Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: S([O-])(O)(=O)=O.[K+].CN(C)[C:9]1[CH2:13][O:12][C:11](=[O:14])[CH:10]=1.[Cl:16][C:17]1[N:22]=[CH:21][C:20]([CH2:23][NH:24][CH2:25][CH:26]([F:28])[F:27])=[CH:19][CH:18]=1>C(#N)CCC>[Cl:16][C:17]1[N:22]=[CH:21][C:20]([CH2:23][N:24]([CH2:25][CH:26]([F:28])[F:27])[C:9]2[CH2:13][O:12][C:11](=[O:14])[CH:10]=2)=[CH:19][CH:18]=1
Reactant: FC(F)CNCc1ccc(Cl)nc1
Reactant: CN(C)C1=CC(=O)OC1
Agent: O=S(=O)([O-])O
Agent: [K+]
Solvent: CCCC#N
Product: O=C1C=C(N(Cc2ccc(Cl)nc2)CC(F)F)CO1
Temperature: 25 °C
Yield: 85.9 %

Procedure:
3.9 g of potassium hydrogen sulphate are added at room temperature to a suspension of 4.1 g of 4-(dimethylamino)furan-2(5H)-one and 5 g of N-[(6-chloropyridin-3-yl)methyl]-2,2-difluoroethylamine in 50 ml of butyronitrile. The mixture is refluxed for 8 h. Thereafter, cooling at room temperature and washing twice with 50 ml of water are effected. The solvent is removed in vacuo. 6 g of 4-[[(6-chloropyridin-3-yl)methyl](2,2-difluoroethyl)amino]furan-2(5H)-one are obtained with a purity of 92% (82% yield).
Reaction SMILES: [C:1]1([S:11]([OH:13])=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[OH-].[Na+].[CH:16]([S:18](Cl)(=[O:20])=[O:19])=[CH2:17]>O.C(#N)C>[CH:16]([S:18](=[O:20])(=[O:19])[S:11]([C:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1)(=[O:13])=[O:12])=[CH2:17]
Reactant: O=S(O)c1cccc2ccccc12
Reactant: C=CS(=O)(=O)Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CC#N
Solvent: O
Product: C=CS(=O)(=O)S(=O)(=O)c1cccc2ccccc12
Yield: 24.9 %

Procedure:
15 ml of water was added to 9.6 g of 1-naphthalene sulfinic acid and a solution of 2 g of sodium hydroxide in 5 ml of water was added to the mixture. To the solution there was added a solution of 6.3 g of vinylsulfonyl chloride in 20 ml of acetonitrile at room temperature with stirring and the mixture was stirred at room temperature for additional 24 hours. The reaction solution was poured into 300 ml of water, the resulting precipitates were recovered through filtration and recrystallized from a mixed solvent of benzene and ethanol to give 3.5 g of vinyl-1-naphthyldisulfone.
Reaction SMILES: [CH:1]([O:4][C:5]1[CH:6]=[C:7]([CH2:11][C:12]([OH:14])=O)[CH:8]=[CH:9][CH:10]=1)([CH3:3])[CH3:2].C(Cl)(=O)C([Cl:18])=O>CN(C)C=O.ClCCl>[CH:1]([O:4][C:5]1[CH:6]=[C:7]([CH2:11][C:12]([Cl:18])=[O:14])[CH:8]=[CH:9][CH:10]=1)([CH3:3])[CH3:2]
Reactant: O=C(Cl)C(=O)Cl
Reactant: CC(C)Oc1cccc(CC(=O)O)c1
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CC(C)Oc1cccc(CC(=O)Cl)c1
Temperature: -5 °C
Reaction time: 1 h

