Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]2[NH:12][C@H:11]([C:13]([F:16])([F:15])[F:14])[CH2:10][CH2:9][N:5]2[C:6](=[O:8])[CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br.Br[CH2:25][C:26]([C:28]1[S:32][CH:31]=[N:30][C:29]=1[CH3:33])=[O:27]>C(#N)C>[Cl:1][C:2]1[N:3]=[C:4]2[N:12]([CH2:25][C:26]([C:28]3[S:32][CH:31]=[N:30][C:29]=3[CH3:33])=[O:27])[C@H:11]([C:13]([F:14])([F:15])[F:16])[CH2:10][CH2:9][N:5]2[C:6](=[O:8])[CH:7]=1
Reactant: Cc1ncsc1C(=O)CBr
Reactant: O=c1cc(Cl)nc2n1CC[C@@H](C(F)(F)F)N2
Agent: Br
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC#N
Product: Cc1ncsc1C(=O)CN1c2nc(Cl)cc(=O)n2CC[C@H]1C(F)(F)F
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 81.8 %

Procedure:
A suspension of 150 mg (0.591 mmol) of (8S)-2-chloro-8-trifluoromethyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one and 578.13 mg (1.77 mmol) of cesium carbonate in 10 mL of acetonitrile is stirred for 15 minutes at room temperature. 213.64 mg (0.709 mmol) of 2-bromo-1-(4-methylthiazol-5-yl)ethanone hydrobromide are then added. After stirring overnight at room temperature, the reaction mixture is evaporated and the residue is taken up in water and extracted with ethyl acetate. The organic phase is dried over magnesium sulfate and evaporated to dryness to give 190 mg of (8S)-2-chloro-9-[2-(4-methylthiazol-5-yl)-2-oxoethyl]-8-trifluoromethyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one, corresponding to the following characteristics:
Reaction SMILES: [CH:1]([O:4][C:5](=[O:22])[CH2:6][N:7]1[C:11]2[C:12]([CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])=[CH:13][CH:14]=[CH:15][C:10]=2[NH:9][C:8]1=[O:21])([CH3:3])[CH3:2].[Cl:23]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl.C(=O)([O-])O.[Na+].N(C(C)(C)C#N)=NC(C)(C)C#N>[CH:1]([O:4][C:5](=[O:22])[CH2:6][N:7]1[C:11]2[C:12]([CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])=[CH:13][CH:14]=[C:15]([Cl:23])[C:10]=2[NH:9][C:8]1=[O:21])([CH3:2])[CH3:3]
Reactant: CCC(CC)c1cccc2[nH]c(=O)n(CC(=O)OC(C)C)c12
Reactant: O=C1CCC(=O)N1Cl
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClC(Cl)(Cl)Cl
Product: CCC(CC)c1ccc(Cl)c2[nH]c(=O)n(CC(=O)OC(C)C)c12
Temperature: 70 °C
Reaction time: 72 h
Yield: 64.9 %

Procedure:
To a solution of isopropyl[7-(1-ethylpropyl)-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl]acetate (5.29 g, 17.4 mmol) in carbon tetrachloride (350 mL) was added N-chlorosuccinimide (2.55 g, 19.1 mmol) and 2,2′-azobisisobutyronitrile (86 mg, 0.522 mmol), and the mixture was stirred at 70° C. for 3 days. The reaction mixture was diluted with saturated aqueous sodium hydrogen carbonate and extracted with dichloromethane (X2). The combined organic layer was washed with water (X1) and brine (X1), dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with a 10-50% ethyl acetate/hexane gradient mixture to give 3.83 g (11.3 mmol, 65.0%) of the title compound as a colorless solid.
Reaction SMILES: [F:1][C:2]([F:28])([C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=1)[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:14]3=[N:15][S:16](=[O:20])(=[O:19])[CH2:17][CH2:18][N:13]3[CH:12]=[CH:11][CH:10]=2)=[CH:5][CH:4]=1>C1COCC1.CO.[Pt](=O)=O>[F:28][C:2]([F:1])([C:21]1[CH:22]=[CH:23][C:24]([CH3:27])=[CH:25][CH:26]=1)[C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:14]3=[N:15][S:16](=[O:20])(=[O:19])[CH2:17][CH2:18][N:13]3[CH2:12][CH2:11][CH2:10]2)=[CH:5][CH:4]=1
Reactant: Cc1ccc(C(F)(F)c2ccc(C3=CC=CN4CCS(=O)(=O)N=C34)cc2)cc1
Agent: O=[Pt]=O
Solvent: C1CCOC1
Solvent: CO
Product: Cc1ccc(C(F)(F)c2ccc(C3CCCN4CCS(=O)(=O)N=C34)cc2)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 45.7 %

