Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: F[C:2]1[C:7]([CH2:8][OH:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[NH:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1.C(N(CC)C(C)C)(C)C>>[N:10]1([C:2]2[C:7]([CH2:8][OH:9])=[CH:6][CH:5]=[CH:4][N:3]=2)[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1
Reactant: C1CNCCN1
Reactant: OCc1cccnc1F
Solvent: CCN(C(C)C)C(C)C
Product: OCc1cccnc1N1CCNCC1

Procedure:
A mixture of (2-fluoro-pyridin-3-yl)methanol (1 g, 8 mmol, Asymchem), piperazine (1.3 g, 15 mmol) and N,N-diisopropylethylamine (1 mL, 5.8 mmol, Aldrich) was reacted under the conditions of Example 43a to give the title compound as a white solid. MS (ESI, pos. ion) m/z: 194 (M+1).
Reaction SMILES: [CH3:1][NH:2][C:3](=[O:13])[O:4][C:5]1[CH:10]=[CH:9][C:8]([NH2:11])=[C:7]([CH3:12])[CH:6]=1.[Cl:14][CH2:15][CH2:16][C:17](Cl)=[O:18]>>[CH3:1][NH:2][C:3](=[O:13])[O:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:17](=[O:18])[CH2:16][CH2:15][Cl:14])=[C:7]([CH3:12])[CH:6]=1
Reactant: O=C(Cl)CCCl
Reactant: CNC(=O)Oc1ccc(N)c(C)c1
Product: CNC(=O)Oc1ccc(NC(=O)CCCl)c(C)c1

Procedure:
According to the general directions described in Example 5, 3-methyl-4-aminophenyl N-methylcarbamate (1.8g., 0.01 mole) was reacted with 3-chloropropionyl chloride (1.52 g., 0.012 mole). The product weighed 2.0g. after recrystallization from ethanol-water and its infrared spectrum showed a double carbonyl absorption at about 5.8 μ and 6.0 μ.
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[C:12]([F:14])[C:11]([Cl:15])=[CH:10][C:9]=1[NH:16][C:17](=[O:34])[CH2:18][C:19]([C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]2[CH:28]=[N:29][C:30]([CH3:33])=[CH:31][CH:32]=2)[CH:22]=1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:15][C:11]1[C:12]([F:14])=[CH:13][C:8]2[N:7]=[C:19]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]4[CH:28]=[N:29][C:30]([CH3:33])=[CH:31][CH:32]=4)[CH:22]=3)[CH2:18][C:17](=[O:34])[NH:16][C:9]=2[CH:10]=1
Reactant: Cc1ccc(-c2cccc(C(=O)CC(=O)Nc3cc(Cl)c(F)cc3NC(=O)OC(C)(C)C)c2)cn1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cc1ccc(-c2cccc(C3=Nc4cc(F)c(Cl)cc4NC(=O)C3)c2)cn1

Procedure:
The title compound was prepared from (4-chloro-5-fluoro-2-{3-[3-(6-methyl-pyridin-3-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamic acid tert-butyl ester (Example M20) (241 mg, 0.48 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an off-white solid (124 mg).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:12]2[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][CH3:20])[CH2:14][CH2:13]2)[CH:6]=[CH:7][C:8]=1[N+:9]([O-])=O.O.NN>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:12]2[CH2:13][CH2:14][N:15]([CH2:18][CH2:19][CH3:20])[CH2:16][CH2:17]2)[CH:6]=[CH:7][C:8]=1[NH2:9]
Reactant: CCCN1CCN(c2ccc([N+](=O)[O-])c(OC)c2)CC1
Agent: NN
Solvent: CO
Solvent: O
Product: CCCN1CCN(c2ccc(N)c(OC)c2)CC1
Yield: 77.8 %

