Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=O)[NH:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[N+:13]([O-:15])=[O:14].P(Cl)(Cl)([Cl:18])=O.CN(C=O)C>S(Cl)(Cl)=O>[Cl:18][C:6]1[C:5]2[C:10](=[CH:11][C:2]([Cl:1])=[C:3]([N+:13]([O-:15])=[O:14])[CH:4]=2)[N:9]=[CH:8][N:7]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: O=c1[nH]cnc2cc(Cl)c([N+](=O)[O-])cc12
Solvent: O=S(Cl)Cl
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1cc2c(Cl)ncnc2cc1Cl
Yield: 81 %

Procedure:
A mixture of 7-chloro-6-nitro-3,4-dihydroquinazolin-4-one (40 g, 0.18 mol), (J. Org. Chem. 1975, 40, 356), phosphorus oxychloride (50 ml) and DMF (1 ml) in thionyl chloride (300 ml) was heated at reflux for 4 hours. The reaction mixture was allowed to cool and the volatiles removed by evaporation and by azeotroping with toluene. The residue was basified with aqueous sodium hydrogen carbonate solution and extracted with methylene chloride (4×100 ml). The extracts were combined, washed with brine and filtered through phase separating paper. The solvent was removed by evaporation and the residue triturated with ether/isohexane to give 4,7-dichloro-6-nitroquinazoline (35.2 g, 81%) as a pale yellow solid.
Reaction SMILES: [C:1]1([C:7]2[NH:8][CH:9]=[C:10]([CH:12]=[O:13])[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[S:16]1[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[CH:18]=[C:17]1[S:25](Cl)(=[O:27])=[O:26].O>O1CCCC1>[S:16]1[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[CH:18]=[C:17]1[S:25]([N:8]1[CH:9]=[C:10]([CH:12]=[O:13])[N:11]=[C:7]1[C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)(=[O:27])=[O:26]
Reactant: O=Cc1c[nH]c(-c2ccccc2)n1
Reactant: O=S(=O)(Cl)c1cc2ccccc2s1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: O=Cc1cn(S(=O)(=O)c2cc3ccccc3s2)c(-c2ccccc2)n1
Reaction time: 0.5 h
Yield: 83.5 %

Procedure:
To a solution of 2-phenyl-1H-imidazole-4-carbaldehyde (700 mg) in tetrahydrofuran (70 mL) was added sodium hydride (60% in oil, 244 mg), and the mixture was stirred for 30 min. 1-Benzothiophene-2-sulfonyl chloride (1.04 g) was added to the reaction mixture, and the mixture was stirred for 1.5 hr. Water was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent:hexane-ethyl acetate=7:3) to give the title compound as a colorless oil (yield 1.25 g, 83%).
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6]Br)=[CH:4][CH:3]=1.[NH:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1>C1COCC1>[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[CH:4][CH:3]=1
Reactant: C1CNCCN1
Reactant: BrCc1ccc(Br)cc1
Solvent: C1CCOC1
Product: Brc1ccc(CN2CCNCC2)cc1

Procedure:
Synthesized according to General Procedure A: 4-bromobenzyl bromide (4{9}, 7 g, 28.0 mmol, 1 equiv.), piperazine (14.5 g, 168.0 mmol, 6 equiv.), THF (61.2 mL). Purification with flash column chromatography on silica gel (4:1 EtOAc:MeOH) afforded 5{9} (6.73 g, 94%) as a white solid. 1H-NMR (400 MHz, CDCl3): δ 7.42 (d, 2H, J=8.4 Hz) 7.19 (d, 2H, J=8.4 Hz), 3.42 (s, 2H) 2.87 (t, 4H, J=4.8 Hz), 2.38 (br s, 4H), 2.07 (br s, 1H). 13C-NMR (100 MHz, CDCl3): δ 137.1, 131.3, 130.9, 120.8, 62.8, 54.2, 45.9.
Reaction SMILES: [CH2:1]([NH:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[C:15]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][C@@H:23]3[CH3:28])[C:16]3[CH2:21][NH:20][CH2:19][C:17]=3[N:18]=2)=[CH:9][CH:8]=1)=[O:5])[CH3:2].[CH3:29][C:30]([CH3:32])=O>>[CH2:1]([NH:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[C:15]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][C@@H:23]3[CH3:28])[C:16]3[CH2:21][N:20]([CH:30]([CH3:32])[CH3:29])[CH2:19][C:17]=3[N:18]=2)=[CH:9][CH:8]=1)=[O:5])[CH3:2]
Reactant: CCNC(=O)Nc1ccc(-c2nc3c(c(N4CCOC[C@@H]4C)n2)CNC3)cc1
Reactant: CC(C)=O
Product: CCNC(=O)Nc1ccc(-c2nc3c(c(N4CCOC[C@@H]4C)n2)CN(C(C)C)C3)cc1

