Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][OH:2].[C:3]([C:5]1[CH:21]=[CH:20][C:8]([CH2:9][N:10]([CH3:19])[CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[CH:7][CH:6]=1)#[N:4]>CCO.O>[NH2:4][C:3](=[N:1][OH:2])[C:5]1[CH:6]=[CH:7][C:8]([CH2:9][N:10]([CH3:19])[CH2:11][C:12]([O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:13])=[CH:20][CH:21]=1
Reactant: CN(CC(=O)OC(C)(C)C)Cc1ccc(C#N)cc1
Reactant: NO
Solvent: O
Solvent: CCO
Product: CN(CC(=O)OC(C)(C)C)Cc1ccc(C(N)=NO)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 95 %

Procedure:
A 50% aqueous solution of hydroxylamine (13.25 mL, 225 mmol) was added at once into a solution of tert-butyl N-(4-cyanobenzyl)-N-methylglycinate (11.70 g, 45 mmol) in EtOH (75 mL). The reaction mixture was stirred at RT overnight. The solvents were removed under reduced pressure to give a white solid. The solid was suspended in water (200 mL) and stirred for 20 minutes, then filtered off, washed with water and dried to give the title compound as a white powder (12.54 g, 95%). 1H NMR (DMSO-d6, 300 MHz) δ 9.58 (s, 1H), 7.62 (d, J=8.3 Hz, 2H), 7.28 (d, J=8.3 Hz, 2H), 5.78 (s, 2H), 3.62 (s, 2H), 3.15 (s, 2H), 2.24 (s, 3H), 1.42 (s, 9H). LC/MS (Method B): 294.0 (M+H)+.
Reaction SMILES: [CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[NH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]CCCC.[CH:19]1([CH2:24][CH2:25][C:26](Cl)=[O:27])[CH2:23][CH2:22][CH2:21][CH2:20]1>C1COCC1>[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:26](=[O:27])[CH2:25][CH2:24][CH:19]1[CH2:23][CH2:22][CH2:21][CH2:20]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(Cl)CCC1CCCC1
Reactant: O=C1N[C@@H](Cc2ccccc2)CO1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: O=C(CCC1CCCC1)N1C(=O)OC[C@@H]1Cc1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 99.8 %

