Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([NH2:4])[CH:2]=[CH2:3].Cl[C:6]1[N:7]=[C:8]([NH:16][CH2:17][C:18]([CH3:21])([CH3:20])[CH3:19])[C:9]2[S:14][CH:13]=[C:12]([CH3:15])[C:10]=2[N:11]=1>O>[CH2:1]([NH:4][C:6]1[N:7]=[C:8]([NH:16][CH2:17][C:18]([CH3:21])([CH3:20])[CH3:19])[C:9]2[S:14][CH:13]=[C:12]([CH3:15])[C:10]=2[N:11]=1)[CH:2]=[CH2:3]
Reactant: Cc1csc2c(NCC(C)(C)C)nc(Cl)nc12
Reactant: C=CCN
Solvent: O
Product: C=CCNc1nc(NCC(C)(C)C)c2scc(C)c2n1
Temperature: 140 °C
Yield: 63.1 %

Procedure:
In 2.28 g (40.0 mmol) of allylamine was dissolved 250 mg (0.9 mmol) of 2-chloro-7-methyl-4-neopentylaminothieno[3,2-d]pyrimidine, and the resulting solution was heated in a sealed tube at 140° C. for 24 hours. After the reaction mixture was cooled, 100 ml of water was added thereto, followed by extraction with ethyl acetate (20 ml×3). The organic layer was washed with 20 ml of water and dried over anhydrous sodium sulfate, and then the solvent was distilled off. The residue was purified by silica gel column chromatography (eluent: ethyl acetate-hexane=1/4) to give 165 mg (yield: 61.3%) of the title compound.
Reaction SMILES: [C:1]([O:5][C:6](=[O:17])[NH:7][CH2:8][CH:9]1[CH2:14][CH2:13][CH:12]([CH2:15][OH:16])[CH2:11][CH2:10]1)([CH3:4])([CH3:3])[CH3:2].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.C([O-])(O)=O.[Na+].[O-]S([O-])(=S)=O.[Na+].[Na+]>C(Cl)Cl>[C:1]([O:5][C:6](=[O:17])[NH:7][CH2:8][CH:9]1[CH2:10][CH2:11][CH:12]([CH:15]=[O:16])[CH2:13][CH2:14]1)([CH3:2])([CH3:4])[CH3:3]
Reactant: CC(C)(C)OC(=O)NCC1CCC(CO)CC1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Agent: O=C([O-])O
Agent: O=S([O-])([O-])=S
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NCC1CCC(C=O)CC1
Temperature: -78 °C
Reaction time: 3 h
Yield: 81.4 %

Procedure:
(4-Hydroxymethyl-cyclohexylmethyl)-carbamic acid tert-butyl ester (965 mg, 4.0 mmol) was dissolved in DCM (20 ml) and cooled down to −78° C. Dess Martin reagent (2.52 g, 6.0 mmol) was dissolved in DCM (30 ml) and added slowly to the stage 2 alcohol in solution. The reaction mixture was then stirred at r.t. for 3 h. The resulting solution was poured into a vigorously stirred saturated NaHCO3 and Na2S2O3 solution (1:1, 100 ml). The organic layer was separated and washed with brine, dried over magnesium sulfate and evaporated to dryness to yield the product (786 mg, 82% yield). 1H NMR (300 MHz, CDCl3), δ: 0.83-1.01 (2H, m, CH2), 1.15-1.24 (2H, m, CH2), 1.34 (9H, s, Boc), 1.75-1.88 (2H, m, CH2), 1.90-2.00 (2H, m, CH2), 2.05-2.18 (1H, m, CH), 2.93 (2H, t, J=6.4 Hz, CH2NH), 4.53 (1H, br. s, CHCHO), 9.55 (1H, s, CHO)
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]([C:6]2[N:10]([CH2:11][C:12]([OH:14])=[O:13])[N:9]=[N:8][N:7]=2)=[CH:2]1.[CH2:15](O)[CH2:16][CH2:17][OH:18].C1(N=C=NC2CCCCC2)CCCCC1.C(O)(=O)C>CN(C)C=O>[OH:18][CH2:17][CH2:16][CH2:15][O:13][C:12](=[O:14])[CH2:11][N:10]1[C:6]([C:3]2[CH:4]=[CH:5][S:1][CH:2]=2)=[N:7][N:8]=[N:9]1
Reactant: OCCCO
Reactant: O=C(O)Cn1nnnc1-c1ccsc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: CN(C)C=O
Solvent: CC(=O)O
Product: O=C(Cn1nnnc1-c1ccsc1)OCCCO
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 54.8 %

