Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[C:2]([C:6]1[O:10][N:9]=[C:8]([NH2:11])[CH:7]=1)([CH3:5])([CH3:4])[CH3:3].C1(C)C=CC=CC=1.C[O:20][C:21](=O)[CH:22]([NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:24][CH3:25]>C1COCC1>[C:30]([O:29][C:27](=[O:28])[NH:26][CH:22]([C:21](=[O:20])[NH:11][C:8]1[CH:7]=[C:6]([C:2]([CH3:5])([CH3:4])[CH3:3])[O:10][N:9]=1)[CH2:23][CH2:24][CH3:25])([CH3:31])([CH3:32])[CH3:33]
Reactant: CC(C)(C)c1cc(N)no1
Reactant: CCCC(NC(=O)OC(C)(C)C)C(=O)OC
Agent: Cl
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: CCCC(NC(=O)OC(C)(C)C)C(=O)Nc1cc(C(C)(C)C)on1
Reaction time: 1 h
Yield: 141.2 %

Procedure:
To a solution of 5-tert-butyl-isoxazol-3-ylamine hydrochloride (1.22 g, 8.69 mmol) in THF was added 2 M AIMe3 in toluene (4.3 ml, 8.6 mmol) at room temperature and stirred for 1 hr. A solution of 2-tert-butoxycarbonylamino-pentanoic acid methyl ester (1.005 g, 4.34 mmol) in THF was added and the resulting mixture was stirred at room temperature over the weekend. The mixture was quenched with Rochelle salt and extracted with ethyl acetate. The organic layer was separated, dried and concentrated to give 2.08 g of the title compound as a crude oil. The oil was purified by silica gel column chromatography using 1% methanl in methylenechloride as eluent to give the title compound as a white solid (0.554 g). 1H NMR (CDCl3) □ 8.8 (brs, 1H), 6.7 (s, 1H), 4.85 (brs, 1H), 4.22 (m, 1H), 1.9 (m, 1H), 1.4-1.7 (m, 3H), 1.45 (s, 9H), 1.44 (s, 9H), 0.97 (t, 3H) ppm. LC-MS M+1=340.3.
Reaction SMILES: [CH:1]1([CH:4]=[O:5])[CH2:3][CH2:2]1.[Si:6]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[Mg]Br)([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7].O1CCCC1.[Cl-].[NH4+]>O1CCCC1>[CH:1]1([CH:4]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[CH2:14][O:13][Si:6]([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:7])[CH3:8])[OH:5])[CH2:3][CH2:2]1
Reactant: O=CC1CC1
Reactant: CC(C)(C)[Si](C)(C)OCc1ccccc1[Mg]Br
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CC(C)(C)[Si](C)(C)OCc1ccccc1C(O)C1CC1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
Magnesium (2.20 g) was suspended in tetrahydrofuran (4 ml) and iodine (2 mg) was added. Thereto was added dropwise a solution of 2-bromo-1-(tert-butyldimethylsilyloxymethyl)benzene (24.0 g) obtained in Step 1 in tetrahydrofuran (10 ml) over 30 min and the reaction mixture was heated under reflux for 1 hr. Thereto was added tetrahydrofuran to give 1M 2-(tert-butyldimethylsilyloxymethyl)phenylmagnesium bromide-tetrahydrofuran solution. Then cyclopropanecarboxaldehyde (2.80 g) was dissolved in tetrahydrofuran (120 ml), and 1M 2-(tert-butyldimethylsilyloxymethyl)phenylmagnesium bromide-tetrahydrofuran solution (80 ml) was added dropwise under ice-cooling over 50 min. The reaction mixture was stirred at room temperature for 12 hr. To the reaction mixture was added saturated aqueous ammonium chloride solution (8 ml) under ice-cooling and the reaction mixture was stirred at room temperature for 30 min. The reaction mixture was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=95:5) to give the title compound (8.20 g).
Reaction SMILES: [C:1]([S:11]C1C=CC(F)=CC=1)([S:3][C:4]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][CH:5]=1)=S.[H-].[Na+].[F:21][C:22]1[CH:27]=[CH:26][C:25]([C:28](=[O:32])[CH2:29][C:30]#[N:31])=[CH:24][CH:23]=1.CN(C=O)C>C1C=CC=CC=1>[C:30]([CH:29]([C:28]([C:25]1[CH:24]=[CH:23][C:22]([F:21])=[CH:27][CH:26]=1)=[O:32])[C:1]([S:3][C:4]1[CH:5]=[CH:6][C:7]([F:10])=[CH:8][CH:9]=1)=[S:11])#[N:31]
Reactant: N#CCC(=O)c1ccc(F)cc1
Reactant: Fc1ccc(SC(=S)Sc2ccc(F)cc2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: c1ccccc1
Solvent: CN(C)C=O
Product: N#CC(C(=O)c1ccc(F)cc1)C(=S)Sc1ccc(F)cc1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 30.6 %

