Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH:4]([O:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[N:14]1[C:18]([C:19]2[S:20][CH:21]=[CH:22][CH:23]=2)=[CH:17][CH:16]=[C:15]1[C:24]1[S:25][CH:26]=[CH:27][CH:28]=1)[CH2:5][CH3:6].CN(C)C=O.[C:34]([C:36]([C:42]#[N:43])=[C:37](C#N)[C:38]#[N:39])#[N:35]>O>[CH3:1][CH2:2][CH2:3][CH:4]([O:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[N:14]1[C:18]([C:19]2[S:20][C:21]([C:37]([C:38]#[N:39])=[C:36]([C:42]#[N:43])[C:34]#[N:35])=[CH:22][CH:23]=2)=[CH:17][CH:16]=[C:15]1[C:24]1[S:25][CH:26]=[CH:27][CH:28]=1)[CH2:5][CH3:6]
Reactant: CCCC(CC)Oc1ccccc1-n1c(-c2cccs2)ccc1-c1cccs1
Reactant: N#CC(C#N)=C(C#N)C#N
Solvent: O
Solvent: CN(C)C=O
Product: CCCC(CC)Oc1ccccc1-n1c(-c2cccs2)ccc1-c1ccc(C(C#N)=C(C#N)C#N)s1
Temperature: 25 °C
Reaction time: 24 h
Yield: 82.9 %

Procedure:
After dissolving 1-[(4-n-hexyloxy)phenyl]-2,5-bis(2-thienyl)pyrrole (205 mg) into N,N-dimetylformamide (30 ml), tetracyanoethylene (126 mg) was added thereto, and then they were stirred for 24 hours at room temperature. After addition of water thereinto, extraction by toluene was conducted. The obtained organic layer is dried over anhydrous sodium sulfate, and then condensation thereof under vacuum was conducted. Subsequently, the condensed substance is separated by silica gel column chromatography using toluene as eluent to obtain 1-[(4-n-hexyloxy)phenyl]-2-(2-thienyl)-5-(5-tricyanoethenyl-2-thienyl)pyrrole (212 mg, yield 83%). After recrystallization from a chloroform-hexane mixture solvent, crystals having a bronzy metallic luster were obtained. FIG. 1 is a photograph showing the appearance of the crystals. Further, physical properties thereabout are shown bellow.
Reaction SMILES: [O:1]([C:6]1[CH:11]=[CH:10][C:9]([S:12](Cl)(=[O:14])=[O:13])=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH2:4][CH3:5].[NH2:16][C:17]1[N:22]=[C:21]([NH:23]C(=O)OC(C)(C)C)[CH:20]=[CH:19][CH:18]=1.FC(F)(F)C(O)=O>N1C=CC=CC=1>[NH2:23][C:21]1[N:22]=[C:17]([NH:16][S:12]([C:9]2[CH:10]=[CH:11][C:6]([O:1][CH2:2][CH2:3][CH2:4][CH3:5])=[CH:7][CH:8]=2)(=[O:14])=[O:13])[CH:18]=[CH:19][CH:20]=1
Reactant: CC(C)(C)OC(=O)Nc1cccc(N)n1
Reactant: CCCCOc1ccc(S(=O)(=O)Cl)cc1
Solvent: O=C(O)C(F)(F)F
Solvent: c1ccncc1
Product: CCCCOc1ccc(S(=O)(=O)Nc2cccc(N)n2)cc1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
The 4-butoxylphenyl sulfonyl chloride (160 μmol, 2.0 eq, 400 μL of a 0.40 M in anhydrous pyridine) and tert-butyl (6-aminopyridin-2-yl)carbamate (80 μmol, 1.0 eq, 400 μL of a 0.20 M in anhydrous pyridine) was added into a test tube (75×10 mm, dried by heating at 110° C. for 16 h before use) equipped with a stir bar. The test tube was covered with Parafilm, and was stirred for 24 h at ambient temperature. The solvent (pyridine) was evaporated in vacuo. Trifluoroacetic acid (320 μL, 52.0 eq., excess, neat) was added into the test tube. The test tube was capped and vortexed for 5 h at ambient temperature. The excess TFA was removed in vacuo, and the residue was dissolved in DMSO (1.340 mL) and purified by HPLC. 1H NMR (500 MHz, DMSO-d6) δ: 7.73 (d, J=7.7 Hz, 2H), 7.21 (t, J=7.2 Hz, 1H), 6.96 (d, J=6.9 Hz, 1H), 6.10 (d, J=6.1 Hz, 1H), 5.92 (d, J=5.9 Hz, 1H), 3.96 (t, J=6.6 Hz, 1H)), 1.64 (m, 2H), 1.37 (m, 2H), 0.87 (t, J=7.4 Hz, 3H). LRMS m/z: 322.0.
Reaction SMILES: [CH3:1][C:2]1[C:3](=[O:12])[CH2:4][CH2:5][C:6]([CH3:11])([CH3:10])[C:7]=1[CH2:8][OH:9].[C:13](OC(=O)C)(=[O:15])[CH3:14]>N1C=CC=CC=1>[CH3:1][C:2]1[C:3](=[O:12])[CH2:4][CH2:5][C:6]([CH3:11])([CH3:10])[C:7]=1[CH2:8][O:9][C:13](=[O:15])[CH3:14]
Reactant: CC1=C(CO)C(C)(C)CCC1=O
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: CC(=O)OCC1=C(C)C(=O)CCC1(C)C
Temperature: 0 °C

