Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CC1(C)C(C)(C)OB([C:9]2[CH:28]=[CH:27][C:12]([CH2:13][N:14]3[C:22]4[C:17](=[CH:18][CH:19]=[CH:20][C:21]=4[C:23]([O:25][CH3:26])=[O:24])[CH:16]=[CH:15]3)=[CH:11][CH:10]=2)O1.[F-].[Cs+].Br[C:33]1[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=1>[Pd].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O1CCOCC1>[N:35]1[CH:36]=[CH:37][CH:38]=[C:33]([C:9]2[CH:28]=[CH:27][C:12]([CH2:13][N:14]3[C:22]4[C:17](=[CH:18][CH:19]=[CH:20][C:21]=4[C:23]([O:25][CH3:26])=[O:24])[CH:16]=[CH:15]3)=[CH:11][CH:10]=2)[CH:34]=1
Reactant: Brc1cccnc1
Reactant: COC(=O)c1cccc2ccn(Cc3ccc(B4OC(C)(C)C(C)(C)O4)cc3)c12
Agent: [Fe+2]
Agent: [Pd]
Agent: [Cs+]
Solvent: C1COCCO1
Product: COC(=O)c1cccc2ccn(Cc3ccc(-c4cccnc4)cc3)c12
Temperature: 100 °C
Reaction time: 21 h
Yield: 99 %

Procedure:
To methyl 1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl]-1H-indole-7-carboxylate (0.15 g), 1,1′-bis(diphenylphosphino)ferrocene palladium (14 mg), cesium fluoride (0.17 g), and 3-bromopyridine (79 mg) was added dioxane (4.5 mL), followed by stirring at 100° C. for 21 hours under an argon atmosphere. The reaction mixture was purified by silica gel column chromatography (hexane/ethyl acetate=2/1-1/1) to obtain methyl 1-(4-pyridin-3-yl benzyl)-1H-indole-7-carboxylate (0.13 g).
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[C:7]([CH3:9])[CH:8]=1.C([O-])([O-])=O.[Na+].[Na+].Br[C:20]1[CH:21]=[C:22]([C:26]2[CH:31]=[C:30]([NH:32][CH2:33][CH3:34])[N:29]=[C:28]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=3)[CH:27]=2)[CH:23]=[N:24][CH:25]=1>COCCOC.C(Cl)Cl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([C:20]2[CH:21]=[C:22]([C:26]3[CH:31]=[C:30]([NH:32][CH2:33][CH3:34])[N:29]=[C:28]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=4)[CH:27]=3)[CH:23]=[N:24][CH:25]=2)[CH:6]=[C:7]([CH3:9])[CH:8]=1
Reactant: CCNc1cc(-c2cncc(Br)c2)cc(-c2ccccn2)n1
Reactant: Cc1cc(CN)cc(B(O)O)c1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: ClCCl
Solvent: COCCOC
Product: CCNc1cc(-c2cncc(-c3cc(C)cc(CN)c3)c2)cc(-c2ccccn2)n1

