Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([NH:10][C:11]2[N:19]=[C:18]([Cl:20])[N:17]=[C:16]3[C:12]=2[N:13]=[CH:14][NH:15]3)[CH:5]=1.C([O-])([O-])=O.[K+].[K+].CN(C=O)C.[CH2:33](I)[CH3:34]>O.CCOC(C)=O>[CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([NH:10][C:11]2[N:19]=[C:18]([Cl:20])[N:17]=[C:16]3[C:12]=2[N:13]=[CH:14][N:15]3[CH2:33][CH3:34])[CH:5]=1
Reactant: CCI
Reactant: COC(=O)c1cccc(Nc2nc(Cl)nc3[nH]cnc23)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCn1cnc2c(Nc3cccc(C(=O)OC)c3)nc(Cl)nc21
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 68.9 %

Procedure:
A 750 ml flask is charged with 25.4 g (83.5 mmol) of 3-(2-chloro-9H-purin-6-yl-amino)-benzoic acid methyl ester, 12.95 g (93.7 mmol) of K2CO3 and 360 ml of DMF. The mixture is stirred at RT for 30 min, then 35.8 ml (443 mmol) ethyliodide are added under slight cooling. After completion, the mixture is poured into water/EtOAc (1.2 l each). The aqueous layer is extracted with ethyl acetate (2 fold). The combined organic layers are washed with water and brine, dried (Na2SO4), filtered and concentrated. After purification by chromatography (silica gel, EtOAc) the desired product, 3-(2-chloro-9-ethyl-9H-purin-6-yl-amino)benzoic acid methyl ester, (19.1 g, 69% yield) is obtained; Rf=0.25; (EtOAc); m.p. 148° C.; ESI-MS: 332 (M+H)+.
Reaction SMILES: [CH2:1]([NH:8][CH2:9][CH:10]([CH2:21][OH:22])[CH:11]([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[C:15]([Cl:20])[CH:14]=1)[OH:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:23]([Si:27](Cl)([CH3:29])[CH3:28])([CH3:26])([CH3:25])[CH3:24].C(N(CC)CC)C>C1COCC1.CN(C)C1C=CN=CC=1>[CH2:1]([NH:8][CH2:9][CH:10]([CH2:21][O:22][Si:27]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:29])[CH3:28])[CH:11]([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[C:15]([Cl:20])[CH:14]=1)[OH:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: OCC(CNCc1ccccc1)C(O)c1ccc(F)c(Cl)c1
Agent: CN(C)c1ccncc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(C)(C)[Si](C)(C)OCC(CNCc1ccccc1)C(O)c1ccc(F)c(Cl)c1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a solution of (1RS,2SR)-2-[(benzylamino)methyl]-1-(3-chloro-4-fluorophenyl)propane-1,3-diol (the above-mentioned crude product) in THF (170 ml) were added tert-butylchlorodimethylsilane (5.38 g), triethylamine (7.1 ml) and 4-(dimethylamino)pyridine (415 mg) under ice-cooling, and the mixture was stirred at room temperature for 18 hr. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with ethyl acetate. The diluted solution was washed with distilled water, saturated aqueous sodium hydrogen carbonate and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give the title compound (14.1 g).
Reaction SMILES: [CH3:1][O:2][C:3]1[N:4]=[CH:5][CH:6]=[C:7]2[CH:11]=[CH:10][O:9][C:8]=12.[Li][CH2:13]CCC.CI>C1COCC1>[CH3:1][O:2][C:3]1[N:4]=[CH:5][CH:6]=[C:7]2[CH:11]=[C:10]([CH3:13])[O:9][C:8]=12
Reactant: [Li]CCCC
Reactant: COc1nccc2ccoc12
Solvent: CI
Solvent: C1CCOC1
Product: COc1nccc2cc(C)oc12
Temperature: -78 °C
Reaction time: 2 h
Yield: 100.1 %