Procedure:
To a solution of (S)-(−)-4-benzyl-2-oxazolidinone (25 g, 141 mmol) in THF (350 mL) at −78° C. was added dropwise n-BuLi (56.4 mL, 2.5M solution in hexane, 141 mmol). After stirring for 60 min at the same temperature, the reaction mixture was then treated with 3-cyclopentylpropionyl chloride (21.6 mL, 141 mmol) over 0.25 h. The reaction mixture was allowed to warm to room temperature and stirred overnight. The reaction was quenched with saturated aqueous NH4Cl solution (320 mL). The aqueous layer was extracted with EtOAc (3×200 mL). The combined organic layers were dried (MgSO4) and evaporated to yield (4S)-benzyl-3-(3-cyclopentylpropanoyl)oxazolidin-2-one as a white solid (42.4 g, 100%). LCMS: (M+H)+: 302.3.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[CH:5][C:6]([S:13][C:14]2[CH:19]=[C:18]([CH3:20])[CH:17]=[CH:16][C:15]=2[CH3:21])=[C:7]([S:9](Cl)(=[O:11])=[O:10])[CH:8]=1)#[N:2].[CH3:22][N:23]([CH3:30])[CH:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1>C(Cl)Cl>[CH3:22][N:23]([CH3:30])[CH:24]1[CH2:29][CH2:28][N:27]([S:9]([C:7]2[CH:8]=[C:3]([CH:4]=[CH:5][C:6]=2[S:13][C:14]2[CH:19]=[C:18]([CH3:20])[CH:17]=[CH:16][C:15]=2[CH3:21])[C:1]#[N:2])(=[O:11])=[O:10])[CH2:26][CH2:25]1
Reactant: Cc1ccc(C)c(Sc2ccc(C#N)cc2S(=O)(=O)Cl)c1
Reactant: CN(C)C1CCNCC1
Solvent: ClCCl
Product: Cc1ccc(C)c(Sc2ccc(C#N)cc2S(=O)(=O)N2CCC(N(C)C)CC2)c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of compound 26 (0.200 g, 0.59 mmol) in DCM was added TEA (0.090 g, 0.89 mmol) and 4-dimethylaminopiperidine (0.114 g, 0.89 mmol). The reaction was monitored by HPLC. The reaction was complete after stirring at room temperature for 16 hrs. DCM was removed in vacuo, and the resulting solid was dissolved in a minimal amount of DCM and purified with chromatography with a gradient of 10 to 30% MeOH in DCM. Pure fractions were combined and evaporated in vacuo to yield an oil, which was triturated with DCM and hexanes, and then filtered to yield compound 72 as a peach solid (0.124 g, 49% yield). HPLC purity: 96.5%; 1H NMR (500 MHz, DMSO-d6): δ 8.22 (d, J=2 Hz, 1H), 7.84 (dd, J1=2 Hz, J2=8 Hz, 1H), 7.41 (d, J=6 Hz, 1H), 7.39 (s, 1H), 7.34 (d, J=8 Hz, 1H), 6.70 (d, J=8 Hz, 1H), 3.8 (d, J=13 Hz, 2H), 2.84 (t, J=12 Hz, 2H), 2.31 (s, 3H), 2.26 (m, 1H), 2.25 (s, 3H), 2.15 (s, 6H), 1.79 (d, J=12 Hz, 2H), 1.43 (m, 2H); MS (ESI, EI+): m/z=430 (MH+); melting point: 136-139° C.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.C1(C)C(C)=CC=CC=1.[C:15]([Si:19]([CH3:22])([CH3:21])Cl)([CH3:18])([CH3:17])[CH3:16].[OH-].[Na+]>C1(C)C=CC=CC=1>[Si:19]([N:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1)([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:22])[CH3:21]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: C1CNCCN1
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1C
Solvent: Cc1ccccc1
Product: CC(C)(C)[Si](C)(C)N1CCNCC1
Temperature: 110 °C
Reaction time: 2 h

Procedure:
A flask equipped with a stirrer, reflux condenser; dropping funnel and thermometer was charged with 1076.3 g (12.5 mol) of piperazine and 500 ml of xylene and heated at 110° C. Once the internal temperature became steady, 1507.0 g (5.0 mol) of a 50 wt % toluene solution of t-butyldimethylchlorosilane was added dropwise over 3 hours. Stirring was continued for 2 hours at the temperature. The reaction solution was cooled to room temperature, to which 2,500 g of a 10 wt % sodium hydroxide aqueous solution was added. The organic layer was separated. On distillation, 646.6 g of a fraction having a boiling point of 70-71° C./0.2 kPa was collected, which was 1-t-butyldimethylsilylpiperazine.
Reaction SMILES: [C:1]1([CH2:17][C:18]([OH:20])=[O:19])[C:14]2[C:15]3=[C:16]4[C:11](=[CH:12][CH:13]=2)[CH:10]=[CH:9][CH:8]=[C:7]4[CH:6]=[CH:5][C:4]3=[CH:3][CH:2]=1.[CH2:21]([OH:27])[CH2:22][O:23][CH2:24][CH2:25]O.C1(C)C=CC(S(O)(=O)=O)=CC=1>>[C:1]1([CH2:17][C:18]([O:20][CH2:25][CH2:24][O:23][CH2:22][CH2:21][OH:27])=[O:19])[C:14]2[C:15]3=[C:16]4[C:11](=[CH:12][CH:13]=2)[CH:10]=[CH:9][CH:8]=[C:7]4[CH:6]=[CH:5][C:4]3=[CH:3][CH:2]=1
Reactant: OCCOCCO
Reactant: O=C(O)Cc1ccc2ccc3cccc4ccc1c2c34
Agent: Cc1ccc(S(=O)(=O)O)cc1
Product: O=C(Cc1ccc2ccc3cccc4ccc1c2c34)OCCOCCO
Temperature: 130 °C
Yield: 83.5 %