Procedure:
To a solution of 5″-(3-Aminomethyl-5-methyl-phenyl boronic acid (Intermediate B27) (2.0 eq, 0.303 mmol, 50 mg) and 2M Na2CO3 (2.0 eq, 0.303 mmol, 0.152 ml) in DME (1 ml) is added (5″-Bromo-[2,2′;4′,3″]terpyridin-6′-yl)-ethylamine (Ex. 1.24) (1 eq, 0.152 mmol, 54 mg) followed by [1,1′-Bis(diphenylphosphino)-ferrocene]dichloropalladium (II), complex with DCM (0.1 eq, 0.015 mmol, 12.3 mg). The reaction mixture is heated using microwave radiation at 90° C. for 90 minutes. The reaction mixture is dissolved in DCM and washed with water. The organic layer is washed with brine, dried over drying agent MgSO4, filtered and the organic solvent is reduced in vacuo. The residue is purified by reverse phase chromatography (Isolute™ C18, 0-20% acetonitrile in water—0.1% TFA). The appropriate fractions by HPLC are combined and concentrated in vacuo. The resulting residue is dissolved in MeOH and loaded onto a SCX-2 cartridge eluting with MeOH and 2M NH3 in MeOH. The methanolic ammonia fractions are combined, concentrated in vacuo and dried under vacuum to afford the title compound; [M+H]+ 397.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[N:13][C:14]([C:18]([F:21])([F:20])[F:19])=[CH:15][CH:16]=3)[N:11]=[CH:10][CH:9]=2)=[CH:4][C:3]=1OS(C(F)(F)F)(=O)=O.[C:30]([C:33]1[CH:34]=[C:35](B(O)O)[CH:36]=[CH:37][CH:38]=1)(=[O:32])[CH3:31]>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[N:13][C:14]([C:18]([F:21])([F:20])[F:19])=[CH:15][CH:16]=3)[N:11]=[CH:10][CH:9]=2)=[CH:4][C:3]=1[C:37]1[CH:36]=[CH:35][CH:34]=[C:33]([C:30](=[O:32])[CH3:31])[CH:38]=1
Reactant: O=S(=O)(Oc1cc(-c2ccnc3nc(C(F)(F)F)ccc23)ccc1F)C(F)(F)F
Reactant: CC(=O)c1cccc(B(O)O)c1
Product: CC(=O)c1cccc(-c2cc(-c3ccnc4nc(C(F)(F)F)ccc34)ccc2F)c1
Yield: 60.2 %

Procedure:
Trifluoromethanesulfonic acid 2-fluoro-5-(7-trifluoromethyl-[1,8]naphthyridin-4-yl)phenyl ester (30.0 mg, 0.068 mmol) was coupled to 3-acetylphenyl-boronic acid (14.5 mg, 0.089 mmol) as described in Example 35 part c), affording 1-[2′-fluoro-5′-(7-trifluoromethyl[1,8]naphthyridin-4-yl)biphenyl-3-yl]ethanone (16.8 mg, 60%). δH (360 MHz, CDCl3) 2.66 (3H, s), 7.39-7.44 (1H, dd, J 9.8 and 8.4), 7.47-7.52 (1H, m), 7.58-7.62 (3H, m), 7.80-7.85 (2H, m), 8.01 (1H, dt, J 7.7, 1.2), 8.18 (1H, d, J 1.4), 8.55 (1H, d, J 8.8), 9.30 (1H, d, J 4.6). m/z (ES+) 411 [MH]+.
Reaction SMILES: O.[O:2]=[CH:3][C@@H:4]([C@@H:6]([C@H:8]([C@H:10]([CH3:12])[OH:11])[OH:9])[OH:7])[OH:5].[C:13]1(=O)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1.S(=O)(=O)(O)O.C(OCC)(=O)C>CCOCC.S([O-])([O-])(=O)=O.[Cu+2].CCCCCC>[OH:9][CH:8]([C@H:6]1[O:7][C:13]2([CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)[O:5][C@H:4]1[CH:3]=[O:2])[CH:10]([OH:11])[CH3:12]
Reactant: C[C@H](O)[C@H](O)[C@@H](O)[C@@H](O)C=O
Reactant: O=C1CCCCC1
Agent: [Cu+2]
Agent: O=S(=O)(O)O
Agent: O=S(=O)([O-])[O-]
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: CCOCC
Product: CC(O)C(O)[C@H]1OC2(CCCCC2)O[C@H]1C=O
Temperature: 29 °C
Reaction time: 8 h
Yield: 56.4 %