Procedure:
To a solution of 7-methoxyfuro[2,3-c]pyridine (2.9 g, 19.6 mmol) in THF (20 mL) stirred under an atmosphere of argon was added n-BuLi (7.8 mL, 19.6 mmol) at −78° C.; the mixture was transferred to a −30° C. ice bath and was stirred for 2 h. The mixture was cooled to −78° C. and MeI (4.2 g, 29.4 mmol) was added. After the mixture was stirred at rt for 18 h, the reaction mixture was quenched with water (30 mL) and extracted with DCM (50 mL×3). The combined organic layers were washed with brine (30 mL×3), dried over Na2SO4 and concentrated in vacuo to afford the title compound (3.2 g, 100%) as a yellow solid. The material was carried forward without any further purification. LCMS (M+H)+=164.
Reaction SMILES: [Mg].[CH2:2](Br)[CH2:3][CH2:4][CH3:5].[Cl:7][CH2:8][CH2:9][CH2:10][C:11]#N.Cl.CC[O:16]CC>>[CH2:2]([C:11]([CH2:10][CH2:9][CH2:8][Cl:7])=[O:16])[CH2:3][CH2:4][CH3:5]
Reactant: CCOCC
Reactant: CCCCBr
Reactant: N#CCCCCl
Agent: Cl
Agent: [Mg]
Product: CCCCC(=O)CCCCl
Reaction time: 2 h

Procedure:
A Grignard reagent is prepared from magnesium (1.9 g), n-butyl bromide (11.2 g) and dried ether (80 ml) and a solution of 4-chlorobutyronitrile (7 g) in ether (15 ml) is added dropwise to the reagent with ice-cooling. The mixture is stirred at the same temperature for 2 hours and then at room temperature for additional 2 hours. 10% Hydrochloric acid is slowly added dropwise to the mixture with ice-cooling to decompose the product and to acidify the mixture to pH about 1. After stirring at room temperature for 1 hour, the mixture is extracted with ether. The ether layer is washed with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride and dried over magnesium sulfate. The solvent is distilled off and the residue is distilled to obtain 3-chloropropyl butyl ketone (1.6 g), b.p. 104°-106° C./30 mmHg.
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:26]#[N:27])=[C:4]([C:8]([NH:10][C@@H:11]2[CH2:16][CH2:15][N:14](C(OCC)=O)[CH2:13][C@@H:12]2[O:22][CH2:23][CH2:24][CH3:25])=[O:9])[NH:5][C:6]=1[CH3:7].[OH-].[K+].O.NN.O>C(O)CO>[Cl:1][C:2]1[C:3]([C:26]#[N:27])=[C:4]([C:8]([NH:10][C@@H:11]2[CH2:16][CH2:15][NH:14][CH2:13][C@@H:12]2[O:22][CH2:23][CH2:24][CH3:25])=[O:9])[NH:5][C:6]=1[CH3:7]
Reactant: CCCO[C@H]1CN(C(=O)OCC)CC[C@H]1NC(=O)c1[nH]c(C)c(Cl)c1C#N
Agent: NN
Agent: [K+]
Agent: [OH-]
Solvent: OCCO
Solvent: O
Product: CCCO[C@H]1CNCC[C@H]1NC(=O)c1[nH]c(C)c(Cl)c1C#N
Temperature: 25 °C
Yield: 70.4 %

Procedure:
A solution of ethyl (3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-propoxypiperidine-1-carboxylate (Intermediate 75, 2.6 g, 6.56 mmol), potassium hydroxide (3.67 g, 65.6. mmol), and hydrazine hydrate (3.28 g, 65.6 mmol) in ethylene glycol (100 mL) was stirred for 60 h at 120° C. The reaction mixture was cooled to room temperature and poured into water (75 mL) and extracted with ethyl acetate (2×100 mL). The combined organic extracts were dried over anhydrous sodium sulphate, filtered, concentrated under vacuum to afford 4-chloro-3-cyano-5-methyl-N-[(3S,4R)-3-propoxypiperidin-4-yl]-1H-pyrrole-2-carboxamide 1.5 g, 71% as solid.
Reaction SMILES: C([Cl:4])(=O)C.[NH2:5][C:6]1[C:15]2=[N:16][N:17]([CH2:29][CH2:30][CH3:31])[C:18]([CH2:19][CH2:20][NH:21]C(=O)OC(C)(C)C)=[C:14]2[C:13]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[N:7]=1>C(O)C>[ClH:4].[ClH:4].[NH2:21][CH2:20][CH2:19][C:18]1[N:17]([CH2:29][CH2:30][CH3:31])[N:16]=[C:15]2[C:14]=1[C:13]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[N:7]=[C:6]2[NH2:5]
Reactant: CC(=O)Cl
Reactant: CCCn1nc2c(N)nc3ccccc3c2c1CCNC(=O)OC(C)(C)C
Solvent: CCO
Product: CCCn1nc2c(N)nc3ccccc3c2c1CCN
Product: Cl
Temperature: 25 °C

