Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O-])([O-])=O.[K+].[K+].Br[C:8]1[CH:9]=[N:10][C:11]([N:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)=[N:12][CH:13]=1.B1([CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)C2CCCC1CCC2>C1COCC1.O.C1COCC1.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>[CH2:36]([C:8]1[CH:9]=[N:10][C:11]([N:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)=[N:12][CH:13]=1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1
Reactant: c1ccc(CB2C3CCCC2CCC3)cc1
Reactant: CC(C)(C)OC(=O)N1CCN(c2ncc(Br)cn2)CC1
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: [K+]
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)OC(=O)N1CCN(c2ncc(Cc3ccccc3)cn2)CC1

Procedure:
A mixture of K2CO3 (6 gm, 43.5 mmol, 3 equiv) and Pd(PPh3)4 (1 gm, 0.86 mmol) were stirred at room temperature in 20 mL THF/water (1:1) for 30 minutes. Tert-butyl 4-(5-bromopyrimidin-2-yl)piperazine-1-carboxylate (5 gm, 14.5 mmol, 1 equiv) was then added with B-benzyl-9-BBN (2 equiv, 49 ml of a 0.5 M solution in THF). The resulting mixture was heated with stirring under argon atmosphere in an oil bath adjusted at 100-110° C. until the reaction had reached completion, as monitored by TLC. The reaction mixture was extracted with CHCl3 (3×200 mL). The combined organic layers were then dried with anhydrous Na2SO4. Chloroform was evaporated under reduced pressure and the residue was purified using flash column chromatography (initially with 4:1 hexane/ethyl acetate and finally with 1:1 hexane/ethyl acetate). Tert-butyl 4-(5-benzylpyrimidin-2-yl)piperazine-1-carboxylate was obtained as a yellow solid (3.8 gm, 74% yield); mp: 121-123° C. 1H-NMR (DMSO-d6): δ 1.47 (s, 9H), 3.47 (t, J=4.68 Hz, 4H), 3.75 (t, J=4.68 Hz, 4H), 3.78 (s, 2H), 7.14-7.29 (m, 5H), 8.16 (s, 2H). 13C-NMR (DMSO-d6): δ 28.4, 35.61, 43.70, 79.92, 122.29, 126.41, 128.51, 128.66, 140.02, 154.84, 157.87, 160.69. MS: calcd 354.21 for C20H26N4O2 [M]+. found, 355.21 [M+1]+. b) 3.7 gm of the obtained product from step a was then deprotected using HCl/MeOH as described above in the preparation of 1. As a result, compound 2 was obtained as a pale yellow solid (2.2 gm, 80% yield); mp: 108-110° C. 1H-NMR (DMSO-d6): δ 1.89 (s, 1H), 2.93 (t, J=4.8 Hz, 4H), 3.76 (t, J=4.8 Hz, 4H), 3.79 (s, 2H), 7.17-7.29 (m, 5H), 8.18 (s, 2H). 13C-NMR (DMSO-d6): δ 35.59, 44.96, 45.92, 121.79, 126.34, 128.48, 128.6, 140.1, 157.8, 160.5. MS: calcd 254.15 for C15H18N4 [M]+. found, 255.15 [M+1]+.
Reaction SMILES: [Cl:1][C:2]1[C:3](=[O:10])[O:4][C:5]([CH3:9])=[CH:6][C:7]=1[OH:8].CN(C=O)C.C([O-])([O-])=O.[K+].[K+].Cl[CH2:23][N:24]1[C:34](=[O:35])[C:33]2[C:28](=[CH:29][C:30]([O:39][CH3:40])=[CH:31][C:32]=2[CH:36]([CH3:38])[CH3:37])[S:25]1(=[O:27])=[O:26]>O>[Cl:1][C:2]1[C:3](=[O:10])[O:4][C:5]([CH3:9])=[CH:6][C:7]=1[O:8][CH2:23][N:24]1[C:34](=[O:35])[C:33]2[C:28](=[CH:29][C:30]([O:39][CH3:40])=[CH:31][C:32]=2[CH:36]([CH3:38])[CH3:37])[S:25]1(=[O:26])=[O:27]
Reactant: Cc1cc(O)c(Cl)c(=O)o1
Reactant: COc1cc(C(C)C)c2c(c1)S(=O)(=O)N(CCl)C2=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1cc(C(C)C)c2c(c1)S(=O)(=O)N(COc1cc(C)oc(=O)c1Cl)C2=O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 19 %