Procedure:
Platinum(IV) oxide (30 mg) was added to a solution of 9-{4-[difluoro(4-methylphenyl)methyl]phenyl}-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide (156 mg) in THF (dry) (20 mL) and MeOH (20 mL). The mixture was stirred at room temperature under hydrogen for 3 h. Activated carbon was added and the insoluble solid was removed by filtration through NH-silica gel/Celite pad (eluted with EtOAc). Platinum(IV) oxide (30 mg) was added and the mixture was stirred at room temperature under hydrogen overnight. Activated carbon was added and the insoluble solid was removed by filtration through NH-silica gel/Celite pad (eluted with EtOAc) and the filtrate was concentrated in vacuo. The residue was crystallized from THF/IPE to give the title compound (72.0 mg) as colorless crystals.
Reaction SMILES: [NH2:1][C:2]1[C:6]2[CH:7]=[N:8][C:9]([NH:11][C:12]([NH:14][C@@H:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH3:16])=[O:13])=[CH:10][C:5]=2[N:4](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[N:3]=1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>C(Cl)Cl>[NH2:1][C:2]1[C:6]2[CH:7]=[N:8][C:9]([NH:11][C:12]([NH:14][C@@H:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH3:16])=[O:13])=[CH:10][C:5]=2[NH:4][N:3]=1
Reactant: C[C@@H](NC(=O)Nc1cc2c(cn1)c(N)nn2C(c1ccccc1)(c1ccccc1)c1ccccc1)c1ccccc1
Agent: CC[SiH](CC)CC
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: C[C@@H](NC(=O)Nc1cc2[nH]nc(N)c2cn1)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 84.9 %

Procedure:
A solution of (R)-1-(3-amino-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea (310 mg, 0.576 mmol) and triethylsilane (184 μl, 1.151 mmol) in DCM (5232 μl) were treated with trifluoroacetic acid (2660 μl, 34.5 mmol) and stirred for 1 hr at room temperature. Reaction mixture was evaporated in vacuo, partioned between EtOAc/saturated aqeous NaHCO3 and extracted with EtOAc (2×). Combined organics were washed with saturated aqeous NaHCO3, brine, dried over Na2SO4 and evaporated in vacuo affording crude product which was purified by normal phase column chromotography eluting with MeOH/EtOAc (0-10%) affording (R)-1-(3-amino-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea (145 mg, 0.489 mmol, 85% yield) as an off white solid. 1H NMR (500 MHz, dmso) δ 11.42 (s, 1H), 8.87 (s, 1H), 8.57 (s, 1H), 8.07 (s, 1H), 7.39-7.27 (m, 4H), 7.27-7.17 (m, 1H), 5.64 (s, 2H), 4.86 (m, 1H), 1.39 (d, 3H). MS ESI calc'd. For C15H16N6O[M+H]+ 297. found 297.
Reaction SMILES: Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[O:17][C@H:16]([C:18]([NH:20][CH2:21][CH3:22])=[O:19])[C@@H:14]([OH:15])[C@H:12]2[OH:13])=[C:4]([NH:23][CH2:24][CH:25]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[N:3]=1.[CH2:38]([NH2:41])[CH2:39][NH2:40].Cl.[N:43]1(C(N)=N)[CH:47]=CC=[N:44]1.N1C=CN=C1>CS(C)=O.CO>[NH2:44][N:43]=[CH:47][NH:40][CH2:39][CH2:38][NH:41][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[O:17][C@H:16]([C:18]([NH:20][CH2:21][CH3:22])=[O:19])[C@@H:14]([OH:15])[C@H:12]2[OH:13])=[C:4]([NH:23][CH2:24][CH:25]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[N:3]=1
Reactant: NCCN
Reactant: N=C(N)n1cccn1
Reactant: CCNC(=O)[C@H]1O[C@@H](n2cnc3c(NCC(c4ccccc4)c4ccccc4)nc(Cl)nc32)[C@H](O)[C@@H]1O
Agent: Cl
Agent: c1c[nH]cn1
Solvent: CS(C)=O
Solvent: CO
Product: CCNC(=O)[C@H]1O[C@@H](n2cnc3c(NCC(c4ccccc4)c4ccccc4)nc(NCCNC=NN)nc32)[C@H](O)[C@@H]1O
Yield: 57.9 %

