Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=CC(F)=[CH:16][CH:15]=2)=[CH:10][C:9]=1[NH:21][C:22](=[O:34])[CH2:23][C:24]([C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([C:32]#[N:33])[CH:27]=1)=O)(C)(C)C.[C:36](O)([C:38]([F:41])(F)F)=O>C(Cl)Cl>[F:41][C:38]1[CH:36]=[CH:19][C:14]([C:11]2[CH:12]=[CH:13][C:8]3[N:7]=[C:24]([C:26]4[CH:27]=[C:28]([CH:29]=[CH:30][CH:31]=4)[C:32]#[N:33])[CH2:23][C:22](=[O:34])[NH:21][C:9]=3[CH:10]=2)=[CH:15][CH:16]=1
Reactant: O=C(O)C(F)(F)F
Reactant: CC(C)(C)OC(=O)Nc1ccc(-c2ccc(F)cc2)cc1NC(=O)CC(=O)c1cccc(C#N)c1
Solvent: ClCCl
Product: N#Cc1cccc(C2=Nc3ccc(-c4ccc(F)cc4)cc3NC(=O)C2)c1

Procedure:
Prepared from {3-[3-(3-cyano-phenyl)-3-oxo-propionylamino]-4′-fluoro-biphenyl-4-yl}-carbamic acid tert.-butyl ester (Example K32) by treatment with TFA in CH2Cl2 according to the general procedure M. Obtained as an orange solid (141 mg).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]([S:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([CH2:30]O)[CH:25]=3)[NH:12][C:13]=2[C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)=[CH:5][CH:4]=1.C(N(C(C)C)CC)(C)C.C1(C)C(S([Cl:50])(=O)=O)=CC=CC=1.O>O1CCCC1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]([S:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([CH2:30][Cl:50])[CH:25]=3)[NH:12][C:13]=2[C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)=[CH:5][CH:4]=1
Reactant: Cc1ccccc1S(=O)(=O)Cl
Reactant: COc1ccc(-c2nc(SCc3cccc(CO)c3)[nH]c2-c2ccc(OC)cc2)cc1
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Solvent: C1CCOC1
Product: COc1ccc(-c2nc(SCc3cccc(CCl)c3)[nH]c2-c2ccc(OC)cc2)cc1

Procedure:
Part C. A solution of the alcohol prepared above (5.96 g, 13.8 mmol), diisopropylethylamine (2.90 mL, 16.6 mmol) and toluenesulfonyl chloride (2.89 g, 15.2 mmol) in tetrahydrofuran (30 mL) was heated to reflux for 18 hours. The mixture was cooled, and poured into water (150 mL). This was extracted with methylene chloride (2×150 mL), and the extracts were combined, dried over magnesium sulfate and evaporated. The residual oil was separated by flash chromatography (3:7 ethyl acetate-hexane)to afford the product, 4,5-bis (4-methoxyphenyl)-2-[3-(chloro-methyl)benzyl]thio-1H-imidazole, as a foam upon vacuum pumping (2.24 g, 4.96 mmol, 36%). 1H NMR (CDCl3): 8.94 (1H, br s); 7.70-7.09 (8H, m); 6.84 (4H, d, J=8.8 Hz); 4.51 (2H, s); 4.19 (2H, s); 3.81 (6H, s).
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[C:11](I)=[C:10]([S:13][CH3:14])[N:9]=[C:8]([NH2:15])[N:7]=1.[CH:16]([Sn](CCCC)(CCCC)CCCC)=[CH2:17].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd]>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[C:11]([CH:16]=[CH2:17])=[C:10]([S:13][CH3:14])[N:9]=[C:8]([NH2:15])[N:7]=1
Reactant: C=C[Sn](CCCC)(CCCC)CCCC
Reactant: CSc1nc(N)nc(-c2ccco2)c1I
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Product: C=Cc1c(SC)nc(N)nc1-c1ccco1
Temperature: 25 °C
Yield: 65.7 %