Procedure:
Method as example 26 using (S)-1-ethyl-3-(4-(4-(3-methylmorpholino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)phenyl)urea (example 7) and acetone as starting materials. Purification by prep HPLC (high pH).
Reaction SMILES: [N:1]([CH:4]1[CH2:13][CH2:12][CH2:11][C:10]2[CH:9]=[C:8]([O:14][S:15]([C:18]([F:21])([F:20])[F:19])(=[O:17])=[O:16])[CH:7]=[CH:6][C:5]1=2)=[N+]=[N-].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.Cl>C1COCC1>[NH2:1][CH:4]1[CH2:13][CH2:12][CH2:11][C:10]2[CH:9]=[C:8]([O:14][S:15]([C:18]([F:21])([F:19])[F:20])(=[O:17])=[O:16])[CH:7]=[CH:6][C:5]1=2
Reactant: [N-]=[N+]=NC1CCCc2cc(OS(=O)(=O)C(F)(F)F)ccc21
Agent: Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: O
Product: NC1CCCc2cc(OS(=O)(=O)C(F)(F)F)ccc21
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of trifluoro-methanesulfonic acid 5-azido-5,6,7,8-tetrahydro-naphthalen-2-yl ester (10.3 g, 32.1 mmol, 1.0 eq) in THF (70 mL) was added PPh3 (Aldrich, 8.4 g, 32.1 mmol, 1.0 eq), and H2O (30 mL) at 0° C. The mixture was warmed to RT and stirred overnight. 2N HCl was added until the mixture was acidic (pH ˜1–2). The mixture was extracted with toluene (3×100 mL). The aqueous phase was neutralized with 5N NaOH to pH around 12–13, and extracted with ether (3×150 mL). The ether solution was dried over Na2SO4, filtered and concentrated in vacuo. The crude was purified by flash chromatography (6% MeOH—CH2Cl2) to provide the title compound.
Reaction SMILES: [Cl:1][C:2]1[NH:3][C:4](I)=[C:5]([N+:7]([O-:9])=[O:8])[N:6]=1.C(N(CC)CC)C>C(O)C.[C].[Pd]>[Cl:1][C:2]1[NH:3][CH:4]=[C:5]([N+:7]([O-:9])=[O:8])[N:6]=1
Reactant: O=[N+]([O-])c1nc(Cl)[nH]c1I
Agent: [Pd]
Solvent: CCN(CC)CC
Solvent: CCO
Product: O=[N+]([O-])c1c[nH]c(Cl)n1
Reaction time: 3 h
Yield: 84.2 %

Procedure:
2-Chloro-5-iodo-4-nitroimidazole (273 mg) was dissolved in ethanol (5 ml), then triethylamine (420 μl ) and 10% palladium-carbon (27 mg) were added, the reaction mixture was subjected to hydrogenation at a room temperature under normal pressure for 3 hours, there was obtained 2-chloro-4-nitroimidazole (124 mg, yield: 84.1%) as colorless solid product.
Reaction SMILES: Cl[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=1)=[O:4].[Na+].[I-].[CH:14]([N:17]1[CH2:24][CH:23]2[CH2:25][CH:19]([CH2:20][NH:21][CH2:22]2)[CH2:18]1)([CH3:16])[CH3:15]>CC#N>[CH:14]([N:17]1[CH2:24][CH:23]2[CH2:25][CH:19]([CH2:20][N:21]([CH2:2][C:3]([C:5]3[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=3)=[O:4])[CH2:22]2)[CH2:18]1)([CH3:16])[CH3:15]
Reactant: CC(C)N1CC2CNCC(C2)C1
Reactant: O=C(CCl)c1ccc(F)cc1
Agent: [I-]
Agent: [Na+]
Solvent: CC#N
Product: CC(C)N1CC2CC(CN(CC(=O)c3ccc(F)cc3)C2)C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 23.9 %