Procedure:
Combine 3-isopropoxy-phenyl-acetic acid (0.5 g, 2.6 mmol) and dichloromethane (5 mL). Cool to -5° C. using a ice-salt bath. Add 2 drops of dimethylformamide followed by dropwise addition of oxalyl chloride (0.34 g, 2.7 mmol). after 1 hour, warm the reaction mixture to ambient temperature. After 2 hours, evaporate the reaction mixture in vacuo to give the title compound as a liquid.
Reaction SMILES: [CH2:1]([N:3]([CH2:20][CH3:21])[CH2:4][CH2:5][N:6]([CH2:8][C:9]1[CH:10]=[C:11]([CH:16]=[C:17]([CH3:19])[CH:18]=1)[C:12]([O:14]C)=[O:13])[CH3:7])[CH3:2]>CO.O1CCCC1>[CH2:20]([N:3]([CH2:1][CH3:2])[CH2:4][CH2:5][N:6]([CH2:8][C:9]1[CH:10]=[C:11]([CH:16]=[C:17]([CH3:19])[CH:18]=1)[C:12]([OH:14])=[O:13])[CH3:7])[CH3:21]
Reactant: CCN(CC)CCN(C)Cc1cc(C)cc(C(=O)OC)c1
Solvent: CO
Solvent: C1CCOC1
Product: CCN(CC)CCN(C)Cc1cc(C)cc(C(=O)O)c1
Reaction time: 8 h

Procedure:
A mixture of methyl 3-{[[2-(diethylamino)ethyl](methyl)amino]methyl}-5-methylbenzoate (296 mg, 1.01 mmol) and 3:1:1 methanol/tetrahydrofuran/2 N sodium hydroxide (10 mL) is stirred overnight and then partitioned between ethyl acetate and water. The aqueous layer is acidified to pH 3 with 1 N hydrochloric acid and extracted with chloroform. The aqueous layer is concentrated under reduced pressure to give the title compound. 1H NMR (300 MHz, DMSO-d6) δ 7.99 (s, 1H), 7.82 (s, 1H), 7.80 (s, 1H), 4.56 (m, 2H), 4.31 (m, 2H), 3.98 (m, 2H), 3.17 (m, 4H), 2.51 (s, 3H), 2.50 (s, 3H), 1.27 (m, 6H).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][CH:3]=1.[Li]CCCC.[CH:14]12[O:20][CH:15]1[CH2:16][CH2:17][CH2:18][CH2:19]2>C(OCC)C>[F:8][C:5]1[CH:6]=[CH:7][C:2]([CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][C:15]2=[O:20])=[CH:3][CH:4]=1
Reactant: C1CCC2OC2C1
Reactant: Fc1ccc(Br)cc1
Agent: [Li]CCCC
Solvent: CCOCC
Product: O=C1CCCCC1c1ccc(F)cc1
Temperature: -50 °C
Yield: 56.8 %

Procedure:
To a solution of 1-bromo-4-fluorobenzene (12.5 mL, 114 mmol) in diethylether (250 mL) at −78° C. was added BuLi (1.6 M, 68 mL, 109 mmol) under argon. After 5 min at this temperature, cyclohexenoxide (11.0 mL, 109 mmol) was added followed by the addition of borontrifluoride-diethyletherate (13.8 mL, 109 mmol) whereby the temperature increased to approx. −50° C. After 4 h at this temperature the reaction was quenched by the addition of ammonium chloride (saturated, 200 mL) and diluted with water (50 mL). The product was then extracted with diethylether (3×100 mL) and the combined organic extracts dried over sodium sulfate. Filtration and evaporation afforded the tide compound (11.9 g, 56%) as white crystals after trituration from hexane. MS: m/e=194.1 (M).
Reaction SMILES: Br[C:2]1[S:3][CH:4]=[C:5]([Br:7])[N:6]=1.O.[CH3:9][N:10](C=O)[CH3:11]>>[CH3:9][N:10]([CH3:11])[C:2]1[S:3][CH:4]=[C:5]([Br:7])[N:6]=1
Reactant: CN(C)C=O
Reactant: Brc1csc(Br)n1
Solvent: O
Product: CN(C)c1nc(Br)cs1
Yield: 89 %

