Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8](Cl)=[O:9])=[CH:6][CH:5]=1)([O-:3])=[O:2].[OH:13][C@H:14]1[C:18]2[N:19]=[CH:20][N:21]=[C:22]([N:23]3[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]3)[C:17]=2[C@H:16]([CH3:36])[CH2:15]1.C(N(CC)CC)C.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:36][C@H:16]1[C:17]2[C:22]([N:23]3[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]3)=[N:21][CH:20]=[N:19][C:18]=2[C@H:14]([O:13][C:8](=[O:9])[C:7]2[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:12][CH:11]=2)[CH2:15]1
Reactant: O=C(Cl)c1ccc([N+](=O)[O-])cc1
Reactant: C[C@@H]1C[C@@H](O)c2ncnc(N3CCN(C(=O)OC(C)(C)C)CC3)c21
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: C[C@@H]1C[C@@H](OC(=O)c2ccc([N+](=O)[O-])cc2)c2ncnc(N3CCN(C(=O)OC(C)(C)C)CC3)c21
Temperature: 25 °C
Reaction time: 8 h
Yield: 84.6 %

Procedure:
4-Nitrobenzoyl chloride (4.27 g, 23.0 mmol) was added to a 0° C. solution of tert-butyl 4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (7.0 g, 20.9 mmol) and triethylamine (4.38 mL, 31.4 mmol) in DCM (110 mL). The reaction mixture was stirred at room temperature overnight, after which saturated NaHCO3 was added. The mixture was stirred for 10 minutes and then extracted with DCM. The combined extracts were dried (Na2SO4), filtered, and concentrated. The crude was flashed on Biotage 65M (3:1 hexanes:ethyl acetate loaded crude, then 2:1 hexanes:ethyl acetate eluted tert-butyl 4-((5R,7R)-5-methyl-7-(4-nitrobenzoyloxy)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate and a few mixed fractions. Then tert-butyl 4-((5R,7S)-5-methyl-7-(4-nitrobenzoyloxy)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate was eluted using 1:2 hexanes:ethyl acetate. The fractions with product were concentrated by rotary evaporation to give tert-butyl 4-((5R,7R)-5-methyl-7-(4-nitrobenzoyloxy)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (8.55 g, 84.5% yield) as a yellow foam. LC/MS (APCI+) m/z 484 [M+H]+. 1H NMR (CDCl3) shows single diastereomer). The fractions with other diastereomers were concentrated by rotary evaporation to give tert-butyl 4-((5R,7S)-5-methyl-7-(4-nitrobenzoyloxy)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (0.356 g, 3.52% yield) as a brown foam. LC/MS (APCI+) m/z 484 [M+H]+.
Reaction SMILES: [CH3:1][C:2]1[CH:6]=[CH:5][NH:4][C:3]=1[C:7]([OH:9])=O.[NH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>>[CH3:1][C:2]1[CH:6]=[CH:5][NH:4][C:3]=1[C:7]([NH:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:9]
Reactant: Cc1cc[nH]c1C(=O)O
Reactant: Nc1ccccc1
Product: Cc1cc[nH]c1C(=O)Nc1ccccc1
Yield: 47.7 %

Procedure:
Prepared following the experimental method described in preparation 1a starting from 1.38 g (11.3 mmol) of 3-methyl-1H-pyrrole-2-carboxylic acid and 1.13 g (12.13 mmol) of aniline. After purification by flash chromatography (0-40% AcOEt in hexane), 1.08 g (49% yield) of the title compound were obtained as a white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8](Cl)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[NH2:12][C:13]1([CH2:19][OH:20])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1.C(N(CC)CC)C>O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:12][C:13]2([CH2:19][OH:20])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1
