Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.Cl.[N:3]1([CH2:9][C:10]2[CH:11]=[C:12]([CH:18]=[CH:19][CH:20]=2)[CH2:13][S:14][C:15](=N)N)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.ClC[CH2:23][C:24]#[N:25].[OH-].[Na+]>O.C(O)C>[N:3]1([CH2:9][C:10]2[CH:11]=[C:12]([CH:18]=[CH:19][CH:20]=2)[CH2:13][S:14][CH2:15][CH2:23][C:24]#[N:25])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1
Reactant: N=C(N)SCc1cccc(CN2CCCCC2)c1
Reactant: N#CCCCl
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: N#CCCSCc1cccc(CN2CCCCC2)c1
Temperature: 20 °C

Procedure:
A stirred solution of the above isothiourea (1.2 g) and 3-chloropropionitrile (0.4 ml) in a mixture of water (7 ml) and ethanol (5 ml) was treated at 0°-5° C. with 2.5N sodium hydroxide (5.3 ml). The reaction mixture was stirred at 0°-5° C. for a further hour and then allowed to warm to 20° C. The reaction mixture was extracted with ethyl acetate and the extracts washed with water, dried and evaporated to provide 3-(3-piperidinomethylbenzylthio)propionitrile as an oil.
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=1.[CH2:15]([NH:22][C:23]([C:25]1[CH:33]=[CH:32][C:28]([C:29](O)=[O:30])=[CH:27][N:26]=1)=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>>[CH2:15]([NH:22][C:23]([C:25]1[CH:33]=[CH:32][C:28]([C:29]([NH:6][C:5]2[CH:7]=[CH:8][C:2]([Cl:1])=[C:3]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=3)[CH:4]=2)=[O:30])=[CH:27][N:26]=1)=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: Nc1ccc(Cl)c(-c2ccccn2)c1
Reactant: O=C(O)c1ccc(C(=O)NCc2ccccc2)nc1
Product: O=C(Nc1ccc(Cl)c(-c2ccccn2)c1)c1ccc(C(=O)NCc2ccccc2)nc1

Procedure:
250 mg of 5-(methoxycarbonyl)picolinic acid was coupled to benzylamine via Procedure G. Crude methyl 6-(benzylcarbamoyl)nicotinate was hydrolyzed via Procedure M to yield 300 mg of 6-(benzylcarbamoyl)nicotinic acid. 60 mg of 4-chloro-3-(pyridin-2-yl)aniline was coupled to 6-(benzylcarbamoyl)nicotinic acid via Procedure G. The crude product was purified by reverse phase HPLC to yield N2-benzyl-N5-(4-chloro-3-(pyridin-2-yl)phenyl)pyridine-2,5-dicarboxamide. MS (Q1) 443.1 (M)+.
Reaction SMILES: [C:1](Cl)(=[O:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[N+:9]([C:12]1[CH:38]=[CH:37][C:15]([CH2:16][O:17][C:18]2[CH:19]=[C:20]([CH:34]=[CH:35][CH:36]=2)[C:21]([NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[S:30](=[O:33])(=[O:32])[NH2:31])=[O:22])=[CH:14][CH:13]=1)([O-:11])=[O:10]>CN(C)C1C=CN=CC=1.O1CCCC1>[N+:9]([C:12]1[CH:13]=[CH:14][C:15]([CH2:16][O:17][C:18]2[CH:19]=[C:20]([CH:34]=[CH:35][CH:36]=2)[C:21]([NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[S:30]([NH:31][C:1](=[O:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])(=[O:33])=[O:32])=[O:22])=[CH:37][CH:38]=1)([O-:11])=[O:10]
Reactant: CCCCCC(=O)Cl
Reactant: NS(=O)(=O)c1ccccc1NC(=O)c1cccc(OCc2ccc([N+](=O)[O-])cc2)c1
Agent: CN(C)c1ccncc1
Solvent: C1CCOC1
Product: CCCCCC(=O)NS(=O)(=O)c1ccccc1NC(=O)c1cccc(OCc2ccc([N+](=O)[O-])cc2)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 869.8 %

