Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:8]=[C:9]3[C:14]4=[C:15]([CH2:17][CH2:18][N:13]4[C:12](=O)[CH2:11][CH2:10]3)[CH:16]=2)[CH:2]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:29])=CC=1.Cl>C1(C)C=CC=CC=1.C1COCC1>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:8]=[C:9]3[C:14]4=[C:15]([CH2:17][CH2:18][N:13]4[C:12](=[S:29])[CH2:11][CH2:10]3)[CH:16]=2)[CH:2]=1
Reactant: O=C1CCc2cc(-c3cccnc3)cc3c2N1CC3
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Agent: Cl
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: S=C1CCc2cc(-c3cccnc3)cc3c2N1CC3

Procedure:
A mixture of 8-pyridin-3-yl-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinoline-4-one (900 mg, 3.60 mmol) and Lawessons reagent (1.45 g, 3.60 mmol) was refluxed in a mixture of 50 ml toluene and 5 ml THF for 2 h. After evaporation of the solvent under reduced pressure, the residue was purified by flash chromatography on silica gel (hexanes/ethyl acetate, 1/1, Rf=0.25). 8-Pyridin-3-yl-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinoline-4-thione was obtained as a yellow solid (155 mg, 0.58 mmol, 26%), mp (HCl salt, THF) 283° C. 1H-NMR (500 MHz, CDCl3): δ=2.96 (t, 3J=7.9 Hz, 2H), 3.25 (t, 3J=7.6 Hz, 2H), 3.29 (t, 3J=8.0 Hz, 2H), 4.42 (t, 3J=8.2 Hz, 2H), 7.23 (s, 1H), 7.33 (s, 1H), 7.34 (ddd, 3J=7.9 Hz, 3J=4.7 Hz, 5J=0.6 Hz, 1H), 7.81 (ddd, 3J=7.9 Hz, 4J=2.5 Hz, 4J=1.9 Hz, 1H), 8.57 (dd, 3J=4.7 Hz, 4J=1.6 Hz, 1H), 8.59 (d, 4J=2.2 Hz, 1H). 13C-NMR (125 MHz, CDCl3): δ=23.5, 27.1, 40.3, 52.0, 122.7, 123.0, 123.6, 125.1, 131.7, 134.2, 135.2, 136.4, 139.6, 148.1, 148.5, 192.5. MS m/z 267.10 (MH+).
Reaction SMILES: C([N:4]1[C:12]2[C:7](=[CH:8][C:9]([O:15][CH3:16])=[C:10]([O:13][CH3:14])[CH:11]=2)[C:6](=[C:17](OCC)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:5]1=[O:27])(=O)C.[NH2:28][C:29]1[CH:39]=[CH:38][C:32]([C:33]([O:35][CH2:36][CH3:37])=[O:34])=[CH:31][CH:30]=1>>[CH2:36]([O:35][C:33]([C:32]1[CH:38]=[CH:39][C:29]([NH:28]/[C:17](=[C:6]2\[C:5](=[O:27])[NH:4][C:12]3[C:7]\2=[CH:8][C:9]([O:15][CH3:16])=[C:10]([O:13][CH3:14])[CH:11]=3)/[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:30][CH:31]=1)=[O:34])[CH3:37]
Reactant: CCOC(=C1C(=O)N(C(C)=O)c2cc(OC)c(OC)cc21)c1ccccc1
Reactant: CCOC(=O)c1ccc(N)cc1
Product: CCOC(=O)c1ccc(N/C(=C2\C(=O)Nc3cc(OC)c(OC)cc32)c2ccccc2)cc1