Procedure:
Acetyl chloride (7.1 mL, 100 mmol) was added to ethanol (100 mL) at 0° C. The resulting solution was added to the tert-butyl 2-(4-amino-2-propyl-2H-pyrazolo[3,4-c]quinolin-1-yl)ethylcarbamate from Part G. The solution was heated at reflux for 9.5 hours. Upon cooling to ambient temperature, a precipitate formed that was isolated after two days by filtration, washed with a small amount of cold ethanol, and dried to yield 5.78 g of 1-(2-aminoethyl)-2-propyl-2H-pyrazolo[3,4-c]quinolin-4-amine dihydrochloride as a white solid.
Reaction SMILES: [CH2:1]([C:5]1=[CH:6][N:7]([C:25]([CH3:28])([CH3:27])[CH3:26])[S:8]/[C:9]/1=[N:10]\[C:11]([C:13]1([CH3:24])[CH2:17][CH2:16][CH:15]([C:18]([O:20]C)=[O:19])[C:14]1([CH3:23])[CH3:22])=[O:12])[CH2:2][CH2:3][CH3:4].[OH-].[K+].C(O)C.Cl>O>[CH2:1]([C:5]1=[CH:6][N:7]([C:25]([CH3:26])([CH3:28])[CH3:27])[S:8]/[C:9]/1=[N:10]\[C:11]([C:13]1([CH3:24])[CH2:17][CH2:16][CH:15]([C:18]([OH:20])=[O:19])[C:14]1([CH3:23])[CH3:22])=[O:12])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1cn(C(C)(C)C)s/c1=N\C(=O)C1(C)CCC(C(=O)OC)C1(C)C
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CCCCc1cn(C(C)(C)C)s/c1=N\C(=O)C1(C)CCC(C(=O)O)C1(C)C
Temperature: 60 °C
Yield: 75 %

Procedure:
To a 20-mL scintillation vial containing a magnetic stir bar were added the product from Example 92C (102 mg, 0.250 mmol) and potassium hydroxide (84 mg, 1.50 mmol). Ethanol (1 mL) and water (0.25 mL) were added. The vial was heated to 60° C. and the reaction mixed for 24 hours. After cooling to room temperature, the pH was adjusted to 1 by addition of 1N hydrochloric acid. The mixture was extracted with dichloromethane (3×10 mL). The combined organic extracts were dried (MgSO4), filtered, and concentrated by rotary evaporator to afford a tan solid. The product was recrystallized from ethyl acetate/hexanes to afford 74 mg (75%) of the title compound. 1H NMR (DMSO-d6) δ 0.63 (br s, 3H), 0.91 (t, J=7.3 Hz, 3H), 1.23-1.38 (m, 8H), 1.57-1.68 (m, 12H), 1.76-1.87 (m, 1H), 2.00-2.11 (m, 1H), 2.65-2.84 (m, 4H), 8.7 (br s, 1H), 11.7 (br s, 1H). MS (ESI+) m/z 395 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[N:9]1[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][N:18]2C(=O)C3C(=CC=CC=3)C2=O)[CH2:11][CH2:10]1.O.NN>CCO>[ClH:1].[ClH:1].[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[N:9]1[CH2:10][CH2:11][N:12]([CH2:15][CH2:16][CH2:17][NH2:18])[CH2:13][CH2:14]1
Reactant: O=C1c2ccccc2C(=O)N1CCCN1CCN(c2cccc(Cl)c2Cl)CC1
Agent: NN
Solvent: O
Solvent: CCO
Product: Cl
Product: NCCCN1CCN(c2cccc(Cl)c2Cl)CC1
Temperature: 25 °C
Reaction time: 6 h
Yield: 218.8 %