Procedure:
To a standard setup was added 2-chloro-4'-fluoroacetophenone (7.55 g, 43.8 mmol) and NaI (9.85 g, 65.7 mmol) in H3CCN (30 ml) which was then heated for 30 minutes with stirrring. The solution was allowed to cool to room temperature (30 mnin) which was followed by dropwise addition of amine 105 (6.7 g, 39.8 mmol) to give a light yellow mixture which was stirred overnight. Filtration (suction) removed excess NaI and the filtrate was diluted with H2O and transferred to a separatory funnel. The resulting homogenous solution (pH~5) was extracted (ether, 3×75 ml) with the latter being discarded, and the pH of the aqueous layer was adjusted to 12 using 10% NaOH. Extraction (ether, 3×75 ml) of the aqueous layer was followed by another extraction (H2CCl2, 3×75 ml) and the ether extracts were discarded. The organic layer (H2CCl2) was dried (Na2SO4, 2 h), filtered, and concentrated (rotary evaporator) to give 2.9 g (86.1 %) of amine 55 as a light yellow solid; mp 193°-194° C. IR (KBr) 3060, 3040 (Ar-H), 2940, 2805 (C-H), 1700 (C=O) cm-1 ; 1H NMR (DCCl3) d 1.45 (d, 6 H, CH3 isopropyl), 1.81 [d, 1 H, H(9)ax, 2.11 [d, 1 H, H(9)eq ], 2.32 [bs, 2 H, H(1,5)], 2.85 (d, 2 H, ring protons), 3.37 (d, 2 H, ring protons), 3.49 (d, 2 H, ring protons), 3.86 (m, 3 H, ring protons, C-H isopropyl), 4.18 (s, 2 H, ArC(O)CH2), 7.15 (t, 2 H, Ar-H), 8.02 (m, 2 H, Ar-H); 13C NMR (DCCl3) ppm 17.01 (CH3 isopropyl), 28.04 [C(1,5)], 30.05 [C(9)], 53.74, 57.2257.34 (ring carbons, C-H isopropyl), 62.22 [ArC(O)CH2 ], 115.58, 115.88, 130.57, 130.70, 131.22, 131.26 (Ar-C), 164.10, 167.49(J=265.8Hz, ArC-F), 194.99 (C=O). Ketone 55 was slightly unstable, and thus was reduced to the corresponding alcohol 110.
Reaction SMILES: Br[C:2]1[S:6][C:5]2=[C:7]([C:10]3[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=3)[N:8]=[CH:9][N:4]2[C:3]=1[CH2:16][O:17][Si:18]([CH2:23][CH3:24])([CH2:21][CH3:22])[CH2:19][CH3:20].C([Mg]Br)C.CN(OC)[C:31](=[O:34])[CH2:32][CH3:33].[Cl-].[NH4+]>O1CCCC1>[C:31]([C:2]1[S:6][C:5]2=[C:7]([C:10]3[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=3)[N:8]=[CH:9][N:4]2[C:3]=1[CH2:16][O:17][Si:18]([CH2:23][CH3:24])([CH2:21][CH3:22])[CH2:19][CH3:20])(=[O:34])[CH2:32][CH3:33]
Reactant: CC[Si](CC)(CC)OCc1c(Br)sc2c(-c3cccnc3)ncn12
Reactant: CCC(=O)N(C)OC
Agent: CC[Mg]Br
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CCC(=O)c1sc2c(-c3cccnc3)ncn2c1CO[Si](CC)(CC)CC
Reaction time: 1 h
Yield: 79.8 %