Procedure:
In a stream of nitrogen and at 0° C., 0.11 ml (0.80 mmol) of hexanoyl chloride was added to an anhydrous tetrahydrofuran (10 ml) solution containing 300 mg (0.07 mmol) of 3-(4-nitrobenzyloxy)-N-(2-sulfamoylphenyl)benzamide produced in Reference Example 5 and 171 mg (1.40 mmol) of 4-dimethylaminopyridine, the mixture was stirred at room temperature for 1 hour and then the solvent was evaporated under a reduced pressure. The resulting residue was dissolved in ethyl acetate, washed with water, a potassium hydrgensulfate aqueous solution and saturated brine in that order and dried over anhydrous sodium sulfate, and then the solvent was evaporated under a reduced pressure. The resulting residue was purified by a silica gel column chromatography to obtain 320 mg (yield: 86.8%) of the title compound.
Reaction SMILES: [C:1]([NH:6][C:7]1[CH:20]=[CH:19][N:10]([C@@H:11]2[O:18][C@H:15]([CH2:16][OH:17])[C@@H:13]([OH:14])[CH2:12]2)[C:9](=[O:21])[N:8]=1)(=[O:5])[CH:2]([CH3:4])[CH3:3].[CH3:22][O:23][C:24]1[CH:45]=[CH:44][C:27]([C:28](Cl)([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C:29]2[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=2)=[CH:26][CH:25]=1.CO>N1C=CC=CC=1>[C:1]([NH:6][C:7]1[CH:20]=[CH:19][N:10]([C@@H:11]2[O:18][C@H:15]([CH:16]([C:28]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)([C:29]3[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=3)[C:27]3[CH:26]=[CH:25][C:24]([O:23][CH3:22])=[CH:45][CH:44]=3)[OH:17])[C@@H:13]([OH:14])[CH2:12]2)[C:9](=[O:21])[N:8]=1)(=[O:5])[CH:2]([CH3:4])[CH3:3]
Reactant: COc1ccc(C(Cl)(c2ccccc2)c2ccc(OC)cc2)cc1
Reactant: CC(C)C(=O)Nc1ccn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)n1
Solvent: CO
Solvent: c1ccncc1
Product: COc1ccc(C(c2ccccc2)(c2ccc(OC)cc2)C(O)[C@H]2O[C@@H](n3ccc(NC(=O)C(C)C)nc3=O)C[C@@H]2O)cc1
Temperature: 0 °C
Reaction time: 17 h

Procedure:
2.5 mmol of compound 5 are dried by successive additions and evaporations of anhydrous pyridine. There is taking up with 25 ml of pyridine, cooling to 0° C. and the addition of 2.75 mmol (1.1 equivalent) of 4,4'-dimethoxy trityl chloride in 25 ml of pyridine at 0° C. The reaction is allowed to continue for 17 hours at 5° C. and then 2 ml of methanol are added to the reaction medium. After 30 minutes, the solvent is expelled with the rotary evaporator and the oily residue taken up by 100 ml of ethyl acetate, followed by washing 3 times with 50 ml of aqueous 5% NaHOO solution and once with 50 ml of bidistilled water. The organic phase is then dried on sodium sulphate and concentrated. By fractionating on a silica gel column, the thus obtained compound 6 is isolated and corresponds to formula (I), in which B is radical of formula (III) derived from cytosine, R1 and R2 are methyl radicals, R3 the 4,4'-dimethoxy trityl radical, R4 a hydrogen atom and R a hydrogen atom.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[N+:8]([O-:10])=[O:9].C(N(CC)CC)C.[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][CH:28]([NH2:31])[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19]>CN(C=O)C>[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][CH:28]([NH:31][C:2]2[CH:7]=[CH:6][N:5]=[CH:4][C:3]=2[N+:8]([O-:10])=[O:9])[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:19])[CH3:20]
Reactant: O=[N+]([O-])c1cnccc1Cl
Reactant: CC(C)(C)OC(=O)N1CCC(N)CC1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1CCC(Nc2ccncc2[N+](=O)[O-])CC1
Temperature: 25 °C
Reaction time: 15 h
Yield: 86 %

