Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[C:7]([CH2:8][OH:9])=[C:6]([CH3:10])[CH:5]=[CH:4][N:3]=1>C(#N)C>[CH3:1][C:2]1[C:7]([CH:8]=[O:9])=[C:6]([CH3:10])[CH:5]=[CH:4][N:3]=1
Reactant: Cc1ccnc(C)c1CO
Solvent: CC#N
Product: Cc1ccnc(C)c1C=O
Temperature: 80 °C
Yield: 83.8 %

Procedure:
A magnetically stirred mixture of (2,4-dimethyl-pyridin-3-yl)-methanol (0.342 g, 2.5 mmol) and IBX (1.40 g, 5 mmol) in acetonitrile (5 mL) placed in a round bottom flask was heated at 80° C. in an oil bath for 1 h. The mixture was cooled to room temperature and filtered. The solid was washed with acetonitrile. The filtrate was concentrated and applied to a short silica gel column and chromatographed using hexane/ethyl acetate solvent mixture (30-60% ethyl acetate). Product containing fractions were combined and the solvent was evaporated to afford 0.283 g of 2,4-dimethyl-pyridine-3-carbaldehyde as a white solid. MS: (M+H)/z=136.
Reaction SMILES: N(C(OC(C)C)=O)=NC(OC(C)C)=O.[OH:15][CH2:16][CH2:17][CH2:18][NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23].O[C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([O:34][CH3:35])[C:29]=1[C:36](=[O:38])[CH3:37].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[C:36]([C:29]1[C:30]([O:34][CH3:35])=[CH:31][CH:32]=[CH:33][C:28]=1[O:15][CH2:16][CH2:17][CH2:18][NH:19][C:20](=[O:26])[O:21][C:22]([CH3:23])([CH3:25])[CH3:24])(=[O:38])[CH3:37]
Reactant: COc1cccc(O)c1C(C)=O
Reactant: CC(C)(C)OC(=O)NCCCO
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COc1cccc(OCCCNC(=O)OC(C)(C)C)c1C(C)=O
Reaction time: 18 h
Yield: 42.3 %

Procedure:
Diisopropyl azodicarboxylate (2.82 g, 14.0 mmol) is added to a stirred solution of tert-butyl 3-hydroxypropylcarbamate (2.45 g, 14.0 mmol), 1-(2-hydroxy-6-methoxyphenyl)ethanone (1.94 g, 11.7 mmol) and triphenylphosphine (3.66 g, 14.0 mmol) in THF (50 mL) at room temperature. After stirring for 18 h, the solvent is removed under reduced pressure and the crude product is chromatographed (hexane-ethyl acetate: 0-60% gradient) to afford 1.60 g of the title compound.
Reaction SMILES: [F:1][C:2]1[CH:25]=[CH:24][CH:23]=[CH:22][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:14]2[N:19]=[C:18]([NH2:20])[C:17]([NH2:21])=[CH:16][N:15]=2)=[N:6]1.[F:26][C:27]([F:37])([F:36])[CH2:28][N:29]1[CH2:34][CH2:33][C:32](=O)[CH2:31][CH2:30]1.C([BH3-])#N.[Na+].C(=O)([O-])O.[Na+]>CO.C(O)(=O)C>[F:1][C:2]1[CH:25]=[CH:24][CH:23]=[CH:22][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:14]2[N:19]=[C:18]([NH2:20])[C:17]([NH:21][CH:32]3[CH2:31][CH2:30][N:29]([CH2:28][C:27]([F:37])([F:26])[F:36])[CH2:34][CH2:33]3)=[CH:16][N:15]=2)=[N:6]1
Reactant: Nc1cnc(-c2nn(Cc3ccccc3F)c3ncccc23)nc1N
Reactant: O=C1CCN(CC(F)(F)F)CC1
Agent: O=C([O-])O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: Nc1nc(-c2nn(Cc3ccccc3F)c3ncccc23)ncc1NC1CCN(CC(F)(F)F)CC1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 90.2 %

