Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][C:6]([NH:10][CH:11]3[CH2:16][CH2:15][C:14](=O)[CH2:13][CH2:12]3)=[CH:7][CH:8]=2)[CH:3]=[N:2]1.[NH2:18][CH:19]([C:21]([CH3:24])([CH3:23])[CH3:22])[CH3:20].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl.CO>CO>[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([NH:10][CH:11]3[CH2:16][CH2:15][CH:14]([NH:18][CH:19]([CH3:20])[C:21]([CH3:24])([CH3:23])[CH3:22])[CH2:13][CH2:12]3)=[CH:7][CH:8]=2)[CH:3]=[N:2]1
Reactant: CC(N)C(C)(C)C
Reactant: O=C1CCC(Nc2ccc3[nH]ncc3c2)CC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: CC(NC1CCC(Nc2ccc3[nH]ncc3c2)CC1)C(C)(C)C
Temperature: 25 °C
Reaction time: 18 h
Yield: 10.2 %

Procedure:
4-(1H-5-Indazolylamino)-1-cyclohexanone (intermediate 3) (57 mg) and (2-amino-3,3-dimethylbutane (51 mg) were dissolved in methanol (1 ml), and sodium triacetoxyborohydride (105 mg) was added by portions to the solution at room temperature. The reaction mixture was stirred at room temperature for 18 hr. Hydrochloric acid-methanol was then added thereto, and the reaction mixture was stirred and was then concentrated. The residue was purified by HPLC [0.5% aqueous trifluoroacetic acid solution/acetonitrile]. A saturated aqueous sodium hydrogencarbonate solution (2 ml) was added to fractions containing respective compounds, followed by extraction with chloroform-propanol (3/1). The organic layers were dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure to give an anti-form compound (8 mg) and a syn-form compound (5 mg).
Reaction SMILES: [C:1]1([N:7]2[CH:12]=[C:11]([CH3:13])[CH:10]=[CH:9][C:8]2=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:24])=CC=1>C1(C)C=CC=CC=1>[C:1]1([N:7]2[CH:12]=[C:11]([CH3:13])[CH:10]=[CH:9][C:8]2=[S:24])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: Cc1ccc(=O)n(-c2ccccc2)c1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Solvent: Cc1ccccc1
Product: Cc1ccc(=S)n(-c2ccccc2)c1

Procedure:
1-phenyl-5-methyl-2-pyridinone (555.7 mg, 3 mmol) was reacted with Lawesson's reagent (606.7 mg, 1.5 mmol) in toluene (5 ml) at 90° C. Reaction mixture was evaporated and the target compound was isolated by column chromatography (20-30% ethyl acetate-hexane) followed by crystallization from methyl-tert-butyl ether. Yield 403 mg (67%), yellow solid. The 1H NMR spectra was consistent with the structure of Compound 18.
Reaction SMILES: [N:1]([C:4]1[C:19]([O:20]CC2C=CC=CC=2)=[CH:18][C:7]([C:8]([O:10]CC2C=CC=CC=2)=[O:9])=[C:6]([NH:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[Cl:35])[C:5]=1[F:36])=[N+]=[N-].[H][H]>CO.[Pd]>[NH2:1][C:4]1[C:19]([OH:20])=[CH:18][C:7]([C:8]([OH:10])=[O:9])=[C:6]([NH:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[Cl:35])[C:5]=1[F:36]
Reactant: [H][H]
Reactant: [N-]=[N+]=Nc1c(OCc2ccccc2)cc(C(=O)OCc2ccccc2)c(Nc2ccccc2Cl)c1F
Agent: [Pd]
Solvent: CO
Product: Nc1c(O)cc(C(=O)O)c(Nc2ccccc2Cl)c1F
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of compound benzyl 4-azido-5-(benzyloxy)-2-((2-chlorophenyl)amino)-3-fluorobenzoate (22.97 g, 45.67 mmol) in MeOH (500 mL) was added and 10% palladium on carbon (3.80 g) under nitrogen atmosphere. Then the nitrogen atmosphere was completely changed to hydrogen atmosphere. The mixture was stirred for 3 h at ambient temperature. After the insoluble matter was filtered off, the solvent was evaporated under reduced pressure to give the desired product, which was used directly in the next step without further purification.
Reaction SMILES: ON=[C:3]1[C:17]2[C:18]3[C:13]([CH:14]=[CH:15][N:16]=2)=[CH:12][CH:11]=[CH:10][C:9]=3[N:8]2[C:4]1=[CH:5][CH:6]=[CH:7]2.[OH-:19].[Na+]>C(O)C.O>[CH:10]1[C:9]2[N:8]3[C:4]([C:3](=[O:19])[C:17]4[C:18]=2[C:13]([CH:14]=[CH:15][N:16]=4)=[CH:12][CH:11]=1)=[CH:5][CH:6]=[CH:7]3
Reactant: [OH-]
Reactant: ON=c1c2nccc3cccc(c32)n2cccc12
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: O=c1c2nccc3cccc(c32)n2cccc12

