Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[CH:10]=[N:9][NH:8][C:5]2=[N:6][CH:7]=1.[N:11]1([C:17]([C:19]2[CH:20]=[C:21](B(O)O)[CH:22]=[CH:23][CH:24]=2)=[O:18])[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1.C(=O)(O)[O-].[Na+].C1(P(=O)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(COC)OC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.ClCCl>[N:11]1([C:17]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:2]3[CH:3]=[C:4]4[CH:10]=[N:9][NH:8][C:5]4=[N:6][CH:7]=3)[CH:20]=2)=[O:18])[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1
Reactant: Brc1cnc2[nH]ncc2c1
Reactant: O=C(c1cccc(B(O)O)c1)N1CCOCC1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])O
Agent: O=P(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: ClCCl
Solvent: COCCOC
Product: O=C(c1cccc(-c2cnc3[nH]ncc3c2)c1)N1CCOCC1
Yield: 98.5 %

Procedure:
A mixture of 5-bromo-1H-pyrazolo[3,4-b]pyridine (1.50 g, 7.57 mmol), 3-(morpholin-4-carbonyl)phenylboronic acid (2.136 g, 9.09 mmol) and tetrakis(triphenylphosphine)palladium(0) (435 mL, 0.376 mmol) in dimethoxyethane (8 mL) and saturated aqueous solution of sodium bicarbonate (8 mL) was irradiated in a Personal Chemistry Optimizer at 175° C. for 60 min. The crude reaction mixture was distributed between dichloromethane and a saturated aqueous solution of sodium bicarbonate. The aqueous phase was then extracted with dichloromethane, and then ethyl acetate and the combined organic phases were dried over sodium sulfate, filtered and concentrated to afford a pale green foam containing 80% of morpholin-4-yl-[3-(1H-pyrazolo[3,4-b]pyridin-5-yl)-phenyl]-methanone (2.30 g, 80% yield) and 20% of triphenylphosphine oxide. 1H-NMR (500 MHz, d6-DMSO) δ 13.75 (s, 1H), 8.87 (d, 1H), 8.54 (d, 1H), 8.21 (d, 1H), 7.85 (m, 1H), 7.77 (m, 1H), 7.58 (t, 1H), 7.41 (m, 1H).
Reaction SMILES: [C:1]1([C:7]2[C:11]([C:12](O)=[O:13])=[C:10](/[CH:15]=[CH:16]/[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[O:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.ClC(OCC)=O.[BH4-].[Na+].[OH-].[Na+]>C1COCC1.O>[C:1]1([C:7]2[C:11]([CH2:12][OH:13])=[C:10](/[CH:15]=[CH:16]/[C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[O:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C(O)c1c(-c2ccccc2)noc1/C=C/c1ccccc1
Agent: CCOC(=O)Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: OCc1c(-c2ccccc2)noc1/C=C/c1ccccc1
Yield: 98.8 %

Procedure:
To a stirred solution of 3-phenyl-5-((E)-styryl)-isoxazole-4-carboxylic acid (2.0 g, 6.9 mmol) in THF (50 mL) was added triethylamine (0.95 mL, 6.9 mmol). Then at room temperature ethyl chloroformate (0.65 mL, 6.9 mmol) was added dropwise. After 30 min the precipitated salt was filtered and washed with a small amount of THF. The filtrate was added to a solution of sodium borohydride (0.65 g, 17.1 mmol) in water (20 mL) at 5° C. After stirring for 1 h at 5° C. aqueous sodium hydroxide (2 M, 40 mL) was added. Extraction with ethyl acetate, drying over sodium sulfate, filtering and concentration afforded the title compound as a white solid (1.89 g, 99%). MS: m/e=278.1 [M+H]+.
Reaction SMILES: C([SiH](CC)CC)C.[CH3:8][O:9][C:10](=[O:24])[C:11]([C:13]1[C:21]2[C:16](=[N:17][C:18]([Cl:22])=[CH:19][CH:20]=2)[NH:15][C:14]=1[CH3:23])=O>C(O)(C(F)(F)F)=O>[CH3:8][O:9][C:10](=[O:24])[CH2:11][C:13]1[C:21]2[C:16](=[N:17][C:18]([Cl:22])=[CH:19][CH:20]=2)[NH:15][C:14]=1[CH3:23]
Reactant: COC(=O)C(=O)c1c(C)[nH]c2nc(Cl)ccc12
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Product: COC(=O)Cc1c(C)[nH]c2nc(Cl)ccc12
Temperature: -10 °C
Reaction time: 1 h

