Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [K:1].CC(C)([O-:5])C.[O:7]([C:14]1[CH:19]=[CH:18][C:17](O)=[CH:16][CH:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>CS(C)=O>[K:1].[O:7]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[O-:5])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: Oc1ccc(Oc2ccccc2)cc1
Reactant: CC(C)(C)[O-]
Agent: [K]
Solvent: CS(C)=O
Product: [O-]c1ccccc1Oc1ccccc1
Temperature: 0 °C

Procedure:
13.2 g of potassium-tert.-butoxide is added portionwise, with slight external cooling (ice water) and with the introduction of nitrogen, to a solution of 20.4 g of 4-phenoxyphenol in 200 ml of dimethylsulphoxide. After potassium-phenoxy-phenolate has formed, with complete dissolving of the potassium-tert.-butoxide, there is added dropwise to the phenolate within 30 minutes at 20°-22° C, with stirring, 21.5 g of 1-bromo-3-phenoxypropane, and the whole is stirred at 30° C for a further 16 hours. In further processing, the reaction mixture is poured, with stirring, into 800 ml of ice water, and the mixture is repeatedly extracted with dichloromethane. The combined dichloromethane phases are thereupon repeatedly washed with ice-cold 10% potassium hydroxide solution, water and saturated sodium chloride solution; they are then dried over sodium sulphate and the solvent is completely removed in vacuo. The 1-phenoxy-4-(3-phenoxy)-1-propoxy-benzene then solidifying in crystalline form is further purified by recrystallisation in isopropanol; m.p. 69°-71° C.
Reaction SMILES: [OH:1][C@@H:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C@@H:3]1[NH:11][C:12](=[O:48])[C@H:13]([O:39][CH2:40][C:41]1[CH:46]=[CH:45][C:44](Br)=[CH:43][CH:42]=1)[C@H:14]([OH:38])[C@@H:15]([OH:37])[C@@H:16]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33](Br)=[CH:32][CH:31]=1)[C:17]([NH:19][C@H:20]([C:24](=[O:27])[NH:25][CH3:26])[CH:21]([CH3:23])[CH3:22])=[O:18].C([Sn](CCCC)(CCCC)[C:54]1[S:55][CH:56]=[CH:57][N:58]=1)CCC>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CN(C=O)C>[OH:1][C@@H:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C@@H:3]1[NH:11][C:12](=[O:48])[C@H:13]([O:39][CH2:40][C:41]1[CH:46]=[CH:45][C:44]([C:54]2[S:55][CH:56]=[CH:57][N:58]=2)=[CH:43][CH:42]=1)[C@H:14]([OH:38])[C@@H:15]([OH:37])[C@@H:16]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([C:54]2[S:55][CH:56]=[CH:57][N:58]=2)=[CH:32][CH:31]=1)[C:17]([NH:19][C@H:20]([C:24](=[O:27])[NH:25][CH3:26])[CH:21]([CH3:23])[CH3:22])=[O:18]
Reactant: CCCC[Sn](CCCC)(CCCC)c1nccs1
Reactant: CNC(=O)[C@@H](NC(=O)[C@H](OCc1ccc(Br)cc1)[C@H](O)[C@@H](O)[C@@H](OCc1ccc(Br)cc1)C(=O)N[C@H]1c2ccccc2C[C@H]1O)C(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CN(C)C=O
Product: CNC(=O)[C@@H](NC(=O)[C@H](OCc1ccc(-c2nccs2)cc1)[C@H](O)[C@@H](O)[C@@H](OCc1ccc(-c2nccs2)cc1)C(=O)N[C@H]1c2ccccc2C[C@H]1O)C(C)C
Temperature: 90 °C
Reaction time: 16 h
Yield: 73 %