Procedure:
The 7-Imino-7H-indolizino[5,6,7-ij]isoquinoline (110 g.) and N sodium hydroxide solution ( ##SPC14## cc.) in ethanol (4.4 liters) and water (4.4 liters) are heated under reflux for 4 hours. After cooling, 7H-indolizino[5,6,7-ij]isoquinolin-7-one (108.1 g.) is obtained in the form of yellow needles melting at 264° C.
Reaction SMILES: [H-].[Li+].[Cl:3][C:4]1[CH:5]=[C:6]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH:7]=[C:8]([Cl:10])[CH:9]=1.[Br:17][C:18]1[S:22][C:21]([C:23](=[O:25])[CH3:24])=[CH:20][C:19]=1[CH3:26].CC(OC)(C)C>C1COCC1>[Br:17][C:18]1[S:22][C:21]([C:23](=[O:25])[CH2:24][C:11]([C:6]2[CH:5]=[C:4]([Cl:3])[CH:9]=[C:8]([Cl:10])[CH:7]=2)([OH:16])[C:12]([F:13])([F:14])[F:15])=[CH:20][C:19]=1[CH3:26]
Reactant: CC(=O)c1cc(C)c(Br)s1
Reactant: O=C(c1cc(Cl)cc(Cl)c1)C(F)(F)F
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: COC(C)(C)C
Product: Cc1cc(C(=O)CC(O)(c2cc(Cl)cc(Cl)c2)C(F)(F)F)sc1Br
Reaction time: 2 h
Yield: 111.4 %

Procedure:
LiH (2.06 g) is added to a solution of 3′,5′-dichloro-2,2,2-trifluoroacetophenone (48.0 g) and 1-(5-bromo-4-methyl-thiophen-2-yl)-ethanone (30.3 g) in THF (1000 ml). After 2 hours at 60° C. MTBE is added (300 ml) and the reaction mixture is poured onto water (500 ml) at 0° C. The organic phase is extracted with water and a saturated aqueous solution of NaCl, dried over Na2SO4 and concentrated in vacuo to yield 71.2 g of 1-(5-bromo-4-methyl-thiophen-2-yl)-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-3-hydroxy-butan-1-one. The crude product is used without further purification.
Reaction SMILES: [CH2:1]1[C:13]2[C:12]3[CH:11]=[C:10]([C:14]([O:16][CH3:17])=[O:15])[CH:9]=[CH:8][C:7]=3[NH:6][C:5]=2[CH2:4][CH2:3][N:2]1[C:18](OC(C)(C)C)=O.C(=O)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(O)(C(F)(F)F)=O>[CH2:18]([N:2]1[CH2:3][CH2:4][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([C:14]([O:16][CH3:17])=[O:15])=[CH:11][C:12]=3[C:13]=2[CH2:1]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: COC(=O)c1ccc2[nH]c3c(c2c1)CN(C(=O)OC(C)(C)C)CC3
Reactant: O=Cc1ccccc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COC(=O)c1ccc2[nH]c3c(c2c1)CN(Cc1ccccc1)CC3
Temperature: 25 °C
Reaction time: 1 h
Yield: 66.6 %