Procedure:
To a solution of triethylsilane (0.343 ml, 2.15 mmol) in TFA (2 ml) cooled to −10° C. is added portionwise (6-chloro-2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-oxo-acetic acid methyl ester (0.155 g, 0.61 mmol). The reaction mixture is stirred at −10° C. for 1 hour and the solvent is removed in vacuo. The residue is washed with saturated sodium hydrogen carbonate solution and this aqueous portion is extracted with DCM (3×10 ml). The organics are combined, dried (Na2SO4) and concentrated in vacuo and the resulting crude is purified by chromatography on silica eluting with methanol/DCM (0-0.5% methanol) to yield the titled product as an off-white powder. (MH+239).
Reaction SMILES: C1CO[C:3]2([CH2:12][CH2:11][C@H:10]3[C@:5]([C:15]4[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[CH:16]=4)([CH2:6][CH2:7][N:8]([CH3:14])[C:9]3=[O:13])[CH2:4]2)[O:2]1.CCOCC.[Na+].[Cl-].C(OCC1C(=O)N(C)CCC=1C1C=CC=C(OC)C=1)=O>C1COCC1>[O:13]=[C:9]1[C@@H:10]2[C@@:5]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[CH:16]=3)([CH2:4][C:3](=[O:2])[CH2:12][CH2:11]2)[CH2:6][CH2:7][N:8]1[CH3:14]
Reactant: COc1cccc([C@]23CCN(C)C(=O)[C@H]2CCC2(C3)OCCO2)c1
Agent: COc1cccc(C2=C(COC=O)C(=O)N(C)CC2)c1
Agent: [Cl-]
Agent: [Na+]
Solvent: CCOCC
Solvent: C1CCOC1
Product: COc1cccc([C@]23CCN(C)C(=O)[C@H]2CCC(=O)C3)c1
Reaction time: 60 h

Procedure:
Ketal cis-34 (Example 16) (20 mg, 0.06 mmol) was dissolved in 1:1 THF/1 N H2SO4 (2 mL) and stirred for 60 h. Ether (2 mL) and saturated NaCl (1 mL) were added, the aqueous phase washed with ether (1 mL), and the combined organic phases washed with saturated NaCl (2 mL), dried, and evaporated to yield 17 mg (99%) of pure cis-9: NMR δ 7.30 (t,J=9 Hz, 1H), 6.9 (m, 3H), 3.78 (s, 3H), 7.87 (s, 3H), 2.63 (s, 2H); IR 1712, 1634, 1603, 1580 cm-1 ; mass spectrum m/e (rel intensity) 287 (32), 218 (26), 55 (100). Anal. Calcd for C17H21NO3 : C, 71.0; H, 7.4; N, 4.9. Found: C, 71.0, H, 7.4; N, 4.9.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[SH:8].[OH:9][C:10]1[CH:18]=[CH:17][C:13]([C:14](O)=O)=[CH:12][C:11]=1[N+:19]([O-:21])=[O:20].O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.CS(O)(=O)=O.C(=O)(O)[O-].[Na+].[OH-].[Na+]>>[S:8]1[C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[N:1]=[C:14]1[C:13]1[CH:17]=[CH:18][C:10]([OH:9])=[C:11]([N+:19]([O-:21])=[O:20])[CH:12]=1
Reactant: Nc1ccccc1S
Reactant: O=C(O)c1ccc(O)c([N+](=O)[O-])c1
Agent: CS(=O)(=O)O
Agent: O=C([O-])O
Agent: O=P12OP3(=O)OP(=O)(O1)OP(=O)(O2)O3
Product: O=[N+]([O-])c1cc(-c2nc3ccccc3s2)ccc1O
Temperature: 90 °C
Yield: 20.2 %

