Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[C:19](=[O:20])[CH2:18][CH2:17][C@@:16]2([CH3:21])[C:3]=1[CH2:4][CH2:5][C@@H:6]1[C@@H:15]2[CH2:14][CH2:13][C@@:11]2([CH3:12])[C@H:7]1[CH2:8][CH2:9][C:10]2=[O:22].[NH4+:23].[OH-]>O1CCOCC1>[NH2:23][C:2]1[C:19](=[O:20])[CH2:18][CH2:17][C@@:16]2([CH3:21])[C:3]=1[CH2:4][CH2:5][C@@H:6]1[C@@H:15]2[CH2:14][CH2:13][C@@:11]2([CH3:12])[C@H:7]1[CH2:8][CH2:9][C:10]2=[O:22]
Reactant: C[C@]12CCC(=O)C(Cl)=C1CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
Reactant: [NH4+]
Agent: [OH-]
Solvent: C1COCCO1
Product: C[C@]12CCC(=O)C(N)=C1CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
Temperature: 25 °C
Reaction time: 24 h
Yield: 31 %

Procedure:
A mixture of 4-chloroandrost-4-ene-3,17-dione (1.93 g, 6 mmole), dioxane (60 ml) and 30% NH4OH aqueous solution (120 ml) is stirred at room temperature during 24 hours. The organic solvent and excess of ammonia are evaporated in vacuo and the resulting aqueous residue is acidified to pH 1 by carefully adding conc. HCl. The aqueous solution is washed twice with ethyl acetate and brought to pH 11 by carefully adding conc. NaOH. The resulting precipitate is filtered off, washed with water and dried under vacuum at 40° C. There are obtained 559 mg (1.86 mmole, 31% yield) of the title compound as a white solid.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]([C:14]3[C:15](=[O:33])[N:16]([CH3:32])[C:17](=[O:31])[N:18]([C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=4)[C:19]=3[CH3:20])=[C:12]([S:34](Cl)(=[O:36])=[O:35])[CH:11]=[N:10]2)=[CH:5][CH:4]=1)#[N:2].O.[NH3:39]>C(#N)C>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]([C:14]3[C:15](=[O:33])[N:16]([CH3:32])[C:17](=[O:31])[N:18]([C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=4)[C:19]=3[CH3:20])=[C:12]([S:34]([NH2:39])(=[O:36])=[O:35])[CH:11]=[N:10]2)=[CH:5][CH:4]=1)#[N:2]
Reactant: N
Reactant: Cc1c(-c2c(S(=O)(=O)Cl)cnn2-c2ccc(C#N)cc2)c(=O)n(C)c(=O)n1-c1cccc(C(F)(F)F)c1
Solvent: CC#N
Solvent: O
Product: Cc1c(-c2c(S(N)(=O)=O)cnn2-c2ccc(C#N)cc2)c(=O)n(C)c(=O)n1-c1cccc(C(F)(F)F)c1
Temperature: 0 °C

Procedure:
A suspension of the compound prepared in Example 204 (50.0 mg) in acetonitrile (20 ml) was cooled to 0° C. and thereto was added ammonia water (28%, 5.0 ml) dropwise and the mixture was stirred for another ten minutes. The reaction solution was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate) to afford 1-(4-cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-sulfonamide (42.0 mg). UPLC/MS 531 (M+H)/0.87 min. (measurement condition 9)
Reaction SMILES: [C:1](Cl)(=[O:5])[C:2]([Cl:4])=[O:3].[CH3:7][C:8]([CH3:12])=[CH:9][CH2:10][OH:11]>CCCCCCC>[C:2]([Cl:4])(=[O:3])[C:1]([O:11][CH2:10][CH:9]=[C:8]([CH3:12])[CH3:7])=[O:5]
Reactant: CC(C)=CCO
Reactant: O=C(Cl)C(=O)Cl
Solvent: CCCCCCC
Product: CC(C)=CCOC(=O)C(=O)Cl
Reaction time: 2 h

