Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[CH2:2][C:3]1[O:7][N:6]=[C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)[N:4]=1.[Cl:21][C:22]1[CH:23]=[C:24]([NH:29][C:30]2[C:39]3[C:34](=[CH:35][C:36]([OH:42])=[C:37]([O:40][CH3:41])[CH:38]=3)[N:33]=[CH:32][N:31]=2)[CH:25]=[CH:26][C:27]=1[Cl:28].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:21][C:22]1[CH:23]=[C:24]([NH:29][C:30]2[C:39]3[C:34](=[CH:35][C:36]([O:42][CH2:2][C:3]4[O:7][N:6]=[C:5]([N:8]5[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]5)[N:4]=4)=[C:37]([O:40][CH3:41])[CH:38]=3)[N:33]=[CH:32][N:31]=2)[CH:25]=[CH:26][C:27]=1[Cl:28]
Reactant: CC(C)(C)OC(=O)N1CCN(c2noc(CCl)n2)CC1
Reactant: COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1nc(N2CCN(C(=O)OC(C)(C)C)CC2)no1
Temperature: 50 °C
Yield: 61.6 %

Procedure:
1,1-dimethylethyl 4-[5-(chloromethyl)-1,2,4-oxadiazol-3-yl]piperazine-1-carboxylate (173.6 mg, 0.57 mmol), 4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-ol (154 mg, 0.46 mmol) and potassium carbonate (315 mg, 2.85 mmol) were taken into DMF (2 mL) and the mixture was heated to 50° C. for one hour. The mixture was then cooled to room temperature and partitioned with ethyl acetate and water. The organic layer was washed once more with water and the organic layer was partitioned again with water. A precipitate forms in the organic layer at this point and hexanes was added to the biphasic mixture in portions until formation of the precipitate is complete. The solid product was then collected by filtration. The solid residue was suspended in hot methanol and diluted with water followed by collection of the solid by filtration. The solid was washed with ethyl ether and dried in vacuo to give 1,1-dimethylethyl 4-[5-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-1,2,4-oxadiazol-3-yl]piperazine-1-carboxylate (170.7 mg, 62% yield) as a tan solid. 1H-NMR (400 MHz, DMSO-d6): 9.65 (s, 1H), 8.54 (s, 1H), 8.23 (d, 1H), 7.88-7.86 (m, 2H), 7.63 (d, 1H), 7.32 (s, 1H), 5.58 (s, 2H), 3.98 (s, 3H), 3.43-3.40 (m, 4H), 3.34-3.32 (m, 4H), 1.41 (s, 9H); MS (EI) for C27H29Cl2N7O5: 602 (MH+).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)O)=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[CH3:25][O:26][C:27]([O:31][Si](C)(C)C)=[C:28]([CH3:30])[CH3:29]>C1COCC1.Cl[Ti](Cl)(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[C:28]([CH3:30])([CH3:29])[C:27]([O:26][CH3:25])=[O:31])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1
Reactant: COC(O[Si](C)(C)C)=C(C)C
Reactant: OC(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1
Agent: Cl[Ti](Cl)(Cl)Cl
Solvent: C1CCOC1
Product: COC(=O)C(C)(C)C(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1
Reaction time: 0.5 h
Yield: 80.5 %