Procedure:
To a stirred solution of 1.00 g (3.00 mmol) 4-furan-2-yl-5-iodo-6-methylsulfanyl-pyrimidin-2-yl-amine in 30 ml dioxane under argon at room temperature were added 0.96 ml (3.30 mmol) vinyltributylstannane, 347 mg (0.30 mmol) tetrakis(triphenylphosphine) palladium(O) and 6.0 ml (12.0 mmol) 2M aqueous sodium carbonate solution. The reaction mixture was heated at reflux for 16 h, then cooled to room temperature, 3 g of kieselgel added, and the mixture concentrated in vacuo. Flash chromatography (1/3 ethyl acetate/hexane) followed trituration in ether/hexane afforded 460mg (66%) 4-furan-2-yl-6-methylsulfanyl-5-vinyl-pyrimidin-2-ylamine as an orange crystalline solid. EI-MS m/e (%): 233 (M+, 48), 218 ([M—CH3]+, 76), 216 ([M—NH3]+, 46), 125 (100).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:14]1([C:20](=[CH2:24])[C:21]([OH:23])=[O:22])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C(O)(C)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:24][CH:20]([C:21]([OH:23])=[O:22])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: C=C(C(=O)O)c1ccccc1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Solvent: CC(C)O
Product: CC(C)(C)OC(=O)N1CCN(CC(C(=O)O)c2ccccc2)CC1
Yield: 54.3 %

Procedure:
Piperazine-1-carboxylic acid tert-butyl ester (17.43 g) and 2-phenylacrylic acid (18 g) in iso-propanol (500 ml) was heated at reflux for four days. The resulting precipitate was filtered, washed with diethyl ether and dried under vacuum to give the title compound as a white solid (17 g; MS: APCI+(M+H) 335).
Reaction SMILES: [C:1]([C:5]1[C:10]([N+:11]([O-])=O)=[CH:9][C:8]([OH:14])=[C:7]([Cl:15])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2]>CO.[Ni]>[C:1]([C:5]1[C:10]([NH2:11])=[CH:9][C:8]([OH:14])=[C:7]([Cl:15])[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)c1cc(Cl)c(O)cc1[N+](=O)[O-]
Agent: [Ni]
Solvent: CO
Product: CC(C)(C)c1cc(Cl)c(O)cc1N
Reaction time: 4 h
Yield: 77.5 %

Procedure:
To a solution of 4-tert-butyl-2-chloro-5-nitro-phenol (12.6 g, 54.9 mmol) in MeOH (50 mL) was added Ni (1.2 g). The reaction was shaken under H2 (1 atm) for 4 h. The reaction mixture was filtered and the filtrate was concentrated. The residue was purified by column chromatography (P.E./EtOAc, 20:1) to give 4-tert-butyl-2-chloro-5-amino-phenol (C-11) (8.5 g, 78%). 1H NMR (DMSO-d6) δ 9.33 (s, 1H), 6.80 (s, 1H), 6.22 (s, 1H), 4.76 (s, 1H), 1.23 (s, 9H); ESI-MS 200.1 m/z (MH+).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[C:5]([F:14])=[CH:4][C:3]=1[N:15]1[CH:20]=[C:19]([O:21][CH3:22])[C:18](=[O:23])[C:17]([C:24](O)=[O:25])=[N:16]1.Cl.[CH3:28][NH:29][O:30][CH3:31].C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.CCN=C=NCCCN(C)C>CN(C=O)C.CCOC(C)=O>[F:1][C:2]1[CH:7]=[C:6]([N:8]2[CH2:9][CH2:10][O:11][CH2:12][CH2:13]2)[C:5]([F:14])=[CH:4][C:3]=1[N:15]1[CH:20]=[C:19]([O:21][CH3:22])[C:18](=[O:23])[C:17]([C:24]([N:29]([O:30][CH3:31])[CH3:28])=[O:25])=[N:16]1
Reactant: CNOC
Reactant: COc1cn(-c2cc(F)c(N3CCOCC3)cc2F)nc(C(=O)O)c1=O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COc1cn(-c2cc(F)c(N3CCOCC3)cc2F)nc(C(=O)N(C)OC)c1=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 57.3 %