Procedure:
A solution of 1-[2-chloro6-[(2,2-diphenylethyl)amino]-9H-purin-9-yl]-1-deoxy-N-ethyl-β-D-ribofuranuronamide (0.382 g, 0.73 mmol) in dimethylsulphoxide (2.5 ml) was heated at 125° for 18h with ethylenediamine (1.15 g, 19.2 mmol) under nitrogen. The cooled mixture was partitioned between ethyl acetate (50 ml) and water (50 ml) and the aqueous phase was separated, extracted with ethyl acetate (20 ml) and the extract was combined with the organic phase from the partitioning. The organic solution was dried (MgSO4) and evaporated to leave a brown froth (0.373 g). This froth (0.353 g) was dissolved in 50% aqueous methanol (20 ml) and the solution was heated at 500 with pyrazole-1-carboxamidine hydrochloride (0.099 g, 0.675 mmol) for 18h. More pyrazole-1-carboxamidine hydrochloride (0.099 g, -0.675 mmol) and imidazole (0.048 g, 0.705 mmol) were added and the reaction was heated at 50° for a further 18h. The mixture was evaporated to leave a red oil which was purified by preparative HPLC (20-60% acetonitrile) to give the title compound (0.23 g) as a solid from ether. The product had MH+ =589, nmr(δ,DMSO-6) includes 1.02(t,3H), 3.05-3.25(m,2H) 3.3-3.5(m,2H), 3.4-3.6(m,1H), 4.8(s,1H), 4.5-4.7(m,2H), 5.85(d,1H), 7.15-7.4(m,10H), 7.57(m,1H), 8.12(s,1H), 8.1-8.25(m,1H).
Reaction SMILES: Cl[C:2]1[CH:7]=[N:6][CH:5]=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)[N:3]=1.P(Br)(Br)[Br:19].N>O>[Br:19][C:2]1[CH:7]=[N:6][CH:5]=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)[N:3]=1
Reactant: FC(F)(F)c1ccc(-c2cncc(Cl)n2)cc1
Reactant: BrP(Br)Br
Agent: N
Solvent: O
Product: FC(F)(F)c1ccc(-c2cncc(Br)n2)cc1
Temperature: 25 °C

Procedure:
To a flask containing 2-chloro-6-[4-(trifluoromethyl)phenyl]pyrazine (0.8 g, 3.1 mmol), was added phosphorus tribromide (20 mL) and the mixture heated at reflux for 6 h under nitrogen. The reaction mixture was cooled to room temperature prior to pouring carefully into iced water (400 mL), the resulting mixture was adjusted to pH 6–7 using aqueous ammonia and extracted with diethylether (3×250 mL). The organic solution was dried (MgSO4) and the solvent removed in vacuo to afford the title compound as a pale yellow crystalline solid (0.97 g).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([Cl:12])[C:6]=2C=O.[N+:15]([C:18]1[CH:23]=[C:22]([N+:24]([O-:26])=[O:25])[CH:21]=[CH:20][C:19]=1[NH:27][NH2:28])([O-:17])=[O:16].O>C(O)C>[Cl:1][C:2]1[CH:3]=[N:4][C:5]2[C:6](=[N:28][NH:27][C:19]3[CH:20]=[CH:21][C:22]([N+:24]([O-:26])=[O:25])=[CH:23][C:18]=3[N+:15]([O-:17])=[O:16])[CH:7]([Cl:12])[CH:8]=[CH:9][C:10]=2[CH:11]=1
Reactant: O=Cc1c(Cl)ccc2cc(Cl)cnc12
Reactant: NNc1ccc([N+](=O)[O-])cc1[N+](=O)[O-]
Solvent: O
Solvent: CCO
Product: O=[N+]([O-])c1ccc(NN=C2c3ncc(Cl)cc3C=CC2Cl)c([N+](=O)[O-])c1
Yield: 85.5 %