Procedure:
A mixture of 14.8 g 2-aminothiophenol, 21.6 g 4-hydroxy-3-nitrobenzoic acid, 18 g phosphorus pentoxide and 180 g methanesulfonic acid was heated at 90° C. for 10 hours. The reaction mixture was brought to pH 5 byaddition of sodium bicarbonate and sodium hydroxide solutions, and the solid product collected. The latter was recrystallized first from ethyl acetate and then from acetonitrile to give 6.5 g of the above-indicated product, orange-brown needles, m.p. 214°-215° C.
Reaction SMILES: [OH:1][C@H:2]1[CH2:6][NH:5][C@H:4]([C:7]([OH:9])=[O:8])[CH2:3]1.[CH2:10]([O:17][C:18](Cl)=[O:19])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>[OH-].[Na+]>[CH2:10]([O:17][C:18]([N:5]1[CH2:6][C@H:2]([OH:1])[CH2:3][C@H:4]1[C:7]([OH:9])=[O:8])=[O:19])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: O=C(O)[C@@H]1C[C@@H](O)CN1
Agent: [Na+]
Agent: [OH-]
Product: O=C(O)[C@@H]1C[C@@H](O)CN1C(=O)OCc1ccccc1
Temperature: 25 °C

Procedure:
Trans-4-hydroxy-L-proline (4.7 g) was dissolved in 2N sodium hydroxide (36 ml), to which benzyloxycarbonylchloride (6.1 g) was slowly added dropwise under cooling with ice water. The mixture was then stirred at room temperature throughout a whole day and night. After the reaction, the mixture was washed with ethyl acetate, and to the aqueous layer was then added sodium chloride to saturation. Then the pH was adjusted to around 3 with 10N hydrochloric acid and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated solution of sodium chloride in water and it was then dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure whereby the titled compound (6.9 g) was obtained.
Reaction SMILES: [Br:1][C:2]1[C:3]([O:9][CH3:10])=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1.[Br:11]N1C(=O)CCC1=O.N(C(C)(C)C#N)=NC(C)(C)C#N>C1C=CC=CC=1.O>[Br:1][C:2]1[C:3]([O:9][CH3:10])=[N:4][CH:5]=[C:6]([CH2:8][Br:11])[CH:7]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: COc1ncc(C)cc1Br
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: c1ccccc1
Solvent: O
Product: COc1ncc(CBr)cc1Br
Temperature: 80 °C
Reaction time: 8 h

Procedure:
3-Bromo-2-methoxy-5-methyl-pyridine (4.0 g, 19.8 mmol), N-bromosuccinimide (4.45 g, 23.8 mmol), and azobisisobutyronitrile (0.163 g, 0.99 mmol) were combined in benzene (40 mL) and stirred overnight at 80° C. The reaction was stirred for another 24 hours at 80° C., and then additional N-bromosuccinimide (1.8 g, 10.1 mmol), and azobisisobutyronitrile (catalytic) were added. After stirring for another 2 hours at 80° C., the mixture was diluted with H2O and extracted with CH2Cl2. The residue was purified by silica gel chromatography to give 3-bromo-5-bromomethyl-2-methoxy-pyridine.
Reaction SMILES: C1(P(=O)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.C([S:43][CH:44]([CH:77]([O:80][CH3:81])[O:78][CH3:79])[CH2:45][NH:46][C:47]([C:49]1[NH:50][C:51]2[C:56]([CH:57]=1)=[CH:55][C:54]([O:58][CH2:59][CH2:60][CH2:61][S:62]([CH3:65])(=[O:64])=[O:63])=[CH:53][C:52]=2[N:66]([CH3:76])[S:67]([C:70]1[CH:75]=[CH:74][CH:73]=[CH:72][N:71]=1)(=[O:69])=[O:68])=O)C1C=CC=CC=1.C1(SC)C=CC=CC=1>ClCCl.C(OCC)(=O)C>[CH3:79][O:78][CH:77]([O:80][CH3:81])[CH:44]1[S:43][C:47]([C:49]2[NH:50][C:51]3[C:56]([CH:57]=2)=[CH:55][C:54]([O:58][CH2:59][CH2:60][CH2:61][S:62]([CH3:65])(=[O:64])=[O:63])=[CH:53][C:52]=3[N:66]([CH3:76])[S:67]([C:70]2[CH:75]=[CH:74][CH:73]=[CH:72][N:71]=2)(=[O:69])=[O:68])=[N:46][CH2:45]1
Reactant: COC(OC)C(CNC(=O)c1cc2cc(OCCCS(C)(=O)=O)cc(N(C)S(=O)(=O)c3ccccn3)c2[nH]1)SCc1ccccc1
Agent: O=P(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Solvent: CSc1ccccc1
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: COC(OC)C1CN=C(c2cc3cc(OCCCS(C)(=O)=O)cc(N(C)S(=O)(=O)c4ccccn4)c3[nH]2)S1
Reaction time: 0.25 h
Yield: 37.6 %