Procedure:
To a solution of 500 mg (2.38 mM) of [5-(3-thienyl) tetrazol-1-yl] acetic acid and 220 mg (2.85 mM) of 1,3-propanediol in 5 ml of N,N-dimethylformamide was added 540 mg (2.62 mM) of dicyclohexylcarbodiimide at room temperature. After the mixture was stirred at room temperature for 30 min, a small amount of acetic acid was added to the mixture and then was stirred for 30 min. The mixture was poured into ice-water. The precipitated crystal was filtered off and washed with water. The filtrate was extracted with ethyl acetate. The organic phase was washed with water, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The resultant residue was subjected to silica gel column chromatography (eluent: chloroform/ethyl alcohol=60/1) for separation and purification, to give 350 mg (yield 54.8%) of [5-(3-thienyl) tetrazol-1-yl] acetic acid 3-hydroxypropyl ester.
Reaction SMILES: C([O:3][C:4](=[O:39])[C:5]([CH3:38])([O:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH2:15][C:16]2[N:17]=[C:18]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[O:19][C:20]=2[CH3:21])=[C:9]([CH2:28][CH2:29][CH3:30])[CH:8]=1)C.[OH-].[Na+].Cl>CCO>[CH3:38][C:5]([O:31][C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH2:15][C:16]2[N:17]=[C:18]([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[O:19][C:20]=2[CH3:21])=[C:9]([CH2:28][CH2:29][CH3:30])[CH:8]=1)[C:4]([OH:39])=[O:3]
Reactant: CCCc1cc(CC(C)(Oc2ccccc2)C(=O)OCC)ccc1OCCc1nc(-c2ccccc2)oc1C
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CCCc1cc(CC(C)(Oc2ccccc2)C(=O)O)ccc1OCCc1nc(-c2ccccc2)oc1C
Temperature: 65 °C
Reaction time: 18 h

Procedure:
A solution of 3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-3-propyl-phenyl}-2-methyl-2-phenoxy-propionic acid ethyl ester in EtOH (1.5 mL) was treated with 5 N NaOH (140 μL) and then warmed to 65° C. After 18 h, the mixture was acidified to pH=1 with 5 N HCl. The mixture was extracted with EtOAc and then the combined organic phases were dried (MgSO4), filtered and concentrated under reduced pressure to yield the title product. MS (EI) 500.2 (M+H)+; LC RT=3.22 min (>99% pure).
Reaction SMILES: C(O[C:4]([C:6]1[C:7]([OH:24])=[C:8]2[CH:14]=[CH:13][N:12]([CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH3:23])[CH:17]=3)[C:9]2=[CH:10][N:11]=1)=[O:5])C.[NH2:25][CH2:26][C:27]([OH:29])=[O:28].C[O-].[Na+].CO>>[OH:24][C:7]1[C:6]([C:4]([NH:25][CH2:26][C:27]([OH:29])=[O:28])=[O:5])=[N:11][CH:10]=[C:9]2[N:12]([CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH3:23])[CH:17]=3)[CH:13]=[CH:14][C:8]=12
Reactant: NCC(=O)O
Reactant: CCOC(=O)c1ncc2c(ccn2Cc2cccc(OC)c2)c1O
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: COc1cccc(Cn2ccc3c(O)c(C(=O)NCC(=O)O)ncc32)c1

Procedure:
Prepared in analogy to that of Example 1(e) from 1-(3-methoxy-benzyl)-4-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid ethyl ester, glycine and NaOMe/HOMe. The title compound, ESI MS (m/z): 356 (M+H)+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)O)=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[CH3:25][O:26][C:27]([O:35][Si](C)(C)C)=[CH:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>C(Cl)Cl.Cl[Ti](Cl)(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH:28]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[C:27]([O:26][CH3:25])=[O:35])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1
Reactant: OC(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1
Reactant: COC(=Cc1ccccc1)O[Si](C)(C)C
Agent: Cl[Ti](Cl)(Cl)Cl
Solvent: ClCCl
Product: COC(=O)C(c1ccccc1)C(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1
Reaction time: 1 h
Yield: 83.5 %

