Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CCN(C(C)C)C(C)C.[OH:10][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]2[C:20]=1[O:19][C:18](=[O:21])[C:17]([C:22]([OH:24])=O)=[CH:16]2.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH:49]1[C:57]2[C:52](=[C:53]([C:58]3[CH:59]=[C:60]([NH2:64])[CH:61]=[CH:62][CH:63]=3)[CH:54]=[CH:55][CH:56]=2)[CH:51]=[CH:50]1>CN(C=O)C>[NH:49]1[C:57]2[C:52](=[C:53]([C:58]3[CH:59]=[C:60]([NH:64][C:22]([C:17]4[C:18](=[O:21])[O:19][C:20]5[C:15]([CH:16]=4)=[CH:14][CH:13]=[CH:12][C:11]=5[OH:10])=[O:24])[CH:61]=[CH:62][CH:63]=3)[CH:54]=[CH:55][CH:56]=2)[CH:51]=[CH:50]1
Reactant: O=C(O)c1cc2cccc(O)c2oc1=O
Reactant: Nc1cccc(-c2cccc3[nH]ccc23)c1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(Nc1cccc(-c2cccc3[nH]ccc23)c1)c1cc2cccc(O)c2oc1=O
Temperature: 25 °C
Yield: 50.5 %

Procedure:
DIEA (0.012 mL, 0.071 mmol) was added to 8-hydroxy-3-carboxy-coumarin (0.013 g, 0.065 mmol) and HATU (0.027 g, 0.071 mmol) in 0.5 mL of DMF with constant stirring at room temperature until a clear solution resulted. Subsequently, 3-(1H-indol-4-yl)-phenylamine (0.014 g, 0.065 mmol) was added and allowed to react overnight. DMF was removed under vacuum and the reaction was resuspended in DMSO. The crude product was purified on a Parallex Flex parallel preparative reverse phase HPLC instrument (Biotage) using a solvent gradient of 10-95% ACN/H2O with 0.05% TFA at a flow rate of 20 mL/min. UV absorbance was monitored at 254 nm and the fractions corresponding to the product peak were collected and the solvent removed under vacuum to give 0.013 g of product in 52% yield: LCMS (ESI) m/z 397 (MH+).
Reaction SMILES: [NH2:1][C:2]1[N:3]=[C:4]([NH:27][NH:28][C:29]([C:31]2[O:32][CH:33]=[CH:34][CH:35]=2)=O)[C:5]2[CH:10]=[CH:9][N:8]([CH2:11][CH2:12][N:13]3[CH2:18][CH2:17][N:16]([C:19]4[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=4[F:26])[CH2:15][CH2:14]3)[C:6]=2[N:7]=1>C[Si](N[Si](C)(C)C)(C)C>[F:26][C:20]1[CH:21]=[C:22]([F:25])[CH:23]=[CH:24][C:19]=1[N:16]1[CH2:17][CH2:18][N:13]([CH2:12][CH2:11][N:8]2[C:6]3[N:7]=[C:2]([NH2:1])[N:27]4[N:28]=[C:29]([C:31]5[O:32][CH:33]=[CH:34][CH:35]=5)[N:3]=[C:4]4[C:5]=3[CH:10]=[CH:9]2)[CH2:14][CH2:15]1
Reactant: Nc1nc(NNC(=O)c2ccco2)c2ccn(CCN3CCN(c4ccc(F)cc4F)CC3)c2n1
Agent: C[Si](C)(C)N[Si](C)(C)C
Product: Nc1nc2c(ccn2CCN2CCN(c3ccc(F)cc3F)CC2)c2nc(-c3ccco3)nn12
Temperature: 120 °C

