Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: N[C@@H:2]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])[C:3]([OH:5])=[O:4].[Br-:14].[K+].OS(O)(=O)=O.N([O-])=O.[Na+]>O>[Br:14][C@@H:2]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])[C:3]([OH:5])=[O:4]
Reactant: [Br-]
Reactant: CCCCCCCC[C@H](N)C(=O)O
Agent: O=N[O-]
Agent: O=S(=O)(O)O
Agent: [K+]
Solvent: O
Product: CCCCCCCC[C@H](Br)C(=O)O
Temperature: 0 °C
Reaction time: 2 h
Yield: 61 %

Procedure:
(S)-2-Aminodecanoic acid from Takasago Research Institute (1.5 g., 8.0 mmol) and potassium bromide (3.8 g, 32 mmol) were dissolved in 16 ml of 2.5 m H2SO4 (40 mmol). Slight heating was necessary to the make the reaction homogeneous. The solution was cooled to 0° C. and sodium nitrite (1.1 g, 16 mmol) dissolved in 2 ml water was added dropwise. Brown gas evolved and foaming occurred. The reaction was stirred at 0° C. for 30 minutes and at rt for 2 hours. The reaction was quenched with 100 ml of 5% sodium thiosulfate and extracted with ethyl acetate (3×100 ml). The concentrated organic phase was purified by silica gel column chromatography (eluent: 100% CH2Cl2) to yield 1.2 g (61% yield) of the desired product: [α]20D=-29.9° (c=0.032, MeOH); 1H NMR (CDCl3 δ10.28 (1H, br s), 4.22 (1H, t, J=7.4 Hz), 2.02 (2H, m), 1.26 (12H, m), 0.87 (3H, t, J=6.8 Hz).
Reaction SMILES: FC(F)(F)C([N:5]1[CH2:11][CH:10]([CH3:12])[C:9]2[CH:13]=[C:14]([Br:21])[C:15]([O:17][CH2:18][CH:19]=[CH2:20])=[CH:16][C:8]=2[CH2:7][CH2:6]1)=O.[OH-].[Na+]>CO.O>[CH2:18]([O:17][C:15]1[C:14]([Br:21])=[CH:13][C:9]2[CH:10]([CH3:12])[CH2:11][NH:5][CH2:6][CH2:7][C:8]=2[CH:16]=1)[CH:19]=[CH2:20]
Reactant: C=CCOc1cc2c(cc1Br)C(C)CN(C(=O)C(F)(F)F)CC2
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: C=CCOc1cc2c(cc1Br)C(C)CNCC2
Reaction time: 8 h
Yield: 99 %