Procedure:
Trithiocarbonate (0.644 g, 2.15 mmol) from step (i) was added to a stirred suspension of sodium hydride (0.165 g, 0.412 mmol) in benzene (2.0 mL). Then, 3-(4-fluorophenyl)-3-oxopropanenitrile (0.320 g, 1.96 mmol) was added as a solution in benzene (2.0 mL). The reaction mixture was stirred for 5 min then DMF (2.0 mL) was added slowly. After addition was complete the reaction mixture was heated to reflux for 30 min and then allowed to cool to ambient temperature before being partitioned between H2O and Et2O. The aqueous layer was separated and washed with two additional portions of Et2O, then acidified with aqueous 2 N HCl. The acidic aqueous layer was then extracted with two portions of EtOAc, which were combined, washed with brine, dried over Na2SO4, and concentrated. The residue was purified by flash chromatography, eluting with a gradient of 25-100% EtOAc/hexanes to afford the product as a yellow solid (0.20 g, 0.60 mmol, 31% yield). MS (M-H)− 332.
Reaction SMILES: [Cl:1][CH2:2][C:3](=[O:36])[C@:4]1([OH:35])[C@:21]2([CH3:22])[C@H:7]([C@H:8]3[C@H:18]([C@@H:19]([OH:23])[CH2:20]2)[C@:16]2([CH3:17])[C:11](=[CH:12][C:13](=[O:24])[CH:14]=[CH:15]2)[CH2:10][CH2:9]3)[CH2:6][C@H:5]1[O:25][CH2:26][CH2:27][O:28]C1CCCCO1>C(O)(=O)C.O>[Cl:1][CH2:2][C:3](=[O:36])[C@:4]1([OH:35])[C@:21]2([CH3:22])[C@H:7]([C@H:8]3[C@H:18]([C@@H:19]([OH:23])[CH2:20]2)[C@:16]2([CH3:17])[C:11](=[CH:12][C:13](=[O:24])[CH:14]=[CH:15]2)[CH2:10][CH2:9]3)[CH2:6][C@H:5]1[O:25][CH2:26][CH2:27][OH:28]
Reactant: C[C@]12C=CC(=O)C=C1CC[C@@H]1[C@@H]2[C@@H](O)C[C@@]2(C)[C@H]1C[C@@H](OCCOC1CCCCO1)[C@]2(O)C(=O)CCl
Solvent: CC(=O)O
Solvent: O
Product: C[C@]12C=CC(=O)C=C1CC[C@@H]1[C@@H]2[C@@H](O)C[C@@]2(C)[C@H]1C[C@@H](OCCO)[C@]2(O)C(=O)CCl