Procedure:
A mixture of 3-chloro-4-hydroxy-6-methyl-2H-pyran-2-one (0.493 g, 3.07 mmol), DMF and K2CO3 (0.467 g, 3.38 mmol) was stirred at room temperature under N2 for 0.5 hours then 2-chloromethyl-4-isopropyl-6-methoxysaccharin (0.978 g, 3.22 mmol) was added in one portion. The mixture was stirred at room temperature for 3 hours, and then at 75° C. for 3 hours. The mixture was poured into water, extracted with ethyl acetate and the organic layer was washed with brine and dried. The solvent was removed in vacuo and the residue was purified by column chromatography on silica eluting with 30% ethyl acetate/hexane to afford 0.25 g (18.1% ) of 2-(3-chloro-6-methyl-2-oxo-2H-pyran-4-yl)oxymethyl-4-isopropyl-6-methoxysaccharin, m.p. 182.5°-183.5° C. after recrystallization from ether/hexane.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([NH:13][C:14]([NH:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3[N:28]4[CH:29]=[CH:30][C:31]([C:33]5[CH:38]=[CH:37][C:36]([S:39]([CH3:42])(=[O:41])=[O:40])=[CH:35][CH:34]=5)=[CH:32][C:27]4=[N:26][CH:25]=3)=[CH:20][CH:19]=2)=[O:15])[N:8]([CH2:10][CH2:11][OH:12])[N:9]=1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:50][S:51](Cl)(=[O:53])=[O:52]>C(Cl)Cl>[C:1]([C:5]1[CH:6]=[C:7]([NH:13][C:14]([NH:16][CH2:17][C:18]2[CH:19]=[CH:20][C:21]([C:24]3[N:28]4[CH:29]=[CH:30][C:31]([C:33]5[CH:34]=[CH:35][C:36]([S:39]([CH3:42])(=[O:40])=[O:41])=[CH:37][CH:38]=5)=[CH:32][C:27]4=[N:26][CH:25]=3)=[CH:22][CH:23]=2)=[O:15])[N:8]([CH2:10][CH2:11][O:12][S:51]([CH3:50])(=[O:53])=[O:52])[N:9]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)(C)c1cc(NC(=O)NCc2ccc(-c3cnc4cc(-c5ccc(S(C)(=O)=O)cc5)ccn34)cc2)n(CCO)n1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)c1cc(NC(=O)NCc2ccc(-c3cnc4cc(-c5ccc(S(C)(=O)=O)cc5)ccn34)cc2)n(CCOS(C)(=O)=O)n1
Yield: 97 %

Procedure:
In a round bottomed flask dissolve 1-[5-tert-butyl-2-(2-hydroxy-ethyl)-2H-pyrazol-3-yl]-3-{4-[7-(4-methanesulfonyl-phenyl)-imidazo[1,2-a]pyridin-3-yl]-benzyl}-urea (0.2 g, 0.34 mmol) and triethyl amine (0.48 mL, 10 equiv.) in DCM (20 mL) under N2. Add methanesulfonyl chloride (0.13 mL, 4.8 equiv.) dropwise and stir the reaction at room temperature for 15 minutes. Load the crude reaction directly onto silica gel and purify (EtOAc to 5% MeOH: DCM) to give a yellow solid (0.22 g, 97%). MS (ES), m/z 665 (M+1).
Reaction SMILES: [O:1]=[CH:2][C@@H:3]([C@H:5]([C@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])[OH:4].[OH:13][CH:14]1[O:21][C@H:20]([CH2:22][OH:23])[C@@H:18](O)[C@H:16]([OH:17])[C@H:15]1[NH:24][C:25]([CH3:27])=[O:26]>>[O:1]([C@@H:18]1[C@@H:20]([CH2:22][OH:23])[O:21][CH:14]([OH:13])[C@H:15]([NH:24][C:25]([CH3:27])=[O:26])[C@H:16]1[OH:17])[C@@H:2]1[O:10][C@H:9]([CH2:11][OH:12])[C@H:7]([OH:8])[C@H:5]([OH:6])[C@H:3]1[OH:4]
Reactant: O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CO
Reactant: CC(=O)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O
Product: CC(=O)N[C@H]1C(O)O[C@H](CO)[C@@H](O[C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2O)[C@@H]1O