Procedure:
The title B compound, N′-(2-amino-7-(2-(4-(2,4-difluorophenyl)piperazin-1-yl)ethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)furan-2-carbohydrazide (53 mg, 0.11 mmol) is dissolved in 0.5 mL of HMDS and 0.5 mL in BSA. The mixture is heated at 120° C. for 16 h, then cooled to RT and evaporated to dryness. The residue is stirred in a mixture of DCM and 6N aqueous HCl for an hour at RT, then the pH is adjusted to 9 with 1M aqueous NaOH. The organic phase is collected and the aqueous phase extracted with additional DCM. The combined organic extracts are dried (Na2SO4), filtered and evaporated. Purification of the residue by flash chromatography, eluting with 3% MeOH in DCM affords 7-(2-(4-(2,4-difluorophenyl)piperazin-1-yl)ethyl)-2-(furan-2-yl)-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine as an off-white solid: LC/MS (M+1=465.2). 1H NMR (CDCl3) δ 3.01 (m, 2H), 3.25 (m, 2H), 3.39 (m, 2H), 3.52 (m, 4H), 4.86 (t, 2H, J=6.6 Hz), 5.76 (br s, 2H), 6.54 (dd, 1H, J=1.8 Hz and 3.4 Hz), 6.8-6.72 (m, 3H), 7.11 (dd, 1H, J=4.6 Hz), 7.19 (m, 2H), 7.57 (t, 1H, J=0.8 Hz).
Reaction SMILES: [F:1][C:2]1[C:7]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:6][CH:5]=[CH:4][C:3]=1[CH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:25][CH2:26][O:27][CH3:28]>C(#N)C>[F:1][C:2]1[C:7]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:6][CH:5]=[CH:4][C:3]=1[CH:12]1[CH2:17][CH2:16][N:15]([CH2:25][CH2:26][O:27][CH3:28])[CH2:14][CH2:13]1
Reactant: COCCBr
Reactant: CS(=O)(=O)c1cccc(C2CCNCC2)c1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: COCCN1CCC(c2cccc(S(C)(=O)=O)c2F)CC1

Procedure:
Preparation according to Example 1: 4-[2-fluoro-3-(methylsulfonyl)-phenyl]-piperidine (0.53 g, 1.64 mmol), acetonitrile (20 ml), potassium carbonate (0.45 g, 3.2 mmol), 1-bromo-2-methoxyethane (0.167 ml, 1.72 mmol). MS m/z (relative intensity, 70 eV) 315 (M+, 1), 271 (14), 270 (bp), 147 (10) 133 (9).
Reaction SMILES: [N:1]1[CH:2]=[CH:3][N:4]2[CH2:9][CH2:8][CH:7]([C:10]([O:12]CC)=[O:11])[CH2:6][C:5]=12.[ClH:15]>>[N:1]1[CH:2]=[CH:3][N:4]2[CH2:9][CH2:8][CH:7]([C:10]([OH:12])=[O:11])[CH2:6][C:5]=12.[ClH:15]
Reactant: CCOC(=O)C1CCn2ccnc2C1
Agent: Cl
Product: O=C(O)C1CCn2ccnc2C1

Procedure:
A solution of 0.18 g ethyl 5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-7-carboxylate in 10 ml of 3N-HCl was heated overnight under reflux, the reaction mixture was concentrated to dryness under reduced pressure, and the residue was dried, thus giving 0.18 g of 5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-7-carboxylic acid·hydrochloride.
Reaction SMILES: C(S[C:4]1[N:9]=[N:8][C:7]2[CH2:10][CH2:11][N:12]([C:14](=[O:21])[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:13][C:6]=2[CH:5]=1)C.C(N1CCC2[N:34]=[N:35]C(S)=CC=2C1)(=O)C1C=CC=CC=1.C(Br)C.C1C=CC=CC=1>C(O)(C)C.CCOCC>[C:14]([N:12]1[CH2:11][CH2:10][C:7]2[N:8]=[N:9][C:4]([NH:34][NH2:35])=[CH:5][C:6]=2[CH2:13]1)(=[O:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: CCSc1cc2c(nn1)CCN(C(=O)c1ccccc1)C2
Reactant: O=C(c1ccccc1)N1CCc2nnc(S)cc2C1
Solvent: CCOCC
Solvent: c1ccccc1
Solvent: CC(C)O
Product: NNc1cc2c(nn1)CCN(C(=O)c1ccccc1)C2

