Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:15][C:16]1[CH:17]=[C:18]([N+:37]([O-])=O)[CH:19]=[CH:20][C:21]=1[O:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].[H][H]>[Pd].C1COCC1.C(OCC)(=O)C>[CH2:1]([O:15][C:16]1[CH:17]=[C:18]([NH2:37])[CH:19]=[CH:20][C:21]=1[O:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]
Reactant: CCCCCCCCCCCCCCOc1ccc([N+](=O)[O-])cc1OCCCCCCCCCCCCCC
Reactant: [H][H]
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCCCCCCCCCCCCCOc1ccc(N)cc1OCCCCCCCCCCCCCC
Yield: 87.7 %

Procedure:
A mixture of 3.5 g of 3,4-bis(tetradecyloxy)nitrobenzene and 0.5 g of 10% palladium on carbon in 80 ml of THF and 40 ml of ethyl acetate was stirred in a hydrogen atmosphere for 4 hours when uptake ceased. The catalyst was removed by filtration and the filtrate was concentrated at reduced pressure to a solid which was recrystallized from ethyl acetate-hexane to give 2.9 g (88% yield, mp 55°-58°) of 3,4-bis(tetradecyloxy)benzenamine.
Reaction SMILES: [C:1]1([S:7][C:8]2[CH:13]=[CH:12][C:11]([CH2:14][C:15]([CH2:17][Cl:18])=[O:16])=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.ClC1C=CC=C(C(OO)=[O:27])C=1>C(Cl)(Cl)Cl>[C:1]1([S:7]([C:8]2[CH:9]=[CH:10][C:11]([CH2:14][C:15]([CH2:17][Cl:18])=[O:16])=[CH:12][CH:13]=2)=[O:27])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: O=C(CCl)Cc1ccc(Sc2ccccc2)cc1
Solvent: ClC(Cl)Cl
Product: O=C(CCl)Cc1ccc(S(=O)c2ccccc2)cc1

Procedure:
The starting 1-(4-phenylsulfinylphenyl)-3-chloro acetone was prepared by mild oxydation in chloroform, of 1-(4-phenylthiophenyl)-3-chloro acetone with meta-chloro perbenzoic acid.
Reaction SMILES: I[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([NH:11][C:12]([CH:14]3[CH2:16][CH2:15]3)=[O:13])[N:10]=2)[N:7]=1.[NH2:17][C:18]1[CH:19]=[CH:20][C:21]([O:25][CH3:26])=[C:22]([OH:24])[CH:23]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[NH2:17][C:18]1[CH:19]=[CH:20][C:21]([O:25][CH3:26])=[C:22]([CH:23]=1)[O:24][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([NH:11][C:12]([CH:14]3[CH2:16][CH2:15]3)=[O:13])[N:10]=2)[N:7]=1
Reactant: COc1ccc(N)cc1O
Reactant: O=C(Nc1cn2nc(I)ccc2n1)C1CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1ccc(N)cc1Oc1ccc2nc(NC(=O)C3CC3)cn2n1
Yield: 36.1 %

Procedure:
Using N-(6-iodoimidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide (800 mg, 2.44 mmol), 5-amino-2-methoxyphenol (408 mg, 2.93 mmol), potassium carbonate (843 mg, 6.10 mmol) and N,N-dimethylformamide (6.0 mL) as starting materials and in the same manner as in Example 91, the title compound (299 mg, 36%) was obtained as a brown powder.
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:9](=[N:24][O:25][CH3:26])[CH2:10][NH:11][C:12](=[O:23])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:19]([F:22])([F:21])[F:20])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1>C(#N)C>[Cl:1][C:2]1[C:3](/[C:9](=[N:24]\[O:25][CH3:26])/[CH2:10][NH:11][C:12](=[O:23])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:19]([F:21])([F:20])[F:22])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1
Reactant: CON=C(CNC(=O)c1ccccc1C(F)(F)F)c1ncc(Cl)cc1Cl
Solvent: CC#N
Product: CO/N=C(/CNC(=O)c1ccccc1C(F)(F)F)c1ncc(Cl)cc1Cl
Yield: 78 %

