Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([NH:10][C@H:11]([C:13]([OH:15])=[O:14])[CH3:12])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.[C:16]([S:19][CH2:20][CH:21]([CH3:25])[C:22](Cl)=[O:23])(=[O:18])[CH3:17].O>CC(N(C)C)=O>[C:16]([S:19][CH2:20][CH:21]([CH3:25])[C:22]([N:10]([CH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1)[C@H:11]([C:13]([OH:15])=[O:14])[CH3:12])=[O:23])(=[O:18])[CH3:17]
Reactant: C[C@H](NC1CCc2ccccc21)C(=O)O
Reactant: CC(=O)SCC(C)C(=O)Cl
Solvent: CC(=O)N(C)C
Solvent: O
Product: CC(=O)SCC(C)C(=O)N(C1CCc2ccccc21)[C@@H](C)C(=O)O
Temperature: 25 °C
Reaction time: 2 h
Yield: 45 %

Procedure:
N-(1-Indanyl)alanine (3.0 g) is suspended in 30 ml of dimethylacetamide, then 3.3 g of 3-acetylthio-2-methylpropionyl chloride is added dropwise with stirring at room temperature, and thereafter stirring is continued at room temperature for 2 hours. The reaction mixture is poured into 200 ml of water, and extracted with 200 ml of ethyl acetate. The extract is washed with 10 ml of 10% hydrochloric acid and with water, and dried. The ethyl acetate is distilled off under reduced pressure, and the residue is crystallized from an ethyl ether-petroleum ether mixture, to give 2.3 g of N-(3-acetylthio-2-methylpropionyl)-N-(1-indanyl)alanine, colorless needles having a melting point of 133°-137° C.
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].[C:7]([Si:11]([CH3:26])([CH3:25])[O:12][C:13]1[CH:21]=[C:20]2[C:16]([CH:17]=[C:18]([C:22](O)=[O:23])[NH:19]2)=[CH:15][CH:14]=1)([CH3:10])([CH3:9])[CH3:8]>C1COCC1>[C:7]([Si:11]([CH3:26])([CH3:25])[O:12][C:13]1[CH:21]=[C:20]2[C:16]([CH:17]=[C:18]([CH2:22][OH:23])[NH:19]2)=[CH:15][CH:14]=1)([CH3:10])([CH3:9])[CH3:8]
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc2cc(C(=O)O)[nH]c2c1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CC(C)(C)[Si](C)(C)Oc1ccc2cc(CO)[nH]c2c1
Temperature: 25 °C
Reaction time: 48 h
Yield: 40.2 %

Procedure:
1M LAH in THF (103 ml) is cooled to 0° C. A solution of 6-(tert-Butyl-dimethyl-silanyloxy)-1H-indole-2-carboxylic acid (6.0 g, 20.60 mmol) in THF (30 ml) is added slowly. The reaction is stirred at room temperature for two days, quenched with water (10 ml), 1N NaOH (10 ml) and water (20 ml). To the mixture MgSO4 is added. The mixture is filtered, washed with 10% methanol in ethyl acetate (200 ml). The filtrate is concentrated to oil. The crude is purified by column chromatography (20% ethyl acetate in hexanes) to provide [6-(tert-Butyl-dimethyl-silanyloxy)-1H-indol-2-yl]-methanol (2.30 g, 40% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.72 (s,1H) , 7.28 (d, 1H), 6.76 (s,1H), 6.50 (m,1H), 6.16 (s,1H), 5.13 (t, 1H), 4.52 (d, 2H), 0.96 (s, 9H), 0.17 (s, 6H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C@@H:9]2[O:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11][C@H:10]2/[CH:23]=[CH:24]/[C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH:5]=[CH:6][C:7]=1[Cl:8]>CO.[Pt]>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:9]2[O:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17])[CH2:11][C@H:10]2[CH2:23][CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: CCOC(=O)/C=C/[C@@H]1CN(C(=O)OC(C)(C)C)CCO[C@H]1c1ccc(Cl)c(Cl)c1
Agent: [Pt]
Solvent: CO
Product: CCOC(=O)CC[C@@H]1CN(C(=O)OC(C)(C)C)CCO[C@H]1c1ccc(Cl)c(Cl)c1
Yield: 112.5 %