Procedure:
23 g of 3,7-dichloroquinoline-8-carbaldehyde and 20 g of 2,4-dinitrophenylhydrazine in 500 ml of ethanol were heated at 80° C. for 5 hours. Water was added to the reaction mixture, and the precipitated solid was filtered off under suction and recrystallized from dimethylformamide to give 34 g (85% of theory) of 3,7-dichloro-8-(2,4-dinitrophenylhydrazono)-quinoline of melting point >280° C.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([NH:12][C:13]([NH:15][C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=1)=[O:14])[C:9]([OH:11])=O.[O:23]=[C:24]1[CH2:29][O:28][CH2:27][CH2:26][N:25]1[C:30]1[CH:35]=[CH:34][C:33]([NH2:36])=[CH:32][CH:31]=1.C(Cl)CCl>CN(C=O)C>[O:23]=[C:24]1[CH2:29][O:28][CH2:27][CH2:26][N:25]1[C:30]1[CH:31]=[CH:32][C:33]([NH:36][C:9](=[O:11])[CH:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[CH3:1])[NH:12][C:13]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=2)=[O:14])=[CH:34][CH:35]=1
Reactant: Cc1ccccc1C(NC(=O)Nc1ccc(Cl)cc1)C(=O)O
Reactant: Nc1ccc(N2CCOCC2=O)cc1
Solvent: ClCCCl
Solvent: CN(C)C=O
Product: Cc1ccccc1C(NC(=O)Nc1ccc(Cl)cc1)C(=O)Nc1ccc(N2CCOCC2=O)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 66.8 %

Procedure:
To a solution of 2-(2-methylphenyl)-2-(4-chlorophenylaminocarbonylamino)-acetic acid (26 mg, 0.082 mmol) and 4-(3-oxo-morpholin-4-yl)phenylamine (23 mg, 0.12 mmol) in DMF (3 mL), EDC (39 mg, 0.20 mmol) was added. The reaction mixture was stirred at room temperature overnight. It was then concentrated in vacuo. The residue was purified by HPLC to give the titled compound as a white powder (27 mg). MS 493.2 and 495.2 (M+H, Cl pattern).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]([O:10][C:11]2[CH:16]=[CH:15][C:14]([C:17](=[O:19])[CH3:18])=[CH:13][CH:12]=2)=[N:8][CH:9]=1)([O-:3])=[O:2].[CH2:20](O)[CH2:21][OH:22].C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>C1C=CC=CC=1>[CH3:18][C:17]1([C:14]2[CH:15]=[CH:16][C:11]([O:10][C:7]3[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:9][N:8]=3)=[CH:12][CH:13]=2)[O:22][CH2:21][CH2:20][O:19]1
Reactant: OCCO
Reactant: CC(=O)c1ccc(Oc2ccc([N+](=O)[O-])cn2)cc1
Agent: CC1(C)C2CCC1(CS(=O)(=O)O)C(=O)C2
Solvent: c1ccccc1
Product: CC1(c2ccc(Oc3ccc([N+](=O)[O-])cn3)cc2)OCCO1
Reaction time: 3 h

Procedure:
380 mg of 1-{4-[(5-nitro-2-pyridinyl)oxy]phenyl}-1-ethanone was dissolved in 5 ml of benzene and, after adding 98 μl of ethylene glycol and 3 mg of (±)-10-camphorsulfonic acid, the mixture was heated at reflux. After 3 hours, the reaction solution was extracted with ethyl acetate. The organic layer was washed in turn with a saturated sodium hydrogencarbonate solution and a saturated sodium chloride solution, dried over magnesium sulfate and then concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (eluent: ethyl acetate/n-hexane (1:4)) to obtain the titled compound (280 mg).
Reaction SMILES: F[C:2]1[N:7]=[C:6]2[NH:8][N:9]=[C:10]([C:11]#[N:12])[C:5]2=[CH:4][CH:3]=1.[CH3:13][N:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1.O>CN1CCCC1=O>[CH3:13][N:14]1[CH2:19][CH2:18][N:17]([C:2]2[N:7]=[C:6]3[NH:8][N:9]=[C:10]([C:11]#[N:12])[C:5]3=[CH:4][CH:3]=2)[CH2:16][CH2:15]1
Reactant: CN1CCNCC1
Reactant: N#Cc1n[nH]c2nc(F)ccc12
Solvent: O
Solvent: CN1CCCC1=O
Product: CN1CCN(c2ccc3c(C#N)n[nH]c3n2)CC1