Procedure:
191 mg of N-[2-(3,5-dichloropyridin-2-yl)-2-(methoxyimino)ethyl]-2-(trifluoromethyl)benzamide in 4 ml of acetonitrile was irradiated with light for 11 hours in a quartz cell (manufactured by Fine, 4 clear windows for spectroscopy) using a 100 W high-pressure mercury lamp (manufactured by USHIO INC., lamp: UM-102, power supply: UM-103B-B). After completion of the reaction, the solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography using ethyl acetate-hexane (with a gradient of from 1:9 to 3:7) as the eluent to obtain 149 mg of the desired product as white crystals.
Reaction SMILES: [CH3:1][O:2][P:3]([CH:7]([OH:17])[C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([N+:14]([O-:16])=[O:15])[CH:9]=1)(=[O:6])[O:4][CH3:5].[O:18]1[CH:23]=[CH:22][CH2:21][CH2:20][CH2:19]1.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH3:1][O:2][P:3]([CH:7]([C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([N+:14]([O-:16])=[O:15])[CH:9]=1)[O:17][CH:19]1[CH2:20][CH2:21][CH2:22][CH2:23][O:18]1)(=[O:6])[O:4][CH3:5]
Reactant: COP(=O)(OC)C(O)c1cccc([N+](=O)[O-])c1
Reactant: C1=COCCC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: COP(=O)(OC)C(OC1CCCCO1)c1cccc([N+](=O)[O-])c1
Temperature: 60 °C
Reaction time: 1 h

Procedure:
[Hydroxy-(3-nitro-phenyl)-methyl]-phosphonic acid dimethyl ester (26.7 g, 0.102 mol) was suspended in dry toluene (340 mL) under nitrogen atmosphere. 3,4-Dihydro-2H-pyrane (20.6 mL, 0.228 mol, 2.2 eq) was added, followed by p-toluensulfonic acid (590 mg, 0.003 mol, 0.03 eq) and the mixture was stirred at 60° C. for 1 h. the reaction mixture was then concentrated under reduced pressure, taken up with ethyl acetate (300 mL) and washed with saturated aqueous NaHCO3 and water. The organic layer was dried over Na2SO4 and concentrated to dryness. The desired product was obtained in quantitative yield as a yellow solid (mixture of 2 diastereoisomers).
Reaction SMILES: CC1(C)[O:9][CH:8]2[CH:4]([C@@H:5]([CH2:19]O)[O:6][C@H:7]2[N:10]2[C:16](=[O:17])[NH:15][C:13](=[O:14])[C:12]([F:18])=[CH:11]2)[O:3]1.C1(C)C=CC(S(Cl)(=O)=O)=CC=1.[I-:33].[Na+]>C(Cl)Cl.N1C=CC=CC=1.C(OCC)(=O)C.O.CC(C)=O>[I:33][CH2:19][C@H:5]1[O:6][C@@H:7]([N:10]2[CH:11]=[C:12]([F:18])[C:13](=[O:14])[NH:15][C:16]2=[O:17])[C@H:8]([OH:9])[C@@H:4]1[OH:3]
Reactant: [I-]
Reactant: CC1(C)OC2C(O1)[C@@H](CO)O[C@H]2n1cc(F)c(=O)[nH]c1=O
Agent: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: [Na+]
Solvent: c1ccncc1
Solvent: O
Solvent: ClCCl
Product: O=c1[nH]c(=O)n([C@@H]2O[C@H](CI)[C@@H](O)[C@H]2O)cc1F
Temperature: 95 °C
Reaction time: 5 h
Yield: 92.2 %