Reactant: O=S(=O)(Cl)c1ccc(Cl)cc1
Reactant: NC1(CO)CCCCC1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: O=S(=O)(NC1(CO)CCCCC1)c1ccc(Cl)cc1
Reaction time: 8 h
Yield: 73.2 %

Procedure:
4-Chlorobenzenesulfonyl chloride (6.92 g, 32.8 mmol) was added to a solution of (1-aminocyclohexyl)methanol (prepared according to Helv. Chirp. Acta, 87:90-105 (2004)) (3.53 g, 27.3 mmol) and triethylamine (4.6 mL, 32.8 mmol) in 100 mL tetrahydrofuran at room temperature. The reaction was stirred overnight and concentrated. The residue was taken up in a mixture of 100 mL ethyl acetate and 100 mL brine. The organic layer was separated, dried over sodium sulfate, and purified by flash chromatography on 120 g silica gel with 20 to 100% ethyl acetate in hexane to yield 4-chloro-N-(1-(hydroxymethyl)cyclohexyl)benzenesulfonamide (6.07 g, 73%). 1H NMR (400 MHz, CDCl3) δ ppm 7.85-7.86 (1H, m), 7.81-7.84 (1H, m), 7.47-7.49 (1H, m), 7.44-7.46 (1H, m), 4.61 (1H, s), 3.60 (2H, d, J=5.54 Hz), 2.25 (1H, t, J=5.92 Hz), 1.57-1.69 (2H, m), 1.22-1.45 (8H, m). LC/MS R.T.=2.39 min; [M+H]+=304.03; [M+Na]+=326.05; [M−H]−=301.98.
Reaction SMILES: Cl[CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.[C:8]1([Mg]Br)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.N1C=CN=CC=1>C1COCC1>[CH:2]1([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1
Reactant: ClC1CCCCC1
Reactant: Br[Mg]c1ccccc1
Solvent: c1cnccn1
Solvent: C1CCOC1
Product: c1ccc(C2CCCCC2)cc1
Yield: 85 %

Procedure:
Chlorocyclohexane (59.5 mg, 0.5 mmol) and a THF solution (0.77 mL, 0.97 M, 0.75 mmol) of phenylmagnesium bromide were used as starting materials, and reacted as in Entry 1. Conditions: The THF solution of phenylmagnesium bromide was added dropwise at 40° C. over 2 hours. 1H-NMR analysis was conducted using pyrazine (19.4 mg, 0.24 mmol) as an internal standard (yield 85%).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[CH:7][CH:8]=[C:9]([C:10]([CH3:22])([CH3:21])[CH2:11][C:12]([C:17]([F:20])([F:19])[F:18])([OH:16])[CH2:13][C:14]#[CH:15])[C:2]1=2.ClC1C=C(C=CC=1)C(OO)=[O:28].[OH-:34].[Na+]>ClCCl>[O:34]=[S:1]1(=[O:28])[CH:5]=[CH:4][C:3]2[CH:6]=[CH:7][CH:8]=[C:9]([C:10]([CH3:22])([CH3:21])[CH2:11][C:12]([C:17]([F:18])([F:19])[F:20])([OH:16])[CH2:13][C:14]#[CH:15])[C:2]1=2
Reactant: C#CCC(O)(CC(C)(C)c1cccc2ccsc12)C(F)(F)F
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: [OH-]
Agent: [Na+]
Solvent: ClCCl
Product: C#CCC(O)(CC(C)(C)c1cccc2c1S(=O)(=O)C=C2)C(F)(F)F
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
To a solution of 150 mg (0.47 mmol) of 6-benzo[b]thiophen-7-yl-6-methyl-4-trifluoromethylhept-1-yn-4-ol in 15 mL of dichloromethane was added 280 mg (˜1.2 mmol) of m-chloroperoxybenzoic acid. After stirring at room temperature for 2.5 hours, the reaction mixture was poured into 30 mL of 1N aqueous NaOH solution and extracted with two 30 mL portions of dichloromethane. The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. The crude 6-(1,1-dioxo-1H-1λ6-benzo[b]thiophen-7-yl)-6-methyl-4-trifluoromethylhept-1-yn-4-ol was used without further purification.