Procedure:
A solution of 21-chloro-11β,17-dihydroxy-16α-[2-(tetrahydropyran-2-yloxy)ethoxy]pregna-1,4-diene-3,20-dione (8.4 mmoles) in 50 ml of acetic acid and 50 ml of water is stirred at room temperature for 6 hours, diluted with cold water, and the resulting solid filtered and dried in vacuo to yield the title compound.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C@@H:12]([C@@H:32]2[CH2:36][CH2:35][CH2:34][N:33]2C(OC(C)(C)C)=O)[C:13]([N:15]2[CH2:20][CH2:19][N:18]([C:21]3[C:22]4[C@H:29]([CH3:30])[CH2:28][C@@H:27]([OH:31])[C:23]=4[N:24]=[CH:25][N:26]=3)[CH2:17][CH2:16]2)=[O:14])[CH:5]=[CH:6][C:7]=1[C:8]([F:11])([F:10])[F:9].CO.Cl.O1CCOCC1>ClCCl>[F:1][C:2]1[CH:3]=[C:4]([C@@H:12]([C@@H:32]2[CH2:36][CH2:35][CH2:34][NH:33]2)[C:13]([N:15]2[CH2:16][CH2:17][N:18]([C:21]3[C:22]4[C@H:29]([CH3:30])[CH2:28][C@@H:27]([OH:31])[C:23]=4[N:24]=[CH:25][N:26]=3)[CH2:19][CH2:20]2)=[O:14])[CH:5]=[CH:6][C:7]=1[C:8]([F:10])([F:9])[F:11]
Reactant: C[C@@H]1C[C@@H](O)c2ncnc(N3CCN(C(=O)[C@@H](c4ccc(C(F)(F)F)c(F)c4)[C@@H]4CCCN4C(=O)OC(C)(C)C)CC3)c21
Agent: Cl
Solvent: C1COCCO1
Solvent: ClCCl
Solvent: CO
Product: C[C@@H]1C[C@@H](O)c2ncnc(N3CCN(C(=O)[C@@H](c4ccc(C(F)(F)F)c(F)c4)[C@@H]4CCCN4)CC3)c21
Temperature: 25 °C
Reaction time: 8 h
Yield: 98.5 %

Procedure:
(S)-tert-Butyl 2-((S)-1-(3-fluoro-4-(trifluoromethyl)phenyl)-2-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-2-oxoethyl)pyrrolidine-1-carboxylate (0.040 g, 0.066 mmol) was dissolved in dichloromethane (4 mL) and MeOH (1 mL) and treated with HCl in dioxane (2 mL, 8.0 mmol). The mixture was stirred at ambient temperature overnight. The reaction was concentrated in vacuo to produce the desired product (0.033 g, 99% yield). MS (APCI+) [M+H] 508.1; 2.13 minutes.
Reaction SMILES: [C:1]([NH2:6])(=[O:5])[CH:2]([CH3:4])[CH3:3].N1C=CC=CC=1.Cl.N1C=CC=CC=1.[CH2:20]=[C:21]1[O:25][C:23](=[O:24])[CH2:22]1>ClC=C(Cl)Cl>[C:23]([NH:6][C:1](=[O:5])[CH:2]([CH3:4])[CH3:3])(=[O:24])[CH2:22][C:21]([CH3:20])=[O:25]
Reactant: C=C1CC(=O)O1
Reactant: CC(C)C(N)=O
Agent: Cl
Solvent: ClC=C(Cl)Cl
Solvent: c1ccncc1
Product: CC(=O)CC(=O)NC(=O)C(C)C
Yield: 83.6 %