Procedure:
A mixture of 1-(2,5-difluoro-4-morpholin-4-ylphenyl)-5-methoxy-4-oxo-1,4-dihydropyridazine-3-carboxylic acid (2.5 g, 6.8 mmol), N,O-dimethylhydroxylamine hydrochloride (0.73 g, 7.5 mmol), HOBt (1.0 g, 7.5 mmol), triethylamine (2.0 mL, 14 mmol) and WSC (1.4 g, 7.5 mmol) in DMF (28 mL) was stirred at room temperature overnight. The mixture was diluted with AcOEt, washed with water and brine, dried over MgSO4 and concentrated under reduced pressure to give the title compound (1.6 g, 58% yield) as a brown solid: 1H NMR (300 MHz, DMSO-d6): δ ppm 3.01-3.19 (4H, m), 3.24 (3H, s), 3.56 (3H, s), 3.62-3.91 (7H, m), 7.17 (1H, dd, J=12.7, 7.7 Hz), 7.62-7.82 (1H, m), 8.48 (1H, s). LC-MS (ESI) m/z 411 [M+H]+.
Reaction SMILES: [F:1][C:2]1[C:3]([C:22]2[S:26][C:25]([C:27]3([OH:31])[CH2:30][CH2:29][CH2:28]3)=[N:24][CH:23]=2)=[C:4]2[CH:10]=[C:9](I)[N:8]([S:12]([C:15]3[CH:21]=[CH:20][C:18]([CH3:19])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:5]2=[N:6][CH:7]=1.[CH3:32][O:33][C:34]1[CH:35]=[C:36](B(O)O)[CH:37]=[C:38]([O:42][CH3:43])[C:39]=1[O:40][CH3:41].C(=O)(O)[O-]>CN(C)C=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:1][C:2]1[C:3]([C:22]2[S:26][C:25]([C:27]3([OH:31])[CH2:30][CH2:29][CH2:28]3)=[N:24][CH:23]=2)=[C:4]2[CH:10]=[C:9]([C:36]3[CH:37]=[C:38]([O:42][CH3:43])[C:39]([O:40][CH3:41])=[C:34]([O:33][CH3:32])[CH:35]=3)[N:8]([S:12]([C:15]3[CH:21]=[CH:20][C:18]([CH3:19])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:5]2=[N:6][CH:7]=1
Reactant: Cc1ccc(S(=O)(=O)n2c(I)cc3c(-c4cnc(C5(O)CCC5)s4)c(F)cnc32)cc1
Reactant: COc1cc(B(O)O)cc(OC)c1OC
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])O
Solvent: CN(C)C=O
Product: COc1cc(-c2cc3c(-c4cnc(C5(O)CCC5)s4)c(F)cnc3n2S(=O)(=O)c2ccc(C)cc2)cc(OC)c1OC
Temperature: 70 °C

Procedure:
To a stirred ambient solution of 1-(5-(5-fluoro-2-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)cyclobutanol (Example 59A) (200 mg, 0.351 mmol) and 3,4,5-trimethoxy phenylboronic acid (112 mg, 0.527 mmol) in N,N-dimethylformamide (2630 μl) was added saturated aqueous bicarbonate solution (880 μl) followed by bis(triphenylphosphine)palladium dichloride (17.26 mg, 0.025 mmol). The mixture was heated to 70° C. for 4 hours and was quenched by the addition of water and dichloromethane. The layers were separated, and the aqueous layer was extracted with additional dichloromethane. The combined organics were dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give crude product. The residue was purified by flash chromatography on silica gel, eluting with a gradient of 0 to 100% ethyl acetate in hexane, to give the title compound. MS ESI(+) m/z 610.2 [M+H]+.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:12]=[CH:11][C:10]([C:13]3([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[O:18]C4C=CC5C(C=4[CH:15]=[CH:14]3)=CC=CC=5)=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.C1C2C(=CC=CC=2)C=CC=1O>>[O:1]1[CH2:2][CH2:3][N:4]([C:7]2[CH:8]=[CH:9][C:10]([C:13]([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)([OH:18])[C:14]#[CH:15])=[CH:11][CH:12]=2)[CH2:5][CH2:6]1
Reactant: C1=CC(c2ccccc2)(c2ccc(N3CCOCC3)cc2)Oc2ccc3ccccc3c21
Agent: Oc1ccc2ccccc2c1
Product: C#CC(O)(c1ccccc1)c1ccc(N2CCOCC2)cc1
Yield: 71 %