Procedure:
1-Pyreneacetic acid (1 g, 3.85 mmol), diethylene glycol (10 ml, 91.0 mmol) and p-toluenesulfonic acid (100 mg, 0.58 mmol) were mixed and heated to 130° C. for 16 h with stirring under N2. After the reaction was completed (confirmed by TLC), the reaction mixture was cooled to 20° C. and poured into 50 ml ice-water drop-wise. The aqueous reaction mixture was extracted with EtOAc (3×100 ml) and the combined organic solutions were washed with 5% aqueous KOH (2×50 ml), H2O (2×50 ml) and brine (1×50 ml), and were subsequently dried over anhydrous MgSO4. The crude product was purified by column chromatography (silica gel, EtOAc/hexanes: 1/1) to yield 1.12 g (83.59%) 15 as a light green oil. Purity: 99+% (HPLC). TLC: Rf=0.17 (EtOAc/hexanes: 1/1). 1H NMR (250 MHz, CDCl3, 20° C.): δ 8.26-7.94 (m, 9H), 4.38 (s, 2H), 4.27 (m, 2H), 3.63 (m, 2H), 3.53 (m, 2H), 3.39 (m, 2H), 2.82 (s broad, 1H). 13C NMR (125 MHz, CDCl3, 20° C.): δ 171.5, 131.3, 130.8, 130.7, 129.4, 128.3, 127.9, 127.4, 127.3, 126.0, 125.3, 125.1, 125.0, 124.8, 124.7, 123.2, 72.2, 68.9, 64.1, 61.6, 39.4.
Reaction SMILES: [C:1]([O-:4])(=[S:3])[CH3:2].[K+].[CH3:6][C:7]([CH3:9])=[O:8]>>[C:1]([O:4][CH2:6][CH:7]1[CH2:9][O:8][C:7]([CH3:9])([CH3:6])[O:8]1)(=[S:3])[CH3:2]
Reactant: CC([O-])=S
Reactant: CC(C)=O
Agent: [K+]
Product: CC(=S)OCC1COC(C)(C)O1

Procedure:
A mixture of 13.3 g of the above product and 7.2 g of potassium thioacetate in 300 ml of acetone was refluxed for 10 hours. The resulting mixture was filtered, most of the solvent evaporated off under vacuum and the remaining solution poured into diethyl ether. The solution was washed with water, the organic solvent removed under vacuum and the residue distilled under vacuum, giving (±)2,2-dimethyl-1,3-dioxolan-4-ylmethyl thioacetate, having a boiling point between 83° C. and 87° C. at a pressure of 0.1 mm Hg.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[OH:10])([O-:3])=[O:2].[CH3:11][O:12][CH2:13][CH2:14]Cl.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH3:11][O:12][CH2:13][CH2:14][O:10][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=1[N+:1]([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1ccccc1O
Reactant: COCCCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COCCOc1ccccc1[N+](=O)[O-]
Temperature: 110 °C