Procedure:
The 3-ethylmercapto-6-benzoyl-5,6,7,8-tetrahydropyrido[4,3-c]pyridazine, required as starting material, may be obtained in a manner analogous to that described in Example 41 (b), from 34.8 g of 6-benzoyl-3-mercapto-5,6,7,8-tetrahydropyrido[4,3-c]pyridazine and 16.8 g of ethyl bromide. Reaction time 19 hours. Working up as described in Example 41 (b), eluant: benzene. M.P. 132°-135° (decomp., from isopropanol/ether).
Reaction SMILES: [CH:1]([CH:4]1[NH:9][CH2:8][CH2:7][N:6]2[C:10]3[CH:16]=[C:15]([S:17]([CH3:20])(=[O:19])=[O:18])[CH:14]=[CH:13][C:11]=3[N:12]=[C:5]12)([CH3:3])[CH3:2].Cl[C:22]1[N:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][N:23]=1.CCN(C(C)C)C(C)C.O>CS(C)=O>[CH:1]([CH:4]1[N:9]([C:22]2[N:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][N:23]=2)[CH2:8][CH2:7][N:6]2[C:10]3[CH:16]=[C:15]([S:17]([CH3:20])(=[O:18])=[O:19])[CH:14]=[CH:13][C:11]=3[N:12]=[C:5]12)([CH3:3])[CH3:2]
Reactant: FC(F)(F)c1ccnc(Cl)n1
Reactant: CC(C)C1NCCn2c1nc1ccc(S(C)(=O)=O)cc12
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: CS(C)=O
Product: CC(C)C1c2nc3ccc(S(C)(=O)=O)cc3n2CCN1c1nccc(C(F)(F)F)n1
Temperature: 100 °C
Reaction time: 2 h
Yield: 23.2 %

Procedure:
To a solution of 1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine (15 mg, 0.05 mmol) in DMSO (3 mL) was added 2-chloro-4-(trifluoromethyl)pyrimidine (19 mg, 0.10 mmol) and DIEA (20 mg, 0.15 mmol) under N2. The mixture was stirred at 100° C. for 2 h. Water (10 mL) was added and the mixture was extracted with EtOAc (3×10 mL). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na2SO4, filtered, concentrated and then purified by preparative TLC to afford 1-isopropyl-7-(methylsulfonyl)-2-(4-(trifluoromethyl)pyrimidin-2-yl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine (5.10 mg, 23% yield) as a white solid. LC-MS m/z 440.2 (MH+). 1H NMR (CDCl3 400 MHz): δ 8.58 (d, J=4.8 Hz, 1H), 8.01 (d, J=0.8 Hz, 1H), 7.90-7.81 (m, 2H), 6.89 (d, J=4.8 Hz, 1H), 6.12 (d, J=8.0 Hz, 1H), 5.39 (dd, J=4.0 and 14.0 Hz, 1H), 4.34-4.30 (m, 1H), 4.23-4.16 (m, 1H), 3.83-3.75 (m, 1H), 3.09 (s, 3H), 2.55-2.49 (m, 1H), 1.33 (d, J=6.8 Hz, 3H), 1.09 (d, J=6.8 Hz, 3H).
Reaction SMILES: [Si:1]([O:18][CH2:19][C@H:20]1[C@H:24]([C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)[O:23][C:22](=[O:33])[N:21]1[C:34]1[CH:39]=[C:38](Cl)[N:37]=[C:36]([N:41]2[CH2:46][CH2:45][O:44][CH2:43][CH2:42]2)[N:35]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:55]2[C:56]([C:62]([F:65])([F:64])[F:63])=[N:57][C:58]([NH2:61])=[N:59][CH:60]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[NH2:61][C:58]1[N:57]=[C:56]([C:62]([F:65])([F:63])[F:64])[C:55]([C:38]2[CH:39]=[C:34]([N:21]3[C@@H:20]([CH2:19][O:18][Si:1]([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]4[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=4)[C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[C@H:24]([C:25]4[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=4)[O:23][C:22]3=[O:33])[N:35]=[C:36]([N:41]3[CH2:46][CH2:45][O:44][CH2:43][CH2:42]3)[N:37]=2)=[CH:60][N:59]=1
Reactant: CC1(C)OB(c2cnc(N)nc2C(F)(F)F)OC1(C)C
Reactant: COc1ccc([C@@H]2OC(=O)N(c3cc(Cl)nc(N4CCOCC4)n3)[C@H]2CO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)cc1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: CCOC(C)=O
Solvent: COCCOC
Solvent: ClCCl
Product: COc1ccc([C@@H]2OC(=O)N(c3cc(-c4cnc(N)nc4C(F)(F)F)nc(N4CCOCC4)n3)[C@H]2CO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)cc1
Yield: 38 %