Procedure:
3(4-Morpholinophenyl)-3-phenyl-3H-naphtho[2,1-b]pyran from 2-naphthol and 1(4-morpholinophenyl)-1-phenylprop-2-yn-1-ol (yield=71% after recrystallisation from EtOAc and hexane, m.p.=186-187° C. (uncorrected), λmax in toluene=500 nm, i.e. red).
Reaction SMILES: Cl[CH:2](Cl)/[C:3](=[N:5]\[NH:6]S(C1C=CC(C)=CC=1)(=O)=O)/[CH3:4].C(N(CC)CC)C.[C:25]([Si:29]([CH3:35])([CH3:34])[O:30][CH2:31][CH2:32][NH2:33])([CH3:28])([CH3:27])[CH3:26]>CO>[C:25]([Si:29]([CH3:35])([CH3:34])[O:30][CH2:31][CH2:32][N:33]1[CH:2]=[C:3]([CH3:4])[N:5]=[N:6]1)([CH3:28])([CH3:27])[CH3:26]
Reactant: C/C(=N/NS(=O)(=O)c1ccc(C)cc1)C(Cl)Cl
Reactant: CC(C)(C)[Si](C)(C)OCCN
Solvent: CO
Solvent: CCN(CC)CC
Product: Cc1cn(CCO[Si](C)(C)C(C)(C)C)nn1
Temperature: 25 °C
Reaction time: 18 h
Yield: 75.2 %