Procedure:
A 1-liter eggplant type flask was charged with 25.4 g (0.20 mol) of oxalyl chloride and 250 ml of n-heptane, to which 21.5 (0.25 mol) of 3-methyl-2-buten-1-ol were added dropwise over 3 hours while bubbling nitrogen at room temperature, followed by stirring further for 2 hours. Thereafter, the reaction mixture was concentrated and distilled to obtain 11.6 g of 3-methyl-2-butenyl chlorooxalate.
Reaction SMILES: C([O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]([OH:14])=O)=[CH:7][C:6]=1[O:15][CH3:16])(=O)C.C(O)(=O)CC1C=CC(O)=C(OC)C=1.P(Cl)(OCC)(OCC)=O.[CH3:39][N:40]([CH3:51])[CH2:41][CH2:42][NH:43][C@H:44]1[CH2:49][CH2:48][C@H:47]([CH3:50])[CH2:46][CH2:45]1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C1C=CN=CC=1.CO.C(Cl)Cl.C(N(CC)CC)C>[CH3:39][N:40]([CH3:51])[CH2:41][CH2:42][N:43]([C@H:44]1[CH2:45][CH2:46][C@H:47]([CH3:50])[CH2:48][CH2:49]1)[C:12](=[O:14])[CH2:11][C:8]1[CH:9]=[CH:10][C:5]([OH:4])=[C:6]([O:15][CH3:16])[CH:7]=1
Reactant: CN(C)CCN[C@H]1CC[C@H](C)CC1
Reactant: COc1cc(CC(=O)O)ccc1OC(C)=O
Agent: CCOP(=O)(Cl)OCC
Agent: CN(C)c1ccncc1
Agent: COc1cc(CC(=O)O)ccc1O
Solvent: CCN(CC)CC
Solvent: CO
Solvent: ClCCl
Product: COc1cc(CC(=O)N(CCN(C)C)[C@H]2CC[C@H](C)CC2)ccc1O

Procedure:
Using 2.3 g of (4-acetoxy-3-methoxyphenyl)acetic acid derived from homovanillic acid by the acetylation thereof, 2.8 ml of diethyl chlorophosphate, 2.7 ml of triethylamine, 100 ml of methylene chloride, 3 ml of N-(2-dimethylaminoethyl)-trans-4-methylcyclohexylamine (Example 78), 0.5 g of 4-dimethylaminopyridine, 100 ml of methanol, and 3 g of potassium carbonate, a reaction similar to that conducted in Example 75 was carried out. As a result, 1.44 g of N-(2-dimethylaminoethyl)-N-(trans-4-methylcyclohexyl)-2-(4-hydroxy-3-methoxyphenyl)acetamide (a compound of the present invention) was obtained as pale yellow crystal, which had the following physiochemical properties:
Reaction SMILES: [CH3:1][N:2]([CH3:17])[CH2:3][C@H:4]([O:15][CH3:16])[C@@H:5]([C:8]1[CH:9]=[C:10]([OH:14])[CH:11]=[CH:12][CH:13]=1)[CH2:6][CH3:7].O.C[Si](C)(C)[Cl:21]>CC(=O)CC>[ClH:21].[CH3:17][N:2]([CH3:1])[CH2:3][C@H:4]([O:15][CH3:16])[C@@H:5]([C:8]1[CH:9]=[C:10]([OH:14])[CH:11]=[CH:12][CH:13]=1)[CH2:6][CH3:7]
Reactant: C[Si](C)(C)Cl
Agent: CC[C@H](c1cccc(O)c1)[C@H](CN(C)C)OC
Solvent: CCC(C)=O
Solvent: O
Product: Cl
Temperature: 22.5 °C
Reaction time: 4 h

Procedure:
Part of the oil obtained in Example 6 is dissolved in 2-butanone (40 mL) at the temperature of 20-25° C. The following are added: purified water (0.3 mL, 0.0167 moles), trimethylchlorosilane (1.2 g). The hydrochloride product precipitates and the suspension is maintained under stirring for 4 hours at the temperature of 20-25° C. Finally, the solid is filtered, and this is dried under vacuum at 30-40° C.
Reaction SMILES: [CH2:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([S:13]CC2C=CC(OC)=CC=2)[CH2:10][C@H:9]1[CH2:23][CH2:24][CH2:25][N:26]1[CH:30]=[CH:29][CH:28]=[CH:27]1)=[O:7])[CH2:2][CH2:3][CH3:4].C([SiH](CC)CC)C>C(O)(C(F)(F)F)=O>[CH2:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([SH:13])[CH2:10][C@@H:9]1[CH2:23][CH2:24][CH2:25][N:26]1[CH:27]=[CH:28][CH:29]=[CH:30]1)=[O:7])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCOC(=O)N1C[C@H](SCc2ccc(OC)cc2)C[C@H]1CCCn1cccc1
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Product: CCCCOC(=O)N1C[C@H](S)C[C@@H]1CCCn1cccc1
Temperature: 0 °C
Reaction time: 22 h
Yield: 21.3 %

