Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][N:14]=[C:15]2[CH2:20][CH2:19][N:18]([C:21]3[N:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[C:24]([C:31](O)=[O:32])=[CH:23][N:22]=3)[CH2:17][CH2:16]2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].CN.C1C=CC2N(O)N=[N:42][C:40]=2C=1.C(Cl)CCl>C(Cl)Cl>[CH:1]([O:4][C:5]([N:7]1[CH2:8][CH2:9][CH:10]([O:13][N:14]=[C:15]2[CH2:16][CH2:17][N:18]([C:21]3[N:26]=[C:25]([C:27]([F:30])([F:28])[F:29])[C:24]([C:31](=[O:32])[NH:42][CH3:40])=[CH:23][N:22]=3)[CH2:19][CH2:20]2)[CH2:11][CH2:12]1)=[O:6])([CH3:2])[CH3:3]
Reactant: On1nnc2ccccc21
Reactant: CC(C)OC(=O)N1CCC(ON=C2CCN(c3ncc(C(=O)O)c(C(F)(F)F)n3)CC2)CC1
Agent: CN
Solvent: ClCCl
Solvent: ClCCCl
Product: CNC(=O)c1cnc(N2CCC(=NOC3CCN(C(=O)OC(C)C)CC3)CC2)nc1C(F)(F)F
Temperature: 25 °C
Reaction time: 18 h

Procedure:
Half of the crude 57b was combined with methylamine (0.06 mmol), HOBT (7 mg, 0.06 mmol) and EDC(10 mg, 0.05 mmol) in 1 mL of DCM. The mixture was stirred at room temperature for 18 h, washed with aqueous NaHCO3 and concentrated. The residue was purified by preparative HPLC to afford 57-1: LC-MS 487.3 (MH+), tR=5.20 (Method 5).
Reaction SMILES: [CH3:1][O:2][C@H:3]1[C@@H:8]([NH:9][CH:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH3:11])[CH2:7][CH2:6][N:5](C(OCC)=O)[CH2:4]1.Cl>>[CH3:1][O:2][C@H:3]1[C@@H:8]([NH:9][CH:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH3:11])[CH2:7][CH2:6][NH:5][CH2:4]1
Reactant: CCOC(=O)N1CC[C@H](NC(C)c2ccccc2)[C@H](OC)C1
Agent: Cl
Product: CO[C@@H]1CNCC[C@@H]1NC(C)c1ccccc1
Yield: 100 %

Procedure:
A solution of 16 parts of (-)-ethyl cis-3-methoxy-4-[(1-phenylethyl)amino]-1-piperidinecarboxylate in 170 parts of a hydrochloric acid solution 6N was stirred and refluxed for 45 hours. The reaction mixture was cooled and washed with dichloromethane. The aqueous phase was cooled in an ice-bath and treated with ammonium hydroxide. The product was extracted three times with 130 parts of dichloromethane. The combined extracts were washed with 10 parts of water, dried, filtered and evaporated. The residue was dissolved in methylbenzene and the latter was evaporated again, yielding 12.2 parts (100%) of (+)-cis-3-methoxy-N-(1-phenylethyl)-4-piperidinamine as a residue (intermediate 105).
Reaction SMILES: Cl[C:2]1[CH:11]=[C:10]([CH2:12][CH2:13][NH:14][C:15](=[O:17])[CH3:16])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:18][CH3:19])[CH:8]=2)[N:3]=1.[CH3:20][O-:21].[Na+].O>CO>[CH3:20][O:21][C:2]1[CH:11]=[C:10]([CH2:12][CH2:13][NH:14][C:15](=[O:17])[CH3:16])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:18][CH3:19])[CH:8]=2)[N:3]=1
Reactant: COc1ccc2nc(Cl)cc(CCNC(C)=O)c2c1
Reactant: C[O-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: COc1ccc2nc(OC)cc(CCNC(C)=O)c2c1
Temperature: 60 °C
Reaction time: 8 h
Yield: 52.4 %