Procedure:
Prepared from 1-acetyl-3-(1-ethoxy-1-phenyl-methylidene)-5,6-dimethoxy-2-indolinone and ethyl 4-aminobenzoate
Reaction SMILES: Cl.Cl.[CH3:3][N:4]([CH3:9])[CH:5]1[CH2:8][NH:7][CH2:6]1.[Cl:10][C:11]1[C:12]([C:30]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[NH:32][CH:31]=2)=[N:13][C:14]([NH:17][C:18]2[CH:23]=[C:22]([N+:24]([O-:26])=[O:25])[C:21](F)=[CH:20][C:19]=2[O:28][CH3:29])=[N:15][CH:16]=1.CCN(C(C)C)C(C)C>FC(F)(F)CO>[Cl:10][C:11]1[C:12]([C:30]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[NH:32][CH:31]=2)=[N:13][C:14]([NH:17][C:18]2[CH:23]=[C:22]([N+:24]([O-:26])=[O:25])[C:21]([N:7]3[CH2:8][CH:5]([N:4]([CH3:9])[CH3:3])[CH2:6]3)=[CH:20][C:19]=2[O:28][CH3:29])=[N:15][CH:16]=1
Reactant: CN(C)C1CNC1
Reactant: COc1cc(F)c([N+](=O)[O-])cc1Nc1ncc(Cl)c(-c2c[nH]c3ccccc23)n1
Agent: Cl
Solvent: OCC(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Product: COc1cc(N2CC(N(C)C)C2)c([N+](=O)[O-])cc1Nc1ncc(Cl)c(-c2c[nH]c3ccccc23)n1
Temperature: 140 °C
Yield: 93.7 %

Procedure:
N,N-dimethylazetidin-3-amine (Intermediate 26, 144 mg, 0.83 mmol) was added to a suspension of 5-chloro-N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1H-indol-3-yl)pyrimidin-2-amine (Intermediate 76, 312 mg, 0.75 mmol) and DIPEA (0.460 mL, 2.64 mmol) in 2,2,2-trifluoroethanol (5 mL). The mixture was heated in a microwave at 140° C. for 1 h. The cooled mixture was purified by ion exchange chromatography, using an SCX column and eluting with 7M methanolic ammonia. Appropriate fractions were combined and concentrated in vacuo onto silica. Further purification by FCC, eluting with 0-4% 7N methanolic ammonia in CH2Cl2 gave the title compound (347 mg, 93%) as an orange solid after trituration with diethyl ether; 1H NMR: 2.14 (6H, s), 3.09-3.18 (1H, m), 3.76 (2H, dd), 3.89 (3H, s), 4.01-4.11 (2H, m), 6.28 (1H, s), 6.98 (1H, t), 7.13-7.20 (1H, m), 7.46 (1H, d), 8.15 (1H, s), 8.23 (1H, d), 8.37 (1H, s), 8.47 (1H, s), 8.49 (1H, s), 11.84 (1H, s); m/z: ES+ MH+ 494.16.
Reaction SMILES: [CH3:1][C:2]1([CH3:23])[CH2:6][O:5][C:4]2=[CH:7][C:8]3[O:9][CH2:10][C:11]4([C:21]=3[CH:22]=[C:3]12)[C:19]1[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=1)[NH:13][C:12]4=[O:20].[H-].[Na+].Br.Br[CH2:28][C:29]1[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=1>CN(C=O)C>[CH3:1][C:2]1([CH3:23])[CH2:6][O:5][C:4]2=[CH:7][C:8]3[O:9][CH2:10][C:11]4([C:21]=3[CH:22]=[C:3]12)[C:19]1[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=1)[N:13]([CH2:28][C:29]1[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=1)[C:12]4=[O:20]
Reactant: CC1(C)COc2cc3c(cc21)C1(CO3)C(=O)Nc2ccccc21
Reactant: BrCc1cccnc1
Agent: Br
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC1(C)COc2cc3c(cc21)C1(CO3)C(=O)N(Cc2cccnc2)c2ccccc21
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 48.3 %