Procedure:
(Method 1): A solution of 0.065 g (0.151 mmol) (2R,4R)-4-(4-methoxy-benzylsulfanyl)-2-(3-pyrrol-1-yl-propyl)-pyrrolidine-1-carboxylic acid butyl ester was dissolved in 2 ml TFA, cooled to 0° C. and treated with 0.24 ml (1.51 mmol) triethylsilane, stirred for 22 h at room temperature and treated again with 0.24 ml (1.51 mmol) triethylsilane after further 30 h the evaporated residue was purified by flash silica gel column (CH2Cl2/EtOAc 99:1) to give 10 mg of (2S,4R)-4-mercapto-2-(3-pyrrol-1-yl-propyl)-pyrrolidine-1-carboxylic acid butyl ester, MS: 311 (MH+).
Reaction SMILES: [NH2:1][C:2]1[C:11](Br)=[N:10][C:9](Br)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[CH3:14][O:15][C:16]1[CH:21]=[CH:20][C:19](B(O)O)=[CH:18][CH:17]=1.[F-].[Cs+]>[Pd].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>[NH2:1][C:2]1[C:11]([C:19]2[CH:20]=[CH:21][C:16]([O:15][CH3:14])=[CH:17][CH:18]=2)=[N:10][C:9]([C:19]2[CH:20]=[CH:21][C:16]([O:15][CH3:14])=[CH:17][CH:18]=2)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]
Reactant: COC(=O)c1cc(Br)nc(Br)c1N
Reactant: COc1ccc(B(O)O)cc1
Agent: [Pd]
Agent: [Cs+]
Agent: [F-]
Product: COC(=O)c1cc(-c2ccc(OC)cc2)nc(-c2ccc(OC)cc2)c1N
Temperature: 80 °C
Yield: 44 %

Procedure:
A mixture of methyl 3-amino-2,6-dibromoisonicotinate (500 mg, 1.61 mmol), 4-methoxyphenylboronic acid (588 mg, 3.87 mmol), Tetrakis(triphenylphosphine)-palladium(0) (93 mg, 0.081 mmol) and cesium fluoride (1176 mg, 7.74 mmol) was placed in a vial and flushed with nitrogen. Dimethoxyethane (10 mL) was added and the reaction was heated at 80° C. for 48 hr. After cooling to room temperature, the reaction was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The organic phase was separated, washed with saturated aqueous sodium bicarbonate solution, brine, and then dried with sodium sulfate. Removal of the solvent followed by silica gel radial chromatography (step gradient elution with hexane containing 0 to 25% ethyl acetate) afforded methyl 3-amino-2,6-bis(4-methoxyphenyl)isonicotinate (258 mg, 0.708 mmol, 43.9% yield) as a yellow oil. MS (ESI) m/z 365.2 (M+H). 1H NMR (CDCl3) δ ppm 8.01 (1H, s), 7.91 (2H, d, J=8.85 Hz), 7.66 (2H, d, J=8.55 Hz), 7.02 (2H, d, J=8.55 Hz), 6.94 (2H, d, J=8.85 Hz), 5.93 (2H, br. s.), 3.94 (3H, s), 3.86 (3H, s), 3.83 (3H, s).
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH:4]([C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-])=O)=[CH:17][CH:16]=2)[C:3]1=[O:24]>C(O)C>[NH2:21][C:18]1[CH:19]=[CH:20][C:15]([CH:4]2[C:3](=[O:24])[N:2]([CH3:1])[CH2:7][CH2:6][N:5]2[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])=[CH:16][CH:17]=1
Reactant: CN1CCN(C(=O)OC(C)(C)C)C(c2ccc([N+](=O)[O-])cc2)C1=O
Solvent: CCO
Product: CN1CCN(C(=O)OC(C)(C)C)C(c2ccc(N)cc2)C1=O
Temperature: 25 °C
Reaction time: 18 h
Yield: 99 %