Procedure:
To a solution of 4-chloro-3-nitro-pyridine (25.0 g, 157.69 mmol, 1.0 equiv; commercially available) and triethylamine (19.15 g, 189.23 mol, 1.2 equiv) in anhydrous DMF (100 mL) was added 4-amino-piperidine-1-carboxylic acid tert-butyl ester (31.58 g, 157.69 mmol, 1.0 equiv; commercially available), dissolved in anhydrous DMF (30 mL), and the reaction mixture stirred at rt for 15 h. The reaction mixture was poured into ice-cold water (1 L) and stirred for 2 h, allowed to settle for another 2 h and then filtered. The orange solid was washed with water and air-dried. The crude material was crystallized from ethyl acetate to obtain 43.7 g (86%) of the title compound. 1H NMR (400 MHz, DMSO): δ 1.41 (s, 9H), 1.48-1.56 (m, 2H), 1.88-1.90 (m, 2H), 2.93 (br s, 2H), 3.90-3.93 (m, 3H), 7.14 (d, J=6.3 HZ, 1H), 8.03 (d, J=7.9 Hz, 1H), 8.27 (s, J=6.2 Hz, 1H), 9.03 (s, 1H).
Reaction SMILES: C[O:2][C:3](=[O:26])/[CH:4]=[C:5](\[CH3:25])/[CH:6]=[CH:7]/[C:8](/[F:24])=[C:9](\[CH3:23])/[CH:10]=[CH:11]/[C:12]1[C:17]([Cl:18])=[CH:16][C:15]([O:19][CH3:20])=[C:14]([CH3:21])[C:13]=1[Cl:22].CO.[OH-].[Na+].C/C(/C=C/C(/F)=C(\C)/C=C/C1C(Cl)=CC(OC)=C(C)C=1Cl)=C\C(O)=O>O>[CH3:25][C:5]([CH:6]=[CH:7]/[C:8](/[F:24])=[C:9](\[CH3:23])/[CH:10]=[CH:11]/[C:12]1[C:17]([Cl:18])=[CH:16][C:15]([O:19][CH3:20])=[C:14]([CH3:21])[C:13]=1[Cl:22])=[CH:4][C:3]([OH:26])=[O:2]
Reactant: COC(=O)/C=C(C)/C=C/C(F)=C(C)/C=C/c1c(Cl)cc(OC)c(C)c1Cl
Agent: COc1cc(Cl)c(/C=C/C(C)=C(F)/C=C/C(C)=C/C(=O)O)c(Cl)c1C
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: COc1cc(Cl)c(/C=C/C(C)=C(\F)C=CC(C)=CC(=O)O)c(Cl)c1C