Procedure:
To a suspension of N′-[(1Z)-2,2-dichloro-1-methylethylidene]-4-methylbenzenesulfonohydrazide (prepared according to WO2007088478 example 13) (5.0 g, 16.9 mmol) in methanol (100 mL), at 0° C. under an atmosphere of nitrogen, was added triethylamine (11.8 mL, 84.7 mmol, 5.0 eq.) over a period of 2 min. To the resulting orange solution was added a solution of 2-{[tert-butyl-(dimethyl)silyl]oxy}ethanamine (prepared according to J.O.C. 74(4), 1791-1793, 2009) (3.3 g, 18.8 mmol, 1.1 eq.) in methanol (70 ml). The reaction mixture was stirred at room temperature for 18 hr. The mixture was then evaporated under reduced pressure and the residue partitioned between tert-butyl methyl ether (250 mL) and aqueous citric acid (10% wt/vol, 100 mL). The organic phase was washed with aqueous sodium hydrogen carbonate (1M, 100 mL), saturated brine (20 mL) and dried over sodium sulphate. The resulting mixture was filtered and the filtrate concentrated under reduced pressure to give a crude brown oil. The crude oil was purified by chromatography on silica gel (200 g) eluting with a gradient of tert-butyl methyl ether in toluene (10:90 to 40:60) to give the title compound as a yellow oil (3.07 g, 75%).
Reaction SMILES: O[C@@H:2]1[C@H:6]([CH2:7]/[CH:8]=[CH:9]\[CH2:10][CH2:11][CH2:12][C:13]([OH:15])=[O:14])[C@@H:5]([CH2:16][CH2:17][C@@H:18]([O:27][CH:28]2[CH2:33][CH2:32][CH2:31][CH2:30][O:29]2)[CH2:19]CC2C=CC=CC=2)[C@H:4]([O:34][CH:35]2[CH2:40][CH2:39][CH2:38][CH2:37][O:36]2)[CH2:3]1.C1C=C(SSC2N=CC=CC=2)N=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:74]1([CH3:81])[C:75](C)=[CH:76][CH:77]=[CH:78][CH:79]=1>>[C:74]1([CH2:81][CH2:19][C@H:18]([O:27][CH:28]2[CH2:33][CH2:32][CH2:31][CH2:30][O:29]2)[CH2:17][CH2:16][C@@H:5]2[C@@H:6]3[C@@H:2]([O:14][C:13](=[O:15])[CH2:12][CH2:11][CH2:10][CH:9]=[CH:8][CH2:7]3)[CH2:3][C@H:4]2[O:34][CH:35]2[CH2:40][CH2:39][CH2:38][CH2:37][O:36]2)[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=1
Reactant: Cc1ccccc1C
Reactant: O=C(O)CCC/C=C\C[C@@H]1[C@@H](CC[C@H](CCc2ccccc2)OC2CCCCO2)[C@H](OC2CCCCO2)C[C@@H]1O
Agent: O=C1CCC/C=C\C[C@@H]2[C@@H](CC[C@H](CCc3ccccc3)OC3CCCCO3)[C@H](OC3CCCCO3)C[C@@H]2O1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Agent: c1ccc(SSc2ccccn2)nc1
Product: O=C1CCCC=CC[C@@H]2[C@@H](CC[C@H](CCc3ccccc3)OC3CCCCO3)[C@H](OC3CCCCO3)C[C@@H]2O1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of (Z)-7-((1R,2R,3R,5S)-5-hydroxy-2-((3R)-5-phenyl-3-((tetrahydro-2H-pyran-2-yl)oxy)pentyl)-3-((tetrahydro-2H-pyran-2-yl)oxy)cyclopentyl)hept-5-enoic acid (52 g from Example 26) in xylene (250 mL) was treated with 2,2′-dipyridyl disulfide (28.9 g, 131.2 mmol) and triphenylphosphine (39.2 g, 149.5 mmol). This mixture was then stirred for 2 hr at room temperature under an atmosphere of nitrogen. The resulting mixture was heated to 80° C. for 18 hr (TLC monitoring), followed by removal of xylene under reduced pressure. The residue was diluted with saturated aqueous solution of sodium bicarbonate (200 mL) and extracted with ethyl acetate (200 mL). The organic layer was dried over magnesium sulfate and concentrated under reduced pressure to give 80.0 g of crude product. The crude product was purified by column chromatography providing 17.1 g of the title compound (68.0% yield, 3 steps).
Reaction SMILES: [NH2:1][C:2]1[C:7]([F:8])=[C:6](Cl)[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[C:3]=1[Cl:14].[F:15][C:16]1[C:17](B2OC(C)(C)C(C)(C)O2)=[CH:18][CH:19]=[C:20]2[C:24]=1[NH:23][CH:22]=[CH:21]2.[F-].[Cs+].[F-].[K+]>C(#N)C.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:17]2[C:16]([F:15])=[C:24]3[C:20]([CH:21]=[CH:22][NH:23]3)=[CH:19][CH:18]=2)[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[C:3]=1[Cl:14]
Reactant: CC1(C)OB(c2ccc3cc[nH]c3c2F)OC1(C)C
Reactant: COC(=O)c1nc(Cl)c(F)c(N)c1Cl
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cs+]
Agent: [F-]
Solvent: O
Solvent: CC#N
Product: COC(=O)c1nc(-c2ccc3cc[nH]c3c2F)c(F)c(N)c1Cl
Yield: 56.3 %