Procedure:
A slurry of copper sulfate (175 g, 1.09 mol, 2 eq) and rhamnose hydrate (100 g, 0.55 mol) in freshly distilled cyclohexanone (330 g) was stirred under nitrogen as concentrated sulfuric acid (1.5 mL) was added at once. The reaction mixture was warmed to about 29° C. internal. The reaction mixture was allowed to stir overnight. The reaction was analyzed by TLC (ethyl acetate) and was complete. The reaction mixture was filtered through a pad of celite and the solid was washed with ethyl acetate. The filtrate was treated with about 1.5 mL of concentrated ammonium hydroxide to pH 7, and the resulting solid was removed by filtration. The filtrate was concentrated under reduced pressure to give a colorless oil. The residue was dissolved in ether and treated with hexane and allowed to stand overnight. Resulting solid was isolated by filtration and dried to give 92.3 g (0.31 mol, 57%) of (2R,3R)-3-(1,2-dihydroxypropyl)-1,4-dioxaspiro[4,5]decane-2-carboxaldehyde, as an off-white solid: [α]D=+0.457 (10.485 mg/cc MeOH); 1H NMR (CDCl3) δ 1.34 (d, 3H), 1.40 (m, 2H), 1.6 (m, 8H), 2.78 (d, 1H), 3.0 (s, 1H), 3.9 (m, 1H), 4.07 (m, 1H), 4.6 (d, 1H), 4.9 (m, 1H), 5.4 (s, 1H) ppm.
Reaction SMILES: [CH3:1][N:2]([CH3:7])[CH2:3][CH2:4][CH2:5]O.[CH3:8][N:9]([CH3:13])[C:10]([NH2:12])=[S:11]>Br>[CH3:8][N:9]([CH3:13])[C:10](=[NH:12])[S:11][CH2:5][CH2:4][CH2:3][N:2]([CH3:7])[CH3:1]
Reactant: CN(C)C(N)=S
Reactant: CN(C)CCCO
Agent: Br
Product: CN(C)CCCSC(=N)N(C)C

Procedure:
A mixture of 3-dimethylaminopropanol (10.3 g), N,N1 -dimethylthiourea (10.4 g) and aqueous hydrobromic acid (48%, 60 ml) was boiled under reflux for 18 hours and evaporated to dryness. The residue was recrystallised from ethanol to give the dihydrobromide of the title compound m.p. 173°-174°.
Reaction SMILES: COP([CH2:7][C:8](=[O:24])[CH2:9][CH2:10][CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1)(OC)=O.[H-].[Na+].[N:27]1[CH:28]=[C:29]2[N:38]3[C:33](=[CH:34][CH:35]=[CH:36][C:37]=13)[S:32][C:31]([CH:39]=O)=[CH:30]2>C1(C)C=CC=CC=1.CN(C)C=O.O>[C:20]([O:19][C:17]([N:14]1[CH2:13][CH2:12][CH:11]([CH2:10][CH2:9][C:8](=[O:24])/[CH:7]=[CH:39]/[C:31]2[S:32][C:33]3[N:38]4[C:29](=[CH:28][N:27]=[C:37]4[CH:36]=[CH:35][CH:34]=3)[CH:30]=2)[CH2:16][CH2:15]1)=[O:18])([CH3:21])([CH3:22])[CH3:23]
Reactant: COP(=O)(CC(=O)CCC1CCN(C(=O)OC(C)(C)C)CC1)OC
Reactant: O=CC1=Cc2cnc3cccc(n23)S1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)N1CCC(CCC(=O)/C=C/C2=Cc3cnc4cccc(n34)S2)CC1
Reaction time: 2 h

Procedure:
To a solution of 4.77 g (13.1 mM) of tert-butyl 4-[4-(dimethoxyphosphoryl)-3-oxobutyl]piperidine-1-carboxylate in 50 ml of toluene was added 0.48 g (12.0 mM) of a 60% suspension of sodium hydride in liquid paraffin at room temperature, and the mixture was stirred at the prevailing temperature for 2 hours. This reaction mixture was added to a solution of the above crude 5-thia-1,8b-diazaacenaphthylene-4-carbaldehyde in N,N-dimethylformamide (30 ml)-toluene (50 ml) with ice-cooling and the mixture was stirred at the prevailing temperature for 3 hours. This reaction mixture was poured in water and extracted with 3 portions of ethyl acetate. The organic layers were pooled and dried over MgSO4 and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate to ethyl acetate/methanol : 9/1) to provide crude (E)-5-[1-(tert-butoxycarbonyl)piperidin-4-yl]-1-(5-thia-1,8b-diazaacenaphthylen-4-yl)-1-penten-3-one. This crude product was not purified but used as it was in the next reaction.
Reaction SMILES: S(S([O-])=O)([O-])=O.[Na+].[Na+].[CH3:9][O:10][C:11]1[C:12](=[O:20])[CH:13]=[CH:14][C:15](=[O:19])[C:16]=1[O:17][CH3:18]>CO.O>[CH3:18][O:17][C:16]1[C:11]([O:10][CH3:9])=[C:12]([OH:20])[CH:13]=[CH:14][C:15]=1[OH:19]
Reactant: COC1=C(OC)C(=O)C=CC1=O
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: COc1c(O)ccc(O)c1OC
Yield: 39.5 %