Procedure:
To a solution of 39.2 g (0.13 m) of 2′,3′-O-isopropylidene-5-fluorouridine in 55 ml of methylene chloride and 159 ml (1.98 m) of pyridine, cooled to +5° C., 60 g (0.315 m) of p-toluenesulfonyl chloride are added. The mixture thus obtained is stirred for 5 hours observing the formation of a plentiful precipitate. Then 160 ml of methylene chloride and 160 ml of water are added thereinto, whereby the temperature rises to 40° C. The phases are separated and the organic one is extracted with about 900 ml of N HCl; then the organic phase is washed with 2×100 ml of water. The organic phase, containing 0.117 m of 2′,3′-O-isopropylidene-5′-O-(p-toluenesulfonyl)-5-fluorouridine (yield —90% of the theoretical), is concentrated under vacuum until an oily residue is obtained, which is taken up with 2×100 ml of acetone. The oily residue is dissolved with 600 ml of acetone and 105 g (0.70 m) of sodium iodide are added to the solution. The mixture is heated for 5 hours at reflux, then cooled, concentrated under vacuum and the residue thus obtained is taken up with 2×80 ml of ethyl acetate. The residual oil is treated with 800 ml of ethyl acetate and 100 ml of water. The phases are separated and the aqueous one is treated with 2×80 ml of ethyl acetate. The collected organic phases are washed with 2×100 ml of a 5% aqueous solution of sodium metabisulphite, then with 100 ml of water. The organic phase, containing 0.113 m of 5′-deoxy-5′-iodo-2′,3′-0-isopropylidene-5-fluoro uridine (yield —97% of the theoretical), is concentrated under vacuum to a small volume; to the residue 560 ml of 80% aqueous acetic acid are added and the mixture is heated to 95° C. After 4-hour heating, a check by HPLC is performed (0.34% of residual starting product) After cooling, the mixture is concentrated under vacuum until an oily residue is obtained, which is taken up with 150 ml of ethyl acetate. The mixture is let to stand at 20÷25° C. for 15 ore. The product is filtered, washed with ethyl acetate and dried under vacuum at 45° C. Thus, 44.5 g of 5′-deoxy-5′-iodo-5-fluorouridine are obtained. M.p.=174÷175° C., purity (HPLC)=99.74% and [α]D=÷8.96° C. (c=1, CH3OH). The mother liquors are concentrate under vacuum and the residue is taken up with 50 ml of ethyl acetate; after 15 hours at +5° C., a further amount of 3.3 g of product are obtained. Total yield. 83% of the theoretical.
Reaction SMILES: [F:1][B-](F)(F)F.N#[O+].N[C:9]1[CH:10]=[C:11]([CH:15]=[C:16]([N+:18]([O-:20])=[O:19])[CH:17]=1)[C:12]([OH:14])=[O:13].ClC1C=CC=CC=1Cl>C(#N)C>[F:1][C:9]1[CH:10]=[C:11]([CH:15]=[C:16]([N+:18]([O-:20])=[O:19])[CH:17]=1)[C:12]([OH:14])=[O:13]
Reactant: F[B-](F)(F)F
Reactant: Nc1cc(C(=O)O)cc([N+](=O)[O-])c1
Agent: N#[O+]
Solvent: Clc1ccccc1Cl
Solvent: CC#N
Product: O=C(O)c1cc(F)cc([N+](=O)[O-])c1
Reaction time: 48 h
Yield: 64.2 %

