Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([CH:13]([CH3:18])[C:14]([O:16]C)=[O:15])[CH:7]=[CH:6]2.C(=O)(O)[O-].[Na+].CS(OC(C)C(OC)(OC)C1C=CC2C(=CC=C(OC)C=2)C=1)(=O)=O>CO.O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([CH:13]([CH3:18])[C:14]([OH:16])=[O:15])[CH:7]=[CH:6]2
Reactant: COC(=O)C(C)c1ccc2cc(OC)ccc2c1
Agent: COc1ccc2cc(C(OC)(OC)C(C)OS(C)(=O)=O)ccc2c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: O
Product: COc1ccc2cc(C(C)C(=O)O)ccc2c1

Procedure:
Depending on the reaction conditions, hydrolysis of an ester, ortho ester or amide formed may be effected concomitantly or sequentially by standard methods. For example, when the protic solvent medium comprises acetic acid and sodium acetate and the ester substrate comprises 1,1-dimethoxy-1-(6-methoxy-2-naphthyl)prop-2-yl methanesulfonate, there is afforded the compound, methyl 2-(6-methoxy-2-naphthyl)propionate. The methyl ester is then hydrolyzed to the corresponding acid by contact with base. Alternatively, the α-arylalkanoic acid can be obtained by concomitant hydrolysis by maintaining the ester substrate in contact with a methanol-water solution containing sodium bicarbonate. Typically, 1,1-dimethoxy-1-(6-methoxy-2-naphthyl)prop-2-yl methanesulfonate is maintained in contact with a methanol-water solution containing sodium bicarbonate to afford 2-(6-methoxy-2-naphthyl)propionic acid.
Reaction SMILES: [C:1]([O:5][C:6](=[O:29])[NH:7][CH:8]([C:12](=O)[NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[NH:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH:9]([CH3:11])[CH3:10])([CH3:4])([CH3:3])[CH3:2].[C:30](O)(=O)C>>[C:1]([O:5][C:6](=[O:29])[NH:7][CH:8]([C:12]1[N:20]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:15]2[CH:16]=[CH:17][C:18]([CH3:30])=[CH:19][C:14]=2[N:13]=1)[CH:9]([CH3:11])[CH3:10])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(=O)O
Reactant: CC(C)C(NC(=O)OC(C)(C)C)C(=O)Nc1ccccc1NCc1ccccc1
Product: Cc1ccc2c(c1)nc(C(NC(=O)OC(C)(C)C)C(C)C)n2Cc1ccccc1
Yield: 90 %

Procedure:
A solution of [1-(2-benzylamino-phenylcarbamoyl)-2-methyl-propyl]-carbamic acid tert-butyl ester (453 mg, 1.14 mmol) in acetic acid (4 ml) was heated at 100° C. for 2 hours. The solvent was removed in vacuo and the resulting solid was dissolved in ethyl acetate. The organic layer was washed with saturated NaHCO3, dried over MgSO4, filtered and the filtrate was concentrated in vacuo. The crude product was purified by flash chromatography to give of [1-(1-benzyl-5-methyl-1H-benzimidazol-2-yl)-2-methyl-propyl]-carbamic acid tert-butyl ester (389 mg, yield 90%).
Reaction SMILES: [Si:1]([O:18][C@@H:19]1[CH2:36][CH2:35][C@@:34]2([CH3:37])[C@H:21]([CH2:22][CH2:23][C@@H:24]3[C@@H:33]2[CH2:32][C@H:31]([OH:38])[C@@:29]2([CH3:30])[C@H:25]3[CH2:26][CH2:27][C@@H:28]2[CH:39]([CH3:55])[CH2:40][CH:41]=[C:42]([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH2:20]1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1(C2C=CN=CC=2)CCCC1.[CH3:67][C:68]([CH3:74])([CH2:72][CH3:73])[C:69](Cl)=[O:70]>N1C=CC=CC=1.CCOCC.CCCCCC>[Si:1]([O:18][C@@H:19]1[CH2:36][CH2:35][C@@:34]2([CH3:37])[C@H:21]([CH2:22][CH2:23][C@@H:24]3[C@@H:33]2[CH2:32][C@H:31]([O:38][C:69](=[O:70])[C:68]([CH3:74])([CH3:67])[CH2:72][CH3:73])[C@@:29]2([CH3:30])[C@H:25]3[CH2:26][CH2:27][C@@H:28]2[CH:39]([CH3:55])[CH2:40][CH:41]=[C:42]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[CH2:20]1)([C:14]([CH3:16])([CH3:15])[CH3:17])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(CC=C(c1ccccc1)c1ccccc1)[C@H]1CC[C@H]2[C@@H]3CC[C@@H]4C[C@H](O[Si](c5ccccc5)(c5ccccc5)C(C)(C)C)CC[C@]4(C)[C@H]3C[C@H](O)[C@]12C
Reactant: CCC(C)(C)C(=O)Cl
Agent: c1cc(N2CCCC2)ccn1
Solvent: CCOCC
Solvent: c1ccncc1
Solvent: CCCCCC
Product: CCC(C)(C)C(=O)O[C@H]1C[C@H]2[C@@H](CC[C@@H]3C[C@H](O[Si](c4ccccc4)(c4ccccc4)C(C)(C)C)CC[C@@]32C)[C@@H]2CC[C@H](C(C)CC=C(c3ccccc3)c3ccccc3)[C@@]12C
Temperature: 110 °C
Reaction time: 1 h