Procedure:
A solution of 1-[3-(methyloxy)-4-nitrophenyl]-4-propylpiperazine (Intermediate B50, 1.5 g, 5.4 mmol), FeCl3 (0.300 g, 1.85 mmol), activated carbon (2.0 g), and hydrazine hydrate (2.1 mL, 65 mmol) was heated in methanol (50 mL) for 3 hours. The mixture was filtered over celite and concentrated to give 2-(methyloxy)-4-(4-propyl-1-piperazinyl)aniline as a white solid (1.03 g, 4.2 mmol, 78% yield). 1H NMR (400 MHz, CDCl3) δ ppm 0.93 (t, J=7.51 Hz, 3 H), 1.51-1.61 (m, 2 H), 2.37 (d, J=8.06 Hz, 2 H), 2.57-2.66 (m, 4 H), 3.09-3.10 (m, 4 H), 3.53 (s, 2 H), 3.83 (s, 3 H), 6.42 (dd, J=8.24, 2.38 Hz, 1H), 6.52 (d, J=2.20 Hz, 1 H), 6.64 (d, J=8.42 Hz, 1 H).
Reaction SMILES: CO[C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[N:6][CH:5]=1.[Cl:13][C:14]1[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:15]=1[CH2:16][C:17]#[N:18].O>C(O)(C)(C)C>[Cl:13][C:14]1[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:15]=1[CH:16]([C:3]([C:4]1[CH:5]=[N:6][C:7]([O:10][CH3:11])=[CH:8][CH:9]=1)=[O:12])[C:17]#[N:18]
Reactant: COC(=O)c1ccc(OC)nc1
Reactant: N#CCc1ccc(Cl)cc1Cl
Solvent: O
Solvent: CC(C)(C)O
Product: COc1ccc(C(=O)C(C#N)c2ccc(Cl)cc2Cl)cn1
Temperature: 100 °C
Yield: 29.3 %

Procedure:
To a suspension of potassium-tert-butylate (2.052 g) in tert-butanol (25 ml) was added methyl-6-methoxynicotinate (2.5 g). 2,4-Dichlorobenzyl cyanide (2.782 g) was added portion wise. The mixture was heated to 100° C. for 1.5 h. After cooling to room temperature, water (100 ml) was added and the mixture was washed with diethyl ether. The aqueous phase was neutralized with concentrated aqueous HCl and extracted with EtOAc. The organic phase was washed with water and with brine, dried (MgSO4), filtered and concentrated to dryness to give the title compound (1.407 g) as a yellow foam that was used in the next step without further purification. MS (m/e)=321.0 [M+H+].
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:12])[CH:10]=2)[N:5]([CH3:13])[C:4](=[O:14])[C:3]=1[C:15]#[N:16].[NH:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1>ClCCl>[F:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]([CH3:13])[C:4](=[O:14])[C:3]([C:15]#[N:16])=[C:2]2[N:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1
Reactant: Cn1c(=O)c(C#N)c(Cl)c2cc(F)ccc21
Reactant: C1CNCCN1
Solvent: ClCCl
Product: Cn1c(=O)c(C#N)c(N2CCNCC2)c2cc(F)ccc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 85.9 %

Procedure:
A solution of Compound 47 (750 mg, 3.17 mmol) in dichloromethane was added slowly to a stirred solution of piperazine (819 mg, 9.50 mmol) in dichloromethane at room temperature. The solution was stirred overnight at room temperature. The solvent was removed under reduced pressure. The residue was taken in water, sonicated briefly, and filtered. The solids were dissolved in ethyl acetate and washed by water. The organic layer was dried over Na2SO4 and concentrated to yield 780 mg (86%) of yellow solids. M.P. 211° C. 1H NMR (DMSO-d6): δ 2.91 (m, 4H), 3.47 (m, 4H), 3.56 (s, 3H), 7.54 (m, 1H), 7.63 (m, 2H). EIMS m/z 287 (M+1).
Reaction SMILES: [N:1]1([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:8][CH2:7][CH2:6][C@H:2]1[C:3](Cl)=[O:4].Cl.[F:20][C:21]([F:33])([C:29]([F:32])([F:31])[F:30])[C:22]([CH:24]1[CH2:28][CH2:27][CH2:26][NH:25]1)=[O:23].CN1CCOCC1>C(Cl)Cl>[F:33][C:21]([F:20])([C:29]([F:30])([F:31])[F:32])[C:22]([CH:24]1[CH2:28][CH2:27][CH2:26][N:25]1[C:3]([CH:2]1[CH2:6][CH2:7][CH2:8][N:1]1[C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10])=[O:4])=[O:23]
Reactant: O=C(C1CCCN1)C(F)(F)C(F)(F)F
Reactant: O=C(Cl)[C@@H]1CCCN1C(=O)OCc1ccccc1
Agent: Cl
Solvent: CN1CCOCC1
Solvent: ClCCl
Product: O=C(OCc1ccccc1)N1CCCC1C(=O)N1CCCC1C(=O)C(F)(F)C(F)(F)F