Procedure:
(1-(4-Fluorophenyl)-1H-indazol-5-yl)(phenyl)methanol (16.0 g, 50 mmol) was dissolved in 400 mL of dry THF and TiCl4 (60 mL of 1.0 M DCM solution, 60 mmol) was added portionwise and then stirred 30 min. The flask was put on a rotary evaporator until the THF began to distill to degas the HCl and then the reaction was treated with 1-methoxy-2-methyl-1-(trimethylsiloxy)propene (17.4 g, 100 mmol). The reaction was quenched with aqueous sodium bicarbonate and extracted 2× EtOAc, the organic layers dried over MgSO4, filtered, concentrated, and then chromatographed using DCM to give 16.2 g (81% yield) of methyl 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropanoate. MS found: (M+H)+=403.
Reaction SMILES: C(OC([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]#[N:29])=[CH:24][CH:23]=2)=[CH:17][CH:16]=1)=O)(C)(C)C.[ClH:30]>O1CCOCC1>[ClH:30].[NH:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]#[N:29])=[CH:24][CH:23]=2)=[CH:17][CH:16]=1
Reactant: CC(C)(C)OC(=O)N1CCCC1COc1ccc(Oc2ccc(C#N)cc2)cc1
Agent: Cl
Solvent: C1COCCO1
Product: N#Cc1ccc(Oc2ccc(OC[C@H]3CCCN3)cc2)cc1
Yield: 85 %

Procedure:
Following the general procedure for Example 11 (step 4), the product from step 3 (0.3 g, 0.76 mmol) was treated with 4M HCl in dioxane (5 mL) to afford the title compound (0.21 g, 85%) as a white solid; 1H NMR (400 MHz, DMSO-d6) 1.75 (m, 1H), 1.88-2.02 (m, 2H), 2.12 (m, 1H), 3.22 (m, 2H), 3.90 (m, 1H), 4.17 (m, 1H), 4.27 (dd, J1=3.8 Hz, J2=10.8 Hz, 1H), 7.03 (d, J=9.2 Hz, 2H), 7.09 (m, 2H), 7.15 (m, 2H), 7.82 (d, J=8.8 Hz, 2H), 9.10 (br s, 1H), 9.65 (br s, 1H); MS (m/z) 295.5 (M+1); LC (95.1%),
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:15]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[CH:18]=2)O)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P([N:38]=[N+:39]=[N-:40])(C2C=CC=CC=2)=O)C=CC=CC=1.N12CCCN=C1CCCCC2>C1(C)C=CC=CC=1>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:15]([N:38]=[N+:39]=[N-:40])[C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[CH:18]=2)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Reactant: OC(c1cccc(Cl)c1)c1cccc(OCc2ccccc2)c1
Solvent: Cc1ccccc1
Solvent: C1CCC2=NCCCN2CC1
Product: [N-]=[N+]=NC(c1cccc(Cl)c1)c1cccc(OCc2ccccc2)c1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a stirred solution of (3-benzyloxyphenyl)(3-chlorophenyl)methanol, as described above in Step A, (4.0 g, 12.3 mmol) and diphenylphosphoryl azide (4.1 g, 14.9 mmol) in dry toluene (35 mL) at 0° C., was added 1,8-diazabicyclo[5.4.0]undec-7-ene (2.1 g, 13.8 mmol). The resulting mixture was allowed to warm to ambient temperature, and stirred under argon for 18 hours, then washed with 5% hydrochloric acid (10 mL). The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by flash column chromatography on silica, eluting with hexane—2% EtOAc to yield the product as a colorless oil.
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]([NH:11][C:12](=[O:14])[CH3:13])([CH3:10])[CH3:9])=[CH:4][CH:3]=1.[CH3:15][O:16][C:17]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][CH:18]=1.C([O-])([O-])=O.[Na+].[Na+]>CC(N(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>[CH3:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([C:2]2[N:7]=[CH:6][C:5]([C:8]([NH:11][C:12](=[O:14])[CH3:13])([CH3:10])[CH3:9])=[CH:4][CH:3]=2)=[CH:19][CH:18]=1
Reactant: CC(=O)NC(C)(C)c1ccc(Cl)nc1
Reactant: COc1ccc(B(O)O)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(=O)N(C)C
Product: COc1ccc(-c2ccc(C(C)(C)NC(C)=O)cn2)cc1
Temperature: 90 °C