Procedure:
Sodium hydrosulphite (Na2S2O4, 26 g) was added portionwise to a stirred solution of 2,3-dimethoxy-1,4-benzoquinone (J. Med. Chem., 1971, 14, 45; 5 g) in a mixture of methanol (50 ml) and water (100 ml). The resultant mixture was stirred at ambient temperature for 1 hour. The mixture was partitioned between ethyl acetate and water. The organic phase was dried (MgSO4) and evaporated to give 2,3-dimethoxyhydroquinone (2 g); NMR Spectrum: (CD3SOCD3) 3.71 (s, 6H), 6.37 (s, 2H), 8.47 (s, 2H).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([Cl:8])[CH:5]=[C:4](Cl)[N:3]=1.[F:10][C:11]([F:18])([F:17])[CH:12]1[CH2:16][CH2:15][CH2:14][NH:13]1.CCN(C(C)C)C(C)C>CC#N>[Cl:8][C:6]1[CH:5]=[C:4]([N:13]2[CH2:14][CH2:15][CH2:16][CH:12]2[C:11]([F:18])([F:17])[F:10])[N:3]=[C:2]([NH2:1])[N:7]=1
Reactant: Nc1nc(Cl)cc(Cl)n1
Reactant: FC(F)(F)C1CCCN1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: Nc1nc(Cl)cc(N2CCCC2C(F)(F)F)n1
Yield: 36.6 %

Procedure:
2-Amino-4,6-dichloropyrimidine (143 mg, 0.870 mmol) was added to a stirring mixture of 2-trifluoromethylpyrrolidine (121 mg, 0.870 mmol) and Hunig's base (0.23 mL, 1.31 mmol) in CH3CN (2.5 mL) in a microwave vessel. The reaction was capped and heated in a microwave reactor for 1 hour. Silica gel chromatography (Analogix RS-12 g cartridge) eluting with 5-10% EtOAc—CHCl3 gave the title compound (85 mg) as a white solid. 1H NMR (400 MHz, CDCl3, * denotes minor rotamer): δ 1.96-2.15 (m, 2H), 2.15-2.32 (m, 2H), 3.37-3.52 (m, 1H), 3.54-3.65 (m, 1H), 4.82, 5.60* (bs, 1H), 5.00 (bs, 2H), 5.94, 6.72* (s, 1H).
Reaction SMILES: N1C=CC=CC=1.P(Cl)(Cl)(Cl)(Cl)Cl.S1C=CC=C1CC([NH:21][C@@H:22]1[C:56](=[O:57])[N:24]2[C:25]([C:40]([O:42][CH:43]([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)[C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)=[O:41])=[C:26]([CH2:29][O:30][C:31](=[O:39])[NH:32][C:33](=[O:38])[C:34]([Cl:37])([Cl:36])[Cl:35])[CH2:27][S:28][C@H:23]12)=O.O.[C:59]1([CH3:69])[CH:64]=[CH:63][C:62]([S:65]([OH:68])(=[O:67])=[O:66])=[CH:61][CH:60]=1>ClCCl.C(OCC)(=O)C.C(OCC)C.O.CO>[C:59]1([CH3:69])[CH:60]=[CH:61][C:62]([S:65]([OH:68])(=[O:66])=[O:67])=[CH:63][CH:64]=1.[NH2:21][C@@H:22]1[C:56](=[O:57])[N:24]2[C:25]([C:40]([O:42][CH:43]([C:44]3[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=3)[C:50]3[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=3)=[O:41])=[C:26]([CH2:29][O:30][C:31](=[O:39])[NH:32][C:33](=[O:38])[C:34]([Cl:36])([Cl:37])[Cl:35])[CH2:27][S:28][C@H:23]12
Reactant: O=C(Cc1cccs1)N[C@@H]1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(COC(=O)NC(=O)C(Cl)(Cl)Cl)CS[C@H]12
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: ClP(Cl)(Cl)(Cl)Cl
Solvent: c1ccncc1
Solvent: O
Solvent: ClCCl
Product: N[C@@H]1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(COC(=O)NC(=O)C(Cl)(Cl)Cl)CS[C@H]12
Reaction time: 0.17 h
Yield: 72.1 %