Procedure:
A mixture of triphenylphosphine oxide (1.17 g), trifluoromethanesulfonic anhydride (1.18 g) and dichloromethane (30 mL) was stirred for 15 min under ice-cooling. A solution of N-[2-(benzylthio)-3,3-dimethoxypropyl]-7-[methyl(pyridin-2-ylsulfonyl)amino]-5-[3-(methylsulfonyl)propoxy]-1H-indole-2-carboxamide (2.65 g) and thioanisole (940 mg) in dichloromethane (10 mL) was added dropwise to the reaction mixture under ice-cooling, and the mixture was stirred for 30 min under ice-cooling. The reaction mixture was diluted with ethyl acetate, and extracted with 3N hydrochloric acid. The aqueous layer was alkalified with 2N aqueous sodium hydroxide solution, and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4), and concentrated. The obtained residue was subjected to silica gel column chromatography, and eluted with hexane-ethyl acetate (2:8-1:9, volume ratio) to give the title compound (840 mg, yield 38%) as a colorless amorphous solid.
Reaction SMILES: CS(O[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]/[CH:14]=[CH:15]\[CH2:16]/[CH:17]=[CH:18]\[CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])(=O)=O.[Br-:24].[Mg+2].[Br-].O>CCOCC>[CH2:6]([Br:24])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]/[CH:14]=[CH:15]\[CH2:16]/[CH:17]=[CH:18]\[CH2:19][CH2:20][CH2:21][CH2:22][CH3:23]
Reactant: CCCCC/C=C\C/C=C\CCCCCCCCOS(C)(=O)=O
Reactant: [Br-]
Agent: [Mg+2]
Solvent: O
Solvent: CCOCC
Product: CCCCC/C=C\C/C=C\CCCCCCCCBr
Reaction time: 21 h
Yield: 109.6 %

Procedure:
A mixture of linoleyl methane sulfonate (6.2 g, 18 mmol) and magnesium bromide etherate (17 g, 55 mmol) in anhydrous ether (300 mL) was stirred under argon overnight (21 hours). The resulting suspension was poured into 300 mL of chilled water. Upon shaking, the organic phase was separated. The aqueous phase was extracted with ether (2×150 mL). The combined ether phase was washed with water (2×150 mL), brine (150 mL), and dried over anhydrous Na2SO4. The solvent was evaporated to afford 6.5 g of colourless oil. The crude product was purified by column chromatography on silica gel (230-400 mesh, 300 mL) and eluted with hexanes. This gave 6.2 g (approximately 100%) of linoleyl bromide (II). 1H NMR (400 MHz, CDCl3) δ: 5.27-5.45 (4H, m, 2×CH═CH), 3.42 (2H, t, CH2Br), 2.79 (2H, t, C═C—CH2—C═C), 2.06 (4H, q, 2× allylic CH2), 1.87 (2H, quintet, CH2), 1.2-1.5 (16H, m), 0.90 (3H, t, CH3) ppm.
Reaction SMILES: [C:1]([O:4][C@:5]1([C@:29]2([CH3:30])[C@H:15]([C@H:16]3[C@H:26]([CH2:27][CH2:28]2)[C@:24]2([CH3:25])[C:19](=[CH:20][C:21](=[O:31])[CH2:22][CH2:23]2)[CH2:18][CH2:17]3)[CH2:14][CH2:13]1)[C:6](=[O:12])[CH2:7][O:8][C:9](=[O:11])[CH3:10])(=[O:3])[CH3:2].[CH3:32]OCOC.C([O-])(=O)C.[Na+].P(Br)(Br)(Br)=O>C(Cl)Cl>[C:1]([O:4][C@:5]1([C@:29]2([CH3:30])[C@H:15]([C@H:16]3[C@H:26]([CH2:27][CH2:28]2)[C@:24]2([CH3:25])[C:19](=[CH:20][C:21](=[O:31])[CH2:22][CH2:23]2)[C:18](=[CH2:32])[CH2:17]3)[CH2:14][CH2:13]1)[C:6](=[O:12])[CH2:7][O:8][C:9](=[O:11])[CH3:10])(=[O:3])[CH3:2]
Reactant: CC(=O)OCC(=O)[C@@]1(OC(C)=O)CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(C)[C@H]3CC[C@@]21C
Reactant: COCOC
Agent: CC(=O)[O-]
Agent: O=P(Br)(Br)Br
Agent: [Na+]
Solvent: ClCCl
Product: C=C1C[C@@H]2[C@H](CC[C@@]3(C)[C@H]2CC[C@]3(OC(C)=O)C(=O)COC(C)=O)[C@@]2(C)CCC(=O)C=C12