Procedure:
A vigorously stirred slurry of nitrosonium tetrafluoroborate (3.53 g, 30.2 mM) in acetonitrile (50 ml) under an atmosphere of argon was cooled in an ice bath, and 3-amino-5-nitrobenzoic acid (5.0 g, 27.5 mM) was added in three portions. The temperature was then allowed to rise to ambient, and the mixture was stirred for 48 hours. 1,2-Dichlorobenzene (50 ml) was added, and acetonitrile distilled from the mixture at reduced pressure. The mixture was then heated to 170° for 30 minutes, when gas evolution had ended. After cooling, the mix was poured into dichloromethane (200 ml), and extracted with NaHCO3 solution. After back washing the aqueous phase with dichloromethane, it was acidified (2M hydrochloric acid), and organics extracted with ethyl acetate (2×100 ml). The combined organic layers were washed with brine, and dried over MgSO4. Crude product was purified by chromatography on silica, eluting with a gradient from dichloromethane/acetic acid (99:1) to dichloromethane/isopropanol/acetic acid (80:20:1), to give 3-fluoro-5-nitrobenzoic acid (3.26 g, 64%). Nmr (DMSO-d6): δ 8.14 (dm, 1H); 8.37 (dt, 1H); 8.46 (m, 1H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:12]([CH2:13][O:14][C:15]3[CH:16]=[C:17]([C:20]([OH:22])=O)[NH:18][N:19]=3)=[C:11]([CH3:23])[O:10][N:9]=2)=[N:6][CH:7]=1.FC1C=CC(C2C(CO[C:38]3[CH:39]=[C:40]([C:43](O)=O)[NH:41][N:42]=3)=C(C)ON=2)=CC=1>>[N:42]1([NH:41][C:20]([C:17]2[NH:18][N:19]=[C:15]([O:14][CH2:13][C:12]3[C:8]([C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][N:6]=4)=[N:9][O:10][C:11]=3[CH3:23])[CH:16]=2)=[O:22])[CH2:43][CH2:40][CH2:39][CH2:38]1
Reactant: Cc1onc(-c2ccc(F)cn2)c1COc1cc(C(=O)O)[nH]n1
Reactant: Cc1onc(-c2ccc(F)cc2)c1COc1cc(C(=O)O)[nH]n1
Product: Cc1onc(-c2ccc(F)cn2)c1COc1cc(C(=O)NN2CCCC2)[nH]n1
Yield: 39 %

Procedure:
As described for example 10b, 5-[3-(5-fluoro-pyridin-2-yl)-5-methyl-isoxazol-4-ylmethoxy]-2H-pyrazole-3-carboxylic acid (38 mg, 0.12 mmol), instead of 5-[3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-2H-pyrazole-3-carboxylic acid, was converted, to the title compound (18 mg, 39%) which was obtained as a white solid. MS: m/e=387.2 [M+H]+.
Reaction SMILES: [CH2:1]([N:5]1[CH2:10][CH2:9][CH:8]([C:11]2[CH:16]=[CH:15][C:14]([N:17]([CH3:19])[CH3:18])=[CH:13][CH:12]=2)[CH:7]([CH2:20][OH:21])[CH2:6]1)[CH2:2][CH2:3][CH3:4].[CH2:22]1[O:26][C:25]2[CH:27]=[C:28](O)[CH:29]=[CH:30][C:24]=2[O:23]1.[OH-].[Na+].[ClH:34].CN1CC[C@@H](C2C=CC([N+]([O-])=O)=CC=2)[C@H](COC2C=CC3OCOC=3C=2)C1>CC(CC(O)C)C>[ClH:34].[CH2:1]([N:5]1[CH2:10][CH2:9][C@@H:8]([C:11]2[CH:12]=[CH:13][C:14]([N:17]([CH3:18])[CH3:19])=[CH:15][CH:16]=2)[C@H:7]([CH2:20][O:21][C:28]2[CH:29]=[CH:30][C:24]3[O:23][CH2:22][O:26][C:25]=3[CH:27]=2)[CH2:6]1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCN1CCC(c2ccc(N(C)C)cc2)C(CO)C1
Reactant: Oc1ccc2c(c1)OCO2
Agent: CN1CC[C@@H](c2ccc([N+](=O)[O-])cc2)[C@H](COc2ccc3c(c2)OCO3)C1
Agent: Cl
Agent: [Na+]
Solvent: CC(C)CC(C)O
Product: CCCCN1CC[C@@H](c2ccc(N(C)C)cc2)[C@H](COc2ccc3c(c2)OCO3)C1