Procedure:
To a solution of (1-(4-fluorophenyl)-1H-indazol-5-yl)(phenyl)methanol (318 mg, 1.0 mmol) and (1-methoxy-2-phenylvinyloxy)trimethylsilane (3 mmol) which was prepared using General Silyl Ketene Acetal Method A in 10 mL of dry DCM was added TiCl4 (1.0 mL of 1.0 M DCM solution, 1.0 mmol) and then stirred 1 h. The reaction was quenched with MeOH, poured into aqueous sodium bicarbonate and extracted 2× EtOAc. The organic layers were dried over MgSO4, filtered, concentrated and purified on SiO2 by MPLC using a EtOAc/hexane gradient to give 376 mg (84% yield) of methyl 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,3-diphenylpropanoate. MS found: (M+H)+=451.
Reaction SMILES: [OH:1][CH:2]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[CH2:3][CH2:4][CH:5]1[C:8](=[O:9])[N:7]([C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=2)[CH:6]1[C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1.N.[H][H]>C(O)C.[Ni]>[NH2:15][CH2:14][C:13]1[CH:16]=[CH:17][C:10]([N:7]2[CH:6]([C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=3)[CH:5]([CH2:4][CH2:3][CH:2]([OH:1])[C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[C:8]2=[O:9])=[CH:11][CH:12]=1
Reactant: COc1ccc(C2C(CCC(O)c3ccccc3)C(=O)N2c2ccc(C#N)cc2)cc1
Reactant: [H][H]
Agent: [Ni]
Agent: N
Solvent: CCO
Product: COc1ccc(C2C(CCC(O)c3ccccc3)C(=O)N2c2ccc(CN)cc2)cc1

Procedure:
7 g of 4-[3-(3-hydroxy-3-phenylpropyl)-2-(4-methoxyphenyl)-4-oxoazetidin-1-yl]-benzonitrile are dissolved in 200 ml of ethanol and, after addition of 15 ml of concentrated ammonia, hydrogenated with 7 g of 50% aqueous Raney nickel under 50 bar of hydrogen. The crude product obtained after removal of the catalyst by filtration with suction and removal of the solvent in vacuo is purified on silica gel with dichloromethane/methanol/ammonia =200:10:1. The amine is obtained. MS (FAB, +LiCI): 423 (M+Li+) [C26H28N2O3 M=416].
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C@:8]2([CH2:32][C:33]([OH:36])([CH3:35])[CH3:34])[O:13][C:12](=[O:14])[N:11]([C@H:15]([C:17]3[CH:22]=[CH:21][C:20](B4OC(C)(C)C(C)(C)O4)=[CH:19][CH:18]=3)[CH3:16])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Br[C:38]1[CH:43]=[C:42]([CH3:44])[N:41]=[C:40]([CH3:45])[CH:39]=1>>[CH3:45][C:40]1[CH:39]=[C:38]([C:20]2[CH:21]=[CH:22][C:17]([C@@H:15]([N:11]3[CH2:10][CH2:9][C@@:8]([C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=4)([CH2:32][C:33]([OH:36])([CH3:34])[CH3:35])[O:13][C:12]3=[O:14])[CH3:16])=[CH:18][CH:19]=2)[CH:43]=[C:42]([CH3:44])[N:41]=1
Reactant: Cc1cc(Br)cc(C)n1
Reactant: C[C@@H](c1ccc(B2OC(C)(C)C(C)(C)O2)cc1)N1CC[C@](CC(C)(C)O)(c2ccc(F)cc2)OC1=O
Product: Cc1cc(-c2ccc([C@H](C)N3CC[C@](CC(C)(C)O)(c4ccc(F)cc4)OC3=O)cc2)cc(C)n1