Procedure:
200 mg (0.596 mmol) of 2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidine-4,5-diamine (synthesis described in US2004/67937; Example V) were initially charged in methanol (16 ml) and admixed with 75 μl (1.312 mmol) of acetic acid, and then 237 mg (1.312 mmol) of 1-(2,2,2-trifluoroethyl)piperidin-4-one were added. After stirring at RT for 15 min, 104 mg (1.67 mmol) of sodium cyanoborohydride were added and the mixture was stirred at RT for 2.5 h. Subsequently, within 2 days, the above-stated amounts of reagents (1-(2,2,2-trifluoroethyl)piperidin-4-one, acetic acid, sodium cyanoborohydride) were added three times, in order to achieve substantially full conversion. Thereafter, saturated aqueous sodium hydrogencarbonate solution (5 ml) was added to the reaction mixture, which was stirred vigorously for 10 min. Subsequently, the reaction mixture was extracted with water and ethyl acetate. The phases were separated and the aqueous phase was extracted twice with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, concentrated and then purified by means of preparative HPLC (acetonitrile:water (+0.05% formic acid) gradient). 269 mg of the title compound were obtained (90% of theory).
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[C:12]2[C:7]([CH:8]=[N:9][NH:10][C:11]2=[O:14])=[CH:6][CH:5]=1)([O-:3])=[O:2].Cl.Cl[CH2:17][C:18]1[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=1>>[N+:1]([C:4]1[CH:13]=[C:12]2[C:7]([CH:8]=[N:9][N:10]([CH2:17][C:18]3[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=3)[C:11]2=[O:14])=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: ClCc1cccnc1
Reactant: O=c1[nH]ncc2ccc([N+](=O)[O-])cc12
Agent: Cl
Product: O=c1c2cc([N+](=O)[O-])ccc2cnn1Cc1cccnc1

Procedure:
Step (b) of Example 125 was repeated, except that the compound prepared in step (b) of Example 137 and 3-(chloromethyl)pyridine hydrochloride were used as the starting compounds. Thus, 7-nitro-2-(pyridin-3-yl)methyl-2H-phthalazin-1-one was obtained.
Reaction SMILES: C([Li])CCC.CN(C)CCN(C)C.[CH2:14]([NH:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[F:28][C:29]([F:41])([F:40])[C:30]1[CH:31]=[C:32]([P:36](Cl)(Cl)=[O:37])[CH:33]=[CH:34][CH:35]=1>CCCCCC.C1CCCCC1>[F:41][C:29]([F:28])([F:40])[C:30]1[CH:31]=[C:32]([P:36]2(=[O:37])[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[CH2:14][N:21]2[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:33]=[CH:34][CH:35]=1
Reactant: O=P(Cl)(Cl)c1cccc(C(F)(F)F)c1
Reactant: c1ccc(CNc2ccccc2)cc1
Agent: CN(C)CCN(C)C
Agent: [Li]CCCC
Solvent: C1CCCCC1
Solvent: CCCCCC
Product: O=P1(c2cccc(C(F)(F)F)c2)c2ccccc2CN1c1ccccc1
Temperature: 26 °C
Reaction time: 2 h
Yield: 29.5 %