Procedure:
To a solution of 5,5-dimethyl-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2′(1′H)-one (0.08 g, 0.26 mmol) in DMF (10 mL) was added sodium hydride (0.03 g, 0.78 mmol) slowly at 0° C. After 30 min, 3-(bromomethyl)-pyridine hydrobromide (0.10 g, 0.39 mmol) was added. The mixture was stirred at ambient temperature overnight, quenched with saturated ammonium chloride (10.0 mL). The mixture was extracted with ethyl acetate (3×20.0 mL). The combined organic layers was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was subjected to column chromatography (ethyl acetate/hexane, 2/1) to give 5,5-dimethyl-1′-(pyridin-3-ylmethyl)-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2′(1′H)-one as a white solid (0.05 g, 48%), which was treated with 2.0 M HCl in diethyl ether to give the title compound: mp 124-126° C.; 1H NMR (300 MHz, CD3OD) δ 8.96 (br, 1H), 8.82 (br, 1H), 8.62 (d, 1H), 7.3 (t, 1H), 7.32 (td, 1H), 7.23-7.17 (m, 1H), 7.16-7.08 (m, 2H), 6.42 (s, 1H), 6.32 (s, 1H), 5.35-5.14 (m, 2H), 4.93-4.84 (m, 1H), 4.74 (d, 1H), 4.18 (s, 2H), 1.18 (s, 3H), 1.14 (s, 3H); 13C NMR (75 MHz, CD3OD) δ 178.9, 161.6, 161.1, 145.4, 141.3, 141.1, 132.5, 130.1, 128.8, 124.0, 123.9, 120.1, 116.2, 108.8, 92.6, 85.1, 80.2, 57.8, 41.0, 40.5, 26.5, 26.4; MS (ES+) m/z 399.5 (M+1).
Reaction SMILES: [CH:1]([C:4]1[S:5][CH:6]=[C:7]([C:9]([N:11]2[CH2:16][C:15]3([CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18][CH2:17]3)[O:14][CH2:13][CH2:12]2)=[O:10])[N:8]=1)([CH3:3])[CH3:2].[ClH:29]>CC(O)C.CC(OC)(C)C>[ClH:29].[CH:1]([C:4]1[S:5][CH:6]=[C:7]([C:9]([N:11]2[CH2:16][C:15]3([CH2:17][CH2:18][NH:19][CH2:20][CH2:21]3)[O:14][CH2:13][CH2:12]2)=[O:10])[N:8]=1)([CH3:3])[CH3:2]
Reactant: CC(C)c1nc(C(=O)N2CCOC3(CCN(C(=O)OC(C)(C)C)CC3)C2)cs1
Agent: Cl
Solvent: COC(C)(C)C
Solvent: CC(C)O
Product: CC(C)c1nc(C(=O)N2CCOC3(CCNCC3)C2)cs1
Temperature: 40 °C
Reaction time: 18 h
Yield: 97 %

Procedure:
To a solution of tert-butyl 4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate in iPrOH (3 volumes) at 40° C. under nitrogen was added a solution of 5-6N HCl in isopropanol (2-2.4 molar equivalents). The mixture was stirred at 40° C. for 18 hours, cooled to room temp and diluted with TBME (4 volumes). Stirred at room temp for 2 hours, collected by filtration, washed with TBME and air dried to leave an off white powder. Yield: 97% of theoretical.
Reaction SMILES: [N+:1]([C:4]1[CH:29]=[CH:28][C:7]([O:8][C:9]2[CH:10]=[C:11]([CH:25]=[CH:26][CH:27]=2)[C:12]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=2)=[O:13])=[CH:6][CH:5]=1)([O-])=O.O1CCCC1.Cl>CO.[C].[Pd]>[NH2:1][C:4]1[CH:29]=[CH:28][C:7]([O:8][C:9]2[CH:10]=[C:11]([CH:25]=[CH:26][CH:27]=2)[C:12]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:22])([F:23])[F:24])=[CH:17][CH:16]=2)=[O:13])=[CH:6][CH:5]=1
Reactant: O=C(Nc1ccc(C(F)(F)F)cc1)c1cccc(Oc2ccc([N+](=O)[O-])cc2)c1
Agent: [Pd]
Agent: Cl
Solvent: C1CCOC1
Solvent: CO
Product: Nc1ccc(Oc2cccc(C(=O)Nc3ccc(C(F)(F)F)cc3)c2)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 85.8 %