Procedure:
To a solution (1.1 mL) of tert-butyl (6R,7R)-7-(3,4-dichlorophenyl)-6-[(1E)-3-ethoxy-3-oxoprop-1-en-1-yl]-1,4-oxazepane-4-carboxylate (100 mg) in methanol was added, under a nitrogen atmosphere, 3% platinum/activated carbon (23 mg), and the mixture was stirred under a hydrogen atmosphere for 1 hr. The reaction mixture was filtered through celite, and concentrated under reduced pressure to give the title compound (113 mg).
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][C:5]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([O:19][CH3:20])[CH:12]=1)([CH:8]([CH3:10])[CH3:9])[C:6]#[N:7].[CH3:21][NH:22][CH2:23][CH2:24][C:25]1[CH:26]=[C:27]([CH:34]=[CH:35][CH:36]=1)[O:28][CH2:29][C:30]([O:32][CH3:33])=[O:31]>>[C:6]([C:5]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([O:19][CH3:20])[CH:12]=1)([CH:8]([CH3:10])[CH3:9])[CH2:4][CH2:3][CH2:2][N:22]([CH3:21])[CH2:23][CH2:24][C:25]1[CH:26]=[C:27]([CH:34]=[CH:35][CH:36]=1)[O:28][CH2:29][C:30]([O:32][CH3:33])=[O:31])#[N:7]
Reactant: COc1ccc(C(C#N)(CCCBr)C(C)C)cc1OC
Reactant: CNCCc1cccc(OCC(=O)OC)c1
Product: COC(=O)COc1cccc(CCN(C)CCCC(C#N)(c2ccc(OC)c(OC)c2)C(C)C)c1

Procedure:
Reaction of 1f with 2l produced 3aq. MS found M+H=483. The oxalate salt of 3aq was recrystallized from methanol/ether; mp 96-100° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][S:9]([C:12]2[CH:20]=[CH:19][CH:18]=[CH:17][C:13]=2[C:14](O)=[O:15])(=[O:11])=[O:10])=[CH:4][C:3]=1[C:21]([F:24])([F:23])[F:22].Cl.[CH2:26]([O:28][C:29](=[O:33])[C@H:30]([CH3:32])[NH2:31])[CH3:27].O.OC1C2N=NNC=2C=CC=1.C(N(CC)CC)C.C1(N=C=NC2CCCCC2)CCCCC1>>[CH2:26]([O:28][C:29](=[O:33])[CH:30]([NH:31][C:14](=[O:15])[C:13]1[CH:17]=[CH:18][CH:19]=[CH:20][C:12]=1[S:9](=[O:11])(=[O:10])[NH:8][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[C:3]([C:21]([F:22])([F:23])[F:24])[CH:4]=1)[CH3:32])[CH3:27]
Reactant: O=C(O)c1ccccc1S(=O)(=O)Nc1ccc(F)c(C(F)(F)F)c1
Reactant: CCOC(=O)[C@H](C)N
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Cl
Agent: Oc1cccc2[nH]nnc12
Solvent: O
Solvent: CCN(CC)CC
Product: CCOC(=O)C(C)NC(=O)c1ccccc1S(=O)(=O)Nc1ccc(F)c(C(F)(F)F)c1

Procedure:
Under the conditions of Example 2(a), 3.633 g (10 mmol) of 2-[N-(4-fluoro-3-trifluoromethylphenyl)sulfamoyl]benzoic acid, 1.536 g (10 mmol) of L-alanine ethyl ester hydrochloride, 1.531 g (10 mmol) of hydroxybenzotriazole, hydrate, as well as 1.012 g (10 mmol) of triethylamine and 2.063 g (10 mmol) of dicyclohexylcarbodiimide are reacted and worked up analogously. The crude product is chromatographed on silica gel. The title compound is eluted with ethyl acetate.
Reaction SMILES: C(=O)([O-])[O-].[Na+].[Na+].[Br:7][C:8]1[N:9]=[C:10]([C:29]#[C:30][Si](C)(C)C)[C:11]([N:14]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[N:12][CH:13]=1>CN(C=O)C.CCOC(C)=O.O>[Br:7][C:8]1[N:9]=[C:10]([C:29]#[CH:30])[C:11]([N:14]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:15](=[O:21])[O:16][C:17]([CH3:19])([CH3:20])[CH3:18])=[N:12][CH:13]=1
Reactant: CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)c1ncc(Br)nc1C#C[Si](C)(C)C
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: O
Product: C#Cc1nc(Br)cnc1N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Temperature: 90 °C
Yield: 94.1 %