Procedure:
The title compound was prepared (S)-6-(4-fluorophenyl)-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one and 4-bromo-2,6-dimethylpyridine following a procedure analogous to that described in Example 1 Step 2. LC-MS Method 2 tR=1.001, m/z=477.1; 1H NMR (CDCl3) 1.05-1.23 (d, 6H), 1.49 (d, 3H), 2.10-2.23 (m, 4H), 2.31-2.42 (m, 1H), 2.56 (s, 6H), 2.89 (m, 1H), 5.67 (m, 1H), 6.92-7.07 (m, 4H), 7.08 (s, 2H), 7.22 (m, 2H), 7.33 (d, 2H).
Reaction SMILES: [CH:1]1([CH:7]2[CH2:21][NH:20][CH2:19][CH2:18][NH:17][CH2:16][CH2:15][NH:14][CH2:13][CH2:12][NH:11][CH2:10][CH2:9][NH:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl-:22].[Mn+2:23].[Cl-:24]>CO>[Cl:22][C:7]1([CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]2)[CH2:21][NH:20][CH2:19][CH2:18][NH:17][CH2:16][CH2:15][NH:14][CH2:13][CH2:12][NH:11][CH2:10][CH2:9][N:8]1[Cl:24].[Mn+2:23]
Reactant: [Cl-]
Reactant: C1CCC(C2CNCCNCCNCCNCCN2)CC1
Agent: [Mn+2]
Solvent: CO
Product: ClN1CCNCCNCCNCCNCC1(Cl)C1CCCCC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 62 %

Procedure:
2-Cyclohexyl-1,4,7,10,13-pentaazacyclopentadecane prepared as in Example 30E (0.50 g, 1.7 mmol) was added to a refluxing anhydrous MeOH solution (50 ml) containing anhydrous manganese(II) chloride (0.21 g, 1.7 mmol) under a dry nitrogen atmosphere. After refluxing for 2 h, the solution was stirred overnight at room temperature. The solution was filtered through celite and then taken to dryness. The solid was recrystallized from EtOH to give 0.44 g (62% yield) of a white solid after washing with ethyl ether and drying in vacuo: FAB mass spectrum (NBA+Li) m/z (relative intensity) 429 (M+ +Li, 5), 387/389 [(M+ -Cl), 100/35]; Anal. calcd for C16H35N5MnCl2 : C, 45.40; H, 8.33; N, 16.54; Cl, 16.75. Found: C, 45.39; H, 8.04; N, 16.33; C1, 16.37.
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([CH2:7][NH2:8])=[CH:4][CH:3]=1.Cl[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[N+:16]([O-:18])=[O:17]>C(N(CC)CC)C>[CH3:1][C:2]1[O:6][C:5]([CH2:7][NH:8][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[N+:16]([O-:18])=[O:17])=[CH:4][CH:3]=1
Reactant: Cc1ccc(CN)o1
Reactant: O=[N+]([O-])c1ccccc1Cl
Solvent: CCN(CC)CC
Product: Cc1ccc(CNc2ccccc2[N+](=O)[O-])o1
Yield: 89 %

Procedure:
a mixture of 40 parts of 5-methyl-2-furanmethanamine, 46 parts of 1-chloro-2-nitrobenzene and 210 parts of N,N-diethylethanamine was stirred and refluxed for 2 days. The reaction mixture was evaporated, water was added and the product was extracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was purified by filtration over silica gel using trichloromethane as eluent. The filtrate was evaporated, yielding 62 parts (89%) of 5-methyl-N-(2-nitrophenyl)-2-furanmethanamine as a residue (intermediate 2).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH:3]([NH:7][C:8]([C:10]2[S:14][C:13]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=3)=[N:12][C:11]=2[CH3:22])=[O:9])[CH2:2]1.[CH:23]([C:25]1[CH:26]=[C:27](OB(O)O)[CH:28]=[CH:29][C:30]=1[F:31])=[O:24]>>[Cl:21][C:18]1[CH:17]=[CH:16][C:15]([C:13]2[S:14][C:10]([C:8]([NH:7][CH:3]3[CH2:4][CH2:5][CH2:6][N:1]([C:27]4[CH:28]=[CH:29][C:30]([F:31])=[C:25]([CH:26]=4)[CH:23]=[O:24])[CH2:2]3)=[O:9])=[C:11]([CH3:22])[N:12]=2)=[CH:20][CH:19]=1
Reactant: Cc1nc(-c2ccc(Cl)cc2)sc1C(=O)NC1CCCNC1
Reactant: O=Cc1cc(OB(O)O)ccc1F
Product: Cc1nc(-c2ccc(Cl)cc2)sc1C(=O)NC1CCCN(c2ccc(F)c(C=O)c2)C1
Yield: 16.9 %