Procedure:
The 1H-NMR spectrum of the difucosylated product (FIG. 3C, Table 3) showed that two fucoses had been transferred to the acceptor, yielding the glycan 4. The H-1 signals of the fucoses resonated at 5.117 ppm and 4.078(α)/5.091(β) ppm (3FucH-1 and 6FucH-1, respectively). In glycan 4 also the H-1 signals of 3Gal and 6Gal were shifted (-0.027 and -0.028 ppm, respectively) compared to the corresponding signals in glycan 3. In contrast, the H-1 signal of the branching galactose was practically unaffected, showing that the GlcNAc in the reducing end was not fucosylated. This confirms and extends previous data showing that branch forming Galβ1-4GlcNAc residues of polylactosamines are not fucosylated under the conditions used (Niemela et al., Glycoconjugate J. 12: 36-44 (1995)).
Reaction SMILES: [CH:1]1([NH:4][C:5]([C:7]2[C:16](=[O:17])[C:15]3[C:10](=[N:11][CH:12]=[CH:13][CH:14]=3)[N:9]([C:18]3[CH:23]=[C:22]([Br:24])[CH:21]=[C:20](Br)[CH:19]=3)[CH:8]=2)=[O:6])[CH2:3][CH2:2]1.[CH3:26][N:27]([CH3:30])C=O>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].Cl[Pd]Cl>[CH:1]1([NH:4][C:5]([C:7]2[C:16](=[O:17])[C:15]3[C:10](=[N:11][CH:12]=[CH:13][CH:14]=3)[N:9]([C:18]3[CH:23]=[C:22]([Br:24])[CH:21]=[C:20]([C:2]4[CH:30]=[N:27][C:26]([C:16]([OH:17])([CH3:7])[CH3:15])=[CH:3][CH:1]=4)[CH:19]=3)[CH:8]=2)=[O:6])[CH2:3][CH2:2]1
Reactant: O=C(NC1CC1)c1cn(-c2cc(Br)cc(Br)c2)c2ncccc2c1=O
Reactant: CN(C)C=O
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: c1ccc(P(c2ccccc2)[c-]2cccc2)cc1
Product: CC(C)(O)c1ccc(-c2cc(Br)cc(-n3cc(C(=O)NC4CC4)c(=O)c4cccnc43)c2)cn1
Temperature: 85 °C
Reaction time: 5 h

Procedure:
A mixture of N-cyclopropyl-1-(3,5-dibromophenyl)-1,4-dihydro[1,8]naphthyridin-4-one-3-carboxamide from Step 2,2-(1-hydroxy-1-methylethyl)-5-tributylstannylpyridine from Step 3 (1.4 eq), 1,1′-bis (diphenylphosphino)ferrocene]dichloropalladium(II) (0.05 eq), and cuprous iodide (0.05 eq) in N,N-dimethylformamide (15 ml/mmol) was stirred at 85° C. for 5 hours. After cooling the resulting mixture was partitioned between ethyl acetate and water. The crude product from the organic phase was chromatographed on silica gel eluting with a 1:6:3 mixture of ethanol, ethyl acetate and methylene chloride to afford the N-Cyclopropyl-1-{5-bromo-3-[6-(1-hydroxy-1-methylethyl)pyridin-3-yl]phenyl}-1,4-dihydro[1,8]naphthyridin-4-one-3-carboxamide compound as a solid.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N:9]2[C:14](=[O:15])[C:13]([O:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)=[C:12]([C:24]3[CH:29]=[CH:28][C:27]([S:30](C)(=[O:32])=[O:31])=[C:26]([F:34])[CH:25]=3)[CH:11]=[N:10]2)[CH:5]=[CH:6][C:7]=1[F:8].[NH3:35]>>[F:1][C:2]1[CH:3]=[C:4]([N:9]2[C:14](=[O:15])[C:13]([O:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)=[C:12]([C:24]3[CH:29]=[CH:28][C:27]([S:30]([NH2:35])(=[O:32])=[O:31])=[C:26]([F:34])[CH:25]=3)[CH:11]=[N:10]2)[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: N
Reactant: CS(=O)(=O)c1ccc(-c2cnn(-c3ccc(F)c(F)c3)c(=O)c2Oc2ccc(F)cc2)cc1F
Product: NS(=O)(=O)c1ccc(-c2cnn(-c3ccc(F)c(F)c3)c(=O)c2Oc2ccc(F)cc2)cc1F

