Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: S(=O)(=O)(O)O.[F:6][C:7]1[CH:8]=[C:9]([CH:15]=[C:16]([F:18])[CH:17]=1)[O:10][CH2:11][CH2:12][CH2:13][OH:14].CC([OH:22])C>CC(C)=O.O.[O-2].[Cr+6].[O-2].[O-2]>[F:6][C:7]1[CH:8]=[C:9]([CH:15]=[C:16]([F:18])[CH:17]=1)[O:10][CH2:11][CH2:12][C:13]([OH:22])=[O:14]
Reactant: OCCCOc1cc(F)cc(F)c1
Reactant: CC(C)O
Agent: [Cr+6]
Agent: O=S(=O)(O)O
Agent: [O-2]
Solvent: CC(C)=O
Solvent: O
Product: O=C(O)CCOc1cc(F)cc(F)c1
Reaction time: 0.17 h

Procedure:
At about −20° C., 17.22 g (172.18 mmol) of chromium(VI) oxide were taken up in 1.2 l of acetone and 38 ml of water, and 19 ml of conc. sulfuric acid were slowly added to the mixture. The mixture was stirred for 10 min and then 8.10 g (43.05 mmol) of the compound from Example 168A in 400 ml of acetone were added dropwise over the course of 1 h. The mixture was stirred at 0° C. for 1.5 h. After addition of 90 ml of propan-2-ol, the reaction mixture was filtered through kieselguhr, the solvents were removed from the filtrate in vacuo, and the residue was taken up in 500 ml of diethyl ether. The solution was washed twice with saturated aqueous sodium chloride solution and dried over sodium sulfate, and the solvents were removed in vacuo. 11.36 g of the title compound were obtained and were reacted further in the next stage without further purification.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][C:12]1[CH:21]=[CH:20][C:15]([C:16]([O:18][CH3:19])=[O:17])=[CH:14][C:13]=1[O:22][CH3:23].[CH:24]1([CH2:29][C:30](Cl)=[O:31])[CH2:28][CH2:27][CH2:26][CH2:25]1>>[CH:24]1([CH2:29][C:30]([NH:1][C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][CH:6]=[C:5]3[CH2:11][C:12]2[CH:21]=[CH:20][C:15]([C:16]([O:18][CH3:19])=[O:17])=[CH:14][C:13]=2[O:22][CH3:23])=[O:31])[CH2:28][CH2:27][CH2:26][CH2:25]1
Reactant: COC(=O)c1ccc(Cc2c[nH]c3ccc(N)cc23)c(OC)c1
Reactant: O=C(Cl)CC1CCCC1
Product: COC(=O)c1ccc(Cc2c[nH]c3ccc(NC(=O)CC4CCCC4)cc23)c(OC)c1

Procedure:
Starting from amino-ester (A), and using a similar procedure to that described in Example 4, except using cyclopentylacetyl chloride (see also Example 98), the title compound was obtained in quantitative yield as a foam; partial NMR (250 MHz, DMSOd6): 1.2-1.8(3m,8H, cyclopentyl ring); 2.24(m,3H, CH2CONH and --CHCH2); 3.83(s,3H, OMe); 3.93(s,3H, OMe); 3.99(br s,2H, CH2Ar); 9.57(br s,1H, NHCO); 10.79(br ™d,1H, --NH--).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3](B(O)O)[CH:2]=1.Cl[C:11]1[S:12][CH:13]=[C:14]([Cl:16])[N:15]=1.C(O)C.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.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>[Cl:16][C:14]1[N:15]=[C:11]([C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)[S:12][CH:13]=1
Reactant: OB(O)c1cccnc1
Reactant: Clc1csc(Cl)n1
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: [K+]
Solvent: Cc1ccccc1
Solvent: CCO
Product: Clc1csc(-c2cccnc2)n1
Temperature: 95 °C
Yield: 78 %

