Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][C:4]1[C:9]2[C:10](=O)[CH2:11][O:12][C:8]=2[CH:7]=[CH:6][CH:5]=1)[CH3:2].C([O-])(=O)C.[Na+].Cl.[NH2:20][OH:21]>C(O)C.O>[CH2:1]([O:3][C:4]1[C:9]2[C:10](=[N:20][OH:21])[CH2:11][O:12][C:8]=2[CH:7]=[CH:6][CH:5]=1)[CH3:2]
Reactant: CCOc1cccc2c1C(=O)CO2
Reactant: NO
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: CCOc1cccc2c1C(=NO)CO2
Temperature: 23 °C
Yield: 93 %

Procedure:
A mixture of 4-ethoxy-benzofuran-3-one (CAS no: 7169-36-0) (4.18 g, 23.5 mmol), sodium acetate (3.96 g, 48.3 mmol) and hydroxylamine hydrochloride (3.34 g, 48.1 mmol) in ethanol (30 mL) was refluxed for 16 h. Cooled to 23° C., diluted with water (50 mL), filtered the precipitate off, washed with water, ethanol and diethyl ether and dried in high vacuum to give the title compound as a white solid (4.2 g, 93%); MS: m/e=194.3 (M+H+).
Reaction SMILES: [H-].[K+:2].[CH3:3][Si:4]([CH3:14])([CH3:13])[O:5][CH2:6][CH2:7][C:8]1[CH2:12][CH:11]=[CH:10][CH:9]=1>O1CCCC1>[CH3:13][Si:4]([CH3:3])([CH3:14])[O:5][CH2:6][CH2:7][C-:8]1[CH:12]=[CH:11][CH:10]=[CH:9]1.[K+:2]
Reactant: C[Si](C)(C)OCCC1=CC=CC1
Agent: [H-]
Agent: [K+]
Solvent: C1CCOC1
Product: C[Si](C)(C)OCC[c-]1cccc1
Reaction time: 2 h
Yield: 81 %

Procedure:
To a suspension of 0.5 g (12.4 mmol) of potassium hydride in tetrahydrofurane, 2.25 g (12.4 mmol) of (2-trimethylsiloxy-ethyl)-cyclopentadiene in tetrahydrofurane is added. The reaction is maintained under stirring for 2 hours and then the volatile compounds are eliminated, leaving an oily solid which is washed with hexane in order to obtain a brown solid. (2.2 g Yield: 81%)
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH2:15][C:14](=[O:16])[O:13][C:11](=[O:12])[CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].[Cl:17][C:18]1[CH:24]=[CH:23][C:21]([NH2:22])=[CH:20][CH:19]=1.C(N(CC)CC)C>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]([CH2:10][C:11]([NH:22][C:21]2[CH:23]=[CH:24][C:18]([Cl:17])=[CH:19][CH:20]=2)=[O:12])[CH2:15][C:14]([OH:13])=[O:16])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: Nc1ccc(Cl)cc1
Reactant: O=C1CC(c2ccc(Cl)c(Cl)c2)CC(=O)O1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(O)CC(CC(=O)Nc1ccc(Cl)cc1)c1ccc(Cl)c(Cl)c1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
3-(3,4-Dichlorophenyl)glutaric anhydride in CH2Cl2 (75 mL) at 0° C. was treated sequentially with 4-chloroaniline (2.25 g), triethylamine (1.79 g) and N,N-dimethylaminopyridine (trace). The mixture was stirred at 0° C. for two hours then allowed to warm to room temperature and stirred for 12 hours. The reaction mixture was washed with 1N HCl (3×50 mL) and water (50 mL). The organic layers were dried over MgSO4, filtered and concentrated to afford the title compound (4.9 g).
Reaction SMILES: [CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:24]([CH2:25][CH:26]([CH3:28])[CH3:27])[CH2:23][CH2:22][C:21]([C:29]([NH:31][C:32]4[CH:37]=[CH:36][C:35]([S:38][CH2:39][C:40]5[N:41]([CH2:46][CH2:47][CH3:48])[C:42]([CH3:45])=[CH:43][N:44]=5)=[CH:34][CH:33]=4)=[O:30])=[CH:20][C:19]=3[CH:49]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4].ClC1C=CC=C(C(OO)=[O:58])C=1>ClCCl>[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:24]([CH2:25][CH:26]([CH3:27])[CH3:28])[CH2:23][CH2:22][C:21]([C:29]([NH:31][C:32]4[CH:33]=[CH:34][C:35]([S:38]([CH2:39][C:40]5[N:41]([CH2:46][CH2:47][CH3:48])[C:42]([CH3:45])=[CH:43][N:44]=5)=[O:58])=[CH:36][CH:37]=4)=[O:30])=[CH:20][C:19]=3[CH:49]=2)=[CH:13][CH:14]=1)[CH2:2][CH2:3][CH3:4]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(SCc4ncc(C)n4CCC)cc2)CCN3CC(C)C)cc1
Solvent: ClCCl
Product: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(S(=O)Cc4ncc(C)n4CCC)cc2)CCN3CC(C)C)cc1
Yield: 73.8 %