Procedure:
In a manner similar to that described in Example 24, 1.2 g. (3 mmol) of methyl-(2E,4E,6Z,8E)-3,7-dimethyl-6-fluoro-9-(2,6-dichloro-3-methyl-4-methoxyphenyl)-nonatetraenoate were dissolved in 10 ml. of methanol and treated with a solution of 0.59 g. of sodium hydroxide in 4 ml. of water. The work-up as described in Example 24 afforded 2E,4E,6Z,8E-3,7-dimethyl-6-fluoro-9-(2,6-dichloro-3-methyl-4-methoxyphenyl)-2,4,6,8-nonatetraenoic acid.
Reaction SMILES: [S:1](=[O:5])(=O)([OH:3])[OH:2].[C:6]1([P:12]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[OH-].[Na+:26]>CC(C)CC(=O)C>[C:19]1([P:12]([C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:13]2[CH:14]=[C:15]([S:1]([O-:3])(=[O:5])=[O:2])[CH:16]=[CH:17][CH:18]=2)[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1.[Na+:26]
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)CC(C)C
Product: O=S(=O)([O-])c1cccc(P(c2ccccc2)c2ccccc2)c1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
A 300-ml three-necked flask equipped with a thermometer, stirrer, dropping funnel and nitrogen inlet and outlet lines was charged with 110 g (1.12 moles) of concentrated sulfuric acid and 60 g (0.23 mole) of triphenylphosphine, and the air in the flask was replaced with nitrogen. To the contents with stirring 220 g of fuming sulfuric acid (content of sulfur trioxide: 25% by weight; moles of sulfur trioxide: 0.69 mole) was added dropwise over 1 hour, while the inside temperature was maintained at 25° C. After completion of the dropping, stirring was continued for 12 hours at an inside temperature of 25° C. The reaction mixture obtained was added dropwise onto 1.8 kg of ice water under an atmosphere of nitrogen and hydrolyzed and diluted. To the obtained aqueous solution, 1.5 liters of 4-methyl-2-pentanone was added at a room temperature and sufficiently mixed. After the mixture had been allowed to stand still, the 4-methyl-2-pentanone layer was separated. To the 4-methyl-2-pentanone layer thus obtained, 120 ml of a 5% by weight aqueous sodium hydroxide solution was added dropwise under an atmosphere of nitrogen, while the inside temperature was maintained at 25° C., to neutralize it. The aqueous layer was taken out from the reaction mixture, washed with 100 ml of 4-methyl-2-pentanone and again taken out by separation. The layer was condensed at 80° C. to a volume of 80 ml and then allowed to cool, to precipitate crystals. The crystals precipitated were separated by filtration and vacuum-dried at 60° C., 0.67 kPa (5 mmHg) for 2 hours, to yield 35 g of a white crystalline sodium 3-(diphenylphosphino)benzenesulfonate dihydrate.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][CH:6]=[CH:5]2.ClC1C=CC=C(C(OO)=[O:20])C=1>CCOCC>[CH3:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N+:7]([O-:20])[CH:6]=[CH:5]2
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: Cc1ccc2cnccc2c1
Solvent: CCOCC
Product: Cc1ccc2c[n+]([O-])ccc2c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 53.8 %

Procedure:
To a stirred solution of 6-methylisoquinoline (2.0 g, 14 mmol) in ether (80 mL) at 0° C. was added 3-chloroperbenzoic acid (57%, 4.3 g, 14 mmol). The mixture was warmed to room temperature, stirred for 3 h and filtered. The filter-cake was partitioned between chloroform (3×30 mL) and aqueous potassium carbonate solution (30 mL). The combined organic extracts were washed (brine), dried (sodium sulfate) and concentrated in vacuo to give the product as an off-white crystalline solid (1.2 g, 53%): mp 140-142° C.; IR νmax (Nujol)/cm−1 3047, 2925, 2855, 1606, 1562, 1466, 1377, 1328, 1270, 1217, 1182, 1133, 984, 920, 878, 858, 823, 803, 766, 600, 500 and 498; NMR δH (400 MHz, CDCl3) 2.53 (3H, s) 7.47 (1H, d, J 8.5 Hz) 7.59 (1H, d, .J 7.5 Hz) 7.64 (1H, d, J 8.5 Hz) 8.11 (1H, dd, J 2,7.5 Hz) 8.73 (1H, s).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)=[O:13])[N:3]=1.CCN(C(C)C)C(C)C.[CH3:30][C:31]1[NH:35][N:34]=[C:33]([NH2:36])[CH:32]=1>CN(C=O)C>[F:20][C:17]1[CH:18]=[CH:19][C:14]([C:12]([C:4]2[N:3]=[C:2]([NH:36][C:33]3[CH:32]=[C:31]([CH3:30])[NH:35][N:34]=3)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)=[O:13])=[CH:15][CH:16]=1
Reactant: O=C(c1ccc(F)cc1)c1nc(Cl)c2ccccc2n1
Reactant: Cc1cc(N)n[nH]1
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1cc(Nc2nc(C(=O)c3ccc(F)cc3)nc3ccccc23)n[nH]1
Temperature: 40 °C
Yield: 29 %