Procedure:
The title compound was prepared according to the method of Example 384 substituting 2-(3,4-difluorophenyl)-4-(4-fluorophenoxy)-5-[3-fluoro-4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone in place of 2-benzyl-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (yield: 125 mg, 31%). mp 224-226° C. 1H NMR (300 MHz, DMSO-d6) δ 7.15 (d, 4H), 7.51 (m, 1H), 7.6 (m, 2H) 7.75 (m, 4H), 7.9 (t, 1H); 8.4 (s, 1H). MS (DCI/NH3) m/z 492 (M+H)+, 509 (M+NH4)+. Anal. calc. for C22H13F4N3O4S: C, 53.77; H, 2.67; N, 8.55. Found, C,; 53.33; H, 2.84; N, 8.22
Reaction SMILES: [CH:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:9]=[CH:10][C:11](=[CH2:13])[CH3:12].O>CCCCCC>[CH3:12][C:11]1[CH2:13][CH:1]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[O:8][CH2:9][CH:10]=1
Reactant: C=CC(=C)C
Reactant: O=Cc1ccccc1
Solvent: CCCCCC
Solvent: O
Product: CC1=CCOC(c2ccccc2)C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 42 %

Procedure:
Bis-trifluoromethanesulphonimide (70, 5 mg, 0.25 mmol) was stirred in hexane (4 ml) at room temperature. Benzaldehyde (510 μl, 5.0 mmol) and isoprene (750 μl, 7.5 mmol) were added and the mixture stirred at room temperature overnight. Water (5 ml) was added and the aqueous layer was extracted with hexane (3×3 ml). The combined organic layers were filtered through celite and analysed by glc. A yield of 42% of 4-methyl-6-phenyl-5,6-dihydropyran was observed.
Reaction SMILES: Cl.[CH3:2][C:3]1[N:4]=[C:5]([NH2:9])[S:6][C:7]=1[CH3:8].C(N(CC)CC)C.[C:17]12([C:27](Cl)=[O:28])[CH2:26][CH:21]3[CH2:22][CH:23]([CH2:25][CH:19]([CH2:20]3)[CH2:18]1)[CH2:24]2>C1COCC1>[CH3:2][C:3]1[N:4]=[C:5]([NH:9][C:27]([C:17]23[CH2:26][CH:21]4[CH2:20][CH:19]([CH2:25][CH:23]([CH2:22]4)[CH2:24]2)[CH2:18]3)=[O:28])[S:6][C:7]=1[CH3:8]
Reactant: Cc1nc(N)sc1C
Reactant: O=C(Cl)C12CC3CC(CC(C3)C1)C2
Agent: Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: Cc1nc(NC(=O)C23CC4CC(CC(C4)C2)C3)sc1C
Yield: 74 %