Procedure:
To a solution of 7-[4-(2-butoxyethoxy)phenyl]-1-isobutyl-N-[4-[[[5-methyl-1-propylimidazol-2-yl]methyl]sulfanyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide (450 mg) in dichloromethane (15 ml) was added dropwise 70% solution of 3-chloroperbenzoic acid (244 mg) in dichloromethane (15 ml) at −78° C. The reaction vessel was removed from a dry ice-acetone bath, and an aqueous solution of sodium thiosulfate was added to the reaction vessel with strongly stirring. The mixture was allowed to be at room temperature, stirred for 30 minutes, and extracted with ethyl acetate. The organic layer was washed with an aqueous solution of saturated sodium bicarbonate, and saturated brine, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (ethyl acetate→methanol:ethyl acetate=1:9), to give 7-[4-(2-butoxyethoxy)phenyl]-1-isobutyl-N-[4-[[[5-methyl-1-propylimidazol-2-yl]methyl]sulfinyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide (340 mg) (Compound 365) as yellow amorphous.
Reaction SMILES: C(O[CH:4](OCC)[CH2:5][N:6]([C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=1)C.[ClH:27].[OH:28][C:29]1[CH:30]=[C:31]([CH:35]=[CH:36][C:37]=1[OH:38])[CH2:32][CH2:33][NH2:34].C(O)CCC>O>[ClH:27].[CH2:17]([O:16][C:14]([N:6]([CH2:5][CH:4]1[C:35]2[C:31](=[CH:30][C:29]([OH:28])=[C:37]([OH:38])[CH:36]=2)[CH2:32][CH2:33][NH:34]1)[C:7]1[CH:8]=[CH:9][C:10]([F:13])=[CH:11][CH:12]=1)=[O:15])[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: NCCc1ccc(O)c(O)c1
Reactant: CCOC(CN(C(=O)OCc1ccccc1)c1ccc(F)cc1)OCC
Agent: Cl
Solvent: CCCCO
Solvent: O
Product: O=C(OCc1ccccc1)N(CC1NCCc2cc(O)c(O)cc21)c1ccc(F)cc1
Yield: 44.6 %