Procedure:
140 g (1010 mmol) 2-nitrophenol, 105 g (1110 mmol) chloroethyl methyl ether, 84.2 g (507 mmol) KI and 153 g (1110 mmol) K2CO3, were suspended in 500 ml DMF, in a 2 l Erlenmeyer flask heated at 110±5° C. for 6 h. The solvent was evaporated and the residue was dissolved in 500 ml CHCl3 and 500 ml water. The organic phase was washed with 2×500 ml 2.5% Na2CO3, 500 ml sat. NaCl and dried over Na2SO4. The solvent was evaporated to afford 201 g (100%) light yellow oil. H1NMR (CDCl3) δ (ppm) 3.45 (s,3H), 3.78(t,2H), 4.25(t,2H), 7.02(dd,1H), 7.10(dd,1H), 7.50(dd,1H), 7.82(dd,1H).
Reaction SMILES: C([C@@H:4]1[CH2:13][CH2:12][C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C@H:5]1[OH:14])(O)=O.[N:15](C(OCC)=O)=NC(OCC)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OCC)(=O)C>O1CCCC1>[OH:14][C@H:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH2:12][CH2:13][C@H:4]1[NH2:15]
Reactant: CCOC(=O)N=NC(=O)OCC
Reactant: O=C(O)[C@@H]1CCc2ccccc2[C@H]1O
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: N[C@@H]1CCc2ccccc2[C@@H]1O

Procedure:
One gram of the hydroxamic acid of (1S,2R)-2-carboxy-1-hydroxytetralin is reacted with equimolar amounts of diethyl azodicarboxylate and triphenylphosphine in tetrahydrofuran at room temperature using the procedure of Bittner, Grinberg and Kartoon (Tet. Lett. 23, 1965-8 (1974)). The product is isolated by acidification and extraction of the reaction mixture with ethyl acetate, followed by basification of the resulting aqueous solution with NaOH, extraction with methyl t-butyl ether, drying of the extracts over MgSO4, filtration, and the removal of solvent by rotary evaporation. The product (1S,2R)-1-hydroxy-2-aminotetralin is isolated as a light yellow oil.
Reaction SMILES: C[O:2][C:3](=[O:17])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([SH:16])=[C:12]2[C:7]=1[CH2:8][CH2:9][CH2:10][O:11]2.Cl[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][N:27]=2)=[CH:22][CH:21]=1>>[F:35][C:32]([F:33])([F:34])[C:29]1[CH:30]=[CH:31][C:26]([C:23]2[CH:24]=[CH:25][C:20]([CH2:19][S:16][C:13]3[CH:14]=[CH:15][C:6]([O:5][CH2:4][C:3]([OH:2])=[O:17])=[C:7]4[C:12]=3[O:11][CH2:10][CH2:9][CH2:8]4)=[CH:21][CH:22]=2)=[N:27][CH:28]=1
Reactant: FC(F)(F)c1ccc(-c2ccc(CCl)cc2)nc1
Reactant: COC(=O)COc1ccc(S)c2c1CCCO2
Product: O=C(O)COc1ccc(SCc2ccc(-c3ccc(C(F)(F)F)cn3)cc2)c2c1CCCO2

Procedure:
The title compound was prepared in the manner analogous to Example 1F using (8-mercapto-chroman-5-yloxy)-acetic acid methyl ester and 18B. MS m/z 490 (M+1).
Reaction SMILES: [OH-].[K+].[F:3][CH2:4][C:5]([CH2:15][F:16])([C:7](=[O:14])[CH2:8][N:9]1[CH:13]=[N:12][CH:11]=[N:10]1)[CH3:6].[CH:17]1([CH2:23]Br)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1>O.CS(C)=O>[F:16][CH2:15][C:5]([CH2:4][F:3])([C:7](=[O:14])[CH:8]([N:9]1[CH:13]=[N:12][CH:11]=[N:10]1)[CH2:23][CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1)[CH3:6]
Reactant: BrCC1CCCCC1
Reactant: CC(CF)(CF)C(=O)Cn1cncn1
Agent: [K+]
Agent: [OH-]
Solvent: CS(C)=O
Solvent: O
Product: CC(CF)(CF)C(=O)C(CC1CCCCC1)n1cncn1
Yield: 54.9 %