Procedure:
Sodium carbonate (918.5 μL of 2 M, 1.837 mmol) was added to a solution of tert-butyl N-[5-bromo-3-(2-trimethylsilylethynyl)pyrazin-2-yl]-N-tert-butoxycarbonyl-carbamate (720 mg, 1.531 mmol) in DMF (2 mL) and the resulting solution heated at 90° C. for 20 minutes. The reaction mixture was allowed to cool to RT and diluted with EtOAc and water and the layers separated. The aqueous layer was extracted further with EtOAc and the combined organics washed with water, dried (MgSO4) and concentrated in vacuo to give the product as a yellow solid (574 mg, 94% Yield). 1H NMR (400.0 MHz, DMSO) d 1.43 (18H, s), 3.53 (1H, s), 8.55 (1H, s); MS (ES+) 400.03
Reaction SMILES: I[CH2:2][CH2:3][CH2:4][NH:5][C:6]1[CH:11]=[CH:10][C:9]([C:12](=[O:26])[C:13]([N:23]([CH3:25])[CH3:24])([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:14][CH3:15])=[CH:8][CH:7]=1.C([O-])(=[S:29])C.[K+].O>CC(N(C)C)=O>[SH:29][CH2:2][CH2:3][CH2:4][NH:5][C:6]1[CH:11]=[CH:10][C:9]([C:12](=[O:26])[C:13]([N:23]([CH3:25])[CH3:24])([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:14][CH3:15])=[CH:8][CH:7]=1
Reactant: CC([O-])=S
Reactant: CCC(Cc1ccccc1)(C(=O)c1ccc(NCCCI)cc1)N(C)C
Agent: [K+]
Solvent: O
Solvent: CC(=O)N(C)C
Product: CCC(Cc1ccccc1)(C(=O)c1ccc(NCCCS)cc1)N(C)C
Temperature: 50 °C
Reaction time: 0.25 h

Procedure:
6.4 g (0.014 mol) of 1-[4-(3-Iodopropylamino)phenyl]-2-dimethylamino-2-benzyl-butan-1-one are dissolved in 50 ml of dimethylacetamide. To the solution are added 2.28 g of potassium thioacetate and heated up to 50° C. After the reaction mixture is stirred at 50° C. for 15 min, it is poured into 150 ml of water and extracted with ethyl acetate. The organic phase is washed with water and saturated sodium chloride solution, and dried over MgSO4. After distilling off the ethyl acetate, the residue is dissolved in 50 ml of ethanol and the solution is bubbled by nitrogen for 30 min. to remove oxygen. To the solution are added 7 ml of 2 N sodium hydroxide solution and stirred at 0° C. for 15 min. After the reaction mixture is neutralized by adding 2% hydrochloric acid solution, the resulting solution is poured into 100 ml of water and extracted with ethyl acetate. The organic phase is washed with water and saturated sodium chloride solution, and dried over MgSO4. After distilling off the ethyl acetate, the residue is purified by means of column chromatography on silica gel with ethyl acetate-hexane (1:3) as an eluent, and an oily product is obtained. The structure is confirmed by the 1H-NMR spectrum (CDCl3): δ [ppm]: 0.68 (t, 3H), 1.41 (t, 1H), 1.83-2.08 (m, 4H), 2.35 (s, 6H), 2.66 (q, 2H), 3.17 (d, 1H), 3.20 (d, 1H), 3.34 (br, 2H), 4.15 (br, 1H), 6.52 (d, 2H), 7.14-7.28 (m, 5H), 8.32 (d, 2H).
Reaction SMILES: [CH:1](=[N:8][OH:9])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[CH:24]([OH:29])[C:25]([O:27][CH3:28])=[O:26].O>CC(C)=O>[CH:1](=[N:8]/[O:9][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[CH:24]([OH:29])[C:25]([O:27][CH3:28])=[O:26])\[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: ON=Cc1ccccc1
Reactant: COC(=O)C(O)c1ccccc1CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC(C)=O
Product: COC(=O)C(O)c1ccccc1CO/N=C/c1ccccc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 17.8 %