Procedure:
A mixture of N-[2-(2-chloro-6-methoxyquinolin-4-yl)ethyl]acetamide (0.9 g, 3.2 mmol) and sodium methoxide (30 g, 28% methanol solution) in methanol (20 ml) was stirred at 60° C. overnight. The reaction mixture was poured into water, and the organic layer was extracted with ethyl acetate. The extract was washed with saturated brine and water and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The resulting residue was purified by column chromatography on silica gel (ethyl acetate) and recrystallized from a mixed solvent of ethyl acetate and hexane to obtain the title compound (0.46 g, 52%).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1C(C2C=CC(C#N)=CC=2)O1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:19][C:20]([CH3:24])([CH3:23])[CH2:21][OH:22]>C(OCC)C>[C:1]([O:5][C:6]([NH:8][NH:19][C:20]([CH3:24])([CH3:23])[CH2:21][OH:22])=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C)(N)CO
Reactant: CC(C)(C)OC(=O)N1OC1c1ccc(C#N)cc1
Solvent: CCOCC
Product: CC(C)(CO)NNC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 39.9 %

Procedure:
A solution of N-(tert-butoxycarbonyl)-3-(4-cyanophenyl)-oxaziridine (CAS #: 150884-56-3, purchased from Acros, 5.17 g, 21 mmol) in anhydrous diethyl ether (20 mL) was added to a solution of 2-amino-2-methyl-propan-1-ol (1.78 g, 20 mmol) in anhydrous diethyl ether (20 mL) at room temperature. The reaction mixture stirred at room temperature for 2 hours. Diethyl ether was evaporated under reduced pressure and the residue was purified by flash chromatography eluting with a gradient of 3-5% methanol/dichloromethane to give N′-(2-hydroxy-1,1-dimethyl-ethyl)-hydrazinecarboxylic acid tert-butyl ester (1.63 g, 40%) which was used without further purification.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH2:10][C:11]([NH:13][CH2:14][C:15]#[CH:16])=[O:12])[CH:8]=2)[CH:3]=[CH:2]1.I[C:18]1[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=1>>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH2:10][C:11]([NH:13][CH2:14][C:15]#[C:16][C:18]3[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=3)=[O:12])[CH:8]=2)[CH:3]=[CH:2]1
Reactant: FC(F)(F)c1ccc(I)cc1
Reactant: C#CCNC(=O)Cc1ccc2cc[nH]c2c1
Product: O=C(Cc1ccc2cc[nH]c2c1)NCC#Cc1ccc(C(F)(F)F)cc1

Procedure:
In analogy to the procedure described for example 8 a], 2-(1H-indol-6-yl)-N-prop-2-ynyl-acetamide (example 13 a]) was reacted with 4-iodobenzotrifluoride in the presence of PdCl2(Ph3P)2 and cuprous iodide to give the title compound as colorless crystals.
Reaction SMILES: [CH2:1]([NH:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH2:19][NH:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[CH:14]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[F:31][C:32]1[CH:37]=[C:36]([F:38])[CH:35]=[CH:34][C:33]=1[N:39]=[C:40]=[O:41]>CCCCCC>[CH2:21]([N:20]([CH2:19][C:15]1[CH:16]=[CH:17][CH:18]=[C:13]([CH2:12][N:11]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10])[C:40]([NH:39][C:33]2[CH:34]=[CH:35][C:36]([F:38])=[CH:37][C:32]=2[F:31])=[O:41])[CH:14]=1)[C:40]([NH:39][C:33]1[CH:34]=[CH:35][C:36]([F:38])=[CH:37][C:32]=1[F:31])=[O:41])[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30]
Reactant: CCCCCCCCCCNCc1cccc(CNCCCCCCCCCC)c1
Reactant: O=C=Nc1ccc(F)cc1F
Solvent: CCCCCC
Product: CCCCCCCCCCN(Cc1cccc(CN(CCCCCCCCCC)C(=O)Nc2ccc(F)cc2F)c1)C(=O)Nc1ccc(F)cc1F
Reaction time: 2 h
Yield: 51.6 %