Procedure:
A solution of 101.4 g (1.81 mol) of potassium hydroxide in 217.2 ml of water was added to a solution of 369.4 g (1.81 mol) of 2,2-bisfluoromethyl-4-(1,2,4-triazol-1-yl)-butan-3-one in 2 liters of dimethylsulphoxide at room temperature, with stirring. 320.5 g (1.81 mol) of cyclohexylmethyl bromide were added dropwise to this mixture, with stirring, the temperature of the reaction mixture being kept between 20° and 40° C. by cooling. The reaction mixture was stirred at 60° C. for a further 15 hours and then poured into 2 liters of water. The resulting mixture was extracted twice with 1 liter of methylene chloride each time, the combined organic phases were washed four times with 2 liters of water each time and dried over sodium sulphate and the solvent was stripped off. The resulting oily product was taken up in acetone, and 326 g of naphthalene-1,5-disulphonic acid were added to the solution. The precipitate which thereby formed was filtered off with suction and suspended in 2 liters of methylene chloride. This suspension was shaken twice with 2 liters of saturated aqueous sodium bicarbonate solution each time. The organic phase was then washed with 2 liters of water and, after drying over sodium sulphate, was concentrated under reduced pressure. 297.5 g (63% of theory) of 2,2-bis-fluoromethyl-5-cyclohexyl-4-(1,2,4-triazol-1-yl)-pentan-3-one were obtained in this manner in the form of an oil. nD20 =1.4837.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[C:30](=[O:31])[N:29]([CH3:32])[C:12]2[N:13]=[C:14]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([CH2:24][C:25]([O:27]C)=[O:26])=[CH:20][CH:19]=3)[N:15]=[CH:16][C:11]=2[CH:10]=1.[OH-].[Na+].C(O)(=O)C>CO>[Cl:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=1[C:9]1[C:30](=[O:31])[N:29]([CH3:32])[C:12]2[N:13]=[C:14]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([CH2:24][C:25]([OH:27])=[O:26])=[CH:20][CH:19]=3)[N:15]=[CH:16][C:11]=2[CH:10]=1
Reactant: COC(=O)Cc1ccc(Nc2ncc3cc(-c4c(Cl)cccc4Cl)c(=O)n(C)c3n2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: CC(=O)O
Product: Cn1c(=O)c(-c2c(Cl)cccc2Cl)cc2cnc(Nc3ccc(CC(=O)O)cc3)nc21

Procedure:
A quantity of 0.065 g (0.14 mmol) of {4-[6-(2,6-dichlorophenyl)-8-methyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino]phenyl}-acetic acid, methyl ester of Example 84 was dissolved in 25 mL of hot methanol with stirring. At the boiling point, 1 mL of 2N sodium hydroxide was added. After 1 hour reflux, the solution was concentrated to 5 mL volume (solid was out of solution). Water (10 mL) was added to give a complete solution. Glacial acetic acid (0.25 mL) was added to precipitate the solid free acid product. The solid was filtered, washed well with water, and dried; wt 0.060 g. Purification was accomplished by dissolution in 60 mL of 50% methanol/methylene chloride. Traces of solids were filtered, and the filtrate was concentrated with stirring to 2 mL volume. The separated solid was filtered and washed with 0.5 mL of methanol and ether; wt 0.050 g; mp 286°-290° C.
Reaction SMILES: [C:1]1([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([OH:13])[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:21][CH2:22][CH2:23][CH2:24][Cl:25]>CN(C)C=O>[Cl:25][CH2:24][CH2:23][CH2:22][CH2:21][N:10]1[CH:11]=[CH:12][C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[N:8][C:9]1=[O:13]
Reactant: Oc1nccc(-c2ccccc2)n1
Reactant: ClCCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=c1nc(-c2ccccc2)ccn1CCCCCl
Temperature: 25 °C
Reaction time: 12 h