Procedure:
To a suspension of pyridin-3-ylboronic acid (3.87 g, 31.5 mmol) in toluene (120 mL) was added 2,4-dichlorothiazole (4.62 g, 30 mmol) followed by ethanol (60 mL) and a 2.0 M solution of K2CO3 (30.0 mL, 60.0 mmol). The solution was degassed by applying vacuum and then purging with nitrogen (3 times). To the reaction mixture was added tetrakis(triphenylphosphine)palladium (0) (1.733 g, 1.500 mmol) and the flask was heated at 95° C. under nitrogen for 16 hours. The aqueous layer was removed and the organic layer was concentrated. The crude product was purified via silica gel chromatography (0-100% ethyl acetate/hexanes) to afford the title compound as a brown solid (4.6 g, 74%): mp 84-86° C.; IR (KBr) 3092 cm−1; 1H NMR (400 MHz, CDCl3) δ 9.16-9.13 (m, 1H), 8.69 (dd, J=4.8, 1.6 Hz, 1H), 8.23 (ddd, J=8.0, 2.2, 1.7 Hz, 1H), 7.40 (ddd, J=8.0, 4.8, 0.8 Hz, 1H), 7.16 (s, 1H).
Reaction SMILES: [C:1]1([P:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)(=[O:9])[OH:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[CH2:17]([N+:19]([CH2:24][CH3:25])([CH2:22][CH3:23])[CH2:20][CH3:21])[CH3:18]>O.CC(O)C>[C:1]1([P:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)(=[O:8])[O-:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1.[CH2:17]([N+:19]([CH2:24][CH3:25])([CH2:22][CH3:23])[CH2:20][CH3:21])[CH3:18]
Reactant: O=P(O)(c1ccccc1)c1ccccc1
Agent: CC[N+](CC)(CC)CC
Agent: [OH-]
Solvent: CC(C)O
Solvent: O
Product: O=P([O-])(c1ccccc1)c1ccccc1

Procedure:
To a flask were added 1.0 g diphenylphosphinic acid, 3.2 g of a 20% solution of tetraethylammonium hydroxide in water and 20 ml 2-propanol. After heating to 50 C under nitrogen for 1 hour, the solvent was removed and another 20 ml of 2-propanol were added and removed by distillation under reduced pressure. After drying, an oil was obtained.
Reaction SMILES: Br[C:2]1[N:3]=[C:4]([NH:11][C:12]2[CH:16]=[C:15]([CH3:17])[NH:14][N:13]=2)[C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[CH:7]=1.[SH:18][C:19]1[CH:24]=[CH:23][C:22]([NH:25][C:26]([CH:28]2[CH2:30][CH2:29]2)=[O:27])=[CH:21][CH:20]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH3:17][C:15]1[NH:14][N:13]=[C:12]([NH:11][C:4]2[C:5]3[N:6]([CH:8]=[CH:9][N:10]=3)[CH:7]=[C:2]([S:18][C:19]3[CH:20]=[CH:21][C:22]([NH:25][C:26]([CH:28]4[CH2:29][CH2:30]4)=[O:27])=[CH:23][CH:24]=3)[N:3]=2)[CH:16]=1
Reactant: O=C(Nc1ccc(S)cc1)C1CC1
Reactant: Cc1cc(Nc2nc(Br)cn3ccnc23)n[nH]1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1cc(Nc2nc(Sc3ccc(NC(=O)C4CC4)cc3)cn3ccnc23)n[nH]1