Reaction SMILES: O[CH2:2][CH2:3][O:4][C:5]1[C:10]([CH3:11])=[CH:9][C:8]([C:12]2[NH:21][C:20](=[O:22])[C:19]3[C:14](=[CH:15][C:16]([O:25][CH3:26])=[CH:17][C:18]=3[O:23][CH3:24])[N:13]=2)=[CH:7][C:6]=1[CH3:27].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[NH:47]1[C:51](=[O:52])[CH2:50][CH2:49][C:48]1=[O:53].C(N(CC)C(C)C)(C)C.CCOC(/N=N/C(OCC)=O)=O>C1COCC1.C(OCC)(=O)C>[CH3:24][O:23][C:18]1[CH:17]=[C:16]([O:25][CH3:26])[CH:15]=[C:14]2[C:19]=1[C:20](=[O:22])[NH:21][C:12]([C:8]1[CH:9]=[C:10]([CH3:11])[C:5]([O:4][CH2:3][CH2:2][N:47]3[C:51](=[O:52])[CH2:50][CH2:49][C:48]3=[O:53])=[C:6]([CH3:27])[CH:7]=1)=[N:13]2
Reactant: O=C1CCC(=O)N1
Reactant: COc1cc(OC)c2c(=O)[nH]c(-c3cc(C)c(OCCO)c(C)c3)nc2c1
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: COc1cc(OC)c2c(=O)[nH]c(-c3cc(C)c(OCCN4C(=O)CCC4=O)c(C)c3)nc2c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 2-[4-(2-hydroxy-ethoxy)-3,5-dimethyl-phenyl]-5,7-dimethoxy-3H-quinazolin-4-one (0.50 g, 1.35 mmol) in anhydrous THF (20 mL) were added triphenyl phosphine (0.53 g, 2.02 mmol), pyrrolidine-2,5-dione (0.20 g, 2.02 mmol), and N,N-diisopropylethyl amine (0.44 g, 3.38 mmol). To this stirred solution was added diethylazodicarboxylate (0.35 g, 2.02 mmol). The reaction mixture was stirred at room temperature for 8 hours under nitrogen. Ethyl acetate (400 mL) was added. The organic phase was separated, washed with water (100 mL), then brine (100 mL), and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure. The crude material was purified by the Simpliflash system (4:96 methanol:CH2Cl2 as eluent) to give the title compound as a white solid. Yield: 0.3 g. (49%). 1H NMR (400 MHz, CDCl3): δ 9.30 (br s, 1H), 7.66 (s, 2H), 6.82 (d, J=2.4 Hz, 1H), 6.46 (d, J=1.6 Hz, 1H), 3.99 (s, 3H), 3.97 (s, 3H), 3.92 (s, 4H), 2.78 (s, 4H), 2.31 (s, 6H). MS (ES) m/z: 452.51 (M+1) (100%).
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][C:6]12[CH2:17][CH2:16][CH2:15][C:13]3[C:14]1=[C:9]([CH:10]=[CH:11][CH:12]=3)[NH:8][C:7]2=[O:18].[CH2:19]([CH:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH2:19]([CH:26]1[CH2:31][CH2:30][N:29]([CH2:2][CH2:3][CH2:4][CH2:5][C:6]23[CH2:17][CH2:16][CH2:15][C:13]4[C:14]2=[C:9]([CH:10]=[CH:11][CH:12]=4)[NH:8][C:7]3=[O:18])[CH2:28][CH2:27]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: c1ccc(CC2CCNCC2)cc1
Reactant: O=C1Nc2cccc3c2C1(CCCCBr)CCC3
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=C1Nc2cccc3c2C1(CCCCN1CCC(Cc2ccccc2)CC1)CCC3

Procedure:
2a-(4-Bromobutyl)-2a,3,4,5-tetrahydro-1H-benz[cd]indol-2-one (190 mg, 0.62 mmol), 4-benzyl-piperidine (110 mg, 0.65 mmol) and potassium carbonate (120 mg, 0.88 mmol) were stirred overnight at 60° C. in anhydrous N,N-dimethylformamide (2 ml). The solvent was removed by evaporation under a reduced pressure, and the residue was mixed with ethyl acetate and water. The reaction product was extracted with ethyl acetate, washed with saturated brine and dried with anhydrous sodium sulfate, the solvent was removed by evaporation under a reduced pressure, and then the thus obtained material was separated and purified by a silica gel column chromatography to obtain 210 mg (1.1 mmol, 85% in yield) of the title compound.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N:17]2[CH2:21][CH:20]([CH2:22][NH:23][C:24](=[O:26])[CH3:25])[O:19][C:18]2=[O:27])[CH:5]=[CH:6][C:7]=1B1OC(C)(C)C(C)(C)O1.Br[C:29]1[CH:48]=[CH:47][C:32]([O:33][CH2:34][C:35]2([CH3:46])[O:39][C:38]3=[N:40][C:41]([N+:43]([O-:45])=[O:44])=[CH:42][N:37]3[CH2:36]2)=[CH:31][CH:30]=1.C([O-])([O-])=O.[K+].[K+]>>[F:1][C:2]1[CH:3]=[C:4]([N:17]2[CH2:21][CH:20]([CH2:22][NH:23][C:24](=[O:26])[CH3:25])[O:19][C:18]2=[O:27])[CH:5]=[CH:6][C:7]=1[C:29]1[CH:48]=[CH:47][C:32]([O:33][CH2:34][C:35]2([CH3:46])[O:39][C:38]3=[N:40][C:41]([N+:43]([O-:45])=[O:44])=[CH:42][N:37]3[CH2:36]2)=[CH:31][CH:30]=1
Reactant: CC(=O)NCC1CN(c2ccc(B3OC(C)(C)C(C)(C)O3)c(F)c2)C(=O)O1
Reactant: CC1(COc2ccc(Br)cc2)Cn2cc([N+](=O)[O-])nc2O1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: CC(=O)NCC1CN(c2ccc(-c3ccc(OCC4(C)Cn5cc([N+](=O)[O-])nc5O4)cc3)c(F)c2)C(=O)O1
Temperature: 80 °C
Reaction time: 3 h

Procedure:
To an oven dried round bottom flask was charged N-{3-[3-Fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide (78 mg, 0.2 mmol), 2-(4-Bromo-phenoxymethyl)-2-methyl-6-nitro-2,3-dihydro-imidazo[2,1-b]oxazole (prepared similarly as described by Sasaki, H. et al: Journal of Medicinal Chemistry (2006), 49(26), 7854-7860; 71 mg, 0.2 mmol), Ph(PPh3)4 (23 mg, 0.02 mmol) and K2CO3 (55 mg, 0.4 mmol). The flask was flushed with nitrogen and was added 3 mL degassed DMF/H2O (10/1, v/v). The resulting mixture was stirred at 80° C. for 3 hours before it was cooled down and partitioned into 50 mL EtOAc/50 mL water. The organic layer was washed with brine and dried over Na2SO4, concentrated, and purified by column chromatography (CH2Cl2/MeOH, v/v, 20:1 to 10:1) gave the titled compound (70 mg) as off-white solid. ESI MS m/z 526 (M+H). 1H NMR (400 MHz, CD3OD) δ 7.86 (s, 1H), 7.52-7.59 (m, 1H), 7.45-7.52 (m, 3H), 7.32-7.38 (m, 1H), 6.96-7.02 (m, 2H), 4.76-4.84 (m, 1H), 4.51 (d, J=6.8 Hz, 1H), 4.38 (d, J=6.8 Hz, 1H), 4.27 (d, J=6.8 Hz, 1H), 4.18 (d, J=6.8 Hz, 1H), 3.89 (s, 1H), 3.83 (dd, J=6.8, 9.2 Hz, 1H), 3.55-3.59 (m, 2H), 1.96 (s, 3H), 1.77 (s, 3H).