Procedure:
Methylene chloride (10 ml) was added to CBZ-L-Pro-Cl which was then reacted under argon with a suspension of 2-(2,2,3,3,3-pentafluoro-1-oxopropyl)pyrrolidine hydrochloride (compound from Example IC; 2.49 mmol) and N-methylmorpholine (0.54 ml; 4.98 mmol) dissolved in methylene chloride (7 ml). After 2.5 hours the reaction was concentrated and brought up in methylene chloride (1 ml) and the product purified by flash chromatography on silica gel column eluting with ethyl acetate/hexane (50:50). Product fractions were collected and concentrated to give the desired product (0.52 g) as a colorless oil.
Reaction SMILES: [Li+].[OH-].C[O:4][C:5](=[O:15])[C:6]1[CH:11]=[C:10]([CH2:12][CH3:13])[CH:9]=[N:8][C:7]=1[Cl:14].ClCCl.Cl>C1COCC1>[Cl:14][C:7]1[N:8]=[CH:9][C:10]([CH2:12][CH3:13])=[CH:11][C:6]=1[C:5]([OH:15])=[O:4]
Reactant: CCc1cnc(Cl)c(C(=O)OC)c1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: ClCCl
Product: CCc1cnc(Cl)c(C(=O)O)c1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A 1 N aqueous LiOH solution (3.3 ml, 3.3 mmol) was added to a solution of 2-chloro-5-ethyl-nicotinic acid methyl ester (325 mg, 1.6 mmol; T. Y. Zhang, E. F. V. Scriven, WO 9318005 A2) in THF (3.3 ml). The reaction mixture was stirred for 3 h at ambient temperature, poured onto ice water/isopropyl acetate 1/1 and acidified with 1 N aqueous HCl solution. The layers were separated and the aqueous layer was extracted two times with isopropyl acetate. The combined extracts were washed with brine, dried over sodium sulfate and the solvent was removed under reduced pressure to give 2-chloro-5-ethyl-nicotinic acid as white solid (292 mg, 1.57 mmol; 97%) which was used in the next step without further purification. MS: m/e=184.1 [M−H−].
Reaction SMILES: [CH3:1][C:2]1[C:8]([OH:9])=[CH:7][CH:6]=[CH:5][C:3]=1[OH:4].[CH3:10][C:11]([CH2:16][CH2:17][CH3:18])=[CH:12][C:13](Cl)=[O:14]>>[OH:4][C:3]1[C:2]([CH3:1])=[C:8]2[C:7]([C:13](=[O:14])[CH2:12][C:11]([CH3:10])([CH2:16][CH2:17][CH3:18])[O:9]2)=[CH:6][CH:5]=1
Reactant: Cc1c(O)cccc1O
Reactant: CCCC(C)=CC(=O)Cl
Product: CCCC1(C)CC(=O)c2ccc(O)c(C)c2O1
Temperature: 60 °C
Reaction time: 2 h
Yield: 69.7 %

Procedure:
To the mixture of 19.8 g. of 2-methyl resorcinol and 50 ml of boron trifluoride-ethyl ether complex were added dropwise 30 g. of 3-methyl-2-hexenoyl chloride with stirring at 45° C. for about 30 minutes. After stirring for 2 hours at about 60° C., the reaction mixture was poured into ice water, and extracted with ether. After washing with water, the ether layer was extracted with 5% aqueous solution of sodium hydroxide. After acidification with hydrochloric acid, the aqueous solution of sodium hydroxide was extracted with ether. The ether layer was washed with water, and dried over magnesium sulfate. The product was purified by subjecting to column chromatography filled with silica gel to obtain 26.1 g. (yield: 69.7%) of the subject compound as oily product.
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[Cl:12][C:13]1[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[CH:15][C:14]=1[C:21]1[C:22]2[N:23]([C:27]([N:32]([CH2:36][CH:37]3[CH2:39][CH2:38]3)[CH2:33][CH2:34][CH3:35])=[C:28]([S:30][CH3:31])[N:29]=2)[CH:24]=[CH:25][N:26]=1.S([O-])([O-])(=O)=S.[Na+].[Na+].C(=O)(O)[O-].[Na+]>ClCCl>[Cl:12][C:13]1[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[CH:15][C:14]=1[C:21]1[C:22]2[N:23]([C:27]([N:32]([CH2:36][CH:37]3[CH2:39][CH2:38]3)[CH2:33][CH2:34][CH3:35])=[C:28]([S:30]([CH3:31])=[O:9])[N:29]=2)[CH:24]=[CH:25][N:26]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CCCN(CC1CC1)c1c(SC)nc2c(-c3ccc(OC)cc3Cl)nccn12
Agent: O=C([O-])O
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: ClCCl
Product: CCCN(CC1CC1)c1c(S(C)=O)nc2c(-c3ccc(OC)cc3Cl)nccn12
Reaction time: 0.33 h
Yield: 12.2 %

