution (20 mL) and the mixture extracted with CHCl3 (5×50 mL). The organic fraction was dried and the solvent evaporated. The residue was chromatographed, eluting with a gradient (0-10%) of MeOH/DCM, to give 1,4-dioxide 19 (125 mg, 31%) as a red solid, mp (MeOH/EtOAc) 150-152° C.; 1H NMR 8.23 (d, J=9.6 Hz, 1 H, H-8), 7.48 (d, J=2.6 Hz, 1 H, H-5), 7.46 (brs, 1 H, NH), 7.03 (dd, J=9.6, 2.6 Hz, 1 H, H-7), 4.25 (q, J=7.0 Hz, 2 H, CH2O), 3.64 (br dd, J=6.0, 5.9 Hz, 2 H, CH2N), 2.61 (t, J=6.0 Hz, 2 H, CH2N), 2.30 [s, 6 H, (CH3)2], 1.49 (t, J=7.0 Hz, 3 H, CH3); 13C NMR δ 165.5, 150.2, 140.3, 125.6, 123.5, 120.6, 95.4, 65.4, 57.5, 45.2 (2), 35.9, 14.3; MS (FAB+) m/z 294 (MH+, 100%), 278 (30), 276 (20); HRMS (FAB+) calcd for C13H19N5O3 (MH+) m/z 294.1566, found 294.1568. Anal. Calcd for C13H19N5O3: C, 53.2; H, 6.5; N, 23.9. Found: C, 53.1; H, 6.3; N, 23.6%.
Reaction SMILES: CON(C)[C:4]([C:6]1[C:15](=[O:16])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:8]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([Br:24])[N:19]=2)[CH:7]=1)=[O:5].[CH3:26][C:27]1[CH:32]=[CH:31][N:30]=[C:29]([Mg]Br)[CH:28]=1>C1COCC1>[Br:24][C:20]1[N:19]=[C:18]([CH2:17][N:8]2[C:9]3[C:14](=[CH:13][CH:12]=[CH:11][CH:10]=3)[C:15](=[O:16])[C:6]([C:4]([C:29]3[CH:28]=[C:27]([CH3:26])[CH:32]=[CH:31][N:30]=3)=[O:5])=[CH:7]2)[CH:23]=[CH:22][CH:21]=1
Reactant: CON(C)C(=O)c1cn(Cc2cccc(Br)n2)c2ccccc2c1=O
Reactant: Cc1ccnc([Mg]Br)c1
Solvent: C1CCOC1
Product: Cc1ccnc(C(=O)c2cn(Cc3cccc(Br)n3)c3ccccc3c2=O)c1

Procedure:
Experimental conditions analogous to those described for Step 6 of Example 60 from 90 mg (0.22 mmol) of 1-(6-bromo-pyridin-2-ylmethyl)-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid methoxy-methyl-amide in 1 mL THF and 1.96 mL 0.25M 4-methyl-2-pyridylmagnesium bromide. Yield: 17 mg of a white solid. LC-MSD, m/z for C22H16BrN3O2 [M+H]+=434.0, 436.0; HPLC retention time: 1.8 min.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](N2CCOCC2)[N:5]=[C:4]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=2)[CH:3]=1.[C:26]([C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[CH:33][CH:34]=1)(=[O:28])[CH3:27].C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([NH:14][C:15]2[CH:16]=[CH:17][C:18]([O:21][C:22]([F:23])([F:24])[F:25])=[CH:19][CH:20]=2)[N:5]=[C:6]([C:33]2[CH:34]=[C:29]([C:26](=[O:28])[CH3:27])[CH:30]=[CH:31][CH:32]=2)[N:7]=1
Reactant: CC(=O)c1cccc(B(O)O)c1
Reactant: FC(F)(F)Oc1ccc(Nc2cc(Cl)nc(N3CCOCC3)n2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(=O)c1cccc(-c2nc(Cl)cc(Nc3ccc(OC(F)(F)F)cc3)n2)c1
Temperature: 25 °C
Yield: 98.9 %