Reaction SMILES: [NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:17]2[CH:22]=[CH:21][C:20]([S:23]([CH:26]3[CH2:31][CH2:30][N:29](C(OC(C)(C)C)=O)[CH2:28][CH2:27]3)(=[O:25])=[O:24])=[CH:19][CH:18]=2)=[N:6][C:7]=1[C:8]#[C:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([OH:16])[CH:11]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:1][C:2]1[C:7]([C:8]#[C:9][C:10]2[CH:11]=[C:12]([OH:16])[CH:13]=[CH:14][CH:15]=2)=[N:6][C:5]([C:17]2[CH:22]=[CH:21][C:20]([S:23]([CH:26]3[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]3)(=[O:24])=[O:25])=[CH:19][CH:18]=2)=[CH:4][N:3]=1
Reactant: CC(C)(C)OC(=O)N1CCC(S(=O)(=O)c2ccc(-c3cnc(N)c(C#Cc4cccc(O)c4)n3)cc2)CC1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Nc1ncc(-c2ccc(S(=O)(=O)C3CCNCC3)cc2)nc1C#Cc1cccc(O)c1
Temperature: 25 °C
Reaction time: 4 h
Yield: 6.9 %

Procedure:
Crude tert-butyl 4-[4-[5-amino-6-[2-(3-hydroxyphenyl)ethynyl]pyrazin-2-yl]phenyl]sulfonylpiperidine-1-carboxylate (184.3 mg, 0.3447 mmol—assumed quantitative yield from Step 3) was dissolved in DCM (5 mL) and TFA (1 mL, 12.98 mmol) was added. The reaction mixture was stirred at ambient temperature for 4 hours. The solvent was removed in vacuo and the residue azeotroped with DCM (×2) and ether (×2). The material was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected and freeze-dried to give the mono-TFA salt of the title compound as a yellow solid (10.3 mg, 5% Yield). 1H NMR (400.0 MHz, DMSO) δ 1.65-1.74 (m, 2H), 2.06 (d, 2H), 2.85-2.90 (m, 2H), 3.36 (d, 2H), 3.59-3.65 (m, 1H), 6.89 (dd, 1H), 7.14-7.21 (m, 2H), 7.27 (t, 1H), 7.90 (d, 2H), 8.23 (br s, 1H), 8.28 (d, 2H), 8.54 (br s, 1H), 8.77 (s, 1H) and 9.78 (s, 1H) ppm; MS (ES+) 435.1.
Reaction SMILES: [C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].C(O)C.[O-]CC.[Na+].Cl[C:20]([C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1)([CH3:24])[CH2:21][S:22][CH3:23].ClCC(C1C=CC(F)=CC=1)(C)SC>C(O)C>[F:31][C:28]1[CH:27]=[CH:26][C:25]([C:20]([CH:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:1]([O:9][CH2:10][CH3:11])=[O:8])([CH3:24])[CH2:21][S:22][CH3:23])=[CH:30][CH:29]=1
Reactant: CCOC(=O)CC(=O)OCC
Reactant: CSCC(C)(Cl)c1ccc(F)cc1
Agent: CC[O-]
Agent: CSC(C)(CCl)c1ccc(F)cc1
Agent: [Na+]
Solvent: CCO
Product: CCOC(=O)C(C(=O)OCC)C(C)(CSC)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 84 %

Procedure:
To a solution of diethyl malonate (12 mL, 81 mmol) in ethanol (40 mL) was added dropwise 21% sodium ethoxide ethanol solution (29 mL, 77 mmol) under nitrogen atmosphere under ice-cooling. The mixture was warmed to room temperature, stirred for 1 hour, and cooled again with ice. The crude product (73 mmol) of 1-(1-chloro-1-methyl-2-methylsulfanyl-ethyl)-4-fluorobenzene or 1-(2-chloro-1-methyl-1-methylsulfanyl-ethyl)-4-fluorobenzene obtained in Example 1-3 was added dropwise to the mixture while maintaining a temperature below 4° C. The obtained solution was stirred for 1 hour at room temperature and concentrated under reduced pressure. The residue was neutralized by adding a 2N aqueous hydrochloric acid solution and the aqueous layer was extracted with ethyl acetate (50 mL). The organic layer was dried over magnesium sulfate, filtrated and the solvent was evaporated. Then the obtained residue was purified by silica gel chromatography (hexane:ethyl acetate=20:1 to 5:1) to give the title compound (24 g, yield 84%) as a pale-yellow oil.