Procedure:
Anhydrous pyridine (31 ml, 0.384 mole) was added to a solution of phosphorus pentachloride (20 g, 96 mmole) in dry dichloromethane (300 ml) at 3°. The suspension was stirred for 10 minutes at 3° and diphenylmethyl (6R,7R)-7-(thien-2-ylacetamido)-3-trichloroacetylcarbamoyloxymethylceph-3-em-4-carboxylate (22.5 g, 32 mmole) was added; the reaction was stirred at ca. 2° for 1 hour. The dark solution was poured slowly into a cold (0°) anhydrous mixture of methanol (80 ml) and dichloromethane (200 ml) with the temperature kept below 5°. The temperature of the solution was then allowed to rise to 23° and, after stirring the solution at this temperature for 1 hour, water (200 ml) was added. The organic layer was separated and washed with 2N-sulphuric acid, water, sodium bicarbonate solution and water, dried over magnesium sulphate, and evaporated in vacuo. The resulting oil was dissolved in ethyl acetate and a solution of toluene-p-sulphonic acid monohydrate (6.0 g, 31.5 mmole) in ethyl acetate was added. The combined solutions (ca. 350 ml) were poured into diethyl ether (ca. 1 liter) and the resulting solid was filtered off and dried in vacuo to give the title compound (17.2 g, 72%), m.p. 150° to 153°; [α]D21° + 7.5° (c 0.82 in DMSO); λmaxEtOH 263 nm (ε 7,600) and λinf.EtOH 267 nm (ε 7,350). IR, NMR and microanalytical data confirmed the structure as that of the title compound.
Reaction SMILES: [CH:1]1([C:4]2[O:8][N:7]=[C:6]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[O:15][C:16]([F:19])([F:18])[F:17])[C:5]=2[CH2:20][O:21][CH:22]2[CH2:28][CH:27]3[N:29]([C:30]4[S:31][C:32]5[CH:38]=[C:37]([C:39]([OH:41])=O)[CH:36]=[CH:35][C:33]=5[N:34]=4)[CH:24]([CH2:25][CH2:26]3)[CH2:23]2)[CH2:3][CH2:2]1.Cl.[CH3:43][O:44][C:45](=[O:48])[CH2:46][NH2:47].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(C(C(C)C)(CC)C([O-])=O)(C)C>ClCCl>[CH:1]1([C:4]2[O:8][N:7]=[C:6]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[O:15][C:16]([F:19])([F:17])[F:18])[C:5]=2[CH2:20][O:21][CH:22]2[CH2:23][CH:24]3[N:29]([C:30]4[S:31][C:32]5[CH:38]=[C:37]([C:39]([NH:47][CH2:46][C:45]([O:44][CH3:43])=[O:48])=[O:41])[CH:36]=[CH:35][C:33]=5[N:34]=4)[CH:27]([CH2:26][CH2:25]3)[CH2:28]2)[CH2:2][CH2:3]1
Reactant: O=C(O)c1ccc2nc(N3C4CCC3CC(OCc3c(-c5ccccc5OC(F)(F)F)noc3C3CC3)C4)sc2c1
Reactant: COC(=O)CN
Agent: CCC(C(=O)[O-])(C(C)C)C(C)C
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Solvent: ClCCl
Product: COC(=O)CNC(=O)c1ccc2nc(N3C4CCC3CC(OCc3c(-c5ccccc5OC(F)(F)F)noc3C3CC3)C4)sc2c1
Reaction time: 1 h