Procedure:
Methyl 4-amino-3,6-dichloro-5-fluoropicolinate (0.650 g, 2.72 mmol), 7-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (0.817 g, 3.13 mmol), bis(triphenylphosphine)palladium(II) chloride (0.191 g, 0.272 mmol), and cesium fluoride (0.826 g, 5.44 mmol, Note: potassium fluoride replaced cesium fluoride in some examples that refer to this particular example) were combined in acetonitrile (4.53 mL) and water (4.53 mL). The reaction mixture was irradiated in a Biotage Initiator microwave at 110° C. in a sealed vial for 30 min. The cooled reaction mixture was partitioned between ethyl acetate and water. The organic phase was dried and concentrated. The product was purified by flash chromatography (SiO2; eluting with 5-40% ethyl acetate in hexanes) to provide the title compound as an white solid (0.517 g, 52.4% yield).
Reaction SMILES: [CH:1]1([C:4]2[N:17]=[C:7]3[C:8]([O:15][CH3:16])=[CH:9][CH:10]=[C:11](B(O)O)[N:6]3[N:5]=2)[CH2:3][CH2:2]1.C([O-])([O-])=O.[K+].[K+].Br[C:25]1[CH:26]=[C:27]([CH:30]=[CH:31][N:32]=1)[C:28]#[N:29]>COCCOC.[Cl-].[Na+].O.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>[CH:1]1([C:4]2[N:17]=[C:7]3[C:8]([O:15][CH3:16])=[CH:9][CH:10]=[C:11]([C:25]4[CH:26]=[C:27]([CH:30]=[CH:31][N:32]=4)[C:28]#[N:29])[N:6]3[N:5]=2)[CH2:3][CH2:2]1
Reactant: COc1ccc(B(O)O)n2nc(C3CC3)nc12
Reactant: N#Cc1ccnc(Br)c1
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: [Cl-]
Solvent: COCCOC
Solvent: O
Product: COc1ccc(-c2cc(C#N)ccn2)n2nc(C3CC3)nc12

Procedure:
In a screw cap vial (2-cyclopropyl-8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-5-yl)boronic acid, compound 303, (26 mg, 0.1 mmol) was dissolved in DME (0.6 mL) and 1 M K2CO3 (0.2 mL) under argon. 2-Bromo-isonicotinonitrile (18 mg, 0.1 mmol) and Pd(PPh3)4 (6 mg, 0.005 mmol) were added. The suspension was shaken at 80° C. for 17 h after which brine was added, and the aqueous phase was extracted with DCM (×3). The combined organic phases were dried, filtered and concentrated. The crude product was purified by flash chromatography, eluent TBME:heptane 4:1->9:1. This afforded the title compound as a solid 1H NMR (300 MHz, DMSO) δ 9.23-9.09 (m, 1H), 9.00 (dd, J=4.9, 0.8 Hz, 1H), 7.95 (dd, J=4.9, 1.5 Hz, 1H), 7.90 (d, J=8.3 Hz, 1H), 7.24 (d, J=8.4 Hz, 1H), 4.03 (s, 3H), 2.29 (tt, J=8.1, 5.0 Hz, 1H), 1.18-0.87 (m, 4H).
Reaction SMILES: [CH2:1]1[C@H:9]([OH:10])[C@H:8]2[N:3]([CH2:4][C@H:5]([OH:13])[C@@H:6]([OH:12])[C@@H:7]2[OH:11])[CH2:2]1.[C:14](OC=C)(=[O:16])[CH3:15]>>[C:14]([O:10][CH:9]1[CH:8]2[N:3]([CH2:4][CH:5]([OH:13])[CH:6]([OH:12])[CH:7]2[OH:11])[CH2:2][CH2:1]1)(=[O:16])[CH3:15]
Reactant: C=COC(C)=O
Reactant: O[C@H]1[C@H](O)[C@@H](O)CN2CC[C@H](O)[C@H]12
Product: CC(=O)OC1CCN2CC(O)C(O)C(O)C12
Yield: 91 %

Procedure:
The same general procedure was repeated using castanospermine and vinyl acetate (2.2 mmol) and a reaction time of 84 hours to give [1S-(1α, 6β,7α, 8β, 8aβ)]-octahydro-1,6,7,8-indolizinetetrol 1-acetate melting at about 151°-153° C. (yield, 91%)
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[CH2:15][CH2:16][CH2:17][Cl:18].C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:15][CH2:16][CH2:17][Cl:18])[CH2:10][CH2:9]1)([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7]
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: ClCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCN(CCCCl)CC1
Temperature: 50 °C
Reaction time: 3 h