Reaction SMILES: COC1C=C2C(=CC=1)N=C(NCCC)C(CO)=C2.[CH:19]([NH:22][C:23]1[C:32]([CH2:33]O)=[CH:31][C:30]2[C:25](=[CH:26][CH:27]=[C:28]([O:35][CH3:36])[CH:29]=2)[N:24]=1)([CH3:21])[CH3:20].O=S(Cl)[Cl:39]>C(Cl)Cl>[ClH:39].[Cl:39][CH2:33][C:32]1[C:23]([NH:22][CH:19]([CH3:21])[CH3:20])=[N:24][C:25]2[C:30]([CH:31]=1)=[CH:29][C:28]([O:35][CH3:36])=[CH:27][CH:26]=2
Reactant: COc1ccc2nc(NC(C)C)c(CO)cc2c1
Reactant: O=S(Cl)Cl
Agent: CCCNc1nc2ccc(OC)cc2cc1CO
Solvent: ClCCl
Product: COc1ccc2nc(NC(C)C)c(CCl)cc2c1
Product: Cl
Temperature: 25 °C
Reaction time: 1 h
Yield: 103.9 %

Procedure:
To a stirred solution of (6-methoxy-2-(propylamino)quinolin-3-yl)methanol SLA 28188 (1.41 g, 5.72 mmol) in dry CH2Cl2 (115 mL) in a 250 mL round-bottomed flask equipped with a magnetic stirrer was added dropwise SOCl2 (8.30 mL, 114 mmol). The mixture was stirred for 1 h at RT then concentrated to dryness at 40° C. under vacuum. The residue was then taken up in CH2Cl2 (20 mL) before concentration back to dryness at 40° C. under vacuum (done 3 times) to give of 3-(chloromethyl)-N-isopropyl-6-methoxyquinolin-2-amine hydrochloride SLA 28190 as a yellow solid (1.79 g, >100% yield).
Reaction SMILES: C(O[CH:5]1[O:28][CH2:27][C@@H:18]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C@H:15]([O:16][CH3:17])[C@H:6]1[O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)(=O)C.[Si]([C:33]#[N:34])(C)(C)C.B(F)(F)F.CCOCC>[N+](C)([O-])=O>[CH2:8]([O:7][C@@H:6]1[C@@H:15]([O:16][CH3:17])[C@H:18]([O:19][CH2:20][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:27][O:28][CH:5]1[C:33]#[N:34])[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1
Reactant: CO[C@H]1[C@H](OCc2ccccc2)COC(OC(C)=O)[C@@H]1OCc1ccccc1
Reactant: C[Si](C)(C)C#N
Agent: FB(F)F
Solvent: CCOCC
Solvent: C[N+](=O)[O-]
Product: CO[C@H]1[C@H](OCc2ccccc2)COC(C#N)[C@@H]1OCc1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 70.7 %

Procedure:
To a stirred solution of 2,4-di-O-benzyl-3-O-methyl-a,b-D-xylopyranosyl acetate (20 g, 0.052 mole) and Me3SiCN (20 ml, 0.16 mole) in anhydrous nitromethane (300 ml) was added boron trifluoride etherate (1.0 g, 0.007 mole) at room temperature. After the mixture was stirred at room temperature for 30 min, the mixture was evaporated to dryness under reduced pressure. The residue was chromatographed on silica gel using CH2Cl2 /AcOEt (99:1) as an eluent to give 2,4-di-O-benzyl-3-O-methyl-a,b-D-xylopyranosyl cyanide as colorless oil (13.0 g, 71% yield); EI-MS: m/z 353 (M+), 262 (M+ -Bn); 1H-NMR of b-cyano-isomer (CDCl3)d; 3.15 (1H,dd,J=10,11 Hz), 3.23 (1H,t,J=10 Hz), 3.49 (1H,m), 3.59 (1H,t,J=10 Hz), 3.66 (3H,s), 3.96 (1H,dd,J=5 & 11 Hz), 3.97 (1 H,d,J=10 Hz), 4.61 (1H,d,J=12 Hz),4.73 (1H,d,J=12 Hz), 4.84 (1H,d,J=11 Hz), 4.88 (1H,d,J=11 Hz), 7.29~7.42 (10H, m).