Procedure:
Using N-(piperidin-3-yl)-2-(4-chlorophenyl)-4-methylthiazole-5-carboxamide (238 mg, 0.709 mmol) and 3-formyl-4-fluorophenylboric acid (238 mg, 1.42 mmol), the same procedure was followed as in Example 2 to give 55.0 mg (17%) of the desired compound as a pale yellow powder.
Reaction SMILES: [N:1]1([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:23][CH2:22][C:17]4(OCC[O:18]4)[CH2:16][CH2:15]3)=[CH:10][CH:9]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[OH-].[Na+]>Cl>[N:1]1([CH2:7][C:8]2[CH:9]=[CH:10][C:11]([N:14]3[CH2:15][CH2:16][C:17](=[O:18])[CH2:22][CH2:23]3)=[CH:12][CH:13]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1
Reactant: c1cc(N2CCC3(CC2)OCCO3)ccc1CN1CCOCC1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: O=C1CCN(c2ccc(CN3CCOCC3)cc2)CC1
Temperature: 100 °C
Yield: 110.9 %

Procedure:
The product of Example 14 (4.5 g) was treated with 6 M HCl (50 mL), heated to 100° C. for 90 min, and then cooled to room temperature. The resulting solution was basified with 10% aqueous NaOH to pH 11, and extracted with DCM (3×5 mL). The combined extracts were dried (MgSO4), and concentrated under reduced pressure, giving the title compound as a brown gummy solid (4.3 g).
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]([C:16]2[NH:25][C:24](=[O:26])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[N:17]=2)[CH3:15])[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH:8]1[CH2:13][CH2:12][CH:11]([CH:14]([C:16]2[NH:25][C:24](=[O:26])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[N:17]=2)[CH3:15])[CH2:10][CH2:9]1
Reactant: CC(c1nc2ccccc2c(=O)[nH]1)C1CCN(C(=O)OC(C)(C)C)CC1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC(c1nc2ccccc2c(=O)[nH]1)C1CCNCC1

Procedure:
A solution of 4-[1-(4-oxo-3,4-dihydro-quinazolin-2-yl)-ethyl]-piperidine-1-carboxylic acid tert-butyl ester and TFA in CH2Cl2 was stirred at r.t. for 6 hr. The precipitated solid was filtered and dried to afford the product as a white solid. (2 g, 90%). 1H NMR (DMSO-d6) δ 8.51 (br, s, 1H), 8.18 (br, s, 1H), 8.06 (d, 1H, J=7.6), 7.74 (t, 1H, J=8.0), 7.57 (d, 1H, J=8.0), 7.44 (t, 1H, J=8.0), 3.29-3.18 (m, 2H), 2.88-2.76 (m, 2H), 2.61-2.57 (m, 1H), 1.95-1.92 (m, 2H), 1.61-1.57 (m, 1H), 1.42-1.25 (m, 2H), 1.25 (d, 3H, J=6.8); ESI-MS m/z 258.1 (M+1)+.
Reaction SMILES: CN(C)C=O.[N+:6]([C:9]1[N:10]=[C:11](S(C2C=CC([N+]([O-])=O)=CC=2)(=O)=O)[N:12]([CH2:14][C@:15]([OH:40])([CH3:39])[CH2:16][N:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][CH2:26][CH:27]=[CH:28][C:29]3[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][CH:30]=3)=[O:24])[CH2:19][CH2:18]2)[CH:13]=1)([O-:8])=[O:7].CC(C)([O-])C.[Na+].O>C(OCC)(=O)C>[CH3:39][C@@:15]1([CH2:16][N:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][CH2:26][CH:27]=[CH:28][C:29]3[CH:34]=[CH:33][C:32]([C:35]([F:37])([F:36])[F:38])=[CH:31][CH:30]=3)=[O:24])[CH2:19][CH2:18]2)[O:40][C:11]2=[N:10][C:9]([N+:6]([O-:8])=[O:7])=[CH:13][N:12]2[CH2:14]1
Reactant: C[C@](O)(CN1CCN(C(=O)OCC=Cc2ccc(C(F)(F)F)cc2)CC1)Cn1cc([N+](=O)[O-])nc1S(=O)(=O)c1ccc([N+](=O)[O-])cc1
Agent: CC(C)(C)[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: O
Product: C[C@]1(CN2CCN(C(=O)OCC=Cc3ccc(C(F)(F)F)cc3)CC2)Cn2cc([N+](=O)[O-])nc2O1
Reaction time: 0.5 h
Yield: 39.8 %