Procedure:
To a mixture of compound (6-chloro-2-morpholin-4-yl-pyrimidin-4-yl)-(4-trifluoromethoxy-phenyl)-amine (0.5 g, 1.54 mmol) and 3-acetyl benzene boronic acid (0.125 g, 0.31 mmol) in DMF (10 mL) was added palladium tetrakis triphenyl phosphine (0.053 g, 0.046 mmol) and 2M Na2CO3 solution (1.3 g, 12.34 mmol) at temperature in the range of 20-40° C. The reaction mixture was heated for 12 hours under nitrogen atmosphere. After cooling to room temperature the mixture was diluted with water and extracted with ethyl acetate (3×10 mL). Combined the organic layers were concentrated and the residue was purified by column chromatography using 15% ethylacetate in petroleum ether to afford the desired compound (0.125 g, 20%) as a white solid.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]([CH:14]1[CH2:16][CH2:15]1)=[O:13])=[C:5]2Cl.[N:18]1([CH2:23][C:24]2[N:29]=[CH:28][C:27]([NH2:30])=[CH:26][CH:25]=2)[CH2:22][CH2:21][CH2:20][CH2:19]1>>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]([CH:14]1[CH2:16][CH2:15]1)=[O:13])=[C:5]2[NH:30][C:27]1[CH:28]=[N:29][C:24]([CH2:23][N:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)=[CH:25][CH:26]=1
Reactant: Nc1ccc(CN2CCCC2)nc1
Reactant: O=C(c1cnc2ccc(Br)cc2c1Cl)C1CC1
Product: O=C(c1cnc2ccc(Br)cc2c1Nc1ccc(CN2CCCC2)nc1)C1CC1
Yield: 78 %

Procedure:
Following general procedure C, (6-bromo-4-chloroquinolin-3-yl)(cyclopropyl)methanone (310 mg, 1.00 mmol) was reacted with 6-(pyrrolidin-1-ylmethyl)pyridin-3-amine (280 mg, 1.50 mmol) to afford the desired product (352 mg, 78%) as a yellow foam: ESI MS m/z 451 [C23H23BrN4O+H]+.
Reaction SMILES: [CH:1]12[CH2:9][CH:5]3[CH2:6][CH:7]([CH2:8]1)[C:3]([NH2:10])([CH2:4]3)[CH2:2]2.C([O-])([O-])=O.[K+].[K+].Cl[CH2:18][C:19]([N:21]1[CH2:25][CH2:24][CH2:23][C@H:22]1[C:26]#[N:27])=[O:20]>CS(C)=O.CCOC(C)=O>[CH:1]12[CH2:9][CH:5]3[CH2:6][CH:7]([CH2:8]1)[C:3]([NH:10][CH2:18][C:19]([N:21]1[CH2:25][CH2:24][CH2:23][C@H:22]1[C:26]#[N:27])=[O:20])([CH2:4]3)[CH2:2]2
Reactant: NC12CC3CC(CC1C3)C2
Reactant: N#C[C@@H]1CCCN1C(=O)CCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CS(C)=O
Product: N#C[C@@H]1CCCN1C(=O)CNC12CC3CC(CC1C3)C2
Temperature: 25 °C
Reaction time: 3 h
Yield: 42.1 %

Procedure:
To a stirred mixture of tricyclo[3.3.1.03,7]nonan-3-amine (0.28 g, 2.0 mmol) and K2CO3 (0.83 g, 6.0 mmol) in DMSO (8 mL) at ice bath temperature under N2 atmosphere was added (S)-1-(2-chloro-acetyl)pyrrolidine-2-carbonitrile (0.34 g, 2.0 mmol). The reaction mixture was gradually warmed to room temperature and stirred for 3 h. Upon completion of the reaction (checked by TLC), the reaction mixture was diluted with EtOAc and washed with water and brine, dried over Na2SO4, and the solvent was removed under reduced pressure. The crude product was purified by column chromatography to obtain (2S)-1-[(tricyclo[3.3.1.03,7]non-3-ylamino)acetyl]pyrrolidine-2-carbonitrile as a viscous liquid (0.23 g) in 42% yield. m/z (M+1) 274; 1H NMR (CDCl3) 300 MHz δ 4.87-4.76 (m, 1H), 3.71-3.40 (m, 2H), 3.41 (s, 2H), 2.35-2.05 (m, 7H), 1.92-1.74 (m, 6H), 1.68-1.48 (m, 4H).
Reaction SMILES: Cl[C:2]1[C:3]2[CH:10]=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:11][C:12]1[CH:13]=[C:14]([NH2:19])[CH:15]=[CH:16][C:17]=1[F:18]>CN(C=O)C.C(OCC)(=O)C.FC(F)(F)S([O-])(=O)=O.[Ag+]>[Cl:11][C:12]1[CH:13]=[C:14]([NH:19][C:2]2[C:3]3[CH:10]=[CH:9][NH:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:15]=[CH:16][C:17]=1[F:18]
Reactant: Nc1ccc(F)c(Cl)c1
Reactant: Clc1ncnc2[nH]ccc12
Agent: [Ag+]
Agent: O=S(=O)([O-])C(F)(F)F
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Fc1ccc(Nc2ncnc3[nH]ccc23)cc1Cl
Temperature: 95 °C
Reaction time: 15 h
Yield: 92.9 %