Procedure:
(6-Bromo-imidazo[1,2-a]pyrazin-8-yl)-(5-methyl-1H-pyrazol-3-yl)-amine (21 mg, 0.072 mmol), N-(4-mercaptophenyl)cyclopropanecarboxamide (28 mg, 0.145 mmol) and potassium carbonate (20 mg) were mixed in DMF (1 ml). This mixture was reacted in a microwave reactor at 170° C. for 15 minutes. DMF was removed in vacuo and the residue was purified by HPLC to afford the title compound Example 8 as an off-white solid. (11.9 mg). 1H NMR (400 MHz, DMSO) δ 10.39 (s, 1H) 7.99 (d, J=0.8 Hz, 1H) 7.96 (s, 1H) 7.70 (s, 1H) 7.69 (d, J=8.4 Hz, 2H) 7.49 (d, J=8.4 Hz, 2H) 6.03 (s, 1H) 2.14 (s, 3H) 1.75-1.82 (m, 1H) 0.77-0.81 (m, 2H). [M+H] calc'd for C20H19N7OS, 406; found, 406.
Reaction SMILES: [O:1]1[C:6]2=[CH:7][CH:8]=[CH:9][C:5]2=[CH:4][C:3](NCCCC)=[CH:2]1.BrC1C=CC(S(O[CH2:26][C@@H:27]2[O:41][C:31]3=[C:32]4[C:37](=[CH:38][CH:39]=[C:30]3[O:29][CH2:28]2)[N:36]=[C:35]([CH3:40])[CH:34]=[CH:33]4)(=O)=O)=CC=1>CS(C)=O.C(=O)(O)[O-].[Na+]>[O:1]1[C:2]2[CH:3]=[CH:4][CH:5]=[CH:9][C:8]=2[C:7]([CH2:32][CH2:33][CH2:34][CH2:35][NH:36][CH2:26][CH:27]2[O:41][C:31]3=[C:32]4[C:37](=[CH:38][CH:39]=[C:30]3[O:29][CH2:28]2)[N:36]=[C:35]([CH3:40])[CH:34]=[CH:33]4)=[CH:6]1
Reactant: CCCCNc1coc2cccc-2c1
Reactant: Cc1ccc2c3c(ccc2n1)OC[C@H](COS(=O)(=O)c1ccc(Br)cc1)O3
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CS(C)=O
Product: Cc1ccc2c3c(ccc2n1)OCC(CNCCCCc1coc2ccccc12)O3
Temperature: 50 °C

Procedure:
To a stirred solution of 4-benzofuran-3-yl-butylamine (770 mg, 4.07 mmol) in 6 mL of anhydrous DMSO was added [(2R)-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methyl 4-bromobenzenesulfonate (611 mg mg, 1.36 mmol). The reaction mixture was heated to 50° C. overnight. The reaction was diluted with saturated aqueous sodium bicarbonate (10 mL) and extracted with ethyl acetate (3×10 mL). The combined organic layers were washed with brine (3×30 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuum. Flash chromatography on SiO2 (5% MeOH/CH2Cl2) afforded 403 mg (74%) of the (S)-enantiomer of the title compound as a yellow oil. The fumarate salt was prepared, yielding 285 mg of a beige solid, m.p. 127-130° C.; MS (ESI) m/z 403 [M+H]+.
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[CH:8][C:9]3[O:13][C:12]([N:14]4[CH2:19][CH2:18][CH:17]([O:20][CH2:21][C@@H:22]([NH:24][C:25](=O)[O:26]C(C)(C)C)[CH3:23])[CH2:16][CH2:15]4)=[N:11][C:10]=3[CH:32]=2)[CH2:3][CH2:2]1.Cl.[C:34](OCC)(=O)C>>[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[CH:8][C:9]3[O:13][C:12]([N:14]4[CH2:19][CH2:18][CH:17]([O:20][CH2:21][C@@H:22]([NH:24][C:25](=[O:26])[CH3:34])[CH3:23])[CH2:16][CH2:15]4)=[N:11][C:10]=3[CH:32]=2)[CH2:3][CH2:2]1
Reactant: C[C@@H](COC1CCN(c2nc3cc(OCC4CC4)ccc3o2)CC1)NC(=O)OC(C)(C)C
Reactant: CCOC(C)=O
Agent: Cl
Product: CC(=O)N[C@@H](C)COC1CCN(c2nc3cc(OCC4CC4)ccc3o2)CC1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To tert-butyl [(1S)-2-({1-[5-(cyclopropylmethoxy)-1,3-benzoxazol-2-yl]piperidin-4-yl}oxy)-1-methylethyl]carbamate (30.1 g) was added 4M hydrogen chloride/ethyl acetate (200 mL), and the mixture was stirred at room temperature for 30 min. After stirring, the mixture was concentrated. Pyridine (100 mL) and acetic anhydride (100 mL) were added to the residue, and the mixture was stirred at room temperature for 15 min. After concentration, the residue was purified by silica gel chromatography (NH, hexane/ethyl acetate), and the obtained crystals were recrystallized from hexane/ethyl acetate to give the title compound (17.4 g) as white crystals.
Reaction SMILES: [C:1]([C:4]1[O:5][CH:6]=[CH:7][CH:8]=1)(=[O:3])[CH3:2].[F:9][C:10]([F:15])([F:14])[C:11]([O-])=[O:12]>>[F:9][C:10]([F:15])([F:14])[C:11](=[O:12])[CH2:2][C:1]([C:4]1[O:5][CH:6]=[CH:7][CH:8]=1)=[O:3]
Reactant: CC(=O)c1ccco1
Reactant: O=C([O-])C(F)(F)F
Product: O=C(CC(=O)C(F)(F)F)c1ccco1