Procedure:
A mixture of N1-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-1-indenyl]-N6-[(1S)-2-methyl-1-(methylcarbamoyl)propyl]-(2R,3R,4R,5R)-2,5-di(4-bromobenzyloxy)-3,4-dihydroxyhexanediamide, prepared analagously to Example 11 of WO98/45330 using 4-bromobenzyl (130 mg, 0.164 mmol), tributyl-2-thiazolyltin (554 mg, 1.47 mmol), PdCl2(PPh3)2 (120 mg, 0.5 M suspension in DMF), and dry DMF (3 ml) was twice degassed and flushed with argon and then stirred at 90° C./16 h, evaporated to near dryness, washed with a little ether and purified by silica gel column chromatography (chloroform-methanol 20:1) to yield 95.5 mg (73%) of off-white solid.
Reaction SMILES: C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.O[CH2:24][CH:25]1[CH2:29][CH2:28][CH:27]([CH2:30]O)[O:26]1.[CH2:32]([NH2:39])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.[OH-].[Na+]>CO>[CH2:32]([N:39]1[CH2:30][CH:27]2[O:26][CH:25]([CH2:29][CH2:28]2)[CH2:24]1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1
Reactant: NCc1ccccc1
Reactant: OCC1CCC(CO)O1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: c1ccc(CN2CC3CCC(C2)O3)cc1
Temperature: 70 °C
Reaction time: 24 h
Yield: 94.9 %

Procedure:
A mixture of 2,5-bis(hydroxymethyl)tetrahydrofuran bis(p-toluenesulfonate) (10 g) and benzylamine (9.7 g) was stirred at 70° C. for 24 hours. To the mixture was added a solution of sodium hydroxide (1.85 g) in methanol (30 ml). After stirring at room temperature for 30 minutes, the mixture was filtered. The filtrate was evaporated, added dichloromethane, and filtered. The filtrate was evaporated under reduced pressure, and purified with column chromatography (silica gel, 250 ml, ethyl acetate:hexane=1:4) to give 3-benzyl-8-oxa-3-azabicyclo[3.2.1]octane (4.05 g) as an oil.
Reaction SMILES: [C:1]([OH:24])(=[O:23])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].[OH-].[Na+].[P].[N+]([O-])([O-])=O.[Ag+:32]>C(OCCCC)(=O)C.O>[C:1]([O-:24])(=[O:23])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].[Ag+:32]
Reactant: CCCCCCCCCCCCCCCCCCCCCC(=O)O
Agent: [Ag+]
Agent: O=[N+]([O-])[O-]
Agent: [Na+]
Solvent: CCCCOC(C)=O
Solvent: O
Product: CCCCCCCCCCCCCCCCCCCCCC(=O)[O-]
Temperature: 30 °C
Reaction time: 1 h

Procedure:
10.6 Grams of behenic acid is mixed with 300 ml of distilled water at 90° C. for 15 minutes, and to the mixture was added 31.1 ml of a 1N sodium hydroxide aqueous solution over a period of 15 minutes with vigorous stirring. The mixture was allowed to stand for 1 hour and cooled to 30° C. Then, 7 ml of a 1N phosphorus acid aqueous solution was added, and to the mixture was further added 0.13 g of the following compound C-1 with vigorous stirring. Then, the silver halide grains C were added in such an amount that the amount of the silver halide became 1.25 mmol. Further, 25 ml of a 1N silver nitrate aqueous solution was continuously added over a period of 2 minutes, and the mixture was stirred for 90 minutes. To the aqueous mixture was added 37 g of a 1.2 wt. % butyl acetate solution of polyvinyl acetate to form flocs in the dispersion, and then water is removed. Thereafter, washing with water and removal of water were further performed twice. Then, 20 g of a 2.5 wt. % solution of polyvinyl butyral (Denka Butyral #3000-K, Denki Kagaku Kogyo K.K.) in a mixed solvent (butyl acetate/isopropyl alcohol=1/2 by volume) was added with stirring. To the resulting gel mixture of organic acid and silver halide, 7.8 g of polyvinyl butyral (Denka Butyral #4000-2, Denki Kagaku Kogyo K.K.) and 57 g of 2-butanone were added, followed by dispersing with a homogenizer, to obtain a silver behenate emulsion containing needle grains (average minor axis: 0.06 μm, average major axis: 1 μm, coefficient of variation: 30%). ##STR14## Preparation of Coating Solution C for Forming Light-sensitive Layer
Reaction SMILES: [CH:1]1([CH2:6][CH:7]([N:11]2[C:16](=[O:17])[CH:15]=[C:14]([O:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[CH:25]3[CH2:29][CH2:28][CH2:27][CH2:26]3)[CH:13]=[N:12]2)[C:8](O)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:30][C:31]1[CH:35]=[CH:34][N:33]([CH2:36][C:37]([CH3:40])([OH:39])[CH3:38])[N:32]=1>>[CH:1]1([CH2:6][CH:7]([N:11]2[C:16](=[O:17])[CH:15]=[C:14]([O:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[CH:25]3[CH2:29][CH2:28][CH2:27][CH2:26]3)[CH:13]=[N:12]2)[C:8]([NH:30][C:31]2[CH:35]=[CH:34][N:33]([CH2:36][C:37]([OH:39])([CH3:40])[CH3:38])[N:32]=2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: O=C(O)C(CC1CCCC1)n1ncc(Oc2ccccc2C2CCCC2)cc1=O
Reactant: CC(C)(O)Cn1ccc(N)n1
Product: CC(C)(O)Cn1ccc(NC(=O)C(CC2CCCC2)n2ncc(Oc3ccccc3C3CCCC3)cc2=O)n1
Yield: 75 %