Procedure:
Under a static nitrogen atmosphere at 0° C., a solution of n-butyllithium (8.06 g, 0.126 mol) in hexane was added to a solution of tetramethylethylenediamine (3.71 g, 0.032 mol) in 60 ml. of anhydrous cyclohexane with constant stirring. While maintaining the temperature of the reaction at 0° C., a solution of N-benzylaniline (11 g, 0.06 mol) in 60 ml. of anhydrous cyclohexane was added to the reaction mixture to produce a suspension containing a dilithio compound. This suspension was stirred for 2 hours at 26° C. and then cooled to 0° C. in an ice bath. A solution of 3-trifluoromethylphenylphosphonic dichloride (16.8 g, 0.064 mol) in 60 ml. of anhydrous cyclohexane was added dropwise to the suspension. The ice bath was removed and the resulting mixture was stirred for 3 hours at 26° C. The reaction was quenched with the rapid addition of 12 ml. of acetic acid. The cyclohexane was removed under vacuum and the resulting residue was partitioned in methylene chloride and water. The layers were separated and the methylene chloride layer was washed with 5% hydrochloric acid, then water, dried over sodium sulfate and concentrated in vacuo to yield a brown oil. The brown oil was separated on a silica gel column using a 3:1 mixture of methylene chloride:ethyl acetate as the eluant. Fractions containing the benzazaphosphole were combined and rechromatographed using methylene chloride as the eluant. Fractions containing the benzazaphosphole were combined and concentrated in vacuo and the residue was triturated in cyclohexane to yield a white solid. The white solid was evacuated under high vacuum to remove any cyclohexane and the resulting residue was recrystallized from diethyl ether and petroleum ether to yield 1-[3-(trifluoromethyl)phenyl]-2-phenyl-2,3-dihydro-1H-2,1-benzazaphosphole-1-oxide (6.6 g, 30% yield) as a beige solid having a melting point of 48°-51° C. and the following analysis:
Reaction SMILES: [O:1]1[CH2:6][CH2:5][O:4][C:3]2[CH:7]=[CH:8][C:9]([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:10][C:2]1=2.[H-].[Na+].I[CH3:20]>CN(C=O)C.O>[O:1]1[CH2:6][CH2:5][O:4][C:3]2[CH:7]=[CH:8][C:9]([CH:11]([CH3:20])[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:10][C:2]1=2
Reactant: CCOC(=O)Cc1ccc2c(c1)OCCO2
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)C(C)c1ccc2c(c1)OCCO2
Temperature: 0 °C
Reaction time: 1 h

Procedure:
A solution of Ethyl 2-(2,3-dihydrobenzo[b][1,4]dioxin-7-yl)acetate (257 mg, 1.16 mmol) in DMF (2 mL) was added NaH (50 mg, 1.25 mmol) and iodomethane (167 mg, 1.18 mmol) in DMF (0.5 mL) at 0° C. The reaction mixture was stirred for 1 hrs at 0° C. then diluted with H2O (20 mL) and extracted with EtOAc (20 mL). The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel using EtOAc:hexanes (1:6) as eluant.
Reaction SMILES: [CH3:1][C:2]1([CH3:19])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:18]=[CH:17][C:12]([C:13]([NH:15][NH2:16])=[O:14])=[CH:11][CH:10]=2)[O:3]1.[CH:20](OCC)(OCC)OCC>C(O)C>[CH3:8][C:6]1([CH3:7])[C:2]([CH3:19])([CH3:1])[O:3][B:4]([C:9]2[CH:18]=[CH:17][C:12]([C:13]3[O:14][CH:20]=[N:16][N:15]=3)=[CH:11][CH:10]=2)[O:5]1
Reactant: CC1(C)OB(c2ccc(C(=O)NN)cc2)OC1(C)C
Reactant: CCOC(OCC)OCC
Solvent: CCO
Product: CC1(C)OB(c2ccc(-c3nnco3)cc2)OC1(C)C

Procedure:
10 g (38 mmol) of 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-benzohydrazide are dissolved in 30 g (20 mmol) of triethyl orthoformate, and the mixture is heated to reflux. The ethanol formed during the reaction is continuously removed by distillation. After the mixture has cooled, the product crystallizes out, is filtered off and washed with a little ethanol. Yield: 8.7 g (32 mmol, 84%). An analogous procedure is carried out using the compounds of the formula (II) shown in Table 4.
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][N:15]([CH2:25][CH3:26])[C:16]2[C:21]([N+:22]([O-])=O)=[CH:20][CH:19]=[CH:18][N:17]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H][H]>[Pd].C(O)C>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][N:15]([CH2:25][CH3:26])[C:16]2[C:21]([NH2:22])=[CH:20][CH:19]=[CH:18][N:17]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: [H][H]
Reactant: CCN(CC1CCN(Cc2ccccc2)CC1)c1ncccc1[N+](=O)[O-]
Agent: [Pd]
Solvent: CCO
Product: CCN(CC1CCN(Cc2ccccc2)CC1)c1ncccc1N