Procedure:
To a solution of 4,5-dimethyl-thiazol-2-ylamine hydrochloride (1.65 g, 10.0 mmol) in THF (100 mL) was added triethylamine (4.2 mL, 30 mmol) and adamantane-1-carbonyl chloride (2.2 g, 11 mmol). The mixture was heated at reflux overnight and then concentrated under reduced pressure. The residue was diluted with ethyl acetate, washed with 1M NaHCO3, dried (Na2SO4), filtered and concentrated. Purification by column chromatography (SiO2, 10% ethyl acetate: 90% hexanes) afforded 2.15 g (74%) of the title compound. MS (ESI+) m/z 291 (M+H)+.
Reaction SMILES: [N+:1]([O-:4])([O-])=[O:2].[K+].[OH:6][C:7]1[C:16]([OH:17])=[N:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]3[CH:20]=[N:19][NH:18][C:13]3=2)[N:8]=1>S(=O)(=O)(O)O>[OH:6][C:7]1[C:16]([OH:17])=[N:15][C:14]2[C:9](=[CH:10][C:11]([N+:1]([O-:4])=[O:2])=[C:12]3[CH:20]=[N:19][NH:18][C:13]3=2)[N:8]=1
Reactant: Oc1nc2ccc3cn[nH]c3c2nc1O
Reactant: O=[N+]([O-])[O-]
Agent: O=S(=O)(O)O
Agent: [K+]
Product: O=[N+]([O-])c1cc2nc(O)c(O)nc2c2[nH]ncc12
Temperature: 0 °C
Reaction time: 1 h
Yield: 52.6 %

Procedure:
Finely powdered potassium nitrate (0.11 g, 1 mmol) was added to a stirred solution of 7,8-dihydroxy-lH-pyrazolo[3,4-f]-quinoxaline (0.2 g, 1 mmol) in 2 ml of conc. sulfuric acid at room temperature. The solution was stirred for 1 h at this temperature and then poured into 50 ml of ice/water. After 30 min the precipitated solid was isolated by filtration and washed with water. Recrystallization from N,N-dimethylformamide/water afforded 0.13 g (53%) of the nitro compound; m.p. >300° C.; IR (KBr): 3300-2500, 1705 cm-1 ; lH-NMR (DMSO-d6) 7.83 (s, lH ArH), 8.37 (s, lH, ArH), 12.2 (broad s, 2H, 20H).
Reaction SMILES: [OH:1][CH:2]([CH2:29][OH:30])[CH2:3][NH:4][C:5]1[CH:12]=[C:11]([N:13]2[C:21]3[CH2:20][C:19]([CH3:23])([CH3:22])[CH2:18][C:17](=[O:24])[C:16]=3[C:15]([C:25]([F:28])([F:27])[F:26])=[N:14]2)[CH:10]=[CH:9][C:6]=1[C:7]#[N:8].[OH-:31].[Na+].OO>CCO.O>[OH:1][CH:2]([CH2:29][OH:30])[CH2:3][NH:4][C:5]1[CH:12]=[C:11]([N:13]2[C:21]3[CH2:20][C:19]([CH3:22])([CH3:23])[CH2:18][C:17](=[O:24])[C:16]=3[C:15]([C:25]([F:27])([F:28])[F:26])=[N:14]2)[CH:10]=[CH:9][C:6]=1[C:7]([NH2:8])=[O:31]
Reactant: CC1(C)CC(=O)c2c(C(F)(F)F)nn(-c3ccc(C#N)c(NCC(O)CO)c3)c2C1
Reactant: [OH-]
Agent: OO
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: CC1(C)CC(=O)c2c(C(F)(F)F)nn(-c3ccc(C(N)=O)c(NCC(O)CO)c3)c2C1
Yield: 29.5 %

Procedure:
2-(2,3-Dihydroxy-propylamino)-4-(6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-indazol-1-yl)-benzonitrile (1.7 g, 4 mmol, 1 eq), NaOH (806 mg, 20 mmol, 5 eq), and H2O2 (3 mL) were dissolved in EtOH-water (4:1) (40 mL). The mixture was microwaved at 120° C. for 15 min, then concentrated to dryness, and purified by flash chromatography, eluted by 10% MeOH in EtOAc to give pure 2-(2,3-Dihydroxy-propylamino)-4-(6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-indazol-1-yl)-benzamide (0.52 g, 29% yield). LCMS (m/z): M+H=441.
Reaction SMILES: N(C(OCC)=O)=NC(OCC)=O.[Si:13]([O:20][CH2:21][CH:22]([OH:33])[CH2:23][CH2:24][P:25](=[O:32])([O:29][CH2:30][CH3:31])[O:26][CH2:27][CH3:28])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14].O[N:35]1[C:39](=[O:40])[C:38]2=[CH:41][CH:42]=[CH:43][CH:44]=[C:37]2[C:36]1=[O:45].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[Si:13]([O:20][CH2:21][CH:22]([O:33][N:35]1[C:36](=[O:45])[C:37]2=[CH:44][CH:43]=[CH:42][CH:41]=[C:38]2[C:39]1=[O:40])[CH2:23][CH2:24][P:25](=[O:32])([O:26][CH2:27][CH3:28])[O:29][CH2:30][CH3:31])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14]
Reactant: O=C1c2ccccc2C(=O)N1O
Reactant: CCOP(=O)(CCC(O)CO[Si](C)(C)C(C)(C)C)OCC
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CCOP(=O)(CCC(CO[Si](C)(C)C(C)(C)C)ON1C(=O)c2ccccc2C1=O)OCC
Temperature: 25 °C
Reaction time: 8 h
Yield: 70.7 %