Procedure:
A 250-mL Parr hydrogenation bottle was purged with nitrogen and charged with 10% palladium on carbon (50% wet, 10 mg dry weight) followed by a solution of tert-butyl 4-methyl-2-(4-nitrophenyl)-3-oxopiperazine-1-carboxylate (102i) (1.00 g, 2.99 mmol) in ethanol (40 mL). The bottle was evacuated, then charged with hydrogen gas to a pressure of 50 psi and shaken at 50 psi for 18 h at room temperature on a Parr hydrogenation apparatus. After this time the hydrogen was evacuated and nitrogen charged into the bottle. The resulting suspension was filtered through a pad of Celite 521. The filter cake was washed with ethanol (2×20 mL), and the filtrate was evaporated to dryness under reduced pressure to afford a 99% yield (904 mg) of tert-butyl 2-(4-aminophenyl)-4-methyl-3-oxopiperazine-1-carboxylate 102j as a yellow syrup: 1H NMR (300 MHz, DMSO-d6) δ 6.93 (d, 2H, J=8.4 Hz), 6.51 (d, 2H, J=8.4 Hz), 5.27 (bs, 1H), 5.09 (s, 1H), 3.83 (d, 1H, J=10.8 Hz), 3.44 (m, 1H), 3.24 (m, 2H), 2.84 (s, 3H), 1.40 (s, 9H); MS (ESI+) m/z 306.2 (M+H).
Reaction SMILES: [Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([Br:9])=[CH:5][CH:4]=1.[CH3:10][C:11]([N:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)(C)[C:12]#N>C1COCC1>[Br:9][C:6]1[CH:7]=[CH:8][C:3]([C:11]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)([CH3:12])[CH3:10])=[CH:4][CH:5]=1
Reactant: Brc1ccc(Br)cc1
Reactant: CC(C)(C#N)N1CCOCC1
Agent: [Mg]
Solvent: C1CCOC1
Product: CC(C)(c1ccc(Br)cc1)N1CCOCC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 10.9 %

Procedure:
Magnesium turnings (190 mg, 7.4 mmol) was added to dry THF (15 mL) under argon. 1,4-dibromobenzene (2.43 g, 10.3 mmol) was added and the solution was heated to reflux for 30 min. 2-Methyl-2-morpholinopropanenitrile (1 g, 6.6 mmol) was dissolved into THF (30 mL) and added dropwise to the solution at reflux. The mixture was stirred for 2 h and cooled to rt. The reaction was quenched with sat. K2CO3 solution and extracted with CH2Cl2 (200 mL), dried over MgSO4 and concentrated to an orange oil. The crude mixture was purified on a Biotage silica column (2-15% MeOH in CH2Cl2) to give the title compound as a yellow oil (204 mg, 10%). MS ESI 284.0, 286.0 [M+H]+, calcd for [C13H18BrNO+H]+ 284.1, 286.1.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][C@@H:11]2[CH3:16])=[O:9])=[CH:4][CH:3]=1.Br[C:18]1[C:19](=[O:26])[N:20]([CH3:25])[CH:21]=[C:22]([Br:24])[CH:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Br:24][C:22]1[CH:23]=[C:18]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([C:8]([N:10]3[CH2:15][CH2:14][O:13][CH2:12][C@@H:11]3[CH3:16])=[O:9])=[CH:6][N:7]=2)[C:19](=[O:26])[N:20]([CH3:25])[CH:21]=1
Reactant: C[C@H]1COCCN1C(=O)c1ccc(N)nc1
Reactant: Cn1cc(Br)cc(Br)c1=O
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Product: C[C@H]1COCCN1C(=O)c1ccc(Nc2cc(Br)cn(C)c2=O)nc1
Temperature: 25 °C
Yield: 68.8 %