Procedure:
A solution of N-trifluoroacetyl-7-allyloxy-8-bromo-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine (1.18 g, 3.00 mmol) in methanol (35 mL) was treated with 15% aqueous NaOH (35 mL), and stirred overnight at 20 C. The product mixture was diluted with water (200 mL), extracted twice with EtOAc (200 mL), the combined organic phases were washed with brine (100 mL), dried with Na2SO4 and concentrated to give 0.880 g of a clear oil. 1H NMR (400 MHz, CDCl3) d 7.29 (s, 1 H), 6.63 (s, 1 H), 6.04 (m, 1 H), 5.47 (d, J=17 Hz, 1 H), 5.29 (d, J=11 Hz, 1 H), 4.58 (s, 2 H), 3.01 (m, 3 H), 2.89 (m, 3 H), 2.75 (m, 1 H), 1.31 (d, J=7 Hz, 3 H). MS calculated for C14H18BrNO+H:296, observed: 296.
Reaction SMILES: [OH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([C:8]2[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[C:10]([CH3:18])[CH:9]=2)[CH2:4][CH2:3]1.[C:19](C1C=CC=C(C(C)(C)C)N=1)(C)(C)C.IC>C(Cl)Cl.FC(F)(F)S([O-])(=O)=O.[Ag+]>[CH3:19][O:1][C@H:2]1[CH2:3][CH2:4][C@H:5]([C:8]2[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[C:10]([CH3:18])[CH:9]=2)[CH2:6][CH2:7]1
Reactant: CC(C)(C)c1cccc(C(C)(C)C)n1
Reactant: COC(=O)c1ccc([C@H]2CC[C@H](O)CC2)cc1C
Agent: [Ag+]
Agent: O=S(=O)([O-])C(F)(F)F
Solvent: ClCCl
Solvent: CI
Product: COC(=O)c1ccc([C@H]2CC[C@H](OC)CC2)cc1C
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a solution of the title compound from Example 13 Step E (234 mg, 0.942 mmol) in DCM (4.7 mL) were added 2,6-di-tert-butylpyridine (0.318 mL, 1.41 mmol) and silver trifluoromethanesulfonate (266 mg, 1.04 mmol). The resulting solution was cooled to 0° C., and iodomethane (0.071 mL, 1.13 mmol) was added. After 30 min, the reaction mixture was allowed to warm to ambient temperature and was held at this temperature for 3 h, whereupon it was filtered through Celite, rinsing with DCM. The reaction mixture was concentrated in vacuo. Purification by flash chromatography on silica gel (0 to 30% EtOAc in hexanes, then 30 to 100% EtOAc in hexanes) provided the title compound. Analytical data for the major isomer (trans cyclohexyl): LCMS m/z 263.17 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 7.85 (d, J=8.5 Hz, 1H), 7.08-7.06 (m, 2H), 3.86 (s, 3H), 3.38 (s, 3H), 3.24-3.17 (m, 1H), 2.58 (s, 3H), 2.49 (dt, J=12.0, 3.5 Hz, 1H), 2.21-2.18 (m, 2H), 1.94-1.92 (m, 2H), 1.54-1.46 (m, 2H), 1.39-1.30 (m, 2H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([NH:22]C(=O)C)[CH:5]=[CH:6][C:7]=1[S:8](=[O:21])(=[O:20])[NH:9][C:10]1[CH:11]=[CH:12][C:13]2[CH2:17][O:16][B:15]([OH:18])[C:14]=2[CH:19]=1.[OH-].[Na+]>O1CCOCC1.Cl>[NH2:22][C:4]1[CH:5]=[CH:6][C:7]([S:8]([NH:9][C:10]2[CH:11]=[CH:12][C:13]3[CH2:17][O:16][B:15]([OH:18])[C:14]=3[CH:19]=2)(=[O:20])=[O:21])=[C:2]([F:1])[CH:3]=1
Reactant: CC(=O)Nc1ccc(S(=O)(=O)Nc2ccc3c(c2)B(O)OC3)c(F)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: Nc1ccc(S(=O)(=O)Nc2ccc3c(c2)B(O)OC3)c(F)c1
Temperature: 25 °C
Yield: 13.7 %

Procedure:
A solution of N-(3-fluoro-4-(N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)sulfamoyl)phenyl)acetamide (1.45 g, 3.98 mmol) in 1,4-dioxane (8 mL) and concentrated hydrochloric acid (2 mL) was refluxed at 100° C. for three hours. The solution was cooled to room temperature and neutralized to pH 5 using 3 N sodium hydroxide. The solution was extracted using ethyl acetate and water. The organic layer was washed three times with water, than washed with brine, dried over sodium sulfate, and filtered. The solvent was removed under reduced pressure. The residue was purified by silica column via CombiFlash using dichloromethane and methanol. The desired fractions were collected and the solvent was removed under reduced pressure. Water and toluene were added and removed under reduced pressure. Diisopropyl ether was used to transfer powder from round bottom flask to Buckner funnel to give 4-amino-2-fluoro-N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)benzenesulfonamide (0.176 g, 14% yield). 1H NMR (400 MHz, DMSO-d6) δ (ppm) 4.85 (s, 2H), 6.23-6.31 (m, 4H), 7.16 (dd, J=2.1 Hz, J=8.1 Hz, 1H), 7.22 (d, J=8.3 Hz, 1H), 7.36 (t, J=8.6 Hz, 1H), 7.43 (d, J=1.8 Hz, 1H), 9.17 (s, 1H), 10.06 (s, 1H).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]([N:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)=[N:8][CH:9]=1)([O-])=O>C(O)C>[N:10]1([C:7]2[N:8]=[CH:9][C:4]([NH2:1])=[CH:5][CH:6]=2)[CH2:14][CH2:13][CH2:12][CH2:11]1
Reactant: O=[N+]([O-])c1ccc(N2CCCC2)nc1
Solvent: CCO
Product: Nc1ccc(N2CCCC2)nc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 98 %