Procedure:
A solution of (4S,5S)-4-(((tert-butyldiphenylsilyl)oxy)methyl)-3-(6-chloro-2-morpholinopyrimidin-4-yl)-5-(4-methoxyphenyl)oxazolidin-2-one (150 mg, 228 μmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)pyrimidin-2-amine (108 mg, 364 μmol), 20% aqueous Na2CO3 (0.24 mL, 2.28 mmol), and PdCl2(dppf)-CH2Cl2 (18.6 mg, 23 μmol) in DME (2 mL) under argon was stirred at 80° C. for 8 h. The reaction mixture was diluted with EtOAc and washed with saturated NaHCO3 solution, H2O and brine, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography using EtOAc in heptane from 0% to 33% in order to give the title compound as a light yellow foam (68 mg, 28%): TLC (heptane/EtOAc 1:1) Rf=0.32; tR=1.663 min (UPLC 1); LC-MS: [M+H] 786; Rt 1.48 min; (LCMS method 2).
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][C:11]([CH3:18])([O:14][CH2:15][CH2:16][OH:17])[CH2:10][CH2:9]1)C1C=CC=CC=1.[H][H].C>C(O)C>[CH3:18][C:11]1([O:14][CH2:15][CH2:16][OH:17])[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]1
Reactant: [H][H]
Reactant: CC1(OCCO)CCN(Cc2ccccc2)CC1
Solvent: CCO
Product: CC1(OCCO)CCNCC1
Yield: 73 %

Procedure:
A solution of 51.5 g of 2-(1-benzyl-4-methyl-4-piperidyloxy)-ethanol in 500 ml of absolute ethanol was reacted with hydrogen at 50° C in the presence of 5 g of 5% palladized charcoal until the theoretical amount of hydrogen was absorbed (about 31/2 hours) and the catalyst was then filtered off. The ethanol was evaporated and the residue was distilled under reduced pressure to obtain 24 g of 2-(4-methyl-4-piperidyloxy) -ethanol as a colorless oil boiling at 80°-86° C at 0.01 mm Hg and having a refractive index nD24 = 1.481.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[N:8]=[CH:7]1.[N:15]1[CH:20]=[CH:19][CH:18]=[N:17][C:16]=1[N:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1.C(N(C(C)C)CC)(C)C.[I-].[K+]>C(#N)C>[N:15]1[CH:20]=[CH:19][CH:18]=[N:17][C:16]=1[N:21]1[CH2:26][CH2:25][N:24]([CH2:2][CH2:3][CH2:4][CH2:5][N:6]2[C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[N:8]=[CH:7]2)[CH2:23][CH2:22]1
Reactant: ClCCCCn1cnc2ccccc21
Reactant: c1cnc(N2CCNCC2)nc1
Agent: [I-]
Agent: [K+]
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: c1cnc(N2CCN(CCCCn3cnc4ccccc43)CC2)nc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 60.4 %

