Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[C:12]([O:13][CH3:14])=[N:11][C:10]2[C:9]([C:15](Cl)=[O:16])=[C:8]([CH3:18])[C:7]([N+:19]([O-:21])=[O:20])=[CH:6][C:5]=2[N:4]=1.[NH:22]1[CH2:28][CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1>>[N:22]1([C:15]([C:9]2[C:8]([CH3:18])=[C:7]([N+:19]([O-:21])=[O:20])[CH:6]=[C:5]3[C:10]=2[N:11]=[C:12]([O:13][CH3:14])[C:3]([O:2][CH3:1])=[N:4]3)=[O:16])[CH2:28][CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1
Reactant: C1CNCCNC1
Reactant: COc1nc2cc([N+](=O)[O-])c(C)c(C(=O)Cl)c2nc1OC
Product: COc1nc2cc([N+](=O)[O-])c(C)c(C(=O)N3CCCNCC3)c2nc1OC
Reaction time: 30 h

Procedure:
Prepared from 2,3-dimethoxy-6-methyl-7-nitro-quinoxaline-5-carbonyl chloride (13) 250 mg (0.80 mmol) and homopiperazine 160 mg (1.60 mmol). Reaction was continued for 30 hours, and the crude product was eluted through a flash column (8% methanol in chloroform), 260 mg (87%), mp 141-143° C.; 1H NMR (CDCl3): δ 8.29 (s, 1H), 4.03 (s, 3H), 3.93 (br s, 7H), 3.02 (br s, 2H), 2.82 (t, 2H, J=5.4, J=5.6 Hz), 2.54 (s, 3H), 1.88 (t, 2H, J=5.6, 5.4 Hz), 1.79 (bs, 1H); MS (APCI): m/z 376 (M+H).
Reaction SMILES: N[C:2]1([CH3:25])[CH2:7][CH2:6][CH:5]([O:8][C:9]2[C:20]3[C:19]4[C@@H:18]([CH2:21][C:22]([NH2:24])=[O:23])[CH2:17][CH2:16][C:15]=4[S:14][C:13]=3[N:12]=[CH:11][N:10]=2)[CH2:4][CH2:3]1.[CH2:26]=O.[BH3-][C:29]#[N:30].[Na+]>CO>[CH3:26][N:30]([CH3:29])[C:2]1([CH3:25])[CH2:7][CH2:6][CH:5]([O:8][C:9]2[C:20]3[C:19]4[C@@H:18]([CH2:21][C:22]([NH2:24])=[O:23])[CH2:17][CH2:16][C:15]=4[S:14][C:13]=3[N:12]=[CH:11][N:10]=2)[CH2:4][CH2:3]1
Reactant: [BH3-]C#N
Reactant: C=O
Reactant: CC1(N)CCC(Oc2ncnc3sc4c(c23)[C@@H](CC(N)=O)CC4)CC1
Agent: [Na+]
Solvent: CO
Product: CN(C)C1(C)CCC(Oc2ncnc3sc4c(c23)[C@@H](CC(N)=O)CC4)CC1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of 2-[(3R)-12-[(4-amino-4-methylcyclohexyl)oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]acetamide (200 mg, 0.55 mmol, 1.00 equiv) in 8 mL of methanol was added HCHO (37%, 1.2 mL). The solution was stirred for 0.5 h at room temperature. Then NaBH3CN (105 mg, 1.67 mmol, 3.01 equiv) was added and the resulting solution was allowed to react, with stirring, for an additional 1 h at room temperature. The reaction was quenched with NH4Cl (aq.) and extracted with 3×60 mL of DCM. The combined organic layers were concentrated under vacuum. The crude product (150 mg) was purified by preparative HPLC under the following conditions (Waters): column: XBridge Prep C18 OBD column: 5 um, 19*150 mm; mobile phase: water with 0.05% NH4HCO3 and CH3CN (5% CH3CN up to 47% in 13 min, up to 95% in 2 min, down to 5% in 2 min); flow rate: 20 mL/min; UV detection at 254 & 220 nm. This resulted in 39.8 mg of 2-[(3R)-12-[[4-(dimethylamino)-4-methylcyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]acetamide as a white solid. MS: m/z 389 (M+H)+. 1H NMR (300 MHz, CD3OD): δ 8.49 (1H, s), 5.41 (1H, m), 3.80 (1H, m), 3.19 (1H, m), 3.04 (1H, m), 2.98 (1H, m), 2.85 (6H, s), 2.76 (1H, m), 2.31 (4H, m), 2.14 (2H, m), 1.96 (4H, m), 1.47 (3H, s).
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][C:11]([C:19]([C:31]2[CH:36]=[CH:35][C:34]([C:37]([F:40])([F:39])[F:38])=[CH:33][CH:32]=2)([C:21]2[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][CH:22]=2)[Cl:20])([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl.C1(C)C=CC=CC=1>[F:39][C:37]([F:38])([F:40])[C:34]1[CH:33]=[CH:32][C:31]([C:19]([C:21]2[CH:22]=[CH:23][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:25][CH:26]=2)([Cl:20])[C:11]2([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]2)=[CH:36][CH:35]=1
Reactant: CCOC(=O)C1(C(Cl)(c2ccc(C(F)(F)F)cc2)c2ccc(C(F)(F)F)cc2)CCN(C(=O)OC(C)(C)C)CC1
Solvent: O=C(O)C(F)(F)F
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: CCOC(=O)C1(C(Cl)(c2ccc(C(F)(F)F)cc2)c2ccc(C(F)(F)F)cc2)CCNCC1
Yield: 100 %