Procedure:
To a solution of 833 mg N,N'-didecyl-m-xylylenediamine in 20 ml n-hexane, was added dropwise with stirring 5 ml of a n-hexane solution containing 620 mg 2,4-difluorophenyl isocyanate under ice cooling. Stirring was continued at room temperature for two hours, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography, giving 750 mg of 1,3-bis[[1-decyl-3-(2,4-difluorophenyl)ureido]methyl]benzene.
Reaction SMILES: Br[CH2:2][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][CH:12]=1)[C:6]([O:8][CH3:9])=[O:7].[C-:13]#[N:14].[K+].C1OCCOCCOCCOCCOCCOC1>C(#N)C>[C:13]([CH2:2][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][CH:12]=1)[C:6]([O:8][CH3:9])=[O:7])#[N:14]
Reactant: COC(=O)c1cccc(CBr)c1
Reactant: [C-]#N
Agent: C1COCCOCCOCCOCCOCCO1
Agent: [K+]
Solvent: CC#N
Product: COC(=O)c1cccc(CC#N)c1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
A mixture of methyl 3-(bromomethyl)benzoate (0.6 gram, 2.6 mmol), potassium cyanide (0.35 gram, 5.2 mmol) and 60 mg of 18-crown-6 in 6 ml acetonitrile was vigorously stirred at room temperature for 24 hours. The mixture was filtered, the filtrate concentrated to half volume, water was added to the remaining mixture and extraction was performed with dichloromethane. The organic phase was dried over MgSO4 and the solvent was evaporated, to give the product as a yellow liquid, which was used without purification.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:13])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH:11]=[CH2:12].C(C1C=C(P(C2C=CC=CC=2)C2C=CC=CC=2)C2[O:28][C:27]3C(=CC(C(C)(C)C)=CC=3P(C3C=CC=CC=3)C3C=CC=CC=3)C(C)(C)C=2C=1)(C)(C)C>>[OH:28][CH2:27][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][C:3]([O:2][CH3:1])=[O:13]
Reactant: CC(C)(C)c1cc(P(c2ccccc2)c2ccccc2)c2c(c1)C(C)(C)c1cc(C(C)(C)C)cc(P(c3ccccc3)c3ccccc3)c1O2
Reactant: C=CCCCCCCCC(=O)OC
Product: COC(=O)CCCCCCCCCCO
Temperature: 85 °C
Reaction time: 16 h

Procedure:
A hydroformylation reaction was carried out in a Parr reactor (300 mL capacity) equipped with a mechanical stirrer, gas inlet tube, heating jacket, pressure transducer and thermocouple. The reactor was charged with methyl-9-decenoate (100 g, 0.54 mol), acetylacetonate(dicarbonyl)-rhodium (II) [Rh(CO)2 acac] (32 mg, 0.12 mmol), and 2,7-di-tert-butyl-9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (342 mg, 0.49 mmol) under nitrogen, and then the reactor was sealed. The reactor was connected to a feed line for delivering synthesis gas (CO/H2, 1:1). The system was flushed with synthesis gas twice and then pressurized to 450 psi (3,103 kPa). The reactor was heated to 85° C. for 16 h while maintaining 450 psi (3,103 kPa) of syn gas pressure. After 16 h, the temperature was raised to 100° C. and heated for an additional 4 h. The reactor was cooled to ambient temperature and the unreacted gas was vented. After flushing the reactor with nitrogen to remove the last traces of syn gas, dioxane (50 ml) and 1 g of 5% Pt/SiO2 were introduced to the reactor. The system was flushed with hydrogen twice and pressurized to 500 psi (3,448 kPa) with hydrogen. The mixture was then heated to 150° C. for 20 h maintaining 500 psi (3,448 kPa) of hydrogen pressure. After cooling, the contents were filtered to remove the solid catalyst, and the solvent was removed by rotary evaporation. The resulting liquid was subjected to distillation under reduced pressure. The fraction boiling at 140-150° C. (1.5 mm pressure) was collected and dissolved in 1200 mL of hexanes. The solution was then allowed to crystallize in a freezer for 18 h. White crystals were collected by cold filtration and washed once with cold hexanes. Drying under reduced pressure yielded methyl 11-hydroxyundecanoate as white solid (77 g; 65% overall yield). Conversion of methyl 11-hydroxyundecanoate via transesterification with a polyol, such as glycerol, to the corresponding polyester polyol, such as the triglyceride of 11-hydroxyundecanoic acid, can be effected by transesterification methods known in the art.
Reaction SMILES: [H-].[Na+].[O:3]=[C:4]([CH3:12])[CH2:5]P(=O)(OC)OC.[CH:13]1([CH2:16][O:17][C:18]2[CH:19]=[CH:20][C:21]3[C:25]([CH:26]=2)=[N:24][N:23]([C@H:27]2[CH2:32][CH2:31][C@H:30]([CH:33]=O)[CH2:29][CH2:28]2)[CH:22]=3)[CH2:15][CH2:14]1.Cl>COCCOC>[CH:13]1([CH2:16][O:17][C:18]2[CH:19]=[CH:20][C:21]3[C:25]([CH:26]=2)=[N:24][N:23]([C@H:27]2[CH2:32][CH2:31][C@H:30](/[CH:33]=[CH:5]/[C:4](=[O:3])[CH3:12])[CH2:29][CH2:28]2)[CH:22]=3)[CH2:15][CH2:14]1
Reactant: COP(=O)(CC(C)=O)OC
Reactant: O=C[C@H]1CC[C@H](n2cc3ccc(OCC4CC4)cc3n2)CC1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: COCCOC
Product: CC(=O)/C=C/[C@H]1CC[C@H](n2cc3ccc(OCC4CC4)cc3n2)CC1
Reaction time: 1 h