Procedure:
3α-tert-butyldiphenylsilyloxy-17β-[(1,1-diphenyl)-1-penten-4-yl]-12α-hydroxy-5β-androstane (10.6 g), 4-pyrrolidinopyridine (0.207 g) and 2,2-dimethylbutyryl chloride (2.25 g) are dissolved in pyridine (55 ml) and the solution warmed to 110° C., stirred for about 1 hour, additional 2,2-dimethylbutyryl chloride (2.25 g) is added and stirring continued for about 14 hours at 110° C. The mixture is cooled, diluted with 20% ether in hexane and washed with water, then 1M hydrochloric acid. The organic solution is dried over magnesium sulfate, filtered and concentrated in vacuo. The crude product is purified by flash chromatography in 10% ether in hexane to give the desired product.
Reaction SMILES: [NH2:1][C:2]1[N:7]2[O:8][C:9](=[O:11])[N:10]=[C:6]2[N:5]=[C:4]([N:12]([CH2:16][CH:17]=[CH2:18])[CH2:13][CH:14]=[CH2:15])[N:3]=1.[C:19](Cl)(=[O:22])[CH:20]=[CH2:21].Cl>O.C(Cl)Cl.C(N(CC)CC)C>[CH2:13]([N:12]([CH2:16][CH:17]=[CH2:18])[C:4]1[N:3]=[C:2]([NH:1][C:19](=[O:22])[CH:20]=[CH2:21])[N:7]2[O:8][C:9](=[O:11])[N:10]=[C:6]2[N:5]=1)[CH:14]=[CH2:15]
Reactant: C=CC(=O)Cl
Reactant: C=CCN(CC=C)c1nc(N)n2oc(=O)nc2n1
Agent: Cl
Solvent: O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: C=CCN(CC=C)c1nc(NC(=O)C=C)n2oc(=O)nc2n1

Procedure:
6.5 g. of 7-amino-5-diallylamino-2H-[1,2,4]oxadiazolo[2,3-a]-s-triazin-2-one are suspended in 120 ml. of methylene chloride and 8 ml. of triethylamine. 3 ml. of acrylyl chloride in 35 ml. of methylene chloride are added dropwise at 0° C. while stirring. The mixture is then stirred for 2 hours, diluted with 100 ml. of water and adjusted to pH 4 with 2-N hydrochloric acid. The two phases are separated and the aqueous phase is extracted with methylene chloride. The combined organic extracts are dried over sodium sulfate and evaporated to dryness under reduced pressure. The residue is chromatographed over silica gel using methylene chloride and methanol for the elution and the desired substance is recrystallized from methylene chloride and diethyl ether, there being obtained pure N-{5-diallylamino-2-oxo-2H-[1,2,4]oxadiazolo[2,3-a]-s-triazin-7-yl}acrylamide having a melting point of 157°-161° C.
Reaction SMILES: [N+:1]([C:4]1[N:8]=[CH:7][NH:6][N:5]=1)([O-:3])=[O:2].[Cl:9][C:10]1[C:11](=[O:19])[NH:12][C:13](=[O:18])[NH:14][C:15]=1[CH2:16]Cl.Cl>[OH-].[K+]>[Cl:9][C:10]1[C:11](=[O:19])[NH:12][C:13](=[O:18])[NH:14][C:15]=1[CH2:16][N:6]1[CH:7]=[N:8][C:4]([N+:1]([O-:3])=[O:2])=[N:5]1
Reactant: O=[N+]([O-])c1nc[nH]n1
Reactant: O=c1[nH]c(CCl)c(Cl)c(=O)[nH]1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Product: O=c1[nH]c(Cn2cnc([N+](=O)[O-])n2)c(Cl)c(=O)[nH]1
Temperature: 80 °C
Yield: 73 %