Procedure:
Using the method described in Example 17, 3-cyclopentyl-2-[4-(2-cyclopentyl-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid (Intermediate 36) and 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (Intermediate 1) afforded 3-cyclopentyl-2-[4-(2-cyclopentyl-phenoxy)-6-oxo-6H-pyridazin-1-yl]-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-propionamide as a white solid (1.03 g, 75%); ES+-HRMS m/e calcd for C30H39N5O4 [M+H+] 534.3075 found 534.3076. 1H-NMR (300 MHz, DMSO-d6) δ ppm 1.05 (s, 3H), 1.06 (s, 3H), 1.09 (m, 1H), 1.20-1.80 (m, 14H), 1.81-2.02 (m, 3H), 2.27 (m, 1H), 3.04 (m, 1H), 3.89 (s, 2H), 4.67 (s, 1H), 5.46 (dd, J=4.4, J=10.7 Hz, 1H), 5.59 (d, J=2.8 Hz, 1H), 6.40 (d, J=2.2 Hz, 1H), 7.19 (m, 1H), 7.27-7.37 (m, 2H), 7.49 (dd, J=3.6, J=5.7 Hz, 1H), 7.52 (d, J=2.2 Hz, 1H), 8.16 (d, J=2.8 Hz, 1H), 10.80 (s, 1H).
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6].[C:11]1(B(O)O)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=C(S([O-])(=O)=O)C=2OC)CCCCC1.[Na+].C([O-])([O-])=O.[K+].[K+]>CC([O-])=O.CC([O-])=O.[Pd+2]>[C:2]1([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:10]=[CH:9][CH:8]=[C:4]([C:5]([OH:7])=[O:6])[CH:3]=1
Reactant: O=C(O)c1cccc(Cl)c1
Reactant: OB(O)c1ccccc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: COc1ccc(S(=O)(=O)[O-])c(OC)c1-c1ccccc1P(C1CCCCC1)C1CCCCC1
Product: O=C(O)c1cccc(-c2ccccc2)c1

Procedure:
The general procedure described in Example 3 was used with 3-chlorobenzoic acid (157 mg, 1.00 mmol), phenylboronic acid (145 mg, 1.20 mmol), Pd(OAc)2 (4.5 mg, 0.020 mmol, 2 mol %), sodium 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl-3′-sulfonate (20.0 mg, 0.040 mmol, 4 mol %), K2CO3 (345 mg, 2.50 mmol), solvent (see FIG. 5) (2.0 mL), 14 h, temperature. The conversion and yield were determined using 1H NMR.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[Li]CCCC.CN([CH:22]=[O:23])C>C1COCC1>[CH:8]1([C:5]2[CH:6]=[CH:7][C:2]([CH:22]=[O:23])=[CH:3][CH:4]=2)[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1
Reactant: Brc1ccc(C2CCCCC2)cc1
Reactant: CN(C)C=O
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: O=Cc1ccc(C2CCCCC2)cc1
Temperature: -78 °C
Reaction time: 1 h
Yield: 38 %

Procedure:
To a solution of 1-bromo-4-cyclohexylbenzene (850 mg, 3.55 mmol) in THF (4.0 mL) was added n-BuLi (3.1 mL, 4.62 mmol) at −78° C. under an inert atmosphere. The reaction mixture was stirred for 60 min at −78° C., and then DMF (2.8 mL) was added. The reaction mixture was then stirred for an additional hour at −78° C., warmed to 0° C., and quenched with a saturated NH4Cl solution. The mixture was then extracted with ethyl acetate (2×30 mL). The combined organic layers were then dried over magnesium sulfate, filtered and concentrated in vacuo to obtain the crude product. The crude material was purified via silica gel column chromatography to afford 4-cyclohexylbenzaldehyde (250 mg, 38%) as a solid.
Reaction SMILES: O=[O+][O-].[C:4]1([CH:10]([NH:14][S:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)(=[O:17])=[O:16])[CH2:11][CH:12]=C)[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[O:24]=O.S(C)C>C(Cl)Cl>[O:24]=[CH:12][CH2:11][CH:10]([NH:14][S:15]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)(=[O:17])=[O:16])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: O=O
Reactant: C=CCC(NS(=O)(=O)c1ccccc1)c1ccccc1
Agent: O=[O+][O-]
Solvent: ClCCl
Solvent: CSC
Product: O=CCC(NS(=O)(=O)c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 72 h
Yield: 84 %