Procedure:
The diketone 19 was synthesized from acetylfuran and trifluoracetate to obtain the 4,4,4-trifluoro-1-(furan-2-yl)butane-1,3-dione 19 product as follows. 2-Acetylfuran 18 (11.0 g, 210 mmol) was dissolved in benzene (210 mL). At room temperature was added KOtBu (23.6 g, 210 mol). The resulting red solution was cooled to 5° C. Ethyl trifluoracetate 6 (25 mL, 29.8 g, 210 mmol) was added dropwise in approximately 20 minutes keeping the temperature below 15° C. Then the mixture was stirred for 16 hours at room temperature. The mixture was poured in ice-water (300 mL) containing concentrated sulfuric acid (5 g). The aqueous mixture was extracted with tBME (3×200 mL). The combined organic layers were washed with brine (200 mL), dried (Na2SO4) and concentrated to give a dark brown oil (20.8 g). The crude product was purified by kugelrohr distillation to give compound 19 (17.0 g, 39%) as a yellowish oil.
Reaction SMILES: [OH2:1].[H-].[Na+].[C:4]([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]Br)([O:6][C:7]([CH3:10])(C)C)=[O:5]>CCOC(C)=O.C(Cl)Cl>[C:4]([NH:11][C@H:12]([C:4]([OH:6])=[O:5])[CH2:13][C:14]1[CH:15]=[CH:16][C:17]([OH:1])=[CH:18][CH:19]=1)([O:6][CH2:7][C:10]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:5]
Reactant: O
Reactant: CC(C)(C)OC(=O)NCCCCCCCCBr
Agent: [H-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: O=C(N[C@@H](Cc1ccc(O)cc1)C(=O)O)OCc1ccccc1
Reaction time: 16 h

Procedure:
H2O (1.5 g, 4.29 mmole) was dissolved in EtOAc/CH2Cl2, dried over MgSO4, filtered and evaporated. The residue was dissolved in DMF and treated with NaH (50% dispersion in oil, 0.43 g, 8.96 mmole) for 1 hour. N-BOC-8-amino-1-bromooctane (1.33 g, 4.34 mmole) was added and the reaction was stirred for 16 hours. The DMF was removed in vacuo, the residue dissolved in water, acidified to pH 3 and extracted with EtOAc. The EtOAc layers were combined, dried and concentrated. Column chromatography (SiO2, 97:3:1 CHCl3 /MeOH/HOAc) gave 2-5.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:13])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8](Br)[CH:7]=1)[CH3:2].O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[CH:33]#[C:34][CH2:35][CH2:36][CH3:37]>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.O>[C:33]([C:8]1[CH:7]=[C:6]([CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:13])[CH:11]=[CH:10][CH:9]=1)#[C:34][CH2:35][CH2:36][CH3:37]
Reactant: C#CCCC
Reactant: CCOC(=O)Cc1cccc(Br)c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: O
Product: CCCC#Cc1cccc(CC(=O)OCC)c1
Temperature: 80 °C
Yield: 80.5 %