Procedure:
47 g (0.28 mole) of 2,4,4-trimethyl-3-hydroxymethylcyclohex-2-en-1-one (IIId) were refluxed with 26.54 g of pyridine and 28.6 g of acetic anhydride for 3 hours. After cooling, the mixture was poured onto 200 ml of ice water and was extracted five times with ether, the combined extracts were washed several times with saturated NaHCO3 solution and dried with sodium sulfate, and the solvent was distilled off under about 20 mbar.
Reaction SMILES: [CH:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:7]=[CH:8][CH3:9].C=CC.[Mg]>C1C=CC=CC=1>[C:1]1([CH:8]([CH3:9])[CH3:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: c1ccccc1
Reactant: C=CC
Agent: [Mg]
Product: CC(C)c1ccccc1

Procedure:
A benzene-propylene alkylation process which comprises contacting benzene with a propylene feedstock, at alkylation conditions comprising a temperature of from about 100° to 275° C., a pressure of from about 100 kPa to 13 MPa, and a liquid hourly space velocity of from about 0.5 to 50 hr-1, with a catalytic composition comprising a MgAPSO molecular sieve, said sieve comprising from about 0.003 to 0.035 mol fraction of magnesium in the microporous crystalline framework structure, to obtain a cumene product.
Reaction SMILES: [F:1][C:2]([F:15])([F:14])[C:3]1[NH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([CH2:12][NH2:13])=[CH:7][CH:6]=2.Cl[C:17]1[CH:22]=[C:21]([CH2:23][CH3:24])[N:20]=[CH:19][N:18]=1>CN1CCCC1=O.C(OCC)(=O)C>[CH2:23]([C:21]1[N:20]=[CH:19][N:18]=[C:17]([NH:13][CH2:12][C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[NH:4][C:3]([C:2]([F:1])([F:14])[F:15])=[CH:11]3)[CH:22]=1)[CH3:24]
Reactant: NCc1ccc2[nH]c(C(F)(F)F)cc2c1
Reactant: CCc1cc(Cl)ncn1
Solvent: CN1CCCC1=O
Solvent: CCOC(C)=O
Product: CCc1cc(NCc2ccc3[nH]c(C(F)(F)F)cc3c2)ncn1
Temperature: 100 °C
Yield: 34.7 %