Procedure:
The product from Step B, 1-B, (37.11 g, 174 mmol), 4-methoxyphenylboronic acid (47.7 g, 314 mmol) and bis(triphenylphosphine)palladium(II) chloride (6.12 g, 8.72 mmol) were suspended in DMA (325 mL) and aq. 2.0 M Na2CO3 (288 mL, 576 mmol). The atmosphere of the reaction vessel was evacuated/purged with N2 (3×) and the reaction mixture was heated at 90° C. over 3 h. The reaction mixture was cooled to rt and partitioned between EtOAc and H2O. The organic layer was separated, washed with H2O, saturated aq. NaCl, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was suspended in CH2Cl2 and the solid were isolated by vacuum filtration and dried under high vacuum. Alternative work-up: The reaction mixture was cooled to rt and diluted with H2O (1.85 L). The solids were collected by vacuum filtration rinsing with hexanes and dried under high vacuum. HPLC/MS: 285.0 (M+1); Rt=1.53 min.
Reaction SMILES: [OH:1][N:2]1[C:6](=[O:7])[C:5]2=[CH:8][CH:9]=[CH:10][CH:11]=[C:4]2[C:3]1=[O:12].[CH2:13](Br)[C:14]#[CH:15].C(N(CC)CC)C>CN(C=O)C>[CH2:15]([O:1][N:2]1[C:3](=[O:12])[C:4]2[C:5](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]1=[O:7])[C:14]#[CH:13]
Reactant: O=C1c2ccccc2C(=O)N1O
Reactant: C#CCBr
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: C#CCON1C(=O)c2ccccc2C1=O
Temperature: 25 °C
Reaction time: 4 h
Yield: 76.3 %

Procedure:
To a stirred solution of N-hydroxyphthalimide (50.5 g) and propargyl bromide (37.0 g) in DMF (250 ml) at 0° C. was added drop-wise triethylamine (50 ml). The cooling bath was removed and the reaction mixture was stirred at room temperature for 4 hours. The mixture was poured into water containing some ice and the precipitated material was isolated by filtration. The crude product was recrystallised from ethanol and gave 2-prop-2-ynyloxy-isoindole-1,3-dione (47.5 g). Step 2: The above obtained phthalimide intermediate (1 mmol) was mixed with p-tolyl isocyanate (2.8 mmol), triethylamine (0.05 mmol) and 1-nitrobutane (1.44 mmol) in toluene (3 ml). The reaction mixture was stirred at room temperature for 48 hours, filtrated and subjected to column chromatography on silica, affording 2-(3-propyl-isoxazol-5-ylmethoxy)-isoindole-1,3-dione. Step 3: The above cycloaddition product was dissolved in methanol+dichloromethane and hydrazine monohydrate (1 eq.) was added. The reaction mixture was stirred at room temperature for 20 hours and placed at 5° C. for 3 hours. The solid material was removed by filtration and the filtrate was evaporated under reduced pressure and gave the title compound. 13C-NMR (DMSO-d6) δ 169.0, 163.2, 103.0, 67.4, 27.2, 21.0, 13.5.
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.C([Li])CCC.[CH3:13][O:14][C:15]1[C:22]([CH3:23])=[C:21]([CH3:24])[C:20]([O:25][CH3:26])=[C:19]([CH3:27])[C:16]=1[CH2:17]Br>C(OCC)C.O>[CH3:26][O:25][C:20]1[C:21]([CH3:24])=[C:22]([CH3:23])[C:15]([O:14][CH3:13])=[C:16]([CH3:17])[C:19]=1[CH2:27][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1
Reactant: Brc1cccnc1
Reactant: COc1c(C)c(C)c(OC)c(CBr)c1C
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: O
Product: COc1c(C)c(C)c(OC)c(Cc2cccnc2)c1C
Yield: 85.7 %