Procedure:
To a solution of 0.88 g of 3-nitro-1,2,4-triazole in a 1 N aqueous solution of KOH (10 ml), 0.50 g of 5-chloro-6-chloromethyluracil was added, followed by heating at 80° C. for 2.5 hours under stirring. The reaction mixture was neutralized with 6 N hydrochloric acid. A precipitate was collected by filtration and then washed with water and methanol, whereby 510 mg of the title compound were obtained (yield: 73%).
Reaction SMILES: [F:1][C:2]([F:8])([F:7])[CH2:3][CH2:4][CH2:5][OH:6].[CH3:9][S:10](Cl)(=[O:12])=[O:11]>C(Cl)Cl>[CH3:9][S:10]([O:6][CH2:5][CH2:4][CH2:3][C:2]([F:8])([F:7])[F:1])(=[O:12])=[O:11]
Reactant: OCCCC(F)(F)F
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Product: CS(=O)(=O)OCCCC(F)(F)F
Temperature: 25 °C
Reaction time: 1 h
Yield: 0.3 %

Procedure:
To a solution of 4,4,4-trifluorobutan-1-ol (100 mg, 83 mmol) in dry DCM (2 mL) was added methanesulfonyl chloride (107.3 mg, 72 mmol) and then by TEA (158 mg, 216 mmol) at 0° C. The reaction was stirred at room temperature for 1 h. The reaction was partitioned between ethyl acetate and water. The organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated to give a yellow oil product (50 mg, 31.1% yield), which was used without purification. Product tlc [petroleum ether/ethyl acetate (3:1) Rf 0.4]
Reaction SMILES: Cl[C:2]1[N:11]=[CH:10][C:9]2[C:4](=[C:5]([O:12][CH3:13])[CH:6]=[CH:7][CH:8]=2)[N:3]=1.[F:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[C:16]=1B(O)O.CCN(C(C)C)C(C)C.[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].C(Cl)Cl.C(O)C.C1(C)C=CC=CC=1>[F:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[C:16]=1[C:2]1[N:11]=[CH:10][C:9]2[C:4](=[C:5]([O:12][CH3:13])[CH:6]=[CH:7][CH:8]=2)[N:3]=1
Reactant: COc1cccc2cnc(Cl)nc12
Reactant: OB(O)c1c(F)cccc1F
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: [Cl-]
Solvent: ClCCl
Solvent: CCO
Solvent: CCN(C(C)C)C(C)C
Product: COc1cccc2cnc(-c3c(F)cccc3F)nc12
Temperature: 130 °C
Reaction time: 0.5 h

Procedure:
2-chloro-8-methoxyquinazoline (1.0 eq), 2,6-difluorophenylboronic acid (1.5 eq), and DIPEA (3 eq) was mixed with toluene and ethanol (1:1, 0.5M) in a microwave vial. The reaction mixture was degassed by anhydrous N2 stream for 5 min followed by the addition of Pd(dppf)Cl2-DCM (0.1 eq). The reaction mixture was stirred at 130° C. for 30 min in microwave. Solvents were removed under reduced pressure. The crude product was purified by column (ethyl acetate:hexanes=1:1) to give the mixture of starting material chloride and desired product. The mixture was treated with 1N HCl in 1,4-dioxane. Solvents were removed under reduced pressure. The residue was dissolved in ethyl acetate (150 mL), and washed with NaHCO3, brine, then dried over MgSO4, filtered, and evaporated under reduced pressure to give crude product, which was purified by column (ethyl acetate:hexanes=1:1) to yield 2-(2,6-difluorophenyl)-8-methoxyquinazoline (46%). LC/MS (m/z): 273.0 (MH+), Rt=0.78.
Reaction SMILES: Cl.[CH3:2][O:3][C:4]([C:6]1[N:7]([CH3:13])[C:8]([CH2:11]Cl)=[N:9][CH:10]=1)=[O:5].[CH3:14][O:15][CH2:16][CH2:17][NH:18][CH3:19]>>[CH3:2][O:3][C:4]([C:6]1[N:7]([CH3:13])[C:8]([CH2:11][N:18]([CH2:17][CH2:16][O:15][CH3:14])[CH3:19])=[N:9][CH:10]=1)=[O:5]
Reactant: CNCCOC
Reactant: COC(=O)c1cnc(CCl)n1C
Agent: Cl
Product: COCCN(C)Cc1ncc(C(=O)OC)n1C