Procedure:
Diethyl azodicarboxylate (4.02 ml, 0.0.26 mol) was added to a solution of diethyl [4-(t-butyldimethylsilyloxy)-3-hydroxybutyl]phosphonate (7.9 g, 0.023 mol), N-hydroxyphthalimide (3.79 g, 0.023 mol) and triphenylphosphine (6.70 g, 0.026 mol) in dry tetrahydrofuran (100 ml). The mixture was stirred overnight at ambient temperature under a nitrogen atmosphere. The solvent was removed in vacuo and the residue dissolved in diethyl ether and kept at 4° C. for 24 hours. The mixture was filtered and the filtrate evaporated to dryness. The residue was chromatographed on silica gel (hexane-acetone 3:1 as eluant) to give the title compound as a pale yellow oil (7.9 g, 70%). IR:υmax (film) 2990, 2960, 2940, 2860, 1790, 1740, 1605, 1420, 1370, 1250, 1190, 1160, 1120, 1060, 1030, 970, 880, 840, 790, 700 cm-1. 1H NMR: δH (CDCl3) 0.0 (6H, s, SiMe2), 0.8 (9H, s, SiBut), 1.3 (6H, t, J=7Hz, (OCH2CH3)2), 1.78-2.4 (4H, m, CH2CH2P), 3.6-4.1 (7H, m, OCH2CH+(OCH2CH3)2), 7.65-7.95 (4H, m, aromatic H).
Reaction SMILES: [C:1](Cl)(=[O:5])[CH:2]([CH3:4])[CH3:3].[NH:7]1[C:16](=[O:17])[C:15]2[NH:14][CH:13]=[N:12][C:11]=2[N:10]=[C:8]1[NH2:9]>N1C=CC=CC=1>[C:1]([NH:9][C:8]1[NH:7][C:16](=[O:17])[C:15]2[NH:14][CH:13]=[N:12][C:11]=2[N:10]=1)(=[O:5])[CH:2]([CH3:4])[CH3:3]
Reactant: CC(C)C(=O)Cl
Reactant: Nc1nc2nc[nH]c2c(=O)[nH]1
Solvent: c1ccncc1
Product: CC(C)C(=O)Nc1nc2nc[nH]c2c(=O)[nH]1
Temperature: 100 °C
Reaction time: 3 h

Procedure:
Isobutyryl chloride (2.02 mL, 19.9 mmol) was added dropwise to a stirred suspension of guanine (3.02 g, 20 mmol) and TEA (1.45 mL, 10.4 mmol) in anhydrous pyridine (40 mL). The mixture was stirred for 3 h at 100° C. The reaction was quenched using methanol, and the solid was filtered, washed with methanol and dried in vacuo to give 10: yield 2.67 g (60%); MS (+ESI): m/z 222 [M+H]+.
Reaction SMILES: C(O[C:4]([C:6]1[N:11]2[N:12]=[C:13]([NH:15][C:16]([NH:18][CH2:19][CH3:20])=[O:17])[N:14]=[C:10]2[CH:9]=[C:8]([Br:21])[CH:7]=1)=[O:5])C.[CH3:22][O:23][C:24]1[CH:25]=[C:26]([CH:29]=[CH:30][C:31]=1[O:32][CH3:33])[CH2:27][NH2:28]>C(O)C>[CH3:22][O:23][C:24]1[CH:25]=[C:26]([CH:29]=[CH:30][C:31]=1[O:32][CH3:33])[CH2:27][NH:28][C:4]([C:6]1[N:11]2[N:12]=[C:13]([NH:15][C:16]([NH:18][CH2:19][CH3:20])=[O:17])[N:14]=[C:10]2[CH:9]=[C:8]([Br:21])[CH:7]=1)=[O:5]
Reactant: CCNC(=O)Nc1nc2cc(Br)cc(C(=O)OCC)n2n1
Reactant: COc1ccc(CN)cc1OC
Solvent: CCO
Product: CCNC(=O)Nc1nc2cc(Br)cc(C(=O)NCc3ccc(OC)c(OC)c3)n2n1