Procedure:
A solution of 5.14 g of 2-bromo-7-(pyridin-3-yl)triethylsilyloxymethylimidazo[5,1-b]thiazole in 36 ml of tetrahydrofuran under an argon atmosphere was cooled to −60° C., 13.3 ml of a 0.89 M tetrahydrofuran solution of ethylmagnesium bromide was added thereto, and the mixture was stirred for one hr. N-Methyl-N-methoxypropionamide (1.71 g) was added thereto at −30° C., and the mixture was stirred at room temperature for 12 hr. A 20% aqueous ammonium chloride solution was added to stop the reaction, and the reaction mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous sodium bicarbonate solution and saturated brine in that order and was then dried over anhydrous magnesium sulfate. The solvent was removed by evaporation, and the residue was purified by column chromatography on silica gel (3 to 6% methanol/methylene chloride) to give 3.88 g of 2-propionyl-7-(pyridin-3-yl)triethylsilyloxymethylimidazo[5,1-b]thiazole.
Reaction SMILES: CCCCCC.C([Li])CCC.CO[B:14]([O:17]C)[O:15]C.Cl.CCCCCC.Br[C:27]1[C:32]2[O:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[C:31]=2[CH:30]=[CH:29][CH:28]=1>O1CCCC1>[CH:30]1[C:31]2[C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=3[O:33][C:32]=2[C:27]([B:14]([OH:15])[OH:17])=[CH:28][CH:29]=1
Reactant: COB(OC)OC
Reactant: Brc1cccc2c1oc1ccccc12
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: OB(O)c1cccc2c1oc1ccccc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 80 %

Procedure:
In a 300 ml three-necked flask, 7.2 g of 4-bromodibenzofuran was dissolved in −78° C. anhydrous tetrahydrofuran (THF) under an argon atmosphere. Then, 20 ml of an n-butyl lithium-n-hexane solution (1.6 M, 1.1 eq) was added and stirred for 1 hour. 4.23 ml (1.3 eq) of trimethoxyborane (B(OMe)3) was added and stirred for 2 hours, and the temperature of the reaction system was increased to room temperature. 200 ml of 1 N hydrochloric acid was added into the reactant and stirred for 3 hours. An organic layer was separated, and solvents were distilled off. In the crude product thus obtained, hexane was added. Precipitated product was filtered to obtain 4.94 g of dibenzofuran-4-boronic acid as a white solid (yield 80%). The product was measured by FAB-MS, and dibenzofuran-4-boronic acid having a molecular weight of 212 was detected.
Reaction SMILES: [CH:1]1N=[CH:4][N:3]([C:6]([N:8]2[CH:12]=[N:11][CH:10]=[CH:9]2)=[O:7])[CH:2]=1.[F:13][C:14]([F:26])([F:25])[C:15]1[CH:16]=[N:17][C:18]2CCNC[C:23]=2[CH:24]=1>C1COCC1.C(Cl)Cl>[N:8]1([C:6]([N:3]2[CH2:2][CH2:1][C:18]3[N:17]=[CH:16][C:15]([C:14]([F:26])([F:25])[F:13])=[CH:24][C:23]=3[CH2:4]2)=[O:7])[CH:9]=[CH:10][N:11]=[CH:12]1
Reactant: FC(F)(F)c1cnc2c(c1)CNCC2
Reactant: O=C(n1ccnc1)n1ccnc1
Solvent: ClCCl
Solvent: C1CCOC1
Product: O=C(N1CCc2ncc(C(F)(F)F)cc2C1)n1ccnc1
Temperature: 60 °C
Yield: 88.5 %

Procedure:
To a suspension of CDI (0.949 g, 5.86 mmol) in THF (10 mL) was added 3-trifluoromethyl-5,6,7,8-tetrahydro-[1,6]naphthyridine (0.988 g, 4.88 mmol) and the reaction mixture was heated at about 60° C. for about 16 h. The reaction mixture was cooled at ambient temperature and concentrated in vacuo to afford a light orange solid. The residue was dissolved in DCM (10 mL), washed with water (2×10 mL), and the organic portion was separated, dried over MgSO4, filtered, and concentrated in vacuo to give imidazol-1-yl-(3-trifluoromethyl-7,8-dihydro-5H-[1,6]naphthyridin-6-yl)-methanone (1.28 g, 88%) as a yellow solid which was used in subsequent reactions without further purification. RP-HPLC (Table 1, Method d) Rt 2.10 min; m/z: (M+H)+ 297.
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]([OH:10])=O)=[CH:6][N:5]=[CH:4][CH:3]=1.[CH:11]([NH2:13])=O>>[N:1]1[C:2]2[CH:3]=[CH:4][N:5]=[CH:6][C:7]=2[C:8](=[O:10])[NH:13][CH:11]=1
Reactant: NC=O
Reactant: Nc1ccncc1C(=O)O
Product: O=c1[nH]cnc2ccncc12
Yield: 47 %