Procedure:
A solution of 190 milligrams (0.320 mmole) of ethyl 1-[(tert-butyl)oxycarbonyl]-4-{bis[4-(trifluoromethyl)phenyl]chloromethyl}piperidine-4-carboxylate and 2 mL of trifluoro acetic acid (TFA) in 0.5 mL of methylene chloride was stirred at room temperature for 10 minutes. The reaction mixture was then diluted with toluene and concentrated under reduced pressure, yielding 158 milligrams of the subject compound. The NMR spectrum was consistent with the proposed structure.
Reaction SMILES: [CH:1]([OH:5])(O)[CH2:2][CH3:3].[H-].[Na+].[CH2:8](Br)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.CN(C)C=[O:19]>>[CH2:8]([O:19][CH2:3][CH2:2][CH2:1][OH:5])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: CN(C)C=O
Reactant: CCC(O)O
Reactant: BrCc1ccccc1
Agent: [H-]
Agent: [Na+]
Product: OCCCOCc1ccccc1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 68 %

Procedure:
38.05 g(0.50 mol) of propandiol was dissolved in 400 ml of dimethylformamide and cooled to 0° C. 20.0 g(0.5 mol) of 60% sodium hydride dispersed in mineral oil was added slowly. After the mixture was stirred for 10 minutes, 51.31 g(0.30 mol) of benzylbromide dissolved in 100 ml of dimethylformamide was added slowly. After stirring for one hour at room temperature, dimethylformamide was removed under reduced pressure, 500 ml of ethylacetate was added, and the organic layer was washed with saturated sodium chloride solution (200 ml×3). The organic layer was dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to column chromatography to give 33.80 g(0.203 mol, Yield 68%) of the title compound.
Reaction SMILES: [Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([CH3:16])([CH3:15])[CH2:7][CH:8]=[C:9]2[CH:12]([CH3:14])[CH3:13])=[CH:4][C:3]=1[OH:17].C(=O)([O-])[O-].[K+].[K+].I[CH2:25][CH2:26][CH3:27]>CC(C)=O>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([CH3:15])([CH3:16])[CH2:7][CH:8]=[C:9]2[CH:12]([CH3:13])[CH3:14])=[CH:4][C:3]=1[O:17][CH2:25][CH2:26][CH3:27]
Reactant: CC(C)C1=CCC(C)(C)c2cc(O)c(Br)cc21
Reactant: CCCI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCCOc1cc2c(cc1Br)C(C(C)C)=CCC2(C)C

Procedure:
As described in General Procedure D-1, 7-bromo-4,4-dimethyl-6-hydroxy-1-isopropyl-3,4-dihydronaphthalene (Compound A-30, U.S. Pat. No. 6,613,917, 0.100 g, 0.339 mmol), potassium carbonate (140 mg) and 1-iodopropane (0.331 mL, 3.39 mmol), were reacted in acetone (3 mL) to produce the title compound as a clear oil after purification by flash column chromatography (silica gel, 98:2 hexane/ethyl acetate).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[CH:4][C:5]2[S:10][C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=3)=[N:8][C:7](=[O:17])[C:6]=2[CH:18]=1.Br[CH2:20][CH2:21][CH2:22][OH:23].C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>O>[OH:23][CH2:22][CH2:21][CH2:20][O:1][C:2]1[CH:3]=[CH:4][C:5]2[S:10][C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=3)=[N:8][C:7](=[O:17])[C:6]=2[CH:18]=1
Reactant: OCCCBr
Reactant: O=c1nc(-c2ccccn2)sc2ccc(O)cc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: O=c1nc(-c2ccccn2)sc2ccc(OCCCO)cc12
Temperature: 25 °C
Reaction time: 15 h
Yield: 57.3 %