Procedure:
N-benzyloxycarbonyl-p-fluoroanilinoacetaldehyde diethyl acetal (6 g) and 3,4-dihydroxyphenethylamine hydrochloride (2.5 g) were added to a mixture of n-butyl alcohol (60 ml) and water (8.5 ml). The mixture was then refluxed for 11 hours in a stream of nitrogen. In the course of the reaction, amounts of the above-mentioned acetal (0.6 g and 1.2 g) were added to the mixture after 4.5 hours and 6 hours, respectively, from the beginning of the reaction. The reaction mixture was concentrated to dryness and the residue was washed with ether and dissolved in water. The solution was washed with ether and concentrated to dryness to give amorphous 1-(N-benzyloxycarbonyl-p-fluoroanilinomethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (2.7 g), mp 122° C. (dec.).
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH:6]=[CH:7][N:8]2[CH2:13][C:14]1[CH:19]=[CH:18][N:17]=[C:16]2[N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH:21]=[CH:22][C:15]=12)([O-])=O>[Pd].C1COCC1>[NH2:1][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH:6]=[CH:7][N:8]2[CH2:13][C:14]1[CH:19]=[CH:18][N:17]=[C:16]2[N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH:21]=[CH:22][C:15]=12
Reactant: CC(C)(C)OC(=O)n1ccc2c(Cn3ccc4c([N+](=O)[O-])cccc43)ccnc21
Agent: [Pd]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)n1ccc2c(Cn3ccc4c(N)cccc43)ccnc21
Reaction time: 2 h
Yield: 95.5 %

Procedure:
In a round-bottom flask was added 4-[(4-nitro-1H-indol-1-yl)methyl]-1-(t-butyloxycarbonyl)-1H-pyrrolo[2,3-b]pyridine (500 mg, 1.3 mmol), Palladium on carbon (50 mg, 10%), and THF (30 mL). The mixture was stirred under a hydrogen atmosphere for 2 h, then filtered, concentrated to afford 4-[(4-amino-1H-indol-1-yl)methyl]-1-(t-butyloxycarbonyl)-1H-pyrrolo[2,3-b]pyridine (450 mg).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6](/[CH:9]=[C:10]2/[C:11](=[O:21])[C:12]3[CH:13]=[C:14]([CH3:20])[CH:15]=[N:16][C:17]=3[CH2:18][CH2:19]/2)=[CH:5][CH:4]=1.[BH4-].[Na+]>CC(O)C>[OH:21][CH:11]1[CH:10]([CH2:9][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)[CH2:19][CH2:18][C:17]2[N:16]=[CH:15][C:14]([CH3:20])=[CH:13][C:12]1=2
Reactant: COc1ccc(/C=C2\CCc3ncc(C)cc3C2=O)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(C)O
Product: COc1ccc(CC2CCc3ncc(C)cc3C2O)cc1
Yield: 78.9 %

Procedure:
(E)-7,8-Dihydro-6-(4-methoxyphenyl)methylene-3-methylquinolin-5[6H]one (5 g, prepared according to Example 5) was suspended in IPA (20 ml) and sodium borohydride (1.5 g) was added. The mixture was heated at reflux for 3 hours and the solvent was then evaporated and the residue treated with 2N HCl. The acidic solution was washed with diethyl ether and was basified with solid sodium carbonate. The aqueous layer was extracted into ethyl acetate and the organic solution dried (MgSO4) and evaporated under reduced pressure. The residue was recrystallised from diisopropyl ether to give the title compound (4 g).
Reaction SMILES: [NH3:1].[CH3:2][CH:3]([C:5]1[CH:10]=[CH:9][C:8]([S:11](Cl)(=[O:13])=[O:12])=[CH:7][CH:6]=1)[CH3:4]>O1CCCC1>[CH3:2][CH:3]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH2:1])(=[O:13])=[O:12])=[CH:7][CH:6]=1)[CH3:4]
Reactant: N
Reactant: CC(C)c1ccc(S(=O)(=O)Cl)cc1
Solvent: C1CCOC1
Product: CC(C)c1ccc(S(N)(=O)=O)cc1