Procedure:
To a solution of 4.94 g tert-Butyl-1-piperazine-carboxylate and 12.66 g 1-Bromo-3-chloropropane in 15 ml DMF (dry) was added 4.08 g K2CO3 and the reaction heated to 50° C. for one minute and stirred at room temperature for additional 3 h. The reaction mixture is pored into 200 ml of water and extracted with DCM. The combined organic phases were washed with water and dried over MgSO4 and evaporated in vacuo. The product was purified by flash column chromatography (n-heptane/ethylacetate 1:1, RF=0.3) Yield 3.9 g.
Reaction SMILES: [OH:1][CH2:2][C:3]1[S:7][C:6]([NH2:8])=[N:5][CH:4]=1.[CH3:9][C:10]([Si:13](Cl)([CH3:15])[CH3:14])([CH3:12])[CH3:11].N1C=CN=C1>CN(C=O)C.CCOCC.O>[Si:13]([O:1][CH2:2][C:3]1[S:7][C:6]([NH2:8])=[N:5][CH:4]=1)([C:10]([CH3:12])([CH3:11])[CH3:9])([CH3:15])[CH3:14]
Reactant: Nc1ncc(CO)s1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: O
Solvent: CN(C)C=O
Solvent: CCOCC
Product: CC(C)(C)[Si](C)(C)OCc1cnc(N)s1
Yield: 44.4 %

Procedure:
A solution of 5-(hydroxymethyl)-thiazol-2-ylamine (0.787 g, 6.05 mmol), TBDMSCl (1.003 g, 6.65 mmol) and imidazole (0.49 g, 7.26 mmol) in DMF (15 mL) is stirred at room temperature for 24 h. The reaction mixture is diluted with ether and water. The organic layer is washed with water (3×). The aqueous washings are backwashed with ether (2×). The organic layers are combined, dried over MgSO4 and condensed. The crude material is purified using a plug of silica and eluting with 1:1 petrol:ethyl acetate to give the product (0.656 g, 44%). 1H-NMR (400 MHz, d6-DMSO) =0.01 (s, 6H, 2×CH3), 0.82 (s, 9H, tBu), 4.61 (s, 2H, CH2), 4.74 (brs, 2H, NH2), 6.8 (s, 1H, CH). LCMS: Rt 2.62 min (92.7%). MS (MH+, m/z) 245.
Reaction SMILES: [CH2:1]([N:8]1[CH2:16][C:15]2[C:10](=[CH:11][C:12]([O:19]C)=[C:13]([O:17]C)[CH:14]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BrH:21]>O>[BrH:21].[CH2:1]([N:8]1[CH2:9][C:10]2[C:15](=[CH:14][C:13]([OH:17])=[C:12]([OH:19])[CH:11]=2)[CH2:16]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COc1cc2c(cc1OC)CN(Cc1ccccc1)C2
Agent: Br
Solvent: O
Product: Oc1cc2c(cc1O)CN(Cc1ccccc1)C2

Procedure:
To 5.38 g (20 mmol) of N-benzyl-5,6-dimethoxyisoindoline, 50 ml of 48% hydrobromic acid was added, and the mixture was heated at reflux for 5 hours at an external temperature of from 110° to 125° C. After cooling, the precipitated crystals were collected by filtration and washed with 5 ml of water and 10 ml of acetone to obtain 6.36 g of the above identified compound as a grayish white powder. The powder was dissolved in 150 ml of hot water, and the solution was subjected to decolorization with 1.0 g of active carbon and then cooled with ice to obtain 4.75 g of prism crystals.
Reaction SMILES: [O:1]=[CH:2][C:3]1[CH:11]=[CH:10][C:8]([OH:9])=[C:5]([O:6][CH3:7])[CH:4]=1.C(N(CC)CC)C.[C:19](OC(=O)C)(=[O:21])[CH3:20]>CN(C)C1C=CN=CC=1.C(Cl)Cl.CCOCC>[C:19]([O:9][C:8]1[CH:10]=[CH:11][C:3]([CH:2]=[O:1])=[CH:4][C:5]=1[O:6][CH3:7])(=[O:21])[CH3:20]
Reactant: COc1cc(C=O)ccc1O
Reactant: CC(=O)OC(C)=O
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCOCC
Solvent: CCN(CC)CC
Product: COc1cc(C=O)ccc1OC(C)=O