Procedure:
1-Benzyl-4-[N-ethyl-N-(3-nitro-2-pyridinyl)amino]methylpiperidine (EXAMPLE 176, 9.8 g, 27.6 mmol) and 10% palladium on carbon (3 g) in ethanol (250 ml) are hydrogenated at 40 p.s.i. hydrogen for one hr. Filtration and evaporation of the solvent gives the title compound, NMR (300 MHz, CD3OD) 7.60, 7.28, 7.05, 6.86, 3.46, 3.01, 2.84, 1.90, 1.70, 1.40, 1.19 and 1.0δ.
Reaction SMILES: [Cl:1][C:2]1[CH:15]=[C:14]([Cl:16])[CH:13]=[CH:12][C:3]=1[CH2:4][NH:5][C:6]1[CH:7]=[N:8][CH:9]=[N:10][CH:11]=1.[C:17](OC(=O)C)(=[O:19])[CH3:18].C(Cl)(Cl)Cl>C(O)(=O)C.S(=O)(=O)(O)O>[Cl:1][C:2]1[CH:15]=[C:14]([Cl:16])[CH:13]=[CH:12][C:3]=1[CH2:4][N:5]([C:6]1[CH:11]=[N:10][CH:9]=[N:8][CH:7]=1)[C:17](=[O:19])[CH3:18]
Reactant: Clc1ccc(CNc2cncnc2)c(Cl)c1
Reactant: CC(=O)OC(C)=O
Agent: O=S(=O)(O)O
Solvent: CC(=O)O
Solvent: ClC(Cl)Cl
Product: CC(=O)N(Cc1ccc(Cl)cc1Cl)c1cncnc1
Yield: 68.5 %

Procedure:
2.80 g (11 mmol) of N-(2,4-dichlorobenzyl)-N-(pyrimidin-5-yl)amine are dissolved in 5 ml of glacial acetic acid and then 5 ml of acetic anhydride and 3 drops of concentrated sulfuric acid are added to the solution. With stirring, the reaction mixture is boiled under reflux for 11/2 hours and subsequently cooled. 30 ml of chloroform are added to the mixture, the acetic acid is removed by extraction with water and the separated solution of chloroform is dried over sodium sulfate. The sodium sulfate is filtered off and the chloroform is then evaporated off in vacuo at 80° C. and the residue is recrystallised from a mixture of 5 ml of toluene and 5 ml of cyclohexane, affording 2.23 g (68.5% of theory) of N-(2,4-dichlorobenzyl)-N-(pyrimidin-5-yl)acetamide, m.p. 134°-136° C. A further 0.90 g (27.6% of theory) of pure product is obtained by purifying the product formed in the filtrate through a column of silica gel (eluant: ethyl acetate).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:19])[CH:5]=[CH:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[O:13][C:12]([CH3:18])([CH3:17])[CH2:11][CH2:10]2)[CH3:2].[H][H]>CO.[Pd]>[CH2:1]([O:3][C:4](=[O:19])[CH2:5][CH2:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[O:13][C:12]([CH3:18])([CH3:17])[CH2:11][CH2:10]2)[CH3:2]
Reactant: [H][H]
Reactant: CCOC(=O)C=Cc1ccc2c(c1)CCC(C)(C)O2
Agent: [Pd]
Solvent: CO
Product: CCOC(=O)CCc1ccc2c(c1)CCC(C)(C)O2
Yield: 78.6 %