Procedure:
To a suspension of 2-(3-(4-(2,3-dichlorophenyl)piperazin-1-yl)propyl)isoindoline-1,3-dione (compound 36, 11.1 g, 26.5 mmol) in EtOH was added hydrazine monohydrate. The reaction mixture was stirred at room temperature for 6 hrs, then the white solid filtered off. The filtrate was concentrated under reduced pressure. The residue was diluted with CH2Cl2, and washed with water. The organic layer was dried over anhydrous MgSO4, filtered, and concentrated in vacuo. To the crude product in diethyl ether was added 2M HCl solution in diethyl ether (10 mL). The obtained product was washed with diethyl ether to provide the title compound (6.98 g, 73%) as a white solid.
Reaction SMILES: F[C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][N:3]=1.[C:9](=O)([O-])[O-:10].[Cs+].[Cs+].C1COCC1.CO>O>[I:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([O:10][CH3:9])[CH:7]=1
Reactant: O=C([O-])[O-]
Reactant: Fc1cc(I)ccn1
Agent: [Cs+]
Solvent: CO
Solvent: C1CCOC1
Solvent: O
Product: COc1cc(I)ccn1
Temperature: 50 °C

Procedure:
To 2-fluoro-4-iodopyridine (500 mg, 2.2 mmol) and cesium carbonate (730 mg, 2.2 mmol) was added THF (5 mL) and MeOH (0.091 mL, 2.2 mmol). The resulting mixture was heated to 50° C. for 24 hours in a sealed tube. The cooled mixture was diluted with water and extracted with EtOAc. The organic layer was dried over sodium sulfate, filtered and concentrated to yield the title compound. MS m/z=236 [M+1]+. Calc'd for C6H61NO: 235.03.
Reaction SMILES: C(OC(=O)N[C@H]1CC2C(=CC=C(Br)C=2)NC1=O)(C)(C)C.[C:21]([O:25][C:26](=[O:47])[NH:27][CH:28]1[CH2:37][C:36]2[C:31](=[CH:32][CH:33]=[C:34]([Br:38])[CH:35]=2)[N:30]([CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C:29]1=[O:46])([CH3:24])([CH3:23])[CH3:22]>>[C:21]([O:25][C:26](=[O:47])[NH:27][C@H:28]1[CH2:37][C:36]2[C:31](=[CH:32][CH:33]=[C:34]([Br:38])[CH:35]=2)[N:30]([CH2:39][C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)[C:29]1=[O:46])([CH3:24])([CH3:22])[CH3:23]
Reactant: CC(C)(C)OC(=O)NC1Cc2cc(Br)ccc2N(Cc2ccccc2)C1=O
Agent: CC(C)(C)OC(=O)N[C@H]1Cc2cc(Br)ccc2NC1=O
Product: CC(C)(C)OC(=O)N[C@H]1Cc2cc(Br)ccc2N(Cc2ccccc2)C1=O

Procedure:
The title compound was prepared from 8B according to the procedures described in 3C.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[N+:4]([O-])[CH:5]=[CH:6][CH:7]=1.[CH3:9][C:10]1([CH3:18])[O:15][C:14](=[O:16])[CH2:13][C:12](=[O:17])[O:11]1>C(OC(=O)C)(=O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5](=[C:13]2[C:14](=[O:16])[O:15][C:10]([CH3:18])([CH3:9])[O:11][C:12]2=[O:17])[NH:4][CH:3]=1
Reactant: CC1(C)OC(=O)CC(=O)O1
Reactant: [O-][n+]1cccc(Br)c1
Solvent: CC(=O)OC(C)=O
Product: CC1(C)OC(=O)C(=C2C=CC(Br)=CN2)C(=O)O1
Reaction time: 8 h
Yield: 20.6 %

Procedure:
3-Bromopyridine N-oxide (10 g, 57.5 mmol) was slowly added into a solution of 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum's acid, 8.28 g, 57.5 mmol) in acetic anhydride (58 mL) at 0° C. The temperature was allowed to come to room temperature overnight. The mixture was filtered and yellow crystals were washed with small amount of acetic anhydride and dried in vacuo. The residue was triturated with warm chloroform and insoluble residue was filtered off. The chloroform soluble fraction was evaporated and the residue triturated with 5% MeOH in DCM. The solid material was filtered off and the soluble fraction was evaporated to give 3.55 g (20%) of 5-(5-Bromopyridin-2(1H)-ylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione. 1H NMR (400 MHz, dMSO): δ 1.61 (s, 6H), 1.64 (s, 1H), 8.20-8.23 (dd, 1H), 8.51-8.52 (d, 1H), 8.62-8.65 (d, 1H).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[N:10]=[C:9]([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=1)[CH:8]=[C:7]2Cl)([O-:3])=[O:2].[CH3:22][NH:23][CH3:24].O>CN1C(=O)CCC1>[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[N:10]=[C:9]([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=1)[CH:8]=[C:7]2[N:23]([CH3:24])[CH3:22])([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1ccc2nc(-c3cccc(F)c3)cc(Cl)c2c1
Reactant: CNC
Solvent: CN1CCCC1=O
Solvent: O
Product: CN(C)c1cc(-c2cccc(F)c2)nc2ccc([N+](=O)[O-])cc12
Temperature: 60 °C