Procedure:
7-Bromo-2-(3-ethyl-ureido)-[1,2,4]triazolo[1,5-a]pyridine-5-carboxylic acid ethyl ester, which may be prepared as in Example 6, (253 mg, 0.714 mmol) and 3,4-dimethoxybenzylamine (0.55 mL) were taken up in ethanol (4.0 mL). After 24 h the precipitate was removed by filtration and washed with ethanol to afford 7-bromo-2-(3-ethyl-ureido)-[1,2,4]triazolo[1,5-a]pyridine-5-carboxylic acid 3,4-dimethoxy-benzylamide MS (APCI+): m/z 478.4 (M+H).
Reaction SMILES: [O:1]1[CH2:6][CH2:5][NH:4][C:3]2[CH:7]=[CH:8][CH:9]=[CH:10][C:2]1=2.[Cl:11][C:12]1[CH:13]=[CH:14][C:15](F)=[C:16]([CH:19]=1)[C:17]#[N:18].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[O:1]1[CH2:6][CH2:5][N:4]([C:15]2[CH:14]=[CH:13][C:12]([Cl:11])=[CH:19][C:16]=2[C:17]#[N:18])[C:3]2[CH:7]=[CH:8][CH:9]=[CH:10][C:2]1=2
Reactant: N#Cc1cc(Cl)ccc1F
Reactant: c1ccc2c(c1)NCCO2
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: N#Cc1cc(Cl)ccc1N1CCOc2ccccc21
Temperature: 100 °C
Yield: 48.1 %

Procedure:
To a solution of 3,4-dihydro-2H-benzo[b][1,4]oxazine (500 mg, 3.69 mmol, Tyger Scientific) and 5-chloro-2-fluorobenzonitrile (573 mg, 3.69 mmol) in DMF (10 mL) was added cesium carbonate (3.61 g, 11.0 mmol). The reaction mixture was heated at 100° C. for 24 h. After completion, the reaction mixture was quenched with ice water (10 mL) and extracted with ethyl acetate (2×15 mL). The organic layer was dried over sodium sulfate and concentrated to get crude material which was purified by column chromatography (12 g column: elution: 5% ethyl acetate in hexane) to provide 2-(2h-benzo[b][1,4]oxazin-4(3h)-yl)-5-chlorobenzonitrile (480 mg, 48.4%) as yellow solid. LCMS (ESI) m/z 270.02 (M+H).
Reaction SMILES: [CH3:1][C:2]([CH3:14])([CH3:13])[C:3]([OH:12])([CH2:6][N:7]1[CH:11]=[N:10][CH:9]=[N:8]1)[C:4]#[CH:5].[Cl:15][O-].[Na+]>C(Cl)Cl>[Cl:15][C:5]#[C:4][C:3]([OH:12])([CH2:6][N:7]1[CH:11]=[N:10][CH:9]=[N:8]1)[C:2]([CH3:14])([CH3:13])[CH3:1]
Reactant: C#CC(O)(Cn1cncn1)C(C)(C)C
Reactant: [O-]Cl
Agent: [Na+]
Solvent: ClCCl
Product: CC(C)(C)C(O)(C#CCl)Cn1cncn1
Yield: 86 %