Procedure:
A suspension of 3-(2,2-Dimethyl-chroman-6-yl)-acrylic acid ethyl ester (1.2 g, 4.61 mmol) in methanol (25 mL) was hydrogenated with 10% palladium on carbon at 60 psi of hydrogen for 6 hours. The catalyst was removed by filtration, and the solvent was evaporated in vacuo to give the product 0.95 g (79%). MS: m/z 263 (MH+). 1H NMR (CDCl3): δ 1.15 (t, 3 H), 1.24 (s, 6 H), 1.70 (t, 2 H), 2.49 (t, 2 H), 2.65 (t, 2 H), 2.76 (t, 2 H), 4.04 (q, 2 H), 6.62 (d, 1 H) and 6.81-6.86 (m, 2 H).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][N:5]1[C:13]([CH2:14][C:15]2[C:23]([I:24])=[CH:22][C:18]3[O:19][CH2:20][O:21][C:17]=3[CH:16]=2)=[N:12][C:11]2[C:6]1=[N:7][C:8]([F:26])=[N:9][C:10]=2[NH2:25].[CH:27]1([S:30](Cl)(=[O:32])=[O:31])[CH2:29][CH2:28]1.C(N(CC)CC)C>CN(C=O)C>[NH2:25][C:10]1[N:9]=[C:8]([F:26])[N:7]=[C:6]2[C:11]=1[N:12]=[C:13]([CH2:14][C:15]1[C:23]([I:24])=[CH:22][C:18]3[O:19][CH2:20][O:21][C:17]=3[CH:16]=1)[N:5]2[CH2:4][CH2:3][CH2:2][NH:1][S:30]([CH:27]1[CH2:29][CH2:28]1)(=[O:32])=[O:31]
Reactant: O=S(=O)(Cl)C1CC1
Reactant: NCCCn1c(Cc2cc3c(cc2I)OCO3)nc2c(N)nc(F)nc21
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: Nc1nc(F)nc2c1nc(Cc1cc3c(cc1I)OCO3)n2CCCNS(=O)(=O)C1CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 68 %

Procedure:
To a solution of 9-(3-aminopropyl)-2-fluoro-8-((6-iodobenzo[d][1,3]dioxol-5-yl)methyl)-9H-purin-6-amine (100 mg, 0.21 mmol) in DMF (3 mL) was added cyclopropanesulfonyl chloride (89 mg, 0.32 mmol) and triethylamine (90 uL, 0.96 mmol). The resulting mixture was stirred at room temperature overnight. The reaction mixture was condensed and purified by flash chromatography to yield WS72 as a white solid (82 mg, 67%). 1H NMR (600 MHz, CDCl3/MeOH-d4): δ 7.32 (s, 1H), 6.79 (s, 1H), 6.02 (s, 2H), 4.27 (s, 2H), 4.22 (t, J=7.3 Hz, 2H), 3.18 (t, J=6.4 Hz, 2H), 2.45-2.50 (m, 1H), 2.00-2.06 (m, 2H), 1.12-1.17 (m, 2H), 0.99-1.04 (m, 2H); 13C NMR (150 MHz, CDCl3/MeOH-d4): δ 159.0 (d, J=209.8 Hz), 156.9 (d, J=19.7 Hz), 152.4 (d, J=18.5 Hz), 151.2 (d, J=2.3 Hz), 149.3, 148.4, 131.4, 119.0, 116.3 (d, J=3.6 Hz), 110.4, 102.4, 88.7, 40.7, 40.1, 39.3, 30.2, 29.9, 5.3; HRMS (ESI) m/z [M+H]+ calcd, for C19H21FIN6O4S, 575.0374. found 575.0390.
Reaction SMILES: Br[CH2:2][C:3]([N:5]([CH:14]([CH3:16])[CH3:15])[C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[CH:8][CH:7]=1)=[O:4].[NH3:17]>CO>[NH2:17][CH2:2][C:3]([N:5]([CH:14]([CH3:16])[CH3:15])[C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[CH:8][CH:7]=1)=[O:4]
Reactant: N
Reactant: COc1ccc(N(C(=O)CBr)C(C)C)cc1
Solvent: CO
Product: COc1ccc(N(C(=O)CN)C(C)C)cc1
Reaction time: 72 h