Procedure:
A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with (S)-(6-aminopyridin-3-yl)(3-methylmorpholino)methanone (222 mg, 1.0 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (320 mg, 1.2 mmol), cesium carbonate (652 mg, 2 mmol), and 1,4-dioxane (10 mL). After bubbling nitrogen through the suspension for 10 minutes, Xantphos (58 mg, 0.10 mmol) and tris(dibenzylideneacetone)dipalladium(0) (46 mg, 0.050 mmol) were added. The system was subject to three cycles of vacuum/argon flush and heated at reflux for 2.5 h. It was then cooled to room temperature and filtered. The solid was washed with dichloromethane (2×30 mL) and the combined filtrate was concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with petroleum ether/ethyl acetate (2:1 to 1:2) to afford 257a (280 mg, 69%) as a yellow solid. MS-ESI: [M+H]+ 407.3
Reaction SMILES: Br[C:2]1[C:3](=[O:16])[N:4]([CH3:15])[C:5]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:6][CH:7]=1.[F:17][C:18]1[CH:23]=[C:22]([O:24][CH3:25])[C:21]([F:26])=[CH:20][C:19]=1B(O)O.[Cl-].[Li+]>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].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>[F:17][C:18]1[CH:23]=[C:22]([O:24][CH3:25])[C:21]([F:26])=[CH:20][C:19]=1[C:2]1[C:3](=[O:16])[N:4]([CH3:15])[C:5]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:6][CH:7]=1
Reactant: COc1cc(F)c(B(O)O)cc1F
Reactant: Cn1c(Nc2ccccc2)ncc(Br)c1=O
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: [Cl-]
Solvent: C1COCCO1
Product: COc1cc(F)c(-c2cnc(Nc3ccccc3)n(C)c2=O)cc1F
Temperature: 100 °C
Reaction time: 0.25 h

Procedure:
A suspension of 5-bromo-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one (Example 143, Step C, 0.100 g, 0.357 mmol), 2,5-difluoro-4-methoxyphenylboronic acid (0.081 g, 0.428 mmol), Pd(PPh3)4 (0.021 g, 0.018 mmol) and lithium chloride (0.076 g, 1.78 mmol) in dioxane (2 mL) and 2M aqueous Na2CO3 (2 mL) was stirred at 100° C. for 15 minutes. The reaction mixture was cooled to room temperature and then partitioned between EtOAc and H2O. The layers were separated and the aqueous layer was re-extracted with EtOAc (1×). The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude product was purified by flash column chromatography, eluting with 5:1 CH2Cl2/EtOAc. The product was obtained (77 mg; 63%) as a grey-white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.95 (br s, 1H), 7.74 (s, 1H), 7.55-7.49 (m, 2H), 7.39-7.28 (m, 3H), 7.18-7.13 (m, 2H), 3.86 (s, 3H), 3.54 (s, 3H). LRMS (ESI pos) m/e 344 (M+1).
Reaction SMILES: C([O:8][C:9]1[C:14](=[O:15])[CH:13]=[CH:12][N:11]([CH2:16][CH2:17][OH:18])[C:10]=1[CH3:19])C1C=CC=CC=1>Br>[OH:8][C:9]1[C:14](=[O:15])[CH:13]=[CH:12][N:11]([CH2:16][CH2:17][OH:18])[C:10]=1[CH3:19]
Reactant: Cc1c(OCc2ccccc2)c(=O)ccn1CCO
Agent: Br
Product: Cc1c(O)c(=O)ccn1CCO
Yield: 61.3 %

Procedure:
3-Benzyloxy-1-(2'-hydroxyethyl)-2-methylpyrid-4-one (2 g) is added to concentrated hydrobromic acid (10 ml) and the mixture is heated on a steam bath for 30 minutes. The resultant product is then recrystallised from water to yield 3-hydroxy-1(2'-hydroxyethyl)-2-methylpyrid-4-one as white crystals (0.8 g), m.p. 164°-165° C.; νmax (nujol) 1630, 3150, 3350 cm-1 ; δ(dbDMSO), 2.5 (s, 3H), 3.7 (t, 2H), 4.35 (t, 2H), 7.25 (3, 1H), 8.15 (d, 1H).
Reaction SMILES: [CH2:1]1[O:11][C@@H:10]([CH2:12][OH:13])[C@H:8]([OH:9])[C@@H:6]([OH:7])[C@@:2]1([OH:5])[CH2:3][OH:4].[CH2:14](Cl)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[OH-].[K+]>O>[CH2:14]([O:4][CH2:3][C@:2]1([CH2:1][O:11][C@@H:10]([CH2:12][O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C@H:8]([O:9][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C@H:6]1[O:7][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[OH:5])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: OC[C@@H]1OC[C@](O)(CO)[C@H](O)[C@H]1O
Reactant: ClCc1ccccc1
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: O[C@]1(COCc2ccccc2)CO[C@@H](COCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Reaction time: 6 h
Yield: 71 %