Procedure:
To a solution of 2-tert-butyl 8-methyl 3,4-dihydro-1H-pyrido[4,3-b]indole-2,8(5H)-dicarboxylate (0.50 g, 1.5 mmol) in DCM (5.0 mL), TFA (5.0 mL) was added. After allowing the reaction mixture to stir at room temperature for 1 h, the volatiles were evaporated, DCM and toluene (20 mL) were added and the volatiles evaporated (2×). The resulting residue was dissolved in THF/MeOH (4:1, 10 mL) and benzaldehyde (0.17 mL, 0.18 g, 1.7 mmol) and sodium triacetoxyborohydride (0.485 g, 2.3 mmol) were added. The reaction mixture was allowed to stir at room temperature overnight and 4 more equivalents of the aldehyde and reducing agent were added to cause the reaction to go to completion. The reaction mixture was then poured into saturated sodium bicarbonate solution (300 mL). The layers were separated, and the aqueous layer was extracted with DCM (3×100 mL). The combined organic layers were washed with brine (2×50 mL), dried (MgSO4), filtered and concentrated to give a foamy residue. Column chromatography (DCM→3% MeOH/DCM) provided methyl 2-benzyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxylate (12a in Scheme 1(h)) as a white solid (0.32 g, 66%). 1H NMR (CD3OD, 300 MHz) 8.17 (d, J=1.1 Hz, 1H), 7.73 (dd, J=8.7, 1.8 Hz, 1H), 7.44-7.27 (m, 6H), 3.88 (s, 3H), 3.83 (s, 2H), 3.73 (s, 2H), 2.95-2.88 (m, 4H) ppm; MS (ES) 321 (M+H).
Reaction SMILES: Br[C:2]1[N:3]=[C:4]([N:14]2[C:22]3[C:17](=[CH:18][C:19]([Cl:24])=[CH:20][C:21]=3[Cl:23])[CH2:16][CH2:15]2)[C:5](=[O:13])[N:6]([CH:8]([CH2:11][CH3:12])[CH2:9][CH3:10])[CH:7]=1.[CH3:25][N:26](C)C=O>O.[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:24][C:19]1[CH:18]=[C:17]2[C:22](=[C:21]([Cl:23])[CH:20]=1)[N:14]([C:4]1[C:5](=[O:13])[N:6]([CH:8]([CH2:11][CH3:12])[CH2:9][CH3:10])[CH:7]=[C:2]([C:25]#[N:26])[N:3]=1)[CH2:15][CH2:16]2
Reactant: CN(C)C=O
Reactant: CCC(CC)n1cc(Br)nc(N2CCc3cc(Cl)cc(Cl)c32)c1=O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [C-]#N
Agent: [Zn+2]
Solvent: O
Product: CCC(CC)n1cc(C#N)nc(N2CCc3cc(Cl)cc(Cl)c32)c1=O
Temperature: 175 °C
Yield: 21 %