Procedure:
2-(3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)benzo[d]thiazole-6-carboxylic acid (34 mg, 0.06 mmol) was combined with glycine methyl ester hydrochloride (8 mg, 0.06 mmol), O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (25 mg, 0.065 mmol), diisopropylethylacetate (0.05 ml) and dichloromethane (2 mL). The mixture was stirred for 1 hour, then the solvent was removed in vacuo. The residue was suspended in ethyl acetate (15 mL) and washed with sodium bicarbonate solution (5 mL). The organics were combined and dried (MgSO4) then evaporated in vacuo. The product was purified by flash silica chromatography with 0-100% ethyl acetate in hexanes and used directly in the next procedure.
Reaction SMILES: [OH:1][CH:2](C=C)[CH2:3][O:4][C:5]1[CH:9]=[C:8]([C:10]([O:12][CH3:13])=[O:11])[O:7][N:6]=1.F[C:17]([F:30])([F:29])S(O[Si](C(C)(C)C)(C)C)(=O)=O.CC1C=CC=C(C)N=1.Cl>C1COCC1>[F:30][CH:17]([F:29])[CH:2]([OH:1])[CH2:3][O:4][C:5]1[CH:9]=[C:8]([C:10]([O:12][CH3:13])=[O:11])[O:7][N:6]=1
Reactant: CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F
Reactant: C=CC(O)COc1cc(C(=O)OC)on1
Agent: Cl
Solvent: Cc1cccc(C)n1
Solvent: C1CCOC1
Product: COC(=O)c1cc(OCC(O)C(F)F)no1
Temperature: 25 °C
Reaction time: 2 h
Yield: 12.3 %

Procedure:
A mixture of methyl 3-[(2-hydroxybut-3-en-1-yl)oxy]isoxazole-5-carboxylate (2.71 g), t-butyldimethylsilyl trifluoromethanesulfonate (4.03 g), 2,6-dimethylpyridine (1.64 g) and THF (30 mL) was stirred at room temperature for 2 hr. To the reaction mixture was added 1M hydrochloric acid, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated aqueous sodium hydrogen carbonate solution, and then saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was mixed with tetraoxide osmium (7% immobilized catalyst, 2.31 g), sodium periodate (13.6 g), acetonitrile (30 mL), acetone (30 mL) and water (20 mL), and the obtained mixture was stirred at room temperature for 3 days. The precipitate was removed by filtration, and the filtrate was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was mixed with toluene (20 mL), diethylaminosulfur trifluoride (5.04 mL) was slowly added dropwise thereto at room temperature, and the obtained mixture was stirred at room temperature for 2 hr. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was mixed with THF (20 mL), tetrabutylammonium fluoride (1.0M THF solution, 25.4 mL) was slowly added dropwise thereto at 0° C., and the obtained mixture was stirred at 0° C. for 30 min. To the reaction mixture was added 1M hydrochloric acid, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound as a white powder (370 mg).
Reaction SMILES: N[CH2:2][CH2:3][NH:4][C:5]([C:7]1[S:8][CH:9]=[CH:10][C:11]=1[NH:12][C:13]1[CH:18]=[CH:17][N:16]=[C:15]2[NH:19][CH:20]=[CH:21][C:14]=12)=[O:6].[CH2:22]([O:29]CCN)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>>[CH2:22]([O:29][CH2:2][CH2:3][NH:4][C:5]([C:7]1[S:8][CH:9]=[CH:10][C:11]=1[NH:12][C:13]1[CH:18]=[CH:17][N:16]=[C:15]2[NH:19][CH:20]=[CH:21][C:14]=12)=[O:6])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: NCCNC(=O)c1sccc1Nc1ccnc2[nH]ccc12
Reactant: NCCOCc1ccccc1
Product: O=C(NCCOCc1ccccc1)c1sccc1Nc1ccnc2[nH]ccc12

Procedure:
This compound was prepared in an analogous manner as 3-(1H-Pyrrolo[2,3-b]pyridin-4-ylamino)-thiophene-2-carboxylic acid (2-amino-ethyl)-amide using 2-(benzyloxy)ethanamine instead of tert-butyl-2-amino ethyl carbamate. LCMS (ESI) 393 (M+H) 1H NMR (400 MHz, DMSO-d6) δ ppm 11.51 (1H, br. s.) 10.24 (1H, s) 8.15 (1H, s) 7.99 (1H, d, J=5.47 Hz) 7.76 (1H, d, J=5.27 Hz) 7.44 (1H, d, J=5.47 Hz) 7.16-7.32 (5H, m) 6.78 (1H, d, J=5.27 Hz) 6.41 (1H, d, J=3.32 Hz) 4.44 (2H, s) 3.48-3.56 (2H, m) 3.39-3.47 (2H, m)
Reaction SMILES: F[C:2]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][C:3]=1[C:4]#[N:5].C(=O)([O-])[O-].[K+].[K+].[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20]>C(O)C>[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][N:29]([C:2]2[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][C:3]=2[C:4]#[N:5])[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:20])[CH3:21]
Reactant: N#Cc1cc([N+](=O)[O-])ccc1F
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Product: CC(C)(C)OC(=O)N1CCN(c2ccc([N+](=O)[O-])cc2C#N)CC1
Temperature: 80 °C
Reaction time: 1 h
Yield: 59.2 %