Procedure:
A stream of ozone was passed through a solution of the product of Step 3 (1.9 g, 6.6 mmol) in CH2Cl2 (90 mL) at −78° C. for 1 h. The solution was then purged with oxygen, Me2S (1.1 mL, 15 mmol) was added, the cooling bath removed and the mixture allowed to warm to RT. The reaction was complete after 3 days and the solvent removed under reduced pressure and the mixture purified by column chromatography on silica eluting 5–10% MeOH/CH2Cl2 to give the benzenesulfonamide as a colourless oil (1.6 g, 84%). 1H NMR (360 MHz, CDCl3) δ 2.90–3.10 (2H, m), 4.79–4.86 (1H, m), 5.45 (1H, d, J=7.4 Hz), 7.03–7.09 (2H, m), 7.13–7.18 (3H, m), 7.35–7.39 (2H, m), 7.46–7.51 (1H, m), 7.69–7.71 (2H, m), 9.64 (1H, s).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH2:9][CH:10]([NH:12][C:13]2[C:18]([CH3:19])=[CH:17][CH:16]=[CH:15][C:14]=2[CH3:20])[CH3:11])=[CH:4][CH:3]=1.CC1C=CC=C(C)[C:23]=1[NH2:24].Cl>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:9][CH:10]([CH3:11])[N:12]([C:13]3[C:18]([CH3:19])=[CH:17][CH:16]=[CH:15][C:14]=3[CH3:20])[C:23]2=[NH:24])=[CH:4][CH:3]=1
Reactant: Cc1cccc(C)c1NC(C)CNc1ccc(Cl)cc1
Reactant: Cc1cccc(C)c1N
Agent: Cl
Product: Cc1cccc(C)c1N1C(=N)N(c2ccc(Cl)cc2)CC1C

Procedure:
1-(4'-Chlorophenyl-amino)-2-(2',6'-dimethylphenylamino)-propane, applied as starting substance, is obtained with a yield of 50.9% by reacting N-(β-chlorophenyl)-4-chloro-aniline, a compound prepared as described in Example 27, point (b), with 2,6-dimethylaniline according to the method given in Example 25, point (a). The hydrochloride of the product melts at 170°-178° C.
Reaction SMILES: [C:1]([O:9][CH2:10][C@H:11]1[S:15][CH2:14][C@H:13]([OH:16])[O:12]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:17][C:18]([Cl:25])([Cl:24])[CH2:19][O:20][C:21](Cl)=[O:22]>N1C=CC=CC=1.ClCCl>[C:1]([O:9][CH2:10][C@H:11]1[S:15][CH2:14][C@H:13]([O:16][C:21]([O:20][CH2:19][C:18]([Cl:25])([Cl:24])[Cl:17])=[O:22])[O:12]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(OC[C@@H]1O[C@@H](O)CS1)c1ccccc1
Reactant: O=C(Cl)OCC(Cl)(Cl)Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: O=C(OCC(Cl)(Cl)Cl)O[C@H]1CS[C@H](COC(=O)c2ccccc2)O1
Yield: 72.9 %