Procedure:
3-benzenesulphonyloxymethyl-1-butyl-4-(4-dimethyl-aminophenyl)piperidine (16) (2 g) (prepared from compound (12), benzenesulphonyl chloride and triethylamine by known procedures) was treated with sesamol (0.73 g) and NaOH (0.21 g) in MIBC as described for the preparation of compound (1). Reflux for 2 h. The crude product was purified several times on a silica gel column using CH2Cl2 /CH3OH 9/1 as eluent. Yield 0.05 g of colorless crystals after precipitation as the hydrochloride. M.p. 211.5°-214° C.
Reaction SMILES: [Br:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:8]=[C:9]([CH3:11])[CH:10]=1)C=O.[CH:12](OC)([O:15][CH3:16])[O:13][CH3:14].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[Br:1][CH2:2][C:3]1[CH:10]=[C:9]([CH3:11])[CH:8]=[C:5]([CH:12]([O:15][CH3:16])[O:13][CH3:14])[CH:4]=1
Reactant: Cc1cc(C=O)cc(CBr)c1
Reactant: COC(OC)OC
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: CO
Product: COC(OC)c1cc(C)cc(CBr)c1
Temperature: 25 °C

Procedure:
A mixture of crude 3-bromomethyl-5-methyl-benzaldehyde (21 g, 98.51 mmol), trimethyl orthoformate (21.88 ml), and p-toluenesulfonic acid monohydrate (1.9 g) in anhydrous methanol (100 ml) was refluxed for 2 hr. After cooling to room temperature, the mixture was evaporated in vacuo. The residue was dissolved in ether, washed with aqueous sodium bicarbonate solution, dried with anhydrous magnesium sulfate, filtered, and evaporated in vacuo to give a crude product as a pale brown oil. The crude product was purified by silica gel column chromatography (eluent, ether:hexanes (1:9)) to afford 7.6 g (29% for 2 steps) of a colorless oil. 1H NMR (300 MHz, CDCl3) δ 2.35 (3H, s), 3.33 (6H, s), 4.47 (2H, s), 5.32 (1H, s), 7.17 (1H, s), 7.19 (1H, s), 7.27 (1H, s).
Reaction SMILES: I[C:2]1[C:3]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)=[N:4][N:5]([CH3:11])[C:6]=1[C:7]([O:9][CH3:10])=[O:8].[CH3:20]B1OB(C)OB(C)O1>C1COCC1.[Pd](Cl)Cl.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2]>[CH3:19][O:18][C:15]1[CH:16]=[CH:17][C:12]([C:3]2[C:2]([CH3:20])=[C:6]([C:7]([O:9][CH3:10])=[O:8])[N:5]([CH3:11])[N:4]=2)=[CH:13][CH:14]=1
Reactant: CB1OB(C)OB(C)O1
Reactant: COC(=O)c1c(I)c(-c2ccc(OC)cc2)nn1C
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: CC(C)(C)P([c-]1cccc1)C(C)(C)C
Solvent: C1CCOC1
Product: COC(=O)c1c(C)c(-c2ccc(OC)cc2)nn1C
Temperature: 60 °C