Procedure:
Then, benzaldehyde oxime (0.28 g, 2.3 mmol) and potassium carbonate (0.43 g, 3.1 mmol) were added to a solution of methyl 2-bromomethyl-α-hydroxyphenylacetate (0.40 g, 1.5 mmol) in acetone (6 ml), and the mixture was stirred at room temperature for 18 hours. Water was added, and the mixture was extracted with ether, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=3/1) to give the desired compound methyl (E)-2-benzylideneaminooxymethyl-α-hydroxy-phenylacetate (0.08 g, 17%) as an oil.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][NH:5][C:6](=[O:12])[O:7][C:8]([CH3:11])([CH3:10])[CH3:9].[CH2:13]([SH:15])[CH3:14].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH2:13]([S:15][CH2:2][CH2:3][CH2:4][NH:5][C:6](=[O:12])[O:7][C:8]([CH3:11])([CH3:10])[CH3:9])[CH3:14]
Reactant: CC(C)(C)OC(=O)NCCCBr
Reactant: CCS
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCSCCCNC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of tert-butyl 3-bromopropylcarbamate (0.30 g) in N,N-dimethylformamide (5 ml) was treated with ethanethiol (0.104 ml) and potassium carbonate (0.29 g), and the mixture stirred at room temperature overnight. The mixture was partitioned between water (20 ml) and dichloromethane (30 ml), and the organic layers evaporated in vacuo to give the title compound (0.236 g).
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][C@H:11]([NH:14][CH2:15][C:16]2[CH:17]=[CH:18][C:19]3[S:24][CH2:23][C:22](=[O:25])[NH:21][C:20]=3[CH:26]=2)[C@H:10]([C:27]([F:30])([F:29])[F:28])[CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:30][C:27]([F:28])([F:29])[C@H:10]1[C@@H:11]([NH:14][CH2:15][C:16]2[CH:17]=[CH:18][C:19]3[S:24][CH2:23][C:22](=[O:25])[NH:21][C:20]=3[CH:26]=2)[CH2:12][CH2:13][NH:8][CH2:9]1
Reactant: CC(C)(C)OC(=O)N1CC[C@H](NCc2ccc3c(c2)NC(=O)CS3)[C@H](C(F)(F)F)C1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C1CSc2ccc(CN[C@H]3CCNC[C@H]3C(F)(F)F)cc2N1
Reaction time: 2 h

Procedure:
(3R,4S)-4-[(3-oxo-3,4-dihydro-2H-benzo-[1,4]thiazin-6-ylmethyl)amino]-3-(trifluoromethyl)piperidine-1-carboxylic acid tert-butyl ester (2e) (1 equiv.) is dissolved in CH2Cl2 and TFA (1:1, v/v). After 2 hrs, the solution is concentrated to dryness under vacuum and the residue is dissolved in 4 M HCl in dioxane. After 30 min, the slurry is triturated with Et2O and filtered. The solid is dissolved in H2O and the solution is made basic with aqueous NaOH. The basic aqueous solution is concentrated under vacuum and the residue is dried under high vacuum. The resulting solid is extracted with CH2Cl2/MeOH (10:1, v/v) and the solution is concentrated. The residue is dried under high vacuum to give the title compound.
Reaction SMILES: [Br:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH2:23])[CH:11]=[CH:12][C:13]=1[O:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=1.[F:24][C:25]1[CH:30]=[CH:29][C:28]([N:31]=[C:32]=[O:33])=[CH:27][CH:26]=1>C(Cl)Cl>[Br:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH:23][C:32]([NH:31][C:28]2[CH:29]=[CH:30][C:25]([F:24])=[CH:26][CH:27]=2)=[O:33])[CH:11]=[CH:12][C:13]=1[O:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=1
Reactant: Cn1ncc(Br)c1-c1cc(N)ccc1OCc1ccc(Cl)cc1
Reactant: O=C=Nc1ccc(F)cc1
Solvent: ClCCl
Product: Cn1ncc(Br)c1-c1cc(NC(=O)Nc2ccc(F)cc2)ccc1OCc1ccc(Cl)cc1
Yield: 50 %