Procedure:
A mixture of ethyl(3-bromophenyl)acetate (0.3 g, 1.24 mmol) and tetrabutylammonium fluoride hydrate (0.97 g, 3.72 mmol), was treated with PdCl2(PPh3)2 (26 mg, 0.037 mmol; 3 mole %) and 1-pentyne (367 μL, 3.72 mmol) in a sealed tube. The tube was heated at 80° C. for 2 h. The mixture was treated with water, and was extracted with diethyl ether. The organic extract was dried over sodium sulfate, filtered and evaporated in vacuo to give the crude product. Purification on a Biotage™ 25 M column (silica), eluting with ethyl acetate/hexane 0:1 to 2:98, gave ethyl (3-(pentyne-1-yl)phenyl)acetate as a pale yellow oil (0.23 g, 79%).
Reaction SMILES: [CH2:1]([C:7]1[CH:15]=[C:14]2[C:10]([C:11](=O)[CH2:12][CH2:13]2)=[CH:9][C:8]=1[O:17][CH2:18][CH2:19][CH2:20][C:21]([OH:23])=[O:22])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].Cl.[NH2:25][OH:26].C([O-])(=O)C.[Na+]>C(O)C>[CH2:1]([C:7]1[CH:15]=[C:14]2[C:10]([C:11](=[N:25][OH:26])[CH2:12][CH2:13]2)=[CH:9][C:8]=1[O:17][CH2:18][CH2:19][CH2:20][C:21]([OH:23])=[O:22])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: CCCCCCc1cc2c(cc1OCCCC(=O)O)C(=O)CC2
Reactant: NO
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: CCCCCCc1cc2c(cc1OCCCC(=O)O)C(=NO)CC2
Temperature: 0 °C
Yield: 50.2 %

Procedure:
A mixture of 50 mg (0.157 mmol) of 4-(6-hexyl-3-oxo-5-indanyloxy)butyric acid, 13 mg (0.188 mmol) of hydroxylamine hydrochloride and 32 mg (0.393 mmol) of sodium acetate in 3 ml of 85% ethanol is heated at reflux for 1 hour. After cooling, the mixture is poured into 50 ml of ice-cold water. The solid formed is isolated by filtration, washed with water and dried to give 26.3 mg (50%) of the expected product.
Reaction SMILES: Cl[C:2]([O:4][CH2:5][CH:6]1[C:18]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:12]2[C:7]1=[CH:8][CH:9]=[CH:10][CH:11]=2)=[O:3].[NH2:19][C@H:20]([C:26]([OH:28])=[O:27])[CH2:21][CH2:22][CH2:23][CH2:24][NH2:25]>>[CH:17]1[C:18]2[CH:6]([CH2:5][O:4][C:2]([NH:19][C@H:20]([C:26]([OH:28])=[O:27])[CH2:21][CH2:22][CH2:23][CH2:24][NH:25][C:2]([O:4][CH2:5][CH:6]3[C:7]4[CH:8]=[CH:9][CH:10]=[CH:11][C:12]=4[C:13]4[C:18]3=[CH:17][CH:16]=[CH:15][CH:14]=4)=[O:3])=[O:3])[C:7]3[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=3)[C:13]=2[CH:14]=[CH:15][CH:16]=1
Reactant: O=C(Cl)OCC1c2ccccc2-c2ccccc21
Reactant: NCCCC[C@H](N)C(=O)O
Product: O=C(NCCCC[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)O)OCC1c2ccccc2-c2ccccc21
Yield: 71 %