Reaction SMILES: [F:1][C:2]1[CH:27]=[CH:26][CH:25]=[CH:24][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:14]2[N:19]=[C:18]([CH3:20])[C:17]([C:21]([OH:23])=O)=[CH:16][N:15]=2)=[N:6]1.C(Cl)CCl.C1C=CC2N(O)N=[N:38]C=2C=1.N>CN(C)C=O.C(OCC)(=O)C>[F:1][C:2]1[CH:27]=[CH:26][CH:25]=[CH:24][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:14]2[N:19]=[C:18]([CH3:20])[C:17]([C:21]([NH2:38])=[O:23])=[CH:16][N:15]=2)=[N:6]1
Reactant: Cc1nc(-c2nn(Cc3ccccc3F)c3ncccc23)ncc1C(=O)O
Reactant: On1nnc2ccccc21
Agent: N
Solvent: ClCCCl
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Cc1nc(-c2nn(Cc3ccccc3F)c3ncccc23)ncc1C(N)=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Under argon, 250 mg (0.688 mmol) of the compound from example 45A were initially charged in dimethylformamide (3.8 ml). Subsequently, 145 mg (0.757 mmol) of EDC and 116 mg (0.757 mmol) of HOBt were added, and finally 77 μl (1.03 mmol) of aqueous ammonia solution (25%) were added. The reaction mixture was stirred at RT overnight and then diluted with ethyl acetate. The organic phase was washed once each with water and saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated by rotary evaporation. The residue was admixed with tert-butyl methyl ether, and the solids were filtered off and dried under high vacuum. This gave 171 mg (66% of theory) of the title compound in solid form.
Reaction SMILES: [SiH3][OH:2].[CH:3]1[C:16]2[C:7](=[CH:8][C:9]3[C:14]([C:15]=2Br)=[CH:13][CH:12]=[CH:11][CH:10]=3)[CH:6]=[CH:5][CH:4]=1.C([Li])CCC.Cl[Si:24](Cl)([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>O>[CH:3]1[C:16]2[C:7](=[CH:8][C:9]3[C:14]([C:15]=2[Si:24]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[OH:2])=[CH:13][CH:12]=[CH:11][CH:10]=3)[CH:6]=[CH:5][CH:4]=1
Reactant: Cl[Si](Cl)(c1ccccc1)c1ccccc1
Reactant: O[SiH3]
Reactant: Brc1c2ccccc2cc2ccccc12
Agent: [Li]CCCC
Solvent: O
Product: O[Si](c1ccccc1)(c1ccccc1)c1c2ccccc2cc2ccccc12

Procedure:
For preparation of the silanol, 20 mmol 9-anthracenyl bromide are metallized with the equimolar amount of n-butyllithium (2 M solution in cyclohexane, 20 mmol) at −20° C. and dichlorodiphenylsilane is then added, in accordance with Example 2.1. When the addition of the dichlorodiphenylsilane has ended, the reaction mixture is heated under reflux for 3 h and then hydrolysed by addition of water (100 g).