Procedure:
To concentrated aqueous ammonia (1.75 mL) in tetrahydrofuran (50 mL) at 0° C. with stirring was added over 2 min via syringe 4-(1-methylethyl)benzenesulfonyl chloride (3.3 g). A white precipitate was observed. Additional concentrated aqueous ammonia (1.75 mL) was added after 5 min. After 4 h volatiles were evaporated and the residue partitioned between EtOAc and aqueous NaHCO3. The organic layer was washed with brine, dried (Na2SO4) and volatiles evaporated to give the title crude compound as a colourless powder that was used without further purification.
Reaction SMILES: [O:1]1[CH2:5][CH2:4][NH:3][C:2]1=[O:6].[CH2:7]1[CH2:11]O[CH2:9][CH2:8]1>[Pd]>[O:1]1[C:5]2[CH:11]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][C:2]1=[O:6]
Reactant: O=C1NCCO1
Reactant: C1CCOC1
Agent: [Pd]
Product: O=c1[nH]c2ccccc2o1
Reaction time: 3 h
Yield: 65 %

Procedure:
A mixture of oxazolidinone of formula 32 (1.00 g, 2.25 mmol) and 10% Pd/C (150 mg) in THF (50 mL) was shaken under an atmosphere of H2 at 50 psi for 3 hours. The reaction vessel was flushed with N2, then Et3N (1.25 mL) and COCl2 (1.20 mL of a 20% solution in toluene, 2.25 mmol) were added and the reaction stirred for 2 hours. The reaction was quenched with saturated NaHCO3, filtered, and the THF removed under reduced pressure. The aqueous solution was extracted with EtOAc. The organic layer was dried (Na2SO4) and the solvent removed under reduced pressure. Purification by chromatography (silica gel 1:2 to 4:5 EtOAc: hexanes) gave a benzoxazolidinone intermediate (510 mg, 65%): 1H NMR (500 MHz, CD3OD+CDCl3) δ 7.59 (br s, 1H), 7.22 (d, J=8 Hz, 1H), 7.06 (d, J=8 Hz, 1H), 4.76-4.70 (m, 2H), 4.16-4.07 (m, 1H), 3.88-3.84 (m, 1H), 3.44 (br s, 2H), 1.41 (s, 9H); CI-MS (m/z): 350 [M+H]+.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][N:4]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)[CH2:3][CH2:2]1.Br[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][N:22]1[C:26](=[O:27])[C:25]2=[CH:28][CH:29]=[CH:30][CH:31]=[C:24]2[C:23]1=[O:32].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[O:1]1[CH2:2][CH2:3][N:4]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][N:22]3[C:26](=[O:27])[C:25]4=[CH:28][CH:29]=[CH:30][CH:31]=[C:24]4[C:23]3=[O:32])=[CH:10][CH:9]=2)[CH2:5][CH2:6]1
Reactant: O=C1c2ccccc2C(=O)N1CCCCCCBr
Reactant: Oc1ccc(CN2CCOCC2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=C1c2ccccc2C(=O)N1CCCCCCOc1ccc(CN2CCOCC2)cc1
Temperature: 90 °C
Reaction time: 8 h