Procedure:
A vigorously stirred mixture of 2,5-O-methylene-L-mannitol (8.0 g.), benzyl chloride (80.0 ml.), and powdered potassium hydroxide (40.0 g.) was slowly heated to 115°-125° and kept in this temperature range for six hours. The mixture was then cooled, water (200 ml.) added, and the mixture was steam distilled for 5 hours. The solution was then cooled, the organic layer (lower) separated in a separatory funnel and the aqueous layer extracted with three 100 ml. portions of ether which were then added to the organic layer. The combined organic layer was then extracted with three 100 ml. portions of water, dried over magnesium sulfate, and evaporated under reduced pressure to a syrup. The syrup was dissolved in methanol (35 ml.) and the solution cooled in an ice bath. Water was added until turbidity persisted and the solution was left to stand at 5° overnight. The crystalline product was removed by filtration, dissolved in isopropyl ether to which was added some methanol, and the resultant solution cooled at 5° while crystallization progressed. The filtered crystals were washed with a solution of pentane-isopropyl ether (1:2, v/v) and air dried to give pure 1,3,4,6-tetra-O-benzyl-2,5-O-methylene-L-mannitol (16.2 g. 71%) having m.p. 53°-54°, and [α]D +6.4° (c 1.09, chloroform) as compared with m.p. 55°-56°, and [α]D -6.6° (c 1.02, chloroform) which were found for the D-isomer.
Reaction SMILES: CCN(C(C)C)C(C)C.F[C:11]1[CH:20]=[CH:19][C:14]([C:15]([O:17][CH3:18])=[O:16])=[CH:13][C:12]=1[N+:21]([O-:23])=[O:22].[CH3:24][O:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32][NH2:33])=[CH:28][CH:27]=1>CN(C)C=O.O>[CH3:24][O:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32][NH:33][C:11]2[CH:20]=[CH:19][C:14]([C:15]([O:17][CH3:18])=[O:16])=[CH:13][C:12]=2[N+:21]([O-:23])=[O:22])=[CH:28][CH:27]=1
Reactant: COC(=O)c1ccc(F)c([N+](=O)[O-])c1
Reactant: COc1ccc(CN)cc1
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(NCc2ccc(OC)cc2)c([N+](=O)[O-])c1
Reaction time: 2 h
Yield: 79 %

Procedure:
DIEA (389.0 g, 3.02 mol) was added to a solution of methyl 4-fluoro-3-nitrobenzoate (200.0 g, 1.00 mol) in N,N-dimethylformamide (2 L) at room temperature. Then (4-methoxyphenyl)methanamine (275 g, 2.00 mol) was added dropwise. After 2 h, the reaction was diluted with water (5 L), the solids were collected by filtration to afford methyl 4-(4-methoxybenzylamino)-3-nitrobenzoate as a yellow solid (250 g, 78%).
Reaction SMILES: C(OC([N:8]([C:10](=[O:23])[CH:11]=[CH:12][C:13]1[CH:22]=[CH:21][C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=1)[NH2:9])=O)(C)(C)C.Cl>C(O)C>[CH:14]1[C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:21]=[CH:22][C:13]=1[CH:12]=[CH:11][C:10]([NH:8][NH2:9])=[O:23]
Reactant: CC(C)(C)OC(=O)N(N)C(=O)C=Cc1ccc2ccccc2c1
Agent: Cl
Solvent: CCO
Product: NNC(=O)C=Cc1ccc2ccccc2c1
Yield: 91.6 %