Procedure:
0.84 g (4.20 mmol) of 4-phenylpyrimidin-2-ol from Example 24.2 was stirred in 8.4 ml of N,N-dimethylformamide (DMF) and 0.58 g (4.20 mmol) of K2CO3 at room temperature for 1 hour. Then 0.72 g (4.20 mmol) of 1-bromo-4-chlorobutane was added dropwise, the reaction mixture was stirred at room temperature for 12 hours, and the reaction mixture was filtered and concentrated. The residue was then taken up in toluene and concentrated, and the residue was again taken up in toluene and concentrated. The resulting residue was stirred with pentane and filtered. Yield: 0.74 g.
Reaction SMILES: [Br:1]N1C(=O)CCC1=O.[CH2:9]([N:13]1[C:17]([CH2:18][OH:19])=[CH:16][N:15]=[C:14]1[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH2:10][CH2:11][CH3:12].O>C(#N)C>[CH2:9]([N:13]1[C:17]([CH2:18][OH:19])=[C:16]([Br:1])[N:15]=[C:14]1[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[CH2:10][CH2:11][CH3:12]
Reactant: O=C1CCC(=O)N1Br
Reactant: CCCCn1c(CO)cnc1-c1ccccc1
Solvent: CC#N
Solvent: O
Product: CCCCn1c(-c2ccccc2)nc(Br)c1CO
Temperature: 0 °C
Reaction time: 1 h
Yield: 50.9 %

Procedure:
N-bromo succinimide (3.56 g, 20 mmol) is added to a solution of alcohol 139 (4.60 g, 20 mmol) in 100 ml of anhydrous acetonitrile cooled to 0° C., in portions over 15 minutes. The resulting mixture is stirred at 0° C. for 60 min, water is added to quench the reaction, the acetonitrile is evaporated, and the residue dissolved in 100 ml of ethyl acetate, washed with water and brine, and dried over Na2SO4 The solvent is evaporated and the residue purified by silica gel flash chromatography (hexanes/ethyl acetate, from 6:1 to 3:1) to give 3.15 g of product 140. 1H NMR (300 MHz, CDCl3) δ 7.48–7.56 (2H, m), 7.40–7.47 (3H, m), 4.67 (2H, s), 4.07 (2H, t, J=7.60 Hz), 1.65 (2H, m), 1.24 (2H, m), 0.83 (3H, t, J=7.5 Hz). MS (+VE) m/z 309 (M+), 311 (M+2).
Reaction SMILES: [CH2:1]([O:4][C:5]([N:7]1[CH2:11][C@H:10]([OH:12])[CH2:9][C@H:8]1[C:13](OC)=[O:14])=[O:6])[CH:2]=[CH2:3].[Li+].[BH4-]>C1COCC1>[CH2:1]([O:4][C:5]([N:7]1[CH2:11][C@H:10]([OH:12])[CH2:9][C@H:8]1[CH2:13][OH:14])=[O:6])[CH:2]=[CH2:3]
Reactant: C=CCOC(=O)N1C[C@H](O)C[C@H]1C(=O)OC
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Product: C=CCOC(=O)N1C[C@H](O)C[C@H]1CO
Temperature: 25 °C
Yield: 99.2 %