Procedure:
Crude 4-amino nicotinic acid (2.72 g, 11.4 mmol) in formamide (20 mL) is heated to 170° C. for 12 h. The volatiles are distilled out under reduced pressure (0.8 mm Hg). The residual solid is then purified on a medium pressure silica gel column, eluting with 10% MeOH in CHCl3 to give 3H-pyrido[4,3-d]pyrimidin-4-one (780 mg, 47%) as a whitish yellow solid. 1H NMR (DMSO) δ 12.64 (1H, brs), 9.28 (1H, s), 8.83 (1H, d, J=5.5 Hz), 8.30 (1H, s), 7.58 (1H, d, J=5.8 Hz).
Reaction SMILES: [NH2:1][C:2]1[CH:36]=[CH:35][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[CH:13]=[C:14]([C:16]4[CH:17]=[C:18]([CH:32]=[CH:33][CH:34]=4)[CH2:19][N:20]([CH2:28][CH2:29][O:30][CH3:31])[C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[S:15][C:8]=23)=[C:4]([F:37])[CH:3]=1.[C:38]1([CH2:44][C:45]([N:47]=[C:48]=[S:49])=[O:46])[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>C1COCC1>[F:37][C:4]1[CH:3]=[C:2]([NH:1][C:48]([NH:47][C:45](=[O:46])[CH2:44][C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)=[S:49])[CH:36]=[CH:35][C:5]=1[O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]2[CH:13]=[C:14]([C:16]3[CH:17]=[C:18]([CH:32]=[CH:33][CH:34]=3)[CH2:19][N:20]([CH2:28][CH2:29][O:30][CH3:31])[C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[S:15][C:8]=12
Reactant: COCCN(Cc1cccc(-c2cc3nccc(Oc4ccc(N)cc4F)c3s2)c1)C(=O)OC(C)(C)C
Reactant: O=C(Cc1ccccc1)N=C=S
Solvent: C1CCOC1
Product: COCCN(Cc1cccc(-c2cc3nccc(Oc4ccc(NC(=S)NC(=O)Cc5ccccc5)cc4F)c3s2)c1)C(=O)OC(C)(C)C
Reaction time: 0.5 h
Yield: 125.6 %

Procedure:
To a solution of 74 (235 mg, 0.5 mmol) in dry THF (5 mL), 2-phenylacetyl isothiocyanate (159 mg, 0.9 mmol) was added and the reaction was allowed to stir for 30 min. The solvent was removed under reduced pressure and the resulting product was purified by chromatography on silica gel using EtOAc/hexane (1:1) as eluting system to give the desired product (440 mg, 90%) as a white solid. 1H NMR (DMSO) δ (ppm): 8.52 (d, J=5.3 Hz, 1H), 8.01 (t, J=6.5 Hz, 2H), 7.79 (d, J=7.4 Hz, 1H), 7.70 (s, 1H), 7.53-7.52 (m, 2H), 7.47 (t, J=7.6 Hz, 1H), 7.34 (d, J=4.5 Hz, 4H), 7.30-7.24 (m, 2H), 6.67 (d, J=5.3 Hz, 1H), 4.49 (s, 2H), 3.83 (s, 2H), 3.42 (s, 2H), 3.22 (s, 3H), 2.50 (q, J=2.2 Hz, 4H), 1.45-1.33 (m, 9H).
Reaction SMILES: C([O:3][C:4]([CH2:6][N:7]1[CH:12]=[CH:11][CH:10]=[C:9]([OH:13])[C:8]1=[O:14])=[O:5])C.[CH2:15](Cl)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[OH-].[Na+]>CO.O>[CH2:15]([O:13][C:9]1[C:8](=[O:14])[N:7]([CH2:6][C:4]([OH:3])=[O:5])[CH:12]=[CH:11][CH:10]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: CCOC(=O)Cn1cccc(O)c1=O
Reactant: ClCc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: O=C(O)Cn1cccc(OCc2ccccc2)c1=O
Yield: 41 %