Procedure:
1-(4-chlorobutyl)-1H-benzimidazole (7.51 g, 0.036 mol) was dissolved into 100 ml of acetonitrile, 4-(2-pyrimidinyl) piperazine (4.9 g, 0.03 mol), diisopropylethylamine (15.5 g, 0.12 mol) and potassium iodide (5.0 g, 0.03 mol) were respectively added. The mixture was stirred for 10 min at ambient temperature, and then heated and refluxed to react for 20 hours. The mixture was cooled down to ambient temperature and filtered. The filtrate was concentrated to produce oily products, and treated by chromatography with neutral Al2O3, eluted with dichloromethane/methanol mixture to produce 6.1 g compound (I-14) with a yield of 60.1%. ESI-MS [M+H]+: m/z 337.2.
Reaction SMILES: [CH3:1][CH:2]1[O:10][C:5]2([CH2:11][OH:12])[O:6][CH:7]([CH3:9])[CH2:8][N:4]2[CH2:3]1.[C:13](OC)(=[O:17])[C:14]([CH3:16])=[CH2:15]>>[CH3:1][CH:2]1[O:10][C:5]2([CH2:11][O:12][C:13](=[O:17])[C:14]([CH3:16])=[CH2:15])[O:6][CH:7]([CH3:9])[CH2:8][N:4]2[CH2:3]1
Reactant: C=C(C)C(=O)OC
Reactant: CC1CN2CC(C)OC2(CO)O1
Product: C=C(C)C(=O)OCC12OC(C)CN1CC(C)O2
Temperature: 110 °C

Procedure:
In an oven dried 300 mL round-bottom flask equipped with a reflux condenser were added 2,6-Dimethyl-tetrahydro-oxazolo[2,3-b]oxazol-7a-yl-methanol (789 g, 0.45 mol), methyl methacrylate (180.0 g, 1.80 mol), Prostab® 5415 (3.00 g, Ciba Specialty Chemicals, Basel, Switzerland) and titanium (iv) n-butoxide (6.00 g, 0.024 mol). The reaction content was heated to 110° C. for ˜8 hours GC analyses indicated ˜44% conversion. The reflux condenser was replaced with an oven dried distillation head and the distillate boiling between 60-70° C. collected. The distillation head was replaced with a reflux condenser and the reaction content heated to 120° C. for ˜4 hours, at the end of which GC analyses indicated the conversion to be ˜75%. Again the reflux condenser was replaced with a distillation head and the distillated boiling between 60-70° C. collected for ˜8 hours, at the end of which GC analyses indicated the conversion to be ˜90%. The reaction content was cooled to room temperature and the unreacted methyl methacrylate removed under vacuum and then the remaining reaction content vaccuum fractionally distilled affording four fractions:
Reaction SMILES: O.O.[Sn](Cl)Cl.[F:6][C:7]([F:24])([F:23])[C:8]([NH:10][CH2:11][C:12]#[C:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([N+:20]([O-])=O)[CH:15]=1)=[O:9]>C(O)C>[NH2:20][C:16]1[CH:15]=[C:14]([C:13]#[C:12][CH2:11][NH:10][C:8](=[O:9])[C:7]([F:6])([F:23])[F:24])[CH:19]=[CH:18][CH:17]=1
Reactant: O=C(NCC#Cc1cccc([N+](=O)[O-])c1)C(F)(F)F
Agent: Cl[Sn]Cl
Solvent: CCO
Solvent: O
Product: Nc1cccc(C#CCNC(=O)C(F)(F)F)c1