Procedure:
6-Fluoro-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile (1.62 g, 10.0 mmole) was dissolved in 20 mL of N-methylpyrrolidone. N-methylpiperazine (3.0 g, 30.0 mmole) was added and the reaction mixture was warmed for 2 hours at 80°. It was poured into H2O and then the product was filtered off and recrystallized from MeOH-H2H2O to give 1.41 g (58%) of analytically pure product, mp 255°(dec).
Reaction SMILES: [CH3:1][C:2]([CH3:4])=[CH2:3].[C:5]([O:9][C:10]([NH:12][N:13]1[CH2:18][C:17](/[C:19](/Cl)=[N:20]/[OH:21])=[N:16][N:15]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C:14]1=[O:30])=[O:11])([CH3:8])([CH3:7])[CH3:6].C(N(CC)CC)C>C(Cl)(Cl)Cl>[C:5]([O:9][C:10]([NH:12][N:13]1[CH2:18][C:17]([C:19]2[CH2:1][C:2]([CH3:4])([CH3:3])[O:21][N:20]=2)=[N:16][N:15]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C:14]1=[O:30])=[O:11])([CH3:8])([CH3:7])[CH3:6]
Reactant: C=C(C)C
Reactant: CC(C)(C)OC(=O)NN1CC(/C(Cl)=N/O)=NN(C(=O)OC(C)(C)C)C1=O
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: CC(C)(C)OC(=O)NN1CC(C2=NOC(C)(C)C2)=NN(C(=O)OC(C)(C)C)C1=O
Temperature: 25 °C
Reaction time: 20 h

Procedure:
Into an argon-flushed round-bottom flask equipped with rubber septa and argon balloon at −78° C. was condensed gaseous 2-methylprop-1-ene (2.97 g, 53.0 mmol) via cannula. After addition of a solution of tert-butyl 4-(tert-butoxycarbonylamino)-6-[(Z)—C-chloro-N-hydroxy-carbonimidoyl]-3-oxo-5H-1,2,4-triazine-2-carboxylate (2.30 g, 5.30 mmol) in CHCl3 (10.0 mL), triethylamine (0.747 mL, 5.30 mmol) was slowly added via syringe. After completion of the addition, the reaction mixture was allowed to slowly warm up to room temperature overnight. After 20 h stirring, the reaction mixture was quenched with sat. NH4Cl, and the aqueous layer extracted with EtOAc. The combined organic layers were dried (Na2SO4) and concentrated in vacuo. The obtained sticky oil was used as obtained. LCMS (Method K) RT 0.96 min. [M−H]− 410.
Reaction SMILES: [CH3:1][S:2]([NH:5][CH2:6][CH2:7][CH2:8][C:9]([NH2:11])=O)(=[O:4])=[O:3].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:21])=CC=1>C1COCC1>[CH3:1][S:2]([NH:5][CH2:6][CH2:7][CH2:8][C:9]([NH2:11])=[S:21])(=[O:4])=[O:3]
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: CS(=O)(=O)NCCCC(N)=O
Solvent: C1CCOC1
Product: CS(=O)(=O)NCCCC(N)=S
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 149.2 %

Procedure:
A suspension of 4-methanesulfonylamino-butyramide (0.50 g, 2.8 mmol) and Lawesson's reagent (0.56 g, 1.4 mmol) in THF (50 mL) was stirred at room temperature for 45 minutes. During this time all of the solid dissolved. The solution was concentrated and purified by flash chromatography (79:1 EtOAc:MeOH) to afford the title compound (0.41 g); 1H NMR (400 MHz, CDCl3) δ 3.29 (s, 3H), 3.07–3.11 (m, 2H), 2.91 (s, 3H), 2.62–2.66 (m, 2H), 1.93–1.99 (m, 2H); MS 197 (M++1).
Reaction SMILES: [CH3:1][C:2]1[N:7]2[C:8](=[O:15])[C:9]([C:12]([OH:14])=O)=[CH:10][N:11]=[C:6]2[CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.ClC(OC)=O.[C:28]([NH2:32])([CH3:31])([CH3:30])[CH3:29]>C(Cl)(Cl)Cl>[C:28]([NH:32][C:12]([C:9]1[C:8](=[O:15])[N:7]2[C:2]([CH3:1])=[CH:3][CH:4]=[CH:5][C:6]2=[N:11][CH:10]=1)=[O:14])([CH3:31])([CH3:30])[CH3:29]
Reactant: CC(C)(C)N
Reactant: Cc1cccc2ncc(C(=O)O)c(=O)n12
Agent: COC(=O)Cl
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: Cc1cccc2ncc(C(=O)NC(C)(C)C)c(=O)n12
Reaction time: 0.08 h
Yield: 74.7 %