Procedure:
3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-(4-chloro-benzyloxy)-phenylamine (0.032 g, 0.08 mmol) was treated with 4-fluorophenyl isocyanate (0.014 g, 11.1 μL, 0.10 mmol, 1.2 equiv.) in CH2Cl2 (1 mL), in a similar manner as described in Example 1.2 to afford Compound 64 (0.023 g, 0.04 mmol, 54%) as a white solid. LCMS m/z (%)=545 (M+H79Br35Cl, 65), 547 (M+H81Br35Cl, 100), 549 (M+H81Br37Cl, 25). 1H NMR (400 MHz, acetone-d6) δ: 8.13 (s, 2H), 7.66 (dd, J=2.7, 9.0 Hz, 1H), 7.51-7.56 (m, 3H), 7.50 (s, 1H), 7.46 (d, J=2.7 Hz, 1H), 7.37 (d, J=8.7 Hz, 2H), 7.33 (d, J=8.7 Hz, 2H), 7.21 (d, J=9.0 Hz, 1H), 7.05-7.75 (m, 2H), 5.14 (AB quartet, J=12.3, 24.8 Hz, 2H), 3.69 (s, 3H).
Reaction SMILES: O=[C:2]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH3:15])[C:3]([O:5][CH2:6][CH3:7])=[O:4].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)(Cl)(Cl)[Cl:36]>>[Cl:36][C:2](=[N:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH3:15])[C:3]([O:5][CH2:6][CH3:7])=[O:4]
Reactant: CCOC(=O)C(=O)Nc1ccccc1C
Reactant: ClC(Cl)(Cl)Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: CCOC(=O)C(Cl)=Nc1ccccc1C

Procedure:
The suspension of ethyl 2-oxo-2-(o-tolylamino)acetate (2.0 g, 10 mmol) and triphenylphosphine (4.0 g, 15 mmol) in carbon tetrachloride (150 mL) was refluxed overnight. The reaction was cooled down and filtered. The filtrate was collected and concentrated and used it without further purification. MS (m/z) 226 [M+H]+.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)=[C:6]([CH:21]=1)[C:7]([NH:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([O:19][CH3:20])[CH:12]=1)=[O:8].[CH3:28][C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[C:33]([CH3:35])[CH:34]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O.CCOC(C)=O.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>[CH3:20][O:19][C:13]1[CH:12]=[C:11]([CH:16]=[CH:15][C:14]=1[O:17][CH3:18])[CH2:10][NH:9][C:7]([C:6]1[CH:21]=[C:2]([C:31]2[CH:32]=[C:33]([CH3:35])[CH:34]=[C:29]([CH3:28])[CH:30]=2)[CH:3]=[CH:4][C:5]=1[C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1)=[O:8]
Reactant: Cc1cc(C)cc(B(O)O)c1
Reactant: COc1ccc(CNC(=O)c2cc(Br)ccc2-c2cccnc2)cc1OC
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: O
Product: COc1ccc(CNC(=O)c2cc(-c3cc(C)cc(C)c3)ccc2-c2cccnc2)cc1OC
Temperature: 150 °C

Procedure:
A solution of 1-3 (90 mg, 0.211 mmol, 1.0 equiv) in DMF (2 ml) in a microwave vial was treated with the 3,5-dimethylphenyl boronic acid (34.7 mg, 0.232 mmol, 1.1 equiv), cesium carbonate (0.632 mL of a 1M solution in water, 0.632 mmol, 3.0 equiv), and PdCl2(dppf)-CH2Cl2 adduct (17.20 mg, 0.021 mmol, 0.1 equiv). The mixture was heated to 150° C. in a microwave reactor for 10 minutes. The mixture was cooled to room temperature and diluted with EtOAc. The organic solution was washed with sat. aq. NH4Cl, dried over Na2SO4, filtered and concentrated. The crude material was purified by gradient elution on silica gel (0 to 100% EtOAc in hexanes) to yield impure material which was precipitated from ether/hexanes and filtered. The solid was isolated to afford the product (1-4) as a tan solid. HRMS [M+H] C26H27N5O3 calc'd 453.2173. found 453.2178.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[C:6]([S:10]([N:13]([CH3:28])[CH2:14][C:15]2[O:16][C:17]([C:20]([N:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)=[O:21])=[N:18][N:19]=2)(=[O:12])=[O:11])=[C:5]([CH3:29])[CH:4]=1.[CH3:30][C:31]1[CH:36]=[C:35]([CH:37]=O)[CH:34]=[CH:33][N:32]=1.ClCCCl>>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[C:6]([S:10]([N:13]([CH3:28])[CH2:14][C:15]2[O:16][C:17]([C:20]([N:22]3[CH2:23][CH2:24][N:25]([CH2:37][C:35]4[CH:34]=[CH:33][N:32]=[C:31]([CH3:30])[CH:36]=4)[CH2:26][CH2:27]3)=[O:21])=[N:18][N:19]=2)(=[O:11])=[O:12])=[C:5]([CH3:29])[CH:4]=1
Reactant: COc1cc(C)c(S(=O)(=O)N(C)Cc2nnc(C(=O)N3CCNCC3)o2)c(C)c1
Reactant: Cc1cc(C=O)ccn1
Solvent: ClCCCl
Product: COc1cc(C)c(S(=O)(=O)N(C)Cc2nnc(C(=O)N3CCN(Cc4ccnc(C)c4)CC3)o2)c(C)c1