Procedure:
To a solution of (4-chloroquinazolin-2-yl)(4-fluorophenyl)methanone (84 mg, 0.30 mmol) in DMF (3 mL) were added DIEA (0.103 mL, 0.6 mmol) and 5-methyl-1H-pyrazol-3-amine (88 mg, 0.9 mmol at rt. The reaction mixture was heated at 40° C. overnight. The reaction was quenched by adding water and the yellow precipitate was collected by filtration and washed with water. The crude product was purified by silica gel chromatography eluting with DCM/MeOH to give (4-fluorophenyl)(4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)methanone (30 mg, 29%). 1H NMR (300 MHz, DMSO-d6) δ 2.19 (s, 3H), 6.54 (s, 1H), 7.40 (m, 2H), 7.68 (t, 1H), 7.9-7.7 (m, 2H), 8.08 (m, 2H), 8.74 (d, 1H), 10.66 (s, 1H), 12.20 (s, 1H); LC-MS (ESI) m/z 348 (M+H)+.
Reaction SMILES: [CH2:1]([O:3][CH:4]([O:13][CH2:14][CH3:15])[C:5]1[CH:12]=[CH:11][C:8]([CH:9]=O)=[CH:7][CH:6]=1)[CH3:2].[CH3:16][NH:17][CH3:18].[BH4-].[Na+]>CO>[CH2:1]([O:3][CH:4]([O:13][CH2:14][CH3:15])[C:5]1[CH:12]=[CH:11][C:8]([CH2:9][N:17]([CH3:18])[CH3:16])=[CH:7][CH:6]=1)[CH3:2]
Reactant: CCOC(OCC)c1ccc(C=O)cc1
Reactant: CNC
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CCOC(OCC)c1ccc(CN(C)C)cc1
Temperature: 25 °C
Reaction time: 0.67 h
Yield: 75.8 %

Procedure:
A mixture of 1-(4-(diethoxymethyl)benzaldehyde (2.08 g, 10 mmol) and dimethylamine (33% aqueous solution, 2.74 g, 20 mmol) in methanol (20 mL) was stirred at room temperature for 40 mins. The mixture was cooled to 0° C., sodium borohydride (0.57 g, 15 mmol) was added portionwise. After the addition, the mixture was stirred at room temperature for 4 hr. Methanol was removed under reduced pressure. The residue was partitioned between water (50 mL) and ethyl acetate (50 mL). The organic layer was separated. The aqueous layer was extracted with ethyl acetate (50 mL×3). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and concentrated to give 1-(4-(diethoxymethyl)phenyl)-N,N,-dimethylmethanamine (1.8 g) as a light yellow oil which was used in the next step without further purification. MS (ESI) m/z: 237 (M+1)+.
Reaction SMILES: [CH:1]1([CH:6]=[C:7]([C:17]2[CH:22]=[CH:21][C:20]([C:23](=O)C)=[CH:19][CH:18]=2)[C:8]2[NH:16][C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[CH:9]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:26][OH:27]>[Pd]>[CH:1]1([CH2:6][CH:7]([C:17]2[CH:22]=[CH:21][C:20]([CH2:23][CH:26]=[O:27])=[CH:19][CH:18]=2)[C:8]2[NH:16][C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[CH:9]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CO
Reactant: CC(=O)c1ccc(C(=CC2CCCC2)c2cc3cccnc3[nH]2)cc1
Agent: [Pd]
Product: O=CCc1ccc(C(CC2CCCC2)c2cc3cccnc3[nH]2)cc1
Temperature: 25 °C
Yield: 35 %