Procedure:
Synthesis of 2-Dimethylamino-4-tremthylstannylthiazole 386 as illustrated in FIG. 53. 2,4-Dibromothiazole (358; 1.0 equiv) was dissolved in DMF (0.1 M) and heated at 150–160° C. for 8 h, upon which completion of the reaction was indicated by TLC. The mixture was poured into water and extracted with ether (2×). Drying (MgSO4) and evaporation of the solvents gave 2-dimethylamino-4-bromothiazole 385, which was isolated after flash column chromatography (silica gel, 5% EtOAc in hexanes) in 89% yield.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([C:10](Cl)=[O:11])=[CH:7][C:6]=2[CH:13]=1.[CH2:14]([N:16](C(C)C)[CH:17](C)[CH3:18])[CH3:15].C1(C)C=CC=CC=1.C(NCC)C>O>[CH2:14]([N:16]([CH2:17][CH3:18])[C:10]([C:8]1[O:9][C:5]2[CH:4]=[CH:3][C:2]([Br:1])=[CH:13][C:6]=2[CH:7]=1)=[O:11])[CH3:15]
Reactant: CCN(C(C)C)C(C)C
Reactant: O=C(Cl)c1cc2cc(Br)ccc2o1
Solvent: O
Solvent: CCNCC
Solvent: Cc1ccccc1
Product: CCN(CC)C(=O)c1cc2cc(Br)ccc2o1
Reaction time: 0.08 h
Yield: 88 %

Procedure:
1.3 g. of 5-bromobenzofuran-2-carbonyl chloride, 1 mL [sic] of ethyldiisopropylamine and 30 mL [sic] of toluene are mixed and 0.62 ml of diethylamine is added to the brown-coloured solution with stirring. A precipitate is formed with a slightly exothermic reaction. After 5 minutes, the mixture was treated with 30 ml of completely deionized water and the phases were separated. The organic phase was washed with 1.) 20 ml of iN HCl 2.) 20 ml of iN NaOH 3.) 20 ml of water and then with 20 ml of saturated NaCl solution and then freed of solvent components in vacuo. After chromatography on silica gel the residual, yellowish oil forms in the eluent MtB ether/heptane 2:1 [sic]. Final weight: 1.3 g of colourless crystals [sic] (yield: 88%), m.p. 79-81°.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([O:8][CH2:9][C:10]([F:13])([F:12])[F:11])[N:5]=[C:4]([NH:14][C:15]2[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][CH:16]=2)[N:3]=1.Cl.[NH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39].CCN(C(C)C)C(C)C>C1COCC1>[C:38]([O:37][C:36]([NH:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][NH:26][C:2]1[N:7]=[C:6]([O:8][CH2:9][C:10]([F:13])([F:12])[F:11])[N:5]=[C:4]([NH:14][C:15]2[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][CH:16]=2)[N:3]=1)=[O:42])([CH3:41])([CH3:40])[CH3:39]
Reactant: CC(C)(C)OC(=O)NCCCCCCCCN
Reactant: COC(=O)c1ccc(Nc2nc(Cl)nc(OCC(F)(F)F)n2)cc1
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: COC(=O)c1ccc(Nc2nc(NCCCCCCCCNC(=O)OC(C)(C)C)nc(OCC(F)(F)F)n2)cc1
Temperature: 70 °C
Yield: 60.4 %

Procedure:
To a suspension of methyl 4-(4-chloro-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)benzoate (600 mg) in THF (20 mL) was added tert-butyl 8-aminooctylcarbamate hydrochloride (465 mg) and iPr2NEt (0.578 mL). The mixture was heated at 70° C. for 16 hours. The solvent was removed under vacuum. The residue was purified by silica gel column (EtOAC/Hexanes=4:1) to give methyl 4-(4-(8-(tert-butoxycarbonylamino)octylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)benzoate (0.57 g).
Reaction SMILES: [Cl:1][C:2]1[S:3][C:4]([Cl:13])=[CH:5][C:6]=1[C:7](N(OC)C)=[O:8].[C:14]1([Mg]Br)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(OCC)C.[Cl-].[NH4+]>C1COCC1>[C:7]([C:6]1[CH:5]=[C:4]([Cl:13])[S:3][C:2]=1[Cl:1])(=[O:8])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: CON(C)C(=O)c1cc(Cl)sc1Cl
Reactant: Br[Mg]c1ccccc1
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOCC
Solvent: C1CCOC1
Product: O=C(c1ccccc1)c1cc(Cl)sc1Cl
Temperature: -30 °C
Reaction time: 4 h
Yield: 56 %