Procedure:
Using 2-chloromethyl-3-methyl-3H-imidazole-4-carboxylic acid methyl ester hydrochloride and (2-methoxy-ethyl)-methyl-amine, the title compound was obtained as light brown viscous oil (92% yield). MS: m/e=242(M+H+).
Reaction SMILES: B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Br[C:25]1[CH:26]=[N:27][C:28]([N:31]2[C:39]3[C:34](=[CH:35][CH:36]=[C:37]([C:40]([N:42]4[CH2:46][CH2:45][CH2:44][CH2:43]4)=[O:41])[CH:38]=3)[C:33]([S:47][CH3:48])=[CH:32]2)=[N:29][CH:30]=1.Br[C:50]1[CH:55]=[C:54]([CH:56]2[CH2:58][CH2:57]2)[CH:53]=[CH:52][N:51]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.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].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:56]1([C:54]2[CH:53]=[CH:52][N:51]=[C:50]([C:25]3[CH:30]=[N:29][C:28]([N:31]4[C:39]5[C:34](=[CH:35][CH:36]=[C:37]([C:40]([N:42]6[CH2:43][CH2:44][CH2:45][CH2:46]6)=[O:41])[CH:38]=5)[C:33]([S:47][CH3:48])=[CH:32]4)=[N:27][CH:26]=3)[CH:55]=2)[CH2:58][CH2:57]1
Reactant: Brc1cc(C2CC2)ccn1
Reactant: CSc1cn(-c2ncc(Br)cn2)c2cc(C(=O)N3CCCC3)ccc12
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: C1COCCO1
Product: CSc1cn(-c2ncc(-c3cc(C4CC4)ccn3)cn2)c2cc(C(=O)N3CCCC3)ccc12
Temperature: 110 °C
Reaction time: 1 h

Procedure:
Bis(pinacolato)diboron (0.584 g, 2.3 mmol) and potassium acetate (0.421 g, 4.29 mmol) were added at room temperature to a solution of 341a) (0.6 g, 1.43 mmol) in dry dioxane (35 mL). The reaction apparatus was flushed with argon, PdCl2(dppf) (58 mg, 0.071 mmol) was added and the resulting mixture was stirred for 1 h at 110° C. (complete consumption of starting material). 2-bromo-4-cyclopropyl-pyridine (0.328 g, 2.14 mmol), potassium carbonate (2M, 2.5 mL) and tetrakis(triphenylphosphine)palladium(0) (83 mg, 0.071 mmol) were added successively and the reaction mixture was stirred for 16 h at 100° C. The mixture was then cooled to ambient temperature and filtered through a sintered funnel. The filtrate was concentrated and the remnant was purified by flash column chromatography [silica; dichloromethane with 2% methanol]. White solid. Yield: 0.28 g (43% of theory)
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]3[CH:37]=[CH:36][C:17]([O:18][CH2:19][C:20]([C:28]4[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][C:29]=4[Cl:35])([OH:27])[CH2:21][N:22]4[CH:26]=[N:25][CH:24]=[N:23]4)=[CH:16][CH:15]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:45](Cl)(=[O:47])[CH3:46]>C(Cl)Cl>[C:45]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]3[CH:37]=[CH:36][C:17]([O:18][CH2:19][C:20]([C:28]4[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][C:29]=4[Cl:35])([OH:27])[CH2:21][N:22]4[CH:26]=[N:25][CH:24]=[N:23]4)=[CH:16][CH:15]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1)(=[O:47])[CH3:46]
Reactant: Nc1ccc(N2CCN(c3ccc(OCC(O)(Cn4cncn4)c4ccc(Cl)cc4Cl)cc3)CC2)cc1
Reactant: CC(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)Nc1ccc(N2CCN(c3ccc(OCC(O)(Cn4cncn4)c4ccc(Cl)cc4Cl)cc3)CC2)cc1
Reaction time: 1 h