Procedure:
A mixture of 6-hydroxy-2-(2-pyridyl)-4H-1,3-benzothiazine-4-one (0.40 g, 1.5 mmol), 3-bromo-1-propanol (0.66 g, 4.7 mmol) and potassium carbonate (0.43 g, 3.1 mmol) and DMF (10 ml) was stirred at room temperature for 15 hrs. The reaction mixture was diluted with water and extracted with a mixture solvent of ethyl acetate and ethanol. The extract was washed with water and dried. The solvent was evaporated. The obtained crystals were recrystallized from ethanol-hexane to give the titled compound (0.27 g, 54%).
Reaction SMILES: [Cl:1][C:2]1[CH:31]=[CH:30][C:5]2[C:6]3[CH2:7][CH2:8][CH2:9][N:10]([C:14](=[O:29])[CH2:15][CH2:16][CH2:17][N:18]4C(=O)C5=CC=CC=C5C4=O)[C:11]=3[CH2:12][CH2:13][C:4]=2[CH:3]=1.O.NN>C(O)C>[ClH:1].[NH2:18][CH2:17][CH2:16][CH2:15][C:14]([N:10]1[C:11]2[CH2:12][CH2:13][C:4]3[CH:3]=[C:2]([Cl:1])[CH:31]=[CH:30][C:5]=3[C:6]=2[CH2:7][CH2:8][CH2:9]1)=[O:29]
Reactant: O=C(CCCN1C(=O)c2ccccc2C1=O)N1CCCC2=C1CCc1cc(Cl)ccc12
Agent: NN
Solvent: CCO
Solvent: O
Product: Cl
Product: NCCCC(=O)N1CCCC2=C1CCc1cc(Cl)ccc12

Procedure:
A suspension of 10.9 g (0.025 mol) of 8-chloro -1,2,3,4,5,6-hexahydro-4-(4-phthalimidobutyryl)benzo[f]-quinoline and 3.2 ml (0.065 mol) of hydrazine hydrate in 150 ml of ethanol is boiled at reflux temperature for 2 hours. The solution is concentrated, extracted with methylene chloride/water dried with sodium sulfate and the solvent is distilled in a vacuum. The residue is dissolved in 10 ml of 5.5N methanolic hydrochloric acid and precipitated with ether. Recrystallization from methanol/ether gives 4-(4-aminobutyryl)-8-chloro -1,2,3,4,5,6-hexahydrobenzo[f]quinoline hydrochloride as beige crystals with melting point 225°.
Reaction SMILES: [OH:1][CH:2]1[CH2:6][N:5]([CH2:7][C:8](OCC)=[O:9])[C:4](=[O:13])[CH2:3]1.[NH3:14]>CC(C)=O>[OH:1][CH:2]1[CH2:6][N:5]([CH2:7][C:8]([NH2:14])=[O:9])[C:4](=[O:13])[CH2:3]1
Reactant: N
Reactant: CCOC(=O)CN1CC(O)CC1=O
Solvent: CC(C)=O
Product: NC(=O)CN1CC(O)CC1=O
Temperature: 25 °C

Procedure:
A solution of 7.1 g ethyl 4-hydroxy-2-oxo-1-pyrrolidineacetate obtained in Example 12, in 7.1 ml ammonia solution (d25 =0.90) is stirred at ambient temperature for 15 h. It is then diluted with 140 ml acetone and the mixture is stirred at ambient temperature until the gum that precipitates solidifies into white crystals. On filtering in vacuo and drying, 4-hydroxy-2-oxo-1-pyrrolidineacetamide is obtained, m.p. 160°-162° C.
Reaction SMILES: [O:1]1[CH:3]2[CH:4]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH2:5][CH2:6][CH:7]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[CH:2]12.C([O-])([O-])=[O:21].[Na+].[Na+].[K+].[Br-]>CC(C)=O>[C:14]1([CH:4]2[CH2:5][CH2:6][CH:7]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[CH:2]([OH:21])[CH:3]2[OH:1])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: O=C([O-])[O-]
Reactant: c1ccc(C2CCC(c3ccccc3)C3OC23)cc1
Agent: [Br-]
Agent: [K+]
Agent: [Na+]
Solvent: CC(C)=O
Product: OC1C(c2ccccc2)CCC(c2ccccc2)C1O
Temperature: 25 °C
Reaction time: 24 h