Procedure:
A mixture 1-{4-[2-cyclopentyl-1-(1H-pyrrolo[2,3-b]pyridin-2-yl)-vinyl]-phenyl}-ethanone (prepared as in Example 64, 280 mg, 0.84 mmol) and 10% palladium on activated carbon (56 mg) in methanol (200 mL) was heated at 50° C. under hydrogen (50 psi) for 5 h. The mixture was cooled to 25° C., the solids filtered off, washed with ethyl acetate and concentrated in vacuo. Purification using a Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water) afforded 2-{4-[2-cyclopentyl-1-(1H-pyrrolo[2,3-b]pyridin-2-yl)-ethyl]-phenyl}-ethanone (100 mg, 35%): LC/MS m/e calcd for C22H24N2O [M+H]+ 333.45, observed 333.1; 1H NMR (400 MHz, CD3OD) δ ppm 8.06 (d, J=4.5 Hz, 1H), 7.85-7.95 (m, 3H), 7.45 (d, J=7.6 Hz, 2H), 6.99-7.05 (m, 1H), 6.35 (s, 1H), 4.25 (t, J=7.8 Hz, 1H), 2.56 (s, 3H), 2.24 (dt, J=13.6, 7.0 Hz, 1H), 2.09 (dt, J=13.6, 7.0 Hz, 1H), 1.57-1.85 (m, 5H), 1.41-1.54 (m, 2H), 1.13-1.27 (m, 2H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[F:10].[Al+3].[Cl-].[Cl-].[Cl-].[C:15](Cl)(=[O:17])[CH3:16].O>C[N+]([O-])=O>[Cl:1][C:2]1[C:3]([F:10])=[CH:4][C:5]([O:8][CH3:9])=[C:6]([C:15](=[O:17])[CH3:16])[CH:7]=1
Reactant: CC(=O)Cl
Reactant: COc1ccc(Cl)c(F)c1
Agent: [Al+3]
Agent: [Cl-]
Solvent: C[N+](=O)[O-]
Solvent: O
Product: COc1cc(F)c(Cl)cc1C(C)=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 46 %

Procedure:
To a stirred solution of DMF (10 mL) and 4-chloro-3-fluorophenol (1 g, 6.84 mmol) at RT, K2CO3 (1.4 g, 10.3 mmol) was added and solution was allowed to stir at room temperature for additional 15 min. Methyl iodide (1.16 g, 8.21 mmol) was added to the mixture and mixture was allowed to stir for overnight at RT. After the completion of reaction 10 mL of water was added and was extracted with ethyl acetate (3×15 mL) and the resulting organic layer was washed with water, brine and dried. 1-chloro-2-fluoro-4-methoxybenzene was obtained via column chromatography (10/1 Hexanes/Ethyl acetate). To a stirred solution of 1-chloro-2-fluoro-4-methoxybenzene (1.09 g, 6.82 mmol) and AlCl3 (1.36 g, 10.23 mmol) in CH3NO2 at 0° C., acetyl chloride (0.80 g, 10.23 mmol) was added and solution was allowed to warm up to room temperature and stir for overnight. After the completion of reaction 10 mL of water was added and was extracted with ethyl acetate (3×15 mL) and the resulting organic layer was washed with water, brine and dried. The solvent was removed in vacuo. The crude was purified by flash column chromatography using 10/1 Hexanes/Ethyl acetate to afford product (46%). 1H NMR: 2.59 (s, 3H), 3.91 (s, 3H), 6.78 (d, 1H, J=10.5 Hz), 7.85 (d, 1H, J=8.7 Hz).
Reaction SMILES: [CH3:1][O:2][C:3]([C@@H:5]1[CH2:10][NH:9][CH2:8][CH2:7][N:6]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:4].[CH2:18](Cl)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(N(CC)CC)C>C(#N)C>[CH3:1][O:2][C:3]([C@@H:5]1[CH2:10][N:9]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:8][CH2:7][N:6]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:4]
Reactant: COC(=O)[C@@H]1CNCCN1C(=O)OC(C)(C)C
Reactant: ClCc1ccccc1
Solvent: CC#N
Solvent: CCN(CC)CC
Product: COC(=O)[C@@H]1CN(Cc2ccccc2)CCN1C(=O)OC(C)(C)C
Temperature: 71 °C
Yield: 52 %