Procedure:
Tin(II) chloride dihydrate was added (6.5 g, 28.67 mmol) to a solution of 2,2,2-trifluoro-N-(3-(3-nitrophenyl)prop-2-ynyl)acetamide (1.95 g, 7.16 mmol) in ethanol and the reaction mixture was stirred under reflux overnight. The mixture was concentrated under reduced pressure to give dark brown viscous liquid which was partitioned between saturated aqueous NaHCO3 and EtOAc. Organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give N(3-(3-aminophenyl)prop-2-ynyl)-2,2,2-trifluoroacetamide as brown oil. Yield (0.75 g, 43%); 1H NMR (400 MHz, DMSO-d6) δ 7.28 (s, 1H), 6.94 (t, J=7.8 Hz, 1H), 6.44-6.37 (m, 3H), 5.09 (bs, 2H), 3.99 (s, 2H).
Reaction SMILES: [OH:1][CH:2]([CH3:13])[CH2:3][NH:4][C:5](=[O:12])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.C[N+]1([O-])CCOCC1>C(Cl)Cl.[Ru]([O-])(=O)(=O)=O.C([N+](CCC)(CCC)CCC)CC>[O:1]=[C:2]([CH3:13])[CH2:3][NH:4][C:5](=[O:12])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: CC(O)CNC(=O)c1ccccc1
Agent: O=[Ru](=O)(=O)[O-]
Agent: CCC[N+](CCC)(CCC)CCC
Agent: C[N+]1([O-])CCOCC1
Solvent: ClCCl
Product: CC(=O)CNC(=O)c1ccccc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 75 %

Procedure:
Prepare a solution of N-(2-hydroxypropyl)benzamide (8.22 g, 45.9 mmol) in methylene chloride (100 mL). Add N-methylmorpholine N-oxide (7.0 g, 60.0 mmol) followed by powdered 4 Å molecular sieves. Cool the mixture to 0° C. and add tetra-n-propylammonium perruthenate in one portion. Stir the mixture for 30 minutes and then warm to room temperature for 1 hour and filter through Celite®. Concentrate the filtrate and flash-chromatograph on silica gel eluting with 100% ethyl acetate to afford 6.1 g of N-(2-oxopropyl)benzamide as a white solid. MS: m/e=178 (MH+)
Reaction SMILES: C([C:3](CC)([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[CH:4]([P:25](=[O:28])([O-:27])[O-:26])[NH:5][S:6]([C:9]1[CH:24]=[CH:23][C:12]2[N:13]=[C:14]([S:16][CH2:17][CH2:18][CH2:19][CH2:20]CC)[S:15][C:11]=2[CH:10]=1)(=[O:8])=[O:7])C.C(C(CC)(C1C=CC=CC=1)C(P(=O)([O-])[O-])NS(C1C=CC2N=C(SCC3CCCCC3)SC=2C=1)(=O)=O)C>>[CH2:17]([S:16][C:14]1[S:15][C:11]2[CH:10]=[C:9]([S:6]([NH:5][CH:4]([P:25](=[O:26])([OH:27])[OH:28])[CH2:3][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)(=[O:7])=[O:8])[CH:24]=[CH:23][C:12]=2[N:13]=1)[CH2:18][CH2:19][CH3:20]
Reactant: CCCCCCSc1nc2ccc(S(=O)(=O)NC(C(CC)(CC)c3ccccc3)P(=O)([O-])[O-])cc2s1
Agent: CCC(CC)(c1ccccc1)C(NS(=O)(=O)c1ccc2nc(SCC3CCCCC3)sc2c1)P(=O)([O-])[O-]
Product: CCCCSc1nc2ccc(S(=O)(=O)NC(Cc3ccccc3)P(=O)(O)O)cc2s1

Procedure:
The following titled compounds were prepared in a similar manner as above, except for employing (±)-diethyl-1-[(2-(n-hexylthio)benzthiazol-6-sulfonyl)amino]-2-phenylethylphosphonate (0.05 g, 0.087 mmol) and (±)-diethyl-1-[(2-(cyclohexylmethylthio)benzthiazol-6-sulfonyl)amino]-2-phenylethylphosphonate (0.05 g, 0.0858 mmol) prepared in Example 35 as starting materials.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=2)[N:9]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[Cl:21])[C:10]=1[CH:11]=[CH:12][O:13]C)=[O:5])[CH3:2].OS(O)(=O)=O.C([O-])([O-])=O.[K+].[K+]>C1COCC1.O>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([C:22]2[CH:23]=[CH:24][C:25]([Cl:28])=[CH:26][CH:27]=2)[N:9]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[Cl:21])[C:10]=1[CH2:11][CH:12]=[O:13])=[O:5])[CH3:2]
Reactant: CCOC(=O)c1nc(-c2ccc(Cl)cc2)n(-c2ccccc2Cl)c1C=COC
Agent: O=C([O-])[O-]
Agent: O=S(=O)(O)O
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Product: CCOC(=O)c1nc(-c2ccc(Cl)cc2)n(-c2ccccc2Cl)c1CC=O
Temperature: 25 °C