Procedure:
To a stirred solution of 2,5-dichloro-N-methoxy-N-methyl-3-thiophenecarboxamide (350 mg, 1.46 mmol) in THF (5 mL) was added 3M solution of phenylmagnesium bromide in diethyl ether (1.2 mL, 3.6 mmol) at −78° C., and the mixture was stirred for 4 hours at −30° C. Saturated ammonium chloride solution was added, and the whole was extracted with ethyl acetate (60 mL×2). The combined organic layers were washed with saturated NaHCO3 solution, brine, dried over MgSO4, and concentrated in vacuo. The resulting residue was purified by flash chromatography eluting with hexane-ethyl acetate (12:1) to provide the title product as a yellow oil. (212 mg, 56% yield).
Reaction SMILES: [C:1]([O:5][C:6](=[O:16])[NH:7][C:8]1[CH:13]=[C:12]([Cl:14])[CH:11]=[C:10]([Cl:15])[CH:9]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH2:19](I)[CH:20]=[CH2:21]>CN(C=O)C.CCOC(C)=O>[C:1]([O:5][C:6](=[O:16])[N:7]([CH2:21][CH:20]=[CH2:19])[C:8]1[CH:13]=[C:12]([Cl:14])[CH:11]=[C:10]([Cl:15])[CH:9]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: C=CCI
Reactant: CC(C)(C)OC(=O)Nc1cc(Cl)cc(Cl)c1
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: C=CCN(C(=O)OC(C)(C)C)c1cc(Cl)cc(Cl)c1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 67 %

Procedure:
To a solution of (3,5-dichloro-phenyl)-carbamic acid-tert-butyl ester (6 g, 22.89 mmol) in DMF (130 mL) at 0° C. under Ar was added NaH (60% dispersion in mineral oil, 1.725 g, 45 mmol, 2 eq). The mixture was stirred at 0° C. for 30 min and then allyl iodide (13.32 mL, 110 mmol, 5 eq) was added over 5 min. The mixture was warmed to room temperature and stirred for 2 h. The mixture was then diluted with EtOAc (200 mL) and washed with saturated aqueous NaHCO3 (200 mL). The aqueous phase was washed with EtOAc (3×60 mL) and the combined organic extracts were washed with saturated aqueous NaCl (200 mL), dried over Na2SO4, filtered and concentrated to give a brown oil which was purified by flash column chromatography eluting with 2% EtOAc/hexanes to give allyl(3,5-dichloro-phenyl)-carbamic acid-tert-butyl ester as a clear oil (4.632 g, 15.33 mmol, 67%).). 1H NMR (300 MHz, CDCl3): δ 7.41 (s, 1H), 7.24 (m, 2H), 6.00 (m, 1H), 5.30 (m, 2H), 4.30 (m, 2H), 1.59 (s, 9H).
Reaction SMILES: [CH2:1]([C@@H:8]1[NH:13][CH2:12][CH2:11][N:10]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[CH:15]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:28]=[C:29]1[NH:33][CH:32]([C:34](O)=[O:35])[CH2:31][NH:30]1.C(N(C(C)C)CC)(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>C(Cl)Cl.CN(C=O)C>[CH2:1]([C@H:8]1[CH2:9][N:10]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[CH:15]=2)[CH2:11][CH2:12][N:13]1[C:34]([CH:32]1[CH2:31][NH:30][C:29](=[O:28])[NH:33]1)=[O:35])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COc1ccc(N2CCN[C@@H](Cc3ccccc3)C2)cc1OC1CCCC1
Reactant: O=C1NCC(C(=O)O)N1
Agent: F[P-](F)(F)(F)(F)F
Agent: c1ccc2c(c1)nnn2O[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: ClCCl
Product: COc1ccc(N2CCN(C(=O)C3CNC(=O)N3)[C@@H](Cc3ccccc3)C2)cc1OC1CCCC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 29.9 %