Procedure:
Sodium hydride (0.292 g) was added to a solution of dimethyl 2-oxopropylphosphonate (2.021 g) in 1,2-dimethoxyethane (50 mL) under ice-cooling in small portions. The reaction mixture was stirred for 1 hr under ice-cooling, and a solution of trans-4-[6-(cyclopropylmethoxy)-2H-indazol-2-yl]cyclohexanecarbaldehyde (3.30 g) in 1,2-dimethoxyethane (50 mL) was added under ice-cooling. The reaction mixture was stirred at room temperature for 3 hr, poured into 1N hydrochloric acid under ice-cooling and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane/ethyl acetate) to give the title compound (2.85 g).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=[O:6].[CH:10]#[C:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]>C(N(CC)CC)C.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I>[C:10]([C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=[O:6])#[C:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]
Reactant: C#CCCCCCCCCC
Reactant: O=Cc1cccc(Br)c1
Agent: Cl[Pd]Cl
Agent: [Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: CCCCCCCCCC#Cc1cccc(C=O)c1
Temperature: 55 °C
Reaction time: 6 h
Yield: 109.1 %

Procedure:
To a solution of 3-bromobenzaldehyde (30.3 g) and 1-undecyne (29.5 g) in triethylamine (120 ml) was added bis(triphenylphosphine)palladium(II)chloride (1.9 g) followed by copper(I) iodide (0.25 g). The mixture was stirred in the dark at 55° C. for 6 hrs, under nitrogen. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate and filtered. The filtrate was washed with water and saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated to yield 45.8 g of 3-(1-undecynyl)benzaldehyde, as an oil.
Reaction SMILES: [Br:1][C:2]1[CH:15]=[CH:14][C:5]2[N:6]=[C:7]([C@@H:9]3[CH2:12][C@H:11](O)[CH2:10]3)[S:8][C:4]=2[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.[NH:37]1[CH2:42][CH2:41][CH:40]([CH2:43][OH:44])[CH2:39][CH2:38]1>ClCCl>[Br:1][C:2]1[CH:15]=[CH:14][C:5]2[N:6]=[C:7]([C@H:9]3[CH2:12][C@H:11]([N:37]4[CH2:42][CH2:41][CH:40]([CH2:43][OH:44])[CH2:39][CH2:38]4)[CH2:10]3)[S:8][C:4]=2[CH:3]=1
Reactant: OCC1CCNCC1
Reactant: O[C@H]1C[C@@H](c2nc3ccc(Br)cc3s2)C1
Agent: O=C([O-])[O-]
Agent: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Agent: [K+]
Solvent: ClCCl
Product: OCC1CCN([C@H]2C[C@H](c3nc4ccc(Br)cc4s3)C2)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
The product of Example 1D (0.177 mmole) was dissolved in anhydrous dichloromethane (2 ml). Potassium carbonate (50 mg, 0.362 mmole) was added followed by trifluoromethanesulfonic anhydride (40 μl, 0.238 mmole). The mixture was allowed to stir at room temperature for 2 hours, then another portion of potassium carbonate (100 mg, 0.724 mmole) was added, followed by 4-piperidinemethanol (61 mg, 0.530 mmole). The resulting mixture was stirred at room temperature overnight. It was then quenched with water, and extracted three times with dichloromethane. The organic layers were combined, washed with brine, dried over sodium sulfate, and concentrated. The crude product was purified by column chromatography (0.3% ammonium hydroxide and 3% methanol in dichloromethane) to give 29 mg (43%) of title compound. 1H NMR (500 MHz, CDCl3) δ ppm 7.98 (d, J=1.83 Hz, 1H) 7.83 (d, J=8.54 Hz, 1H) 7.56 (dd, J=8.54, 1.83 Hz, 1H) 3.74-3.86 (m, 1H) 3.52 (d, J=6.10 Hz, 2H) 3.08-3.19 (m, 1H) 2.95 (d, J=10.68 Hz, 2H) 2.51-2.62 (m, 4H) 1.79 (d, J=10.68 Hz, 4H) 1.48-1.59 (m, 2H) 1.25-1.38 (m, 2H). MS: (M+H)+=381/383.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[C:12]([Cl:14])[CH:11]=[CH:10][C:9]=2[O:15][CH2:16][CH3:17])[N:5]=[C:4]([NH2:18])[N:3]=1.Cl.[CH3:20][C:21]1[CH:22]=[CH:23][C:24]([NH2:27])=[CH:25][CH:26]=1>C(O)C.O1CCOCC1>[Cl:14][C:12]1[CH:11]=[CH:10][C:9]([O:15][CH2:16][CH3:17])=[C:8]([C:6]2[N:5]=[C:4]([NH2:18])[N:3]=[C:2]([NH:27][C:24]3[CH:25]=[CH:26][C:21]([CH3:20])=[CH:22][CH:23]=3)[CH:7]=2)[CH:13]=1
Reactant: CCOc1ccc(Cl)cc1-c1cc(Cl)nc(N)n1
Reactant: Cc1ccc(N)cc1
Agent: Cl
Solvent: C1COCCO1
Solvent: CCO
Product: CCOc1ccc(Cl)cc1-c1cc(Nc2ccc(C)cc2)nc(N)n1
Reaction time: 8 h
Yield: 53.2 %