Procedure:
A solution of 2-(4-chloro-phenyl)-1-(2-chloro-phenyl)-5-(2-methoxy-vinyl)-1H-imidazole-4-carboxylic acid ethyl ester I-5g (275 mg, 0.659 mmol) and H2SO4 (200 μl) in 5:1 THF/H2O (18 ml) was heated at 70° C. for 3 hours. The reaction mixture was cooled to room temperature and treated with 1M K2CO3 until the pH of the reaction mixture was ˜6. The aqueous solution was extracted with CH2Cl2 and the combined organic extracts were washed with sat'd aq. NaCl, dried, and concentrated in vacuo to give a mixture of the starting material and product (I-5h): +APCI MS (M+1) 403.3
Reaction SMILES: [Si:1](Cl)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Br:19][C:20]1[CH:27]=[CH:26][C:23]([CH2:24][OH:25])=[CH:22][CH:21]=1.C(N(CC)CC)C.CN(C1C=CC=CN=1)C>ClCCl>[Si:1]([O:25][CH2:24][C:23]1[CH:26]=[CH:27][C:20]([Br:19])=[CH:21][CH:22]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OCc1ccc(Br)cc1
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Agent: CN(C)c1ccccn1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)[Si](OCc1ccc(Br)cc1)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Tert-butyldiphenylsilyl chloride (10.4 mL, 40.1 mmol) was added to a solution of 4-bromobenzyl alcohol ( 5.0 g, 26.7 mmol) and 50 mL of dichloromethane. The solution was treated with triethylamine (3.72 mL, 26.7 mmol) and (dimethylamino)pyridine (163 mg, 1.34 mmol) and stirred overnight at room temperature. The solution was diluted with 300 mL of dichloromethane and washed with 50 mL of 10% aqueous HCl. The layers were separated and the aqueous layer was extracted with 50 mL of dichloromethane. The combined organic extracts were washed with brine, and dried (MgSO4), and filtered, and the solvents were removed in vacuo. The residue was filtered through a plug (6@X 2@) of silica gel using a solution of 97% hexane/ethyl acetate. After removal of the solvent the residue was heated under vacuum (3 torr) to 170° C. for 1 hour to remove a low-boiling impurity. The remaining material is the title compound.
Reaction SMILES: [CH:1](=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4].Cl.Cl[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>C(O)(C)C>[N:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[CH2:12][O:4][C:3]1[CH:5]=[CH:6][CH:7]=[CH:8][C:2]=1[CH:1]=[O:9]
Reactant: O=Cc1ccccc1O
Reactant: ClCc1ccccn1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [I-]
Solvent: CC(C)O
Product: O=Cc1ccccc1OCc1ccccn1