Procedure:
Isobutyramide (8.7 g, 0.1 mole), pyridine (0.40 g, 0.005 mole), pyridine hydrochloride (1.73 g, 0.015 mole), diketene (8.4 g, 0.1 mole) and trichloroethylene (100 ml) were placed in a 250 ml, 3-neck flask equipped with a magnetic stirrer, a thermometer, a condenser, a drying tube and a heating mantle. The mixture was slowly heated to 80°, and the temperature range of 75°-81° was maintained for 1 hour. The slightly cooled reaction mixture was poured into a 500 ml, r.b. flask and the solvent was stripped off to give an orange oil. Crude N-acetoacetylisobutyramide thus obtained was dissolved in toluene (100 ml) and placed in a 250 ml, 3-neck flask equipped similarly as in Example 1. After addition of acetic acid (3 g, 0.05 mole), ammonia gas was bubbled in as the reaction mixture was heated at reflux for 1 hour and was further refluxed for 1 hour after the ammonia was turned off. Chloroform (~50 ml) was added to the cooled reaction mixture and the insoluble solid was filtered and washed with chloroform (~ 50 ml). The solvent of the filtrate was stripped off and 15.51 g (81.9%, by weight, of oxypyrimidine) of yellow crystals having m.p. 148°-160° were obtained. The yield was 83.6%.
Reaction SMILES: C1(C)C=CC(S([CH2:10][N+:11]#[C-:12])(=O)=O)=CC=1.[C:14]([O:21][CH3:22])(=[O:20])/[CH:15]=[CH:16]/[CH2:17][CH2:18][CH3:19].CC(C)([O-])C.[K+]>>[CH2:17]([C:16]1[C:15]([C:14]([O:21][CH3:22])=[O:20])=[CH:10][NH:11][CH:12]=1)[CH2:18][CH3:19]
Reactant: [C-]#[N+]CS(=O)(=O)c1ccc(C)cc1
Reactant: CCC/C=C/C(=O)OC
Agent: CC(C)(C)[O-]
Agent: [K+]
Product: CCCc1c[nH]cc1C(=O)OC
Yield: 38 %

Procedure:
Using p-toluenesulfonylmethyl isocyanide (8.6 g), methyl (2E)-hex-2-enoate (5.67 g) and potassium tert-butoxide (5.9 g), a procedure as in Reference Example 39 was performed to give the title compound as colorless crystals (yield 2.8 g, 38%).
Reaction SMILES: C([Mg]Cl)(C)C.[Cl:6][C:7]1[C:12]([O:13][Si](C)(C)C)=[C:11]([C:18]([O:20][Si](C)(C)C)=[CH2:19])[CH:10]=[CH:9][C:8]=1[O:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30](I)=[CH:29][CH:28]=1.[H-].[Na+].[O:36]=[C:37]1[O:41][N:40]=[C:39]([C:42]2[CH:43]=[C:44]([CH:47]=[CH:48][CH:49]=2)[CH:45]=[O:46])[NH:38]1>O1CCCC1>[C:18]([C:11]1[CH:10]=[CH:9][C:8]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][C:30]([CH:45]([OH:46])[C:44]3[CH:43]=[C:42]([C:39]4[NH:38][C:37](=[O:36])[O:41][N:40]=4)[CH:49]=[CH:48][CH:47]=3)=[CH:29][CH:28]=2)=[C:7]([Cl:6])[C:12]=1[OH:13])(=[O:20])[CH3:19]
Reactant: C=C(O[Si](C)(C)C)c1ccc(OCc2ccc(I)cc2)c(Cl)c1O[Si](C)(C)C
Reactant: O=Cc1cccc(-c2noc(=O)[nH]2)c1
Agent: CC(C)[Mg]Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(=O)c1ccc(OCc2ccc(C(O)c3cccc(-c4noc(=O)[nH]4)c3)cc2)c(Cl)c1O
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
Add isopropyl magnesium chloride (2M solution in tetrahydrofuran, 1.01 ml, 2.02 mmol) to a solution of 2-chloro-1-(4-iodo-benzyloxy)-3-trimethylsilanyloxy-4-(1′-trimethylsilanyloxy-vinyl)-benzene (1.00 g, 1.83 mmol) in tetrahydrofuran (0.1M) at 0° C. After 15 minutes, warm to room temperature. After 1 hour, cool to −78° C. Add sodium hydride (60% dispersion, 80 mg, 2.01 mmol) to a solution of 3-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)-benzaldehyde (348 mg, 1.83 mmol) in tetrahydrofuran (0.1M). Sonicate the solution for 5 minutes, then add it via syringe to the gringard reagent. After 30 minutes, warm the reaction to room temperature. Quench with 10% aq hydrochloric acid. Pour the reaction into brine and extract with 25% isopropyl alcohol:75% dichloromethane. Combine the organic layers, dry with sodium sulfate, filter, and concentrate under reduced pressure to give a residue. Purify the residue by flash chromatography eluting with 5% methanol:methylene chloride to yield the title product as a off white solid (389 mg, 46%): 1H NMR (DMSO-d6) δ 2.61 (s, 3H), 5.31 (s, 2H), 5.80 (d, 1H), 6.12 (d, 1H), 6.87 (d, 1H), 7.43 (m, 4H), 7.51 (t, 1H), 7.64 (tt, 2H), 7.90 (t, 1H), 7.91 (d, 1H), 12.96 (bs, 1H), 13.12 (s, 1H); MS (esi negative) m/z (rel intensity) 465 (100).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.[CH2:8]([NH:11][CH2:12][CH:13]=[CH2:14])[CH:9]=[CH2:10]>>[CH2:8]([N:11]([CH2:12][CH:13]=[CH2:14])[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1)[CH:9]=[CH2:10]
Reactant: Clc1ccncc1
Reactant: C=CCNCC=C
Product: C=CCN(CC=C)c1ccncc1
Temperature: 130 °C
Yield: 64.9 %