Procedure:
To a solution of 3-(4-nitrophenoxy)-N-[4-(trifluoromethyl)phenyl]benzamide (6.75 g, 16.8 mmol) in methanol (20 mL)/tetrahydrofuran (10 mL) were added 10%-palladium carbon (2 g) and concentrated hydrochloric acid (1 mL), and the mixture was vigorously stirred under a hydrogen atmosphere at room temperature for 3 hr. The catalyst was filtered off through celite, the filtrate was concentrated under reduced pressure, and the obtained residue was triturated with diethyl ether to give the title compound (5.37 g, 86%) as a white solid.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:16]=[CH:15][C:14]2[C:13](=[O:17])[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[C:6](=[O:18])[C:5]=2[CH:4]=1.[CH2:19]([OH:22])[CH2:20][OH:21]>>[OH:21][CH2:20][CH2:19][O:22][CH2:2][C:3]1[CH:16]=[CH:15][C:14]2[C:13](=[O:17])[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[C:6](=[O:18])[C:5]=2[CH:4]=1
Reactant: O=C1c2ccccc2C(=O)c2cc(CCl)ccc21
Reactant: OCCO
Product: O=C1c2ccccc2C(=O)c2cc(COCCO)ccc21
Yield: 80.92 %

Procedure:
10 g (0.039 mol) of 2-chloromethylanthraquinone (prepared in accordance with the instructions of G. Izoret, Ann. Chim. 7, 151 (1962)) in 200 ml of ethylene glycol are refluxed for 3 hours, with stirring and with exclusion of moisture. The product which has crystallised out on cooling is washed with water and recrystallised from ethanol. 8.9 g (80.92% of theory) of 2-(2-hydroxyethoxymethyl)anthraquinone are obtained. 8 g (0.03 mol) of 2-(2-hydroxyethoxymethyl)-anthraquinone are dissolved in 180 ml of tetrahydrofuran, 4.34 ml (0.05 mol) of triethylamine are added and the mixture is cooled to 5° C. 3 ml (0.03 mol) of methacryloyl chloride in 10 ml of tetrahydrofuran are then added dropwise, with stirring and under an inert gas, such that the temperature does not exceed 5° C. When the dropwise addition has ended, stirring is continued at room temperature for 5 hours. The solvent is then stripped off on a rotary evaporator and the solid product is washed several times with 1% citric acid and water and dried in vacuo. 7.76 g of (2-anthraquinonyl)-7-oxa-4-oxa-3-oxo-2-methyloct-1-ene are obtained, and 7.48 g (71.17% of theory) after recrystallisation from ethanol.
Reaction SMILES: CS(O)(=O)=O.[NH2:6][CH2:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[C:13](=[O:17])[N:12]([CH:18]1[CH2:23][CH2:22][C:21](=[O:24])[NH:20][C:19]1=[O:25])[CH2:11]2.[F:26][C:27]1[CH:32]=[CH:31][C:30]([N:33]=[C:34]=[O:35])=[CH:29][CH:28]=1.C(N(CC)CC)C.Cl>C(#N)C>[O:25]=[C:19]1[CH:18]([N:12]2[CH2:11][C:10]3[C:14](=[CH:15][CH:16]=[C:8]([CH2:7][NH:6][C:34]([NH:33][C:30]4[CH:31]=[CH:32][C:27]([F:26])=[CH:28][CH:29]=4)=[O:35])[CH:9]=3)[C:13]2=[O:17])[CH2:23][CH2:22][C:21](=[O:24])[NH:20]1
Reactant: O=C=Nc1ccc(F)cc1
Reactant: NCc1ccc2c(c1)CN(C1CCC(=O)NC1=O)C2=O
Agent: CS(=O)(=O)O
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CC#N
Product: O=C1CCC(N2Cc3cc(CNC(=O)Nc4ccc(F)cc4)ccc3C2=O)C(=O)N1
Reaction time: 1 h
Yield: 69 %