Procedure:
m-chloroperbenzoic acid (148 mg) was added to N-[8-(2-chloro-4-methoxyphenyl)-2-(methylsulfanyl)imidazo[1,2-a]pyrazin-3-yl]-N-cyclopropylmethyl-N-propylamine (166 mg) and dichloromethane (2 mL) at room temperature, and the mixture was stirred for 20 minutes. An aqueous sodium thiosulfate solution and an aqueous sodium bicarbonate solution were added thereto, which was extracted with ethyl acetate and evaporated. The resulting residue was separated and purified by silica gel column chromatography (ethyl acetate:n-hexane=1:3) to give the title compound (21 mg) as a pale yellow oil.
Reaction SMILES: N1([C:6]2[CH:11]=[CH:10][C:9]([NH:12][C:13]([C:15]3([NH2:20])[CH2:19][CH2:18][CH2:17][CH2:16]3)=[O:14])=[CH:8][CH:7]=2)C=NC=N1.[O:21]1[C:25](C2C=CC(N)=CC=2)=[CH:24][N:23]=[CH:22]1>>[NH2:20][C:15]1([C:13]([NH:12][C:9]2[CH:8]=[CH:7][C:6]([C:25]3[O:21][CH:22]=[N:23][CH:24]=3)=[CH:11][CH:10]=2)=[O:14])[CH2:16][CH2:17][CH2:18][CH2:19]1
Reactant: Nc1ccc(-c2cnco2)cc1
Reactant: NC1(C(=O)Nc2ccc(-n3cncn3)cc2)CCCC1
Product: NC1(C(=O)Nc2ccc(-c3cnco3)cc2)CCCC1

Procedure:
The title compound was prepared as described above for N-(4-(1H-1,2,4-triazol-1-yl)phenyl)-1-aminocyclopentanecarboxamide using 4-(oxazol-5-yl)benzenamine as the amine counterpart. LCMS: m/e 272 (M+H)+, ret time 1.03 min, column 3, 2 minute gradient.
Reaction SMILES: [Br:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9](=[O:11])[CH3:10].[F:12][C:13]([F:21])(S(F)(=O)=O)C(O)=O.O>C(#N)C.[Cu]I>[Br:1][C:2]1[C:7]([O:8][CH:13]([F:21])[F:12])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9](=[O:11])[CH3:10]
Reactant: CC(=O)c1cccc(O)c1Br
Reactant: O=C(O)C(F)(F)S(=O)(=O)F
Agent: [Cu]I
Solvent: CC#N
Solvent: O
Product: CC(=O)c1cccc(OC(F)F)c1Br
Temperature: 55 °C
Reaction time: 3 h
Yield: 18 %

Procedure:
1-(2-Bromo-3-hydroxy phenyl)ethanone (6.50 g, 30.2 mmol), which had been obtained in Reference example 3 (3c), and copper (I) iodide (2.51 g, 13.2 mmol) were dissolved in acetonitrile (150 mL), followed by addition of a solution of difluoro(fluorosulfonyl)acetic acid (50.0 g, 281 mmol) dissolved in acetonitrile (50 mL) over 1 hour and 30 minutes under heating at 55° C. Upon the completion of the dropwise addition, the reaction solution was stirred at 55° C. for 3 hours, cooled to room temperature, added with water, and then extracted with ethyl acetate/hexane (2:1, V/V). The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (neutral silica gel, hexane:ethyl acetate, 100:0-75:25, V/V and basic silica gel, hexane:ethyl acetate, 100:0-50:50, V/V) to give the title compound as a colorless oily substance (1.53 g, yield 18%).
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[C:12]([N:14]([CH3:16])[CH3:15])[C:11]([Cl:17])=[CH:10][C:9]=1[NH2:18])(C)(C)C.C(O[C:25](=[O:48])[CH2:26][C:27](=O)[C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([C:34]2[O:35][CH:36]=[C:37]([CH2:39][O:40]C3CCCCO3)[N:38]=2)[CH:29]=1)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:17][C:11]1[C:12]([N:14]([CH3:16])[CH3:15])=[CH:13][C:8]2[N:7]=[C:27]([C:28]3[CH:33]=[CH:32][CH:31]=[C:30]([C:34]4[O:35][CH:36]=[C:37]([CH2:39][OH:40])[N:38]=4)[CH:29]=3)[CH2:26][C:25](=[O:48])[NH:18][C:9]=2[CH:10]=1
Reactant: CN(C)c1cc(NC(=O)OC(C)(C)C)c(N)cc1Cl
Reactant: CC(C)(C)OC(=O)CC(=O)c1cccc(-c2nc(COC3CCCCO3)co2)c1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CN(C)c1cc2c(cc1Cl)NC(=O)CC(c1cccc(-c3nc(CO)co3)c1)=N2