Procedure:
The title compound was prepared by hydrosilation of 4-diallylaminopyridine with dimethyl(ethoxy)silane, (ETO)Me2SiH. The 4-diallylaminopyridine was obtained by reaction of 4-chloropyridine with diallylamine. Thus, in an experiment similar to that described in Example 1, 4-chloropyridine (11.2 g; 0.10 mol) and diallylamine (14.6 g; 0.15 mol) were combined in an ampoule, degassed under vacuum, sealed and heated for three days at 130° C. The product mixture was dissolved in water, neutralized with 10% NaOH and extracted with several portions of diethyl ether. The ether solution was filtered, the solvent was evaporated, and the residue was distilled to give 4-diallylaminopyridine (11.3 g; 65%; b.p. 92° C. @0.25 torr). 4-Diallylaminopyridine (5.2 g; 0.030 mol), (ETO)Me2SiH (8.3g; 0.080 mol), and H2PtCl6 (60 μL; 0.080 mol/L in isopropylalcohol (i-PrOH); 4.6×10-6 mol) were combined as in Example 1 and heated for 10 hours at 130° C. After reaction the product mixture was distilled under vacuum to give Silane 2a, N,N[bis(3-(dimethyl(ethoxy)silyl)propyl)-4-aminopyridine, as a colorless liquid (5.75 g; 50%; b.p. 142°-146° C. @0.05 torr), which was also characterized by elemental analysis, infrared, 1H and 13C-NMR spectroscopy, and gas chromatography-mass spectrometry.
Reaction SMILES: [F:1][C:2]1[C:3]([F:11])=[C:4]([F:10])[C:5]([F:9])=[C:6]([F:8])[CH:7]=1.C(OCC)C.C([Li:21])(C)(C)C>CCCCC>[F:1][C:2]1[C:7]([Li:21])=[C:6]([F:8])[C:5]([F:9])=[C:4]([F:10])[C:3]=1[F:11]
Reactant: Fc1cc(F)c(F)c(F)c1F
Reactant: [Li]C(C)(C)C
Solvent: CCOCC
Solvent: CCCCC
Product: [Li]c1c(F)c(F)c(F)c(F)c1F
Temperature: -65 °C