Procedure:
A solution of 5-bromo-3-(5,7-dichloro-2,3-dihydro-1H-indol-1-yl)-1-(1-ethylpropyl)-2(1H)-pyrazinone (Example 507) (100 mg, 0.23 mmol), zinc cyanide (32 mg, 0.28 mmol), and tetrakis(triphenylphosphine)palladium(0) (32 mg, 25 μmol) in dimethylforamide (3 ml) was degassed with nitrogen and heated to 175° C. in a microwave for 5 min. The reaction mixture was diluted with water (5 mL) and extracted with ethyl acetate (5 mL×2). The combined organic extracts were dried (MgSO4), filtered, and concentrated in vacuo to give a crude residue. Purification by HPLC (reverse phase C18, 95% water in acetonitrile containing 0.1% trifluroacetic acid to 5% water in acetonitrile containing 0.1% trifluroacetic acid, flow rate 18 ml/min, retention time 38.4 min) gave the product (18 mg, 21%) as a yellow solid. mp 197–199° C.; 1H NMR (300 MHz, CDCl3): δ 7.27 (s, 1 H), 7.19 (d, J=2.2 Hz, 1 H), 7.14 (d, J=1.8 Hz, 1 H), 4.82–4.77 (m, 1 H), 4.33 (t, J=7.9 Hz, 2 H), 3.15 (t, J=7.7 Hz, 2 H), 1.92–1.78 (m, 2 H), 1.75–1.60 (m, 2 H), 0.89 (t, J=7.3 Hz, 6 H); HRMS (ESI) calcd for C18H19N4OCl2 (M+H)+: 377.0936; Found m/z 377.0910.
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].C([O:9][C:10](=[O:42])[C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([CH2:17][CH:18]([NH:32][C:33]([C:35]2[O:39][CH:38]=[N:37][CH:36]=2)=[O:34])[B:19]2[O:27]C3C(C)(C4CC(C3)C4(C)C)[O:20]2)[C:12]=1OC)(C)(C)C>C(Cl)Cl>[OH:20][B:19]1[C@@H:18]([NH:32][C:33]([C:35]2[O:39][CH:38]=[N:37][CH:36]=2)=[O:34])[CH2:17][C:13]2[CH:14]=[CH:15][CH:16]=[C:11]([C:10]([OH:9])=[O:42])[C:12]=2[O:27]1
Reactant: COc1c(CC(NC(=O)c2cnco2)B2OC3CC4CC(C4(C)C)C3(C)O2)cccc1C(=O)OC(C)(C)C
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: O=C(N[C@H]1Cc2cccc(C(=O)O)c2OB1O)c1cnco1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
Aluminum chloride (0.132 g, 0.990 mmol) was added to a solution of 2-Methoxy-3-[2-[(oxazole-5-carbonyl)-amino]-2-(2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]dec-4-yl)-ethyl]-benzoic acid tert-butyl ester (0.064 g, 0.122 mmol) in CH2Cl2 (3.0 mL). The reaction was stirred at room temperature for 16 hr. The reaction was quenched with H2O and CH3OH and extracted with hexane (2×). The crude product remained in the aqueous layer and was purified by reverse phase preparative HPLC and dried using lyophilization. ESI-MS m/z 303 (MH)+.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([C:20]#[N:21])=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:22][Mg]Br.[Cl-].[NH4+]>O1CCCC1>[NH2:21][CH:20]([C:17]1[CH:18]=[CH:19][C:14]([N:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10]2)=[N:15][CH:16]=1)[CH3:22]
Reactant: C[Mg]Br
Reactant: CC(C)(C)OC(=O)N1CCN(c2ccc(C#N)cn2)CC1
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CC(N)c1ccc(N2CCN(C(=O)OC(C)(C)C)CC2)nc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
900 mg of the t-butyl-4-(5-cyanopyridin-2-yl)piperazin-1-carboxylate [140-1] was dissolved in 40 mL of tetrahydrofuran, then 2.5 mL of methylmagnesium bromide (3.0M diethyl ether solution) was added under an ice-cold condition, and stirred at the same temperature for 1 hour. Thereafter, the temperature was increased back to room temperature and stirred overnight. Thereto, a saturated aqueous solution of ammonium chloride was added under an ice-cold condition, and extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The insolubles were filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was dissolved in 50 mL of methanol, then 850 mg of sodium boronhydride was added under an ice-cold condition, and the mixture was stirred at the same temperature for 2 hours and a half. The reaction mixture was added with water, and extracted with chloroform. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the insolubles were filtered. The filtrate was concentrated under reduced pressure, and the thus obtained residue was purified by silica gel column chromatography, to obtain 950 mg of t-butyl 4-[5-(1-aminoethyl)pyridin-2-yl]piperazin-1-carboxylate [140-2] as a white solid.
Reaction SMILES: Cl.[SH:2][CH:3]([CH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]2[N:20]([CH3:21])[C:19]3[CH:22]=[C:23]([O:26][CH3:27])[CH:24]=[CH:25][C:18]=3[N:17]=2)=[CH:10][CH:9]=1)[C:4]([OH:6])=[O:5].N1C=CC=CC=1.[O:34]1CC[CH2:36][CH2:35]1.C(OC(=O)C)(=O)C>CN(C)C=O>[C:35]([S:2][CH:3]([CH2:7][C:8]1[CH:9]=[CH:10][C:11]([O:14][CH2:15][C:16]2[N:20]([CH3:21])[C:19]3[CH:22]=[C:23]([O:26][CH3:27])[CH:24]=[CH:25][C:18]=3[N:17]=2)=[CH:12][CH:13]=1)[C:4]([OH:6])=[O:5])(=[O:34])[CH3:36]
Reactant: COc1ccc2nc(COc3ccc(CC(S)C(=O)O)cc3)n(C)c2c1
Reactant: C1CCOC1
Agent: Cl
Solvent: CN(C)C=O
Solvent: c1ccncc1
Solvent: CC(=O)OC(C)=O
Product: COc1ccc2nc(COc3ccc(CC(SC(C)=O)C(=O)O)cc3)n(C)c2c1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
To a mixture of 2-mercapto-3-[4-(6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy)phenyl]propionic acid hydrochloride (1.5 g), pyridine (0.87 g), tetrahydrofuran (30 ml) and N,N-dimethylformamide (30 ml) was added acetic anhydride (0.56 g). The mixture was stirred at room temperature for 5 hours and allowed to stand for 36 hours and then concentrated. The residual insoluble material was collected by filtration and washed with ethyl acetate to afford the title compound (1.55 g, mp 209-214° C., pale yellow powder).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[CH:4][C:3]=1[C:9]1[S:10][CH:11]=[C:12](C)[N:13]=1.NC1C=CC(N)=CC=1C1SC(C)=CN=1.NC1C=CC(N)=CC=1C1SC=C(Cl)N=1.NC1C=CC(N)=CC=1C1SC(Cl)=CN=1.NC1C=CC(N)=CC=1C1SC([N+]([O-])=O)=CN=1.NC1C=CC(N)=CC=1C1SC(C)=C(C)N=1.NC1C=CC(N)=CC=1C1SC(CCO)=C(C)N=1.NC1C=CC(N)=CC=1C1SC=C(C2C=CC=CC=2)N=1.NC1C=CC(N)=CC=1C1SC(C2C=CC=CC=2)=CN=1.NC1C=CC(NC)=CC=1C1SC=CN=1.NC1C=CC(NCCO)=CC=1C1SC=CN=1.NC1C=CC(N(CCO)CCO)=CC=1C1SC=CN=1>>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[CH:4][C:3]=1[C:9]1[S:10][CH:11]=[CH:12][N:13]=1
Reactant: Cc1csc(-c2cc(N)ccc2N)n1
Agent: CNc1ccc(N)c(-c2nccs2)c1
Agent: Cc1cnc(-c2cc(N)ccc2N)s1
Agent: Cc1nc(-c2cc(N)ccc2N)sc1C
Product: Nc1ccc(N)c(-c2nccs2)c1