Procedure:
To a solution of 4-(morpholinomethyl)phenol (776 mg, 4.0 mmol) and N-(6-bromohexyl)phthalimide (1.24 g, 4.0 mmol) in DMF (10 mL) was added K2CO3 over 2 min. The reaction was heated to 90° C. for 3 h, then stirred at r.t. overnight. The mixture was concentrated and water (10 mL) added. This was extracted with ether (3×30 mL) and the combined organics washed with pH 7 phosphate buffer (20 mL), dried with Na2SO4, and concentrated to give the title compound as a clear oil.
Reaction SMILES: C(O[C:6]([N:8]1[CH2:12][CH:11]([CH2:13][O:14][CH3:15])[CH2:10][CH:9]1[C:16]1[NH:17][C:18]([C:21]2[CH:26]=[CH:25][C:24]([Br:27])=[CH:23][CH:22]=2)=[CH:19][N:20]=1)=[O:7])(C)(C)C.Cl.[CH3:29][O:30][C:31]([NH:33][CH:34]([CH:38]([CH3:40])[CH3:39])C(O)=O)=[O:32].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>C(Cl)Cl.CN(C=O)C.CCOC(C)=O>[CH3:29][O:30][C:31](=[O:32])[NH:33][CH:34]([C:6]([N:8]1[CH2:12][CH:11]([CH2:13][O:14][CH3:15])[CH2:10][CH:9]1[C:16]1[NH:17][C:18]([C:21]2[CH:22]=[CH:23][C:24]([Br:27])=[CH:25][CH:26]=2)=[CH:19][N:20]=1)=[O:7])[CH:38]([CH3:40])[CH3:39]
Reactant: COC(=O)NC(C(=O)O)C(C)C
Reactant: COCC1CC(c2ncc(-c3ccc(Br)cc3)[nH]2)N(C(=O)OC(C)(C)C)C1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: ClCCl
Product: COCC1CC(c2ncc(-c3ccc(Br)cc3)[nH]2)N(C(=O)C(NC(=O)OC)C(C)C)C1
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 97.8 %

Procedure:
2-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-4-methoxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (334 mg, 0.765 mmol) was dissolved in DCM (4 mL) and treated with HCl (4.0M in dioxane, 0.960 mL, 3.83 mmol). After 2.5 h, the solution was concentrated and the residue was treated with 2-Methoxycarbonylamino-3-methyl-butyric acid (146 mg, 0.832 mmol) and HATU (316 mg, 0.832 mmol). The solids were suspended in DMF (4 mL) and the reaction mixture was cooled to 0° C. before triethylamine (0.67 mL, 3.83 mmol) was added in a dropwise fashion. After 30 min, the mixture was warmed to RT. After another 1 h, it was diluted with EtOAc and washed with saturated aqueous NaHCO3 and brine. Then it was dried over MgSO4, filtered and concentrated. The crude residue was purified by silica column chromatography (80% to 100% EtOAc/Hex) to afford the title compound (369 mg, 98%).
Reaction SMILES: [C:1]1([N:7]2[CH:16]=[C:15]3[C:9]([CH2:10][CH2:11][NH:12][CH2:13][CH2:14]3)=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:17]1(=O)[CH2:20][CH2:19][CH2:18]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl>ClCCl.C(O)(=O)C>[CH:17]1([N:12]2[CH2:13][CH2:14][C:15]3=[CH:16][N:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[N:8]=[C:9]3[CH2:10][CH2:11]2)[CH2:20][CH2:19][CH2:18]1
Reactant: O=C1CCC1
Reactant: c1ccc(-n2cc3c(n2)CCNCC3)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Solvent: ClCCl
Solvent: CC(=O)O
Product: c1ccc(-n2cc3c(n2)CCN(C2CCC2)CC3)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a suspension of 2-phenyl-2,4,5,6,7,8-hexahydropyrazolo[3,4-d]azepine (may be prepared as described in Description 46) (39 mg, 0.18 mmol) in dichloromethane (4 ml) was added 3 drops of acetic acid, cyclobutanone (28 μl, 0.36 mmol) and sodium triacetoxyborohydride (77 mg, 0.36 mmol). The resulting mixture was allowed to stir at room temperature for 1 hour. The resulting reaction mixture was acidified with 2M hydrochloric acid and applied to an pre equilibrated ion exchange cartridge (SCX), washed with methanol and then a 2M ammonia in methanol solution. The basic fractions were then evaporated in vacuo to afford the title product (E45); MS (ES+) m/e 268 [M+H]+ as a 95:5 mixture of the title compound and 7-cyclobutyl-2-phenyl-2,4,5,6,7,8-hexahydropyrazolo[3,4-c]azepine.
Reaction SMILES: [CH:1]1([C:5]2[C:6]([C:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH:19]=3)=[C:7]([NH2:17])[N:8]([CH2:10][C:11]3[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=3)[N:9]=2)[CH2:4][CH2:3][CH2:2]1.C(N=[C:27]=[O:28])C>N1C=CC=CC=1>[CH:1]1([C:5]2[C:6]3[C:18]4[CH2:23][CH2:22][CH2:21][CH2:20][C:19]=4[C:27](=[O:28])[NH:17][C:7]=3[N:8]([CH2:10][C:11]3[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=3)[N:9]=2)[CH2:4][CH2:3][CH2:2]1
Reactant: Nc1c(C2=CCCCC2)c(C2CCC2)nn1Cc1cccnc1
Reactant: CCN=C=O
Solvent: c1ccncc1
Product: O=c1[nH]c2c(c(C3CCC3)nn2Cc2cccnc2)c2c1CCCC2
Temperature: 50 °C