Procedure:
Inside of a 100 ml volume glass three-neck flask equipped with a 50 ml volume glass dropping funnel, temperature resistor and septum rubber was sufficiently replaced with nitrogen. Into the flask, 5 g (29.8 mmol) of pentafluorobenzene and 30 ml of diethyl ether were charged, of which solution was cooled to -65° C. Thereafter, 12.3 g (29.8 mmol) of 15.5 wt. % pentane solution of tert-butyllithium charged into the dropping funnel were added dropwise while making the inner temperature not to exceed -55° C. After the completion of dropwise addition, the reaction mixture was kept at a temperature of -65°~-55° C. with stirring to give pentafluorophenyllithium.
Reaction SMILES: [H-].[Na+].[C:3]1([CH2:9][C:10]#[N:11])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Br[CH2:13][CH2:14][CH2:15]Br.O.C1(C)C=CC=CC=1>CN(C=O)C>[C:3]1([C:9]2([C:10]#[N:11])[CH2:15][CH2:14][CH2:13]2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: BrCCCBr
Reactant: N#CCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Solvent: Cc1ccccc1
Product: N#CC1(c2ccccc2)CCC1
Temperature: 0 °C
Reaction time: 2 h
Yield: 64.9 %

Procedure:
Sodium hydride (1.54 g, 64.1 mmol) dissolved in DMF (15 ml) and cooled to 0° C. Phenyl acetonitrile (3 g, 25.6 mmol) and 1,3-dibromopropane (5.2 g, 25.6 mmol) were dissolved in DMF (15 ml) and added to above mixture drop-wise at 0° C. This mixture was heated to rt and continued stirring for 2 h. Work up (H2O/Toluene) afforded the title compound (2.61 g) as crude, which was used in the next without further purification.
Reaction SMILES: [C:1]([O-:4])([O-])=O.[K+].[K+].[F:7][C:8]1[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=1C=O.O.C[S:18]([CH3:20])=O>>[F:7][C:8]1[CH:9]=[CH:12][C:13]([S:18][C:20]2[CH:14]=[CH:15][CH:8]=[CH:9][C:12]=2[CH:1]=[O:4])=[CH:14][CH:15]=1
Reactant: O=C([O-])[O-]
Reactant: O=Cc1ccccc1F
Reactant: CS(C)=O
Agent: [K+]
Solvent: O
Product: O=Cc1ccccc1Sc1ccc(F)cc1
Temperature: 100 °C
Yield: 64 %

Procedure:
To a suspension of 4-fluorophenylthiol (0.86 ml, 8.06 mmol) and K2CO3 (2.50 g, 18.12 mmol) in DMSO (5 ml) was added 2-fluorobenzaldehyde (1.00 g, 8.06 mmol) under N2 and the mixture heated at 100° C. for 3 hours. The reaction was cooled to room temperature and water (20 ml) added. This mixture was extracted with ethyl acetate, the combined organic extracts were washed with saturated brine, dried over MgSO4 and concentrated in vacuo to give a yellow solid (1.20 g, 5.17 mmol, 64%) δH (300 MHz, 4-DMSO) 10.23 (1H, s, CHO), 7.98 (1H, dd, J 7.3 and 1.7 Hz, Ar), 7.63-7.49 (3H, m, Ar), 7.45-7.32 (3H, m, Ar) and 6.88 (1H, d, J=7.7 Hz, Ar).
Reaction SMILES: [C:1]([OH:5])(=[O:4])[CH:2]=[CH2:3].[F:6][C:7]([F:25])([C:21]([F:24])([F:23])[F:22])[C:8]([F:20])([F:19])[O:9][C:10]([F:18])([F:17])[C:11]([F:16])([F:15])[CH2:12][CH2:13]O.C1(C)C=CC(S(O)(=O)=O)=CC=1>>[F:15][C:11]([F:16])([C:10]([F:17])([F:18])[O:9][C:8]([F:19])([F:20])[C:7]([F:6])([F:25])[C:21]([F:22])([F:24])[F:23])[CH2:12][CH2:13][O:4][C:1](=[O:5])[CH:2]=[CH2:3]
Reactant: OCCC(F)(F)C(F)(F)OC(F)(F)C(F)(F)C(F)(F)F
Reactant: C=CC(=O)O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Product: C=CC(=O)OCCC(F)(F)C(F)(F)OC(F)(F)C(F)(F)C(F)(F)F