Procedure:
A solution of 3-benzyl-1-(3-cyclopentyloxy-4-methoxy-phenyl)-piperazine (Example 2, Compound 90) (100 mg, 0.273 mmol), in CH2Cl2:DMF (1:1, 3 mL), then treated with 2-oxo-imidazolidine-4-carboxylic acid (50 mg, 0.321 mmol), followed by the addition of diisopropylethylamine (100 μL, 0.819 mmol) and PyBOP (198 mg, 0.383 mmol). The reaction stirred at room temperature for 8 h. The solution was washed with a saturated aqueous solution of NaHCO3 (10 mL) followed by brine (10 mL). The organic portion was dried over MgSO4, filtered and evaporated to an oil which was purified by reversed phase HPLC to afford product as a colorless solid (39 mg, 30%). LC/MS (Method B) 3.60 min, [M+1]+ 479. Potency class A.
Reaction SMILES: [NH2:1][C:2]1[CH:14]=[CH:13][C:5]([O:6][C:7]([CH3:12])([CH3:11])[C:8]([OH:10])=[O:9])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:21](Br)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C(O)C>[CH2:21]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][C:7]([CH3:12])([CH3:11])[C:8]([OH:10])=[O:9])=[CH:13][CH:14]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: CC(C)(Oc1ccc(N)cc1)C(=O)O
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Product: CC(C)(Oc1ccc(NCc2ccccc2)cc1)C(=O)O

Procedure:
A mixture of 1.95 g (0.01 mole) of 4-aminophenoxyisobutyric acid, 25 ml of ethanol, 1.76 g (0.02 mole) of potassium carbonate and 1.2 ml (0.01 mole) of benzyl bromide was stirred and refluxed for 24 hours. Most of the ethanol was evaporated. The residue was dissolved in water, charcoaled, filtered, and acidified water acetic acid to give an oily material which by cooling turned into a solid with a melting point of 194-196° C. The structure (shown below as Formula EX1) was confirmed by NMR spectroscopy.
Reaction SMILES: [Cl:1][C:2]1[CH:23]=[C:22]([NH2:24])[CH:21]=[CH:20][C:3]=1[C:4]([N:6]1[CH2:12][C:11]2[CH:13]=[CH:14][S:15][C:10]=2[CH2:9][C:8]2[N:16]=[CH:17][CH:18]=[CH:19][C:7]1=2)=[O:5].C(N(CC)CC)C.[F:32][C:33]1[CH:34]=[CH:35][C:36]([CH3:42])=[C:37]([CH:41]=1)[C:38](Cl)=[O:39]>ClCCl>[S:15]1[C:10]2[CH2:9][C:8]3[N:16]=[CH:17][CH:18]=[CH:19][C:7]=3[N:6]([C:4]([C:3]3[CH:20]=[CH:21][C:22]([NH:24][C:38](=[O:39])[C:37]4[CH:41]=[C:33]([F:32])[CH:34]=[CH:35][C:36]=4[CH3:42])=[CH:23][C:2]=3[Cl:1])=[O:5])[CH2:12][C:11]=2[CH:13]=[CH:14]1
Reactant: Nc1ccc(C(=O)N2Cc3ccsc3Cc3ncccc32)c(Cl)c1
Reactant: Cc1ccc(F)cc1C(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1ccc(F)cc1C(=O)Nc1ccc(C(=O)N2Cc3ccsc3Cc3ncccc32)c(Cl)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 2 mmol of 5-(2-chloro-4-aminobenzoyl)-4,10-dihydro-5H-pyrido[3,2-b]thieno[2,3-e]azepine and 10 mmol of triethylamine in 25 ml of dichloromethane is added 2.1 mmol of 5-fluoro-2-methyl-benzoyl chloride. After stirring at room temperature overnight, the mixture is washed with H2O, 1M NaHCO3 and brine. The solution is dried (Na2SO4) and the solvent removed to give the product as a solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:17]=[C:16]3[C:12]([CH2:13][C:14](=[O:18])[NH:15]3)=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.[N:19]1([CH2:24][CH2:25][O:26][C:27]2[CH:28]=[C:29]3[C:33](=[CH:34][CH:35]=2)[NH:32][C:31]([CH:36]=O)=[CH:30]3)[CH2:23][CH2:22][CH2:21][CH2:20]1>>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[CH:17]=[C:16]3[C:12]([C:13](=[CH:36][C:31]4[NH:32][C:33]5[C:29]([CH:30]=4)=[CH:28][C:27]([O:26][CH2:25][CH2:24][N:19]4[CH2:23][CH2:22][CH2:21][CH2:20]4)=[CH:35][CH:34]=5)[C:14](=[O:18])[NH:15]3)=[CH:11][CH:10]=2)=[CH:7][CH:8]=1
Reactant: O=Cc1cc2cc(OCCN3CCCC3)ccc2[nH]1
Reactant: COc1ccc(-c2ccc3c(c2)NC(=O)C3)cc1
Product: COc1ccc(-c2ccc3c(c2)NC(=O)C3=Cc2cc3cc(OCCN4CCCC4)ccc3[nH]2)cc1