Procedure:
To a solution of Example 85C (4 g, 18 mmol) in anhydrous pyridine (50 mL) was added ethyl isocyanate (3 mL) under nitrogen. The solution was heated at 50° C. for 6 h and under reflux overnight. The volatile were removed and the residual solid was purified by flash chromatography to give Example 85D. Yield: 4.2 g (70%). MS (DCI): m/z 335 (M+H)+, 1H NMR (300 MHz, CDCl3) δ 1.58 (s, 1H), 1.72-1.86 (m, 5H), 1.87-2.17 (m, 2H), 2.27-2.61 (m, 6H), 2.84 (s, 2H), 3.62-3.90 (m, 1H), 7.20 (dd, J=7.80, 4.75 Hz, 1H), 7.78 (d, J=7.80 Hz, 1H), 8.48 (d, J=3.05 Hz, 1H), 8.77 (s, 1H).
Reaction SMILES: [OH:1][C:2]1[C:3]([CH3:27])=[C:4]2[C:9](=[C:10]([CH3:13])[C:11]=1[CH3:12])[O:8][C:7]([CH3:26])([C:14]([NH:16][CH2:17][CH2:18][CH2:19][N:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1)=[O:15])[CH2:6][CH2:5]2.[O:28]=[N+]([O-])[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[Ce+4].[NH4+].[NH4+].[Na+].[Cl-].C([O-])(O)=O.[Na+]>C(C#N)(C)=O.O.CCOC(C)=O>[OH:28][C:7]([CH3:26])([CH2:6][CH2:5][C:4]1[C:9](=[O:8])[C:10]([CH3:13])=[C:11]([CH3:12])[C:2](=[O:1])[C:3]=1[CH3:27])[C:14]([NH:16][CH2:17][CH2:18][CH2:19][N:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1)=[O:15]
Reactant: O=[N+]([O-])[O-]
Reactant: Cc1c(C)c2c(c(C)c1O)CCC(C)(C(=O)NCCCN1CCOCC1)O2
Agent: CC(=O)C#N
Agent: O=C([O-])O
Agent: [Ce+4]
Solvent: O
Solvent: CCOC(C)=O
Product: CC1=C(C)C(=O)C(CCC(C)(O)C(=O)NCCCN2CCOCC2)=C(C)C1=O
Yield: 15.3 %