Procedure:
1,4-diamino-2-(4-methylthiazol-2-yl)benzene; 1,4-diamino-2-(5-methylthiazol-2-yl)benzene; 1,4-diamino-2-(4-chlorothiazol-2-yl)-benzene; 1,4-diamino-2-(5-chlorothiazol-2-yl)benzene; 1,4-diamino-2-(5-nitrothiazol-2-yl)benzene; 1,4-diamino-2-(4,5-dimethylthiazol-2-yl)benzene; 1,4-diamino-2-[4-methyl-5-(2-hydroxyethyl)thiazol-2-yl]benzene; 1,4-diamino-2-(4-phenylthiazol-2-yl)-benzene; 1,4-diamino-2-(5-nitrothiazol-2-yl)benzene; 1,4-diamino-2-(5-phenylthiazol-2-yl)benzene; 1-amino-4-methylamino-2-(thiazol-2-yl)benzene; 1-amino-4-(2-hydroxyethyl)amino-2-(thiazol-2-yl)benzene and 1-amino-4-bis(2-hydroxyethyl)amino-2-(thiazol-2-yl)benzene.
Reaction SMILES: I[CH2:2][C:3]1([CH3:20])[O:18][C:6]2=[C:7]3[C:12](=[C:13]([CH3:15])[CH:14]=[C:5]2[CH:4]1[CH3:19])[NH:11][C:10](=[O:16])[C:9]([CH3:17])=[CH:8]3.[N-:21]=[N+:22]=[N-:23].[Na+]>CN(C)C=O>[N:21]([CH2:2][C:3]1([CH3:20])[O:18][C:6]2=[C:7]3[C:12](=[C:13]([CH3:15])[CH:14]=[C:5]2[CH:4]1[CH3:19])[NH:11][C:10](=[O:16])[C:9]([CH3:17])=[CH:8]3)=[N+:22]=[N-:23]
Reactant: [N-]=[N+]=[N-]
Reactant: Cc1cc2c3c(cc(C)c2[nH]c1=O)C(C)C(C)(CI)O3
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1cc2c3c(cc(C)c2[nH]c1=O)C(C)C(C)(CN=[N+]=[N-])O3
Temperature: 150 °C
Reaction time: 3 h
Yield: 82.9 %