Procedure:
A mixture of cis and trans 2-benzoyloxymethyl-5-hydroxy-1,3-oxathiolane 4.47 g (19.8 mmol) (as prepared in example 1) was reacted with 8.2 mL (59.4 mmol) of 2,2,2-trichloroethylchloroformate in pyridine (4.8 mL) and dichloromethane (150 mL) as described in example 2 to give 6.0 g of the title compound in 2:1 ratio.
Reaction SMILES: C[O:2][C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][C:7]([C:13]3[CH:18]=[CH:17][C:16]([O:19]C)=[CH:15][CH:14]=3)=[CH:8][CH:9]=2)[CH:4]=1.Cl.[NH+]1C=CC=CC=1>Cl>[OH:19][C:16]1[CH:17]=[CH:18][C:13]([C:7]2[CH:6]=[C:5]3[C:10]([CH:11]=[CH:12][C:3]([OH:2])=[CH:4]3)=[CH:9][CH:8]=2)=[CH:14][CH:15]=1
Reactant: COc1ccc(-c2ccc3ccc(OC)cc3c2)cc1
Agent: Cl
Agent: c1cc[nH+]cc1
Product: Oc1ccc(-c2ccc3ccc(O)cc3c2)cc1
Temperature: 190 °C
Reaction time: 3 h
Yield: 39.5 %

Procedure:
2-Methoxy-7-(4-methoxy-phenyl)naphthalene (1.02 g, 3.86 mmol) was added to of pyridinium HCl (10 g) at 190° C. The solution was stirred for 3 hr at 190° C. and cooled to room temperature and stirred with 200 mL of 1N HCl. The resulting suspension was filtered and dissolved ethyl acetate (500 mL). The combined organic layers were washed with water (200 mL), dried over magnesium sulfate, filtered, the solvent removed under vacuum, and the product purified by silica chromatography (40% ethyl acetate-hexanes to yield 0.36 g (39%) of a white solid: mp 210° C.; 1H NMR (DMSO-d6): δ 6.89 (2H, d, J=8.58 Hz), 7.05 (1H, dd, J=2.42 Hz, J=8.77 Hz), 7.17 (1H, d, J=2.24 Hz), 7.52 (1H, dd, J=1.68 Hz, J=8.40 Hz), 7.61. (2H, d, J=8.58 Hz), 7.74 (1H, d, J=8.58 Hz), 7.79 (1H, d, J=8.58 Hz), 7.86 (1H, d, J=1.12 Hz), 9.60 (1H, bs), 9.72 (1H, bs); MS (ESI) m/z 235 (M−H)−.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:9]2[NH:14][C:13](=O)[C:12]([CH3:17])([CH3:16])[CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[F:8].[H-].C([Al+]CC(C)C)C(C)C>C1COCC1.C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH2:10][CH2:11][C:12]([CH3:17])([CH3:16])[CH2:13][NH:14]2)[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: CC1(C)CCC(c2ccc(F)c(F)c2)NC1=O
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: CC1(C)CCC(c2ccc(F)c(F)c2)NC1

Procedure:
To a stirred solution of 6-(3,4-difluorophenyl)-3,3-dimethylpiperidin-2-one (50.0 mg, 0.209 mmol, prepared according to Intermediate 14, Step A) in THF (1 mL) at 0° C. was added diisobutylaluminum hydride (1.05 mL of a 1 M solution in toluene, 1.05 mmol). The reaction mixture was stirred for 4 days, with additional diisobutylaluminum hydride (1.05 mL of a 1 M solution in toluene, 1.05 mmol) added on the 2nd and 3rd days. The reaction was quenched with saturated potassium sodium tartrate (5 mL) and extracted with EtOAc (3×10 mL). The combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of MeOH:CH2Cl2-0:100 to 5:95, to give the title compound. MS: m/z=226 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:22][CH:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)[C:13]([NH:15][C:16]2[CH:20]=[CH:19][N:18]([CH3:21])[N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].C(Cl)(=O)C(Cl)=O.N1C(C)=CC=CC=1C.NC1C=CN(C[C:49]([NH2:51])=[O:50])N=1>C(Cl)Cl>[C:49]([CH2:21][N:18]1[CH:19]=[CH:20][C:16]([NH:15][C:13](=[O:14])[C@@H:12]([C:4]2[CH:5]=[CH:6][C:7]([S:8]([CH3:11])(=[O:10])=[O:9])=[C:2]([Cl:1])[CH:3]=2)[CH2:22][CH:23]2[CH2:24][CH2:25][CH2:26][CH2:27]2)=[N:17]1)(=[O:50])[NH2:51]
Reactant: Cn1ccc(NC(=O)[C@H](CC2CCCC2)c2ccc(S(C)(=O)=O)c(Cl)c2)n1
Reactant: NC(=O)Cn1ccc(N)n1
Agent: O=C(Cl)C(=O)Cl
Solvent: Cc1cccc(C)n1
Solvent: ClCCl
Product: CS(=O)(=O)c1ccc([C@@H](CC2CCCC2)C(=O)Nc2ccn(CC(N)=O)n2)cc1Cl
Temperature: 25 °C
Reaction time: 1 h
Yield: 28 %