Procedure:
A stirred mixture of {[2-(trifluoromethyl)-1H-indol-5-yl]methyl}amine (Intermediate 34, 171 mg, 0.8 mmol), 4-chloro-6-ethylpyrimidine (Intermediate 12, 171 mg, 1.200 mmol) and DI PEA (0.279 mL, 1.600 mmol) in N-methyl-2-pyrrolidone (1 mL) was heated at 100° C. for 2 hours. After cooling to room temperature the reaction mixture was diluted with ethyl acetate. The solution was washed with water and brine, dried and evaporated. The residue was purified by silica gel chromatography eluting with 50-100% ethyl acetate in isohexane to give the crude product which was triturated with ether/isohexane and the resulting colourless solid was collected, washed with cold ether and dried to give the title compound (89 mg).
Reaction SMILES: [NH2:1][C@@H:2]([CH2:5][CH:6]([CH3:8])[CH3:7])[CH2:3][SH:4].[H-].[Na+].[CH2:11](I)[CH3:12]>C1COCC1>[NH2:1][C@@H:2]([CH2:5][CH:6]([CH3:8])[CH3:7])[CH2:3][S:4][CH2:11][CH3:12]
Reactant: CC(C)C[C@H](N)CS
Reactant: CCI
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCSC[C@@H](N)CC(C)C
Reaction time: 18 h

Procedure:
(S)-2-Amino-4-methyl-1-pentanethiol (6.66 g, 50 mmol) is added over 45 minutes to a well stirred slurry of 60% sodium hydride (2.0 g, 50 mmol) in THF (50 mL) at room temperature under N2. After all of the sodium hydride has reacted, a solution of ethyl iodide (4 mL, 50 mmol) in THF (50 mL) is added and the reaction stirred at 20°-25° C. for 18 hours. THF is removed under reduced pressure and the residue partitioned between diethylether and brine. The ether extract is dried (Na2SO4), filtered and concentrated under reduced pressure. Flash chromatograp
Reaction SMILES: [C:1]([Li])#[C:2][CH3:3].FC(F)(F)S(O[Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])(=O)=O>CCOCC>[CH3:13][CH:12]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[C:1]#[C:2][CH3:3])[CH3:14]
Reactant: [Li]C#CC
Reactant: CC(C)[Si](OS(=O)(=O)C(F)(F)F)(C(C)C)C(C)C
Solvent: CCOCC
Product: CC#C[Si](C(C)C)(C(C)C)C(C)C
Temperature: 25 °C
Yield: 83.9 %

Procedure:
1-Propynyllithium (7.18 g, 156 mmol) was stirred in 160 mL of anhydrous ether at -40° C. under nitrogen and treated dropwise with triisopropylsilyl trifluoromethanesulfonate (47.8 g, 41.93 mL, 156 mmol). The reaction was warmed to room temperature, washed with 2×100 mL of water and 1×100 mL of brine. The organic phase was dried over MgSO4 and concentrated in vacuo. Flash chromatography (95 mm column, petroleum ether eluent, 51/2 inches of silica gel) afforded 25.7 g (84%) of product as a colorless oil.
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][C:5]2[CH:8]=[N:9][N:10]([C:11]3[N:16]=[C:15]([N:17]4[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]4)[CH:14]=[CH:13][CH:12]=3)[C:4]=2[CH:3]=1.C([Sn](CCCC)(CCCC)[C:35]1[S:39][N:38]=[C:37]([CH3:40])[CH:36]=1)CCC>CN(C)C(=O)C>[CH3:40][C:37]1[CH:36]=[C:35]([C:2]2[N:7]=[CH:6][C:5]3[CH:8]=[N:9][N:10]([C:11]4[N:16]=[C:15]([N:17]5[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:27])[CH3:28])=[O:24])[CH2:19][CH2:18]5)[CH:14]=[CH:13][CH:12]=4)[C:4]=3[CH:3]=2)[S:39][N:38]=1
Reactant: CC(C)(C)OC(=O)N1CCN(c2cccc(-n3ncc4cnc(Cl)cc43)n2)CC1
Reactant: CCCC[Sn](CCCC)(CCCC)c1cc(C)ns1
Solvent: CC(=O)N(C)C
Product: Cc1cc(-c2cc3c(cn2)cnn3-c2cccc(N3CCN(C(=O)OC(C)(C)C)CC3)n2)sn1
Temperature: 150 °C
Yield: 46.9 %