Procedure:
The reaction of 9-fluorenylmethyl chloroformate with L-lysine according to the conditions described in example 2 provided the title product in 71% yield.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[C:6]([CH2:11][C:12]([O:14]CC)=[O:13])[CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.[OH-].[Na+].O>OS(O)(=O)=O>[CH:1]1[C:10]2[C:5](=[C:6]([CH2:11][C:12]([OH:14])=[O:13])[CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1
Reactant: CCOC(=O)Cc1cccc2cnccc12
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C(O)Cc1cccc2cnccc12
Temperature: 100 °C

Procedure:
Ethyl 5-isoquinolinylacetate (1.15 g, 5.34 mmol) was dissolved in concentrated H2SO4 (12 mL) and heated at 100° C. for 2 hours. The reaction mixture was poured into ice (20 g) and the pH was adjusted to 6 with 50% NaOH/H2O. The mixture was allowed to set of several hours, filtered, and the filter cake was rinsed with water to provide the title compound. MS (ESI+) m/z 188 (M+H)+; 1H NMR (DMSO, 300 MHz) δ 4.07 (s, 2H), 7.67 (m, 2H), 7.83 (d, J 5.7, 1H), 8.05 (d, J 8.1, 1H), 8.53 (d, J 6.1, 1H), 9.32 (s, 1H), 12.50 (s, 1H); 13C NMR (DMSO, 75 MHz) δ 37.6 (CH2CO), 117.1 (CH, C4), 126.8, 127.0 (CH, C7 & C8), 128.4 (C), 131.1 (C), 132.0 (CH, C6), 134.4 (C), 143.0 (CH, C3), 152.7 (CH, C1), 172.3 (CO); Anal. Calcd for C11H9NO2: C, 70.58; H, 4.85; N, 7.48. Found: C, 70.42; H, 4.93; N, 7.34.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([C:12](Cl)=[O:13])[CH:6]=[CH:5]2.[Si]([CH:19]=[N+:20]=[N-:21])(C)(C)C>ClCCl>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([C:12](=[O:13])[CH:19]=[N+:20]=[N-:21])[CH:6]=[CH:5]2
Reactant: O=C(Cl)c1ccc2cc(Br)ccc2c1
Reactant: C[Si](C)(C)C=[N+]=[N-]
Solvent: ClCCl
Product: [N-]=[N+]=CC(=O)c1ccc2cc(Br)ccc2c1
Temperature: 0 °C
Reaction time: 16 h

Procedure:
6-Bromonaphthalene-2-carbonyl chloride (27.0 g, crude) was dissolved in dichloromethane (330 mL) and cooled to 0° C. TMS diazomethane solution (100 mL, 2 M in DCM) was added, and ice bath was removed. Reaction mixture was stirred for 16 hours and evaporated under vacuum, giving 1-(6-bromonaphthalen-2-yl)-2-diazoethanone (34.7 g, crude) as an orange solid.
Reaction SMILES: [CH3:1][O:2][CH:3]([O:23][CH3:24])[C:4]1[CH:9]=[C:8]([N+:10]([O-:12])=[O:11])[C:7](OS(C(F)(F)F)(=O)=O)=[C:6]([O:21][CH3:22])[CH:5]=1.C([O-])(=O)C.CC#N>CCOC(C)=O.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH3:24][O:23][CH:3]([O:2][CH3:1])[C:4]1[CH:9]=[C:8]([N+:10]([O-:12])=[O:11])[CH:7]=[C:6]([O:21][CH3:22])[CH:5]=1
Reactant: COc1cc(C(OC)OC)cc([N+](=O)[O-])c1OS(=O)(=O)C(F)(F)F
Agent: [Fe+2]
Agent: CC(=O)[O-]
Agent: c1ccc(P(c2ccccc2)[c-]2cccc2)cc1
Solvent: CC#N
Solvent: CCOC(C)=O
Product: COc1cc(C(OC)OC)cc([N+](=O)[O-])c1
Temperature: 90 °C
Yield: 35.3 %