Procedure:
A solution of vanillin (60.8 g), triethylamine (60 ml), acetic anhydride (44 ml), and 4-dimethylaminopyridine (1.0 g) in methylene chloride (800 ml) is stirred at room temperature for about 30 minues, and the volume then reduced by 50% in vacuo. The residue is diluted with ether and the solution washed with water, brine, dried over magnesium sulfate, filtered and concentrated in vacuo to give the desired product.
Reaction SMILES: [NH2:1][C:2]1[C:3]([NH:16][C@@H:17]2[CH2:22][CH2:21][C@H:20]([C:23]([NH:25][CH:26]([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]2)=[CH:4][C:5]([O:8][CH:9]2[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]2)=[N:6][CH:7]=1.[F:29][C:30]1[CH:64]=[CH:63][C:33]([C:34](/[N:36]=[C:37]2/N([C@H]3CC[C@@H](C(=O)NC(C)C)CC3)C3C=C(OCCOC)N=CC=3N/2)=[O:35])=[CH:32][CH:31]=1>>[F:29][C:30]1[CH:31]=[CH:32][C:33]([C:34](/[N:36]=[C:37]2/[N:16]([C@H:17]3[CH2:22][CH2:21][C@@H:20]([C:23](=[O:24])[NH:25][CH:26]([CH3:28])[CH3:27])[CH2:19][CH2:18]3)[C:3]3[CH:4]=[C:5]([O:8][CH:9]4[CH2:10][CH2:11][N:12]([CH3:15])[CH2:13][CH2:14]4)[N:6]=[CH:7][C:2]=3[NH:1]/2)=[O:35])=[CH:63][CH:64]=1
Reactant: CC(C)NC(=O)[C@H]1CC[C@@H](Nc2cc(OC3CCN(C)CC3)ncc2N)CC1
Reactant: COCCOc1cc2c(cn1)[nH]/c(=N\C(=O)c1ccc(F)cc1)n2[C@H]1CC[C@@H](C(=O)NC(C)C)CC1
Product: CC(C)NC(=O)[C@H]1CC[C@@H](n2/c(=N/C(=O)c3ccc(F)cc3)[nH]c3cnc(OC4CCN(C)CC4)cc32)CC1

Procedure:
The title compound was prepared from cis-4-(5-amino-2-(1-methylpiperidin-4-yloxy)pyridin-4-ylamino)-N-isopropylcyclohexanecarboxamide using a procedure analogous to that used for (E)-4-fluoro-N-(1-(cis-4-(isopropylcarbamoyl)cyclohexyl)-6-(2-methoxyethoxy)-1H-imidazo[4,5-c]pyridin-2 (3H)-ylidene)benzamide. The product was isolated as an off-white solid (94 mg, 72% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.10 (d, J=8H, 6H) 1.48-1.78 (m, 7H) 1.84-2.03 (m, 2H) 2.04-2.10 (m, 2H) 2.13-2.34 (m, 5H) 2.65 (m, 4H) 3.95-4.05 (m, 1H) 4.65-4.80 (m, 1H) 4.89-5.03 (m, 1H) 6.96 (s, 1H) 7.26 (dd, J=8.75 Hz, 2H) 7.68 (d, J=7.63 Hz, 1H) 8.23 (s, 1H) 8.31 (dd, J=8.56, 5.82 Hz, 2H) 12.60 (br. s., 1H). M/Z calc'd for C29H37FN6O3: 536.64. found 537 [M+H].