Procedure:
The title compound was prepared according to general procedure CD using 4-methoxy-N,2,6-trimethyl-N-{[5-(piperazin-1-ylcarbonyl)-1,3,4-oxadiazol-2-yl]methyl}benzenesulfonamide (42 mg, 0.10 mmol), 2-methylpyridine-4-carbaldehyde (15 mg, 0.12 mmol), STAB (42 mg, 0.2 mmol) DCE (0.8 mL) and a few 4 Å molecular sieves. The crude product was purified using prep method D.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]2[O:9][CH:10]=[CH:11][CH:12]=2)[C:5]([C:13]#[N:14])=[C:4](SC)[N:3]=1.[CH3:17][CH2:18][O-:19].[Na+]>C(O)C>[NH2:1][C:2]1[N:3]=[C:4]([O:19][CH2:18][CH3:17])[C:5]([C:13]#[N:14])=[C:6]([C:8]2[O:9][CH:10]=[CH:11][CH:12]=2)[N:7]=1
Reactant: CSc1nc(N)nc(-c2ccco2)c1C#N
Reactant: CC[O-]
Agent: [Na+]
Solvent: CCO
Product: CCOc1nc(N)nc(-c2ccco2)c1C#N

Procedure:
From 2-amino-4-(2-furyl)-6-(methylthio)-5-pyrimidinecarbonitrile and sodium ethylate in ethanol. Anal. found C 57.39%, H 4.38%, N 24.34%. C 11H10N4O2 requires C 57.43%, H 4.47%, N 24.42%.
Reaction SMILES: [C:1]1([C:7]2[N:22]=[C:10]3[CH:11]=[C:12]([C:16]4[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=4)[CH:13]=[C:14]([NH2:15])[N:9]3[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[CH2:30][C:31](Cl)=[O:32]>>[Cl:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[CH2:30][C:31]([NH:15][C:14]1[N:9]2[N:8]=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[N:22]=[C:10]2[CH:11]=[C:12]([C:16]2[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=2)[CH:13]=1)=[O:32]
Reactant: Nc1cc(-c2ccncc2)cc2nc(-c3ccccc3)nn12
Reactant: O=C(Cl)Cc1ccccc1Cl
Product: O=C(Cc1ccccc1Cl)Nc1cc(-c2ccncc2)cc2nc(-c3ccccc3)nn12

Procedure:
The title compound, MS m/e (%): 440 (M+H+, 100), was prepared in accordance with the general method of example 31 from 2-phenyl-7-pyridin-4-yl-[1,2,4]triazolo[1,5-a]pyridin-5-ylamine and 2-chlorophenylacetyl chloride.
Reaction SMILES: [F:1][C:2]([F:12])([S:9]([O-:11])=[O:10])[C:3]([F:8])([F:7])[CH2:4][CH2:5][OH:6].[CH2:13]([NH+:15]([CH2:18][CH3:19])[CH2:16][CH3:17])[CH3:14].OO.S([O-])([O-])=[O:23].[Na+].[Na+]>O>[F:12][C:2]([F:1])([S:9]([O-:23])(=[O:11])=[O:10])[C:3]([F:7])([F:8])[CH2:4][CH2:5][OH:6].[CH2:13]([NH+:15]([CH2:18][CH3:19])[CH2:16][CH3:17])[CH3:14]
Reactant: O=S([O-])C(F)(F)C(F)(F)CCO
Reactant: O=S([O-])[O-]
Agent: CC[NH+](CC)CC
Agent: OO
Agent: [Na+]
Solvent: O
Product: O=S(=O)([O-])C(F)(F)C(F)(F)CCO
Temperature: 40 °C
Reaction time: 6 h
Yield: 40 %