Procedure:
5-Nitrophenyl triflate 26 (7 g, 18.7 mmol), palldium (II) acetate (88 mg, 0.39 mmol), 1,1'-bis(diphenylphosphino)ferrocene (430 mg, 0.78 mmol) and hplc grade CH3CN (10 ml) were mixed well in a teflon-linked stainless steel bomb. After adding freshly made, pulverized proton sponge formate (5.1 g, 19.6 mmol), the bomb was sealed and heated at 90° C. for 2 h. The reaction mixture was taken up in EtOAc, passed through a silica gel plug, and then purified on a silica gel column, eluting with 0-30% EtOAc/hexanes to yield 1.5 g (35%) methoxynitrobenzaldehyde acetal 27.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1.C(N(CC)CC)C.Cl[S:21]([C:24]1[CH:32]=[CH:31][C:27]([C:28]([OH:30])=[O:29])=[CH:26][CH:25]=1)(=[O:23])=[O:22]>C(Cl)Cl>[NH:6]1[C:7]2[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:4]([CH2:3][CH2:2][NH:1][S:21]([C:24]2[CH:25]=[CH:26][C:27]([C:28]([OH:30])=[O:29])=[CH:31][CH:32]=2)(=[O:23])=[O:22])=[CH:5]1
Reactant: NCCc1c[nH]c2ccccc12
Reactant: O=C(O)c1ccc(S(=O)(=O)Cl)cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(O)c1ccc(S(=O)(=O)NCCc2c[nH]c3ccccc23)cc1
Reaction time: 2 h

Procedure:
To 3.0 g (18.7 mmol) of tryptamine in 20 ml of CH2Cl2 was added, 2.5 ml (18.7 mmol) of triethylamine followed by 2.06 g (9.4 mmol) of 4-(chlorosulphonyl) benzoic acid. After stirring for 2 h, the mixture was extracted with CH2Cl2 (3×50 ml) and the combined organic extracts were washed with water and dried and evaporated. The residue was chromatographed on silica gel using 2:98:0.5 MeOH/CH2Cl2/AcOH to afford the title compound as a solid. MS m/e 345; HPLC retention time 2.52 min.
Reaction SMILES: [C:1]([CH:6]1[C:10]2([CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)[C:9](C(OCC)=O)(C(OCC)=O)[C:8](=[O:26])[CH2:7]1)([O:3][CH2:4][CH3:5])=[O:2].O.[Cl-].[Li+]>CS(C)=O.[Cl-].[Na+].O>[C:1]([CH:6]1[C:10]2([CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)[CH2:9][C:8](=[O:26])[CH2:7]1)([O:3][CH2:4][CH3:5])=[O:2]
Reactant: CCOC(=O)C1CC(=O)C(C(=O)OCC)(C(=O)OCC)C12CCCCC2
Agent: [Cl-]
Agent: [Li+]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: CCOC(=O)C1CC(=O)CC12CCCCC2
Temperature: 170 °C
Reaction time: 4 h
Yield: 74.7 %

Procedure:
1,4,4-Tricarboethoxy-3-oxospiro[4.5]decane (990 mg), water (196 μl) and lithium chloride (350 mg) were dissolved in dimethylsulfoxide (25 ml), and the mixture was stirred at 170° C. for 4 hours. After cooling to room temperature, saturated brine (40 ml) was added and the mixture was extracted with ethyl acetate. The organic layer was separated, dried over magneium sulfate and concentrated to dryness. The residue was purified through silica gel column chromatography (hexane-ethyl acetate=5:1) to give pure 1-carboethoxy-3-oxospiro[4.5]decane (450 mg), which was added to 5N hydrochloric acid (20 ml), and the mixture was refluxed for 3 hours. After cooling to room temperature, the mixture was concentrated and the residue was adjusted to pH 10 with aqueous solution of sodium hydroxide, followed by washing with ether. The aqueous layer was acidified with 5N hydrochloric acid to pH 2, followed by extraction with ether. The ethereal solution was dried, and concentrated to dryness to afford the title compound (310 mg) as colorless crystals.
Reaction SMILES: [CH2:1]([O:3][CH:4]([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[CH2:5][OH:6])[CH3:2].[C:21]1([CH3:31])[CH:26]=[CH:25][C:24]([S:27](Cl)(=[O:29])=[O:28])=[CH:23][CH:22]=1>N1C=CC=CC=1>[C:21]1([CH3:31])[CH:26]=[CH:25][C:24]([S:27]([O:6][CH2:5][CH:4]([O:3][CH2:1][CH3:2])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])(=[O:29])=[O:28])=[CH:23][CH:22]=1
Reactant: CCCCCCCCCCCCCCC(CO)OCC
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: c1ccncc1
Product: CCCCCCCCCCCCCCC(COS(=O)(=O)c1ccc(C)cc1)OCC