Procedure:
To a solution containing 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in PCT WO 2004/052869 A1, Example 1, 100 mg, 0.30 mmol) in methylene chloride (20 mL), was then added a 2.0 M solution of oxalylchloride in methylene chloride (166 μL, 0.33 mmol) at 0° C. and allowed to stir at 25° C. for 1 h, after which time 2,6-lutidine (46 μL, 0.39 mmol) was added to the solution at 0° C. After 1 h, the crude 2-(3-amino-pyrazol-1-yl)-acetamide (0.30 mmol based on theory) was added and the reaction was allowed to proceed for 16 h. The reaction solution was washed with 1.0 M aqueous hydrochloric acid solution, dried over sodium sulfate, concentrated in vacuo and purified by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 10 g; 0% methanol/methylene chloride to 10% methanol/methylene chloride) to afford N-(1-Carbamoylmethyl-1H-pyrazol-3-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (38 mg, 28%) as a white solid: ESI-LRMS m/e calcd for C20H25ClN4O4S [M+] 452.13, found 453.2 [M+H+]; 1H NMR (400 MHz, CD3OD) δ ppm 1.11-1.27 (m, 2H, CH2), 1.46-1.92 (m, 8H, 4×CH2), 2.07-2.27 (m, 1H, CH), 3.28 (s, 3H, SO2CH3), 3.85 (dd, J=8.6, 6.4 Hz, 1H, CH), 4.73 (s, 2H, NCH2), 6.55 (d, J=2.4 Hz, 1H, Ar), 7.53 (d, J=2.4 Hz, 1H, Ar), 7.59 (dd, Jo=8.2, Jm=1.5 Hz. 1H, Ar), 7.71 (d, Jm=1.5 Hz, 1H, Ar), 8.05 (d, Jo=8.2 Hz, 1H, Ar).
Reaction SMILES: [CH3:1][CH:2]([N:4]1[C:12](/[CH:13]=[CH:14]/[C@H:15]([OH:24])[CH2:16][C@H:17]([OH:23])[CH2:18][C:19]([O:21]C)=[O:20])=[C:11]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)[C:10]2[C:5]1=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH3:3].[OH-].[Na+:33].CC(O)C>CCO>[CH3:3][CH:2]([N:4]1[C:12](/[CH:13]=[CH:14]/[CH:15]([OH:24])[CH2:16][CH:17]([OH:23])[CH2:18][C:19]([O-:21])=[O:20])=[C:11]([C:25]2[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=2)[C:10]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]1=2)[CH3:1].[Na+:33]
Reactant: COC(=O)C[C@@H](O)C[C@@H](O)/C=C/c1c(-c2ccc(F)cc2)c2ccccc2n1C(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)O
Solvent: CCO
Product: CC(C)n1c(/C=C/C(O)CC(O)CC(=O)[O-])c(-c2ccc(F)cc2)c2ccccc21
Temperature: 25 °C
Yield: 94.7 %

Procedure:
In a 100 ml flask were placed Fluvastatin methyl ester (2.0 g) and a solution of NaOH (0.19 g) in EtOH (5 ml). The mixture was stirred at reflux for 3.5 h and propan-2-ol (40 ml) was added. The slurry was cooled to room temperature and stirred over night. The product was isolated by filtration under nitrogen, washed with propan-2-ol (20 ml) and dried at 50° C. in a vacuum oven for 24 h to obtain 1.93 g (95%) of fluvastatin sodium crystal Form XXXIX.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:20](=[O:21])[C:19]3[C:14](=[C:15]([O:22]C)[CH:16]=[CH:17][CH:18]=3)[N:13]=[C:12]2[C:24]2[CH:29]=[CH:28][C:27]([O:30]C)=[CH:26][CH:25]=2)=[CH:7][CH:6]=1.B(Br)(Br)Br.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[Cl:1][CH2:2][CH2:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([N:11]2[C:20](=[O:21])[C:19]3[C:14](=[C:15]([OH:22])[CH:16]=[CH:17][CH:18]=3)[N:13]=[C:12]2[C:24]2[CH:29]=[CH:28][C:27]([OH:30])=[CH:26][CH:25]=2)=[CH:9][CH:10]=1
Reactant: COc1ccc(-c2nc3c(OC)cccc3c(=O)n2-c2ccc(OCCCl)cc2)cc1
Agent: BrB(Br)Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: O=c1c2cccc(O)c2nc(-c2ccc(O)cc2)n1-c1ccc(OCCCl)cc1
Temperature: 0 °C
Reaction time: 0.33 h