Procedure:
A solution of methyl 4-iodo-3-(4-methoxyphenyl)-1-methyl-1H-pyrazole-5-carboxylate (587.8 mg, 1.579 mmol), trimethylboroxine (883 μL, 6.32 mmol) and 1,1′-bis(di-tert-butylphosphino)ferrocene palladium dichloride (103 mg, 0.158 mmol) in THF (2.6 mL) was degassed by bubbling N2 through the solution. 1N K2CO3 (2.6 mL) was added and N2 was bubbled through the mixture for 30 s. The mixture was heated in a sealed tube at 60° C. overnight. Another 4 eq. of trimethylboroxine was added and the reaction was subjected to microwave irradiation (120° C., 30 min). The reaction mixture was filtered through a plug of silica, eluted with EtOAc and the filtrate was washed with 1N aq. NaOH (2×30 mL), dried (Na2SO4) and concentrated in vacuo to afford the crude product. This was purified by flash chromatography (Biotage Horizon, 25M, Si, ˜20 mL/min, 100% hexanes for 144 mL, gradient to 20% EtOAc in hexanes over 2394 mL) to afford methyl 3-(4-methoxyphenyl)-1,4-dimethyl-1H-pyrazole-5-carboxylate, as a colorless solid. Rf=0.33 (20% EtOAc/hexanes). LCMS calc.=261.03. found=261.12 (M+H)+. 1H NMR (600 MHz, CDCl3): δ 7.51 (d, J=8.5 Hz, 2H); 6.96 (d, J=8.5 Hz, 2H); 4.16 (s, 3H); 3.92 (s, 3H); 3.83 (s, 3H); 2.36 (s, 3H).
Reaction SMILES: [CH2:1]([S:4][CH2:5][C:6]1[N:10]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:19]([C:24]([O:26]C(C)(C)C)=[O:25])=[CH:20][CH:21]=[CH:22][CH:23]=3)=[CH:14][CH:13]=2)[C:9]2[CH:31]=[CH:32][CH:33]=[CH:34][C:8]=2[N:7]=1)[CH2:2][CH3:3].FC(F)(F)C(O)=O>>[CH2:1]([S:4][CH2:5][C:6]1[N:10]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:19]([C:24]([OH:26])=[O:25])=[CH:20][CH:21]=[CH:22][CH:23]=3)=[CH:14][CH:13]=2)[C:9]2[CH:31]=[CH:32][CH:33]=[CH:34][C:8]=2[N:7]=1)[CH2:2][CH3:3]
Reactant: CCCSCc1nc2ccccc2n1Cc1ccc(-c2ccccc2C(=O)OC(C)(C)C)cc1
Solvent: O=C(O)C(F)(F)F
Product: CCCSCc1nc2ccccc2n1Cc1ccc(-c2ccccc2C(=O)O)cc1

Procedure:
Prepared in analogous manner to Example 9 from tert.butyl 4'-[(2-n-propylthiomethyl-benzimidazol-1-yl)-methyl]biphenyl-2-carboxylate and trifluoroacetic acid.
Reaction SMILES: [C:1]1(=[O:14])[C:6]2=[N:7][C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=3[N:5]2[CH2:4][CH2:3][NH:2]1>[Pd].C(O)(=O)C>[C:1]1(=[O:14])[C:6]2=[N:7][C:8]3[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=3[N:5]2[CH2:4][CH2:3][NH:2]1
Reactant: O=C1NCCn2c1nc1ccccc12
Agent: [Pd]
Solvent: CC(=O)O
Product: O=C1NCCn2c1nc1c2CCCC1
Temperature: 95 °C
Reaction time: 16 h
Yield: 71.1 %

Procedure:
A 250-mL stainless steel pressure reactor was charged with 10% palladium on carbon (50% wet, 150 mg dry weight) and a solution of 152b (670 mg, 3.58 mmol) in acetic acid (25 mL). The reactor was evacuated, charged with hydrogen gas to a pressure of 350 psi and stirred at 95° C. for 16 h. After this time, the hydrogen was evacuated, and nitrogen was charged into the reactor. Celite 521 (1.00 g) was added, and the mixture was filtered through a pad of Celite 521. The filter cake was washed with ethanol (2×25 mL), and the combined filtrates were concentrated to dryness under reduced pressure. To the resulting residue was added water (10 mL), and followed by potassium carbonate to adjust pH to 9. The mixture was extracted with methylene chloride (4×20 mL), and the organic extracts were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure to afford a 71% yield 152c (487 mg) as a white solid: mp>250° C.; 1H NMR (500 MHz, DMSO-d6) d 7.86 (s, 1H), 3.98 (t, 2H, J=6.5 Hz), 3.51 (m, 2H), 2.50 (m, 4H), 1.75 (m, 4H); MS (APCI+) m/z 192.6 (M+H).
Reaction SMILES: [Mg].[CH:2]1(Br)[CH2:4][CH2:3]1.[CH3:6][N:7]1[CH:11]=[CH:10][CH:9]=[C:8]1[C:12]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:13].[Cl-].[NH4+]>O1CCCC1.O>[CH:2]1([C:12]([C:8]2[N:7]([CH3:6])[CH:11]=[CH:10][CH:9]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[OH:13])[CH2:4][CH2:3]1
Reactant: Cn1cccc1C(=O)c1ccccc1
Reactant: BrC1CC1
Agent: [Cl-]
Agent: [Mg]
Agent: [NH4+]
Solvent: O
Solvent: C1CCOC1
Product: Cn1cccc1C(O)(c1ccccc1)C1CC1
Yield: 60.5 %