Procedure:
6-(4-Methoxy-phenyl)-1,3-dihydro-indol-2-one was condensed with 5-(2-pyrrolidin-1-yl-ethoxy)-1H-indole-2-carbaldehyde to give the title compound.
Reaction SMILES: [N:1]1[C:10]2[C@@H:9]([NH2:11])[CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[CH3:12][C:13]1[C:14]([CH:20]=O)=[N:15][CH:16]=[C:17]([CH3:19])[CH:18]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[CH3:12][C:13]1[C:14]([CH2:20][NH:11][C@@H:9]2[C:10]3[N:1]=[CH:2][CH:3]=[CH:4][C:5]=3[CH2:6][CH2:7][CH2:8]2)=[N:15][CH:16]=[C:17]([CH3:19])[CH:18]=1
Reactant: N[C@H]1CCCc2cccnc21
Reactant: Cc1cnc(C=O)c(C)c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Product: Cc1cnc(CN[C@H]2CCCc3cccnc32)c(C)c1

Procedure:
Using General Procedure B: Reaction of (S)-5,6,7,8-tetrahydro-quinolin-8-ylamine in CH2Cl2 with 3,5-dimethyl-pyridine-2-carbaldehyde and NaBH(OAc)3 gave (S)-(3,5-dimethyl-pyridin-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine. 1H NMR (CDCl3) δ 1.75 (m, 1H), 1.91 (m, 2H), 2.26 (s+m, 4H), 2.33 (s, 3H), 2.80 (m, 2H), 3.96 (t, 1H, J=6.0 Hz), 4.02 (d, 1H, J=15.0 Hz), 4.17 (d, 1H, J=15.0 Hz), 5.41 (br s, 1H), 7.06 (dd, 1H, J=7.5, 3.0 Hz), 7.25 (s, 1H), 7.37 (d, 1H, J=9.0 Hz), 8.24 (s, 1H), 8.40 (d, 1H, J=3.0 Hz).
Reaction SMILES: [C:1](Cl)(=[O:4])[CH:2]=[CH2:3].[CH3:6][O:7][C:8]1[CH:13]=[C:12]([N:14]2[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][CH2:15]2)[C:11]([NH2:21])=[CH:10][C:9]=1[NH:22][C:23]1[N:28]=[C:27]([C:29]2[C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[N:31]([CH3:38])[CH:30]=2)[C:26]([CH3:39])=[CH:25][N:24]=1.CCN(C(C)C)C(C)C>C1COCC1.O.C(Cl)Cl.C(OCC)C>[CH3:6][O:7][C:8]1[C:9]([NH:22][C:23]2[N:28]=[C:27]([C:29]3[C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[N:31]([CH3:38])[CH:30]=3)[C:26]([CH3:39])=[CH:25][N:24]=2)=[CH:10][C:11]([NH:21][C:1](=[O:4])[CH:2]=[CH2:3])=[C:12]([N:14]2[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][CH2:15]2)[CH:13]=1
Reactant: COc1cc(N2CCN(C)CC2)c(N)cc1Nc1ncc(C)c(-c2cn(C)c3ccccc23)n1
Reactant: C=CC(=O)Cl
Solvent: O
Solvent: ClCCl
Solvent: CCOCC
Product: C=CC(=O)Nc1cc(Nc2ncc(C)c(-c3cn(C)c4ccccc34)n2)c(OC)cc1N1CCN(C)CC1
Temperature: 0 °C
Reaction time: 1 h
Yield: 52.1 %