Procedure:
To a chilled (0° C.) solution of 3.5 g (0.00801 mol) of 3-[4-(2-chloro-ethoxy)-phenyl]-8-methoxy-2-(4-methoxy-phenyl)-3H-quinazolin-4-one in 100 mL of dry methylene chloride was added 35 mL (0.0352 mol) of boron tribromide (1M solution in dichloroethane (Aldrich Chemicals)). The reaction mixture was stirred at 0° C. for 20 minutes, under nitrogen, and then at room temperature overnight. The crude reaction mixture was added to 400 mL of aqueous sodium bicarbonate. The solution was stirred vigorously for 1 hour at room temperature. The precipitate which formed was collected by vacuum filtration. An analytical sample (mp 274-276° C.) was obtained by recrystallization from methanol.
Reaction SMILES: Cl[C:2]1[CH:11]=[C:10]([O:12][CH2:13][CH3:14])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[NH2:15][CH2:16][CH2:17][CH2:18][NH2:19]>>[NH2:15][CH2:16][CH2:17][CH2:18][NH:19][C:2]1[CH:11]=[C:10]([O:12][CH2:13][CH3:14])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1
Reactant: CCOc1cc(Cl)nc2ccccc12
Reactant: NCCCN
Product: CCOc1cc(NCCCN)nc2ccccc12
Temperature: 60 °C
Reaction time: 48 h
Yield: 76.8 %

Procedure:
To 2-chloro-4-ethoxyquinoline (J. Chem. Soc. Perkin Trans. 1, 1993, 181; 323 mg, 1.56 mmol) was added 1,3-diaminopropane (3.9 ml, 47 mmol). The mixture was stirred under argon at 60° C. for 48 h. Excess diamine was removed in vacuo to leave a cream residue which was purified by flash chromatography on silica gel eluting with 6% (9:1 MeOH/NH3) in DCM to give the title compound as a white solid (294 mg, 77%): δH (CD3OD) 1.49 (3H, t), 1.79 (2H, m), 2.74 (2H, t), 3.51 (2H, t), 4.13 (2H, q), 6.09 (1H, s), 7.12 (1H, t), 7.45 (1H, t), 7.55 (1H, d), 7.90 (1H, d); MS (APCI−) 244 (100%, [M−H]−), 216 (34).
Reaction SMILES: [C:1]([NH:9][CH2:10][C:11]1([CH2:20][OH:21])[CH:16]([OH:17])[CH:15]([OH:18])[CH:14]([OH:19])[CH2:13][NH:12]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:22]1[O:24][CH2:23]1>O.C(O)(=O)C>[OH:24][CH2:23][CH2:22][N:12]1[CH2:13][CH:14]([OH:19])[CH:15]([OH:18])[CH:16]([OH:17])[C:11]1([CH2:10][NH:9][C:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH2:20][OH:21]
Reactant: C1CO1
Reactant: O=C(NCC1(CO)NCC(O)C(O)C1O)c1ccccc1
Solvent: CC(=O)O
Solvent: O
Product: O=C(NCC1(CO)C(O)C(O)C(O)CN1CCO)c1ccccc1
Reaction time: 24 h

Procedure:
4.44 g of 2-benzoylaminomethyl-2-hydroxymethyl-3,4,5-trihydroxypiperidine (Preparation example 3) are dissolved in 65 ml of water and, after adding one drop of acetic acid, 6 ml of ethylene oxide are added at about 5° C. After stirring the mixture for 24 hours, the reaction has ended. The mixture is concentrated, the residue is dissolved in about 40 ml of methanol/water 2:1 and the solution is discharged onto a column 20 cm long and 3 cm wide which contains Amberlite® IR 120, H+ form. The column is washed thoroughly with methanol/water 2:1 and then eluted with 0.1% strength ammonia. The individual fractions are investigated by thin layer chromatography to determine their content and the fractions containing the desired product are concentrated. 2.4 g of N-hydroxyethyl-2-benzoylaminomethyl-2-hydroxymethyl-3,4,5-trihydroxypiperidine are obtained in the form of a solid foam.