Procedure:
A solution of 2.86 g of 2-bromo-N-isopropyl-N-(4-methoxy-phenyl)-acetamide (10 mmol) in 100 mL methanol is saturated with ammonia at 0° C. and left for 3 days at ambient temperature in a sealed flask. Methanol and ammonia were removed in vacuo and the residue is dissolved in 100 mL of chloroform and washed with water (2×50 mL). The organic layer is dried over anhydrous MgSO4, filtered, concentrated in vacuo and dried under high vacuum to afford 2.7 g of 2-Amino-N-isopropyl-N-(4-methoxy-phenyl)-acetamide as an oil: 1H NMR (300 MHz, CDCl3) δ6.96 (m, 4H), 4.99 (m, 1H), 3.84 (s, 3H), 2.97 (s, 2H), 1.58 (s, 2H), 1.05 (d, 6H, J=6.6); low resolution MS (ESI)m/e 223 (MH+).
Reaction SMILES: Cl[CH:2]([C:8]([CH3:10])=O)[C:3]([O:5][CH2:6][CH3:7])=[O:4].[C:11]([NH2:15])(=[S:14])[CH2:12][CH3:13]>C(O)C>[CH2:6]([O:5][C:3]([C:2]1[S:14][C:11]([CH2:12][CH3:13])=[N:15][C:8]=1[CH3:10])=[O:4])[CH3:7]
Reactant: CCOC(=O)C(Cl)C(C)=O
Reactant: CCC(N)=S
Solvent: CCO
Product: CCOC(=O)c1sc(CC)nc1C
Yield: 81.5 %

Procedure:
A solution of ethyl 2-chloroacetoacetate (2.00 g, 10.04 mmol) and thiopropionamide (1.00 g, 11.22 mmol) in ethanol (100 mL) was heated at reflux overnight. The solvent was evaporated and dichloromethane (100 mL) added. The solution was washed with water (2×100 mL) and brine (100 mL), dried (MgSO4), filtered, evaporated and the concentrate was chromatographed over silica gel (10% ethyl acetate/hexanes) to give 2-ethyl-4-methylthiazole-5-carboxylic acid ethyl ester (1.63 g, 81% yield) as a colorless liquid.
Reaction SMILES: [C:1]1([CH3:38])[CH:6]=[CH:5][C:4]([S:7]([N:10]2[CH2:14][C@H:13](OS(C3C=CC(C)=CC=3)(=O)=O)[CH2:12][C@H:11]2[CH2:26]OS(C2C=CC(C)=CC=2)(=O)=O)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[CH3:39][NH2:40]>CO>[C:1]1([CH3:38])[CH:6]=[CH:5][C:4]([S:7]([N:10]2[CH2:14][C@@H:13]3[CH2:12][C@H:11]2[CH2:26][N:40]3[CH3:39])(=[O:9])=[O:8])=[CH:3][CH:2]=1
Reactant: CN
Reactant: Cc1ccc(S(=O)(=O)OC[C@@H]2C[C@@H](OS(=O)(=O)c3ccc(C)cc3)CN2S(=O)(=O)c2ccc(C)cc2)cc1
Solvent: CO
Product: Cc1ccc(S(=O)(=O)N2C[C@@H]3C[C@H]2CN3C)cc1
Temperature: 90 °C
Yield: 90 %