Procedure:
A solution of 15.5 g (98.1 mmol) of 3-bromopyridine in 200 ml of ethyl ether was cooled to -78° C., to which 61.3 ml (98.1 mmol) of n-butyllithium (1.6M hexane solution) was added dropwise. For 20 minutes after completion of the addition, the mixture was stirred at the same temperature, and then a solution of 26.8 g (98.1 mmol) of 2,5-dimethoxy-3,4,6-trimethylbenzyl bromide in 100 ml of ethyl ether was added dropwise. After stirring at 78° C. to room temperature for 1 hour, the reaction mixture was diluted with water and extracted with ethyl acetate. Then the extract was extracted reversely with 2N-hydrochloric acid, and the water layer was made weakly alkaline with a saturated aqueous solution of sodium hydrogen carbonate and extracted with ethyl acetate. The extract was washed with water, dried, and concentrated. The residue was purified with silica gel column chromatography (ethyl acetate), to give 22.8 g (85.8%) of 3-(2,5-dimethoxy-3,4,6-trimethylbenzyl)pyridine.
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][CH:11]=[C:10]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=2)[CH2:9]1)C1C=CC=CC=1.Cl[C:23]([O:25][CH2:26][CH3:27])=[O:24]>C1C=CC=CC=1>[CH3:21][O:20][C:16]1[CH:15]=[C:14]([C:10]2[CH2:9][N:8]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:13][CH2:12][CH:11]=2)[CH:19]=[CH:18][CH:17]=1
Reactant: CCOC(=O)Cl
Reactant: COc1cccc(C2=CCCN(Cc3ccccc3)C2)c1
Solvent: c1ccccc1
Product: CCOC(=O)N1CCC=C(c2cccc(OC)c2)C1

Procedure:
A solution of 11.4 g of the product of Step B, 25 ml of benzene and 5.9 ml of ethyl chloroformate was refluxed for 3 hours and was then evaporated to dryness under reduced pressure. Excess ethyl chloroformate was entrained with benzene to obtain 11 g of ethyl 3-(3-methoxyphenyl)-1,2,5,6-tetrahydro-1-pyridine-carboxylate.
Reaction SMILES: [OH-].[K+:2].[Cl:3][C:4]1[C:8]([Cl:9])=[C:7]([C:10]([OH:12])=[O:11])[S:6][N:5]=1>O.C(O)C>[Cl:3][C:4]1[C:8]([Cl:9])=[C:7]([C:10]([O-:12])=[O:11])[S:6][N:5]=1.[K+:2]
Reactant: O=C(O)c1snc(Cl)c1Cl
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: O=C([O-])c1snc(Cl)c1Cl

Procedure:
Potassium hydroxide (0.27 g) dissolved in 3 ml of water was added to a solution of 3,4-dichloroisothiazole-5-carboxylic acid (0.95 g) in 4 ml of ethanol. The solvent was distilled off under reduced pressure. The crystals thus obtained were washed with a small quantity of ethanol.
Reaction SMILES: [CH2:1]1[NH:3][CH2:2]1.[CH2:4]1[O:12][CH:5]1[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[OH-].[K+]>O>[C:6]1([CH:5]([OH:12])[CH2:4][N:3]2[CH2:2][CH2:1]2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: c1ccc(C2CO2)cc1
Reactant: C1CN1
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: OC(CN1CC1)c1ccccc1

Procedure:
To a solution of 43.0 g. (1.0 mole) of ethyleneimine and 60.0 g. (0.5 mole) of styrene oxide is added 3 drops of water and 0.2 g. of potassium hydroxide. The mixture is heated at reflux for 11/2 hours. Distillation of the excess ethyleneimine from the crude product gives 55.6 g. (68%) of the crystalline product. Recrystallization gives pure dl-α-phenyl-1-aziridineethanol with melting point 74°-76° C.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[NH:12][C:11](=O)[C:10]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=2)=[N:9][N:8]=1.S(Cl)(Cl)=O.[C:28]1([CH2:34][SH:35])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(N(CC)CC)C>C(Cl)Cl.O1CCCC1>[CH2:34]([S:35][C:11]1[N:12]=[C:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)[N:8]=[N:9][C:10]=1[C:14]1[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
Reactant: O=c1[nH]c(-c2ccccn2)nnc1-c1ccc(C(F)(F)F)cc1
Reactant: SCc1ccccc1
Solvent: CCN(CC)CC
Solvent: O=S(Cl)Cl
Solvent: ClCCl
Product: FC(F)(F)c1ccc(-c2nnc(-c3ccccn3)nc2SCc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 92.7 %