Procedure:
To a mixture of 2-iodomethyl-2,3,5,8-tetramethyl-2,3,6,7-tetrahydrofuro[2,3-f]quinoline-7-one (1.75 g, 4.57 mmol) and sodium azide (3.5 g, 53.8 mmol), dimethylformamide (24 ml) was added, and the mixture was stirred for 3 hours in a bath at 150° C. After cooling, post-treatment and recrystallization (chloroform-n-hexane) were performed in a manner similar to that described in Example 278 to obtain 1.13 g of the title compound as pale yellow crystals (83.0%).
Reaction SMILES: [CH3:1][N:2]1[C:6]([CH:7]=[N:8][O:9][CH2:10][CH2:11][OH:12])=[C:5]([CH3:13])[N:4]=[C:3]1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.O[C:21]1[CH:53]=[CH:52][C:24]([CH2:25][CH:26]2[S:30][C:29](=[O:31])[N:28]([C:32]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:27]2=[O:51])=[CH:23][CH:22]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>>[CH3:1][N:2]1[C:6]([CH:7]=[N:8][O:9][CH2:10][CH2:11][O:12][C:21]2[CH:53]=[CH:52][C:24]([CH2:25][CH:26]3[S:30][C:29](=[O:31])[N:28]([C:32]([C:45]4[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=4)([C:39]4[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=4)[C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[C:27]3=[O:51])=[CH:23][CH:22]=2)=[C:5]([CH3:13])[N:4]=[C:3]1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: O=C1SC(Cc2ccc(O)cc2)C(=O)N1C(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: Cc1nc(-c2ccccc2)n(C)c1C=NOCCO
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: Cc1nc(-c2ccccc2)n(C)c1C=NOCCOc1ccc(CC2SC(=O)N(C(c3ccccc3)(c3ccccc3)c3ccccc3)C2=O)cc1
Yield: 73.4 %

Procedure:
Following a procedure similar to that described in Example 1(a), but using 420 mg of 2-(1,4-dimethyl-2-phenylimidazol-5-ylmethyleneaminooxy)ethanol (prepared as described in Preparation 24), 580 mg of 5-(4-hydroxy-benzyl)-3-tritylthiazolidine-2,4-dione, 425 mg of triphenylphosphine and 282 mg of diethyl azodicarboxylate, 646 mg of the title compound were obtained as a foam-like solid.
Reaction SMILES: C[C:2]1[C:3]([CH:8]2[CH:13](C)[CH2:12][CH2:11][CH:10]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=3)[N:9]2[CH2:21][CH:22]2[CH2:25][N:24](S(C3C=CC=CC=3[N+]([O-])=O)(=O)=O)[CH2:23]2)=[N:4][CH:5]=[CH:6][CH:7]=1.C1(S)C=CC=CC=1.C([O-])([O-])=O.[K+].[K+]>CC#N>[NH:24]1[CH2:23][CH:22]([CH2:21][N:9]2[CH:10]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=3)[CH2:11][CH2:12][CH2:13][CH:8]2[C:3]2[CH:2]=[CH:7][CH:6]=[CH:5][N:4]=2)[CH2:25]1
Reactant: Cc1cccnc1C1C(C)CCC(c2ccccn2)N1CC1CN(S(=O)(=O)c2ccccc2[N+](=O)[O-])C1
Agent: O=C([O-])[O-]
Agent: Sc1ccccc1
Agent: [K+]
Solvent: CC#N
Product: c1ccc(C2CCCC(c3ccccn3)N2CC2CNC2)nc1
Temperature: 25 °C
Reaction time: 17 h
Yield: 74.5 %

Procedure:
A mixture of 3,3′-dimethyl-1′-[1-(2-nitro-benzenesulfonyl)-azetidin-3-ylmethyl]-1′,2′,3′4′,5′,6′-hexahydro-[2,2′;6′,2″]terpyridine (168 mg, 0.322 mmol), thiophenol (0.3 mL), K2CO3 (500 mg) in CH3CN (5 mL) were stirred at room temperature for 17 hours. The volatiles were removed under reduced pressure and saturated NaHCO3 (15 mL) was added and the mixture was extracted with CH2Cl2 (3×30 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated. The crude material was subjected to column chromatography on silica gel (10:1:0.1 CH2Cl2:CH3OH:NH4OH; then 10:1:0.5) to provide 1′-azetidin-3-ylmethyl-1′,2′,3′4′,5′,6′-hexahydro-[2,2′;6′,2″]terpyridine (74 mg, 80% pure by LC/MS).
Reaction SMILES: [Si]([O:18][CH2:19][C:20]1[N:25]=[CH:24][N:23]=[C:22]([CH:26]([CH:33]2[CH2:35][CH2:34]2)[CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH:21]=1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O>C1COCC1>[CH:33]1([CH:26]([C:22]2[CH:21]=[C:20]([CH2:19][OH:18])[N:25]=[CH:24][N:23]=2)[CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:34][CH2:35]1
Reactant: CCOC(=O)CC(c1cc(CO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)ncn1)C1CC1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: O
Product: CCOC(=O)CC(c1cc(CO)ncn1)C1CC1
Reaction time: 0.08 h
Yield: 71.1 %