Procedure:
2-Ethoxyhexadecyl p-toluenesulfonate was prepared by treating 2-ethoxyhexadecanol (1.72 g) with p-toluenesulfonylchloride (1.5 g) in pyridine (2.3 ml) at room temperature over night. There was obtained 2.47 g of a crude product, which by thin layer chromatography was shown to contain very small amounts of impurities.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][OH:11].[CH3:12][CH:13]([CH3:19])[CH2:14][CH2:15][CH2:16][CH2:17]Br>>[CH3:12][CH:13]([CH3:19])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][OH:11]
Reactant: CC(C)CCCCBr
Reactant: OCCCCCCCCCBr
Product: CC(C)CCCCCCCCCCCCCO
Yield: 55 %

Procedure:
14-methylpentadecan-1-ol was prepared from 9-bromononanol and 5-methylhexylbromide in 55% yield. The 1H NMR and MS-ESI data matched those reported by Yuasa et al. (Yuasa and Tsuruta (2004) Flavour and Fragrance Journal 19:199-204).
Reaction SMILES: [OH-].[NH4+:2].[CH2:3]([C:5]1[N:6]([CH2:29][CH:30]([CH3:32])[CH3:31])[C:7]2[C:16]3[CH:15]=[CH:14][C:13]([O:17][CH2:18][C:19]([N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)=[O:20])=[CH:12][C:11]=3[N+:10]([O-])=[CH:9][C:8]=2[N:28]=1)[CH3:4].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>ClCCl>[CH2:3]([C:5]1[N:6]([CH2:29][CH:30]([CH3:32])[CH3:31])[C:7]2[C:16]3[CH:15]=[CH:14][C:13]([O:17][CH2:18][C:19]([N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)=[O:20])=[CH:12][C:11]=3[N:10]=[C:9]([NH2:2])[C:8]=2[N:28]=1)[CH3:4]
Reactant: [NH4+]
Reactant: CCc1nc2c[n+]([O-])c3cc(OCC(=O)N4CCOCC4)ccc3c2n1CC(C)C
Agent: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: [OH-]
Solvent: ClCCl
Product: CCc1nc2c(N)nc3cc(OCC(=O)N4CCOCC4)ccc3c2n1CC(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Ammonium hydroxide (0.5 mL) was added to a solution of 2-ethyl-1-(2-methylpropyl)-7-(2-morpholin-4-yl-2-oxoethoxy)-5-oxido-1H-imidazo[4,5-c]quinoline (0.53 g, 1.28 mmol) in dichloromethane (3 mL), and the mixture was cooled to 0° C. p-Toluenesulfonyl chloride (0.29 g, 1.5 mmol) was added in small portions over a period of 20 minutes. The reaction was stirred at ambient temperature overnight. The reaction mixture was partitioned between dichloromethane and 1% aqueous sodium carbonate. The organic fraction was washed with 1% aqueous sodium carbonate (2×30 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude product was recrystallized from ethyl acetate, isolated by filtration, washed with cold hexanes, and dried under high vacuum at 55° C. to provide 0.391 g of 2-ethyl-1-(2-methylpropyl)-7-(2-morpholin-4-yl-2-oxoethoxy)-1H-imidazo[4,5-c]quinolin-4-amine as off-white needles, mp 219-220° C.