Procedure:
A solution of the ester 13 (19.5 g, 85 mmol) in THF (326 mL) was cooled to 0° C. (ice/acetone) and treated with LiBH4 (2.78 g, 128 mmol) in portions. The reaction mixture was allowed to warm to room temperature and stirred under a nitrogen atmosphere for 2.5 hours at which time TLC (50% EtOAc/Petroleum Ether) revealed complete consumption of ester 13. The mixture was cooled to 0° C. and water (108 mL) was carefully added followed by 2 N HCl (54 mL). After evaporation of the THF in vacuo, the mixture was neutralised to pH 7 with 10 N NaOH and saturated with solid NaCl. The saturated aqueous solution was then extracted with EtOAc (5×100 mL), the combined organic layers washed with brine (200 mL), dried (MgSO4), filtered and evaporated in vacuo to furnish the pure diol 14 as a clear colourless oil (16.97 g, 99%): [α]24D=−57.0° (c=0.61, CHCl3); 1H NMR (270 MHz, CDCl3) δ6.01-5.87 (m, 1H, NCO2CH2CH═CH2), 5.36-5.20 (m, 2H, NCO2CH2CH═CH2), 4.84 (br s, 1H, NCHCH2OH), 4.60 (d, 2H, J=5.31 Hz, NCO2CH2CH═CH2), 4.39 (br s, 1H, NCHCH2OH), 4.18-4.08 (m, 1H, 3.35, NCH2CHOH), 3.90-3.35 (m, 4H, NCH2CHOH, NCHCH2OH, and OH), 3.04 (br s, 1H, OH), 2.11-2.03 (m, 1H, NCH2CHOHCH2), 1.78-1.69 (m, 1H, NCH2CHOHCH2); 13C NMR (67.8 MHz, CDCl3) δ157.1 (NC═O), 132.6 (NCO2CH2CH═CH2), 117.7 (NCO2CH2CH═CH2), 69.2 (NCH2CHOH), 66.4 and 66.2 (NCO2CH2CH═CH2 and NCHCH2OH), 59.2 (NCHCH2OH), 55.5 (NCH2CHOH), 37.3 (NCH2CHOHCH2); MS (EI), m/z (relative intensity) 201 (M+., 2), 170 (M—CH2OH, 100), 144 (M—OC3H5, 6), 126 (26), 108 (20), 68 (9); IR (Neat) 3394 (br, OH), 2946, 2870, 1679 (C═O), 1413, 1339, 1194, 1126, 1054, 980, 772 cm−1; exact mass calcd for C9H11NO4 m/e 201.1001, obsd m/e 201.1028.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:24]=[CH:23][C:6]([CH2:7][NH:8][C:9]2[CH:14]=[CH:13][C:12]([CH2:15][N:16]([CH2:20][CH2:21][CH3:22])[CH2:17][CH2:18][CH3:19])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.[NH:25]1[CH:29]=[CH:28][N:27]=[C:26]1[CH:30]=O>CO>[CH2:17]([N:16]([CH2:15][C:12]1[CH:13]=[CH:14][C:9]([NH:8][CH2:7][C:6]2[CH:5]=[CH:4][C:3]([CH2:2][NH:1][CH2:30][C:26]3[NH:25][CH:29]=[CH:28][N:27]=3)=[CH:24][CH:23]=2)=[CH:10][CH:11]=1)[CH2:20][CH2:21][CH3:22])[CH2:18][CH3:19]
Reactant: CCCN(CCC)Cc1ccc(NCc2ccc(CN)cc2)cc1
Reactant: O=Cc1ncc[nH]1
Solvent: CO
Product: CCCN(CCC)Cc1ccc(NCc2ccc(CNCc3ncc[nH]3)cc2)cc1
Temperature: 25 °C
Reaction time: 17 h
Yield: 59.8 %

Procedure:
The compound (63.1 mg) obtained in Example 39-2 was dissolved in methanol (2.0 ml) and then added with 2-imidazole carboxaldehyde (17.9 mg), followed by stirring at room temperature for 17 hours. After the solvent had been distilled off, the residue was dried under vacuum and then dissolved in methanol (2.5 ml). Subsequently, the solution was added with sodium borohydride (14.5 mg) and stirred at room temperature for 1 hour. The reaction solution was added with a saturated aqueous ammonium chloride solution (4.0 ml) and stirred at room temperature for 30 minutes. Then, the reaction solution was added with saturated saline solution and subjected to extraction with chloroform, followed by drying with anhydrous sodium sulfate. After the solvent had been distilled off, the residue obtained was purified through silica gel column chromatography (chloroform/acetone), thereby obtaining the subject compound (45.2 mg) as a yellow solid.
Reaction SMILES: [C:1]([OH:6])(=[O:5])[C:2]([CH3:4])=[CH2:3].[O:7]1[CH:11]=[CH:10][CH2:9][CH2:8]1>ClCCl>[C:1]([O:6][CH:8]1[CH2:9][CH2:10][CH2:11][O:7]1)(=[O:5])[C:2]([CH3:4])=[CH2:3]
Reactant: C1=COCC1
Reactant: C=C(C)C(=O)O
Solvent: ClCCl
Product: C=C(C)C(=O)OC1CCCO1
Temperature: 25 °C
Reaction time: 14 h
Yield: 34 %