Procedure:
To a suspension of magnesium turnings (5.29 g, 0.22 mole) in anhydrous tetrahydrofuran (70 ml), cyclopropyl bromide (26.35 g, 0.22 mole) in tetrahydrofuran (50 ml) was added dropwise under nitrogen. The reaction mixture was heated at reflux for one h after the initial exotherm had subsided before (N-methylpyrrol-2-yl)phenylketone (13.3 g, 0.072 mole) (J. White and G. McGillivray, J. Org. Chem., (1977), 42, 4248, R. Greenhouse and C. Ramirez, J. Org. Chem., (1985), 50, 2961) in anhydrous tetrahydrofuran (50 ml ) was introduced dropwise. After heating the reaction mixture at reflux for 3 h it was cooled and saturated, aqueous ammonium chloride solution (95 ml) and water (150 ml) were added. The mixture was extracted with ethyl acetate (3×200 ml) and the combined extracts were dried (MgSO4). Flash chromatography of the residue on evaporation on silica gel eluting with heptane/tetrahydrofuran (9:1) provided the title compound as an oil (9.9 g, 46%) which solidified on standing. T.l.c. rf=0.35 (SiO2, heptane/THF (7:3)).
Reaction SMILES: CC(C)([O-])C.[K+].[Br:7][C:8]1[NH:9][C:10]([Br:16])=[C:11]([Br:15])[C:12]=1[C:13]#[N:14].[N:17]#[C:18]Br>O1CCCC1.O>[Br:7][C:8]1[N:9]([C:18]#[N:17])[C:10]([Br:16])=[C:11]([Br:15])[C:12]=1[C:13]#[N:14]
Reactant: N#Cc1c(Br)[nH]c(Br)c1Br
Reactant: N#CBr
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Product: N#Cc1c(Br)c(Br)n(C#N)c1Br
Temperature: 25 °C
Reaction time: 8 h
Yield: 74.4 %

Procedure:
Potassium t-butoxide (614 mg, 5.74 mmol) is added in portions at room temperature to a solution of 2,4,5-tribromopyrrole-3-carbonitrile (1.50 g, 4.56 mmol) in anhydrous tetrahydrofuran (20 mL). After 15 minutes a solution of cyanogen bromide (177 mg, 5.74 mmol) in tetrahydrofuran (5 mL) is added dropwise. The reaction solution is stirred at room temperature overnight as it turns cloudy. The mixture is diluted with water and extracted with ethyl acetate. The organic layer is washed with water and saturated sodium chloride and dried over (Na2SO4). Evaporation of the solvent and crystallization of the residue from ether gives a white solid (1.20 g); mp 195.0°-197.5° C.
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH2:10][OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P([O-])([O-])(O)=O.[K+].[K+].Cl[O-].[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+]>O.ClCCl>[CH2:1]([O:8][CH2:9][CH:10]=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OCCOCc1ccccc1
Agent: O=P([O-])([O-])O
Agent: O=S([O-])([O-])=S
Agent: [K+]
Solvent: O
Solvent: ClCCl
Product: O=CCOCc1ccccc1
Temperature: 0 °C
Reaction time: 0.08 h
Yield: 30.6 %