Procedure:
To a solution of the above hydrazine carboxylic acid tert butyl ester (4.5 g, 14.4 mmol) in ethanol (25 ml) was added 2 N hydrochloric acid and the mixture was refluxed for 1 h. The solvent was evaporated in vacuo and the residue was dissolved in water (100 ml) and made alkaline to pH=9 with 1 N sodium hydroxide. The precipitated was filtered off and washed with water (2×30 ml) and heptane (2×30 ml) and dried in vacuo at 50° C. which afforded 2.8 g (92%) of 3-naphthalen-2-yl-acrylic acid hydrazide as a solid.
Reaction SMILES: [C:1]([CH:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=[CH:5][N:4]1[C:13](=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)#[N:2].[OH-].[Na+].[CH:23](Br)([CH3:25])[CH3:24]>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1>[C:1]([C:3]1([CH:23]([CH3:25])[CH3:24])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=[CH:5][N:4]1[C:13](=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)#[N:2]
Reactant: N#CC1c2ccccc2C=CN1C(=O)c1ccccc1
Reactant: CC(C)Br
Agent: CC[N+](CC)(CC)Cc1ccccc1
Agent: [Cl-]
Agent: [Na+]
Product: CC(C)C1(C#N)c2ccccc2C=CN1C(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
(a-1-1) A mixture of 26 g of 1-cyano-2-benzoyl-1,2-dihydroisoquinoline [Org. Synth. Coll. vol. 4, 641 (1963)] and 1 g of benzyl triethyl ammonium chloride was dissolved in 50 ml of isopropyl bromide. Then, 80 g of a 50% aqueous solution of sodium hydroxide was added, and the mixture was stirred at room temperature for 30 minutes. The product was extracted with benzene. The solvent was distilled off, and the residue was recrystallized from ethanol to afford 20 g of 1-cyano-1-isopropyl-2-benzoyl-1,2-dihydroisoquinoline as colorless scales having a melting point of 123.8° to 126.0° C.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([NH:7][C:8]([C:10]2[C:14]3[N:15]=[CH:16][N:17]=[C:18]([C:19]4[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][C:20]=4[O:27][CH2:28][CH:29]4[CH2:31][CH2:30]4)[C:13]=3[NH:12][CH:11]=2)=[O:9])[CH2:3][CH2:2]1.[C:32](Cl)(=[O:34])[CH3:33]>>[C:32]([N:1]1[CH2:2][CH2:3][CH:4]([NH:7][C:8]([C:10]2[C:14]3[N:15]=[CH:16][N:17]=[C:18]([C:19]4[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][C:20]=4[O:27][CH2:28][CH:29]4[CH2:30][CH2:31]4)[C:13]=3[NH:12][CH:11]=2)=[O:9])[CH2:5][CH2:6]1)(=[O:34])[CH3:33]
Reactant: COc1ccc(-c2ncnc3c(C(=O)NC4CCNCC4)c[nH]c23)c(OCC2CC2)c1
Reactant: CC(=O)Cl
Product: COc1ccc(-c2ncnc3c(C(=O)NC4CCN(C(C)=O)CC4)c[nH]c23)c(OCC2CC2)c1

Procedure:
Starting from 4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid piperidin-4-ylamide (example A152) and acetyl chloride the title compound is obtained as colorless solid.
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][CH:3]=1.Cl.[H][H]>>[CH:10]1[C:11]2[C:6](=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:7]=[CH:8][CH:9]=1.[ClH:1]
Reactant: [H][H]
Reactant: Clc1cccc2ccccc12
Agent: Cl
Product: c1ccc2ccccc2c1

Procedure:
High conversions of 1-chloro- or 1-bromonaphthalene coupled with a long catalyst life can be achieved by the zeolites used according to the invention. The conversion of 1-chloronaphthalene over an amorphous aluminosilicate, in spite of an HCl atmosphere, dropped from 51 to 41% in the course of 4 hours (temperature 400° C., LHSV 0.2 h-1, N. N. Vorozhtsov, Jr. and A. M. Beskin, J. Gen. Chem. USSR, 24, 667/672 (1954) English edition). In contrast, an HEU-1 zeolite converted 56% of 1-chloro-naphthalene after 1 hour and 41% after 7 hours in a hydrogen atmosphere at the same temperature but 2.5 times the LHSV. The selectivity for the isomerization of 1-chloronaphthalene over HEU-1 is very high and is more than 98% at reaction temperatures of between 300° and 400° C. Naphthalene above all is formed as a by-product by elimination of HCl. Less than 0.05% of dichloronaphthalenes is formed. In the reaction of 1-bromonaphthalene, however, transbromination to naphthalene and dibromonaphthalenes occurs. The selectivity for 2-bromo-naphthalene is nevertheless very high, at 95% at 350° C. and 50% conversion.