Procedure:
Acryloyl chloride (0.358 mL, 1M in THF, 0.36 mmol) was added dropwise to a mixture of 4-methoxy-N′-[5-methyl-4-(1-methylindol-3-yl)pyrimidin-2-yl]-6-(4-methylpiperazin-1-yl)benzene-1,3-diamine (Intermediate 77, 164 mg, 0.36 mmol) and DIPEA (0.069 mL, 0.39 mmol) in THF (15 mL) at 0° C. under N2. The resulting suspension was stirred at 0° C. for 1 h, then allowed to warm to r.t. The mixture was then diluted with water (15 mL) and concentrated in vacuo. The resulting material was dissolved in a mixture of CH2Cl2 (20 mL) and CH3OH (5 mL). The resulting solution was washed with water, and sat. brine. The organic solution was then dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with 1-8% 7M methanolic ammonia in CH2Cl2 gave a pale yellow dry film after concentration of the appropriate fractions in vacuo. This material was dissolved in CH2Cl2 and the resulting solution was diluted with diethyl ether, which resulted in a beige solid precipitating from the solution. This solid was collected by filtration, washed with diethyl ether and then dried to give the title compound (96 mg, 52%); 1H NMR: 2.26 (3H, s), 2.37 (3H, s), 2.51 (4H, s), 2.87 (4H, s), 3.83 (3H, s), 3.89 (3H, s), 5.70 (1H, d), 6.17 (1H, d), 6.60 (1H, dd), 6.86 (1H, s), 7.09 (1H, t), 7.22 (1H, t), 7.48 (1H, d), 7.87 (1H, s), 8.05 (1H, s), 8.21 (1H, s), 8.37 (1H, d), 8.46 (1H, s), 9.00 (1H, s); m/z: ES+ MH+ 512.46.
Reaction SMILES: [F:1][C:2]([F:18])([F:17])[O:3][C:4]1[CH:16]=[CH:15][C:7]([O:8][CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[CH:6][CH:5]=1.[C:19]1(=O)[CH2:24][CH2:23][C:22](=[O:25])[CH2:21][CH2:20]1.C(N(CC)CC)C.O.[C:35]1([CH3:45])[CH:40]=[CH:39][C:38]([S:41]([OH:44])(=[O:43])=[O:42])=[CH:37][CH:36]=1>C(O)C>[C:35]1([CH3:45])[CH:36]=[CH:37][C:38]([S:41]([OH:44])(=[O:42])=[O:43])=[CH:39][CH:40]=1.[OH:25][C:22]1[CH:23]=[CH:24][C:19]([N:12]2[CH2:11][CH2:10][CH:9]([O:8][C:7]3[CH:15]=[CH:16][C:4]([O:3][C:2]([F:1])([F:17])[F:18])=[CH:5][CH:6]=3)[CH2:14][CH2:13]2)=[CH:20][CH:21]=1
Reactant: FC(F)(F)Oc1ccc(OC2CCNCC2)cc1
Reactant: O=C1CCC(=O)CC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCN(CC)CC
Solvent: O
Solvent: CCO
Product: Oc1ccc(N2CCC(Oc3ccc(OC(F)(F)F)cc3)CC2)cc1
Yield: 63.6 %