Procedure:
A mixture of 3-(2-pyridyl)-6-(4-trifluoromethylphenyl)-1,2,4-triazin-5-one (200 mg, 0.63 mmol) and thionyl chloride (5 ml) was heated under reflux for 30 minutes. The mixture was allowed to cool to room temperature, and the solvent was distilled off. To the residue were added tetrahydrofuran (4 ml), phenyl methanethiol (195 mg, 1.57 mmol, 2.5 eq.), and triethylamine (159 mg, 1.57 mmol, 2.5 eq.), and the mixture was stirred at room temperature for one hour. To the reaction mixture was added methylene chloride (50 ml), and the mixture was washed with water (20 ml), a saturated aqueous sodium hydrogen carbonate solution (20 ml) and a saturated brine (20 ml). The organic layer was dried over magnesium sulfate, filtered, and concentrated under reduced pressure to remove the solvent. The resulting solid was purified by flash silica gel column chromatography (chloroform) to give the title compound (248 mg, 93%) as pale yellow crystals.
Reaction SMILES: [C:1](=O)([O-])[O-].[K+].[K+].CI.[Br:9][C:10]1[C:11]([N:13]([CH3:27])[C:14](=[O:26])[C:15]=1[C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([CH3:25])[CH:23]=2)[NH:18][CH:17]=1)=[O:12].[Cl-].[Na+]>CN(C=O)C>[Br:9][C:10]1[C:11]([N:13]([CH3:27])[C:14](=[O:26])[C:15]=1[C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([CH3:25])[CH:23]=2)[N:18]([CH3:1])[CH:17]=1)=[O:12]
Reactant: O=C([O-])[O-]
Reactant: Cc1ccc2[nH]cc(C3=C(Br)C(=O)N(C)C3=O)c2c1
Agent: [Cl-]
Agent: [K+]
Agent: [Na+]
Solvent: CI
Solvent: CN(C)C=O
Product: Cc1ccc2c(c1)c(C1=C(Br)C(=O)N(C)C1=O)cn2C
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 96.8 %

Procedure:
Potassium carbonate (130 mg, 0.94 mmol) and methyl iodide (0.06 mL, 0.94 mmol) were added under ice cooling to 2-bromo-3-(5-methyl-1H-indol-3-yl)-N-methylmaleimide (100 mg, 0.31 mmol) dissolved in DMF (5 mL), and the whole was stirred for 1.5 hours. The reaction mixture was warmed to room temperature, added with saturated aqueous sodium chloride solution, and extracted with ethyl acetate. The extract was dried over sodium sulfate, and then concentrated under reduced pressure. The residue was purified by column chromatography over silica gel (ethyl acetate:n-hexane=1:2) to obtain 2-bromo-3-(1,5-dimethyl-1H-indol-3-yl)-N-methylmaleimide (100 mg, 95.8%) as red solids.
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:16]=[C:17]([CH3:21])[CH:18]=[CH:19][CH:20]=2)[CH2:10][CH2:9]1)C1C=CC=CC=1>C(O)C>[C:17]1([CH3:21])[CH:18]=[CH:19][CH:20]=[C:15]([O:14][CH:11]2[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]2)[CH:16]=1
Reactant: Cc1cccc(OC2CCN(Cc3ccccc3)CC2)c1
Solvent: CCO
Product: Cc1cccc(OC2CCNCC2)c1