Procedure:
A solution of tert-butyl 4-[6-(6-chloropyrazolo[4,3-c]pyridin-1-yl)-2-pyridyl]piperazine-1-carboxylate (120 mg, 0.290 mmol) and palladium(0)tetrakis(triphenylphosphine) (34 mg, 0.0290 mmol) in N,N-dimethylacetamide 1.0 mL was added tributyl-(3-methylisothiazol-5-yl)stannane (224 mg, 0.579 mmol). The reaction mixture heated at 150° C. for 45 min in a microwave (Biotage Inc.). The reaction mixture was filtered through celite and concentrated. The crude product was diluted with EtOAc then washed with water. The organic layers was dried with sodium sulfate, filtered, and concentrated in vacuum. The crude product was purified by flash chromatography (EtOAc/Heptane eluted at 20% EtOAc) to give tert-butyl 4-[6-[6-(3-methylisothiazol-5-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]piperazine-1-carboxylate (65 mg) 47% yield:
Reaction SMILES: [CH:1]([C:3]1[CH:18]=[CH:17][C:6]([O:7][C:8]2[N:9]=[CH:10][C:11]([C:14]([NH2:16])=[O:15])=[N:12][CH:13]=2)=[C:5]([O:19][CH3:20])[CH:4]=1)=O.[CH:21]([O:24][CH2:25][CH2:26][NH2:27])([CH3:23])[CH3:22].[BH4-].[Na+]>CO>[CH:21]([O:24][CH2:25][CH2:26][NH:27][CH2:1][C:3]1[CH:18]=[CH:17][C:6]([O:7][C:8]2[N:9]=[CH:10][C:11]([C:14]([NH2:16])=[O:15])=[N:12][CH:13]=2)=[C:5]([O:19][CH3:20])[CH:4]=1)([CH3:23])[CH3:22]
Reactant: COc1cc(C=O)ccc1Oc1cnc(C(N)=O)cn1
Reactant: CC(C)OCCN
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: COc1cc(CNCCOC(C)C)ccc1Oc1cnc(C(N)=O)cn1
Reaction time: 8 h
Yield: 55.5 %

Procedure:
Place 5-(4-formyl-2-methoxyphenoxy)pyrazine-2-carboxamide (Example 719, Part A) (0.700 g, 2.56 mmol), 2-isopropoxyethylamine (0.278 g, 2.69 mmol) and 3 {acute over (Å)} molecular sieves in a vial. Add methanol (12.8 mL), cap and stir overnight. Add NaBH4 (0.0969 g, 2.56 mmol) and stir until the gasses stop evolving. Load the reaction mixture directly onto a 25 g ISCO® pre-load column. Dry the column in a vacuum oven at room temperature. Purify by eluting through a 40 g ISCO® column with 5% to 20% (2.0 M NH3 in methanol) in ethyl acetate over 45 minutes. Concentrate the fraction containing the product, then take it up in EtOAc (100 mL). Wash the organic solution with 1.0 N NaOH (2×25 mL), dry it over Na2SO4, filter and concentrate to give the title compound (0.512 g, 55.5%): TOF MS ES+ 361.2 (M+H)+, HRMS calcd for C18H25N4O4 361.1876 (M+H)+, found 361.1891, time 0.38 min; HPLC [YMC-Pro pack C-18 (150×4.6 mm, S-5 microm), 0.05% TFA/acetonitrile in 0.05% TFA/water at 1.0 mL/min, 10-20% over 5 min, 20-95% over 18], tR=9.4 min, 100% purity.
Reaction SMILES: [C:1]([NH:11][CH2:12][C:13]([OH:15])=O)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].[C:16]([O:20][C:21](=[O:24])[CH2:22][NH2:23])([CH3:19])([CH3:18])[CH3:17].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C>C(#N)C>[C:16]([O:20][C:21](=[O:24])[CH2:22][NH:23][C:13](=[O:15])[CH2:12][NH:11][C:1]([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2])([CH3:19])([CH3:18])[CH3:17]
Reactant: O=C(O)CNC(=O)OCc1ccccc1
Reactant: CC(C)(C)OC(=O)CN
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)CNC(=O)CNC(=O)OCc1ccccc1
Yield: 77.6 %