Procedure:
12.2 g of salicylaldehyde and 16.4 g of 2-(chloromethyl)-pyridine-hydrochloride are, after the addition of 55.2 g of potassium carbonate and 0.2 g of potassium iodide in 200 ml of isopropanol, refluxed for 12 hours with thorough stirring. The hot reaction mixture is filtered, and concentrated in vacuo. The residue is dissolved in 100 ml of chloroform, and the solution extracted with 2 N sodium hydroxide solution and then with water. The chloroform solution is subsequently dried over anhydrous sodium sulphate, and concentrated in vacuo. The oil remaining is dissolved in benzene, and filtered through 200 g. of aluminium oxide (2% water). The filtrates are concentrated by evaporation, and the residue distilled in high vacuum to obtain 2-(2-pyridylmethoxy)-benzaldehyde as colourless viscous oil, B.P. 135°-164°/0.04 Torr, which, after solidification, melts at 69°-71°. This substance is heated for 30 minutes at 300° in a nitrogen atomosphere; after cooling, it is dissolved in methylene chloride, and the solution filtered through aluminium oxide (2% water). From the filtrate there is obtained 2-(2-benzofuranyl)-pyridine in the form of yellowish crystals, M.P. 86°-87° (from isopropanol).
Reaction SMILES: [Cl:1][C:2]1[C:3]([N:8]2[CH:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:11][C:10](=[O:18])[NH:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.S(=O)(=O)(O)O.S(OOS([O-])(=O)=O)([O-])(=O)=O.[K+].[K+]>C(#N)C>[Cl:1][C:2]1[C:3]([N:8]2[C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][C:10]([OH:18])=[N:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)C1CC(=O)NN1c1ncccc1Cl
Agent: O=S(=O)(O)O
Agent: O=S(=O)([O-])OOS(=O)(=O)[O-]
Agent: [K+]
Solvent: CC#N
Product: CCOC(=O)c1cc(O)nn1-c1ncccc1Cl
Temperature: 25 °C
Yield: 60.7 %

Procedure:
To a mixture of 12.0 g of ethyl 2-(3-chloro-2-pyridinyl)-5-oxo-3-pyrazolidinecarboxylate, 90 ml of acetonitrile and 4.8 ml of sulfuric acid was added 14.5 g of potassium persulfate. The resulting mixture was heated to reflux for 3.5 hours. The reaction mixture was allowed to cool to room temperature, and filtered. Water was poured into the filtrate, and the mixture was extracted with methyl tert-butyl ether three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography to obtain 7.23 g of ethyl 1-(3-chloro-2-pyridinyl)-3-hydroxy-1H-pyrazole-5-carboxylate of the formula:
Reaction SMILES: B1(C)OC(C2C=CC=CC=2)(C2C=CC=CC=2)[C@@H]2N1CCC2.B.CSC.[O:26]=[C:27]1[CH2:36][CH2:35][CH2:34][C:33]2[CH:32]=[C:31]([O:37][S:38]([C:41]([F:44])([F:43])[F:42])(=[O:40])=[O:39])[CH:30]=[CH:29][C:28]1=2>C1(C)C=CC=CC=1.C1COCC1>[OH:26][CH:27]1[CH2:36][CH2:35][CH2:34][C:33]2[CH:32]=[C:31]([O:37][S:38]([C:41]([F:44])([F:42])[F:43])(=[O:40])=[O:39])[CH:30]=[CH:29][C:28]1=2
Reactant: O=C1CCCc2cc(OS(=O)(=O)C(F)(F)F)ccc21
Agent: B
Agent: CB1OC(c2ccccc2)(c2ccccc2)[C@H]2CCCN12
Solvent: C1CCOC1
Solvent: CSC
Solvent: Cc1ccccc1
Product: O=S(=O)(Oc1ccc2c(c1)CCCC2O)C(F)(F)F
Temperature: 0 °C
Reaction time: 0.67 h

Procedure:
To a dry three-necked flask containing (R)-2-methyl-CBS-oxazaborolidine (Aldrich, 1.94 mL, 1.0 M in toluene, 1.93 mmol, 0.05 eq) under N2 was added a solution of borane-methylsulfide (BMS) (Aldrich, 3.30 mL, 34.80 mmol, 0.9 eq) in toluene (200 mL) through an additional funnel at RT. After the addition, the reaction was cooled to 0° C. A solution of trifluoro-methanesulfonic acid 5-oxo-5,6,7,8-tetrahydro-naphthalen-2-yl ester (11.37 g, 38.67 mmol, 1.0 eq) in THF (180 mL) was added drop-wise through an additional funnel. Following the addition, the reaction was warmed to RT and stirred for additional 40 min, then quenched with MeOH. The solvent was removed in vacuo. The residue was treated with H2O (50 mL), and extracted with ether (3×150 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The title compound was obtained as an off-white solid after flash chromatography purification (16–22% EtOAc-hexane).