Procedure:
1-Ethoxycarbonylmethyl-3-hydroxypyrid-2-one (10 g) is dissolved in methanol/water (9:1 v/v) (400 ml). To this solution is added benzyl chloride (3 molar excess) and NaOH until the pH is above 12. The mixture is then refluxed for six hours to give a clear orange solution. The methanol is removed by rotary evaporation and the aqueous solution is extracted with dichloromethane to remove excess benzyl chloride. The aqueous phase is diluted slightly by adding extra water and then acidified to pH 2 using concentrated hydrochloric acid which results in the precipitation of a beige solid. The mixture is cooled and the precipitate filtered off and washed with diethyl ether. The crude product is recrystallised from ethanol to give 3-benzyloxy-1-carboxymethylpyrid2-one (5.4 g, 41%), m.p. 176°-177° C.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][CH:3]=1.CS(O[CH2:16][CH2:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][S:25]([CH3:28])(=[O:27])=[O:26])=[CH:20][CH:19]=1)(=O)=O.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH3:28][S:25]([O:24][C:21]1[CH:22]=[CH:23][C:18]([CH2:17][CH2:16][O:1][C:2]2[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][CH:3]=2)=[CH:19][CH:20]=1)(=[O:27])=[O:26]
Reactant: CS(=O)(=O)OCCc1ccc(OS(C)(=O)=O)cc1
Reactant: CC(=O)c1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CC(=O)c1ccc(OCCc2ccc(OS(C)(=O)=O)cc2)cc1
Yield: 67.9 %

Procedure:
13.6 g (0.1 mole) p-hydroxyacetophenone, 29.4 g (0.1 mole) 4-(methylsulfonyloxy)phenethyl methanesulfonate and 42.4 g (0.3 mole) potassium carbonate in acetonitrile were refluxed over night. The salts were filtered off and the solvent was evaporated in vacuo. The residue was crystallized in isopropyl alcohol. The crystals were dissolved in dichloromethane, washed with diluted potassium carbonate, dried (magnesium sulfate), filtered and evaporated to give 22.7 g (yield 68%) 4-[2-(4-acetylphenoxy)ethyl]phenyl methanesulfonate.
Reaction SMILES: C(O[C:9]1[CH:20]=[CH:19][C:12]([C:13]([N:15]([O:17][CH3:18])[CH3:16])=[O:14])=[CH:11][CH:10]=1)C1C=CC=CC=1.[CH:21]([Si:24]([CH:39]([CH3:41])[CH3:40])([CH:36]([CH3:38])[CH3:37])[O:25][CH2:26]C1C=CC(C(O)=O)=CC=1)([CH3:23])[CH3:22]>>[CH3:18][O:17][N:15]([CH3:16])[C:13](=[O:14])[C:12]1[CH:11]=[CH:10][C:9]([CH2:26][O:25][Si:24]([CH:21]([CH3:23])[CH3:22])([CH:39]([CH3:41])[CH3:40])[CH:36]([CH3:38])[CH3:37])=[CH:20][CH:19]=1
Reactant: CC(C)[Si](OCc1ccc(C(=O)O)cc1)(C(C)C)C(C)C
Reactant: CON(C)C(=O)c1ccc(OCc2ccccc2)cc1
Product: CON(C)C(=O)c1ccc(CO[Si](C(C)C)(C(C)C)C(C)C)cc1

Procedure:
Following the procedure for the preparation of 4-benzyloxy-N-methoxy-N-methyl-benzamide but substituting 4-Triisopropylsilanyloxymethyl-benzoic acid provided the title compound. MS: (M+H m/z=352.1).
Reaction SMILES: [Na].[CH3:2][Sn:3](Cl)([CH3:5])[CH3:4].Br[C:8]1[C:17]([O:18][CH3:19])=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[N:9]=1>COCCOC.C(Cl)(Cl)Cl>[CH3:2][Sn:3]([CH3:5])([CH3:4])[C:8]1[C:17]([O:18][CH3:19])=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[N:9]=1
Reactant: COc1cc2ccccc2nc1Br
Reactant: C[Sn](C)(C)Cl
Agent: [Na]
Solvent: ClC(Cl)Cl
Solvent: COCCOC
Product: COc1cc2ccccc2nc1[Sn](C)(C)C
Temperature: -10 °C
Reaction time: 4 h