Procedure:
Around-bottom flask, containing a solution of 5-nitro-2-(pyrrolidin-1-yl)pyridine (compound 40.1, 1.93 g, 10.00 mmol, 1.00 equiv) in ethanol (30 mL) was purged with nitrogen. Palladium on carbon (0.4 g, 10%, 60% water) was added. After further purging the system with nitrogen, the atmosphere was changed to hydrogen and the resulting mixture was stirred overnight at room temperature. After purging the system with nitrogen, the solids were filtered off and the filtrate was concentrated under reduced pressure and dried to yield 1.6 g (98%) of the title compound as a brown solid.
Reaction SMILES: [C:1]([CH2:6][N:7]1[C:11]([SH:12])=[N:10][N:9]=[N:8]1)([C:3]([OH:5])=[O:4])=O.Cl.[NH2:14][OH:15].[OH-].[Na+].Cl>O>[C:3]([C:1](=[N:14][OH:15])[CH2:6][N:7]1[C:11]([SH:12])=[N:10][N:9]=[N:8]1)([OH:5])=[O:4]
Reactant: O=C(O)C(=O)Cn1nnnc1S
Reactant: NO
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C(O)C(Cn1nnnc1S)=NO
Temperature: 25 °C
Reaction time: 3.5 h
Yield: 52 %

Procedure:
A solution of 1-oxalomethyl-1H-tetrazole-5-thiol (10.0 g) and hydroxylamine hydrochloride (4.8 g) in water (100 ml) was adjusted to pH 6.0 with 2 N aqueous solution of sodium hydroxide and stirred at room temperature for 3.5 hours. The solution was acidified with 10% hydrochloric acid to pH 2.0, extracted with a mixture of tetrahydrofuran and ethyl acetate (1:1). The extract was washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and evaporated to give 1-(2-carboxy-2-hydroxyiminoethyl)-1H-tetrazole-5-thiol (5.61 g).
Reaction SMILES: [OH:1][N:2]=[C:3](Cl)[C:4]1[CH:9]=[CH:8][CH:7]=[N:6][CH:5]=1.[C:11]([C:13]1[CH:14]=[C:15]([CH:17]=[CH:18][CH:19]=1)[NH2:16])#[CH:12].N>>[NH2:16][C:15]1[CH:14]=[C:13]([C:11]2[O:1][N:2]=[C:3]([C:4]3[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=3)[CH:12]=2)[CH:19]=[CH:18][CH:17]=1
Reactant: ON=C(Cl)c1cccnc1
Reactant: C#Cc1cccc(N)c1
Agent: N
Product: Nc1cccc(-c2cc(-c3cccnc3)no2)c1

Procedure:
The titled compound was prepared according to Method CB using the product of Example 1A (78 mg, 0.5 mmol) and 3-ethynylaniline (Aldrich, 59 mg, 0.5 mmol). 1H NMR (300 MHz, MeOH-d4) δ 6.83 (dt, J=7.5, 1.9 Hz, 1H), 7.10-7.33 (m, 4H), 7.59 (dd, J=8.0, 4.9 Hz, 1H), 8.35 (dt, J=8.1, 1.9 Hz, 1H), 8.65 (dd, J=4.9, 1.5 Hz, 1H), 9.08 (d, J=1.4 Hz, 1H) ppm; MS (DCI/NH3) m/z 238 (M+H)+.
Reaction SMILES: [Mg].[O:2]([CH2:20][C:21]1[CH:22]=[C:23](Br)[CH:24]=[CH:25][CH:26]=1)[Si:3]([C:16]([CH3:19])([CH3:18])[CH3:17])([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[Cl-].[NH4+].C1C[O:33][CH2:32]C1>>[O:2]([CH2:20][C:21]1[CH:22]=[C:23]([CH:24]=[CH:25][CH:26]=1)[CH2:32][OH:33])[Si:3]([C:16]([CH3:19])([CH3:18])[CH3:17])([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: C1CCOC1
Reactant: CC(C)(C)[Si](OCc1cccc(Br)c1)(c1ccccc1)c1ccccc1
Agent: [Cl-]
Agent: [Mg]
Agent: [NH4+]
Product: CC(C)(C)[Si](OCc1cccc(CO)c1)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 64 %