Procedure:
N-Carbobenzyloxy-glycine (2.1 g, 10 mmol) and glycine-tert-butyl ester (1.3 g, 10 mmol) were coupled using benzotriazol-1-yloxytris(dimethylamino) phosphonium hexafluorophosphate (4.4 g, 10 mmol) and triethylamine (1.5 g, 15 mmol) in acetonitrile following the method described in Example 23 to give 2.5 g(79%) of N-carbobenzyloxy-glycylglycine-tert-butyl ester after chromatography on silica gel.
Reaction SMILES: [CH3:1][C:2]1([C:9]2[CH:10]=[C:11]([CH:15]=[CH:16][CH:17]=2)[C:12]([OH:14])=O)[CH2:7][O:6][CH2:5][C:4](=[O:8])[NH:3]1.[NH2:18][C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:20]=1O.[OH-].[Na+]>O>[Cl:25][C:22]1[CH:23]=[CH:24][C:19]2[N:18]=[C:12]([C:11]3[CH:10]=[C:9]([C:2]4([CH3:1])[NH:3][C:4](=[O:8])[CH2:5][O:6][CH2:7]4)[CH:17]=[CH:16][CH:15]=3)[O:14][C:20]=2[CH:21]=1
Reactant: CC1(c2cccc(C(=O)O)c2)COCC(=O)N1
Reactant: Nc1ccc(Cl)cc1O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CC1(c2cccc(-c3nc4ccc(Cl)cc4o3)c2)COCC(=O)N1
Temperature: 130 °C
Reaction time: 3 h
Yield: 83.8 %

Procedure:
A mixture of 3-((RS)-3-methyl-5-oxo-morpholin-3-yl)-benzoic acid (intermediate XXVI-1) (250 mg, 1.1 mmol) and 2-amino-5-chloro-phenol (230 mg, 1.6 mmol) in polyphosphoric acid (1 g) was heated under stirring at 130° C. for 3 hours. For the workup, the reaction mixture was cooled and water was added. The mixture was neutralized with an aqueous solution of sodium hydroxide (10%), then extracted with dichloromethane. The organic layer was dried over sodium sulphate and evaporated to yield the (RS)-5-[3-(6-chloro-benzooxazol-2-yl)-phenyl]-5-methyl-morpholin-3-one (316 mg, 87% of theory) in a quality suited to be engaged in the next step without further purification. MS (ISP): m/z=343 [M+H]+.
Reaction SMILES: [CH:1]1([CH2:4][N:5]2[C:10](=[O:11])[C:9]([CH2:12][OH:13])=[CH:8][C:7]([C:14]3[CH:15]=[CH:16][C:17]4[O:21][CH2:20][CH2:19][C:18]=4[CH:22]=3)=[N:6]2)[CH2:3][CH2:2]1.C(N(CC)CC)C.[CH3:30][S:31](Cl)(=[O:33])=[O:32].C(=O)([O-])O.[Na+]>C(Cl)Cl>[CH:1]1([CH2:4][N:5]2[C:10](=[O:11])[C:9]([CH2:12][O:13][S:31]([CH3:30])(=[O:33])=[O:32])=[CH:8][C:7]([C:14]3[CH:15]=[CH:16][C:17]4[O:21][CH2:20][CH2:19][C:18]=4[CH:22]=3)=[N:6]2)[CH2:3][CH2:2]1
Reactant: O=c1c(CO)cc(-c2ccc3c(c2)CCO3)nn1CC1CC1
Reactant: CS(=O)(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)OCc1cc(-c2ccc3c(c2)CCO3)nn(CC2CC2)c1=O
Reaction time: 1 h