Procedure:
To a solution of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (767.9 mg, 5 mmol) and 3-chloro-4-fluoro-phenylamine (873.4 mg, 6 mmol) in 25 mL of dry DMF under nitrogen was added silver trifluoromethanesulfonate (1.54 g, 6 mmol). The mixture was stirred at 95° C. for 15 hours. The cooled reaction was diluted with ethyl acetate (70 mL) and filtered through celite, washed thoroughly with ethyl acetate. The filtrate was washed with brine (5×). The brine was extracted with ethyl acetate which was then washed with brine. The combined ethyl acetate was dried (magnesium sulfate), concentrated and purified to give 1.22 g (93%) of (3-chloro-4-fluoro-phenyl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine as an off-white solid. m.p. 274-275° C. 1H NMR (360 MHz, DMSO-d6) δ 11.78 (br s, 1H, NH), 9.41 (s, 1H), 8.31 (s, 1H), 8.28 (m, 1H), 7.79 (m, 1H), 7.37 (t, 1H), 7.25 (m, 1H), 6.76 (m, 1H). MS 263.4 [M++1].
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[CH:9]([CH3:14])[CH2:10][SiH:11]([Cl:13])[Cl:12].[CH2:15]=[CH:16][CH2:17][CH2:18][CH2:19][CH3:20]>C(O)(C)C.[H+].[H+].Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl>[Cl:13][Si:11]([Cl:12])([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[CH2:10][CH:9]([C:3]1[CH:4]=[C:5]([CH3:8])[CH:6]=[CH:7][C:2]=1[CH3:1])[CH3:14]
Reactant: Cc1ccc(C)c(C(C)C[SiH](Cl)Cl)c1
Reactant: C=CCCCC
Agent: Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl
Agent: [H+]
Solvent: CC(C)O
Product: CCCCCC[Si](Cl)(Cl)CC(C)c1cc(C)ccc1C
Yield: 65.7 %

Procedure:
In the same apparatus and procedures as EXAMPLE 1, 8.5 g (0.034 mole of 3-(2,5-dimethylphenyl)-1,1-dichloro-1-silabutane, 8.7 g (0.10 mole) of 1-hexene, and 120 μl of 1% chloroplatinic acid in isopropanol were placed and refluxed under the dry nitrogen atmosphere for 3 hours. Vacuum distillation of the reaction products gave 7.4 g (bp, 130°-3° C./0.6 mmHg) of 4,4-dichloro-2-(2,5-dimethylphenyl)-4-siladecane.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:22])[C:5]1[CH:10]=[CH:9][C:8]([O:11][C:12]2[C:17]([N+:18]([O-])=O)=[CH:16][N:15]=[C:14]([Cl:21])[N:13]=2)=[CH:7][CH:6]=1)[CH3:2]>CC(O)=O.CO.[Zn]>[CH2:1]([O:3][C:4](=[O:22])[C:5]1[CH:10]=[CH:9][C:8]([O:11][C:12]2[C:17]([NH2:18])=[CH:16][N:15]=[C:14]([Cl:21])[N:13]=2)=[CH:7][CH:6]=1)[CH3:2]
Reactant: CCOC(=O)c1ccc(Oc2nc(Cl)ncc2[N+](=O)[O-])cc1
Agent: [Zn]
Solvent: CO
Solvent: CC(=O)O
Product: CCOC(=O)c1ccc(Oc2nc(Cl)ncc2N)cc1
Temperature: 25 °C
Reaction time: 6 h

Procedure:
To a solution of Compound 16a (2.12 g; 6.55 mmol) in AcOH (15 mL) and CH3OH (20 mL) was added Zn (2.57 g; 39.31 mmol) in portions at room temperature. The reaction mixture was stirred at room temperature for 6 h. The solid was collected by filtration and washed with CH3OH. The filtrate was concentrated. The residue was quenched with aqueous NaOH (<1 N) and adjusted to pH ˜7, and extracted with EtOAc (2×20 mL). The organic layer was dried over MgSO4 and concentrated. The crude product was purified by normal phase chromatography (SiO2) to give Compound 16b. 1H NMR (300 MHz, CDCl3): δ 8.15 (d, 2H), 7.95 (s, 1H), 7.25 (d, 2H), 4.45 (q, 2H), 1.4 (t, 3H); MS: m/z 294.1 (M+H)+.