Procedure:
A Parr bottle was charged with 115 g (198.4 mmol) of (2S, 4R)-1-(4-toluenesulfonyl)-2-(p-toluenesulfonyl- oxymethyl)-4-(4-toluenesulfonyloxy)-pyrrolidine and 690 ml of methanol and the bottle was then tared. Methylamine gas was bubbled through the methanol solution until 62 g (2 mol) of the gas has dissolved. The bottle was then sealed and heated to 90° C. After heating for 16 hours the reaction was cooled and the solvent was evaporated at reduced pressure. The residual solids were then partitioned between 500 ml of methylene chloride and 400 ml of 10% aqueous sodium hydroxide solution. The layers were separated and the organic layer was washed with 400 additional ml of 10% aqueous sodium hydroxide solution, and then dried over sodium sulfate. Evaporation of the solvent under reduced pressure provided 47.5 g of the desired product which represents a 90% yield. M.P.=87°-88° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]2[CH2:12][O:11][C:10](=[O:13])[N:9]2[C:14]2[CH:19]=[CH:18][N:17]3[N:20]=[CH:21][C:22]([C:23]4[CH:28]=[CH:27][C:26]([C:29]5[N:33]=[CH:32][N:31](COCC[Si](C)(C)C)[N:30]=5)=[C:25]([F:42])[CH:24]=4)=[C:16]3[N:15]=2)[CH:5]=[CH:6][CH:7]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]2[CH2:12][O:11][C:10](=[O:13])[N:9]2[C:14]2[CH:19]=[CH:18][N:17]3[N:20]=[CH:21][C:22]([C:23]4[CH:28]=[CH:27][C:26]([C:29]5[N:33]=[CH:32][NH:31][N:30]=5)=[C:25]([F:42])[CH:24]=4)=[C:16]3[N:15]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: C[Si](C)(C)CCOCn1cnc(-c2ccc(-c3cnn4ccc(N5C(=O)OC[C@@H]5c5cccc(Cl)c5)nc34)cc2F)n1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C1OC[C@H](c2cccc(Cl)c2)N1c1ccn2ncc(-c3ccc(-c4nc[nH]n4)c(F)c3)c2n1
Temperature: 25 °C
Reaction time: 6 h
Yield: 42 %

Procedure:
To (S)-4-(3-chlorophenyl)-3-(3-(3-fluoro-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)oxazolidin-2-one (65 mg, 0.11 mmol) in DCM (5 mL) was added TFA (1 mL) and the reaction was stirred at ambient temperature for 6 hours. The reaction was concentrated to dryness and the residue dissolved in MeOH/ammonia (7N). After stirring at ambient temperature for 30 minutes, the reaction was concentrated then purified by reverse phase chromatography (SP4, 12M, water/CH3CN 100:0 to 0:100, 20 column volumes) to yield (S)-4-(3-chlorophenyl)-3-(3-(3-fluoro-4-(1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)oxazolidin-2-one (22 mg, 43% yield) as a pale yellow solid. LCMS (APCI+) m/z 476.3 [M+H]+.
Reaction SMILES: [N+:1]([O-:4])(O)=[O:2].[O:5]=[C:6]1[NH:12][C:11]2[CH:13]=[CH:14][CH:15]=[CH:16][C:10]=2[N:9]2[CH2:17][CH2:18][N:19]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:20][CH:8]2[CH2:7]1.O>C(O)(=O)C>[N+:1]([C:14]1[CH:15]=[CH:16][C:10]2[N:9]3[CH2:17][CH2:18][N:19]([C:21]([O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:22])[CH2:20][CH:8]3[CH2:7][C:6](=[O:5])[NH:12][C:11]=2[CH:13]=1)([O-:4])=[O:2]
Reactant: O=[N+]([O-])O
Reactant: CC(C)(C)OC(=O)N1CCN2c3ccccc3NC(=O)CC2C1
Solvent: O
Solvent: CC(=O)O
Product: CC(C)(C)OC(=O)N1CCN2c3ccc([N+](=O)[O-])cc3NC(=O)CC2C1
Reaction time: 3 h

Procedure:
Nitric acid (65% solution, 0.20 mL, 3.2 mmol) was added to a solution of Example 1C (1.0 g, 3.2 mmol) in acetic acid (5 mL) at room temperature. The solution was stirred for 3 hours, and then the reaction mixture was poured into water (200 mL). The precipitate was collected by filtration from the aqueous solution to afford the title compound. 1H NMR (300 MHz, DMSO-d6) d ppm 8.00 (dd, J=8.92, 2.58 Hz, 1H), 7.79 (d, J=2.78 Hz, 1H), 7.24 (d, J=9.12 Hz, 1H), 3.86-4.10 (m, 2H), 3.36-3.50 (m, 1H), 3.20-3.29 (m, 1H), 2.81-2.99 (m, 1H), 2.62-2.77 (m, 1H), 2.18 (d, J=13.48 Hz, 1H); MS (APCI+) m/z 307 (M+H-tBu)+.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH:3]2[CH2:7][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:9][CH:2]12.Br[CH2:18][CH2:19][CH2:20][Cl:21].C([O-])([O-])=O.[K+].[K+]>CC(C)=O>[Cl:21][CH2:20][CH2:19][CH2:18][N:1]1[CH2:6][CH2:5][CH2:4][CH:3]2[CH2:7][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:9][CH:2]12
Reactant: CC(C)(C)OC(=O)N1CC2CCCNC2C1
Reactant: ClCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CC(C)(C)OC(=O)N1CC2CCCN(CCCCl)C2C1
Temperature: 25 °C
Yield: 65 %