Procedure:
To a dry 100.0 ml one necked round bottom flask equipped with a stirring bar is added (S)-1-N-Boc-piperazine-2-carboxylic methyl ester (800 mg, 3.275 mmol) under N2. Anhydrous acetonitrile (20 ml) is added to the flask followed by benzyl chloride (0.38 ml, 3.275 mmol) and triethylamine (1.28 ml, 9.17 mmol). Condenser is then put on to the flask and the reaction mixture is heated at 71° C. for 20 minutes. The reaction mixture is allowed to come to room temperature and concentrated under reduced pressure. It is then diluted with dicholoromethane and washed with water and brine. The organic layer is dried over Na2SO4, filtered and concentrated under reduced pressure. The crude compound is flash column purified using hexane and ethylacetate gradient solvent system to yield 570 mg (52%) of the desired product.
Reaction SMILES: [C:1]1(=[O:6])[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl[CH2:8][CH2:9][CH2:10][CH:11]1[CH2:16][CH:15]2[CH2:17][CH:12]1[CH:13]=[CH:14]2>>[CH:12]12[CH2:17][CH:15]([CH:14]=[CH:13]1)[CH2:16][CH:11]2[CH2:10][CH2:9][CH2:8][C:1]1([OH:6])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=C1CCCC1
Reactant: ClCCCC1CC2C=CC1C2
Product: OC1(CCCC2CC3C=CC2C3)CCCC1
Yield: 86 %

Procedure:
1-{3-(5-Norbornen-2-yl)propyl}cyclopentanol (yield: 86%) was obtained in the same manner as in Synthesis Example 1, except that cyclopentanone and 1-chloro-3-(5-norbornen-2-yl)propane were used in place of acetone and 1-chloro-4-(5-norbornen-2-yl)butane, respectively.
Reaction SMILES: [CH3:1][N:2]([CH2:11][CH2:12][OH:13])[C:3](=[O:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[C:14](Cl)(=[O:30])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]>>[CH3:1][N:2]([CH2:11][CH2:12][O:13][C:14](=[O:30])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])[C:3](=[O:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: CN(CCO)C(=O)c1ccccc1
Reactant: CCCCCCCCCCCCCCCC(=O)Cl
Product: CCCCCCCCCCCCCCCC(=O)OCCN(C)C(=O)c1ccccc1

Procedure:
N-methyl-N-(2-palmitoyloxyethyl)benzamide was prepared by the procedure of example 1 from 18 gms. (0.1 mole) of N-methyl-N-(2-hydroxyethyl)benzamide and 26 gms. (0.1 mole) of palmitoyl chloride. The structure of the final product was characterized on the basis of IR and NMR spectral analyses as described in example 1.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:20])[CH2:4][C:5]1[N:10]=[C:9]([O:11]C)[C:8]([Cl:13])=[C:7]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[N:6]=1.O1CCOCC1>C(OCC)C>[CH3:1][O:2][C:3](=[O:20])[CH2:4][C:5]1[NH:10][C:9](=[O:11])[C:8]([Cl:13])=[C:7]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[N:6]=1
Reactant: COC(=O)Cc1nc(OC)c(Cl)c(N2CCOCC2)n1
Solvent: C1COCCO1
Solvent: CCOCC
Product: COC(=O)Cc1nc(N2CCOCC2)c(Cl)c(=O)[nH]1
Yield: 86.8 %