Procedure:
To a stirred suspension of 4-chloro-6-(5-chloro-2-ethoxy-phenyl)-pyrimidin-2-ylamine (0.030 g, 0.106 mmol) in ethanol (5 ml) was added a solution of hydrogen chloride in dioxane (4.0 M, 0.015 ml) followed by p-tolylamine (0.014 g, 0.127 mmol). After heating under reflux for 3.5 hours, the volatiles were evaporated under reduced pressure. The residue was treated with 1.0 M hydrochloric acid (10 ml) and stirred overnight. After filtration, the solid was dissolved in methanol (10 ml) and treated with aqueous sodium carbonate solution (1.0 M, 1 ml). After stirring for 0.5 hours, the volatiles were evaporated under reduced pressure, the solid was stirred with water (10 ml) for 15 minutes, and filtered to provide the title compound (0.020 g, 53% yield) as a white powder. 1H NMR (DMSO-d6) δ 1.37 (t, 3H, J=6.8 Hz, CH3), 2.27 (s, 3H, CH3), 4.12 (q, 2H, J=6.6 Hz, CH2), 6.25 (s, 2H, NH2), 6.75 (s, 1H, Ar), 7.10-7.14 (m, 3H, Ar), 7.40-7.42 (m, 1H, Ar), 7.55 (d, 2H, J=8.0 Hz, Ar), 7.92 (s, 1H, Ar), 9.05 (s, 1H, NH).
Reaction SMILES: [O:1]=[CH:2][C@@H:3]([C@H:5]([C@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])O.[FH:13]>>[C@H:11]1([F:13])[O:12][C@H:3]([CH2:2][OH:1])[C@H:5]([OH:6])[C@H:7]([OH:8])[C@H:9]1[OH:10]
Reactant: O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CO
Reactant: F
Product: OC[C@H]1O[C@H](F)[C@H](O)[C@@H](O)[C@H]1O
Reaction time: 1 h
Yield: 98.9 %

Procedure:
In an apparatus and by the procedure according to Example 1, 1 g of D-galactose was reacted with 10 g of hydrogen fluoride, the mixture was left to stand for 1 hour at -30° to -40° C. and the hydrogen fluoride was then stripped out within 15 minutes by blowing in nitrogen. The working-up gave α-D-galactosyl fluoride (about 1 g) which was identified by elemental analysis, thin-layer chromatogram and 19F and 13C nuclear magnetic resonance spectra (cf. J. E. C. Barnett et al., Biochem. J. 105 (1967), page 669). Melting point: 130° (decomposition).
Reaction SMILES: [F:1][C:2]1[CH:20]=[CH:19][CH:18]=[CH:17][C:3]=1[CH2:4][O:5][C:6]1[CH:7]=[C:8]([CH:13]=[C:14]([OH:16])[CH:15]=1)[C:9]([O:11]C)=[O:10].[OH-].[Na+].Cl>CO>[F:1][C:2]1[CH:20]=[CH:19][CH:18]=[CH:17][C:3]=1[CH2:4][O:5][C:6]1[CH:7]=[C:8]([CH:13]=[C:14]([OH:16])[CH:15]=1)[C:9]([OH:11])=[O:10]
Reactant: COC(=O)c1cc(O)cc(OCc2ccccc2F)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(O)c1cc(O)cc(OCc2ccccc2F)c1