Procedure:
1,2-Epoxy-3,6-diphenylcyclohexane (32 mg, 0.13 mmol) was dissolved in acetone (10 mL). HClO4 (6%, 10 mL) was added and the mixture was stirred at room temperature for 24 hours. The reaction solution was neutralized with Na2CO3 and the reaction mixture was reduced to approximately half volume under reduced pressure. Extraction with CH2Cl2 and removal of the solvent yielded crude product (93% yield) as a white solid. Based upon the analyses of NMR spectra of crude and recrystallized product, reaction gave a single product. Recrystallization from hexane/CH2Cl2 gave pure product as a white crystalline solid: mp 134°-135° C.; IR (KBr) 3303, 3086, 3059, 3026, 2935, 2858, 1603, 1495, 1454, 1041, 760, 698 cm-1 ; 1H NMR (200 MHz, CDCl3) δ 7.20-7.60 (m, 10 H), 4.08 (t, J=9.8 Hz, 1 H), 3.95 (dd, J= 9.5, 5.5 Hz, 1 H), 3.56 (m, 1 H), 2.67 (ddd, J=11.7, 9.9, 4.3 Hz, 1 H), 1.65-2.39 (m, 6 H); 13C NMR (50 MHz, CDCl3) δ 142.3, 140.8, 129.7, 128.8, 128.4, 127.8, 126.9, 126.5, 76.8, 74.6, 50.6, 44.7, 29.9, 29.2; MS (EI) m/e (relative intensity) 268 (M+, 61.9), 250 (12.9), 237 (11.5), 219 (7.3), 146 (30.1), 131 (94.9), 117 55.4), 104 (100.0), 91 (73.6), 77 (15.3); HRMS calcd. for C18H20O2 m/e 268.1463, found m/e 268.1464.
Reaction SMILES: [C:1]([C:5]1[NH:9][C:8]([C:10]([OH:12])=O)=[C:7]([N+:13]([O-:15])=[O:14])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].P(Cl)(Cl)(Cl)(Cl)Cl.[CH3:22][C:23]1([CH3:30])[NH:28][CH2:27][CH2:26][NH:25][C:24]1=[O:29].CCN(C(C)C)C(C)C>ClCCl>[C:1]([C:5]1[NH:9][C:8]([C:10]([N:28]2[CH2:27][CH2:26][NH:25][C:24](=[O:29])[C:23]2([CH3:30])[CH3:22])=[O:12])=[C:7]([N+:13]([O-:15])=[O:14])[CH:6]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C)(C)c1cc([N+](=O)[O-])c(C(=O)O)[nH]1
Reactant: CC1(C)NCCNC1=O
Agent: ClP(Cl)(Cl)(Cl)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(C)(C)c1cc([N+](=O)[O-])c(C(=O)N2CCNC(=O)C2(C)C)[nH]1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 53.1 %