Procedure:
By following the manipulative procedure described in Example 1(b), a solution of 16.6 g of 1-benzyl-4-(m-tolyloxy)piperidine in 105 ml. of ethanol produces a clear oil of 4-(m-tolyloxy)piperidine. The oil is dissolved in 150 ml. of ether, and 50 ml. of a saturated ethereal-HCl solution is slowly added. The salt precipitates out of solution, is collected, and dried. The salt is recrystallized from an ethanol and ether mixture to give white needles of the piperidine hydrochloride.
Reaction SMILES: CC1C=CC(S(O)(=O)=O)=CC=1.[C:12]([Si:16]([O:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]([CH3:30])=[C:27]([CH3:29])[CH3:28])=[CH:22][CH:21]=1)([CH3:18])[CH3:17])([CH3:15])([CH3:14])[CH3:13]>C1C=CC=CC=1>[C:12]([Si:16]([O:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]([CH:27]([CH3:29])[CH3:28])=[CH2:30])=[CH:22][CH:21]=1)([CH3:18])[CH3:17])([CH3:15])([CH3:14])[CH3:13]
Reactant: CC(C)=C(C)c1ccc(O[Si](C)(C)C(C)(C)C)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: c1ccccc1
Product: C=C(c1ccc(O[Si](C)(C)C(C)(C)C)cc1)C(C)C
Temperature: 50 °C

Procedure:
To a benzene (20 mL) solution of the alcohol (1.7588 g, 5.97 mmol) from (6b) was added pTsOH (0.1136 g, 0.1 eq) and the mixture was warmed up to 50° C. for 6 h. A 1:1 mixture (1.2871 g) of tert-butyl[4-(1-isopropylvinyl)phenoxy]dimethylsilane and tert-butyl [4-(1,2-dimethylpropenyl)phenoxy]dimethylsilane was obtained as colorless oil by flash column chromatography (1% ethyl acetate-hexanes). MS Found: (M+H)+=277.
Reaction SMILES: [CH3:1][C:2]1([C:7]2[O:11][C:10]([CH2:12][N:13]3[N:17]=[C:16]([NH2:18])[CH:15]=[N:14]3)=[CH:9][CH:8]=2)[O:6]CCO1.[Cl:19][C:20]1[CH:25]=[CH:24][C:23](/[CH:26]=[CH:27]/[C:28](O)=[O:29])=[CH:22][CH:21]=1>>[C:2]([C:7]1[O:11][C:10]([CH2:12][N:13]2[N:17]=[C:16]([NH:18][C:28](=[O:29])/[CH:27]=[CH:26]/[C:23]3[CH:24]=[CH:25][C:20]([Cl:19])=[CH:21][CH:22]=3)[CH:15]=[N:14]2)=[CH:9][CH:8]=1)(=[O:6])[CH3:1]
Reactant: CC1(c2ccc(Cn3ncc(N)n3)o2)OCCO1
Reactant: O=C(O)/C=C/c1ccc(Cl)cc1
Product: CC(=O)c1ccc(Cn2ncc(NC(=O)/C=C/c3ccc(Cl)cc3)n2)o1

Procedure:
Following general procedure A followed by L, starting from 2-[5-(2-methyl-[1,3]dioxolan-2-yl)-furan-2-ylmethyl]-2H-[1,2,3]triazol-4-ylamine and (E)-3-(4-chloro-phenyl)-acrylic acid.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:10](I)=[CH:9][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.[N:22]1[CH:27]=[CH:26][CH:25]=[C:24](B(O)O)[CH:23]=1.C(#N)C.C([O-])([O-])=O.[Na+].[Na+]>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.ClCCl>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([C:24]3[CH:23]=[N:22][CH:27]=[CH:26][CH:25]=3)=[CH:9][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: OB(O)c1cccnc1
Reactant: Cc1ccc(S(=O)(=O)n2cc(I)c3cc(Br)cnc32)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CC#N
Product: Cc1ccc(S(=O)(=O)n2cc(-c3cccnc3)c3cc(Br)cnc32)cc1
Temperature: 60 °C