Procedure:
A solution of 2-fluoro-5-nitrobenzonitrile (500 mg, 3.0 mmol) in ethanol (35 mL) was treated with potassium carbonate (420 mg, 3.0 mmol) and piperazine-1-carboxylic acid tert-butyl ester (560 mg, 3.0 mmol). The reaction mixture was stirred at 80° C. for 1 h, then cooled and partitioned between ethyl acetate and water. The organic layer was then collected, dried over sodium sulfate, filtered and evaporated to a yellow residue. Purification using flash chromatography yielded 4-(2-cyano-4-nitro-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (590 mg, 59% yield) as a bright yellow solid. HRMS calcd for C16H20N4O4 (M+Na) 355.1377, obsd 355.1376.
Reaction SMILES: [N+:1]([C:3]1[CH:19]=[CH:18][CH:17]=[CH:16][C:4]=1[CH2:5][N:6]1[C:11](=O)[CH2:10][C:9](=[O:13])[N:8]([CH3:14])[C:7]1=[O:15])#[C-:2].P(Cl)(Cl)([Cl:22])=O.P(Cl)(Cl)(Cl)(Cl)Cl>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.C(#N)C>[Cl:22][C:11]1[N:6]([CH2:5][C:4]2[CH:16]=[CH:17][CH:18]=[CH:19][C:3]=2[N+:1]#[C-:2])[C:7](=[O:15])[N:8]([CH3:14])[C:9](=[O:13])[CH:10]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: [C-]#[N+]c1ccccc1CN1C(=O)CC(=O)N(C)C1=O
Agent: CC[N+](CC)(CC)Cc1ccccc1
Agent: ClP(Cl)(Cl)(Cl)Cl
Agent: [Cl-]
Solvent: CC#N
Product: [C-]#[N+]c1ccccc1Cn1c(Cl)cc(=O)n(C)c1=O
Yield: 70.5 %

Procedure:
In an alternate embodiment, a solution of 1-(2-isocyanobenzyl)-3-methylpyrimidine-2,4,6(1H,3H,5H)-trione (18 mmol), phosphorus oxychloride (85 ml), benzyltriethylammonium chloride (16.5 g, 72 mmol) and phosphorus pentachloride (3.8 g, 18 mol) in acetonitrile (80 ml) was refluxed for 4-5 h with stirring. After evaporation under reduced pressure, the resulting oily residue was mixed with methylene chloride (or chloroform) and the mixture was poured into water and ice (50 ml). The layers were separated and the aqueous layer was extracted with dichloromethane (200 ml). The combined organic extracts were washed with water and brine, dried over sodium sulphate and concentrated under reduced pressure. Crude product was crystallized from THF-hexanes to give desired compound in 70.5% yield.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.C([Li])CCC.Br[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23].[Cl-].[NH4+]>CCCCCC.CCOCC>[CH2:23]([C:2]1[O:1][CH:5]=[CH:4][CH:3]=1)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH3:12]
Reactant: CCCCCCCCCCCCBr
Reactant: c1ccoc1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCOCC
Solvent: CCCCCC
Product: CCCCCCCCCCCCc1ccco1

Procedure:
A mixture of 68.1 g (1.0 mole) of furan and 500 ml of anhydrous ether is stirred at -20° C. after which 1.1 moles (458 ml of a 2.4 molar hexane solution) of butyllithium is added slowly with stirring. The reaction mixture is stirred for 1 hour, then 284 g (1.2 moles) of 1-bromododecane is added. The reaction mixture is stirred at room temperature for 4 hours after which it is poured into a saturated ammonium chloride solution. The organic layer is separated and washed with water and brine, dried over sodium sulfate and distilled under reduced pressure to give 2-dodecylfuran.