Procedure:
2-Cyclopropylmethyl-6-(2,3-dihydro-1-benzofuran-5-yl)-4-hydroxymethyl-2H-pyridazin-3-one (540 mg, 1.81 mmol) was dissolved in methylene chloride (12 mL), and triethylamine (238 mg, 2.35 mmol) and methanesulfonyl chloride (249 mg, 2.17 mmol) were added to the solution under cooling with ice, followed by stirring for one hour. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction mixture, and the resultant mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate anhydrate. The solvent was removed under reduced pressure, and the residue was recrystallized from chloroform-hexane, to thereby yield 607 mg of the title compound as a pale yellow crystalline powder (89.1%).
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C@@H:10]([NH2:14])[CH2:11][O:12][CH3:13])[N:7]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=3)[C:6]=2[CH:21]=1.[NH2:22][C:23]1[C:28]([C:29]#[N:30])=[C:27](Cl)[N:26]=[CH:25][N:24]=1.CCN(C(C)C)C(C)C>CC(O)C>[NH2:22][C:23]1[C:28]([C:29]#[N:30])=[C:27]([NH:14][C@H:10]([C:8]2[N:7]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=3)[C:6]3[CH:21]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=3[N:9]=2)[CH2:11][O:12][CH3:13])[N:26]=[CH:25][N:24]=1
Reactant: N#Cc1c(N)ncnc1Cl
Reactant: COC[C@H](N)c1nc2ccc(F)cc2n1-c1ccccn1
Solvent: CC(C)O
Solvent: CCN(C(C)C)C(C)C
Product: COC[C@H](Nc1ncnc(N)c1C#N)c1nc2ccc(F)cc2n1-c1ccccn1
Temperature: 90 °C
Yield: 80.4 %

Procedure:
A mixture of (R)-1-(6-fluoro-1-pyridin-2-yl-1H-benzoimidazol-2-yl)-2-methoxyethylamine (69 mg, 0.24 mmol), 4-amino-6-chloropyrimidine-5-carbonitrile (37 mg, 0.24 mmol) and DIPEA (0.21 mL, 1.2 mmol) in IPA (1 mL) was heated for 16 h at 90° C. After cooling to RT, the volatiles were removed under reduced pressure and the resulting residue was loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH followed by 2M NH3/MeOH. The basic fractions were combined, concentrated in vacuo and the resulting residue purified by column chromatography (Si—PCC, gradient 0-20% DCM in EtOAc) to afford 271 as a yellow solid (78 mg, 80%). LCMS (Method K): RT 3.52 min [M+H]+ 405.0. 1H NMR (DMSO-d6, 400 MHz): δ 8.68-8.64 (1H, m), 8.11 (1H, td, J=7.76, 1.94 Hz), 7.84 (1H, s), 7.79-7.73 (2H, m), 7.66 (1H, d, J=7.94 Hz), 7.56 (1H, ddd, J=7.52, 4.87, 0.98 Hz), 7.30-7.13 (4H, m), 6.03-5.95 (1H, m), 3.83 (2H, d, J=6.59 Hz), 3.19 (3H, s)
Reaction SMILES: C(#N)C.[Cl:4][C:5]1[CH:10]=[C:9]([Cl:11])[C:8]([OH:12])=[CH:7][C:6]=1[N:13]1[C:17](=[O:18])[C:16](=[C:19]([CH2:21][CH3:22])[CH3:20])[O:15][C:14]1=[O:23].C(=O)([O-])[O-].[K+].[K+].Br[CH:31]([CH3:37])[C:32]([O:34][CH2:35][CH3:36])=[O:33]>CCOCC>[Cl:4][C:5]1[CH:10]=[C:9]([Cl:11])[C:8]([O:12][CH:31]([C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH3:37])=[CH:7][C:6]=1[N:13]1[C:17](=[O:18])[C:16](=[C:19]([CH2:21][CH3:22])[CH3:20])[O:15][C:14]1=[O:23]
Reactant: CCC(C)=C1OC(=O)N(c2cc(O)c(Cl)cc2Cl)C1=O
Reactant: CCOC(=O)C(C)Br
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOCC
Solvent: CC#N
Product: CCOC(=O)C(C)Oc1cc(N2C(=O)OC(=C(C)CC)C2=O)c(Cl)cc1Cl
Yield: 73 %