Procedure:
A 300-ml three-necked flask was charged with 15.2 g (0.1 mole) of 2-benzyloxyethanol, 100 ml of dichloromethane and 20 ml of water, and further with 2.6 g (15 mmoles ) of dipotassium hydrogenphosphate and 32 mg (0.15 mmole) of 4-acetoxy-2,2,6,6-tetramethyl-piperidinyl-1-oxy, and the mixture was cooled with ice water to 0 to 5° C. with stirring. To the mixed solution, with stirring, 46.6 g (75 mmoles ) of a 12% aqueous solution of sodium hypochlorite was added dropwise over 2 hours, while care was being taken not to permit the temperature to exceed 20° C. After completion of the addition, the mixture was stirred at the same temperature for 30 minutes. To the obtained mixture, 30 ml of a 5% aqueous solution of sodium thiosulfate was added, and the resulting mixture wasstirred for 5 minutes. The organic layer was then separated from the mixture. The organic layer separated was washed with 30 ml of saturated aqueous solution of sodium chloride and the solvent was distilled off. The residue obtained was further subjected to vacuum distillation, to yield 7.5 g of benzyloxyacetaldehyde as a fraction at a boiling point of 118 to 120° C./13 mmHg and 4.6 g of unreacted 2-benzyloxyacetaldehyde as a fraction at a boiling point of 128 to 130° C./13 mmHg (yield of benzyloxyacetaldehyde based on the 2-benzyloxyethanol that had reacted: 71.4%, ratio of recovery of 2-benzyloxyethanol: 30.2%).
Reaction SMILES: CS(O[CH2:6][CH2:7][C:8]1[O:9][C:10]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([N:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[O:24])=[CH:19][N:18]=3)=[CH:13][C:11]=2[CH:12]=1)(=O)=O.[NH:31]1[CH2:35][CH2:34][CH2:33][CH2:32]1>>[N:31]1([CH2:6][CH2:7][C:8]2[O:9][C:10]3[CH:16]=[CH:15][C:14]([C:17]4[N:18]=[CH:19][C:20]([C:23]([N:25]5[CH2:26][CH2:27][O:28][CH2:29][CH2:30]5)=[O:24])=[CH:21][CH:22]=4)=[CH:13][C:11]=3[CH:12]=2)[CH2:35][CH2:34][CH2:33][CH2:32]1
Reactant: CS(=O)(=O)OCCc1cc2cc(-c3ccc(C(=O)N4CCOCC4)cn3)ccc2o1
Reactant: C1CCNC1
Product: O=C(c1ccc(-c2ccc3oc(CCN4CCCC4)cc3c2)nc1)N1CCOCC1

Procedure:
The product from Example 44E and pyrrolidine were processed as described in Example 1D to provide the titled compound. 1H NMR (300 MHz, CD3OD) δ8.70 (m, 1H), 8.24 (d, J=1.8 Hz, 1H), 7.98 (m, 3H), 7.60 (d, J=8.7 Hz, 1H), 6.84 (s, 1H), 3.3-3.8 (m, 12H), 3.18 (m, 2H), 2.0-2.25 (m, 6H); MS (DCI) m/z 406 (M+H)+;
Reaction SMILES: C([O:4][CH2:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]([C:16]([O:18][CH3:19])=[O:17])=[CH:8][CH:7]=1)(=O)C.[OH-].[Na+].Cl>CO>[OH:4][CH2:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]([C:16]([O:18][CH3:19])=[O:17])=[CH:8][CH:7]=1
Reactant: COC(=O)c1ccc(COC(C)=O)c2ccccc12
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: COC(=O)c1ccc(CO)c2ccccc12
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 85.1 %

Procedure:
To a solution of methyl 4-((acetyloxy)methyl)-1-naphthalenecarboxylate (3.91 g, 15.1 mmol) in methanol (20 ml) was added 1N aqueous sodium hydroxide solution (15.1 ml, 15.1 mmol), and the mixture was stirred at room temperature for 5 min. 1N Hydrochloric acid was added to the reaction solution (20 ml) and the mixture was extracted with ethyl acetate (50 ml×2). The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1) to give methyl 4-(hydroxymethyl)-1-naphthalenecarboxylate (2.78 g, 85%).