Procedure:
6-Nitro-4-chloro-2-(3-fluoro-phenyl)-quinoline, 20 g (59.4 mmoles), was placed in a 500 mL three-neck round-bottom flask equipped with magnetic stirrer, nitrogen inlet, gas outlet, condenser and heating bath. The material was dissolved in 150 mL of N-methyl pyrrolidinone, stirred and 250 mL of a 40% aq. solution of dimethylamine was added. The mixture was then warmed to 60° C. for 48 hrs. At the end of this time the reaction was cooled, poured into 3 L of water in a 4 L Erlenmeyer flask and the mixture stirred until solids formed. The solids were collected by vacuum filtration and dried in a vacuum oven. The product was recrystallised from-ethanol in a −20° C. freezer to give 19.6 g (95%) yield of the desired product.
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][NH:14][CH2:13][C@@H:12]1[C:17](=[O:29])[NH:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][CH2:27][CH3:28])=[CH:22][CH:21]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.C1C2C(COC([N:54]=[C:55]=[S:56])=O)C3C(=CC=CC=3)C=2C=CC=1.N1CCCCC1>C(Cl)(Cl)Cl>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:55](=[S:56])[NH2:54])[CH2:13][C@@H:12]1[C:17](=[O:29])[NH:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][CH2:27][CH3:28])=[CH:22][CH:21]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCCc1ccc(CNC(=O)[C@H]2CNCCN2C(=O)OCc2ccccc2)cc1
Reactant: O=C(N=C=S)OCC1c2ccccc2-c2ccccc21
Solvent: C1CCNCC1
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: CCCc1ccc(CNC(=O)[C@H]2CN(C(N)=S)CCN2C(=O)OCc2ccccc2)cc1
Temperature: 25 °C
Yield: 88.7 %

Procedure:
To a solution of the compound (1.59 g) obtained in Step 3 in chloroform (16 ml) was added, with stirring at room temperature, triethylamine (840 μl), and 9-fluorenylmethoxycarbonyl isothiocyanate (1.13 g) was added. After stirring at room temperature for 4 hr, piperidine (805 μl) was added. After stirring overnight at room temperature, the reaction mixture was concentrated under reduced pressure. The residue was partitioned by adding ethyl acetate and water. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtrated, and concentrated under reduced pressure. The residue was purified by column chromatography (ethyl acetate:n-hexane=1:1-4:1) to give the title compound (1.62 g).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:13][N:12](CC2C=CC=CC=2)[C@@H:11]([CH3:21])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H][H]>CO.[Pd]>[C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:13][NH:12][C@@H:11]([CH3:21])[CH2:10]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: C[C@H]1C[C@H](NC(=O)OC(C)(C)C)CN1Cc1ccccc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: C[C@H]1C[C@H](NC(=O)OC(C)(C)C)CN1