Procedure:
4.00 g of 4-(4-trifluoromethoxyphenoxy)piperidine, 2.575 g of 1,4-cyclohexanedione and 2.16 ml of triethylamine were heated in 60 ml of ethanol and reacted at 50° C. to 60° C. for 6 hours. After the completion of the reaction, the reaction mixture was concentrated under reduced pressure and ethyl acetate was added thereto to prepare an ethyl acetate solution, to which 4.37 g of p-toluenesulfonic acid monohydrate was added. After leaving at room temperature for 30 minutes, the precipitate was filtrated, washed with ethyl acetate and air-dried, and 5.116 g of 1-(4-hydroxyphenyl)-4-(4-trifluoromethoxyphenoxy)piperidine p-toluenesulfonate was obtained (yield 63.75%).
Reaction SMILES: O1[CH:5]=[CH:4][CH:3]=[CH:2]1.[C:6]12[CH2:12][C:9](=[CH:10][CH:11]=1)[C:8]1C=CC=C[C:7]2=1>>[CH:2]1[C:3]2[C:4](=[CH:5][C:8]3[C:9]([CH:2]=2)=[CH:10][C:11]2[C:6](=[CH:12][C:11]4[C:6]([CH:12]=2)=[CH:7][CH:8]=[CH:9][CH:10]=4)[CH:7]=3)[CH:5]=[CH:4][CH:3]=1
Reactant: c1ccoc1
Reactant: C1=C2CC(=C1)c1ccccc12
Product: c1ccc2cc3cc4cc5ccccc5cc4cc3cc2c1
Temperature: 128 °C
Yield: 40 %

Procedure:
In summary, a new stable and soluble pentacene precursor 2 was synthesized in 40% yield from the cycloaddition of a furan derivative 3 and a benzonorbornadiene 4. Compound 2 releases a unit of CO upon heating at 128° C. or by irradiation with UV light (366 nm) to produce pentacene in nearly quantitative yield. Thin films of pentacene were prepared by spin-coating followed by thermal annealing, and found to display typical FET characteristics.
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:4].[C:11]1(=[O:21])[NH:15][C:14](=[O:16])[C:13]2=[CH:17][CH:18]=[CH:19][CH:20]=[C:12]12.[K].O>CN(C=O)C>[C:11]1(=[O:21])[N:15]([CH2:2][C:3]([C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=2)=[O:4])[C:14](=[O:16])[C:13]2=[CH:17][CH:18]=[CH:19][CH:20]=[C:12]12
Reactant: O=C(CBr)c1ccccc1
Reactant: O=C1NC(=O)c2ccccc21
Agent: [K]
Solvent: CN(C)C=O
Solvent: O
Product: O=C(CN1C(=O)c2ccccc2C1=O)c1ccccc1
Temperature: 40 °C
Yield: 85.6 %

Procedure:
A solution of 2-bromoacetophenone (30.0 g, 151 mmol) in DMF (120 ml) was treated with potassium phthalimide (30.8 g, 166 mmol) portionwise at ambient temperature, and then heated to 40° C. for 3.5 hr. The cooled mixture was poured into water (600 ml) and extracted with chloroform (300 ml then 100 ml). The combined organic phases were washed with sodium hydroxide (200 ml, 0.2 N), water (2×100 ml) and brine (100 ml), dried over magnesium sulfate and concentrated in vacuo. The resulting cream solid was suspended in ether (100 ml), recovered by filtration, washed with ether (100 ml) and dried in vacuo to yield pure 2-phthalimido-acetophenone as a white solid (34.3 g, 86%).