Procedure:
The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example J2) (170 mg) and (RS)-3-oxo-3-{3-[4-(tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl]-phenyl}-propionic acid tert-butyl ester (Example K11) (270 mg) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (110 mg).
Reaction SMILES: Cl[C:2]1[N:7]=[N:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([N:14]([CH3:22])[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:10][CH2:9]2)=[C:4]([CH3:23])[C:3]=1[CH3:24].[F:25][C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O>[F:25][C:26]1[CH:31]=[CH:30][C:29]([C:2]2[N:7]=[N:6][C:5]([N:8]3[CH2:13][CH2:12][CH:11]([N:14]([CH3:22])[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:10][CH2:9]3)=[C:4]([CH3:23])[C:3]=2[CH3:24])=[CH:28][CH:27]=1
Reactant: Cc1c(Cl)nnc(N2CCC(N(C)C(=O)OC(C)(C)C)CC2)c1C
Reactant: OB(O)c1ccc(F)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: C1COCCO1
Product: Cc1c(-c2ccc(F)cc2)nnc(N2CCC(N(C)C(=O)OC(C)(C)C)CC2)c1C
Yield: 59.9 %

Procedure:
Heat a mixture of tert-butyl 1-(6-chloro-4,5-dimethylpyridazin-3-yl)piperidin-4-yl(methyl)carbamate (1.5 g, 4.23 mmol), 4-fluorophenylboronic acid (887 mg, 6.34 mmol), Cs2CO3 (5.51 g, 16.9 mmol) and (SP-4-1)-bis[bis(1,1-dimethylethyl)(4-methoxyphenyl)phosphine-κP]dichloro-palladium (J. Org. Chem. 2007, 72, 5104-5112) (29 mg, 0.042 mmol) in a mixture of 1,4-dioxane (30 mL) and H2O (10 mL) under N2 at 90° C. overnight. Partition the reaction mixture between H2O and CH2Cl2. Separate the layers, and extract the aqueous layer with CH2Cl2. Combine the organic layers, dry over Na2SO4, filter, and concentrate under reduced pressure. Purify the residue by flash silica gel chromatography (gradient of 0 to 2% 2 M NH3/MeOH in CH2Cl2) to provide the title compound as a white foam (1.05 g, 60%). ES/MS m/z 415.2 (M+1).
Reaction SMILES: C1(O[C:8](=[O:20])[NH:9][C:10]2[C:11]([O:18][CH3:19])=[N:12][C:13]([CH3:17])=[C:14]([CH3:16])[CH:15]=2)C=CC=CC=1.[OH:21][C:22]1[CH:27]=[C:26]([CH3:28])[CH:25]=[CH:24][C:23]=1[N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1>>[CH3:16][C:14]1[CH:15]=[C:10]([NH:9][C:8]([N:32]2[CH2:31][CH2:30][N:29]([C:23]3[CH:24]=[CH:25][C:26]([CH3:28])=[CH:27][C:22]=3[OH:21])[CH2:34][CH2:33]2)=[O:20])[C:11]([O:18][CH3:19])=[N:12][C:13]=1[CH3:17]
Reactant: COc1nc(C)c(C)cc1NC(=O)Oc1ccccc1
Reactant: Cc1ccc(N2CCNCC2)c(O)c1
Product: COc1nc(C)c(C)cc1NC(=O)N1CCN(c2ccc(C)cc2O)CC1
Yield: 77 %