Procedure:
To a solution of 100 mg (0.266 mmol) of 6-hydroxy-2,5,7,8-tetramethyl-N-(3-morpholinopropyl)chroman-2-carboxamide in 5 mL AcCN and one drop of H2O at 0° C., was added a solution of 320.3 mg CAN (0.584 mmol) in 3 mL H2O dropwise. The solution was treated with 5 mL EtOAc and 5 mL saturated NaCl followed by ˜1 g of NaHCO3 and 1 h of vigorous stirring. The suspension was then extracted 3×5 mL 4:1 isopropyl alcohol:isopropyl acetate solution and the combined organics dried over Na2SO4, concentrated to a yellow oil and flashed chromatographed to yield 16 mg of 2-hydroxy-2-methyl-N-(3-morpholinopropyl)-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyl)butanamide as a dark yellow oil.
Reaction SMILES: [CH3:1][CH:2]1[CH2:11][C:10]2[N:9]([CH:12]([CH3:14])[CH3:13])[C:8](=[O:15])[N:7]=[C:6]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:5]=2[CH2:4][CH2:3]1.[S]>C1(C)C(C)=CC=CC=1>[CH3:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[N:7][C:8](=[O:15])[N:9]2[CH:12]([CH3:14])[CH3:13])=[CH:4][CH:3]=1
Reactant: CC1CCc2c(-c3ccccc3)nc(=O)n(C(C)C)c2C1
Agent: [S]
Solvent: Cc1ccccc1C
Product: Cc1ccc2c(-c3ccccc3)nc(=O)n(C(C)C)c2c1
Reaction time: 8 h

Procedure:
To 50 ml. of xylene are added 1.35 g. of 7-methyl-1-isopropyl-4-phenyl-5,6,7,8-tetrahydro-2(1H)-quinazolinone and 0.32 g. sulfur. The mixture is boiled overnight (about 16 hours). The resulting solution is evaporated under pressure and the crystalline residue is recrystallized from ether/petroleum ether to give 7-methyl-1-isopropyl-4-phenyl-2(1H)-quinazolinone.
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.[CH2:13]([O:20][N:21]1[C:30](=[O:31])[C:29]2[CH:32]=[C:33]([C:36]#[N:37])[C:34](Cl)=[C:27]3[C:28]=2[C:23](=[CH:24][CH:25]=[CH:26]3)[C:22]1=[O:38])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C(#N)C>[CH2:13]([O:20][N:21]1[C:30](=[O:31])[C:29]2[CH:32]=[C:33]([C:36]#[N:37])[C:34]([N:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)=[C:27]3[C:28]=2[C:23](=[CH:24][CH:25]=[CH:26]3)[C:22]1=[O:38])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: C1CCNC1
Reactant: N#Cc1cc2c3c(cccc3c1Cl)C(=O)N(OCc1ccccc1)C2=O
Solvent: CCN(CC)CC
Solvent: CC#N
Product: N#Cc1cc2c3c(cccc3c1N1CCCC1)C(=O)N(OCc1ccccc1)C2=O
Temperature: 0 °C
Yield: 68.6 %

Procedure:
To a solution of pyrrolidine (0.070 g, 0.98 mmol) and triethyl amine (0.11 g, 1.1 mmol) in acetonitrile (5 mL) at reflux was added 2-benzyloxy-6-chloro-5-cyano-benzo[de]isoquinoline-1,3-dione (0.20 g, 0.55 mmol, from Example A2). The reaction was heated at reflux for 20 minutes, then cooled to 0° C. The resulting precipitate was removed by filtration, washed with cold acetonitrile, and dried to give 0.15 g of the title compound.
Reaction SMILES: C(OC([NH:8][C:9]1([C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:22][CH2:21][N:20]([C:23]4[CH:28]=[CH:27][C:26]([CH2:29][CH2:30][C:31]([O:33][CH3:34])=[O:32])=[CH:25][CH:24]=4)[C:19]3=[O:35])=[CH:14][CH:13]=2)[CH2:11][CH2:10]1)=O)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[NH2:8][C:9]1([C:12]2[CH:13]=[CH:14][C:15]([N:18]3[CH2:22][CH2:21][N:20]([C:23]4[CH:28]=[CH:27][C:26]([CH2:29][CH2:30][C:31]([O:33][CH3:34])=[O:32])=[CH:25][CH:24]=4)[C:19]3=[O:35])=[CH:16][CH:17]=2)[CH2:10][CH2:11]1
Reactant: COC(=O)CCc1ccc(N2CCN(c3ccc(C4(NC(=O)OC(C)(C)C)CC4)cc3)C2=O)cc1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COC(=O)CCc1ccc(N2CCN(c3ccc(C4(N)CC4)cc3)C2=O)cc1