Procedure:
To a stirred mixture of 3-(5-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione methane sulfonate (0.50 g, 1.80 mmol) and 4-fluorophenylisocyanate (0.25 g, 1.80 mmol) in acetonitrile (20 mL), was added triethylamine (0.51 mL, 3.60 mmol) at room temperature under nitrogen. After 1 h, 1N aq. HCl (20 mL) was added and the mixture was stirred for 10 min. The product was isolated by filtration, washed with 1N aq. HCl (20 mL), acetonitrile (20 mL) and dried overnight in vacuo to give 1-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-3-(4-fluoro-phenyl)-urea as an off-white solid (0.51 g, 68% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 40/60 CH3CN/0.1% H3PO4, 2.13 min (98.98%); mp: 262-264° C.; 1H NMR (DMSO-d6) δ 1.92-2.13 (m, 1H), 2.29-2.47 (m, 1H), 2.54-2.69 (m, 1H), 2.82-3.00 (m, 1H), 4.31 (d, J=17.4 Hz, 1H), 4.37-4.55 (m, 3H), 5.11 (dd, J=13.2, 5.1 Hz, 1H), 6.73 (t, J=5.9 Hz, 1H), 7.06 (t, J=8.9 Hz, 2H), 7.37-7.48 (m, 3H), 7.52 (s, 1H), 7.70 (d, J=7.9 Hz, 1H), 8.67 (s, 1H), 10.99 (s, 1H); 13C NMR (DMSO-d6) δ 22.5, 31.2, 42.8, 47.1, 51.6, 115.1 (d, J=22.0 Hz,), 119.4 (d, J=6.6 Hz), 121.9, 122.9, 126.9, 130.3, 136.8, 142.4, 144.9, 155.3 (d, J=4.4 Hz), 158.5, 168.0, 171.0, 172.9; LCMS: MH=411; Anal Calcd for C21H19FN4O4: C, 61.46; H, 4.67; N, 13.65. Found: C, 61.44; H, 4.53; N, 13.46.
Reaction SMILES: [CH:1]([C:3]1[CH:4]=[CH:5][C:6]([N:11]2[CH:15]=[N:14][CH:13]=[N:12]2)=[C:7]([CH:10]=1)[C:8]#[N:9])=O.C(O)(=O)[CH2:17][C:18]([OH:20])=[O:19].N1CCCCC1>N1C=CC=CC=1>[C:8]([C:7]1[CH:10]=[C:3](/[CH:1]=[CH:17]/[C:18]([OH:20])=[O:19])[CH:4]=[CH:5][C:6]=1[N:11]1[CH:15]=[N:14][CH:13]=[N:12]1)#[N:9]
Reactant: N#Cc1cc(C=O)ccc1-n1cncn1
Reactant: O=C(O)CC(=O)O
Solvent: c1ccncc1
Solvent: C1CCNCC1
Product: N#Cc1cc(/C=C/C(=O)O)ccc1-n1cncn1

Procedure:
2.05 g (10.3 mmol) of 5-formyl-2-(1H-1,2,4-triazol-1-yl)benzonitrile (lit.: WO-A-2008/019760), 1.60 g (16.6 mmol) of malonic acid and 176 mg (2.07 mmol) of piperidine were stirred in 20 ml of pyridine at 80° C. for 48 hours. The pyridine was distilled off under reduced pressure. The residue was added to ice-water and adjusted to pH 1 with concentrated hydrochloric acid. The aqueous phase was extracted repeatedly with ethyl acetate and dried over sodium sulphate, and the solvent was distilled off under reduced pressure.
Reaction SMILES: Cl[C:2]1[CH:7]=[N:6][CH:5]=[C:4]([Cl:8])[N:3]=1.[NH2:9][CH2:10][CH2:11][OH:12].CCN(C(C)C)C(C)C>C(O)CCC>[Cl:8][C:4]1[N:3]=[C:2]([NH:9][CH2:10][CH2:11][OH:12])[CH:7]=[N:6][CH:5]=1
Reactant: NCCO
Reactant: Clc1cncc(Cl)n1
Solvent: CCCCO
Solvent: CCN(C(C)C)C(C)C
Product: OCCNc1cncc(Cl)n1
Temperature: 80 °C
Yield: 50 %