Procedure:
To a solution of 3-(4-[4-(4-aminophenyl)piperazin-1-yl]phenoxy)-2-(2,4-dichlorophenyl)-1-(1H-1,2,4-triazol-1-yl)propan-2-ol (see Preparation 1) (0.2 g, 0.37 mmole) and triethylamine (0.1 g, 1 mmole) in methylene chloride (20 ml) at 0° was added, dropwise, a solution of acetyl chloride (0.1 g, 1.2 mmole) in methylene chloride (1 ml). After completion of the addition the mixture was stirred at 0° for a further 1 hour and then partitioned between ethyl acetate and sodium bicarbonate solution. The separated organic phase was dried over magnesium sulphate and concentrated under reduced pressure to give a gum which on trituration with ethyl acetate yielded the desired product as a pale yellow solid, m.p. 169°-171° (0.098 g, 45%).
Reaction SMILES: [F:1][C:2]1[CH:31]=[CH:30][C:5]([C:6]([NH:8][C:9]([CH3:29])([CH3:28])[C:10]([NH:12][C:13]2[S:14][C:15]([C:25]([OH:27])=O)=[C:16]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[N:17]=2)=[O:11])=[O:7])=[CH:4][CH:3]=1.[CH:32]1([C:35]([NH:37][NH2:38])=O)[CH2:34][CH2:33]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CC[N+](S(N=C(OC)[O-])(=O)=O)(CC)CC>C1COCC1>[CH:32]1([C:35]2[O:27][C:25]([C:15]3[S:14][C:13]([NH:12][C:10]([C:9]([NH:8][C:6](=[O:7])[C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:31][CH:30]=4)([CH3:29])[CH3:28])=[O:11])=[N:17][C:16]=3[C:18]3[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=3)=[N:38][N:37]=2)[CH2:34][CH2:33]1
Reactant: CC(C)(NC(=O)c1ccc(F)cc1)C(=O)Nc1nc(-c2ccc(F)cc2)c(C(=O)O)s1
Reactant: NNC(=O)C1CC1
Agent: CC[N+](CC)(CC)S(=O)(=O)N=C([O-])OC
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: C1CCOC1
Product: CC(C)(NC(=O)c1ccc(F)cc1)C(=O)Nc1nc(-c2ccc(F)cc2)c(-c2nnc(C3CC3)o2)s1
Temperature: 150 °C

Procedure:
To a stirred solution of 2-(2-(4-Fluorobenzamido)-2-methylpropanamido)-4-(4-fluorophenyl)thiazole-5-carboxylic acid (100 mg, 0.224 mmol) and cyclopropanecarbohydrazide (27 mg, 0.27 mmol) were added HATU (128 mg, 0.34 mmol) and TEA (78 uL, 0.56 mmol). Volatiles were removed in vacuo. The residue was taken up in EtOAc and washed with 1N HCl (2×10 mL) followed by sat. NaHCO3 (2×10 mL). Organic layer was dried over magnesium sulfate and filtered. The filtrate was concentrated to dryness to afford a solid. The solid was dissolved in THF (5 mL) and treated with Burgess reagent (68 mg, 0.28 mmol) and heated in microwave at 150° C. for 30 minutes. Purification by silica gel chromatography (30-45% EtOAc/Heptanes) gave the title compound. 1H NMR (400 MHz, DMSO-d6) 0.82 (dd, J=4.74, 2.59 Hz, 3H) 1.08 (dd, J=8.34, 2.78 Hz, 3H) 2.19 (s, 1H) 7.33 (t, J=8.91 Hz, 3H) 7.25 (t, J=8.91 Hz, 3H) 7.71 (dd, J=8.84, 5.56 Hz, 3H) 8.03 (dd, J=8.78, 5.62 Hz, 3H) 8.65 (s, 1H) 12.61 (s, 1H). MS m/z 510.4 (M+H), 508.4 (M−1). HRMS cald for C25H18N2O4S=509.1333, found=509.1334. (M+H)+ 510.4, Rt=1.37 min, method A.
Reaction SMILES: C([O:4][C:5]1[C:6]2[C:11]([CH:12]=[C:13]([O:17][CH3:18])[C:14]=1[O:15][CH3:16])=[N:10][C:9](=[O:19])[C:8](=[O:20])[N:7]=2)(=O)C.[OH-].[Na+].Cl>O>[OH:4][C:5]1[C:6]2[C:11]([CH:12]=[C:13]([O:17][CH3:18])[C:14]=1[O:15][CH3:16])=[N:10][C:9](=[O:19])[C:8](=[O:20])[N:7]=2
Reactant: COc1cc2c(c(OC(C)=O)c1OC)=NC(=O)C(=O)N=2
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: COc1cc2c(c(O)c1OC)=NC(=O)C(=O)N=2
Yield: 91 %