Procedure:
Prepared from 1-[4-(1-tert.butyloxycarbonylamino-cyclopropyl)-phenyl]-3-[4-(2-methoxycarbonyl-ethyl)-phenyl]-imidazolidin-2-one by stirring for two hours in a 1:1 mixture of methylene chloride and trifluoroacetic acid.
Reaction SMILES: [C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([NH:17][C:18]3[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=3)[N:15]=2)[N:10](COCC[Si](C)(C)C)[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].FC(F)(F)C(O)=O>ClCCl.CO.[OH-].[NH4+]>[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([NH:17][C:18]3[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=3)[N:15]=2)[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)NC(=O)c1cn(COCC[Si](C)(C)C)c2ncc(Nc3cccnc3)nc12
Agent: [NH4+]
Agent: [OH-]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Solvent: CO
Product: CC(C)(C)NC(=O)c1c[nH]c2ncc(Nc3cccnc3)nc12
Temperature: 25 °C
Reaction time: 16 h
Yield: 77.4 %

Procedure:
To a solution of N-tert-butyl-2-(pyridin-3-ylamino)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (44 mg, 99.9 mol) in dichloromethane (1.6 mL) was added trifluoroacetic acid (228 mg, 154 μL, 2.00 mmol) and the reaction mixture stirred at room temperature for 16 h. The reaction mixture was concentrated in vacuo and the residue obtained diluted with dichloromethane (1.6 mL), methanol (0.8 mL) and ammonium hydroxide (0.2 mL) and stirred at room temperature for 1 h. The mixture was concentrated and triturated with water. The solid was collected by filtration and washed with water and ether to give N-tert-butyl-2-(pyridin-3-ylamino)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (24 mg, 77.3 mol, 77%) as a brown solid. 1H NMR (400 MHz, DMSO-d) δ ppm: 12.26 (s, 1H), 9.54 (s, 1H), 8.77 (d, J=2.5, 1 H), 8.04 (d, J=4.6, 1 H), 7.98 (d, J=8.5, 1 H), 7.92 (d, J=3.3, 1 H), 7.91 (s, 1H), 7.57 (s, 1H), 7.19 (m, 1H), 1.31 (s, 9H); MS (EI/CI) m/z: 311.1 [M+H].
Reaction SMILES: [CH2:1]([C:6]([CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])=[CH2:7])[CH2:2][CH2:3][CH2:4][CH3:5].CC(C)([O-])C.[K+].[CH:19]([Br:22])(Br)[Br:20].Cl>O>[Br:20][C:19]1([Br:22])[CH2:7][C:6]1([CH2:1][CH2:2][CH2:3][CH2:4][CH3:5])[CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: C=C(CCCCC)CCCCC
Reactant: BrC(Br)Br
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: O
Product: CCCCCC1(CCCCC)CC1(Br)Br
Temperature: 25 °C
Reaction time: 8 h
Yield: 83.3 %

Procedure:
To a solution of 4.16 g (0.0247 mol) of 2-pentyl-hept-1-ene in 31 ml of pentanes, was added 4.95 g (0.0441 mol) of potassium t-butoxide. While cooling the resulting mixture to an internal temperature of 5° C., 4.01 ml ( 0.0459 mol) of bromoform was added slowly via addition funnel. The reaction mixture was allowed to warm naturally to room temperature and left overnight. To the reaction mixture was added 25 ml of water then 36 ml of 1 N hydrochloric acid. The resulting mixture was transferred to a separatory funnel and the phases were separated. The organic layer was dried over MgSO4 and filtered. The solvent was removed from the filtrate in vacuo to yield 7.00 g (83.4% of theory) of 2,2-dibromo-1,1-dipentyl-cyclopropane as an oil.