Procedure:
A mixture of tert-butyl hexahydro-1H-pyrrolo[3,4-b]pyridine-6(2H)-carboxylate (1.60 g), 1-bromo-3-chloropropane (1.50 mL) and K2CO3 (3.00 g) in acetone was heated to reflux for 9 h. The reaction mixture was cooled to rt and filtered. The filtrate was concentrated in vacuo and the residue was chromatographed with a silica gel column (eluting agent: 1:1 (v/v) PE/EA) to give the title compound as yellow oil (0.53 g, 65.00%), HPLC: 89.00%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 303.2 (M+1).
Reaction SMILES: [C:1]([NH:4][C:5]1[S:6][C:7]([S:10][C:11]2[CH:16]=[CH:15][C:14]([NH2:17])=[CH:13][CH:12]=2)=[CH:8][N:9]=1)(=[O:3])[CH3:2].ClC1C=CC=C(C(OO)=[O:26])C=1>ClCCl.CN(C)C=O>[C:1]([NH:4][C:5]1[S:6][C:7]([S:10]([C:11]2[CH:16]=[CH:15][C:14]([NH2:17])=[CH:13][CH:12]=2)=[O:26])=[CH:8][N:9]=1)(=[O:3])[CH3:2]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CC(=O)Nc1ncc(Sc2ccc(N)cc2)s1
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CC(=O)Nc1ncc(S(=O)c2ccc(N)cc2)s1
Yield: 71.4 %

Procedure:
To a solution of 2-acetylamino-5-(4-aminophenylthio)thiazole (6.6 g) in a mixture of dichloromethane (300 ml) and N,N-dimethylformamide (50 ml) was dropwise added the solution of 3-chloroperbenzoic acid (5.9 g) in dichloromethane (100 ml) at 5° C. with stirring. The mixture was stirred at 5° C. for 2 hours with stirring. The reaction mixture was concentrated under reduced pressure and the residue was poured into 10% aqueous sodium bicarbonate. The solution was extracted with a mixture of tetrahydrofuran and ethyl acetate (1:1), washed with saturated aqueous sodium chloride and dried over magnesium sulfate. The solvent was concentrated under reduced pressure to give 2-acetylamino-5-(4-aminophenylsulfinyl)thiazole (5.0 g, yield: 71.1%).
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[S:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[NH2:18].ClC1C=C(C=CC=1)C(OO)=[O:24]>C(Cl)(Cl)Cl>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[S:10]([CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[NH2:18])=[O:24]
Reactant: Nc1ccccc1CSc1nc2ccccc2[nH]1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClC(Cl)Cl
Product: Nc1ccccc1CS(=O)c1nc2ccccc2[nH]1
Temperature: -10 °C
Yield: 62.4 %

Procedure:
The title product of Example 2 (830 mg, 3.25 mmole) was dissolved in about 200 ml of boiling chloroform and then cooled to about −10° C. A solution of 662 mg (ca. 3.25 mmole) of ca. 85% m-chloroperoxybenzoic acid in 10 ml of chloroform was then added with stirring over about ten minutes. After another thirty minutes, the reaction was quenched with 4 drops of dimethylsulfide and a white solid was collected by filtration. The solid was washed sequentially with chloroform and diethyl ether, then air dried, giving 550 mg of the title compound: m.p. 164-165° C. Analysis. Calc'd. for C14H13N3OS*½ H2O: C,59.98; H,5.03; N, 15.00; S, 11.44. Found: C, 60.11; H, 4.82; N, 14.93; S, 11.44.