Procedure:
To a solution of ethyl 3-(6-(((tert-butyldiphenylsilyl)oxy)methyl)pyrimidin-4-yl)-3-cyclopropylpropanoate (6.70 g) in THF (50 mL) was added a 1.0 M solution of tetrabutylammonium fluoride in THF (27.4 mL) at room temperature, and the mixture was directly stirred for 5 min. Water was added to the reaction mixture at room temperature, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (2.44 g) as a yellow oil.
Reaction SMILES: [CH2:1]([C:4]1[O:8][N:7]=[CH:6][C:5]=1[C:9](Cl)=[O:10])[CH2:2][CH3:3].[NH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1>>[CH2:1]([C:4]1[O:8][N:7]=[CH:6][C:5]=1[C:9]([N:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)=[O:10])[CH2:2][CH3:3]
Reactant: CCCc1oncc1C(=O)Cl
Reactant: C1CCNCC1
Product: CCCc1oncc1C(=O)N1CCCCC1

Procedure:
of boiling point (4 mbar) 84° to 92° C., prepared from 5-propyl-4-isoxazolecarboxylic acid chloride and piperidine.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][C:2]1=[O:10].[CH3:11][C:12]1[CH:16]=[C:15]([CH3:17])[NH:14][C:13]=1[CH:18]=O>N1CCCCC1.C(O)C>[CH3:17][C:15]1[NH:14][C:13]([CH:18]=[C:3]2[C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[NH:1][C:2]2=[O:10])=[C:12]([CH3:11])[CH:16]=1
Reactant: O=C1Cc2ccccc2N1
Reactant: Cc1cc(C)c(C=O)[nH]1
Solvent: C1CCNCC1
Solvent: CCO
Product: Cc1cc(C)c(C=C2C(=O)Nc3ccccc32)[nH]1
Temperature: 90 °C
Reaction time: 3 h
Yield: 57 %

Procedure:
A reaction mixture of 134.0 mg of oxindole, 147.8 mg of the 3,5-dimethylpyrrole-2-carboxaldehyde, and 3 drops of piperidine in 2 mL of ethanol was stirred at 90° C. for 3 h. After cooling, the precipitate was filtered, washed with cold ethanol, and dried to yield 136.7 mg (57%) of the title compound as a yellow solid.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:15])[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11].C(N(CC)CC)C.C(NC1C=CC(S([N:36]=[N+:37]=[N-])(=O)=O)=CC=1)(=O)C>C(#N)C>[N+:36](=[C:9]([C:8]([C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[F:1])=[O:15])[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[N-:37]
Reactant: CC(=O)Nc1ccc(S(=O)(=O)N=[N+]=[N-])cc1
Reactant: CCOC(=O)CC(=O)c1ccccc1F
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CCOC(=O)C(=[N+]=[N-])C(=O)c1ccccc1F
Temperature: 0 °C

Procedure:
Ethyl 3-(2-fluorophenyl)-3-oxopropanoate (1.00 g, 4.76 mmol) was dissolved in acetonitrile (14 mL) and treated with triethylamine (0.760 ml, 5.47 mmol, 1.15 equiv). The mixture was cooled to 0° C., treated with 4-acetamidobenzenesulfonylazide (1.26 g, 5.23 mmol, 1.1 equiv) and warmed to ambient temperature over 1.5 hours. The mixture was partially concentrated in vacuo, cooled to 0° C., treated with sodium hydroxide (50 mL, 1 N aqueous) and extracted with chloroform (3×50 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified via silica gel gradient chromatography (100:0 to 85:15; hexanes:ethyl acetate) providing the titled compound as a yellow oil.