Procedure:
Acrylic acid was esterified with 2-[2-(heptafluoropropoxy)-tetrafluoroethyl]-ethyl alcohol (US 2008113199 A1) in the presence catalytic amounts of p-toluene sulfonic acid to yield acrylic acid 3,3,4,4-tetrafluoro-4-heptafluoropropyloxy-butyl ester quantitatively. The ester was washed with water and distilled prior to the reaction with APTES (Aminopropyl triethoxysilane, CAS#919-30-2). A solution of one equivalent of APTES and two equivalents acrylic acid 3,3,4,4-tetrafluoro-4-heptafluoropropyloxy-butyl in absolute ethanol were allowed to stir at 60° C. for 5 h. The solvent was distilled of under reduced pressure to provide the desired twin-tail silane (tertiary amine fluorosilane) quantitatively as a colorless oil.
Reaction SMILES: N1C=[C:5]([CH2:7][O:8][C:9]2[N:14]=[CH:13][C:12]([NH2:15])=[CH:11][CH:10]=2)[CH:4]=[CH:3][CH:2]=1.[NH:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18]([C:25]([OH:27])=O)=[CH:17]1.C1CC[CH:31]([N:34]=C=NC2CCCCC2)CC1>CN(C=O)C>[N:34]1[CH:31]=[CH:2][CH:3]=[CH:4][C:5]=1[CH2:7][O:8][C:9]1[N:14]=[CH:13][C:12]([NH:15][C:25]([C:18]2[C:19]3[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=3)[NH:16][CH:17]=2)=[O:27])=[CH:11][CH:10]=1
Reactant: C(=NC1CCCCC1)=NC1CCCCC1
Reactant: Nc1ccc(OCc2cccnc2)nc1
Reactant: O=C(O)c1c[nH]c2ccccc12
Solvent: CN(C)C=O
Product: O=C(Nc1ccc(OCc2ccccn2)nc1)c1c[nH]c2ccccc12
Temperature: 80 °C
Reaction time: 8 h
Yield: 22.4 %

Procedure:
The 6-(pyridine-5-ylmethoxy)-pyridine-3-ylamine (114 mg, 0.57 mmol) and indole-3-carboxylic acid (91 mg, 0.57 mmol) were dissolved in DMF (3 ml), DCC (117 mg, 0.57 mmol) was added to the solution, and then the mixture was stirred at 80° C. for 8 hours. After the reaction was completed, the product was washed and filtered to yield a target compound as a white solid (44 mg, 23%) by chromatography (methanol:dichloromethane=2:30).
Reaction SMILES: [C:1]([O:4][CH2:5][CH:6]([CH2:10]Br)[CH:7]([CH3:9])[CH3:8])(=[O:3])[CH3:2].[S-:12][C:13]#[N:14].[K+].O>CN(C)C=O>[C:1]([O:4][CH2:5][CH:6]([CH2:10][S:12][C:13]#[N:14])[CH:7]([CH3:9])[CH3:8])(=[O:3])[CH3:2]
Reactant: N#C[S-]
Reactant: CC(=O)OCC(CBr)C(C)C
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(=O)OCC(CSC#N)C(C)C

Procedure:
A mixture of 2-bromomethyl-3-methylbutyl acetate (6 g) and potassium thiocyanate (7.3 g) in dry dimethylformamide (50 ml) was heated at 140° for 2 hours. After cooling, the reaction mixture was poured into water (150 ml) and then extracted with diethylether (3×50 ml). The combined ethereal extracts were washed with water (3×50 ml) before drying over anhydrous magnesium sulphate and evaporation in vacuo. 2-Thiocyanatomethyl-3methylbutyl acetate was obtained and was used without further purification.
Reaction SMILES: [C:1]([O:5][C:6](=[O:28])[NH:7][CH:8]([CH2:17][O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[CH2:26]O)[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([Br:16])=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].C1C(=O)N([Br:36])C(=O)C1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(=O)OCC>C1COCC1>[C:1]([O:5][C:6](=[O:28])[NH:7][CH:8]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([Br:16])=[CH:12][CH:11]=1)[CH2:17][O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[CH2:26][Br:36])([CH3:4])([CH3:3])[CH3:2]
Reactant: O=C1CCC(=O)N1Br
Reactant: CC(C)(C)OC(=O)NC(COCc1ccccc1CO)Cc1ccc(Br)cc1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)NC(COCc1ccccc1CBr)Cc1ccc(Br)cc1
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 48.7 %