Procedure:
500 mg of (5-chloro-4-methoxy-6-morpholin-4-ylpyrimidin-2-yl)acetic acid methyl ester and 5 ml of 4N hydrochloric dioxane are placed in a microwave tube. After microwave irradiation for 30 minutes at a temperature of 110° C., the reaction medium is concentrated under reduced pressure. The residue obtained is taken up in ethyl ether. The solid formed is filtered off so as to give 414 mg of (5-chloro-4-morpholin-4-yl-6-oxo-1,6-dihydropyrimidin-2-yl)acetic acid methyl ester, the characteristics of which are the following:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][N:11]3[C:16]=2[CH2:17][N:18]2[CH2:22][C:21](NCCN(C)C)=[CH:20][C:19]2=[O:29])=[CH:4][CH:3]=1.ClC1C=CC(C2N=C3C=CC=CN3C=2CN2CC(OC)=CC2=O)=CC=1.[NH:55]1[CH2:60][CH2:59][CH:58]([OH:61])[CH2:57][CH2:56]1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][N:11]3[C:16]=2[CH2:17][N:18]2[CH2:22][C:21]([N:55]3[CH2:60][CH2:59][CH:58]([OH:61])[CH2:57][CH2:56]3)=[CH:20][C:19]2=[O:29])=[CH:6][CH:7]=1
Reactant: CN(C)CCNC1=CC(=O)N(Cc2c(-c3ccc(Cl)cc3)nc3ccccn23)C1
Reactant: OC1CCNCC1
Agent: COC1=CC(=O)N(Cc2c(-c3ccc(Cl)cc3)nc3ccccn23)C1
Product: O=C1C=C(N2CCC(O)CC2)CN1Cc1c(-c2ccc(Cl)cc2)nc2ccccn12

Procedure:
The title compound was prepared according to the experimental for compound 237 from 1-((2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl)methyl)-4-methoxy-1H-pyrrol-2(5H)-one and piperidin-4-ol. (49 mg, 41%) m/e+=423 (M+H+). 1H-NMR (400 MHz, CDCl3, δ): 8.47 (d, 1H, D, J=7.0 Hz), 7.73 (d, 2H, D, J=8.4 Hz), 7.62 (d, 1H, D, J=9.2 Hz), 7.47 (d, 2H, D, J=8.8 Hz), 7.25 (t, 1H, D, J=7.3 Hz), 6.85 (t, 1H, D, J=7.3 Hz), 5.09 (s, 2H), 4.73 (s, 1H), 3.87 (m, 1H), 3.57 (s, 2H), 3.25 (m, 2H), 2.87 (m, 2H), 1.7 (m, 4H).
Reaction SMILES: P(Cl)(Cl)(Cl)(Cl)Cl.[CH3:7][C:8]([CH3:20])([O:10][CH2:11][CH:12](O)[CH2:13][N:14]1[CH2:18][CH2:17][CH2:16][CH2:15]1)[CH3:9].[ClH:21]>C1(C)C=CC=CC=1.O1CCCC1>[Cl:21][CH:12]([CH2:11][O:10][C:8]([CH3:20])([CH3:9])[CH3:7])[CH2:13][N:14]1[CH2:18][CH2:17][CH2:16][CH2:15]1
Reactant: Cl
Reactant: CC(C)(C)OCC(O)CN1CCCC1
Agent: ClP(Cl)(Cl)(Cl)Cl
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: CC(C)(C)OCC(Cl)CN1CCCC1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
To a stirred, cooled suspension of 34.7 g (0.167 ml) of phosphorous pentachloride in 20 ml of dry toluene (argon atmosphere) was added a solution of 31.93 g (0.159 m) of 1-[3-(1,1-dimethylethoxy)-2-hydroxypropyl]pyrrolidine (the product of Example 13a) and excess hydrogen chloride (gas) in 46 ml of dry toluene and 50 ml of dry tetrahydrofuran at a rate to keep the reaction temperature at 10°-25° C. When the addition was completed, the cooling bath was removed and the reaction mixture was stirred at ambient temperature for 1.5 hr. The reaction mixture was added portionwise, with stirring to a cooled solution of 122 ml of 45% potassium hydroxide and 230 g of ice at a rate to keep the reaction temperature at 25°-35° C. The reaction mixture was partitioned between ether and water. The ether portion was dried and concentrated in vacuo to give 31.69 g of oily title compound.