Procedure:
Methyl 3-(2-fluorobenzyloxy)-5-hydroxybenzoate (224a), 10 mL of Methyl alcohol and 10 mL of 1N NaOH were stirred at ambient temperature for 4 h, acidified with 1N HCl until neutral and extracted into ethyl acetate. The combined organic extracts were dried over magnesium sulfate, filtered and evaporated. The LC/MS gave a calculated and found (M+H+)=263.
Reaction SMILES: [F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([C:13]([CH3:33])([CH3:32])[C:14]([N:16]([C:18]2[CH:19]=[N:20][C:21](Cl)=[CH:22][C:23]=2[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[Br:30])[CH3:17])=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.CS(C)=O.[OH:40][CH2:41][C@@H:42]1[CH2:46][C@@H:45]([OH:47])[CH2:44][NH:43]1>C(OCC)(=O)C>[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([C:13]([CH3:33])([CH3:32])[C:14]([N:16]([C:18]2[CH:19]=[N:20][C:21]([N:43]3[CH2:44][C@H:45]([OH:47])[CH2:46][C@H:42]3[CH2:41][OH:40])=[CH:22][C:23]=2[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[Br:30])[CH3:17])=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1
Reactant: OC[C@@H]1C[C@@H](O)CN1
Reactant: CN(C(=O)C(C)(C)c1cc(C(F)(F)F)cc(C(F)(F)F)c1)c1cnc(Cl)cc1-c1ccccc1Br
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: CN(C(=O)C(C)(C)c1cc(C(F)(F)F)cc(C(F)(F)F)c1)c1cnc(N2C[C@H](O)C[C@H]2CO)cc1-c1ccccc1Br
Temperature: 130 °C
Reaction time: 24 h
Yield: 47.6 %

Procedure:
A mixture of 800 mg (1.38 mmol) 2-(3,5-bis-trifluoromethyl-phenyl)-N-[4-(2-bromo-phenyl)-6-chloro-pyridin-3-yl]-N-methyl-isobutyramide, 4 ml dimethyl sulfoxide and 1.15 g (6.9 mmol) (2S,4R)-2-(hydroxymethyl)-4-hydroxypyrrolidine was stirred at 130° C. for 24 h. The reaction mixture was cooled to room temperature, diluted with 100 ml ethyl acetate and washed with 200 ml 1 N sodium carbonate solution and 100 ml water. The combined aqueous layers were extracted twice with 100 ml ethyl acetate. The combined organic layers were dried over sodium sulfate and evaporated. Purification by flash chromatography gave 434 mg (48%) of the title compound as a yellow foam.
Reaction SMILES: [Br:1][CH:2]([CH:6]([CH3:8])[CH3:7])[C:3](Cl)=[O:4].N1C=CC=CC=1.Cl.[CH3:16][O:17][C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][C:27]=1[O:28][CH3:29])[CH2:24][NH:23][CH2:22][CH2:21]2>CN(C1C=CN=CC=1)C.C(Cl)(Cl)Cl>[CH3:16][O:17][C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][C:27]=1[O:28][CH3:29])[CH2:24][N:23]([C:3](=[O:4])[CH:2]([Br:1])[CH:6]([CH3:8])[CH3:7])[CH2:22][CH2:21]2
Reactant: CC(C)C(Br)C(=O)Cl
Reactant: COc1cc2c(cc1OC)CNCC2
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClC(Cl)Cl
Solvent: c1ccncc1
Product: COc1cc2c(cc1OC)CN(C(=O)C(Br)C(C)C)CC2
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Racemic body α-bromoisovaleryl chloride (327 mg, 1.64 mmol) on the market and 4-(N,N-dimethylamino)pyridine (about 10 mg) were added to a pyridine (8 ml) suspension of 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (472 mg, 2.05 mmol), and the mixture was stirred at room temperature for 3 hours. The reaction solution was diluted with chloroform (50 ml), washed with 1 N hydrochloric acid (50 ml) and a 1 N aqueous sodium hydroxide solution (50 ml), dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and used, without isolating and purifying the obtained gummy substance, in the reactions in Examples 27 and 28.
Reaction SMILES: [N+:1]([CH2:4][C:5]([CH3:9])=[CH:6][CH2:7][OH:8])([O-:3])=[O:2].CC(C)=[O:12].OS(O)(=O)=O.O=[Cr](=O)=O>CC(C)=O>[N+:1]([CH2:4][C:5]([CH3:9])=[CH:6][C:7]([OH:12])=[O:8])([O-:3])=[O:2]
Reactant: CC(=CCO)C[N+](=O)[O-]
Reactant: CC(C)=O
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Product: CC(=CC(=O)O)C[N+](=O)[O-]
Reaction time: 2 h