Procedure:
To N,N-dimethylformamide (0.5 ml) solution of 3-(4-trifluoromethylphenyl)-2-propenyl (S)-4-{3-[4-nitro-2-(4-nitrobenzenesulfonyl)imidazol-1-yl]-2-hydroxy-2-methylpropyl}piperazin-1-carboxylate (45 mg) was added sodium tert-butoxide (8 mg) at 0° C., and stirred at the same temperature for 30 minutes. To the reaction mixture was added water and ethyl acetate, the organic layer was taken by separation. The ethyl acetate layer was washed with an aqueous solution of 5%-potassium carbonate, water, and an aqueous solution being saturated with sodium chloride, then dried over anhydrous sodium sulfate. The residue obtained by removal of the solvent by distillation was purified by use of a thin layer chromatography (eluent: dichloromethane/ethyl acetate/methanol=15/15/1), there was obtained 3-(4-trifluoromethylphenyl)-2-propenyl (S)-4-(2-methyl-6-nitro-2,3-dihydroimidazo-[2,1-b]oxazol-2-ylmethyl)piperazin-1-carboxylate (13 mg, yield: 39%) as pale yellow amorphous product.
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH:10]([CH3:15])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].C(I)C.O.[O:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1>C(OCC)(=O)C>[CH2:1]([N:8]1[CH2:13][CH:25]([CH2:24][CH3:23])[C:26](=[O:22])[C:10]([CH2:11][CH3:12])([CH3:15])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C1CCOC1
Reactant: CC1CN(Cc2ccccc2)CCC1=O
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CCI
Product: CCC1CN(Cc2ccccc2)CC(C)(CC)C1=O
Reaction time: 1 h

Procedure:
1-Benzyl-3-methyl-piperidin-4-one (50 g, 246 mmole) was added to the stirred suspension of sodium hydride (12.0 g, 300.0 mmole) in tetrahydrofuran (500 ml) at ambient temperature and stirring was continued for 1 hr. Ethyl iodide (42.5 ml, 520.0 mmole) in dry tetrahydrofuran (100 ml) was added it at 0-5° C. The resulting mixture stirred at room temperature for 18 hr, water (100 ml) and ethyl acetate (800 ml) were added respectively. Organic layer was separated, dried (Na2SO4) and concentrated to give crude product, which was purified through column chromatography. Elute from 5% ethyl acetate in hexane afforded 1-benzyl-3,5-diethyl-3-methylpiperidin-4-one. Yield 12.0 g (19%), C17H25NO, m/z 260 (M+1).
Reaction SMILES: [CH3:1][N:2]1[CH2:15][CH2:14][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.N1CCC[C@H]1C(O)=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[CH:33]=[C:34]([C:36]1[CH:41]=[CH:40][C:39]([Cl:42])=[C:38]([Cl:43])[CH:37]=1)[CH3:35]>CN(C=O)C.[Cu]I>[Cl:43][C:38]1[CH:37]=[C:36](/[C:34](/[CH3:35])=[CH:33]\[N:6]2[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]3[CH2:3][N:2]([CH3:1])[CH2:15][CH2:14][C:5]2=3)[CH:41]=[CH:40][C:39]=1[Cl:42]
Reactant: CC(=CBr)c1ccc(Cl)c(Cl)c1
Reactant: Cc1ccc2[nH]c3c(c2c1)CN(C)CC3
Agent: [Cu]I
Agent: O=C(O)[C@@H]1CCCN1
Agent: O=P([O-])([O-])[O-]
Solvent: CN(C)C=O
Product: C/C(=C/n1c2c(c3cc(C)ccc31)CN(C)CC2)c1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
2,8-Dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (200 mg, 1 mmol) was dissolved in DMF. Copper (I) iodide (19 mg, 0.1 mmol), L-proline (23 mg, 0.2 mmol) and potassium phosphate (424 mg, 2 mmol) were added and the reaction mixture was stirred for 10 min. at RT. (1-Bromoprop-1-en-2-yl)-3,4-dichlorobenzene (318 mg, 1.2 mmol) was added dropwise and the reaction mixture was purged with nitrogen. The reaction mixture was heated overnight at 85° C. (prolonged heating in some cases was required). DMF was evaporated under reduced pressure, the residue was diluted with water and the solid was filtered. The solid material was purified by silica gel chromatography (100-200 mesh) eluting with 0-5% MeOH-DCM. The product was further purified by HPLC. Yield: 10 mg as the TFA salt. 1H NMR (CD3OD, TFA salt) δ (ppm): 7.30 (d, 1H), 7.22 (d, 2H), 7.10 (d, 1H), 7.0 (d, 1H), 6.92 (d, 1H), 6.85 (d, 1H), 4.40 (d, 1H), 4.30 (d, 1H), 3.70 (m, 1H), 3.40 (m, 1H), 3.0 (s, 3H), 2.80 (m, 2H), 2.40 (s, 3H), 2.30 (s, 3H).
Reaction SMILES: [CH2:1]([C:3]1[C:4](=[O:20])[NH:5][C:6](=[O:19])[NH:7][C:8]=1[C:9](=[O:18])[C:10]1[CH:15]=[C:14]([CH3:16])[CH:13]=[C:12]([CH3:17])[CH:11]=1)[CH3:2].[CH3:21][C:22]1[CH:23]=[C:24]([CH:27]=[C:28]([CH3:30])[CH:29]=1)[CH2:25]Br>>[CH3:21][C:22]1[CH:29]=[C:28]([CH:27]=[C:24]([CH3:25])[CH:23]=1)[CH2:30][N:7]1[C:8]([C:9](=[O:18])[C:10]2[CH:11]=[C:12]([CH3:17])[CH:13]=[C:14]([CH3:16])[CH:15]=2)=[C:3]([CH2:1][CH3:2])[C:4](=[O:20])[NH:5][C:6]1=[O:19]
Reactant: Cc1cc(C)cc(CBr)c1
Reactant: CCc1c(C(=O)c2cc(C)cc(C)c2)[nH]c(=O)[nH]c1=O
Product: CCc1c(C(=O)c2cc(C)cc(C)c2)n(Cc2cc(C)cc(C)c2)c(=O)[nH]c1=O
Yield: 73.8 %