Procedure:
A mixture containing 16.32 g (0.08 mol) of 6-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylic acid and 12.4 ml (0.088 mol) of triethylamine in 480 ml of chloroform is cooled below -10° C. by ice-salt. A solution of 6.5 ml (0.08 mol) of methyl chloroformate in 40 ml of chloroform is dropped to the above mixture at -20° C. during 20 minutes. After stirring for 5 minutes, 6.47 g (0.088 mol) of tert.-butylamine dissolved in 80 ml of chloroform are dropped to the above solution at a temperature between -18° C. and -20° C. during 50 minutes. The reaction mixture is stirred for 1 hour at the same temperature and then let to stand in the refrigerator overnight. For working up, the mixture is washed 3 times with 150 ml of 5% sodium hydrogen carbonate each and then 3 times with 150 ml of water each. The organic phase is dried over anhydrous sodium sulfate and evaporated to give 15.5 g (74.7%) of the named product as light beige crystals alter recrystallization from ethanol, m.p.: 164°-166° C.
Reaction SMILES: [CH2:1]([C:7]1CCC(=O)[CH:8]=1)[CH2:2][CH2:3]CC=C.[CH2:13]1[CH2:17][O:16][CH2:15][CH2:14]1.C(C(Br)CCC[O:29][CH2:30][CH2:31][CH2:32][CH:33](Br)[CH2:34][C:35]1[CH:40]=CC=CC=1)C1C=CC=CC=1.C(OC1CCC(=O)C=1)C>C(OCC)(=O)C>[CH2:17]([O:16][CH:15]([CH3:14])[CH2:40][CH2:35][C:34]1[C:30](=[O:29])[CH2:31][CH2:32][CH:33]=1)[C:13]1[CH:8]=[CH:7][CH:1]=[CH:2][CH:3]=1
Reactant: C=CCCCCC1=CC(=O)CC1
Reactant: BrC(CCCOCCCC(Br)Cc1ccccc1)Cc1ccccc1
Reactant: C1CCOC1
Agent: CCOC1=CC(=O)CC1
Solvent: CCOC(C)=O
Product: CC(CCC1=CCCC1=O)OCc1ccccc1
Yield: 48 %

Procedure:
A solution of a Grignard reagent was prepared following the procedure described in the synthesis of 3-(5-hexenyl)cyclopent-2-enone, using Mg turnings (302 mg, 12 mmol), THF (11 mL), and benzyl 4-bromobutylether (2.75 g, 11.3 mmol). The general procedure for the preparation of substrates using 3-ethoxycyclopentenone (0.67 mL, 5.65 mmol), gave, after 12 h and flash chromatography (3:1, then 2:1 hexanes:ethyl acetate), the title compound as a white solid (0.662 g, 48%). m.p. 46-47° C. 1H NMR (300 MHz, CDCl3): δ 7.34-7.25 (m, 5H), 5.94 (s, 1H), 4.50 (s, 2H), 3.49 (t, J=6.0 Hz, 2H), 2.58-2.55 (m, 2H), 2.41-2.38 (m, 3H), 1.70-1.67 (m, 4H). 13C NMR (75 MHz, CDCl3): δ 210.2, 182.9, 138.6, 129.7, 128.6, 127.8 (2 peaks partially resolved), 73.3, 70.0, 35.6, 33.6, 31.8, 29.8, 24.2. IR (neat): 2941, 2853, 1710, 1613, 1451, 1366, 1185, 1119, 1000, 842, 749 cm−1.
Reaction SMILES: C(OC([NH:8][C:9]1[C:10]([NH:22][C:23](=[O:34])[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[C:30]([CH3:33])([CH3:32])[CH3:31])=[CH:11][C:12]([O:15][CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:13][CH:14]=1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[C:30]([C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=1[C:23]([NH:22][C:10]1[C:9]([NH2:8])=[CH:14][CH:13]=[C:12]([O:15][CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH:11]=1)=[O:34])([CH3:31])([CH3:32])[CH3:33]
Reactant: CCOC(=O)COc1ccc(NC(=O)OC(C)(C)C)c(NC(=O)c2ccccc2C(C)(C)C)c1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCOC(=O)COc1ccc(N)c(NC(=O)c2ccccc2C(C)(C)C)c1
Reaction time: 12 h
Yield: 98 %