Procedure:
To an acetonitrile solution (30 ml) of a mixture of 3-(2',4'-dichloro-5'-hydroxyphenyl)-5-(sec-butylidene)-1,3-oxazolidine-2,4-dione (1.58 g, 5 mmol) was added potassium carbonate (0.69 g), and the mixture was heated at reflux for 2 hours. After the addition of ethyl 2-bromopropionate (0.93 g, 5.1 mmol), the reaction mixture was further refluxed for 1 hour. Ether was added to the reaction mixture and the solution was washed with 1N hydrochloric acid and extracted with ether. The ethereal extracts combined were dried and then evaporated as small a volume as possible. The resulting residue was purified by silica gel column chromatography to give 3-{2',4'-dichloro-5'-(1"-ethoxycarbonylethyloxy)phenyl}-5-(sec-butylidene)-1,3-oxazolidine-2,4-dione. (1.51 g, 73% yield)
Reaction SMILES: [BH4-].[Na+].O1CCCC1.[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:16]=[C:17]([N:27]3[CH:31]=[CH:30][N:29]=[C:28]3[CH3:32])[O:18][C:19]=2[C:20](=[O:26])[C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:11][CH:10]=1>CC(O)C>[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[N:16]=[C:17]([N:27]3[CH:31]=[CH:30][N:29]=[C:28]3[CH3:32])[O:18][C:19]=2[CH:20]([OH:26])[C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:13][CH:14]=1
Reactant: CCOC(=O)C(=O)c1oc(-n2ccnc2C)nc1-c1ccc(Cl)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(C)O
Solvent: C1CCOC1
Product: CCOC(=O)C(O)c1oc(-n2ccnc2C)nc1-c1ccc(Cl)cc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 74.7 %

Procedure:
Sodium borohydride(95 mg) was added to a tetrahydrofuran(60 ml)-2-propanol(30 ml) solution of ethyl 2-(4-(4-chlorophenyl)-2-(2-methyl-1-imidazolyl)-5-oxazolyl]-2-oxoacetate(2.93 g) at 0° C. After stirring for 30 minutes, the reaction mixture was poured into ice water, and extracted with ethyl acetate. The ethyl acetate layer was washed with water, and dried(MgSO4). The solvent was evaporated to give ethyl 2-[4-(4-chlorophenyl)-2-(2-methyl-1-imidazolyl)-5-oxazolyl]-2-hydroxyacetate(2.20 g, 75%). This was recrystallized from acetone-ethyl acetate to give colorless prisms. mp 197-198° C. (degradation)
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4](Cl)[N:3]=1.[NH:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1>>[O:12]1[CH2:13][CH2:14][N:9]([C:4]2[N:3]=[C:2]([NH2:1])[CH:7]=[CH:6][CH:5]=2)[CH2:10][CH2:11]1
Reactant: Nc1cccc(Cl)n1
Reactant: C1COCCN1
Product: Nc1cccc(N2CCOCC2)n1
Temperature: 225 °C

Procedure:
A mixture of 2-amino-6-chloropyridine in 100 mL of morpholine was heated at 225° C. for 60 mins. The mixture was cooled and precipitate filtered off, the filtrate was concentrated to give the 17 gram product as a brown oil.
Reaction SMILES: C([Mg]Br)C.I[C:6]1[N:7]=[CH:8][N:9]([C:11]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:10]=1.[N+:30]([C:33]1[CH:34]=[C:35]([CH2:39][CH:40]=[O:41])[CH:36]=[CH:37][CH:38]=1)([O-:32])=[O:31]>ClCCl>[N+:30]([C:33]1[CH:34]=[C:35]([CH2:39][CH:40]([C:6]2[N:7]=[CH:8][N:9]([C:11]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH:10]=2)[OH:41])[CH:36]=[CH:37][CH:38]=1)([O-:32])=[O:31]
Reactant: O=CCc1cccc([N+](=O)[O-])c1
Reactant: Ic1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
Agent: CC[Mg]Br
Solvent: ClCCl
Product: O=[N+]([O-])c1cccc(CC(O)c2cn(C(c3ccccc3)(c3ccccc3)c3ccccc3)cn2)c1
Reaction time: 1 h