Procedure:
The previously prepared 5-tert-butyl-3-nitro-1H-pyrrole-2-carboxylic acid (0.203 g, 1.11 mmol) and PCl5 (0.232 g, 1.11 mmol) were dissolved in dichloromethane (4 mL) and stirred at room temperature for 5 minutes. The resulting solution was added in one portion to a solution of 3,3-dimethylpiperazin-2-one (0.214 g, 1.67 mmol) and DIEA (0.288 g, 2.23 mmol) in dichloromethane (3 mL) and stirred at room temperature for 5 minutes. The reaction mixture was diluted with dichloromethane and washed sequentially with 1N aqueous HCl, saturated sodium bicarbonate, dried and the solvent removed under vacuum. The crude product was purified by chromatographic column (silica gel, dichloromethane:methanol, 95:5) to afford 0.190 g of expected 4-(2-tert-butyl-4-nitro-1H-pyrrole-5-carbonyl)-3,3-dimethylpiperazin-2-one.
Reaction SMILES: C[Si](Cl)(C)C.[C:6]1(=[O:13])[CH2:11][CH2:10][CH2:9][C:8](=[O:12])[CH2:7]1.[CH:14]([C:16]1[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][CH:17]=1)=O.[F:24][C:25]([F:37])([F:36])[C:26]1[CH:27]=[C:28]([NH:32][C:33]([NH2:35])=[O:34])[CH:29]=[CH:30][CH:31]=1>CN(C)C=O.C(#N)C.O>[C:20]([C:19]1[CH:22]=[CH:23][C:16]([CH:14]([C:7]2[C:8](=[O:12])[CH2:9][CH2:10][CH2:11][C:6]=2[OH:13])[NH:35][C:33]([NH:32][C:28]2[CH:29]=[CH:30][CH:31]=[C:26]([C:25]([F:36])([F:37])[F:24])[CH:27]=2)=[O:34])=[CH:17][CH:18]=1)#[N:21]
Reactant: N#Cc1ccc(C=O)cc1
Reactant: O=C1CCCC(=O)C1
Reactant: NC(=O)Nc1cccc(C(F)(F)F)c1
Agent: C[Si](C)(C)Cl
Solvent: CN(C)C=O
Solvent: O
Solvent: CC#N
Product: N#Cc1ccc(C(NC(=O)Nc2cccc(C(F)(F)F)c2)C2=C(O)CCCC2=O)cc1
Temperature: 25 °C

Procedure:
Trimethylsilyl chloride (50.7 mL, 400 mmol) is added to a solution of cyclohexane-1,3-dione (11.2 g, 100 mmol), 4-formylbenzonitrile (13.8 g, 105 mmol) and 1-(3-(trifluoromethyl)phenyl)urea (20.4 g, 100 mmol) in a mixture of N,N-dimethylformamide (100 mL) and acetonitrile (150 mL), and the mixture is stirred at room temperature over night. The reaction mixture is poured into a mixture of water and ice (2 L) and stirred for 2 h. The mixture is filtered and the precipitate is dried under reduced pressure. Yield: 41.9 g; ESI mass spectrum [M+H]+=430, Retention time HPLC: 0.91 min (Z018_S04).
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Br[C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1.[CH2:28]([OH:32])[CH2:29][C:30]#[CH:31]>C(N(CC)CC)C.C(OC)(C)(C)C.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[F:27][C:24]1[CH:25]=[CH:26][C:21]([C:31]#[C:30][CH2:29][CH2:28][OH:32])=[CH:22][CH:23]=1
Reactant: Fc1ccc(Br)cc1
Reactant: C#CCCO
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: COC(C)(C)C
Solvent: O
Product: OCCC#Cc1ccc(F)cc1
Reaction time: 5 h
Yield: 86 %

Procedure:
1 g of bis-(triphenylphosphine)-palladium(II) chloride, 3.8 g of copper(I) iodide and 8.7 g of triphenylphosphine were added in succession to a solution of 100 g of 4-bromofluorobenzene in 350 ml of triethylamine. The mixture was heated to reflux temperature, after which 43.4 g of 3-butynol were added dropwise in the course of 20 minutes at this temperature (about100° C.). Stirring was carried out for a further 5 hours at this temperature. After the mixture had cooled, the triethylamine was distilledoff. The residue was taken up in methyl tert-butyl ether and water. The aqueous phase was extracted twice more with methyl tert-butyl ether, and the combined organic extracts were washed in succession with 1 N hydrochloric acid and with 10% strength by weight sodium bicarbonate solution and dried over sodium sulfate. After removal of the solvent, the crude product was distilled under greatly reduced pressure. Yield: 86%.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[C:10](Br)=[C:9]([NH2:12])[N:8]=[C:7]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([O:20][CH3:21])[C:14]=2[F:22])[N:6]=1)=[O:4].[CH2:23]([Sn](CCCC)(CCCC)C=C)[CH2:24]CC>ClCCCl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:1][O:2][C:3]([C:5]1[C:10]([CH:23]=[CH2:24])=[C:9]([NH2:12])[N:8]=[C:7]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([O:20][CH3:21])[C:14]=2[F:22])[N:6]=1)=[O:4]
Reactant: C=C[Sn](CCCC)(CCCC)CCCC
Reactant: COC(=O)c1nc(-c2ccc(Cl)c(OC)c2F)nc(N)c1Br
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: ClCCCl
Product: C=Cc1c(N)nc(-c2ccc(Cl)c(OC)c2F)nc1C(=O)OC
Temperature: 130 °C
Yield: 81.7 %