Procedure:
In a sealed tube, 2,6-dichloropyrazine (1 g, 6.71 mmol) was mixed with 2-aminoethanol (0.492 g, 8.05 mmol), Hunig's base (1.13 g, 8.73 mmol) in BuOH (7 mL) and the reaction mixture was heated to 80° C. over night. The mixture was concentrated in vacuo and the residue partitioned between NaHCO3 (20 mL) and EtOAc (100 mL). The organic phase was separated, washed with brine, dried over Na2SO4, filtered and evaporated to dryness to give the title compound (0.583 g, 50%) as a light yellow foam. MS: 174.1 (M+H+).
Reaction SMILES: C(OC([NH:8][C@:9]([CH3:40])([CH2:20][CH2:21][C:22]1[N:23]([CH3:39])[C:24]([C:27](=[O:38])[CH2:28][CH2:29][CH2:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[CH:25][CH:26]=1)[CH2:10][CH2:11][P:12](=[O:19])([O:16]CC)[O:13]CC)=O)(C)(C)C.Br[Si](C)(C)C>ClCCl>[NH2:8][C@:9]([CH3:40])([CH2:20][CH2:21][C:22]1[N:23]([CH3:39])[C:24]([C:27](=[O:38])[CH2:28][CH2:29][CH2:30][CH2:31][C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)=[CH:25][CH:26]=1)[CH2:10][CH2:11][P:12](=[O:13])([OH:16])[OH:19]
Reactant: CCOP(=O)(CC[C@@](C)(CCc1ccc(C(=O)CCCCc2ccccc2)n1C)NC(=O)OC(C)(C)C)OCC
Agent: C[Si](C)(C)Br
Solvent: ClCCl
Product: Cn1c(CC[C@@](C)(N)CCP(=O)(O)O)ccc1C(=O)CCCCc1ccccc1
Temperature: 25 °C
Reaction time: 5 h
Yield: 61.8 %

Procedure:
To a solution of diethyl (3R)-3-t-butoxycarbonylamino-3-methyl-5-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]pentylphosphonate (114.0 mg, 0.20 mmol) obtained in Example (44c) in dichloromethane (2.0 ml) was added bromotrimethylsilane (0.26 ml, 1.97 mmol), and the resulting mixture was stirred at room temperature under a nitrogen atmosphere for 5 hours. After stirring, the reaction mixture was evaporated in vacuo, and the residue was diluted with aqueous ethanol and then adjusted to pH 4 with aqueous ammonia and acetic acid. The crystals precipitated were collected by filtration, washed successively with water and ethanol and dried to afford the title compound (52.0 mg, yield: 63%).
Reaction SMILES: [CH3:1][C:2]1[CH:6]=[CH:5][O:4][C:3]=1[C:7]([OH:9])=[O:8]>C(OCC)(=O)C.[Rh]>[CH3:1][CH:2]1[CH2:6][CH2:5][O:4][CH:3]1[C:7]([OH:9])=[O:8]
Reactant: Cc1ccoc1C(=O)O
Agent: [Rh]
Solvent: CCOC(C)=O
Product: CC1CCOC1C(=O)O
Reaction time: 6.5 h