Procedure:
5-Acetyloxy-6,7-dimethoxy-2,3-quinoxalinedione (47) (30 mg, 0.107 mmol) was added to a single-necked 15-mL flask. Sodium hydroxide aqueous solution (2 N, 1 mL) was added to the flask under nitrogen with stirring. The solution was then stirred at room temperature for 24 h. The solution was diluted with water (3 mL) and then acidified with HCl (4 N, 1 mL) to pH=2 to give a brown solid, which was collected by filtration and dried in vacuo, giving 23 mg (86%) of the title compound; mp 285-286° C. (dec); 1H NMR (DMSO-d6, 300 MHz) δ 3.688 (s, 3H), 3.694 (s, 3H), 6.227 (s, 1H), 9.769 (s, 1H), 11.016 (s, 1H), 11.658 (s, 1H). EIMS m/e 238 (100, M+), HPLC purity>96%.
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16]1[N:17]=[C:18]2[C:23](Br)=[CH:22][CH:21]=[CH:20][N:19]2[CH:25]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:26][O:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16]1[N:17]=[C:18]2[C:23]([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=3[O:27][CH3:26])=[CH:22][CH:21]=[CH:20][N:19]2[CH:25]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(OCc1ccccc1)N1CCC[C@H]1c1cn2cccc(Br)c2n1
Reactant: COc1ccccc1B(O)O
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [K+]
Product: COc1ccccc1-c1cccn2cc([C@@H]3CCCN3C(=O)OCc3ccccc3)nc12
Yield: 101.6 %

Procedure:
Following the procedures of example 14, (S)-benzyl-2-(8-bromoimidazo[1,2-a]pyridin-2-yl)pyrrolidine-1-carboxylate (0.250 g, 0.62 mmol), 2-methoxyphenyl boronic acid (0.1231 g, 0.81 mmol), potassium carbonate (0.1292 g, 0.93 mmol), and tetrakis(triphenylphosphine)-palladium(0) (0.0360 g, 0.03 mmol) produced the crude material which was adsorbed onto silica gel and purified by flash chromatography (4 g SiO2, 0-100% ethyl acetate in hexanes) to give (2S)-benzyl-2-(8-(2-methoxyphenyl)imidazo[1,2-a]pyridin-2-yl)pyrrolidine-1-carboxylate (0.269 g, 0.63 mmol, 78%).
Reaction SMILES: [CH3:1][NH:2][C:3]1[C:4]([C:15]([O:17]C)=O)=[N:5][C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:7][N:8]=1.[NH3:19]>CO>[CH3:1][NH:2][C:3]1[C:4]([C:15]([NH2:19])=[O:17])=[N:5][C:6]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)=[CH:7][N:8]=1
Reactant: N
Reactant: CNc1ncc(-c2ccccc2)nc1C(=O)OC
Solvent: CO
Product: CNc1ncc(-c2ccccc2)nc1C(N)=O
Temperature: 82.5 °C
Yield: 25 %

Procedure:
A solution of of methyl 3-(methylamino)-6-phenylpyrazine-2-carboxylate (31 mg, 0.13 mmol) in methanol (5 ml) was saturated with ammonia at 0° C. The pressure tube was sealed and heated at 80-85° C. overnight. The reaction was cooled to room temperature and the solvent removed at reduced pressure to afford crude solid product. Reverse-phase BPLC purification gave 3-(methylamino)-6-phenylpyrazine-2-carboxamide (7 mg, 25% yield) as a yellow solid: 1H NM (400 MHz, CDCl3): δ 8.42 (s, 1H), 8.50 (br s, 1H), 7.90 (d, 3H), 7.45 (m, 2H), 7.40 (m, 1H), 3.10 (br s, 3H); MS (EI) for C12H12N40: 229 (MH+).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8]Br)=[CH:4][CH:3]=1.[NH:10]1[CH:14]=[CH:13][N:12]=[N:11]1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:11]2[N:12]=[CH:13][CH:14]=[N:10]2)=[CH:4][CH:3]=1
Reactant: BrCc1ccc(Br)cc1
Reactant: c1c[nH]nn1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Brc1ccc(Cn2nccn2)cc1
Temperature: 50 °C