Procedure:
Analogously to Example 9, 2.0 g of 17,21-diacetoxy-4-pregnene-3,20-dione in 60 ml of methylene chloride is reacted with 60 ml of formaldehyde dimethylacetal, 2.0 g of sodium acetate, and 12.6 g of phosphorus oxybromide, and worked up, thus isolating 1.68 g of 17,21-diacetoxy-6-methylene-4-pregnene-3,20-dione, mp 226°-228° C.
Reaction SMILES: [CH2:1]([C@@:4]1([CH3:30])[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C@@H:7]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[N:6]([C@@H:24]([CH2:27][CH3:28])[CH:25]=O)[C:5]1=[O:29])[CH:2]=[CH2:3].Cl.[NH2:32][CH2:33][CH2:34][CH2:35][C:36]([O:38]CC)=O.[Na]>C(O)(=O)C.C1COCC1.CO>[CH2:1]([C@@:4]1([CH3:30])[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C@@H:7]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[N:6]([C@@H:24]([CH2:27][CH3:28])[CH2:25][N:32]2[CH2:33][CH2:34][CH2:35][C:36]2=[O:38])[C:5]1=[O:29])[CH:2]=[CH2:3]
Reactant: CCOC(=O)CCCN
Reactant: C=CC[C@@]1(C)C[C@H](c2cccc(Cl)c2)[C@@H](c2ccc(Cl)cc2)N([C@H](C=O)CC)C1=O
Agent: Cl
Agent: [Na]
Solvent: C1CCOC1
Solvent: CC(=O)O
Solvent: CO
Product: C=CC[C@@]1(C)C[C@H](c2cccc(Cl)c2)[C@@H](c2ccc(Cl)cc2)N([C@@H](CC)CN2CCCC2=O)C1=O
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a solution of (S)-2-((3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-1-yl)butanal (84 mg, 0.189 mmol; Example 91, Step C), ethyl 4-aminobutyrate hydrochloride (127 mg, 0.756 mmol) and acetic acid (3 drops) in DCE/MeOH (3/1, 4.0 mL) was added sodium triacetoxyhydroborate (200 mg, 0.945 mmol) at 25° C. After being stirred at 25° C. for 18 h, the reaction was quenched by adding ice-cold saturated aqueous NaHCO3 solution and was extracted with DCM. The combined organic layers were washed (1×sat. aq. NaCl solution) and concentrated under reduced pressure. The residue was purified by reverse phase preparatory HPLC (acetonitrile in water with 0.1% TFA, gradient elution) to give the title compound as a white solid.
Reaction SMILES: ON1C=CC=CC1=S.C(Cl)(Cl)=O.[C:13](O)(=O)[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]C.C([SnH](CCCC)CCCC)CCC.CC(N=NC(C#N)(C)C)(C#N)C.II.[F-].[K+]>C1C=CC=CC=1.ClC(Cl)(Cl)Cl.N1C=CC=CC=1>[CH3:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH3:13]
Reactant: CCCCCCCCCCCCCCCCCC(=O)O
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Agent: CCCC[SnH](CCCC)CCCC
Agent: II
Solvent: c1ccncc1
Solvent: ClC(Cl)(Cl)Cl
Solvent: c1ccccc1
Product: CCCCCCCCCCCCCCCCC
Yield: 70 %