Procedure:
3-Methyl-2-furoic acid (5g) in ethyl acetate (100ml) and 5% rhodium on charcoal catalyst (0.5g) were hydrogenated at ambient temperature and the atmosphere for 6-7h. The catalyst was filtered off and replaced with a further quantity (lg) of catalyst. The reaction mixture was hydrogenated for a further 7h. This procedure was repeated again until no more hydrogen was absorbed. After filtration through kieselguhr and removal of solvent under reduced pressure, the title compound was obtained as a colourless oil (5.096g, quant.); vmax (CH2Cl2) 3674, 3377(br), 1770 and 1722cm-1 ; δH (CHCl3) 1.08 (3H, d, J 7.1Hz), 1.72 (1H, m), 2.16 (1H, m), 2.68 (1H, m), 3.94 (1H, m), 4.18 (1H, m), 4.47 (1H, d, J 7.5Hz) and 9.42 (1H, v. br s, exch). [Mass spectrum: +ve ion (ammonia) MNH4+ (148)].
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][N:9]=2)[C:4]([CH:11]=[O:12])=[CH:3][CH:2]=1.[CH3:13][Mg]Br.[Cl-].[NH4+]>C1(C)C=CC=CC=1.C1COCC1>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][N:9]=2)[C:4]([CH:11]([OH:12])[CH3:13])=[CH:3][CH:2]=1
Reactant: C[Mg]Br
Reactant: O=Cc1ccnc2ncccc12
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: CC(O)c1ccnc2ncccc12
Temperature: 0 °C
Reaction time: 1 h

Procedure:
[1,8]Naphthyridine-4-carbaldehyde (0.300 g, 1.90 mmol) was dissolved in a mixture of anhydrous toluene (10 mL) and anhydrous THF (10 mL). The solution was cooled to 0° C. and methyl magnesium bromide (1.62 mL of 1.4M in THF/toluene) was added slowly and the solution stirred 1 h while allowing to warm to RT. Satd. aq. ammonium chloride was added until the solution reached a bright yellow color and precipitate was apparent. The solution was passed through a syringe filter and into water, where it was extracted with EtOAc (3×30 mL). The combined organic fractions were dried over Na2SO4, filtered, and concentrated under vacuum. The product was purified (SGC using MeCN:hexanes eluant in 1:1 ratio initially, then switching to DCM:MeOH:NH4OH eluant in 89:10:1 ratio to finish the compound elution) yielding the title compound (0.079 g). MS (ESI+) for m/z 175 (M+H)+. 1H NMR (CDCl3) δ 8.73 (m, 1H), 8.64 (d, 1H), 8.38 (m, 1H), 7.52 (d, 1H), 7.25 (dd, 1H), 6.32 (bs, 1H), 5.58 (dd, 1H), 1.48 (s, 3H).
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[C:11]([F:14])([F:13])[F:12].Cl.[NH:16]1[CH2:19][CH2:18][CH2:17]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.Cl>ClCCl>[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([N:16]2[CH2:19][CH2:18][CH2:17]2)=[O:8])=[CH:4][C:3]=1[C:11]([F:14])([F:13])[F:12]
Reactant: C1CNC1
Reactant: O=C(O)c1ccc(F)c(C(F)(F)F)c1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: O=C(c1ccc(F)c(C(F)(F)F)c1)N1CCC1
Temperature: 25 °C
Reaction time: 4 h
Yield: 77.6 %

Procedure:
Commercially available 4-fluoro-3-(trifluoromethyl)benzoic acid (230 mg, 1.10 mmol) was dissolved in dichloromethane (50 mL), and azetidine hydrochloride (120 mg, 1.28 mmol), HATU (550 mg, 1.45 mmol) and N,N-diisopropylethylamine (0.50 mL, 2.87 mmol) were added, followed by stirring at room temperature for 4 hours under nitrogen atmosphere. 0.5N hydrochloric acid (100 mL) was added, and extraction was carried out with dichloromethane (100 mL). The organic layer was washed with saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=60%-80%) to afford the desired compound (211 mg, yield 78%) as a colorless liquid.
Reaction SMILES: [CH2:1]([O:8][C@H:9]1[C@H:15]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@@H:14]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C@H:13]([CH2:32][O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[O:12][C@H:10]1O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)([Cl:43])=O>C1C=CC=CC=1.[Cl-].[Zn+2].[Cl-]>[CH2:1]([O:8][C@H:9]1[C@H:15]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@@H:14]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C@H:13]([CH2:32][O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[O:12][CH:10]1[Cl:43])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O[C@@H]1O[C@@H](COCc2ccccc2)[C@H](OCc2ccccc2)[C@@H](OCc2ccccc2)[C@@H]1OCc1ccccc1
Reactant: O=S(Cl)Cl
Agent: [Cl-]
Agent: [Zn+2]
Solvent: c1ccccc1
Product: ClC1O[C@@H](COCc2ccccc2)[C@H](OCc2ccccc2)[C@@H](OCc2ccccc2)[C@@H]1OCc1ccccc1