Procedure:
To a mixture of N1-(t-butoxycarbonyl)-N2-(t-butylbenzoyl)-4-(ethoxycarbonylmethoxy)-1,2-benzenediamine (878 mg, 1.87 mmol) and CH2Cl2 (20 mL) was added TFA (1.5 mL, 19.5 mmol). After 12 h, the reaction was diluted with CH2Cl2 (300 ml) and washed with sat. aq. NaHCO3 (3×50 mL). The organic layer was MgSO4 dried, and concentrated. The crude material was chromatographed (65 g silica, 20% EtOAc/hexanes to 50% EtOAc/hexanes) to give the title compound (98%); IR(CHCl3): 1176, 1512, 1668, 1755, 2968 cm−1; NMR(300 MHz, DMSO-d6): 1.22 (t, 3H, J=7.2 Hz); 1.33 (s, 9H); 4.17 (q, 2H, J=7.2 Hz); 4.62 (s, 2H); 6.64 (d, 1H, J=8.7 Hz); 6.74 (d, 1H, J=8.7 Hz); 6.95 (d, 1H, J=3.0 Hz); 7.54 (d, 2H, J=8.7 Hz); 7.91 (d, 2H, J=8.1 Hz); 9.59 (s, 1H); MS(FD): 370.
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[CH3:11])[CH:4]=[CH:3]1.[CH3:12][N:13](CCN(C)C)[CH3:14].C([Li])CCC.CN(C=O)C.[NH4+].[Cl-]>C(OCC)C>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[CH3:11])[CH:4]=[C:3]1[CH2:12][NH:13][CH3:14]
Reactant: CN(C)CCN(C)C
Reactant: Cc1cccc2ccn(C)c12
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CN(C)C=O
Solvent: CCOCC
Product: CNCc1cc2cccc(C)c2n1C
Temperature: 25 °C
Reaction time: 8 h
Yield: 42.5 %

Procedure:
To a solution of 1,7-dimethylindole (2.85 g, 19.6 mmol) and TMEDA (3.3 mL, 21.6 mmol) in diethyl ether (30 mL) at −30° C. under N2 was added n-butyllithium (13.5 mL of a 1.6 M solution in hexanes, 21.6 mmol) dropwise. The resulting orange solution was heated to reflux for 1 h and then DMF (4.6 mL, 58.8 mmol) was added in one portion. The solution was stirred at room temperature overnight. Saturated aqueous NH4Cl solution was added and the mixture was then extracted with ethyl acetate (3×150 mL). The combined organics were washed with water (100 mL) and brine (100 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to provide an orange oil. Purification by flash column chromatography (silica gel, hexanes/ethyl acetate, 95:5) gave the title compound (1.57 g, 46%) as a yellow solid: 1H NMR (300 MHz, CDCl3) δ 9.83 (s, 1H), 7.54 (d, J=7.8 Hz, 1H), 7.21 (s, 1H), 7.09-7.02 (m, 2H), 4.39 (s, 3H), 2.79 (s, 3H).
Reaction SMILES: [CH2:1]([CH:3]([C:7](=O)[CH3:8])[C:4](=O)[CH3:5])[CH3:2].[NH2:10][NH2:11]>C(O)C>[CH3:8][C:7]1[C:3]([CH2:1][CH3:2])=[C:4]([CH3:5])[NH:11][N:10]=1
Reactant: NN
Reactant: CCC(C(C)=O)C(C)=O
Solvent: CCO
Product: CCc1c(C)n[nH]c1C
Reaction time: 5 h
Yield: 123.9 %

Procedure:
At room temperature, to a mixture of 3-ethyl-2,4-pentanedione 5 g and ethanol 50 ml was added hydrazine one hydrate 2.9 g and the resulting mixture was stirred for five hours. The ethanol was distilled off and the resulting residue was subjected to a silica gel column chromatography to give 3,5-dimethyl-4-ethyl-1H-pyrazole 6.0 g.