Procedure:
140 mg (1.1 mmol) of N-hydroxypyridine-2-thione in 5 ml of benzene are added dropwise at room temperature under an atmosphere of nitrogen to a solution of 120 mg (1.2 mmol) of phosgene in 5 ml of benzene, and this leads to the instantaneous precipitation of a white solid. 286 mg (1 mmol) of stearic acid and 0.5 ml of pyridine are added in 5 ml of benzene, and the reaction medium is taken to reflux for 4 hours. 3 mmol of tri-n-butylstannane in 5 ml of benzene with 10 mg of AIBN are added to the reaction medium during 10 minutes and refluxing is maintained for 2 and half hours. The reaction is carried out in the presence of tetrachloromethane, iodine and potassium fluoride, as indicated earlier. By filtration on silica (100% pentane), 168 mg of n-heptadecane are obtained. Yield 70%.
Reaction SMILES: [OH:1][CH2:2][C@@:3]12[C@@H:20]3[C@H:11]([C@H:12]4[C@@:16]([CH2:18][CH2:19]3)([CH3:17])[C:15](=[O:21])[CH2:14][CH2:13]4)[CH2:10][CH2:9][C:8]1=[CH:7][C:6](=[O:22])[CH2:5][CH2:4]2.C1(Cl)C(=O)C(Cl)=C(Cl)C(=O)C=1Cl>C(O)(C)(C)C>[OH:1][CH2:2][C@@:3]12[C@@H:20]3[C@H:11]([C@H:12]4[C@@:16]([CH2:18][CH2:19]3)([CH3:17])[C:15](=[O:21])[CH2:14][CH2:13]4)[CH:10]=[CH:9][C:8]1=[CH:7][C:6](=[O:22])[CH2:5][CH2:4]2
Reactant: C[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)CC[C@@]43CO)[C@@H]1CCC2=O
Agent: O=C1C(Cl)=C(Cl)C(=O)C(Cl)=C1Cl
Solvent: CC(C)(C)O
Product: C[C@]12CC[C@H]3[C@@H](C=CC4=CC(=O)CC[C@@]43CO)[C@@H]1CCC2=O

Procedure:
19-Hydroxy-4-androstene-3,17-dione and chloranil are dissolved in t-butanol and rapidly brought to reflux. The t-butanol is removed by distillation at atmospheric pressure at such a rate so that the total reflux and distillation time equals one hour. The dark pasty residue is triturated with hot chloroform and cooled. The solid which remains is removed by filtration and the filtrate successively extracted with water, a 2% sodium hydroxide solution and again with water. The organic layer is dried over magnesium sulfate and the solvent removed under vacuum to yield 19-hydroxy-4,6-androstadiene-3,17-dione. The diene so prepared is dissolved in acetone and chilled in an ice bath. Jones reagent is added over a period of about 10 minutes and stirring continued for an additional 45 minutes. The mixture is poured onto water. The solid which forms is filtered and recrystallized from benzene to yield 4,6-androstadiene-3,17,19-trione.
Reaction SMILES: [CH2:1]([NH:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[C:18]([C:22]1[CH:23]=[C:24]([CH:28]=[C:29]([C:32]([CH3:35])([CH3:34])[CH3:33])[C:30]=1[OH:31])[C:25]([OH:27])=O)([CH3:21])([CH3:20])[CH3:19]>>[CH2:10]([N:9]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])[C:25](=[O:27])[C:24]1[CH:28]=[C:29]([C:32]([CH3:34])([CH3:35])[CH3:33])[C:30]([OH:31])=[C:22]([C:18]([CH3:20])([CH3:19])[CH3:21])[CH:23]=1)[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17]
Reactant: CCCCCCCCNCCCCCCCC
Reactant: CC(C)(C)c1cc(C(=O)O)cc(C(C)(C)C)c1O
Product: CCCCCCCCN(CCCCCCCC)C(=O)c1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1