Procedure:
Magnesium turnings (1.45 g, 59.5 mmol) were weighed into a flask which was then flame-dried under vacuum. An argon atmosphere was introduced, and anhydrous THF (30 mL) and dibromoethane (approx. 0.1 mL) were added. The mixture was stirred at room temperature. Approximately 25 mL of a solution of 22 (21.1 g, 49.6 mmol) in anhydrous THF (120 mL) was added via cannula. Within 10 min, the solution became dark yellow-brown. The remainder of the solution of 22 was then added via cannula, and the entire reaction solution was heated at reflux for 2 h. The solution was allowed to cool to room temperature, and p-formaldehyde (2.98 g, 99.2 mmol) was added. The reaction mixture was stirred at room temperature for 19 h and then poured into a separatory funnel containing saturated ammonium chloride solution. The aqueous mixture was extracted twice with diethyl ether. The organic layers were combined, washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered, and concentrated to give 19.1 g of a clear, yellow liquid. Purification by column chromatography (10:1 ratio silica gel/crude product; gradient elution with 10% to 30% ethyl acetate/hexanes) provided 11.9 g (64%) of 23 as a pale yellow oil. 1H NMR (300 MHz, CDCl3) δ7.69-7.73 (m, 4H, ArH), 7.25-7.46 (m, 10 H, ArH), 4.79 (s, 2H, CH2OSi), 4.68 (s, 2H, CH2OH), and 1.11 (s, 9H, SiC(CH3)3); 13C NMR (75 MHz, CDCl3) δ141.32, 140.67, 135.48, 133.35, 129.61, 128.41, 127.62, 125.46, 125.29, 124.54, 65.32 (CH2OSi, CH2OH), 26.75 (SiC(CH3)3), and 19.22 (SiC(CH3)3); IR (film) 3340 (br, OH), 2940, 2860, 1475, 1430, 1150, and 1110 cm-1 ; MS (FAB) m/e 399 (M+Na)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:13][C:12]([CH3:14])=[C:11]([CH:15]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([C:27]([N:29]([CH3:37])[CH2:30][CH2:31][C:32]([O:34]CC)=[O:33])=[O:28])=[CH:23][CH:22]=3)[CH2:16][CH:17]([CH3:19])[CH3:18])[CH:10]=2)=[CH:5][CH:4]=1.O1CCCC1.[OH-].[Li+]>C(O)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:13][C:12]([CH3:14])=[C:11]([CH:15]([NH:20][C:21]3[CH:22]=[CH:23][C:24]([C:27]([N:29]([CH3:37])[CH2:30][CH2:31][C:32]([OH:34])=[O:33])=[O:28])=[CH:25][CH:26]=3)[CH2:16][CH:17]([CH3:19])[CH3:18])[CH:10]=2)=[CH:5][CH:4]=1
Reactant: CCOC(=O)CCN(C)C(=O)c1ccc(NC(CC(C)C)c2cc(-c3ccc(OC)cc3)oc2C)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: CCO
Solvent: C1CCOC1
Product: COc1ccc(-c2cc(C(CC(C)C)Nc3ccc(C(=O)N(C)CCC(=O)O)cc3)c(C)o2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 34 %