Procedure:
To a solution of compound 3h (4.15 g, 9.2 mmol) in dry THF (50 mL) was added NBS (4.1 g, 23 mmol) and PPh3 (6 g, 23 mmol) at 0° C. The mixture was stirred at 0° C. for 20 min. Then the mixture was stirred at rt for 2 hr. The solvent was evaporated in vacuo and purified by CC eluting with PE:EA=4:1 to give 3i as a white solid (2.3 g, 50% yield).
Reaction SMILES: [CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:25]([CH:26]=[O:27])[CH2:24][CH2:23][CH2:22][C:21]([C:28]([O:30]C)=[O:29])=[CH:20][C:19]=3[CH:32]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4].O1CCCC1.[OH-].[Na+].Cl>O.CO>[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:25]([CH:26]=[O:27])[CH2:24][CH2:23][CH2:22][C:21]([C:28]([OH:30])=[O:29])=[CH:20][C:19]=3[CH:32]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)OC)CCCN3C=O)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Solvent: C1CCOC1
Product: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)O)CCCN3C=O)cc1
Temperature: 90 °C
Reaction time: 19 h
Yield: 50.7 %

Procedure:
To methyl 8-(4-(2-butoxyethoxy)phenyl)-1-formyl-1,2,3,4-tetrahydro-1-benzoazocine-5-carboxylate (4.5 g) were added tetrahydrofuran (66 ml) and methanol (66 ml), followed by adding aqueous 1N sodium hydroxide solution (22 ml). The mixture was stirred at 90° C. for 19 hours. After cooling to 0° C., water was added and the mixture was neutralized with 1N hydrochloric acid. After extracting with ethyl acetate, the organic layer was washed with saturated brine, and dried with magnesium sulfate. The solvent was distilled off under reduced pressure, and the reaction material was re-crystallized from hexane-ethyl acetate to give 8-(4-(2-butoxyethoxy)phenyl)-1-formyl-1,2,3,4-tetrahydro-1-benzoazocine-5-carboxylic acid (2.21 g) as yellow crystals.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[Si:16]([CH3:19])([CH3:18])[CH3:17].CCN(CC)CC>CN(C=O)C.CCOCC>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH:10]=[C:11]([O:14][Si:16]([CH3:19])([CH3:18])[CH3:17])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Reactant: C[Si](C)(C)Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: CCOCC
Product: CC(C)(C)OC(=O)N1CC=C(O[Si](C)(C)C)CC1
Temperature: 80 °C
Reaction time: 16 h
Yield: 26.1 %

Procedure:
4-Oxo-piperidine-1-carboxylic acid tert-butyl ester (10.0 g, 501 mmol) was dissolved in DMF (20 mL). Chlorotrimethylsilane (6.6 g, 60.6 mmol) was added, followed by Et3N (12.3 g, 122 mmol). The mixture was stirred at 80° C. for 16 hours, cooled to ambient temperature, diluted with Et2O, and then washed with water, followed by brine. The organic layer was separated, dried over Na2SO4, filtered and concentrated. Purification by flash chromatography on silica gel (EtOAc/heptanes 0-50%) afforded 4-trimethylsilanyloxy-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (4.3 g, 32% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 4.80 (br. s., 1H), 3.88 (br. s., 2H), 3.53 (t, J=5.81 Hz, 2H), 2.11 (br. s., 2H), 1.49 (s, 9H), 0.20 (s, 9H).