Procedure:
6-Amino-5-bromo-2-(4-chloro-2-fluoro-3-methoxyphenyl)-pyrimidine-4-carboxylic acid methyl ester (1.5 g, 3.84 mmol), tributyl(vinyl)tin (2.436 g, 7.68 mmol), bis(triphenylphosphine)palladium(II) dichloride (0.270 g, 0.384 mmol) were combined in 1,2-dichloroethane (4 mL) and heated at 130° C. for 15 min in a CEM microwave reactor. The cooled reaction mixture was concentrated onto silica gel and purified by flash chromatography on silica gel (ethyl acetate/hexane gradient) to yield the title compound (1.06 g, 82% yield): mp 145-147° C.: 1H NMR (CDCl3) δ 7.64 (m, 1H), 7.22 (m, 1H), 6.84 (dd, 1H), 5.68 (m, 2H), 5.43 (br s, 2H), 3.99 (d, 3H), 3.95 (s, 3H).
Reaction SMILES: [CH3:1][S:2][C:3]1[C:4](=[O:27])[C:5](=[CH:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]([O:25][CH3:26])=[O:24])[C:6]([OH:16])([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])[CH:7]=1.ClC1C=CC=C(C(OO)=[O:36])C=1.C(=O)([O-])O.[Na+]>ClCCl>[CH3:1][S:2]([C:3]1[C:4](=[O:27])[C:5](=[CH:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]([O:25][CH3:26])=[O:24])[C:6]([OH:16])([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])[CH:7]=1)=[O:36]
Reactant: CCCCCCCCC1(O)C=C(SC)C(=O)C1=CCCCCCC(=O)OC
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CCCCCCCCC1(O)C=C(S(C)=O)C(=O)C1=CCCCCCC(=O)OC
Temperature: 0 °C
Reaction time: 1 h
Yield: 61 %

Procedure:
To a solution of 12 mg of 2-methylthio-4-hydroxy-5-(6-methoxycarbonylhexylidene)-4-octyl-2-cyclopentenone obtained in Example 579 dissolved in 2 ml of dichloromethane was added 6.5 mg of 3-chloroperbenzoic acid. After the mixture was stirred at 0° C. for 1 hour, saturated aqueous sodium hydrogencarbonate was added, and the mixture was extracted with ethyl acetate. After washing with saturated aqueous sodium chloride, the product was subjected to silica gel chromatography to obtain 7.3 mg (yield 61%).
Reaction SMILES: [CH2:1]([CH:5]1[C:18]2[C:17](=[O:19])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10](=[O:20])[C:9]=2[CH2:8][CH:7]=[CH:6]1)[CH2:2][CH:3]=[CH2:4].[H][H]>[Pd].C(OCC)(=O)C>[CH2:1]([CH:5]1[C:18]2[C:17](=[O:19])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10](=[O:20])[C:9]=2[CH2:8][CH2:7][CH2:6]1)[CH2:2][CH2:3][CH3:4]
Reactant: C=CCCC1C=CCC2=C1C(=O)c1ccccc1C2=O
Reactant: [H][H]
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CCCCC1CCCC2=C1C(=O)c1ccccc1C2=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 83 %