Procedure:
9.65 (50 mmol) of 4,4-dimethyl-3-hydroxy-3-[(1,2,4-triazol-1-yl)-methyl]-1-pentine in 20 ml of methylene chloride are stirred for 3 days with 400 ml (150 mmol) of a solution of sodium hypochlorite at room temperature. The reaction mixture is then extracted by shaking with methylene chloride. After drying the organic phase and stripping off the solvent in vacuo, there are obtained 9.8 g (43 mmol; 86% of theory) of 1-chloro-4,4-dimethyl-3-hydroxy-3-[(1,2,4-triazol-1-yl)-methyl]-1-pentine having a melting point of 88° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[CH:13]=[O:14])[NH:9][C:8](=[O:15])[CH2:7][CH2:6]2.[CH3:16]C(C)([O-])C.[K+].COS(OC)(=O)=O>C1COCC1.C(=O)(O)[O-].[Na+]>[CH3:16][N:9]1[C:10]2[C:5](=[CH:4][C:3]([O:2][CH3:1])=[C:12]([CH:13]=[O:14])[CH:11]=2)[CH2:6][CH2:7][C:8]1=[O:15]
Reactant: COc1cc2c(cc1C=O)NC(=O)CC2
Reactant: CC(C)(C)[O-]
Agent: O=C([O-])O
Agent: [K+]
Agent: [Na+]
Solvent: COS(=O)(=O)OC
Solvent: C1CCOC1
Product: COc1cc2c(cc1C=O)N(C)C(=O)CC2
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
6-Methoxy-2-oxo-1,2,3,4-tetrahydro-quinoline-7-carbaldehyde 30 mg (0.146 mmol) was dissolved in 5 ml of anhydrous THF and the solution was cooled to 0° C. The reaction mixture was treated with 16 mg (0.146 mmol) of potassium t-butoxide whereupon it became yellow in color. After stirring for 30 minutes, the mixture was treated with 14 μl (0.146 mmol) dimethylsulfate and slowly warmed to room temperature while stirring for 16 hours. The reaction mixture was diluted with saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic phase was dried over sodium sulfate and concentrated to an oil. The residue was chromatographed on silica gel eluting with 6/4 ethyl acetate/hexane to afford 16 mg (50%) as a white solid. MS APCI m/e 220 (p+1)
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[CH:12][C:13]3[N:14]([CH:16]=[N:17][N:18]=3)[CH:15]=2)=[CH:6][CH:5]=1)([O-])=O>[Pd]>[NH2:1][C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[CH2:15][N:14]3[CH:16]=[N:17][N:18]=[C:13]3[CH2:12][CH2:11]2)=[CH:6][CH:5]=1
Reactant: O=[N+]([O-])c1ccc(-c2ccc3nncn3c2)cc1
Agent: [Pd]
Product: Nc1ccc(C2CCc3nncn3C2)cc1

Procedure:
6-(4-Nitrophenyl)-1,2,4-triazolo[4,3-a]pyridine is hydrogenated in the presence of palladium on carbond to give the product of the Example.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH:7]=[CH:8][C:9]([C:17]([OH:19])=O)=[C:10]2[O:13][CH:14]([CH3:16])[CH3:15])=[CH:5][CH:4]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH2:32]([NH2:39])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>C1COCC1.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH:7]=[CH:8][C:9]([C:17]([NH:39][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[O:19])=[C:10]2[O:13][CH:14]([CH3:15])[CH3:16])=[CH:5][CH:4]=1
Reactant: NCc1ccccc1
Reactant: COc1ccc2ccc(C(=O)O)c(OC(C)C)c2c1
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: COc1ccc2ccc(C(=O)NCc3ccccc3)c(OC(C)C)c2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 73 %

Procedure:
To a room temperature solution of 7-methoxy-1-(1-methylethoxy)-2-naphthalenecarboxylic acid (200 mg, 0.77 mmol) in 5 mL of THF is added N,N-carbonyldiimidazole (162 mg, 1.00 mmol). The solution is heated at reflux for 1 hour and cooled slightly. Benzylamine (0.50 mn) is added and the reaction mixture is stirred at room temperature overnight. The mixture is diluted with ethyl acetate and washed with brine. The organic layer is dried over MgSO4, filtered, and concentrated in vacuo. The crude product is chromatographed on silica gel eluting with hexane:ethyl acetate (2:1) to provide 7-methoxy-1-(1-methylethoxy)-N-(phenylmethyl)-2-naphthalene-carboxamide in 73% yield; mp 88°-90° C.