Procedure:
Phenyl-N-(5,6-dimethyl-2-methoxypyridin-3-yl)carbamate and 1-(2-hydroxy-4-methylphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound.
Reaction SMILES: [SH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[CH2:7][CH2:6][CH2:5]2.Cl[CH2:14][C:15]1[S:19][C:18]([C:20]2[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=2)=[N:17][C:16]=1[CH3:30].C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C.O>[CH3:30][C:16]1[N:17]=[C:18]([C:20]2[CH:21]=[CH:22][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:24][CH:25]=2)[S:19][C:15]=1[CH2:14][S:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[CH2:7][CH2:6][CH2:5]2
Reactant: O=C1CCCc2cc(S)ccc21
Reactant: Cc1nc(-c2ccc(C(F)(F)F)cc2)sc1CCl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CC#N
Product: Cc1nc(-c2ccc(C(F)(F)F)cc2)sc1CSc1ccc2c(c1)CCCC2=O
Reaction time: 16 h

Procedure:
To a solution of 6-mercapto-3,4-dihydro-2H-naphthalen-1-one (3.5 g, 20 mmol) in acetonitrile (100 mL), under nitrogen atmosphere, was added %-chloromethyl-4-methyl-2-(4-trifluoromethylphenyl)thiazole (5.7 g, 20 mmol) followed by cesium carbonate (6.4 g, 20 mmol). The resulting mixture was stirred 16 h, diluted with water (100 mL). The precipitate was collected by filtration, dried, dissolved in EtOAc, and filtered through a plug of silica gel. The filtrate was concentrated under vacuum and the residue purified by recrystallization in iso-propanol to give 5.21 g (61%) of cream colored crystals. (mp 123–124° C.) Analyzed for C22H18F3NOS2: Calcd: C, 60.95%; H, 4.19%; N, 3.23%; Found: C, 60.79%; H, 4.09%; N, 3.09%.
Reaction SMILES: Cl.[N:2]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[C:4](=O)[CH2:3]2.[I:11][C:12]1[CH:18]=[CH:17][C:15]([NH2:16])=[CH:14][CH:13]=1>>[I:11][C:12]1[CH:18]=[CH:17][C:15]([NH:16][CH:4]2[CH:5]3[CH2:8][CH2:9][N:2]([CH2:7][CH2:6]3)[CH2:3]2)=[CH:14][CH:13]=1
Reactant: O=C1CN2CCC1CC2
Reactant: Nc1ccc(I)cc1
Agent: Cl
Product: Ic1ccc(NC2CN3CCC2CC3)cc1

Procedure:
3-Quinuclidinone hydrochloride (Aldrich, 3.22 g, 20 mmol) was treated with 4-iodo-aniline (2.19 g, 10 mmol) according to the procedure of Example 30A. The title product was purified by chromatography (SiO2, CH2Cl2:MeOH:NH3.H2O, 90:10:2, Rf. 0.10) as oil (3.24 g, yield, 98%). 1H NMR (MeOH-d4, 300 MHz) δ 1.70–1.81 (m, 1H), 1.93–2.04 (m, 2H), 2.08–2.24 (m, 2H), 2.89 (ddd, J=12.9, 5.1, 2.7 Hz, 1H), 3.12–3.28 (m, 4H), 3.64 (ddd, J=12.9, 9.5, 2.4 Hz, 1H), 3.79–3.85 (m, 1H), 6.46 (dt, J=9.0, 2.7 Hz, 2H), 7.39 (dt, J=9.1, 2.7 Hz, 2H) ppm. MS (DCl/NH3) m/z 329 (M+H)+.
Reaction SMILES: [Si:1]([O:8][CH2:9][C@H:10]([NH:17][C:18]([C:20]1[N:24]2[CH:25]=[CH:26][CH:27]=[C:28]([OH:29])[C:23]2=[N:22][C:21]=1[CH3:30])=[O:19])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH:31]1([CH2:36]O)[CH2:35][CH2:34][CH2:33][CH2:32]1.C(P(=CC#N)(CCCC)CCCC)CCC>C1(C)C=CC=CC=1>[Si:1]([O:8][CH2:9][C@H:10]([NH:17][C:18]([C:20]1[N:24]2[CH:25]=[CH:26][CH:27]=[C:28]([O:29][CH2:36][CH:31]3[CH2:35][CH2:34][CH2:33][CH2:32]3)[C:23]2=[N:22][C:21]=1[CH3:30])=[O:19])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: OCC1CCCC1
Reactant: Cc1nc2c(O)cccn2c1C(=O)N[C@@H](CO[Si](C)(C)C(C)(C)C)c1ccccc1
Agent: CCCCP(=CC#N)(CCCC)CCCC
Solvent: Cc1ccccc1
Product: Cc1nc2c(OCC3CCCC3)cccn2c1C(=O)N[C@@H](CO[Si](C)(C)C(C)(C)C)c1ccccc1
Temperature: 110 °C
Reaction time: 16 h