Procedure:
A stirred solution of 0.1 Mol of 4-Nitro-3-methyl-2-butenol in acetone at 10°-15° was titrated with approximately 0.26 Mol of Jones reagent until the reaction mixture stayed dark orange colored. After 2 hours stirring at 10°-15° C. the mixture was decanted from the green chromium salts and the acetone removed. The residue was dissolved in ether and washed several times with saturated NaCl solution. After evaporation, the residue was crystallized from hot benzene and off-white crystals, mp 85°, were obtained. Two more recrystallizations from benzene yielded the pure nitroacid, mp 100°-102°.
Reaction SMILES: [Cl:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][C:7]2[N:8]=[C:9]([C:17]3[C:18]([CH3:28])=[N:19][N:20]4[CH:25]=[CH:24][C:23]([CH:26]=O)=[CH:22][C:21]=34)[S:10][C:11]=2[C:12]2[NH:16][CH:15]=[N:14][N:13]=2)=[CH:4][CH:3]=1.[N:31]1([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[Cl:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][C:7]2[N:8]=[C:9]([C:17]3[C:18]([CH3:28])=[N:19][N:20]4[CH:25]=[CH:24][C:23]([CH2:26][N:34]5[CH2:35][CH2:36][N:31]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:32][CH2:33]5)=[CH:22][C:21]=34)[S:10][C:11]=2[C:12]2[NH:16][CH:15]=[N:14][N:13]=2)=[CH:4][CH:3]=1
Reactant: Cc1nn2ccc(C=O)cc2c1-c1nc(Cc2ccc(Cl)cc2)c(-c2nnc[nH]2)s1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Solvent: CC(=O)O
Product: Cc1nn2ccc(CN3CCN(C(=O)OC(C)(C)C)CC3)cc2c1-c1nc(Cc2ccc(Cl)cc2)c(-c2nnc[nH]2)s1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 70.3 %

Procedure:
A mixture of 3-[4-(4-chlorobenzyl)-5-(4H-1,2,4-triazol-3-yl)-1,3-thiazol-2-yl]-2-methylpyrazolo[1,5-a]pyridine-5-carbaldehyde (0.0563 g, 0.109 mmol), tert-butyl 1-piperazinecarboxylate (60.8 mg, 0.326 mmol) and acetic acid (0.0800 mL, 1.41 mmol) in dry methylene chloride (10 mL) was stirred at rt for 15 min. Sodium triacetoxyborohydride (69.1 mg, 0.326 mmol) was added and the mixture was stirred at rt for 15 hours. The mixture was washed with saturated NaHCO3 solution and the aqueous layer was extracted with DCM. The DCM extract was washed with water, brine, dried over Na2SO4, filtered and evaporated to give a crude product which was purified by column chromatography on silica gel column using MeOH/DCM (0/100 to 5/95) to give solid product (0.0464 g, yield 70.5%). LCMS: (FA) ES+ 605, 607; ES− 603, 605. 1H NMR (400 MHz, CDCl3 and d4-methanol) δ: 8.23-8.25 (d, J=7.03 Hz, 1H), 8.20 (s, 1H), 7.94 (s, 1H), 7.29-7.31 (d, J=8.28 Hz, 2H), 7.15-7.17 (d, J=8.53 Hz, 2H), 6.86-6.89 (dd, J=7.28, 1.76 Hz, 1H), 4.53 (s, 2H), 3.45 (s, 2H), 3.33-3.36 (m, 4H), 2.62 (s, 3H), 2.35 (s, br, 4H), 1.37 (s, 9H).