Procedure:
A mixture of 5-[4-(1-chloro-3-methylbutyl)-5-methylfuran-2-yl]-2-methoxypyridine (382 mg), ethyl 3-{[(4-aminophenyl)carbonyl](methyl)amino}propanoate (400 mg), sodium carbonate (170 mg) and sodium iodide (240 mg) in N,N-dimethylacetamide (10 mL) was stirred overnight at 80° C. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography (25% ethyl acetate/hexane to 65% ethyl acetate/hexane) to give ethyl 3-[{[4-({1-[5-(4-methoxyphenyl)-2-methylfuran-3-yl]-3-methylbutyl}amino)phenyl]carbonyl}(methyl)amino]propanoate. Ethyl 3-[{[4-({1-[5-(4-methoxyphenyl)-2-methylfuran-3-yl]-3-methylbutyl}amino)phenyl]carbonyl}(methyl)amino]propanoate was dissolved in ethanol (2 mL) and tetrahydrofuran (2 mL) and 1N lithium hydroxide (1.0 mL) was added, and the mixture was stirred at room temperature for 1 hr. The solvent was evaporated under reduced pressure, and water (10 mL) was added. The mixture was neutralized with 1N hydrochloric acid under ice-cooling, and stirred for 1 hr. The resulting precipitate was collected by filtration and dried to give the title compound (210 mg, 34%).
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][S:5](Cl)(=[O:7])=[O:6].[Br:9][C:10]1[CH:16]=[CH:15][C:13]([NH2:14])=[C:12]([F:17])[CH:11]=1.N1C=CC=CC=1>ClCCl>[Br:9][C:10]1[CH:16]=[CH:15][C:13]([NH:14][S:5]([CH2:4][CH2:3][CH2:2][Cl:1])(=[O:7])=[O:6])=[C:12]([F:17])[CH:11]=1
Reactant: O=S(=O)(Cl)CCCCl
Reactant: Nc1ccc(Br)cc1F
Solvent: c1ccncc1
Solvent: ClCCl
Product: O=S(=O)(CCCCl)Nc1ccc(Br)cc1F
Reaction time: 1 h

Procedure:
3-chloropropane-1-sulfonyl chloride (3.16 ml, 0.026M) was added to a solution of 4-bromo-2-fluoroaniline (5.00 g, 0.026M) and pyridine (2.12 ml, 0.026M) in dichloromethane (100 ml) at 0° C. The reaction mixture was stirred for 1 hr, after which time it was partitioned between dichloromethane (100 ml) and 1N hydrochloric acid (100 ml). The organics were separated and dried over magnesium sulfate, filtered and concentrated in vacuuo to afford the title compound as a yellow oil (8.3 g). 1H NMR (CDCl3): δ2.54 (m, 2H), 2.90 (m, 2H), 3.64 (d, J=2.56 Hz, 2H), 6.91 (d, J=3.56 Hz, 1H), 7.07 (m, 2H).
Reaction SMILES: S(=O)(=O)(O)O.[CH3:6][C:7]1[C:12]([CH2:13]Cl)=[CH:11][CH:10]=[CH:9][CH:8]=1>C1C=CC=CC=1>[CH2:13]([C:12]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH3:6])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: Cc1ccccc1CCl
Agent: O=S(=O)(O)O
Solvent: c1ccccc1
Product: Cc1ccccc1Cc1ccccc1
Reaction time: 5 h
Yield: 83 %

Procedure:
850 parts of 80 per cent strength by weight sulfuric acid are introduced into a vessel equipped with an impeller stirrer. A solution of 70 parts of o-xylyl chloride and 156 parts of benzene in 200 parts of ligroin are run in at from 75° to 80° C, whilst stirring thoroughly. After a further 5 hours at 80° C, the organic phase is separated off and 75 parts (83% of theory) of o-benzyltoluene boiling at from 97 to 100° C at 0.2 mm Hg are isolated by distillation.
Reaction SMILES: [CH:1]1[C:13]2[CH:12]([N:14]=[C:15]=[S:16])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[NH3:17]>CCOCC>[CH:1]1[C:13]2[CH:12]([NH:14][C:15]([NH2:17])=[S:16])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1
Reactant: S=C=NC1c2ccccc2-c2ccccc21
Reactant: N
Solvent: CCOCC
Product: NC(=S)NC1c2ccccc2-c2ccccc21
Reaction time: 8 h