Procedure:
A mixture of 120 mg of N-[(1R)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-phenylethyl]-8-hydroxy-2-methylimidazo[1,2-a]pyridine-3-carboxamide, 60 μl of cyclopentylmethanol, 156 μl of (tributylphosphoranylidene)acetonitrile, and 2.4 ml of toluene was stirred at 110° C. for 16 hours, followed by purification using silica gel chromatography, to obtain 100 mg of N-[(1R)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-phenylethyl]-8-(cyclopentylmethoxy)-2-methylimidazo[1,2-a]pyridine-3-carboxamide.
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([N+:12]([O-:14])=[O:13])[CH:8]=2)[N:3]=1.[Se](=O)=[O:16].O1CCOCC1.O>O>[N+:12]([C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([CH:1]=[O:16])[CH:11]=[CH:10]2)([O-:14])=[O:13]
Reactant: Cc1ccc2cc([N+](=O)[O-])ccc2n1
Reactant: O=[Se]=O
Solvent: C1COCCO1
Solvent: O
Product: O=Cc1ccc2cc([N+](=O)[O-])ccc2n1
Temperature: 90 °C

Procedure:
2-Methyl-6-nitroquinoline (0.4 ml, 0.5M solution in dioxane) was treated with selenium dioxide 90.2 ml, 0.9M solution in 9/1 dioxane/water) and heated to 90° C. overnight. The mixture was cooled to room temperature and diluted with water (1 ml). The mixture was then extracted with ethyl acetate (3×2 ml). The organic extract was then dried in vacuo to give 6-nitro-2-quinolinecarboxaldehyde which was carried forward without further purification. Daptomycin (1 ml, 0.1 M in dry dimethylformamide) was treated successively with 6-nitro-2-quinolinecarboxaldehyde prepared above in dry dimethylformamide (0.2 ml) and sodium triacetoxyborohydride (0.4 ml, 1.5M solution in dry dimethylformamide). The mixture was capped and shaken briefly. After 24 h, the mixture was treated with water (0.2 ml) and loaded onto an IBSIL-C87 5μ 250×20.2 mm column. The column was eluted at 25 ml/min under the gradient conditions of 30-60% acetonitrile in 5 mM ammonium phosphate buffer over 25 min followed by holding at 60% acetonitrile in 5 mM ammonium phosphate buffer for another 10 min. The desired fractions were collected and the acetonitrile was removed by evaporation. The residue was applied to a Bondesil 40μ C8 resin column, washed with water and the product was eluted with methanol. Evaporation of the methanol gave compound 282 as a pale yellow solid.
Reaction SMILES: [C:1]1([C:7]2[N:22]=[C:10]3[CH:11]=[C:12]([C:16]4[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=4)[CH:13]=[C:14]([NH2:15])[N:9]3[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Br:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[CH2:30][C:31](Cl)=[O:32]>>[Br:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[CH2:30][C:31]([NH:15][C:14]1[N:9]2[N:8]=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[N:22]=[C:10]2[CH:11]=[C:12]([C:16]2[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=2)[CH:13]=1)=[O:32]
Reactant: O=C(Cl)Cc1ccccc1Br
Reactant: Nc1cc(-c2ccncc2)cc2nc(-c3ccccc3)nn12
Product: O=C(Cc1ccccc1Br)Nc1cc(-c2ccncc2)cc2nc(-c3ccccc3)nn12

Procedure:
The title compound, MS m/e (%): 484,486 (M+H+, 100), was prepared in accordance with the general method of example 31 from 2-phenyl-7-pyridin-4-yl-[1,2,4]triazolo[1,5-a]pyridin-5-ylamine and o-bromphenylacetyl chloride.