Procedure:
A 500 mL reactor was charged with 112 g (46% purity, 0.17 moles) of triethylammonium 1,1,2,2-tetrafluoro-4-hydroxy-butane-1-sulfinate, 200 g of water and 41 g (0.36 mole) of 30% hydrogen peroxide, at room temperature, followed by 6 hours of stirring at 40° C. Upon confirming the termination of the reaction, a reaction liquid underwent cooling and 7.5 g of sodium sulfite was added to the reaction liquid, followed by stirring. Subsequently, a liquid obtained by distilling the solvent out of the reaction liquid was rinsed with 50 g of hexane, and then extracted with 100 g of chloroform. It was heated under a reduced pressure so as to distill a volatile component off and then dried, thereby obtaining 43 g of a target triethylammonium 1,1,2,2-tetrafluoro-4-hydroxy-butane-1-sulfonate. It exhibited a purity of 50% and a yield of 40% at this time. As a result of analysis, it was found that 4-bromo-3,3,4,4-tetrafluorobutan-1-ol which had been confirmed to disappear by the 1st step (sulfination step) was formed during this 2nd step (oxidation step) as a by-product in an amount of 9%.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[CH:12]=[C:13]4[C:17](=[CH:18][CH:19]=3)[NH:16][CH:15]=[CH:14]4)=[CH:9][N:8]([S:20]([C:23]3[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:5]2=[N:6][CH:7]=1.[CH:30]([C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1)=[O:31].C([O-])([O-])=O.[Na+].[Na+]>CC#N.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>[NH:16]1[C:17]2[C:13](=[CH:12][C:11]([C:10]3[C:4]4[C:5](=[N:6][CH:7]=[C:2]([C:35]5[CH:36]=[CH:37][C:32]([CH:30]=[O:31])=[CH:33][CH:34]=5)[CH:3]=4)[N:8]([S:20]([C:23]4[CH:24]=[CH:25][C:26]([CH3:27])=[CH:28][CH:29]=4)(=[O:21])=[O:22])[CH:9]=3)=[CH:19][CH:18]=2)[CH:14]=[CH:15]1
Reactant: Cc1ccc(S(=O)(=O)n2cc(-c3ccc4[nH]ccc4c3)c3cc(Br)cnc32)cc1
Reactant: O=Cc1ccc(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#N
Product: Cc1ccc(S(=O)(=O)n2cc(-c3ccc4[nH]ccc4c3)c3cc(-c4ccc(C=O)cc4)cnc32)cc1
Temperature: 150 °C

Procedure:
To a solution of 5-bromo-3-(1H-indol-5-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine [Intermediate B] (0.20 g, 0.43 mmole) in CH3CN (4 mL) in a Personal Chemistry microwave reaction vial was added 4-formylphenylboronic acid (64 mg, 0.43 mmol), bis(triphenylphosphine)-palladium(II) dichloride (40 mg, 0.057 mmol), and 1 M Na2CO3 (2 mL). The resulting mixture was de-gassed with Ar for 10 min, after which it was heated at 150° C. for min in a Personal Chemistry Optimizer. The organic layer was separated, filtered, and partitioned between EtOAc and brine. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo to give Intermediate AJ. HPLC retention time: 3.01 minutes. MS ESI (m/z): 492.4 (M+H)+, calc. 491.
Reaction SMILES: [Br:1][CH:2]([CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:3](O)=[O:4].S(Cl)([Cl:15])=O>>[Br:1][CH:2]([CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:3]([Cl:15])=[O:4]
Reactant: O=C(O)C(Br)Cc1ccccc1
Reactant: O=S(Cl)Cl
Product: O=C(Cl)C(Br)Cc1ccccc1

Procedure:
60.5g of 2-bromo-3-phenylpropionic acid was mixed with 100 ml of thionylchloride and the mixture was refluxed for 3 hours and, after the excess thionylchloride had been distilled off, was distilled under reduced pressure to give 46.2g of 2-bromo-3-phenylpropionylchloride. (b.p. 100°- 101°C/4 mmHg)