Procedure:
To 16.52 g (0.074 mole) of 9-fluorenylisothiocyanate in ether is added excess anhydrous NH3 with cooling. The reaction mixture is capped and allowed to stand overnight at 0° C. Filtration gives the product, N-(9-fluorenyl)-thiourea, m.p. (158°) 182°-189° C.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:15]([O:17][CH3:18])=[O:16])[C:5]2[C:6]([CH3:14])=[CH:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=1.[F:19][C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][C:21]=1[CH:29]=[O:30].P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>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.CCOC(C)=O>[F:19][C:20]1[CH:25]=[CH:24][C:23]([C:2]2[CH:3]=[C:4]([C:15]([O:17][CH3:18])=[O:16])[C:5]3[C:6]([CH3:14])=[CH:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=3[CH:10]=2)=[CH:22][C:21]=1[CH:29]=[O:30]
Reactant: O=Cc1cc(B(O)O)ccc1F
Reactant: COC(=O)c1cc(Br)cc2c1c(C)cn2C(C)C
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=P([O-])([O-])[O-]
Solvent: CCOC(C)=O
Solvent: ClCCl
Solvent: O
Product: COC(=O)c1cc(-c2ccc(F)c(C=O)c2)cc2c1c(C)cn2C(C)C
Temperature: 110 °C
Reaction time: 4 h
Yield: 98.3 %

Procedure:
To a glass pressure vessel was added methyl 6-bromo-3-methyl-1-(1-methylethyl)-1H-indole-4-carboxylate (500 mg, 1.612 mmol), 4-fluoro-3-formylbenzeneboronic acid (375 mg, 2.233 mmol), Potassium phosphate (1.1 g, 5.18 mmol), dioxane (12 mL) and water (3 mL). The reaction was purged with N2 and charged with PdCl2(dppf)-CH2Cl2 adduct (120 mg, 0.147 mmol). The reaction was capped and stirred at 110° C. for 4 hr. LCMS showed that the reaction was complete. The reaction was diluted with water, extracted with EtOAc, washed with brine, dried (MgSO4), filtered, and concentrated under vacuum. Purification by silica gel chromatography (Analogix, SF25-60 g, 0 to 50% EtOAc in hexanes) gave the product methyl 6-(4-fluoro-3-formylphenyl)-3-methyl-1-(1-methylethyl)-1H-indole-4-carboxylate (560 mg, 1.585 mmol, 98% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ=10.30 (s, 1H), 8.24-8.13 (m, 2H), 8.10 (d, J=1.5 Hz, 1H), 7.75 (d, J=1.8 Hz, 1H), 7.57-7.46 (m, 2H), 4.98 (quin, J=6.6 Hz, 1H), 3.91 (s, 3H), 2.31 (s, 3H), 1.46 (d, J=6.6 Hz, 6H). MS(ES)+m/e 354.2 [M+H]+.
Reaction SMILES: [CH2:1]([CH:3]1[CH:29]=[C:28]([CH3:30])[CH2:27][CH:26]([CH3:31])[CH2:25][CH:24]([O:32][CH3:33])[CH:23]2[O:34][C:19]([OH:38])([CH:20]([CH3:37])[CH2:21][CH:22]2[O:35][CH3:36])[C:18](=[O:39])[C:17](=[O:40])[N:16]2[CH:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[C:10](=[O:41])[O:9][CH:8]([C:42]([CH3:70])=[CH:43][CH:44]2[CH2:49][CH2:48][C:47]([O:60][Si:61]([CH2:66][CH3:67])([CH2:64][CH3:65])[CH2:62][CH3:63])([CH2:50][CH2:51][CH:52]([C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)[OH:53])[CH:46]([O:68][CH3:69])[CH2:45]2)[CH:7]([CH3:71])[CH:6]([O:72][Si:73]([C:76]([CH3:79])([CH3:78])[CH3:77])([CH3:75])[CH3:74])[CH2:5][C:4]1=[O:80])[CH3:2].CC([O-])=O.[Na+].C1C=C[NH+]=CC=1.[O-][Cr](Cl)(=O)=O.CC(C)=O>C(Cl)Cl.C(OCC)C.CCCCCC>[CH2:1]([CH:3]1[CH:29]=[C:28]([CH3:30])[CH2:27][CH:26]([CH3:31])[CH2:25][CH:24]([O:32][CH3:33])[CH:23]2[O:34][C:19]([OH:38])([CH:20]([CH3:37])[CH2:21][CH:22]2[O:35][CH3:36])[C:18](=[O:39])[C:17](=[O:40])[N:16]2[CH:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[C:10](=[O:41])[O:9][CH:8]([C:42]([CH3:70])=[CH:43][CH:44]2[CH2:49][CH2:48][C:47]([O:60][Si:61]([CH2:66][CH3:67])([CH2:62][CH3:63])[CH2:64][CH3:65])([CH2:50][CH2:51][C:52]([C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)=[O:53])[CH:46]([O:68][CH3:69])[CH2:45]2)[CH:7]([CH3:71])[CH:6]([O:72][Si:73]([C:76]([CH3:77])([CH3:79])[CH3:78])([CH3:74])[CH3:75])[CH2:5][C:4]1=[O:80])[CH3:2]
Reactant: CCC1C=C(C)CC(C)CC(OC)C2OC(O)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C)=CC3CCC(CCC(O)c4ccccc4)(O[Si](CC)(CC)CC)C(OC)C3)C(C)C(O[Si](C)(C)C(C)(C)C)CC1=O)C(C)CC2OC
Agent: O=[Cr](=O)([O-])Cl
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CCCCCC
Solvent: ClCCl
Solvent: CCOCC
Product: CCC1C=C(C)CC(C)CC(OC)C2OC(O)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C)=CC3CCC(CCC(=O)c4ccccc4)(O[Si](CC)(CC)CC)C(OC)C3)C(C)C(O[Si](C)(C)C(C)(C)C)CC1=O)C(C)CC2OC
Temperature: 25 °C
Reaction time: 1 h
Yield: 57.8 %