Procedure:
To a solution of 10 g methacrylic acid in 10 ml dichloromethane was added a solution of 9.28 ml 2,3-dihydrofuran in 30 ml dichloromethane. The reaction was allowed to stir for 14 hr at room temperature. The mixture was washed with a saturated solution of sodium bicarbonate. The organic layer was dried with MgO/MgSO4 and concentrated in vacuo. The residue was distilled at 38° C./0.3 torr, to give 6.2 g (34% yield) of tetrahydrofuran-2-yl methacrylate. A solution of 6.0 g tetrahydrofuran-2-yl methacrylate and 0.066 g AIBN in 6 ml of MEK was heated to 60° C. for two days and 12 ml of MEK was added. This solution was used for further evaluation.
Reaction SMILES: [F:1][C:2]([F:26])([F:25])[C:3]1[N:8]2[N:9]=[CH:10][C:11]([C:12](O)=[O:13])=[C:7]2[N:6]=[C:5]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=2)[CH:4]=1.[NH2:27][C:28]1[CH:29]=[C:30]([S:35]([NH2:38])(=[O:37])=[O:36])[CH:31]=[CH:32][C:33]=1[CH3:34]>>[CH3:34][C:33]1[CH:32]=[CH:31][C:30]([S:35](=[O:37])(=[O:36])[NH2:38])=[CH:29][C:28]=1[NH:27][C:12]([C:11]1[CH:10]=[N:9][N:8]2[C:3]([C:2]([F:1])([F:25])[F:26])=[CH:4][C:5]([C:15]3[CH:20]=[CH:19][C:18]([C:21]([F:23])([F:22])[F:24])=[CH:17][CH:16]=3)=[N:6][C:7]=12)=[O:13]
Reactant: Cc1ccc(S(N)(=O)=O)cc1N
Reactant: O=C(O)c1cnn2c(C(F)(F)F)cc(-c3ccc(C(F)(F)F)cc3)nc12
Product: Cc1ccc(S(N)(=O)=O)cc1NC(=O)c1cnn2c(C(F)(F)F)cc(-c3ccc(C(F)(F)F)cc3)nc12

Procedure:
The title compound was prepared from 7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (example C.2) and 3-amino-4-methyl-benzenesulfonamide [CAS-No. 6274-28-8; commercially available] according to general procedure II. Yellow solid. MS (ISP) 542.1 [(M−H−]; mp 310° C.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:6]([C:7]([OH:9])=[O:8])[C:5]([SH:11])=[CH:4][CH:3]=1.Cl[CH2:13][C:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:15].[OH-].[Na+].C(O)C>O>[CH2:13]([S:11][C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:10][C:6]=1[C:7]([OH:9])=[O:8])[C:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:15]
Reactant: O=C(CCl)c1ccccc1
Reactant: O=C(O)c1cc(Cl)ccc1S
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: O=C(CSc1ccc(Cl)cc1C(=O)O)c1ccccc1

Procedure:
A solution of 18.9 g. (0.1 mole) of 5-chlorothiosalicylic acid, 15.4 g. (0.1 mole) of α-chloroacetophenone and 8 g. (0.2 mole) of sodium hydroxide in 200 ml. of ethanol containing 45 ml. of water is heated to reflux for 2 hours. After removing one-fourth the alcohol under reduced pressure, the mixture is acidified with hydrochloric acid and the resulting precipitated product filtered, 5.0 g., m.p. 154°-156° C. The analytical sample has a melting point of 156°-157.5° C.