Procedure:
Method B--2,3,4,6-Tetra-O-benzyl-α-L-glucopyranose (400 mg.) was dissolved in dry benzene (25 ml.) in a round-bottomed flask equipped with a calcium chloride drying tube and an inlet for nitrogen. To the magnetically stirred solution was added zinc chloride (1.1 g.) followed by thionyl chloride (0.55 ml.) care being taken to exclude atmospheric moisture. The reaction, which was monitored by t.l.c. (Solvent D), was complete after approximately 45 minutes. The solution was then filtered through a 3 cm. thickness of silica gel on a sintered glass funnel and the residue washed with dry benzene. The filtrate was then concentrated under reduced pressure to a colourless syrup which was co-evaporated with benzene (40 ml.) at 30° bath to remove traces of thionyl chloride. The colourless syrup (0.31 g.) was homogeneous on t.l.c. (benzene/diethyl ether 10:1 v/v) and had [α]D -62.5° (c 2.1, chloroform) and the following p.m.r. data: τ2.7 (20 aromatic protons), τ3.9 (1 proton, H-1, doublet with J1,2 ≃3 Hz.), τ5.1-6.6 (15 protons, ring protons and benzylic --CH2 --). The corresponding D-isomer has [α]D +109° (c 1, benzene), +62° (c 1, chloroform) as found by Grob et al [Carbohyd. Res. 10 595 (1964)] and [α]D +95° (c 4.0, benzene), +66° (c 6.3, benzene) as found by Austin et al [J. Chem. Soc., 2128 (1964)].
Reaction SMILES: C([NH:11][C:12]([CH3:33])([C:14]([NH:16][CH2:17][CH:18]1[O:32][C:21]2=[C:22]3[C:27](=[C:28]([CH3:30])[CH:29]=[C:20]2[CH2:19]1)[NH:26][C:25](=[O:31])[CH:24]=[CH:23]3)=[O:15])[CH3:13])(OCC1C=CC=CC=1)=O.[H][H]>CN(C)C=O.CO.[Pd]>[CH3:30][C:28]1[CH:29]=[C:20]2[CH2:19][CH:18]([CH2:17][NH:16][C:14](=[O:15])[C:12]([CH3:13])([CH3:33])[NH2:11])[O:32][C:21]2=[C:22]2[C:27]=1[NH:26][C:25](=[O:31])[CH:24]=[CH:23]2
Reactant: Cc1cc2c(c3ccc(=O)[nH]c13)OC(CNC(=O)C(C)(C)NC(=O)OCc1ccccc1)C2
Reactant: [H][H]
Agent: [Pd]
Solvent: CN(C)C=O
Solvent: CO
Product: Cc1cc2c(c3ccc(=O)[nH]c13)OC(CNC(=O)C(C)(C)N)C2
Yield: 95.5 %

Procedure:
2-(N-Carbobenzyloxy-α-methylalanyl]aminomethyl-5-methyl-2,3,6,7-tetrahydrofuro-[2,3-f]quinoline-7-one (2.46 g, 5.48 mmol) was dissolved in dimethylformamide (190 ml). To the obtained solution, 10% palladium-on-carbon (2.46 g) was added, followed by stirring at room temperature for 3 hours in the atmosphere of hydrogen. The reaction mixture was filtered, and the filtrate was condensed. The resultant residue was dissolved in methanol (70 ml). To the obtained solution, 1.37 N-HCl--methanol (4.39 ml) was added at room temperature, followed by condensing under reduced pressure. The resultant residue was submitted to a recrystallizing procedure using methanol to obtain 1.65 g of the title compound as pale yellow powdery crystals (85.6%).