Procedure:
To a solution of 17-ethyl-1-hydroxy-12-[2'-(4"-triethylsilyloxy-4"-[3-phenyl-3-hydroxypropyl]-3"-methoxycyclohexyl)-1'-methylvinyl]-14-t-butyl-dimethylsilyloxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9 ]octacos-18-ene-2,3,10,16-tetraone (10 mg, 0.009 mmole) in CH2Cl2 (2 mL) was added NaOAc (1.6 mg, 0.020 mmole) and PCC (3 mg, 0.014 mmole). The reaction mixture was then stirred 1 hour at room temperature when reaction was complete (TLC, silica, 1:4 acetone: hexane). Celite was added and the reaction was diluted with diethyl ether. After 20 min. the reaction mixture was filtered and concentrated in vacuo to give 6 mg of the title compound. MASS:(FAB) 1158(M+ + Li).
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[CH:9]1.[NH:17]1[CH2:22][CH2:21][CH:20]([C:23]2[CH:28]=[CH:27][C:26]([NH:29][C:30](=[O:33])[CH2:31][CH3:32])=[CH:25][CH:24]=2)[CH2:19][CH2:18]1>>[N:8]1([CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][N:17]2[CH2:22][CH2:21][CH:20]([C:23]3[CH:28]=[CH:27][C:26]([NH:29][C:30](=[O:33])[CH2:31][CH3:32])=[CH:25][CH:24]=3)[CH2:19][CH2:18]2)[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[CH:9]1
Reactant: CCC(=O)Nc1ccc(C2CCNCC2)cc1
Reactant: ClCCCCCCn1ccc2ccccc21
Product: CCC(=O)Nc1ccc(C2CCN(CCCCCCn3ccc4ccccc43)CC2)cc1

Procedure:
Prepared by Procedure AH and Scheme P using 1-(6-chlorohexyl)-1H-indole and N-[4-(4-piperidinyl)phenyl]propanamide: ESMS m/e: 432.3 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6](Cl)[N:5]=[CH:4][N:3]=1.[CH3:9][S-:10].[Na+]>C1COCC1.C(OCC)(=O)C.O>[Cl:1][C:2]1[CH:7]=[C:6]([S:10][CH3:9])[N:5]=[CH:4][N:3]=1
Reactant: Clc1cc(Cl)ncn1
Reactant: C[S-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CSc1cc(Cl)ncn1
Temperature: 60 °C
Reaction time: 8 h
Yield: 90.5 %