Procedure:
3.00 g (130 mmol) of sodium are introduced in a sealed Schlenck-type apparatus under argon inert gas into 3 ml of absolute DME. The sodium is cut into very small pieces and, before being added to the reaction solution, is washed with absolute DME to remove any adhering paraffin. After the sodium has been suspended in DME, the reaction solution remains clear, and only a slight evolution of gas can be observed. The reaction mixture is cooled to -10° C. using an ice/common salt mixture and 1.16 g (5.84 mmol) of trimethyltin chloride are then added in solid form. After the addition, the reaction solution still remains clear. After a reaction time of 1 h, the reaction solution has a milky cloudy color. After a reaction time of 3 hours, the reaction solution becomes milky, gray and cloudy. Shortly afterwards, the reaction solution turns deep green. The solution is stirred for a total of 4 hours. The last hour of the reaction is carried out without ice cooling. In order to remove excess sodium, the reaction solution is filtered under argon inert gas through a D-2 Schlenck-type frit. 0.70 g (2.92 mmol) of 2-bromo-3-methoxyquinoline dissolved in 3 ml of absolute DME is added dropwise to the filtered cloudy and green reaction solution. Upon dropwise addition of the educt, the reaction solution spontaneously turns blood red. During the addition of the educt, the reaction solution is cooled with ice. After a short time, the reaction solution has a dark brown color, which, after a reaction time of 1.5 hours, clears to light brown. After a reaction time of 4 hours with ice cooling, the reaction mixture is filtered through a D-4 frit to remove the solids formed. This gives a light yellow reaction solution. A gray solid remains in the frit. The solvent is washed with more [lacuna], the runoff being dark brown. After evaporation of the solvent, a dark brown oil is obtained. A thin-layer chromatogram obtained in chloroform shows that the desired product is obtained. Slight traces of the hydrolysis product 3-methoxyquinoline can be detected by 1H-NMR spectroscopy.
Reaction SMILES: C(O)(=O)C.[CH2:5]([O:7][C:8]1[CH:17]=[C:16]2[CH:11]([CH2:12][CH2:13][N:14]([CH2:18][C:19]3[CH:24]=[C:23]([O:25][CH3:26])[C:22]([O:27][CH3:28])=[C:21]([O:29][CH3:30])[CH:20]=3)[CH2:15]2)[CH2:10][C:9]=1[O:31]CC1C=CC=CC=1)[CH3:6]>C(O)C>[CH2:5]([O:7][C:8]1[CH:17]=[C:16]2[CH:11]([CH2:12][CH2:13][N:14]([CH2:18][C:19]3[CH:20]=[C:21]([O:29][CH3:30])[C:22]([O:27][CH3:28])=[C:23]([O:25][CH3:26])[CH:24]=3)[CH2:15]2)[CH2:10][C:9]=1[OH:31])[CH3:6]
Reactant: CCOC1=C(OCc2ccccc2)CC2CCN(Cc3cc(OC)c(OC)c(OC)c3)CC2=C1
Solvent: CCO
Solvent: CC(=O)O
Product: CCOC1=C(O)CC2CCN(Cc3cc(OC)c(OC)c(OC)c3)CC2=C1
Reaction time: 0.5 h
Yield: 96.9 %

Procedure:
7-Ethoxy-6-benzyloxy-2-(3,4,5-trimethoxybenzyl)-tetrahydroisoquinoline acetate (307 mg, 0.66 mmol) was dissolved in ethanol and ethyl acetate (5 mL each), degassed, treated with 10% Pd/C (50 mg) then placed under an atmosphere of hydrogen. After 0.5 h no starting material was evident by TLC and the reaction was filtered through celite and evaporated. The resultant oil was precipitated from ethyl acetate/hexane to give a yellow powder (240 mg, 97%). 1H NMR δ 1.39 (3H, t, J 7.0), 2.68 (2H, t, J 5.7), 2.75 (2H, t, J 5.7), 3.52 (2H, s), 3.58 (2H, s), 3.83 (3H, s), 3.84 (6H, s), 4.01 (2H, q, J 7.0), 5.50 (1H, br), 6.46 (1H, s), 6.61 (2H, s) and 6.67 (1H, s).