Procedure:
To a screw top reaction tube was placed 5-bromo-3-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridine (1.2 g, 2.52 mmol, prepared according to WO2011/149950), pyridin-3-ylboronic acid (371 mg, 3.02 mmol) and trans-dichlorobis(triphenylphosphine)palladium (II) (177 mg, 0.25 mmol). Degassed acetonitrile (16 mL) and 1 N Na2CO3 (16 mL) was added and the reaction tube was purged with argon, sealed and heated at 60° C. for 2 h. The reaction was cooled, filtered through a Celite pad and concentrated under reduced pressure. The residue was partitioned between EtOAc/water and extracted. The organic layer was washed with brine, dried over Na2SO4 and concentrated to give a solid. Trituration of the solid with hexanes and dichloromethane gave the desired compound. LCMS-ESI+: calc'd for C19H14BrN3O2S: 428.0 (M+H+); found: 428.2 (M+H+).
Reaction SMILES: [Br:1][C:2]1[CH:10]=[C:9]([NH2:11])[CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.[CH3:12][S:13](Cl)(=[O:15])=[O:14]>>[Br:1][C:2]1[CH:10]=[C:9]([NH:11][S:13]([CH3:12])(=[O:15])=[O:14])[CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2
Reactant: CS(=O)(=O)Cl
Reactant: Nc1cc(Br)c2cc[nH]c2c1
Product: CS(=O)(=O)Nc1cc(Br)c2cc[nH]c2c1

Procedure:
4-Bromo-1H-indol-6-amine (200 mg, 0.81 mmol) was treated with methanesulfonyl chloride (66 μl, 0.85 mmol) according to the method described in Preparation 15b.
Reaction SMILES: C1C=CC=CC=1.[CH3:7][O:8][C:9]([C@H:11]1[N:14]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][C:17]=2[O:24][CH3:25])[C:13](=[O:26])[C@H:12]1[N:27]1[C:31](=[O:32])[C:30]2=[CH:33][CH:34]=[CH:35][CH:36]=[C:29]2[C:28]1=[O:37])=[O:10].C1CCN2C(=NCCC2)CC1>C(OCC)(=O)C>[CH3:7][O:8][C:9]([C@@H:11]1[N:14]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][C:17]=2[O:24][CH3:25])[C:13](=[O:26])[C@H:12]1[N:27]1[C:31](=[O:32])[C:30]2=[CH:33][CH:34]=[CH:35][CH:36]=[C:29]2[C:28]1=[O:37])=[O:10]
Reactant: COC(=O)[C@@H]1[C@H](N2C(=O)c3ccccc3C2=O)C(=O)N1Cc1ccc(OC)cc1OC
Solvent: C1CCC2=NCCCN2CC1
Solvent: c1ccccc1
Solvent: CCOC(C)=O
Product: COC(=O)[C@H]1[C@H](N2C(=O)c3ccccc3C2=O)C(=O)N1Cc1ccc(OC)cc1OC

Procedure:
To 200 ml of benzene are added 8.5 g of cis-1-(2,4-dimethoxybenzyl)-3-phthalimido-2-oxoazetidine-4-carboxylic acid methyl ester and 3.1 g of 1,8-diazabicyclo[5,4,0]-7-undecene, and the mixture is heated under reflux for 72 hours. To the reaction mixture, after cooling, is added 100 ml of ethyl acetate, followed by washing with 10 ml and 50 ml of 1N-HCl, and 100ml of water in this order. To the resulting mixture is added 100 ml of chloroform and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. To the residue is added 50 ml of ethyl acetate. The resulting insolubles are collected by filtration, and washed with 30 ml of ethyl acetate to yield 6.4 g of crude product, which is recrystallized from 220 ml of ethyl acetate to yield trans-1-(2,4-dimethoxybenzyl)-3-phthalimido-2-oxoazetidine-4-carboxylic acid methyl ester, m.p. 186°-188° C.