Procedure:
At ambient temperature, 4.2 ml of 3M ethylmagnesium bromide are poured into 5.48 g of 4-iodo-1-trityl-1H-imidazole dissolved in 30 ml of dichloromethane. After 1 hour, 1 g of the product obtained in Step 1 is dissolved in 20 ml of dichloromethane. After hydrolysis with a saturated solution of ammonium chloride, extraction with dichloromethane, and then washing the organic phase with water, the solvent is evaporated off and the residue is purified by chromatography on silica gel, using as eluant a 98/2 dichloromethane/methanol mixture.
Reaction SMILES: C([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]2[CH2:18][CH2:19][N:20]1[CH2:25][CH2:24][C:23]([OH:32])([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:22][CH2:21]1)C1C=CC=CC=1>[Pd].C(O)C>[OH:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]2[CH2:18][CH2:19][N:20]1[CH2:21][CH2:22][C:23]([OH:32])([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH2:24][CH2:25]1
Reactant: OC1(c2ccccc2)CCN(CCc2c[nH]c3ccc(OCc4ccccc4)cc23)CC1
Agent: [Pd]
Solvent: CCO
Product: Oc1ccc2[nH]cc(CCN3CCC(O)(c4ccccc4)CC3)c2c1

Procedure:
A solution of 10 g. of 5-benzyloxy-3-[2-(4-hydroxy-4-phenylpiperidinyl)ethyl]indole in 10 ml. of ethanol was shaken on the Parr apparatus at room temperature at an initial pressure of 50 p.s.i., using a 10% palladium on charcoal catalyst. After debenzylation was complete the solution was filtered and the catalyst washed thoroughly with three 100 ml. portions of hot ethanol. Concentration of the original filtrate gave 3 g. of an oil which solidified and was recrystallized from ethyl acetate-methanol to give 1.85 g. of material which melted at 150° C., resolidified and melted again at 235°-240° C. The combined alcohol washes on concentration gave 4 g. of a white solid which after recrystallization from ethyl acetate-methanol gave 3.4 g. of material which melted at 150° C., recrystallized and melted again at 235°-240° C. A nuclear magnetic resonance spectrum indicated the above solids to be solvated with methanol. A sample was dried in vacuo at 110° for 24 hours; the dried sample melted at 238°-240° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][CH:12]=[C:13]2[C:18](=[O:19])OC(C)(C)OC2=O)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.CCCCCC>C1(OC2C=CC=CC=2)C=CC=CC=1>[CH3:10][O:9][C:7]1[CH:8]=[C:3]([O:2][CH3:1])[CH:4]=[C:5]2[C:6]=1[C:18]([OH:19])=[CH:13][CH:12]=[N:11]2
Reactant: COc1cc(NC=C2C(=O)OC(C)(C)OC2=O)cc(OC)c1
Solvent: c1ccc(Oc2ccccc2)cc1
Solvent: CCCCCC
Product: COc1cc(OC)c2c(O)ccnc2c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A solution of 5-((3,5-dimethoxyphenylamino)methylene)-2,2-dimethyl-1,3-dioxane-4,6-dione (9.23 g, 30.0 mmol) in diphenyl ether was heated at 200° C. for 20 min., then cooled down to RT. Hexane was added and the mixture was stirred at RT for 30 mins. The solvent was removed to furnish 5,7-dimethoxyquinolin-4-ol as a light brown solid, which was used for next step without further purification. MS Found m/z=[M+H]+. 206.2 Calc'd for C11H11NO3: 205.2.