Procedure:
A 5.0 g. sample of 1,4-dihydro-1-(3-butenyl)anthraquinone (6a, R = H) was dissolved in 100 ml. of ethyl acetate. The solution was then hydrogenatd using 0.2 g. 10% Pd/C catalyst. After the absorption of three equivalents of hydrogen, the mixture was filtered to remove the catalyst. It was then stirred at room temperature overnight while exposed to air to oxidize the hydroquinone. After removal of the solvent, the residue was recrystallized from methanol to give 4.2 g. product (83% yield). The gas chromatographic retention time, infrared spectrum, and nmr spectrum of this sample were identical with those of an authentic sample.
Reaction SMILES: CC(C)([O-:4])C.[K+].C[O:8][C:9](=[O:21])[C:10]([C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[NH:14][CH:13]=1)=O.[Cl:22][C:23]1[C:24]([CH2:37][C:38]([NH2:40])=[O:39])=[C:25]2[C:30](=[CH:31][CH:32]=1)[N:29]=[CH:28][C:27]([CH2:33][N:34]([CH3:36])[CH3:35])=[N:26]2.[NH4+].[Cl-]>O1CCCC1.CCOC(C)=O>[Cl:22][C:23]1[C:24]([C:37]2[C:38](=[O:39])[NH:40][C:9](=[O:21])[C:10]=2[C:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[NH:14][CH:13]=2)=[C:25]2[C:30](=[CH:31][CH:32]=1)[N:29]=[CH:28][C:27]([CH2:33][N:34]([CH3:35])[CH3:36])=[N:26]2.[CH3:35][N:34]([CH2:33][C:27]1[CH:28]=[N:29][C:30]2[C:25]([N:26]=1)=[C:24]([C:37]1[C:38](=[O:39])[NH:40][C:9](=[O:8])[C:10]=1[C:12]1[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[NH:14][CH:13]=1)[C:23]([OH:4])=[CH:32][CH:31]=2)[CH3:36]
Reactant: COC(=O)C(=O)c1c[nH]c2ccccc12
Reactant: CN(C)Cc1cnc2ccc(Cl)c(CC(N)=O)c2n1
Reactant: CC(C)(C)[O-]
Agent: [Cl-]
Agent: [K+]
Agent: [NH4+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CN(C)Cc1cnc2ccc(Cl)c(C3=C(c4c[nH]c5ccccc45)C(=O)NC3=O)c2n1
Product: CN(C)Cc1cnc2ccc(O)c(C3=C(c4c[nH]c5ccccc45)C(=O)NC3=O)c2n1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 27 %
Yield: 12 %

Procedure:
Potassium tert-butoxide (1.0 M in THF, 0.86 ml, 0.86 mmol, 4.0 equiv) was added at room temperature under an atmosphere of argon to a solution of (1H-indol-3-yl)-oxo-acetic acid methyl ester (66 mg, 0.32 mmol, 1.5 equiv) and of 2-(6-chloro-3-dimethylaminomethyl-quinoxalin-5-yl)-acetamide (60 mg, 0.22 mmol) in anhydrous tetrahydrofuran (3.0 ml, dried over molecular sieves). The reaction mixture was stirred for 15 minutes at room temperature. It was then diluted with EtOAc and poured into a saturated aqueous NH4Cl solution. After three extractions with EtOAc, the combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. Purification of the residue via preparative HPLC afforded the title compound (32 mg, 27%) and 3-(3-dimethylaminomethyl-6-hydroxy-quinoxalin-5-yl)-4-(1H-indol-3-yl)-pyrrole-2,5-dione (14 mg, 12%) as their trifluoroacetate salts. Data for 3-(6-chloro-3-dimethylaminomethyl-quinoxalin-5-yl)-4-(1H-indol-3-yl)-pyrrole-2,5-dione: 1H NMR (400 MHz, d6-DMSO): δ=11.97 (s, 1H), 11.26 (s, 1H), 9.86 (s, 1H), 9.01 (s, 1H) 8.29 (d, J=9.0 Hz, 1H), 8.06-8.04 (m, 2H), 7.35 (d, J=8.0 Hz, 1H), 6.96 (dt, J=7.6/1.0 Hz, 1H), 6.49 (dt, J=8.1/1.0 Hz, 1H), 6.09 (d, J=8.3 Hz, 1H), 4.68 (s, 2H), 2.66 (s, 6H). MS (ES+): 432.2 (M+H)+. Data for 3-(3-dimethylaminomethyl-6-hydroxy-quinoxalin-5-yl)-4-(1H-indol-3-yl)-pyrrole-2,5-dione: 1H NMR (400 MHz, d6-DMSO): δ=11.80 (s, 1H), 11.01 (s, 1H), 10.64 (s, 1H), 9.79 (s, 1H), 8.75 (s, 1H), 8.08 (d, J=9.3 Hz, 1H), 7.95 (d, J=2.9 Hz, 1H), 7.51 (d, J=9.0 Hz, 1H), 7.32 (d, J=8.1 Hz, 1H), 6.93 (dt, J=7.6/0.9 Hz, 1H), 6.48 (dt, J=8.1/1.0 Hz, 1H), 6.34 (d, J=8.3 Hz), 4.58 (s, 2H), 2.67 (s, 6H). MS (ES+): 414.3 (M+H)+.