Reaction SMILES: [N+:1]([O-:4])(O)=[O:2].C(OC(=O)C)(=O)C.[O:12]=[C:13]1[N:22]2[C:17]([CH:18]=[CH:19][CH:20]=[CH:21]2)=[CH:16][CH:15]=[C:14]1[C:23]([O:25][CH2:26][CH3:27])=[O:24]>C(OCC)(=O)C>[N+:1]([C:16]1[CH:15]=[C:14]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:13](=[O:12])[N:22]2[C:17]=1[CH:18]=[CH:19][CH:20]=[CH:21]2)([O-:4])=[O:2]
Reactant: CCOC(=O)c1ccc2ccccn2c1=O
Reactant: O=[N+]([O-])O
Solvent: CC(=O)OC(C)=O
Solvent: CCOC(C)=O
Product: CCOC(=O)c1cc([N+](=O)[O-])c2ccccn2c1=O
Temperature: -10 °C
Reaction time: 0.08 h
Yield: 45.1 %

Procedure:
Nitric acid (1.08 g, 17 mmol) was added slowly to acetic anhydride (7 mL) at 5° C. Stirring was continued for 5 min and the reaction mixture was cooled to −10° C. (ice/salt bath). Ethyl 4-oxo-4H-quinolizine-3-carboxylate (1) (920 mg, 4.2 mmol) was added in one portion. After 5 min, an orange precipitate formed. The reaction was complete after 15 min as indicated by thin layer chromatography (ethyl acetate). The reaction mixture was poured into 250 g crushed ice and stirred for 30 min to give an orange suspension, which was extracted three times with 100 mL dichloromethane. The combined organic layers were washed three times with 100 ml water. Evaporation of the solvent gave a deep red solid. Purification by flash chromatography gave a bright yellow solid (497 mg, 50% yield). M.p. 169-170° C. 1H NMR (δ, CDCl3): 1.44 (t, J=7.0 Hz, 3H), 4.45 (q, J=7.0 Hz, 2H), 7.55 (dd, J=7.0 Hz, J=7.0 Hz, 1H), 8.15 (dd, J=9.7 Hz, 7.0 Hz, 1H), 9.31 (d, J=9.1 Hz, 1H), 9.47 (s, 1H), 9.60 (d, J=7.0 Hz, 1H). MS: m/z 262.0601; required for C12H10N2O5: 262.0590.
Reaction SMILES: [C:1]1([CH2:7][C:8]([N:10]([C:16]([CH3:24])([CH3:23])[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:11][C:12](OC)=[O:13])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CO.C[O-].[Na+]>C(O)C>[CH3:23][C:16]([N:10]1[CH2:11][C:12]([OH:13])=[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[C:8]1=[O:9])([CH3:24])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: COC(=O)CN(C(=O)Cc1ccccc1)C(C)(C)c1ccccc1
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Solvent: CCO
Product: CC(C)(c1ccccc1)N1CC(O)=C(c2ccccc2)C1=O
Yield: 45.5 %

Procedure:
10 g (30 mmol) of methyl 2-(N-phenylacetyl-α,α-dimethylbenzylamino)acetate was dissolved in 100 ml of ethanol, and 17.4 g (90 mmol) of a methanol solution of 28% sodium methylate was added thereto. The mixture was refluxed under heating for 0.5 hour. The reaction solvent was distilled off under reduced pressure, and the residue was poured into ice water and acidified with 10% hydrochloric acid. Precipitated crude crystals were collected by filtration and recrystallized from ethanol to obtain 4.0 g (yield: 46%) of the desired compound.
Reaction SMILES: CN(C)C1C=CC=CC=1.[CH:10]1([CH2:15][OH:16])[CH2:14][CH2:13][CH2:12][CH2:11]1.[C:17](Cl)([Cl:19])=[O:18].C1(C)C=CC=CC=1>>[Cl:19][C:17]([O:16][CH2:15][CH:10]1[CH2:14][CH2:13][CH2:12][CH2:11]1)=[O:18]
Reactant: O=C(Cl)Cl
Reactant: OCC1CCCC1
Solvent: Cc1ccccc1
Solvent: CN(C)c1ccccc1
Product: O=C(Cl)OCC1CCCC1
Reaction time: 0.5 h
Yield: 81 %

Procedure:
A mixture of 24.2 g (0.20 mole) N,N-dimethylaniline and 20.3 g (0.20 mole) of cyclopentylmethanol was slowly added to a 20% solution of phosgene in toluene (104 ml, 0.20 mole) cooled to -5° to +5° C. After the addition the reaction mixture was allowed to attain room temperature and was kept at room temperature for 30 min. The precipitate was filtered off and the solvent was evaporated. Distillation in vacuo gave 26.3 g (81%) of cyclopentylmethyl chloroformate. Bp17-20 82°-84° C., nD21 1.4541. Analysis for C7H11ClO2. Found (calculated): Cl 21.37 (21.80). IR (neat) cm-1 : 1790 (CO).