Procedure:
To a solution of 4,6-dichloro-pyrimidine (10.0 g, 67 mmol) in THF (55 ml), sodium thiomethylate (5.175 g, 74 mmol) is added under inert gas atmosphere. The reaction mixture is stirred at 60° C. overnight. After cooling down to r.t., the reaction mixture is diluted with ethyl acetate and water (100 ml each). The organic phase is removed and the aqueous phase is extracted with ethyl actetate. The combined organic phases are washed and dried, and the solvent is evaporated to give 9.74 g (90%) of a pale yellow solid (contains ca. 9% of starting material and ca. 9% of 4,6-dimethylsulfanyl-pyrimidine) which is used without any further purification.
Reaction SMILES: CC1C=CC(S(O[CH2:12][CH:13]2[CH2:17][C:16]3[CH:18]=[C:19]([C:29]([F:32])([F:31])[F:30])[CH:20]=[C:21]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([CH3:28])[CH:23]=4)[C:15]=3[O:14]2)(=O)=O)=CC=1.[CH3:33][NH2:34]>>[CH3:33][NH:34][CH2:12][CH:13]1[CH2:17][C:16]2[CH:18]=[C:19]([C:29]([F:32])([F:31])[F:30])[CH:20]=[C:21]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([CH3:28])[CH:23]=3)[C:15]=2[O:14]1
Reactant: CN
Reactant: Cc1ccc(S(=O)(=O)OCC2Cc3cc(C(F)(F)F)cc(-c4cccc(C)c4)c3O2)cc1
Product: CNCC1Cc2cc(C(F)(F)F)cc(-c3cccc(C)c3)c2O1

Procedure:
The title compound was prepared (0.026 g, 67%) following the general procedure of Example 390 as a white solid, hydrochloride salt from [7-(3-methylphenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.050 g, 0.11 mmol) and methylamine (0.12 g, 3.9 mmol). mp 228-230° C.
Reaction SMILES: [Br:1][C:2]([Br:5])(Br)Br.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:25]([C@H:30]1[CH2:35][CH2:34][C@H:33]([C:36]2[CH:43]=[CH:42][C:39]([CH:40]=O)=[CH:38][CH:37]=2)[CH2:32][CH2:31]1)[CH2:26][CH2:27][CH2:28][CH3:29].CCCCCC>C(Cl)Cl>[Br:1][C:2]([Br:5])=[CH:40][C:39]1[CH:42]=[CH:43][C:36]([C@H:33]2[CH2:34][CH2:35][C@H:30]([CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])[CH2:31][CH2:32]2)=[CH:37][CH:38]=1
Reactant: BrC(Br)(Br)Br
Reactant: CCCCC[C@H]1CC[C@H](c2ccc(C=O)cc2)CC1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCCCCC
Solvent: ClCCl
Product: CCCCC[C@H]1CC[C@H](c2ccc(C=C(Br)Br)cc2)CC1
Temperature: 0 °C
Reaction time: 0.08 h

Procedure:
A solution of 16.6 g of tetrabromomethane in 230 ml of methylene chloride was placed at 0° C. in a sulphonation flask under an argon atmosphere and treated portionwise within 10 minutes with 26.2 g of solid triphenylphosphine; there thereby resulted a clear, deep orange solution. After completion of the addition, the mixture was stirred at 0° C. for a further 5 minutes and then a solution of 6.46 g of p-(trans-4-pentylcyclohexyl)benzaldehyde in 20 ml of methylene chloride was added dropwise within 10 minutes. After stirring at 0° C. for a further 1 hour, the orange mixture was poured into 750 ml of hexane and the precipitate which thereby separated was filtered off (rinsing with hexane). The concentrated filtrate (20.4 g) was digested with 250 ml of warm hexane, filtered (rinsing with warm hexane) and the filtrate was concentrated. Low-pressure chromatography (0.5 bar) of the residual oil (9.70 g) on silica gel with 3% ethyl acetate/petroleum ether gave 8.08 g (78%) of β,β-dibromo-p-(trans-4-pentylcyclohexyl)styrene as colourless crystals (purity 97.5%); m.p. 48° C.