Procedure:
A 4.500 g (15.50 mmol) sample of (2S,4S)-4-t-butoxycarbonylamino-2-methyl-1-N-benzylpyrrolidine, from Example 2 above, was dissolved in 150 mL of methanol, 0.90 g of 10% Pd/C was added and the mixture shaken under 4 atm of hydrogen at room temperature for 13 hours. The mixture was concentrated, the catalyst was removed by filtration, and the solvent removed to afford 3.081 g of the title compound as a white solid. MS M/Z: 201 (M+H). NMR (CDCl3) δ: 1.15 (d, 3H, J=6 Hz), 1.44 (s, (1H), 1.54-1.63 (m, 2H), 1.75 (m, 1H), 2.64 (dd, 1H, J=5, J=12 Hz), 3.26 (m, 1H), 3.38 (dd, 1H, J=7, J=12 Hz), 4.12 (br, 1H), 4.63 (br, 1H). IR (KBr): 1685 cm-1.
Reaction SMILES: C1(=O)[NH:5]C(=O)C2=CC=CC=C12.[K].Br[CH2:14][CH2:15][O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18].[OH-].[Na+]>CN(C=O)C>[Si:17]([O:16][CH2:15][CH2:14][NH2:5])([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18]
Reactant: CC(C)(C)[Si](C)(C)OCCBr
Reactant: O=C1NC(=O)c2ccccc21
Agent: [K]
Agent: [Na+]
Agent: [OH-]
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)OCCN
Temperature: 75 °C
Reaction time: 5 h
Yield: 150.1 %

Procedure:
Nine grams (9 g) of potassium phthalimide was suspended in 100 mL of DMF to which 10 g of 1-bromo-2-t-butyldimethylsilyloxyethane (BrCH2CH2OTBDMS) was added and the mixture heated at 75° C. overnight. The mixture was added to 300 mL of a 5% sodium hydroxide (NaOH) solution and extracted with 300 mL of ether. The ether phase was washed twice with water, dried over Na2SO4 and the solvent removed under reduced pressure. The resulting solid was dissolved in 100 mL of CH3OH, then 3 mL of hydrazine (H2NNH2) was added. After 5 hr, 300 mL ether was added and the organic phase separated from the white precipitate by filtration. Removal of the solvent under reduced pressure yielded 11 g of O-(t-butyldimethylsilyl)ethanolamine. Five grams (5 g) of O (t butyldimethylsilyl)ethanolamine was dissolved in 40 mL of THF and 8 mL of (i-Pr)2NEt. Five milliliters (5 mL) of diphenylphosphinic chloride (Ph2P(O)Cl) was slowly added which produced a white precipitate. After 2 hr, the THF was removed under reduced pressure and the residue dissolved in 200 mL of CH2Cl2. The CH2Cl2 solution was washed with a saturated bicarbonate solution and brine. Removal of CH2Cl2 under reduced pressure followed by flash chromatography on SiO2 gel using CH2Cl2 produced the product (9 g).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([O:7][C:8]2[CH:9]=[C:10]([CH:13]=[CH:14][CH:15]=2)[C:11]#N)[CH:2]=1.[OH-:16].[Na+].Cl.C[OH:20].C(Cl)Cl>C(O)C>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([O:7][C:8]2[CH:9]=[C:10]([CH:13]=[CH:14][CH:15]=2)[C:11]([OH:20])=[O:16])[CH:2]=1
Reactant: N#Cc1cccc(Oc2cccnc2)c1
Reactant: CO
Reactant: [OH-]
Agent: Cl
Agent: [Na+]
Solvent: ClCCl
Solvent: CCO
Product: O=C(O)c1cccc(Oc2cccnc2)c1

Procedure:
Compound 1 (571 mg, 2.91 mmol, 1.00 eq) was dissolved in ethanol (12 mL) and 1N NaOH (6 mL) was added. The mixture was refluxed for 18 h and after cooling the reaction was neutralized with 1N HCl (6 mL) and the reaction was concentrated in vacuo. The crude reaction was dissolved in 10% MeOH/CH2Cl2 and the undissolved salt was filtered off and the solvents were removed in vacuo to afford the title compound as a pale-yellow solid: 1H NMR (400 MHz, DMSO-d6) δ 8.47 (d, J=2.4 Hz, 1H), 8.44 (d, J=4.7 Hz, 1H), 7.75 (d, J=7.7 Hz, 1H), 7.60-7.48 (m, 4H), 7.36 (dd, J=8.0, 1.9 Hz, 1H)); ES-MS [M+1]+: 216.1.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([S:11]([C:14]3[CH:20]=[CH:19][C:17]([CH3:18])=[CH:16][CH:15]=3)(=[O:13])=[O:12])[CH:9]=[CH:10][C:3]=12.C([N-]C(C)C)(C)C.[Li+].CCCCCCC.O1CCCC1.C(C1C=CC=CC=1)C.[I:49]I>O1CCCC1>[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([S:11]([C:14]3[CH:20]=[CH:19][C:17]([CH3:18])=[CH:16][CH:15]=3)(=[O:13])=[O:12])[C:9]([I:49])=[CH:10][C:3]=12
Reactant: Cc1ccc(S(=O)(=O)n2ccc3c(Br)ccnc32)cc1
Reactant: II
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: CCc1ccccc1
Solvent: CCCCCCC
Solvent: C1CCOC1
Product: Cc1ccc(S(=O)(=O)n2c(I)cc3c(Br)ccnc32)cc1
Temperature: -78 °C
Reaction time: 1 h