Procedure:
In the manner of Example 7, di-n-octylamine was reacted with 3,5-di-t-butyl-4-hydroxybenzoic acid to produce N,N-di-n-octyl-3,5-di-t-butyl-4-hydroxybenzamide; an oil product. When tested by the procedure of Example 2, this compound lasted over 1400 hours, over 4.7 times as long as the control.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH2:11][CH3:12])[C:5]2OC[O:7][C:6]=2[CH:10]=1.C([Li])CCC.C[O:19]C(C1N(C2C=CC=CC=2C(F)(F)F)S(=O)(=O)C2C=CC=CC=2C=1OS(C(F)(F)F)(=O)=O)=O>O1CCCC1.[Br-].[Zn+2].[Br-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[Br:1][C:2]1[CH:10]=[C:6]([OH:7])[CH:5]=[C:4]([CH2:11][CH2:12][OH:19])[CH:3]=1
Reactant: COC(=O)C1=C(OS(=O)(=O)C(F)(F)F)c2ccccc2S(=O)(=O)N1c1ccccc1C(F)(F)F
Reactant: CCc1cc(Br)cc2c1OCO2
Agent: [Pd]
Agent: [Br-]
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: OCCc1cc(O)cc(Br)c1
Temperature: -78 °C
Reaction time: 0.75 h
Yield: 53 %

Procedure:
To tetrahydrofuran (30 mL) was added (6-bromo-4-ethyl-benzo[1,3]dioxole) (1.24 g, 5.41 mmol). After cooling to −78° C., a solution of n-butyllithium (1.6 M in hexane, 3.54 mL) was added. After stirring for 45 minutes, a solution of anhydrous zinc bromide (1.27 g, 5.69 mmol) in tetrahydrofuran (20 mL) was added, and the mixture was stirred at −72° C. for 45 minutes, followed by warming to −25° C. To this mixture was added 1,1-dioxo-4-(trifluoro-methanesulfonyloxy)-2-(2-trifluoromethyl-phenyl)-1,2-dihydro-1λ6-benzo[e][1,2]thiazine-3-carboxylic acid methyl ester (1.49 g, 2.80 mmol), and palladium tetrakis(triphenyl phosphine) (1.30 g, 1.05 mmol). The mixture was heated to 70° C. for 2.5 hours and was evaporated in vacuo to an oil. The mixture was resuspended in ethyl acetate, washed with 1N citric acid solution, brine, filtered, and dried over anhydrous magnesium sulfate. The suspension was filtered and stripped to an oil which was partially crystallized from ethyl ether giving a solid. The filtrate was concentrated in vacuo and was chromatographed on 50 g silica gel eluted with a mixture of ethyl acetate and hexane (30:70). The appropriate fractions were concentrated in vacuo and crystallized from ethyl ether. These solids were combined with those recovered from the initial crystallization and were dried in vacuo giving a solid, 0.836 g, 53% yield. NMR spectra and elemental analysis were consistent with the structure.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:18]2[C:13](=[CH:14][C:15]([F:21])=[C:16](F)[C:17]=2[F:19])[C:12](=[O:22])[C:11]([C:23]([OH:25])=[O:24])=[CH:10]1.Cl.Cl.[CH3:28][NH:29][CH2:30][CH:31]1[O:36][CH2:35][CH2:34][NH:33][CH2:32]1.N12CCCN=C1CCCCC2>C(#N)C>[F:19][C:17]1[CH:16]=[C:15]([F:21])[CH:14]=[CH:13][C:18]=1[N:9]1[C:3]2[C:4](=[CH:5][C:6]([F:8])=[C:7]([N:33]3[CH2:34][CH2:35][O:36][CH:31]([CH2:30][NH:29][CH3:28])[CH2:32]3)[C:2]=2[F:1])[C:12](=[O:22])[C:11]([C:23]([OH:25])=[O:24])=[CH:10]1
Reactant: O=C(O)c1cn(-c2ccc(F)cc2F)c2c(F)c(F)c(F)cc2c1=O
Reactant: CNCC1CNCCO1
Agent: Cl
Solvent: C1CCC2=NCCCN2CC1
Solvent: CC#N
Product: CNCC1CN(c2c(F)cc3c(=O)c(C(=O)O)cn(-c4ccc(F)cc4F)c3c2F)CCO1

Procedure:
A solution of 710 mg of 1-(2,4-difluorophenyl)-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, 487 mg of 2-(methylaminomethyl)morpholine dihydrochloride and 1035 mg of 1,8-diazabicyclo[5.4.0]undec-7-ene in 10 ml of acetonitrile is refluxed for 21 hours. The reaction mixture is concentrated under reduced pressure and to the residue is added 10 ml of methanol. The obtained crystals are collected by filtration and washed with methanol, water and then acetone to give 1-(2,4-difluorophenyl)-7-[2-(methylaminomethyl)morpholino]-6,8-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, melting at 224°-227° C. with decomposition.