Procedure:
5-Ethyl-6-(3,5-dimethylbenzoyl)-2,4-pyrimidinedione and 3,5-dimethylbenzyl bromide were reacted by the same way with the example 1 to obtain the titled compound (288 mg, yield: 73.8%).
Reaction SMILES: [CH:1]([C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10])=[O:2].Br[C:15]1[N:16]=[CH:17][S:18][CH:19]=1.C(=O)([O-])[O-].[Na+].[Na+]>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.O.C(OCC)(=O)C.COCCOC>[CH3:10][O:9][C:8]1[CH:7]=[CH:6][C:5]([C:15]2[N:16]=[CH:17][S:18][CH:19]=2)=[CH:4][C:3]=1[CH:1]=[O:2]
Reactant: Brc1cscn1
Reactant: COc1ccc(B(O)O)cc1C=O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Solvent: CCOC(C)=O
Solvent: O
Product: COc1ccc(-c2cscn2)cc1C=O
Temperature: 80 °C
Yield: 55 %

Procedure:
(3-Formyl-4-methoxyphenyl)boronic acid (309 mg, 1.71 mmol), 4-bromothiazole (250 mg, 1.52 mmol, prepared as described by J. Trybulski and H. J. Brabander, U.S. Pat. No. 4,990,520, 1991), and tetrakis(triphenylphosphine)palladium(0) (88 mg, 0.076 mmol) were added to a mixture of water (3.5 mL), ethylene glycol dimethyl ether (3.5 mL), and sodium carbonate (805 mg, 7.6 mmol). The mixture was heated in an oil bath at 80° C. for 3 h, allowed to cool to 25° C., and partioned between ethyl acetate (40 mL) and water (20 mL). The aqueous layer was extracted with 2×40 mL of dichioromethane and the combined organic layers dried (sodium sulfate), decanted, and evaporated. The residue was purified by flash column chromatography on silica gel, eluting with 10% ethyl acetate in hexane to give 182 mg (55% yield) of the title compound as a white solid. NMR (400 MHz, CDCl3): δ 10.51 (s, 1H), 8.88 (d, 1H, J=2 Hz), 8.32 (d, 1H, J=2 Hz), 8.24 (dd, 1H, J=9,2 Hz), 7.54 (d, 1H, J=2 Hz), 7.09 (d, 1H, J=9 Hz), 3.99 (s, 3H). Mass spectrum (NH3 /CI): 220 (M+1).