Procedure:
To a solution of Example 369A (25 g, 71.2 mmol) in tetrahydrofuran (600 mL) at −78° C. was slowly added 2M lithium diisopropylamide in heptane/tetrahydrofuran/ethylbenzene (39.1 mL, 78 mmol) and the mixture was stirred at −78° C. for 1 hour. A solution of iodine (19.87 g, 78 mmol) in tetrahydrofuran (100 mL) was added slowly and the reaction was allowed to warm to room temperature gradually. The reaction mixture was stirred at room temperature for 3 hours and was quenched with saturated aqueous sodium thiosulfate, water and ethyl acetate. The aqueous layer was extracted with ethyl acetate and the combined organics were dried over sodium sulfate, filtered and concentrated to give the title compound. MS (CI) m/z 477 (M+H)+.
Reaction SMILES: CS(C)=O.C(Cl)(=O)C(Cl)=O.[CH2:11]([N:17]1[C:21]([CH2:22][OH:23])=[CH:20][N:19]=[CH:18]1)[CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].C(N(CC)CC)C>ClCCl>[CH2:11]([N:17]1[C:21]([CH:22]=[O:23])=[CH:20][N:19]=[CH:18]1)[CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: CCCCCCn1cncc1CO
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Product: CCCCCCn1cncc1C=O
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 90.3 %

Procedure:
A solution of dimethyl sulphoxide (0.49 ml, 7.74 mmol) in dichloromethane (2.5 ml) was added dropwise to a solution of oxalyl chloride (0.3 ml, 3.78 mmol) in dichloromethane (15 ml) at -78° C. with stirring under argon. After effervescence had ceased (15 min), a solution of the product of step (ii) (313 mg, 1.72 mmol) in dichloromethane (7.5 ml) was added dropwise. The solution was stirred for 15 minutes before triethylamine (2.3 ml, 19 mmol) was added slowly. After a further 15 minutes the solution was allowed to warm to room temperature, stirred for 30 minutes and then quenched by the addition of a saturated aqueous solution of sodium bicarbonate (10 ml). The mixture was extracted with ethyl acetate (3×10 ml). The extracts were washed with brine (1×10 ml), dried (MgSO4) and concentrated. The residue was purified by column chromatography, eluting with 10% methanol/dichloromethane (v/v), to give 1-hexyl-imidazole-5-carboxaldehyde (280mg, 90% yield) as an oil;
Reaction SMILES: [C:1]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[NH:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[CH3:23])=[CH:13][CH:12]=[C:11](CC(=O)C1C=CC=CC=1)[CH:10]=2)(=[O:5])[CH2:2][CH2:3][CH3:4].[OH-:33].[Na+].[CH3:35]O>>[C:1]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[NH:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[CH3:23])=[CH:13][CH:12]=[C:11]([CH2:35][OH:33])[CH:10]=2)(=[O:5])[CH2:2][CH2:3][CH3:4]
Reactant: CO
Reactant: CCCC(=O)c1cnc2cc(CC(=O)c3ccccc3)ccc2c1Nc1ccccc1C
Reactant: [OH-]
Agent: [Na+]
Product: CCCC(=O)c1cnc2cc(CO)ccc2c1Nc1ccccc1C
Reaction time: 18 h

Procedure:
To a stirring suspension of 3-butyryl-4-(2-methyl-phenylamino)-7-benzoylmethylquinoline (2.74 g, 6.25 mmol) in methanol (25 ml) was added 2N sodium hydroxide (6.24 ml). Stirring was continued for 18 hours, then the solvent evaporated in vacuo and the residue treated with water and extracted with chloroform. The combined extracts were dried (Na2SO4) and evaporated to a solid, which was purified by column chromatography (silica, chloroform-methanol) to give the title compound (1.31 g), m.p. 176°-8°, from methanol.