Procedure:
1-bromo-4-(bromomethyl)benzene (300 mg, 1.200 mmol), 1H-1,2,3-triazole (84 μl, 1.440 mmol), and potassium carbonate (332 mg, 2.401 mmol) were taken up in dimethylformamide (1500 μl) and heated to 50° C. overnight. The reaction was quenched with water and extracted using ethyl acetate. The organic layers were combined, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. Purification was performed via silica gel chromatography (50-100% ethyl acetate in hexanes) to yield the title compound.
Reaction SMILES: [CH2:1]([Cl:4])[CH:2]=[CH2:3].[CH2:5]([SiH:8]([Cl:10])[Cl:9])[CH:6]=[CH2:7]>>[Cl:9][Si:8]([Cl:10])([CH2:3][CH2:2][CH2:1][Cl:4])[CH2:5][CH:6]=[CH2:7]
Reactant: C=CCCl
Reactant: C=CC[SiH](Cl)Cl
Product: C=CC[Si](Cl)(Cl)CCCCl
Yield: 61.5 %

Procedure:
To a 100 ml, three neck, round bottomed flask equipped with a mechanical stirrer, a dropping funnel, and a condenser were added under the dried nitrogen atmosphere, 542 g (7.08 mol) of allyl chloride and 600 μl of 1% chloroplatinie acid catalyst. Through the dropping funnel was added dropwise 100 g (0.71 mol) of allyldichlorosilane for 30 min while refluxing. After confirming by gas chromatography to complete the reaction, the product was fractionally distilled under vacuum (60°-64° C./0.5 torr) to give 95 g (62.5 % ) of 4,4,7-trichloro-4-sila-1-heptene. Allyltrichlorosilane 30.0 g (19.7 % ) was also obtained as a by-product.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:8]=[C:9]2[C:14]=1[O:13][C:12](=[O:15])[CH:11]=[CH:10]2)=[O:4].C(O[CH2:28][C:29](=[CH2:35])[CH2:30][Si](C)(C)C)(=O)C.P(OC(C)C)(OC(C)C)OC(C)C>C1COCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:8]=[C:9]2[C:14]=1[O:13][C:12](=[O:15])[CH:11]1[CH2:30][C:29](=[CH2:28])[CH2:35][CH:10]21)=[O:4]
Reactant: COC(=O)c1cc(OCc2ccccc2)cc2ccc(=O)oc12
Reactant: C=C(COC(C)=O)C[Si](C)(C)C
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)OP(OC(C)C)OC(C)C
Solvent: C1CCOC1
Product: C=C1CC2C(=O)Oc3c(C(=O)OC)cc(OCc4ccccc4)cc3C2C1
Temperature: 60 °C
Reaction time: 8 h

Procedure:
To a solution of preparation 4 (198 mg, 0.64 mmol) and Pd(OAc)2 (17 mg, 0.076 mmol) in 4 mL THF add 2-(acetoxymethyl)allyl-trimethylsilane (0.163 mL, 0.122 mmol) followed by triisopropyl phosphite (0.12 mL, 0.49 mmol). After stirring at 60° C. overnight, cool the solution to room temperature, concentrate under reduced pressure, and dilute with EtOAc. Wash the solution with saturated aqueous sodium bicarbonate and brine. Dry over Na2SO4, and then concentrate to an oil. Purify the material by silica gel chromatography (10 g, 10 to 30% EtOAc/Hex over 30 min at 35 mL/min) to give 80 mg (0.208 mol, 63%) of preparation 6 and 30 mg (0.091 mmol, 27%) of recovered starting material. 1H NMR (400 MHz, CDCl3) δ 7.48-7.36 (m, 6H), 7.01 (d, 1H, J=3.1 Hz), 5.10 (s, 2H), 5.01 (m, 2H), 3.97 (s, 3H), 3.43 (dt, 1H, J=7.5, 3.1 Hz), 3.21-3.10 (m, 2H), 2.86-2.74 (m, 2H), 2.43 (m, 1H).